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pmc-6260776-2
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Case 2 is a 55-year-old European man with a history of hypertension who presented to the emergency room with seizures in December 2013; Case 2 is summarized in Fig. . A brain CT scan and further MRI showed three tumors surrounded by cerebral edema. A left kidney tumor and two lung nodules were identified by CT scan and, finally, clinical examination found some hypervascularized lesions of his scalp. The cutaneous tumors were surgically removed and the pathological report identified metastases of a type 2 papillary renal tumor. This patient was classified in the favorable risk group according to the International Metastatic RCC Database Consortium (IMDC) []. Brain metastases were all treated by stereotaxic radiation. Pazopanib another TKI directed to VEGFr was initiated at 800 mg/day. This treatment induced a partial response in lung metastases and in the primary renal tumor; the three brain metastases were also reduced. The disease remained stable for 2.5 years under pazopanib, except in his brain. In fact, two new brain metastases appeared 12 months later and three others after 24 months. Stereotaxic radiation was performed on each new brain tumor and pazopanib at 800 mg per day was resumed. Some neurological symptoms appeared with several transient episodes of aphasia together with some degree of mental confusion, 4 months after the last radiation treatment. Pazopanib treatment was completed and brain MRI indicated a radionecrosis with surrounding cerebral edema in one of the recently irradiated brain metastases. Two months after pazopanib completion, a CT scan showed significant progression in all other metastatic sites including previously irradiated brain metastases. Cabozantinib was started after our patient gave consent. Neurological symptoms rapidly resolved and a brain MRI at 2.5 months evidenced tumor regression of the different brain metastases (Fig. ). Cabozantinib was ongoing for 6 months but had to be reduced to 40 mg/day due to grade 3 diarrhea. Sequencing was performed on the metastatic tumor sample but no MET mutation was identified and no MET gene amplification was observed.
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pmc-6260884-1
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The patient is a 69-year-old woman. She was infected with pneumonia at the age of three and had a high fever for a long period. After the fever abated, she became aware of hearing loss. Because she lived in a mountain village, she rarely visited medical facilities. Since then, she had never worn a hearing aid, had gone to a school for the deaf from elementary school to high school, and communicated with people in sign language. Her husband also used sign language, so she had not used oral communication from elementary school to the present. In 2011, family stress triggered the onset of tinnitus. Because around the same time, she began suffering from sleep onset disorder (it took about one hour until sleep onset), nocturnal awakening, and palpitations, she went to a nearby psychosomatic medicine clinic. She received medication at the clinic but her tinnitus did not improve, so she was referred to our department in 2014.
Various questionnaires were given at her consultation. The result of THI (Tinnitus Handicap Inventory) [], which is used to evaluate the severity of tinnitus, was a high of 94, which indicates the most severe form of tinnitus. Also, an SDS (Self-rating Depression Scale) [] score, which is used to measure depression tendency, was as high as 61, showing that she had a tendency toward depression. The STAI (State-Trait Anxiety Inventory) [], which is used to measure anxiety tendency, returned a State Anxiety (STAIs) score of 69 and a Trait Anxiety (STAIt) score of 67, indicating that she had an extremely high anxiety tendency. As one of the personal features of her tinnitus, she had no concept of the “loudness of tinnitus” because she had been deaf since childhood.
In imaging tests, there were no abnormal findings except for a slight enlargement of the inner ear canals observed by temporal bone CT scan. Head MRI showed no abnormal findings within the skull or in the internal auditory canals.
For treatment, we started oral administration of a serotonin reuptake inhibitor (SSRI) (paroxetine hydrochloride, Paxil®, 12.5 mg, started as one tablet a day, increased to three tablets a day) and a sleep-inducing agent (suvorexant, Belsomra®, 15 mg, one tablet a day). One and a half months later, the sleep onset disorder and nocturnal awakening improved, but early morning arousal persisted. Then, a benzodiazepine anxiolytic was added (etizolam, Depas®, 0.5 mg, one tablet a day). At four months after the initial visit, THI was 84, SDS 43, STAIs 50, and STAIt 48, which showed that her psychological condition had improved, although the tinnitus distress level did not change.
At this time, there was no improvement in perceived palpitations, and “pulsatile tinnitus” that seemed to synchronize with the heartbeat became the chief complaint concerning tinnitus, which led us to suspect that she had autonomic disorders. Six months after the initial visit, she started to receive psychotherapy (autogenic training). After the start of the treatment, we treated the patient with psychotherapy once a month, which continued until the 7th therapy session was completed. At the end of psychotherapy, our test results showed THI at 60, SDS 45, STAIs 32, and STAIt 43, showing a further improvement trend. The THI score was still high at 60, but the subjective tinnitus distress became “not so annoying,” and the “echoing tinnitus” that was the cause of the patient’s discomfort at the time of the initial visit disappeared. Only the pulsatile tinnitus, which seemed to be related to palpitations, remained.
One year and seven months after the initial visit, palpitations and pulsatile tinnitus, as well as anxiety and insomnia, were aggravated due to work stress. She restarted psychotherapy. At the same time, SSRIs were replaced by noradrenergic and specific serotonergic antidepressants (NaSSAs) (mirtazapine, Reflex®, 15 mg, started as one tablet a day, increased to two tablets a day). As a result, improvement of the palpitations and insomnia gradually occurred, and two years and one month after the initial visit, our test results showed THI at 40, SDS 47, STAIs 40, and STAIt 46.
By three years after the initial visit, the symptoms had stabilized and the anxiolytic drug was discontinued, but oral administration of the NaSSA and sleep induction drugs continued. The subjective tinnitus and palpitations at the time of sleep almost disappeared, and the sleep onset disorder and nocturnal awakening rarely occurred.
Now 4.5 years have passed and she is taking only a low dose NaSSA (mirtazapine, Reflex®, 15 mg, 0.5 Tablets a day). The latest test results were THI 0, SDS 43, STAIt 47, and STAIs 50, indicating that the tinnitus distress had disappeared completely.
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pmc-6260906-1
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A 77-year-old-man was admitted to our respiratory department for an organized, unilateral pleural effusion. He reported a severe former smoking habit (150 pack/years). He worked mainly as a tailor and, for some years, as a metalworker; he is currently retired, and he spends his time in his garden. His medical history demonstrated that he suffered from arterial hypertension, treated with 10 mg of Olmesartan once daily. He underwent partial gastrectomy some years before for a peptic ulcer. In the month before the admission, he reported a stroke, which led to slight dysarthria; because of this, he is currently on therapy of 300 mg Aspirin once daily. He denied any clinical history of ischaemic heart disease, heart failure, or diabetes. No apparent sources of asbestos exposure were known.
In the month of April 2018, he came to the emergency department of our hospital for acute dyspnoea and tachyarrhythmia (166 beats/min) with a normal arterial pressure (120/80 mmHg). He had a partial arterial oxygen pressure (PaO2) of 57 mmHg with normal partial arterial carbon dioxide pressure (PaCO2) and pH. The patient also complained of exertional dyspnoea from a few months. He denied fever, cough, and chest pain in the previous months. Blood tests showed macrocytic anaemia (haemoglobin 11 g/dL, mean cell volume 104 fL), a slight value of inflammatory response (leucocytes 10.5 × 109/L with 80% neutrophils, C-reactive protein 28.70 mg/L). The electrocardiograph showed a paroxysmal atrial fibrillation, which was treated with amiodarone and oral anticoagulation therapy. The chest X-ray showed a unilateral, organized pleural effusion (Fig. ). A chest CT scan showed a right, organized pleural effusion and a thickening of the right parietal and mediastinal pleura, suggestive of malignant pleural disease, without mediastinal lymph node involvement but with a compressive atelectasis of the adjacent lung parenchyma (Fig. ).
On the suspicion of pleural mesothelioma or a pleural localization of a lymphoproliferative disease, the patient underwent medical thoracoscopy, in which multiple biopsies were performed and a pleural drainage was performed, with a removal of 850 mL of pleural fluid. Physical examination of the pleural fluid showed a corpusculated, orange-coloured liquid with many cords of fibrin; chemical analysis showed an acid pH (7.18) and lactate 9.9 mmol/L, with pleural fluid lactate dehydrogenase (LDH) of 7849 IU/L and total proteins of 5.7 g/dL. Light’s criteria were positive for an exudative pleural effusion. Cytology showed a relevant inflammatory pattern, mainly composed of neutrophils (60.9% of total) and lymphocytes (36.5% of total); no neoplastic cells were described. The research of mycobacteria tuberculosis through in vitro culture was negative. A peripheral lymphocyte subset typing method by cytofluorometry excluded lymphoid malignancies.
Histological exam performed on biopsies and pleural fluid showed a “purulent pleuritis” with evidence of Bacillus megaterium infection, which was sensible to all antibiotics tested, except for clindamycin. Therapy with meropenem of 3 g/day and levofloxacin of 500 mg/day was started, with benefits. A chest CT scan after two weeks of the antibiotic therapy showed a significant improvement (Fig. ) with normality of blood exams. The patient was no longer dyspnoeic, without a need for oxygen. The patient achieved completed resolution.
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pmc-6260989-1
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A 71-year-old Asian woman presented for the evaluation of persistent nasal congestion, cough and fever. She was born in India but lived most of her life in the United States. Her past medical history was significant for seasonal allergic rhinosinusitis that was most severe in early summer. During the last recurrence, the symptoms of nasal congestion were unresponsive to antihistamines. Subsequently, she developed cough and low-grade fever and received two courses of oral prednisone and antibiotics for 6 weeks, without symptom resolution. A computer tomography (CT) scan revealed mucosal thickening in the maxillary sinuses, bilaterally. Two months after the initial onset of symptoms, functional endoscopic sinus surgery was performed and a polypoid nasal mass was removed. Upon histopathological evaluation at an outside institution, a diagnosis of ENKTCL-NT was rendered. Serological studies for EBV IgM were within normal limits, while EBV capsid IgG was elevated. Polymerase chain reaction (PCR) for EBV DNA performed on the patient’s serum yielded results below the limit of detection for the assay. The patient subsequently transferred her care to our institution, and by then she had been completely asymptomatic for several weeks. A follow-up CT scan showed persistent mucosal thickening, and a repeat nasal biopsy was performed at our institution.
The repeat nasal biopsy contained fragments of fibrotic sinonasal mucosa with a diffuse infiltrate (Fig. and ) composed of atypical small to medium-sized lymphoid cells (Fig. and ) with hyperchromatic, irregularly folded nuclei (Fig. ). The overlying sinonasal mucosa showed focal ulceration and although there was focal angiocentricity, no necrosis was observed. Immunohistochemical evaluation demonstrated that the atypical lymphoid cells were positive for cytoplasmic CD3 (Fig. ), CD2 (Fig. ), CD5 (Fig. ), granzyme B (Fig. ), perforin (Fig. ) and EBER (Fig. ). The Ki-67 proliferative rate was low (< 1% overall) (Fig. ). The atypical cells were negative for CD56 (Fig. ), CD20 (Fig. ), CD4, CD7, CD8, TIA-1, CD30 and CD57.
Flow cytometric studies performed on tissue fragments from the nasal biopsy demonstrated a subset of lymphoid cells, comprising 6% of total events, with the following immunophenotype: CD2+, surface CD3-, CD4-, CD8-, CD5(dim)+, CD7(dim)+, CD16-, CD25-, CD56- and CD57- (Fig. ). Also present were CD3+ T cells without significant loss of pan T-cell antigens and a CD4:CD8 ratio of 4:1 (53% of total events) as well as few unremarkable CD3- CD7+ NK cells and polyclonal B-cells.
T-cell receptor gamma gene rearrangement studies by PCR revealed a prominent 239 base pair peak in one reaction, and 192 and 193 base pair peaks in an irregular polyclonal distribution in a second reaction (Fig. ).
Next-generation sequencing studies performed at the University of Pennsylvania using a custom, targeted sequencing amplicon panel for 68 hematologic malignancy-associated genes [, ] revealed a missense variant in exon 3 of the KIT gene at amino acid 167, converting the wild type residue lysine to methionine (p.K167 M, c.500A > T), with an allele frequency of 23%.
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pmc-6261077-1
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The patient was a 50-year-old male, 173 cm tall, and 85 kg in weight (body mass index (BMI): 27.7 kg/m2). He had a medical history of urinary tract cancer, type 2 diabetes mellitus, hypertension, and Hashimoto's disease. He underwent a robot-assisted radical cystectomy in lithotomy position. The total operation time was 419 min. The operative position was lithotomy position with his lower leg flexed and elevated by soft stirrups. Continuous compression devices on both calves were used for venous thrombosis prophylaxis throughout the procedure. No bleeding-promoting drug was used before and after the surgery.
Sixteen hours after the surgery, he complained of severe bilateral lower leg pain and swelling. Initial evaluation of lower extremities revealed foot drop, swelling and tightness of the anterolateral aspects, and stretch pain on passive ankle planter flexion. No remarkable finding was appreciated on the posterior aspects of his lower legs. Serum creatine kinase was elevated to at 28000 U/l. The compartment pressure was measured by an arterial line set with simple 18-gauge needle under the diastolic blood pressure of 98 mmHg. The measurement was performed at three places of each compartment, and the average value was recorded. The anterior and lateral compartment pressures in both legs had increased to 200 mmHg despite normal posterior compartment pressure (35 mmHg) or thigh compartment pressure (35 mmHg). Contrasting computed tomography (CT) showed swelling of the bilateral muscles in the anterior and lateral compartments without contrasting effect compared to the posterior compartments (). Based on these findings, WLCS localized in the anterior and lateral compartments was diagnosed.
An emergency fasciotomy was performed twenty hours after initial surgery. Anterior and lateral compartments were released with single incision (). Discoloration of the muscles improved within a few minutes after the fasciotomy (). Shoe-race procedure was added to prepare for secondary wound closure (). Symptoms such as unbearable pain or decreased sensation were drastically improved after the fasciotomy. The serum creatine kinase decreased and normalized eight days after the surgery. He recovered well without any motor and sensory dysfunction in both lower extremities. The fasciotomy wound was closed on the ninth postoperative day without additional stage procedure. Three months after the surgery, he had no neuromuscular dysfunction.
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pmc-6261084-1
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A 79-year-old female patient visited the authors’ clinic with gingival swelling and pain on the left mandibular region. She was in a mandible edentulous state. The lesion range was from the alveolar crest on the mandible left to the floor of the mouth. Incisional biopsy was done. The biopsy result indicated the presence of squamous cell carcinoma (cT4aN2cMx). After incisional biopsy, the patient was given neoadjuvant chemotherapy (Doxetaxel) for 1 day. Modified radical neck dissection (mRND) was done on the left side. On the right side, supraomohyoid neck dissection (SOHND) was done. Wide excision and segmental mandibulectomy was also done. Reconstruction was done with a reconstruction plate. Instead of free tissue transfer, a pectoralis major myocutaneous flap was used to cover the intraoral defect due to the patient’s poor general condition. The biopsy result indicated the presence of squamous cell carcinoma (pT4N2cMx). The patient was given postoperative radiotherapy 25 times (45 Gy) (Fig. ).
Fourteen months postoperatively, reconstruction using ready-made type T-mesh (Striker-Leibinger, Freibrug, Germany) and iliac PCBM was done to repair the mandible left body defect (7 × 2.5 × 1.0 cm). After the reconstruction plate removal, corticocancelous block bone harvest was performed, including the iliac crest, and the Ti-mesh tray was filled with iliac PCBM. After that, the tray was adapted to the mandible and fixated using eight screws onto the anterior area, and seven screws onto the ramus area (Fig. ).
The patient did not come back for follow-up for 2 years and 3 months. Seven years and 6 months postoperatively, the patient revisited with orocutaneous fistula on the left chin, but neither intraoral fistula nor pus discharge was observed. Fistulectomy on the chin area was done at first to cover the T-mesh.
Eight years and 8 months after the mandible reconstruction, there was T-mesh exposure on the left mandible area. As such, a Ti-mesh removal operation was scheduled. Eight years postoperatively (after the reconstruction surgery using T-mesh), the Ti-mesh tray and Leibinger screws (15 ea) were completely removed. The reconstruction site was found intact, and no inflammation was observed. Since after the Ti-mesh removal, no inflammation and complication have been observed. Also, an aesthetic contour of the mandible, with adequate functions, was achieved (Figs. and ).
A 62-year-old female patient visited the authors’ clinic with pain on the right mandibular region. Incisional biopsy was done. The biopsy result indicated the presence of squamous cell carcinoma (cT4aN0M0). After incisional biopsy (20 days later), SOHND was done, along with wide excision and segmental mandibulectomy. Reconstruction was also done with a reconstruction plate and a right fibula free flap (Fig. ). The biopsy result indicated the presence of squamous cell carcinoma (pT4aN0M0). One month postoperatively, the intraoral fibular skin flap was infected due to the emergency care that was given to the patient (due to a cardiologic problem that arose after the operation). The infected fibular segment was removed 1 month postoperatively. One year postoperatively, fibular bone exposure was observed. The two screws on the mandible posterior area, which had been used for fibular bone fixation, were removed. Complete curettage was done on the infected fibular bone. Although no wound dehiscence was observed after the curettage for 1 year and 4 months, reconstruction was done using custom-made type T-mesh and iliac PCBM and platelet-rich plasma (PRP), which has growth factors for bone healing enhancement [], to repair the mandibular defect. The CAD-CAM T-mesh was made prior to the operation, at the laboratory. After the reconstruction plate removal, the iliac crest including a 7 × 5 cm block bone and PCBM was harvested and fixated using two mini-plates. The T-mesh tray was then adapted to the mandible, and the T-mesh tray was filled with an additional particulate iliac bone (Figs. and ).
One year and 6 months postoperatively (after the reconstruction surgery), no fistula and swelling were observed. The T-mesh tray (except the mini-plate) was completely removed. The reconstruction site was found intact, and no inflammation was observed. Since after the T-mesh removal, no inflammation and complication have been observed (Figs. and ).
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pmc-6261092-1
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A 69-year-old female presented to our hospital with a one-month history of epigastric discomfort. Physical examination was unremarkable, and laboratory examination was normal other than slightly elevated amylase levels. Abdominal contrast-enhanced computed tomography (CT) revealed a low-density mass with a diameter of 30 mm at the pancreatic head, with segmental superior mesenteric vein (SMV) attachment. There was neither stenosis nor arteriosclerosis around the celiac axis at that time (Fig. ). Endoscopic ultrasonography was performed, and a fine-needle biopsy sample showed adenocarcinoma of the pancreas.
The patient then underwent PD with superior mesenteric vein resection and reconstruction, and a lymphadenectomy including right half dissection of the lymph nodes without the nerve plexus around the celiac trunk. Intraoperative exploration ruled out latent peritoneal or liver metastasis and showed normal anatomy of the celiac trunk, mesenteric vessels, and related branches. A clamp test of the GDA showed normal hepatic artery pulsation. The pancreatic body needed to be mobilized more than usual for the pancreaticojejunostomy because it was a hard pancreas. The duration of surgery was 549 min, and the blood loss was 863 mL; blood transfusion was not performed.
On POD 3, her liver function tests were still abnormal and bloody fluids were found in the drain. Abdominal CT showed a characteristic hook-pattern on the anterior proximal celiac axis from compression of the MAL, which had not been detected in the preoperative CT (Fig. a). In addition, ischemic changes in the remnant pancreas, hepatic lateral segment, and gastrojejunostomy site were also observed, although all celiac branches—left gastric artery; splenic artery; common hepatic artery; and right and left hepatic artery—were visible (Fig. b, c). We tried interventional radiology first, but the procedure failed due to the tight compression against the outside of the celiac axis. The patient underwent an urgent re-laparotomy. There were almost no pulsations in those celiac branches, showing a markedly decreased blood flow at the celiac axis and stenosis at the root of the celiac artery. No surgery-related damage was detected in any of those branches. Necrosis of the pancreaticojejunostomy site and pancreatic body was also detected. This was considered to be related to the mobilization of the pancreatic body, making this part more susceptible to ischemic damage. The MAL was released, with subsequent dramatic resumption of pulsation in the celiac artery and the common hepatic artery (Fig. ). Resection of the remnant pancreas and splenectomy was also performed.
Abdominal CT on POD 20 showed re-occlusion of the celiac artery at its root, which was almost same as the first stenotic site (Fig. ). However, although the right and left hepatic arteries and the left gastric artery were visible, taking from collaterals, the patient experienced rupture of the gastrojejunostomy site, severe hepatic cytolysis and choledochojejunostomy stricture thereafter (Fig. a, b). She underwent percutaneous drainage for each. She was discharged to her home at POD 216 with a percutaneous transhepatic cholangial drainage tube.
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pmc-6261093-1
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An 80-year-old woman was brought to our hospital complaining of fever and difficulty with body movement. Her medical and surgical histories were unremarkable. She had a body temperature of 37.7 °C, blood pressure 147/113 mmHg, heart rate 124 beats/min, and respiration rate 17/min. On physical examination, subcutaneous emphysema was found from the left lower abdomen to the left femoral region. Muscular defense was not found. Blood tests revealed an elevated white blood cell (WBC) count and C-reactive protein (CRP) level, and decreased hemoglobin (Hb) and platelet count. The examination also revealed acute kidney injury. Blood glucose was 137 mg/dL, and HbA1c was 6.4% (Table ). On the first day, the sequential organ failure assessment (SOFA) score was 1, and the Quick SOFA score was 0.
Enhanced computed tomography (CT) showed a thickened wall of the descending colon and retroperitoneal abscess formation in this area. From these findings, penetrating descending colon cancer was suspected (Fig. a). Emphysema was present from the retroperitoneal abscess around the descending colon to the left thigh through the left femoral ring (Fig. b, c). Lymph node metastasis and distant metastasis were not detected.
The patient was suspected to have NF due to penetration of descending colon cancer. Left hemicolectomy and open drainage of the left femoral region were performed (Fig. a, b). A microbiological culture of the abscess revealed the presence of group C β-Streptococcus, Escherichia coli, Prevotella species, and Corynebacterium species. Histopathological findings showed a tumor with a histological type of well-differentiated adenocarcinoma. The tumor had grown through the serosa (T4a), but there was no metastasis to lymph nodes (N0).
After surgery, the patient received intensive care for sepsis and underwent lavage of the open drainage site. Drainage was insufficient, and so additional open drainage was performed on postoperative day (POD) 1 (Fig. a, b). After additional drainage, control of focal infection was successful and sepsis was gradually controlled. Follow-up CT on POD 11 showed no residual abscess, and so negative pressure wound therapy was tried. Closure of the drainage site was performed on POD 22, and the patient was transferred to a different hospital on POD 26. She has now achieved 6-month relapse-free survival.
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pmc-6261094-1
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A 60-year-old man was admitted to our hospital with a liver tumor, which was discovered during fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) as a cancer examination. He had a history of hepatitis B virus infection (positive for hepatitis B virus antigen), but was asymptomatic, showed no positive signs when examined, and had not had any medical interventions.
Analysis of serum tumor markers showed no elevated carbohydrase antigen-19-9 (11.2 U/ml), carbohydrase antigen-125 (18.1 U/ml), or carcinoembryonic antigen (1.0 ng/ml). Other parameter levels were within normal ranges. Gastroscopy and colonoscopy also showed normal findings.
Plane computed tomography (CT) scan revealed a well-defined low-density mass, 6.0 cm in diameter, in the caudate liver (Fig. a), which showed two different components in the enhanced CT scan. Contrast-enhanced CT scan showed the right tumor enhancement during the arterial phase and delayed washout in the late phase, but showed the left component as a hypovascular lesion (Fig. b–d). Magnetic response imaging (MRI) showed both of these components with low intensity on T1-weighted images (Fig. a), and right component of iso-high intensity and left component of heterogeneously high on T2-weighted images (Fig. b). It also showed higher intensity than with normal liver parenchyma on diffusion-weighted imaging (DWI), with a high b value of 1000 (Fig. c). Apparent diffusion coefficient (ADC) mean values of these two separated components were 1.19 × 10− 3 mm2/s (right component) and 1.95 × 10− 3 mm2/s (left component). It was described as a high-intensity mass on the ADC map (Fig. d). Gadolinium-ethoxybenzyl-diethylene-triaminepentaacetic-acid (Gd-EOB-DTPA)-MRI showed the right tumor as a hyperintense in the arterial phase (Fig. e) and the whole tumor as a hypointense mass in the hepatobiliary phase (Fig. f). [18F]-fluorodeoxyglucose positron tomography (FDG-PET) showed accumulation of [18F]-FDG at both components (Fig. g).
The preoperative diagnosis, based on the imaging studies, was an atypical ICC. After the patient underwent left and caudate lobectomy of the liver, macropathology of the resected specimen showed that the tumor measured 7.5 cm in the largest dimension. The cut surface showed two different components, with a well-demarcated, yellowish, and nodular lobulated solid formation in the right, and an elastic soft and cystic formation on the left (Fig. a).
Micropathologically, the right tumor component (indicated as a hypervascular lesion on enhanced CT) showed an adenocarcinomatous element, composed of moderately to poorly differentiated adenocarcinoma, arranged in trabecular and irregular tubular patterns, infiltrated into the liver parenchyma (Fig. b). The left component (which appeared with heterogeneous high intensity on T2WI) was a sarcomatous element, mainly composed of oval- to spindle-shaped cells with a focal dilated gland ductal structure (Figs. c and a). These two components were mostly separate but with a small intermingled area with well-differentiated adenocarcinomatous and sarcomatous elements. There was no evidence of transitional feature between adenocarcinomatous and sarcomatous elements. The surrounding parenchyma showed no cirrhotic change.
In immunohistochemical (IHC) tests, the adenocarcinoma cells were positive for cytokeratin-7 (CK7), cytokeratin-19 (CK19), CD56, and epithelial membrane antigen (EMA), but negative for hepatocellular carcinoma markers such as Glypican-3 (date not shown). There were no histologic elements suggesting HCC. The sarcomatous cells were positive for S-100, α-smooth muscle actin (SMA), and CD10, but negative for CK7, CK19, CD56, and EMA (Fig. b–g). The Ki67 index was 22% in the sarcomatous elements (Fig. h). These findings led to a pathological diagnosis of carcinosarcoma (ICC with sarcomatous stroma). The patient recovered uneventfully from the surgery, and at present, 14 months later, he remains well with no evidence of tumor recurrence.
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pmc-6261234-1
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We present a 56-year-old gentleman who worked as a computer programmer, with no significant past medical history. The patient was referred to the haematology department by his general practitioner with pancytopenia and splenomegaly. He described progressive left leg swelling and abdominal discomfort over the last 2 weeks prior to presentation. He had an increasing dyspnoea for one week. The patient was admitted to the hospital with ongoing fever with temperature > 38 degree Celsius.
Family history revealed an increased incidence of malignancies. His father was diagnosed and was being treated for low-grade lymphoma at that time. His sister had a history of renal cell carcinoma and was in remission following nephrectomy.
Clinical examination revealed marked splenomegaly (12 cm below the costal margin), markedly swollen left leg, and several small skin nodules over the anterior aspect of his leg ().
Similar lesions were present on the right upper back. The left inguinal region was difficult to palpate due to oedema; however, there was no palpable lymphadenopathy elsewhere. There were petechial rashes on both lower limbs, being more extensive on the left side.
The initial investigations with peripheral blood smear and flow cytometry was suggestive of HCL. Staging CT scan showed lymphadenopathy in the para-aortic and iliac/inguinal region. Bone marrow biopsy confirmed concurrent HCL and MCC as described in Investigations. The biopsy from the skin lesion also confirmed MCC.
MCC has a poor overall prognosis, and confirmation of this diagnosis in this patient precluded him from treatment with curative intent.
Initial investigations showed positive direct antiglobulin test (DAT) indicating autoimmune haemolytic anaemia with haemoglobin (Hb) of 50 g/L. The patient also had severe pancytopenia with a platelet count of 6 × 109/L (N. 150-400 × 109/L) and a white cell count of 0.4 × 109/L (N. 4.0-11.0 × 109/L). The LDH was elevated at 410 U/L (N. <250 U/L). The remaining serum chemistry values were within the normal reference range.
The peripheral blood film showed the presence of occasional hairy cells. Flow cytometry of the peripheral blood demonstrated a small clonal population of B lymphocytes expressing kappa-light chain restriction and the following cell surface immunophenotype: CD19+, CD20+, CD11c+, CD25+, CD103+, FMC7+, CD10−, and CD5−. This picture was consistent with HCL.
Staging CT scan showed enlarged para-aortic, left common iliac, left external iliac, left internal iliac, and left inguinal lymph nodes. The lumens of the left common iliac and external iliac veins were nearly completely obliterated by the adjacent enlarged lymph nodes; however, no thrombosis was noted.
Bone marrow biopsy revealed a hypercellular marrow with distortion of the normal marrow architecture by the presence of a diffuse lymphocytic infiltration, increased fibrosis, and areas replaced by large, immature, and undifferentiated malignant cells.
The bone marrow trephine demonstrated a “fried egg appearance,” a morphological feature considered highly suggestive of HCL (). Bone marrow trephine also showed large nonhaematopoietic tumor cells appearing to grow in organoid formation suggestive of an undifferentiated carcinoma (). They displayed conspicuous nucleoli and lamellar structures within the cytoplasm. Immunohistochemical stains were positive for cytokeratin-20 (CK-20), chromogranin A () and synaptophysin and negative for CD45, CD20, and cytokeratin-7 (CK-7). The characteristic cytoplasmic hairy projections of the lymphoid cells are demonstrated in Figures and .
Subsequent biopsy of the skin lesions demonstrated dermal infiltration by “small round blue cells.” These neoplastic cells formed nests and sheets that insinuated between the dermal collagen bundles. The tumor cells had no appreciable cytoplasm, with round to irregular nuclei, fine granular chromatin, and strong positive labelling with the neuroendocrine marker synaptophysin. These cells stained positively for pancytokeratin (AE1/3) in a dot distribution and did not stain with lymphoid markers CD20 or CD3. The morphology was classic for MCC and similar in appearance to the nonhaematopoietic cell infiltrate present in bone marrow trephine.
metastatic visceral neuroendocrine carcinomas cutaneous lymphoma dermatologic manifestations of systemic immunologic disorders, like scleroderma, polymyositis, and polyarteritis nodosa other skin malignancies, like squamous cell carcinoma viral infection
The patient was treated with weekly intravenous infusions of carboplatin, supported with granulocyte colony stimulating factor (G-CSF) and combined with pulsed high-dose steroids and intravenous immunoglobulin. The patient received the above therapy for approximately 6 weeks. Involved field radiotherapy to the left inguinal region was also administered in an effort to reduce the extent of left lower limb oedema and provide symptomatic relief.
There was some transient improvement in his neutrophil and red cell counts; however, he continued to be refractory to platelet transfusion. The symptoms in the left lower limb continued to progress with increasing oedema, despite involved field radiotherapy to the left inguinal region. As the symptoms continued to worsen despite treatment, it was decided to opt for palliation thereafter. Because of metastatic MCC and associated poor prognosis, it was decided not to commence the treatment for hairy cell leukemia.
The patient passed away after 8 weeks of palliation as a consequence of worsening cytopenias and systemic bacterial infection.
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pmc-6261242-1
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An 80-year-old man of Caucasian origin diagnosed with late-onset plaque psoriasis was referred to our Department for a “second-opinion” evaluation and eventually administration of systemic treatment. All lesions appeared at least 2 years before the dermatologic assessment at our department. The patient had received topical therapy with fixed combination of calcipotriol/betamethasone once daily for 3 months and subsequently with clobetasol for around 4 months once daily without any response. The family history of the patient was negative for psoriasis or other chronic skin diseases. Our patient had no previous dermatologic history and was medicating for hypertension, GERD, and hyperlipidemia.
The clinical examination revealed well-demarcated erythematosquamous plaques with irregular shapes on the upper and the low extremities of the patient (Figures and ). The clinical differential diagnosis included psoriasis, lupus erythematosus, tinea incognita, mycosis fungoides as well as leprae, leishmaniasis, sarcoidosis, and tuberculosis.
The dermatoscopic evaluation of the lesions revealed yellow-orange clods and focused, fine horizontal telangiectasias (Figures and ). These findings are repetitively reported as suggestive for granulomatous skin diseases such as sarcoidosis, tuberculosis, and granuloma annulare. The correlation of the clinical and dermatoscopic features of the lesion suggested a diagnosis of a granulomatous disease such as cutaneous tuberculosis or sarcoidosis.
Biopsy of a representative lesion was performed and the histological examination revealed the presence of tuberculoid granulomas accompanied by caseation necrosis. The tuberculin skin test was found positive. PCR for M. Tuberculosis DNA done on a tissue sample was positive. The clinical, dermatoscopic, and microscopic features were consistent with the diagnosis of lupus vulgaris. The screening for an extracutaneous focus of TB was negative. Our patient was treated with a 2-month course of isoniazide 5 mg/kg/d, rifampicin 10 mg/kg/d, pyrazinamide 35 mg/kg/d, and ethambutol 20 mg/d followed by rifampicin and isoniazid for a further 4 months. Complete resolution of the rash with minimal residual scarring was observed in follow-up examination at the end of the treatment.
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pmc-6261391-1
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A 65-year-old, left hand-dominant female with no significant past medical history presented to her primary care physician with acute onset of progressive left wrist pain, erythema, and swelling of a five-day duration. The patient denied any history of recent trauma. She was diagnosed with cellulitis and was given ceftriaxone 1000 mg intramuscular injection in the clinic followed by cephalexin 500 mg to take orally four times a day as an outpatient. However, her aforementioned symptoms did not improve with prescribed antimicrobial therapy. As such, she was subsequently referred to the rheumatology department two days later for further evaluation and management.
The patient was afebrile with stable vital signs. Her white blood cell count and inflammatory markers were also within the normal limits. On physical examination, the patient had tenderness, edema, erythema, and warmth over the ulnar aspect of the left volar wrist. The pain was aggravated by ulnar deviation and flexion of the wrist joint. Plain radiographs of the left wrist revealed a 1.3 × 0.7 cm area of calcific deposit about the volar aspect of the pisiform bone (). Upon further questioning, specifically about repetitive activities, she endorsed typing on the keyboard all day at work and having cleaned horse stalls over the weekend prior to the onset of her symptoms.
Although her clinical presentation was initially concerning for an infectious etiology, taking a thorough history, performing a comprehensive physical examination and a careful review of the radiographs confirmed the diagnosis of acute calcific tendonitis of the flexor carpi ulnaris. As such, her ongoing antibiotic treatment was discontinued. Instead, she was prescribed nonsteroidal anti-inflammatory drugs (NSAIDs) and a wrist splint for immobilization. Her symptoms subsequently improved significantly within 48 hours and she was symptom-free at 2-week follow-up visit.
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pmc-6261403-1
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A 78-year-old woman was referred for anemia investigation. She had a medical history of idiopathic normal pressure hydrocephalus (iNPH) and required LP shunt insertion. The patient underwent LP shunt insertion in 2016; however, the type of LP shunt tube used was unknown. Abdominal computed tomography (CT) showed a tumor in the ascending colon. Colonoscopy revealed cancer of the ascending colon with constriction. Regional lymph node metastasis was suspected, but there were no findings of distant metastasis. CT revealed that the LP shunt was routed from the subarachnoid space at the level of fourth and fifth lumber spine through the subcutaneous tissue of the left back and left flank and into the abdominal cavity (). Although there was a certain risk of causing LP shunt-related complications during the perioperative period, her colorectal cancer was progressing, due to which we recommended a surgery.
During the perioperative period, no procedures, such as externalizing and clamping the shunt tube, were performed. Under general anesthesia, the patient was placed in the supine position. The first trocar was inserted through the umbilicus. After peritoneal insufflation using carbon dioxide, trocars were inserted, avoiding the left abdomen (). Pneumoperitoneum was maintained at a pressure of 10 mmHg. The position of the shunt tube was confirmed in the abdominal cavity, and surgery was performed without any interference (). Laparoscopically, lymph node dissection and mobilization were performed. Furthermore, minilaparotomy was performed to connect the incision of the upper abdomen to the umbilicus, and right hemicolectomy was performed with extracorporeal, ileocolonic anastomosis using a linear stapler. After the anastomosis, the abdominal cavity was cleaned with 2 L saline, and the wound was closed. No drain was inserted.
The patient's postoperative course was uneventful, with no shunt-related complications or neurological deficit. She underwent postoperative rehabilitation and was discharged 1 month postoperatively.
The patient's pathological diagnosis was primary double adenocarcinoma of the ascending colon, T4a, N0, M0, stage II and T2, N0, M0, stage I. Considering her performance status, she did not receive any adjuvant chemotherapy postoperatively. She remains well, with no findings of recurrence at 6 months postoperatively.
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pmc-6261630-1
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Case 1: A 35 year old male presented with a complaint of sharp pain in the right eye the previous night lasting few minutes with associated itching and photophobia. There was no previous history of similar complaints. The left eye was normal. Ocular examination revealed; unaided visual acuity of 6/5 both eyes, palpebral conjunctival papillae and mild bulbar conjunctival hyperemia in both eyes. He received topical Olopatadine (a prescription eye drop with mast cell stabilizing and antihistamine effect) for treatment of the presumed ocular allergic condition.
He returned 3 days later with a complaint of a worm moving in the right eye the previous morning. There was no ocular pain or itching and no generalized pruritus, skin rashes, swelling or joint aches. His vision remained unchanged in both eyes, with obvious right eyelid swelling.
He had hematological and dermatological investigations, which include; Full Blood Count, peripheral blood film and skin snip test for microfilaria. Results came out as normal, with no eosinophilia noted. However, upon repeat slit lamp examination of the right eye a mobile worm was noticed in the nasal sub conjunctival space "". Dilated funduscopy showed cup-to-disc ratio (CDR) 0.3 pink, normal macula, vessels and flat retinae. Systemic examination was normal, no evidence of cutaneous lesions, subcutaneous swellings or nodules. Upon further questioning he gave a history of having worked in swampy rural community farmlands as a child.
He was taken to the operating room the same day and with a retrobulbar anesthesia, a small conjunctival incision was made inferonasally adjacent to the worm. A white colored live worm was grasped with toothless forceps and extracted carefully, intact. Topical antibiotic and steroid preparations were given post surgery. Oral Albendazole was given as therapy targeting any remaining adult worms, and oral Ivermectin targeting microfilaria. Microscopic evaluation of the specimen done at the histopathology laboratory revealed a 7 cm adult male Loa loa worm "Figs and ".
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pmc-6261630-2
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Case 2: A 23 year old male, presented with symptoms of crawling sensation and foreign body sensation in his right eye, and had observed a worm in this eye. He had no previous symptoms prior to his presentation. He gave a history of having worked in a cocoa farm plantation during his childhood years and had severally suffered from bites from unknown flies. He had no systemic symptoms nor signs and aside from his ocular complains was healthy. There was no swelling anywhere in the body and no itching. Upon ocular examination his visual acuity was 6/6 in both eyes. The only significant finding was the presence of an actively mobile worm in the nasal subconjunctival space of the right eye "". This worm soon migrated upwards towards the superior fornix and away from view during the examination and before removal could be attempted "". The patient was immediately asked to adopt a face down position and within 30minutes of this time; he could feel a crawling sensation again in the same eye indicating that the worm was back. He was quickly taken to the operating room and the worm was extracted successfully using a local infiltration of the conjunctiva with lignocaine anesthesia. Histological examination revealed it to be an adult Loa loa worm.
Cases 3: A 25 year old female who had suffered sensation of movement and foreign body sensation in both eyes for the past 10 years and gave a past history of swimming in rural streams during childhood years. There was no history of swelling on the body and no itching. She had noticed an increasingly frequent occurrence of a worm like movement in both eyes over these years. Following ingestion of diethyl carbamazepine she noticed a sudden appearance of a red patch in the right eye. Upon examination her visual acuity was 6/5 in both eyes. The only significant finding was a localized hyperemic raised lesion on the surface of the right eye. This turned out to be a subconjuctival worm in the inferotemporal subconjunctival space of the right eye. The worm was found to be lifeless and covered by a surrounding cyst wall "". Care was taken to dissect the conjunctival and subtenons tissue away from the encysted worm, which was carefully extracted with a toothless forceps. Conjunctival incision site was closed with interrupted sutures. Histology revealed an adult Loa loa worm.
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pmc-6261630-3
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Case 4: A 30 year old female who presented with symptoms of redness in the right eye and seeing a worm moving in the left eye. She also gave a history of exposure to rural streams in childhood. On ocular examination, visual acuity was 6/5 in both eyes. She had a temporal subconjunctival hemorrhage as the only ocular finding. The left eye worm she had seen earlier was no longer present. She was reassured and informed to return to the clinic upon seeing the worm again. She re-presented eleven months later upon seeing the worm again, with symptoms of left eye recurrent redness and feeling of something moving in the eye. This was associated with generalized body itching worse at night times. Ocular examination revealed a mobile worm in the temporal subconjunctival area of this eye. The worm soon migrated to the superior bulbar conjunctiva "".
Through a conjunctival incision the life worm was extracted using a forceps and the wound was repaired. Histology confirmed an adult Loa loa. Blood work up including investigations for microfilaria was negative; but there was a positive eosinophilia of 44.4%. She was treated with oral Albendazole.
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pmc-6261832-1
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A 35-year-old woman was treated for severe asthma with high-dose inhaled corticosteroid and long-acting beta-2 agonist, along with omalizumab. However, she continued to experience frequent asthma exacerbations despite regular systemic steroid use. Her asthmatic symptoms started when she was 2 years old. She required hospitalization several times a year during childhood and in her 20s because of asthma exacerbation, and then, she started taking omalizumab. Because of poorly controlled symptoms despite maximal pharmacological treatment, she was admitted to our hospital for BT. Her chest exam demonstrated wheeze only during forced expiration but no crackles. No other abnormalities were observed by physical examination. She is allergic to cedar pollen and has allergic rhinitis.
Blood testing showed IgE of 109 U/mL, Aspergillus-specific IgE was 20.9 UA/mL, and the white blood cell count was 7790/μL, including 2570/μL of lymphocyte without any eosinophils; at this time, she was taking 4 mg of prednisolone and omalizumab. She took 32 mg/day of methylprednisolone from three days before to the next day of the BT procedure. Her lymphocyte count dropped to 426/μL the day before the procedure.
Chest computed tomography (CT) at the expiratory phase showed scattered areas of air trapping, but there was no thickening or dilatation of the bronchial walls or mucus plugging. Sinus CT demonstrated no evidence of chronic sinusitis (data not shown). The first BT procedure was completed properly. The bronchial epithelium was oedematous and easy to bleed, but there were no ulcers or purulent mucus (Fig. A). The total number of activations on the right lower bronchi was 81. No abnormal pathogens were cultured from the bronchial mucus.
The second BT procedure was conducted after one month. White ulcerous lesions were found on the right B9 bronchus, where the first BT procedure was performed (Fig. B). Aspergillus fumigatus with neutrophilic, and eosinophilic bronchial inflammation was detected from the bronchial brushing at the right B9 bronchus (Fig. D). Therefore, she was given voriconazole for seven months for the treatment of bronchial aspergillosis. Three months after the second BT procedure, a third BT procedure was performed (Fig. C); culture of endobronchial mucus at this time demonstrated Nocardia spp., for which she was prescribed trimethoprim-sulfamethoxazole for three months.
Chest CT at one month after the third BT procedure showed partial consolidation around the right B9 bronchus at the location of the endobronchial aspergillosis (Fig. B). Seven months after the last BT procedure, CT showed resolution of the right B9 occlusion, but there was a new consolidation around the right B8 bronchus (Fig. C). Pathological examination of the transbronchial biopsy from this lesion showed obstructive bronchiolitis with eosinophilic infiltration, without abnormal pathogen on culture. This consolidation resolved one year after the last BT (Fig. D).
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pmc-6261833-1
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A 67-year-old male was referred to our hospital in the summer of 2016 in order to control his ascites and leg oedema. He was diagnosed with thymoma in 1992, for which he had an extended thymectomy and received radiotherapy. Until our referral, he had two recurrent episodes. The first one was in 1996. He had an operation for a relapsed tumour and received chemotherapy. The second one was in 2004. He had an extensive operation for a widespread metastasis, but the operation was not able to remove the tumour completely. After the second recurrent episode, he received neither chemotherapy nor radiotherapy. Computed tomography (CT) scan at our referral showed left peritoneal mass, peritoneal dissemination with massive ascites, and multiple bone metastases (Fig. ). At this time, a small amount of pleural effusion was present (Fig. ). He was diagnosed with a recurrent type B1 thymoma from a biopsy of the left peritoneal mass.
In September 2016, as a first-line therapy, the patient was administered carboplatin (AUC 6) on day 1 and paclitaxel (200 mg/m2) on day 1 for a 3-week cycle. On day 6, due to hypo-gammaglobulinemia, he developed severe pneumonia with febrile neutropenia. He recovered following the administration of antibiotics. In October 2016, a second-line therapy of everolimus was prescribed at a dose of 5 mg per day, with a reduction to every other day after 15 days due to the development of thrombocytopenia. As right pleural effusion and ascites continued to increase, everolimus was stopped after 1 month.
In December 2016, paclitaxel (80 mg/m2) was administered every 3–4 weeks as a third-line therapy. During treatment, the patient’s abdomen gradually became enlarged, and right pleural effusion was increased. After four cycles, thoracentesis was performed, resulting in the removal of 800 mL of fluid. Seventy minutes into of the thoracentesis, the patient presented with acute dyspnoea. He required 7 L of oxygen using a non-rebreathing mask with a reservoir bag to maintain >90% of SpO2. Chest X-ray showed nearly opacified right hemithorax, and CT scan demonstrated massive pleural effusion (Fig. ). Immediate tube thoracostomy yielded 10 L of sanguineous fluid. As fluid was removed, the distended abdomen became flat, and dyspnoea was improved. From the next day onwards, fluid in the chest tube decreased but did not stop. OK-432 (picibanil, Chugai Pharmaceutical Co., Tokyo, Japan) is an immuno-stimulant obtained from Streptococcus pyogenes, which is widely used in Japan for chemical pleurodesis. While pleurodesis with OK-432 was attempted, it was not effective in stopping fluid from the chest tube. His general condition gradually deteriorated, and he passed away 12 days later. Autopsy examination showed one hole (1 mm diameter) on the right diaphragm, which did not match the position by thoracentesis (Fig. ). In addition, there were no metastases at the hole, while there were several metastases on the diaphragm (Fig. ).
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pmc-6261927-1
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A 65-year-old man with ischaemic stroke, hypertension, and end-stage renal failure on regular haemodialysis presented with a two-week history of shortness of breath and non-productive cough. There was no history of fever, heart failure symptoms, or constitutional symptoms, and he had no limitations of his daily activities. He was compliant with fluid restrictions and achieved his target dry weight. He worked as a surveyor in a lead factory for 20 years and was a lifelong non-smoker with no known exposure to asbestos.
Clinical examination demonstrated stony dullness and reduced breath sounds over the right lower hemithorax. He had an elevated white cell count of 20 × 109/L and C-reactive protein (CRP) of 10 mg/dL. Chest X-ray (CXR) showed pleural effusion involving 25% of the right hemithorax. A diagnostic thoracentesis drained 1.5 L of exudative straw-coloured fluid (pleural to serum protein ratio: 0.88, pleural to serum lactate dehydrogenase (LDH) ratio: 0.75). Gram-positive cocci were detected in pleural fluid; however, the culture was negative. He was treated for a parapneumonic effusion with two weeks of antibiotics and was subsequently lost to follow-up.
He represented seven months later with a massive pleural effusion on the same side. A repeat thoracentesis was once again exudative (pleural to serum protein ratio: 0.68, pleural to serum LDH ratio: 0.85) with pleural pH of 8. Pleural fluid acid-fast bacilli culture and sensitivity were negative. There were no malignant cells, and the cytospinned showed few lymphocytes admixed with neutrophils and macrophages. He was initially started on empirical broad-spectrum antibiotics. We proceeded with a pleuroscopic examination (Fig. A and B), which demonstrated diffuse areas of hyperpigmentation at both parietal and visceral pleura. Histopathological examination of the parietal pleura (Fig. C) showed foreign body-type granuloma with multinucleated giant cell. There was no evidence of fungal bodies and acid-fast bacilli but evidence of malignancy. This was further supported by the findings from contrast-enhanced computed tomography (CECT) of thorax (Fig. ) performed two weeks later, which showed the presence of heterogeneously enhancing focal pleural plaque with foci calcification at the medio-posterior aspect of the right lower lobe. Immunoglobulin levels and N-terminal pro-brain natriuretic peptide (NT-proBNP) were not sent as they were not available in our centre.
He completed 14 days of antibiotics, and he was discharged well. A repeat chest radiograph a month later showed minimal pleural effusion. Bronchoscopy was not offered in view that repeated chest radiograph did not show any evidence of atelectasis as sequelae of anthracosis of the lung. He was given further follow-up to monitor his progress.
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pmc-6261928-1
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A 45-year-old lady was admitted with acute pleuritic chest pain, haemoptysis, and dyspnoea. Her background was significant for a 1.4 cm left renal angiomyolipoma, myofascial pain syndrome, and depression. Regular medications included a combination umeclidinium and vilanterol inhaler and escitalopram. She was an ex-smoker, with a 5 pack-year history, and denied any relevant family history or occupational exposures. A computed tomography (CT) pulmonary angiogram was performed on admission. This was negative for a pulmonary embolism but demonstrated diffuse, well-circumscribed cystic change throughout both lungs, with no zonal predominance. Small foci of ground-glass change were noted to be interspersed between the cysts. There were no associated parenchymal nodules or lymphadenopathy (Fig. ). She was treated for a lower respiratory tract infection and subsequently referred to a tertiary centre for further assessment.
On review, she reported modified medical research council (mMRC) grade 2 dyspnoea at baseline. A bronchoscopy demonstrated a normal tracheobronchial tree, and a bronchoalevolar lavage was auramine stain and tuberculosis culture negative. Autoimmune serology was also unremarkable. Pulmonary function tests demonstrated forced expiratory volume in 1 second (FEV1) of 1.79 L (62%), forced vital capacity (FVC) of 2.33 L (70%), a positive bronchodilator response of 390 mL (23%), and a normal DLCO. A diagnosis of tuberous sclerosis-associated LAM was subsequently suspected based on a history of a renal angiomyolipoma and the presence of cortical tubers on a screening magnetic resonance imaging (MRI) brain, and a lung biopsy was requested for confirmation. This initially demonstrated predominantly non-caseating granulomas. She was also subsequently found to have an elevated serum ACE of 68 U/L (reference range 0–45 U/L). A diagnosis of pulmonary sarcoidosis was made. Further biopsy sectioning demonstrated focal areas of positive HMB-45 staining, confirming LAM (Fig. ). A diagnosis of cystic lung disease secondary to coexistent sarcoidosis and LAM was established.
Our patient was switched to an inhaled corticosteroid and long-acting beta agonist given reversibility on spirometric testing and is monitored closely in the respiratory outpatient department. At present, she is not prescribed targeted therapy for sarcoidosis or LAM and remains clinically stable from a respiratory perspective.
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pmc-6262114-1
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A 30-year-old woman who spent her childhood summers in northern Iran raising sheep was hospitalized with hemoptysis. Initial chest computed tomography (CT) revealed a right lower lobe cyst, 9 by 11 cm. Several days after admission, she developed respiratory distress with hypoxia. Repeat CT scan demonstrated air within the pulmonary cyst with a floating wavy membrane at the air-fluid level, indicative of the sign of the camalote (). She underwent urgent lobectomy. Upon intubation, clear cystic fluid was suctioned from the endotracheal tube. Her right lower lobe contained a large ruptured cyst (). Histopathology demonstrated echinococcal scolices (). Her preoperative ecchinococcal enzyme-linked immunosorbent IgG antibody assay tested negative; it was positive postoperatively (7.15 IV, Arup Laboratories). She recovered fully and completed a 4-week course of albendazole.
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pmc-6262175-1
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We describe the case of a 22 year-old woman (II2), known to be affected by PRS. She is the second-born of a mother who had had three term pregnancies (Figure ). The two brothers are in good health, without signs of congenital abnormalities. The pregnancy was 38 weeks. After a natural childbirth, she weighed 2.1 kg and showed neonatal respiratory distress syndrome. She displayed a typical PRS (micrognathia, glossoptosis, cleft palate) and triphalangeal thumbs. She was also diagnosed with a congenital perimebranous ventricular defect, without haemodynamic effects.
On follow-up examinations, a neurodevelopmental delay was observed: she gained head control at 4–5 months, the ability to sit and to stand unassisted, respectively, at 11 months and at 13 months, and learned to walk, precariously, at 20 months. By this time, she gained a poor verbal language.
In her first months of life, she was hospitalized for the management of her congenital abnormalities; therefore, she was diagnosed with an inherited hyporigenerative anemia that required regular blood transfusion therapy throughout her life. She is currently transfused with four units of packed red blood cells per month.
Genetic characterization of the congenital anemia by multiplex ligation-dependent probe amplification (MLPA) assay led to the discovery of a de novo chromosomal deletion involving RPS26 (data not shown), allowing diagnosis of DBA (Doherty et al., ; Quarello et al., ).
The clinical examination on admission to our institute, when she was 21 years old, showed a peculiar face, skeletal abnormalities in a complex malformation syndrome and a mental deficiency. Dysmorphic facial features included, beside PRS, prominent nose bridge, low-set ears, bilateral external auditory meatus abnormalities, ocular asymmetry with buphthalmos, intermittent exotropia with left eye dominance, severe myopia, tooth decay and cavities. In addition, skeletal malformations consisted mainly of short stature, right-convex thoracic scoliosis with dorsal hump, hip dysmetria with heterometry of lower limbs, shortness and clinodactyly of fingers with hypoplasia of the distal phalanges of 1th fingers, cutis laxa with characteristic wrinkled palms and soles and multiple skin nevi. She also had several endocrinological alterations as primary amenorrhea, mild hyper-prolactinaemia and moderate familiar hyper-cholesterolaemia.
She showed trigeminal nerve palsy, bilateral mixed hearing loss, rhinolalia, dysarthria and acquired dysphagia for solid foods. She suffers by severe neck pain. Functional limitations in shoulder abduction were detected with lower limbs antigravity muscle weakness and decreased functional ability. Reflexes were normal, except for a bilateral indifferent plantar response.
She was properly informed about all the procedures and about the intent of anonymously publishing the data obtained; to confirm her acceptance, she signed informed consent forms agreeing to the procedures and to publication.
The complex physical malformations required a neuro-radiological evaluation with Computed tomography (CT) study of the temporal bone, cranio-cervical junction (CCJ) and cervical spine.
Brain and spine Magnetic Resonance Imaging (MRI) studies were performed to evaluate neuro-radiological anomalies.
CCJ study focused on bone malformations, showing atlanto-occipital assimilation (AOA) caused by a complete fusion of the C1 anterior arch and lateral masses and by partial fusion of the posterior arch to the foramen magnum. Arcuate foramen was also observed on the left side (Figure ). The atlanto-dental interval (AADI: distance, on the sagittal plane, between the anterior assimilated C1 arch and the odontoid process) (Zong et al., ) appeared increased (10 mm) suggesting an atlanto-axial instability (AAI) (Figure ), defined for atlanto-dental interval >3 mm (Gamble and Rinsky, ; Ferreira and Botelho, ).
The odontoid process was smaller (Figure ) than normal average (Zong et al., ). Sites of embryogenesis for the atlas' anterior arch and the atlantoaxial ligaments system are the same, so that the assimilation of the anterior arch of the atlas is often associated with AAI (Ferreira and Botelho, ). Very few authors already reported, as in this case, the association between PRS and AAI (Gamble and Rinsky, ; Molnar et al., ) due to AOA. The patient is affected as well by a right occipito-condylar hyperplasia, producing narrowing and malformation of both the foramen magnum and the upper cervical spine canal (Figure ). This hyperplasia causes the compression and displacement of the right side of the bulbo-medullary junction (Figure ). Basilar invagination (radiologically defined when the tip of the odontoid is located above the Chamberlin line) (Molnar et al., ) and platybasia (flattening of the skull base) were ruled out on both CT and MRI (Kisker et al., ; Zong et al., ).
Temporal bone CT study showed right hypoplasia and anomalous course of the external auditory channels, absence of pneumatization at the right mastoid, a chronic right ear otitis media, widening of the third part of the ipsilateral facial nerve bone canal, partial calcification of the left tympanic membrane and ossicular chain ankyloses (Figure ).
Whole spinal cord MRI study added further information, showing not only rotoscoliosis, but also cervical (C2 – C3, C4 – C5) and lumbar (L4 – L5) vertebral fusion and bilateral L5 sacralisation (Figure ). The spine malformations led to a diagnosis of KFS type II (Samartzis et al., ), without malformations neither of the meninges nor of the nervous system.
Dysmorphic features and malformations observed in the patient suggested to further investigate the initially identified genomic deletion affecting RPS26. We then carried out array-CGH analysis in the proband and her parents, confirming the presence of a wider de novo heterozygous microdeletion on chromosome 12q13.2-q13.3 (Figure ). By Real-Time PCR, we further refined 5' and 3' breakpoint boundaries of the deletion, resulting in a minimal critical region of about 500 Kb in size (Figure and Table ). The microdeletion encompassed at least 26 coding genes (Table ) and expression profiling by Taqman assay confirmed about 50% reduction of the expression for many of these genes (Table ; data not shown). Some of them, in particular SARNP, DNAJC14, ORMDL2, DNAJC14, ANKRD52, COQ10A and CS, although heterozygously deleted, were not tested for expression (Table ). At least three genes (MMP19, RPS26 and SLC39A5) already cause autosomal dominant diseases, while further 12 genes may be sensitive to haploinsufficiency, as they showed a pLI > 0.75 (Table ). In addition, no similar deletions were annotated in Decipher (decipher.sanger.ac.uk) or have been previously described in literature.
The index patient shows features at the boundaries of the three reported syndromes.
The hypoplastic mandible, the glossoptosis and the U-shaped cleft palate are strictly related to PRS and contribute to airway obstruction (Butow et al., ; Cielo and Marcus, ) as found in the described patient. In PRS, there is a 10.5% incidence rate of ear malformations (Breugem et al., ), which consist of multiple architectural anomalies involving the entire ear, including abnormal auricles, anomalies of the ossicular chain, abnormal stapes footplates and middle ear infection. Middle ear disturbances, as in the index case, are common and are mostly related to the cleft palate and associated to the Eustachian tube dysfunction (Sando et al., ; Yamaguchi et al., ; Robinson et al., ; Gruen et al., ). Chronic mucotympanum, chronic middle ear otitis, tympanic membrane retraction pockets and choleastotomas are the most frequent issues related to the middle ear (Gruen et al., ). Other anomalies include abnormal course of the facial nerve, as in the described case (Gruen et al., ; Rotondo et al., ), abnormal insertion of the tensor tympani tendon, ankylosis of the ossicules, and anomalous stapedial footplates, most of which can be related to anomalies of the branchial arches.
Typical elements of KFS are, instead, vertebral fusions, short and webbed neck, decreased range of motion in the cervical spine, deformed chest wall, high placed scapulae, abnormal curvature of the spine (scoliosis), raised scapula (Sprengel's scapula), rib defects, low hair line. The index case shows KF deformity with multiple fusions of non-contiguous cervical and lumbar vertebrae corresponded to type II of KFS, described by Samartzis et al. (Samartzis et al., ).
Radiological evaluation pointed out diffuse and severe CCJ bone malformations.
PRS and KFS could both display failure of segmentation between the fourth occipital sclerotome and the first cervical sclerotome resulting in AOA (Menezes and Vogel, ; Smoker and Khanna, ). The displacement of the assimilated atlas and the right occipito-condylar hyperplasia resulted, instead, in a narrowed foramen magnum, which was responsible for both severe compression of the underlying bulbo-medullary junction and AAI (Gamble and Rinsky, ; Yamaguchi et al., ; Molnar et al., ; Rotondo et al., ; Ferreira and Botelho, ; Zong et al., ). The described Occipito-condylar hyperplasia is an extremely rare congenital entity and only 3 other cases were previously described (Smoker and Khanna, ; Rojas et al., ; Lofrese et al., ). This bone malformation may be due to the excessive growth of the proatlas during the embryogenesis (Smoker and Khanna, ; Rojas et al., ; Lofrese et al., ). Upon birth, the displaced AOA and the overall shift in the head's balance could cause progressive growing of osteophytes, gradually constrain the bulb and the spinal cord. Therefore, neurological decline may occur due to the progressive degenerative ossification (Rojas et al., ; Lofrese et al., ; Shih et al., ). The ossification on the ligamentous interface and ligamentous holding forces may also increase axial instability (Gamble and Rinsky, ; Yamaguchi et al., ; Molnar et al., ; Rotondo et al., ; Ferreira and Botelho, ; Zong et al., ).
The patient's CCJ imbalance (due to skull-cervical spine malformation), coupled with the lack of stable articular joints, exposes her to a high risk of sudden neurological manifestations. It has been shown that common pathways exist between the neural cresta and the paraxial mesoderm embryogenesis during CCJ development (Menezes and Vogel, ).
Among genes deleted in the index case, three of them are involved in ribosomal biogenesis (RPS26, PA2G4, RPL41). Ribosomes catalyze for protein synthesis and their function impairment have been extensively involved in DBA pathogenesis. The deletion of this gene cluster could aggravate hematological features linked to DBA. Other genes in the deleted region are related to different pathways.
MMP19 is a gene related to autosomal dominant inherited congenital cavitary optic disc anomalies (Moore et al., ), encoding for a zinc-binding endopeptidases that degrades several components of the extracellular matrix. Zinc is an essential cofactor for hundreds of enzymes, thus being fundamental for hundreds of functions.
The identified deletion also included SLC39A5 that encodes for a protein showing structural characteristics of zinc transporters and it has been linked with an autosomal dominant severe form of myopia (Guo et al., ), as in the described patient.
Other genes involved in the deletion where expected to be extremely intolerant to Loss of Function (LoF) because of their pLI.
SAP domain containing ribonucleoprotein (SARNP) has a putative role in cell cycle progression acting as a single-stranded DNA binding protein (Fukuda et al., ).
DNAJC14 (DnaJ Heat Shock Protein Family (Hsp40) Member C14) regulates target proteins' export from the endoplasmic reticulum to the cell surface and it seems to be involved in protection from flavivirus infections (Yi et al., ). The exon junction complex (EJC) serves as a positional landmark for the intron exon structure of genes; the index patient has a deletion of PYM1, a key member of this complex, actin as a disassembly factor; it also associates with the 40S ribosomal subunit (Gehring et al., ). DGKA, instead, encodes for a Diacylglycerol kinase, ultimately removing it; it plays a role in intracellular signaling and phospholipid synthesis. Cell cycle control has been vaguely related to developmental syndromes (Tessadori et al., ). The index patient has an allelic deletion for CDK2, a key cell cycle related serine/threonine protein kinase. IKZF4 encodes a zinc-finger transcription factor required during early B cell development. The protein encoded by SMARCC2 displays helicase and ATPase activities, whose enzymatic disruption often leads to development disorders. Type 1 cytokine receptor signalling impairment has been, instead, linked previously to congenital Immunodeficiency, although their functions are redundant; NABP2 encodes for a Single-stranded DNA-binding protein, usually necessary for several DNA-related metabolic processes.
Ankyrin repeat domain 52 (ANKRD52) is a protein acting as a regulatory subunit of protein phosphatase 6 (PP6), involved in the recognition of phosphoprotein substrates (Watanabe et al., ). Citrate synthase is, instead, a protein codified by CS, acting as a Krebs tricarboxylic acid cycle enzyme catalazying the synthesis of citrate from oxaloacetate and acetyl coenzyme A (Hayward and Berendsen, ).
New studies focused on the role played by these genes, in developmental control and their regulatory functions and accurate craniometrical studies of CVJ anomalies, may offer early diagnosis, new therapeutic targets and specific treatment before neurological damage occurs.
This case-report points out that DBA, and mostly PRS and KF have a further genetic heterogeneity and it underlines the need for a careful genetic evaluation and a detailed phenotype-genotype correlation in each complex malformative syndrome.
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pmc-6262278-1
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A 62-year-old man weighing 76 kg experienced melena for two days. He also had alcoholic liver cirrhosis complicated by hepatocellular carcinoma (HCC) (T2N0M0, Barcelona-Clinic Liver Cancer stage A) and he had undergone transcatheter arterial embolization (TAE) and laparoscopic radiofrequency ablation. He also had esophageal varices and gastric varices, and received endoscopic variceal band ligation due to bleeding esophageal variceal bleeding. He smoked 20 cigarettes per day and drank an average of 100 g alcohol daily for about 40 years without quitting. On admission, his blood pressure was 116/74 mmHg, pulse rate was 80 beats/min, respiratory rate was 20 breaths/min, and body temperature was 35.9 °C. The hemoglobin level decreased to 8.3 g/dL (baseline hemoglobin level: 9.2 g/dL). Abdominal computed tomography (CT) showed cirrhosis and recurrent HCC in S4, S6, and S7 with thrombosis in the right posterior branch of the portal vein.
He was transferred to the intensive care unit for hemorrhagic shock. Both emergent esophagogastrodudenoscopy (EGD) and colonoscopy failed to reveal the source of hemorrhage. Under the impression of massive obscure gastrointestinal bleeding and suspicion of small bowel bleeding, we decided to perform anterograde SBE (Olympus Medical systems, Tokyo, Japan). In the proximal jejunum, a large amount of fresh blood and 1 engorged cystic lesion with persistent bleeding from the central depression were observed (). A soft sensation (not induration) was felt through the biopsy forceps, and ectopic jejunal varices were initially diagnosed. A 3.5 mL glue mixture (3.0 mL of cyanoacrylate and 0.5 mL of lipiodol) was injected into the varix. Because of persistent bleeding (), a second attempt of sclerotherapy with 2.0 mL of cyanoacrylate was performed. The sclerosant filled the varices and bleeding ceased ().
Four days later, abdominal contrast-enhanced CT confirmed the deposition of dense lipiodol in the proximal jejunum (). Melena stopped after the procedures were completed, and no sclerotherapy-related complications occurred. The patient was discharged on admission day 15 uneventfully. He eventually died of underlying liver disease six months later without any bleeding diathesis.
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pmc-6262380-1
|
A 35-year-old woman, with no particular predisposing risk factors, consulted for a progressive motor deficit with loss of balance. Her past medical history revealed the presence of dysesthesias of the lower limbs with wet foot sensation and heat in the thighs since January 2017. These dysaesthesias progressively worsened over six months until the loss of balance and the appearance of a motor deficit leading to falls. At admission (24 May 2017), the clinical examination showed a motor deficit of the right foot elevator muscle and a sensory disturbance of the lower limbs. The biological investigations reported an inflammatory syndrome with thrombocytosis and inflammatory anemia without hyper-eosinophilia.
The magnetic resonance imaging (MRI) and the computed tomography scan (CT scan) revealed a spinal lesion of the ninth dorsal vertebra (). The lesion was an encapsulated multi-compartmented cyst of about 15 mm height involved in medullary compression, suggesting at first an aneurysmal bone cyst associated with shrinkage of the medullary canal and compression of the spinal cord. A posterior corporectomy of the ninth dorsal vertebra (T9) with laminectomy and osteosynthesis were performed, associated with a complete exeresis of the lesion, which was composed of fibrous tissue consisting of several rounded cavities developed from the ninth dorsal vertebra, causing spinal cord compression. Multiples biopsies of the lesion were performed for microbiological and histopathological investigations.
Histopathological and parasitological analyses reported fragments of the typical laminated layered structure of a hydatid cyst (A). On the internal surface of the hydatid cyst, the germinative membrane displayed cuboid cells with abundant eosinophilic cytoplasm (A). Inside the cystic structure, protoscoleces were observed with visible hooks (B), and free hooks were also observed (C). Serological investigations were carried out by the French National Reference Center for Echinococcosis (FNRCE), which reported the presence of anti-Echinococcus antibodies (i.e., positive E. granulosus hemagglutination (Fumouze, Levallois, France) at a 1:640 titer and a positive Western blot with a p7 and p26/28 positive band pattern (LDBio Products, Lyon, France)), although these data were not able to differentiate a cystic echinococcosis from an alveolar echinococcosis []. DNA extraction was carried out from a paraffin-embedded T9 biopsy fragment using the QIAamp DNA mini kit (Qiagen, Hilden, Germany) and then sent to the FNRCE for molecular identification of the Echinococcus species involved in the cystic lesion. Specific PCRs targeting the E. multilocularis [] and E. granulosus s.s. [] 12S RNA mitochondrial gene (target sizes of 200 bp and 255 bp, respectively) were negative, while a specific Echinococcus spp. PCR targeting a 350 bp fragment [] of the 12S RNA mitochondrial gene with primers (12S-Echino-Fwd: 5’-AAAKGGTTTGGCAGTGAGYGA-3’; 12S-Echino-Rev: 5’-GCGGTGTGTACCTGAGCTAAAC-3’) designed to amplify all Echinococcus species was positive. DNA sequencing allowed the identification of Echinococcus ortleppi by comparison with the online genetic databases, by using the Basic Local Alignment Search Tool (BLAST) available on the NCBI website. A 100% identity was obtained with the reference sequence KY766908.1 on a 201 bp sequence alignment [].
After surgery, oral albendazole 800 mg/day was initiated for a planned total duration of two years. The thoraco-abdomino-pelvic CT scan reported no arguments for hepatic, pulmonary or visceral echinococcosis. No infectious intercurrent event was observed after surgery and anti-parasitical therapy. Six months later, the clinical evolution was favorable with normal neurological examination. Serologic investigations carried out at the FNRCE reported a significant decrease in hemagglutination antibody titers and a lower intensity profile in Western blot.
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pmc-6262382-1
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The patient was a 9 year old male with a 10-day history of severe headache, vomiting, and numbness in the right arm and foot. Bilateral papilledema was found at the ophthalmic examination. Magnetic resonance imaging (MRI) displayed a mass with homogenous contrast enhancement in the left brain hemisphere and brainstem (). On the operation, a subtotal excision was performed. Histopathological examination of the excisional piece revealed a malignant tumor that had anaplasia, marked cellularity, necrotic areas, and a remarkable neoangiogenesis with proliferation of endothelium of the capillaries. The tumor was histopathologically diagnosed as a glioblastoma multiforme. The subtotal excisional surgery was followed by cranial radiotherapy with a total dose of 60 Gy. Then we applied temozolomide (200 mg/m2/day peroral for 5 days; every 4 weeks for 10 cycles) and bevacizumab (10 mg/kg IV; every 2 weeks for 6 cycles) plus irinotecan (125 mg/m2 IV; every 2 weeks for 6 cycles) as first and second-line treatments. However, in the control magnetic resonance imaging, the tumor showed progression despite these treatments. Therefore, we began to use nivolumab as a third-line treatment.
Nivolumab therapy was started at a dose of 3 mg/kg intravenously every two weeks. Two days after the second dose, the patient was admitted to the hospital with a rapidly progressive decline in visual acuity of the eyes. On ophthalmic examination, the visual acuity of the right eye was counting fingers at 1 m and was very low on his left eye (limited to light perception). At the posterior segment examination, there was an optic disc swelling bilaterally. Other vital findings, such as blood electrolyte levels and neurological examination, were normal. An urgent MRI showed bilateral thickening of the optic nerves suggestive of optic neuritis, with normal intracranial pressure (). Bilateral optic neuritis was diagnosed with the combination of clinical features, ophthalmic examination and radiological findings. Bilateral optic neuritis was diagnosed four days after the progressive decline in visual acuity of the eyes and, first we stopped nivolumab therapy and then the patient began pulse dose steroids; he received intravenous corticosteroids (1 g/day) for 5 days, which resulted in a progressive improvement in visual acuity. After a week, the vision improved to 20/20 in both eyes and he did not need any additional treatment at the next follow-up.
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pmc-6262580-1
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A 55-year-old woman presented to our emergency department because of a four-week history of memory loss, which was of insidious onset and progressive worsening. Her past medical history was relevant for Crohn’s disease and partial colectomy. The latter took place two months prior to presentation and was complicated by peritonitis, which was successfully treated with antibiotics. There was no history of alcohol consumption or vascular risk factors, and no family history of cognitive disturbances.
On examination, she was alert and cooperative, but disoriented to time and place, and unable to recall three objects on a mini-mental status exam. For the latter exam, the score was 18/30 on admission. Other cognitive domains were intact. In addition, cranial nerves as well as motor, sensory, and cerebellar functions were normal. The patient underwent brain MRI imaging which revealed normal T1, T2, and fluid-attenuated inversion recovery (FLAIR) sequences (). However, T1 gadolinium-enhanced sequences demonstrated an isolated enhancement of the mammillary bodies ().
Laboratory tests demonstrated an important decrease of blood thiamine levels (12.7 ng/mL (normal range: 21.3–81.9 ng/mL); obtained on a 2-mL sample of whole blood using High Performance Liquid Chromatography, Eurofins Biomnis, Lyon, France). Therefore, an intravenous thiamine supplementation was started with 1500 mg per day for three days (VITAMINE B1 STEROP solution containing 100 mg/2 mL, STEROP laboratories, Brussels, Belgium). The drug solution was diluted in 50 mL of sodium chloride 0.9 % and administered over 30 min.
The patient showed a partial memory improvement three days later. She was discharged home on oral thiamine therapy for one month (100 mg per os per day). At that time, she completely recovered and regained her normal eating habits (i.e., diet including meat, dairy products, fruits, vegetables, and other sources of carbohydrates).
The local ethics committee approved case publication, and written informed consent was obtained from the patient.
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pmc-6262590-1
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A 55-year-old woman who had a medical history of hypertension treated with a calcium blocker (amlodipine 5 mg/d) and an angiotensin converting enzyme (ACE) inhibitor (perindopril 5 mg/d) was referred to our nephrology department for the investigation of a proteinuria (10 g/day). Physical examination was unremarkable, with a blood pressure of 125/75 mmHg. Laboratory investigations showed a nephrotic syndrome associated with microscopic hematuria at 105/mm3, without renal failure (creatinine level of 80 µmol/L, eGFR (estimated glomerular filtration rate) of 69 mL/min/1.73 m2 according to the MDRD (Modification of Diet in Renal Disease) formula). Serum protein electrophoresis showed low gamma globulin levels of 4 g/L (normal range 8–12 g/L) associated with a monoclonal IgM kappa spike (<1 g/L). Urine protein electrophoresis did not detect Bence Jones proteinuria, and the serum kappa/lambda free light chain ratio assessed by immunonephelometric assays was within the normal range (ratio: 0.7; normal range: 0.7–1.56).
A percutaneous renal biopsy was performed in April 2013 (description of detailed methods in ). The renal biopsy specimen consisted of renal cortex with 14 glomeruli including two obsolescent glomeruli. Other glomeruli exhibited diffuse mesangial expansion and focal thickening of glomerular basement membrane (A). Congo-Red staining was negative and the tubulointerstitial areas showed mild interstitial fibrosis (<10%). Immunofluorescence studies demonstrated intense mesangial and capillary loop smudgy staining for IgG (3+) (B), associated with glomerular deposition of complement component 3 (C3) (3+) (C). Immunofluorescence revealed positive staining for both kappa and lambda light chains. We observed weak capillary wall staining for IgM (D). Analysis of the glomerular IgG subclass distribution demonstrated positive staining for IgG4, and was negative for other IgG subclasses (E). Electron microscopy showed typical features of FGN, i.e., the presence of diffuse mesangial infiltration by randomly oriented fibrils with a diameter of 16 nm (F).
Bone marrow examination revealed no tumoral infiltration and positron emission tomography-computed tomography (PET-CT) did not detect highly hypermetabolic lesions.
Proteinuria decreased from 10 g/day to 7.3 g/day after increasing the dose of ACE inhibitor in April 2013, however proteinuria remained in a nephrotic range and albuminemia levels were unchanged (25 g/L). In July 2013, the patient received two doses of rituximab intravenously (375 mg/m2), separated by one week. Five months after rituximab administration, she achieved partial remission with a decrease of proteinuria levels > 50% (2.5 g/day) (A). However, eight months after the first administration of rituximab, relapse of nephrotic syndrome (proteinuria 12.8 g/day) occurred, which was successfully treated by a single infusion of rituximab (375 mg/m2). Two new relapses of nephrotic syndrome occurred during the follow-up and were each successfully treated by a single infusion of rituximab (administered 15 days and one month, respectively, after confirmation of FGN relapse) (A). Each relapse occurred between seven and eight months after the previous rituximab administration. Renal function was stable (eGFR = 68 mL/min/1.73 m2) at the 36-month follow-up. Strikingly, each relapse occurred in the context of B cell recovery (51, 48, and 38/mm3) (A).
We next analyzed the distribution of circulating B cell subsets at the time of the third relapse (15 months after the last rituximab infusion) by flow cytometry and compared our results to those observed in healthy blood donors (HBD) (description of detailed methods in , ; gating strategy used to study B cell subpopulations are shown in supplementary materials). The CD19+ count was within the normal range (133/mm3), however the distribution of B cell subpopulations was different from that of HBD (B). The proportion of transitional (immature) B cells (CD19+CD24hiCD38hi) was higher in our patient (20.8%) than in HBD (mean ± SEM: 9.7 ± 1.6%). Moreover, the proportion of memory B cells (CD19+CD27+) among CD19+ cells was much lower in our patient (5%) than in HBD (mean ± SEM: 28.3 ± 5%). Among memory CD19+CD27+ B cells, the proportion of switched memory B cells was higher than HBD (C), whereas proportion of plasmablasts (0.6%) was in the same range as HBD (mean ± SEM: 0.42 ± 0.05%).
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pmc-6262624-1
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An 11-year-old, previously healthy boy presented to the emergency department with a 1-week history of dry cough, shortness of breath, and low-grade fever, with no associated symptoms of expectoration, hemoptysis, wheezing, contact with sick people, or recent travel, and no history of weight loss. His past medical history was unremarkable, and he was fully vaccinated in accordance with his age. Physical examination revealed an afebrile child with remarkable tachypnea with moderate respiratory distress, desaturation requiring oxygen, subcostal and intercostal retractions, and decreased air entry bilaterally on lung auscultation without wheeze or crackles. A chest X-ray (CXR) showed bilateral diffuse miliary nodules (). The child required pediatric intensive care unit (PICU) admission for close observation and further management. He was started on IV cefuroxime and oral clarithromycin and Tamiflu as treatment of viral pneumonitis with possible secondary bacterial infection and required a high-flow nasal cannula (HFNC) for oxygen support. Respiratory virus polymerase chain reaction (PCR) showed bocavirus positive, at which point Tamiflu was discontinued. The child remained tachypneic with persistent respiratory distress and continued to require high oxygen therapy. Repetition of his CXR imaging showed persistent diffuse bilateral miliary infiltrations. A CT scan of the chest showed diffusely reticular-nodular opacities in both lungs involving lung bases and the posterior segments of the right and left upper and lower lobes with irregular bronchovascular marking (). Purified protein derivative (PPD) and QuantiFERON-Gold showed negative results. The child showed improvement of his symptoms on day 10 of his hospital admission and was able to be weaned off oxygen support, and he was discharged in a stable general condition with a mild dry cough.
A few days after discharge, the child presented again to the emergency department with a worsening cough and progressive shortness of breath, also with physical findings of hypoxia and respiratory distress, and he required admission to our tertiary hospital. His physical examination revealed an afebrile child with tachypnea and hypoxia requiring 2 L of oxygen via nasal cannula, grade 1 digital clubbing, mild respiratory distress with nasal flaring, and decreased air entry bilaterally on lung auscultation without wheezing or crackles. His arterial blood gas showed a PH of 7.39, a PCO2 of 45 mmHg, a PO2 of 60 mmHg, and a BE of 2 and he was unable to perform a pulmonary function test (PFT) initially due to poor effort. A detailed environmental history review noted exposure to birds (pigeons) for a duration of around one year, as the family were keeping them in-house. Testing for specific bird IgG to pigeon test was not available in our institute and hence this was sent to the Mayo Clinic, USA. Further tests showed complete blood count showed leukocytosis with neutrophilia, an erythrocyte sedimentation rate (ESR) of 37 mm/h (N: 0–10 mm/h), and a C-reactive protein (CRP) count of 78 mg/L (N: 0–8 mg/L). Renal function and liver enzymes were normal, A sweat chloride test showed normal results, and measures of immunoglobulins A, M, G, E, IgG subclasses, the flow cytometry lymphocytic subset, and the HIV combo test all came back normal. Autoimmune work up showed a negative antinuclear antigen screen (ANA) and anti-glomerular basement membrane antibodies. Echocardiography showed normal cardiac function and no signs of pulmonary hypertension. The child underwent a flexible bronchoscopy evaluation that showed normal airway anatomy and dynamics, with no signs of chronic airway inflammation. The bronchoalveolar lavage (BAL) sample showed unsatisfactory results for cell and differential counts, but the BAL microbiology and virus results were negative.
The child’s symptoms continued to worsen with progressive dyspnea and dry cough, and the decision was made to undergo an open lung biopsy with histopathology findings suggestive of acute hypersensitivity pneumonitis (HP) (a,b). All pigeons were removed from the household, and lifetime avoidance of exposure to pigeons was recommended. He was further treated with pulse steroid therapy (30 mg/kg/day) for 3 days with the plan to give 3–6 cycles of monthly pulse steroids with follow up in an outpatient clinic.
The child was seen on a monthly basis in the outpatient clinic, and his specific bird IgG to pigeon feathers came back positive (131 mcg/mL, normal <22). He showed dramatic clinical improvement after removal of all pigeons from the house and on monthly pulse steroid therapy, and he was subsequently weaned off oxygen with improvement in his lung volume in his PFT results ().
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pmc-6262767-1
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A 61 year old male presented with painless swelling of right scrotum of 10 years duration. There was no history of any trauma,orchitis or any inguino-scrotal surgery. Systemic examination was normal. Local examination revealed a large swelling soft, non tender, non reducible with no expansile cough impulse having free overlying skin reaching base of scrotum. Transillumination test was positive. Scrotal USG showed 371 ml fluid filled unilocular cyst suggestive of the spermatocele. Exploration of scrotum revealed a large unilocular cyst arising from rete testis and partially covered by a thin membranous sheath (, ) This giant spermatocele was dissected from testicle and released of sac. Testicle and spermatic cord were enclosed in this thin sac like structure and traced to deep ring going into peritoneal cavity (). Palpation of deep ring admitted index finger with omentum at deep ring Diagnosis of an indirect hernia of a complete type with spermatocele, cord, testicle and omentum as a contents was made. Sac was dissected upto deep ring, incised laterally and cord with testicle kept out of sac (Extrasacal) (). Twisting of incised sac with high ligation of sac done, released into peritoneal cavity. Histopathology confirmed diagnosis of spermatocele and that of sac of hernia showed fibrous type. Follow up period was uneventful.
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pmc-6262802-1
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A 65 year old man was referred to our clinic with a diagnosis of CVA, he developed multiple vomiting and sever dysphagia in every meal. The patient had been candidate to percutaneous endoscopic gastrostomy. Incidentally, the full upper endoscopy detected a gastric outlet obstruction; there was no intraluminal mass or ulceration on mucosa. This finding terminated the procedure without performing the gastrostomy. The patient underwent the full study, the CT scan of the abdomen showed a submucosal well encapsulated mass at the lower pyloric partition of stomach with a fatty like nature that measured 4.5 by 8 cm2 with no other remarkable findings []. The patient was prepared for surgery. Open laparotomy was done; the mass was excised [] and a gastrostomy was established. The microscopical study stated that the lesion consisted of mature adipocytes without cytological atypia, arranged in lobules delimited by conjunctivovascular bays.
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pmc-6262803-1
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A 30-year-old female presented with a 5-week history of a painful rapidly-growing mass over the proximal phalanx of the right ring finger (). The patient also complained of numbness along the distribution of the radial digital nerve of the finger. There was no history of trauma. Examination showed a firm tender mass measuring 3.5 × 2 cm with an overlying skin erythema. The patient was unable to fully extend or flex the finger because of pain. There was also a flexion contracture of the proximal interphalangeal joint. Static two-point discrimination on the radial side of the ring finger was 10 mm. Plain x-rays showed no bony abnormalities or calcifications. Magnetic resonance imaging showed an iso-intense (similar to intensity of muscle) lesion on T1-weighted images (). T2-weighted images showed high intensity in the center of the lesion and low intensity at the periphery of the lesion ().
Surgical excision was done under general anesthesia. The mass infiltrated the entire flexor sheath over the proximal phalanx as well as the checkrein ligament of the proximal interphalangeal joint. The common digital artery of the 3rd web space was obliterated by the tumor. The radial digital nerve of the ring finger was stretched and attenuated (). Total excision was done and this required excision of the flexor sheath over the proximal phalanx (including the entire A2 pulley), the checkrein ligament and the common digital artery. The digital nerve was preserved (, ).
Histology showed the classic 3 histological zones of myositis ossificans: a central cellular / fibroblastic zone, an intermediate zone of osteoid (immature bone) and an outer zone of mature bone (). The patient was followed up for one year after surgery with no evidence of recurrence. At final follow up, there was full flexion of the digit, but the proximal interphalangeal joint had an extension lag of 30o (). Upon palpation, bowstringing of the flexor tendon was felt over the proximal phalanx. The static two-point discrimination on the radial side of the ring finger improved to 6 mm.
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pmc-6262955-1
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Our patient is a 13-year-old Lebanese-Armenian boy born in March 2004 from non-consanguineous and healthy parents, and after normal pregnancy and delivery. On neonatal examination, he was found to have hypertelorism, broad nasal bridge, choanal atresia by failing to pass nasal tube, heart murmur uncovering an interventricular communication, polysyndactyly, anal stenosis, micropenis (length, 1 cm; normal length for the age, 2–4.5 cm), and cryptorchidism. Because of the midline structural abnormalities, a magnetic resonance imaging (MRI) of his brain was performed and showed a hypothalamic hamartoma which was the key for the diagnosis of PHS (Fig. ).
At the age of 3 days, he was operated on for his choanal atresia. This operation revealed a narrow esophageal opening necessitating the use of smashed food late in his pediatric age. Imaging results, including upper gastrointestinal series and barium enema, confirmed the esophageal narrowing and revealed anal stenosis for which he was operated on at the age of 6 months. However, he remained severely constipated despite the surgical and medical treatment. During the same period, he developed seizures and was controlled by anticonvulsive treatment despite a normal electroencephalogram (EEG).
Regarding congenital limb malformations, he showed dysplastic nails with brachydactyly and post-axial polydactyly of his right hand. He also had broad great toes with syndactyly of the right fourth and fifth metatarsi. These malformations were managed subsequently.
At the age of 4 years, he started complaining of abnormal gait and an inability to keep up with peers during playing. A T2-weighted MRI sequence of his spine showed a tethered cord at L3 level by a fibrolipoma of the filum (thickness, 4 cm) (Fig. ), which was immediately and surgically removed.
Meanwhile, and because of bad school performance, a work-up was done including electric conductance of the acoustic nerve showing absent conductance on the right side and 20% activity on the left side. His condition was ameliorated after implantation of an acoustic nerve device. Although a hypoplastic pituitary gland with interrupted stalk and growth retardation with genital abnormalities were present, his thyroid panel and cortisol levels were normal. Growth hormone (GH) deficiency was confirmed by ornithine test where peak GH reached 0.20 μIU/ml (normal stimulated value > 20 μIU/ml) and by glucagon-propranolol test where peak GH reached 0.0082 μIU/ml (normal stimulated value > 20 μIU/ml). Also, his insulin-like growth factor 1 (IGF1) was at the lower normal value for age (24.6 ng/ml; normal values, 16–215 ng/ml). Therefore, he was started on GH treatment at the age of 4 years.
Due to the presence of a micropenis and undescended testes, he was treated with human chorionic gonadotrophin (HCG). As a result, his penis doubled (length, 2.5 cm) and his testes were in the scrotum. Note that his karyotype was normal male. He received his first testosterone course (100 mg/m2; four intramuscular injections at 2-week intervals) at the age of 1 year and 3 months leading to a slight increase in his bone age (2 years and 3 months) as well as penile length (3.5 cm).
At the age of 4 years and 6 months, he received a second course of testosterone which was stopped after two injections because of sudden increase in height (11 cm in 3 months) and bone age (9 years). Random luteinizing hormone and follicle stimulating hormone were low (levels not available) and his testes were in the prepubertal range (2 × 2 cm) ruling out the possibility of a central precocious puberty and this manifestation was related to the second course of testosterone treatment. GH treatment was stopped to slow down the growth velocity and resumed after 3 years during which he was lost to follow-up, and at IGF1 level of 60.8 ng/ml (88–474 ng/ml).
At present, at the age of 13 years, he has a spontaneous puberty (Figs. and ). His bone age is 13 years and 9 months, he measures 154.5 cm (+ 0.5 standard deviation; SD), he weighs 50 kg (+ 1.5 SD), with a Tanner staging of A2G2. His testes are both in the scrotum and his phallus length is 5 cm.
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pmc-6263045-1
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A 13-year-old previously healthy girl presented to the emergency department (ED) for evaluation of fever, bilateral foot pain, and rash. Her symptoms began 6 months prior to presentation, occurring 1–2 times per month, lasting for 2–3 days, and improving with ibuprofen. A few weeks prior to ED presentation, she noted onset of fatigue, pain in her hip and calf, which she attributed to her competitive soccer playing, and acute abdominal pain with diarrhea and emesis.
Patient denied fever, headaches, visual changes, oral ulcers, muscle pain, or changes in bowel and bladder functions. She had no other medication use or recent travel. Her family history was negative for autoimmune diseases.
Her vital signs upon presentation showed a temperature of 39.2 degrees Celsius, heart rate of 90 beats per minute, respiratory rate of 20 breaths per minute, blood pressure of 114/62 mmHg, and 97% oxygen saturation on room air. She had a blanchable, retiform, violaceous patches with few areas of true purpura on her bilateral lower extremities and duskiness of her right second toe (Fig. ). The remainder of her physical exam was unremarkable: a regular heart rate and rhythm with normal S1, S2 and no murmurs, rubs, or gallops; 2+ symmetric peripheral pulses; and joints with full range of motion without effusion or warmth. Her neurological exam was normal with no focal deficits. Her inflammatory markers were elevated (Table ) and she was admitted for further evaluation.
Initial diagnostic considerations were vasculitis, including cutaneous polyarteritis nodosa, leukocytoclastic vasculitis (associated with lupus erythematosus, infection or idiopathic), versus a vasculopathy due to antiphospholipid antibody syndrome, cryoglobulinemia, coagulopathy or septic emboli (Table ).
Skin biopsy of a non-palpable purpuric area on the dorsum of her left foot demonstrated subtle ischemia, vascular congestion, purpura, and focal eccrine gland necrosis without evidence of vasculitis, which was concerning for a vasculopathic process. Direct immunofluorescence of the skin biopsy was negative. Extensive systemic work-up was unremarkable and included: hepatitis panel, cryoglobulins, lupus anticoagulant panel, cardiolipins, beta-2-microglobulin, beta-2-glycopreotin, complements 3 and 4, antistreptolysin O (ASO) titers, anti-DNAse B, and aldolase. Abdominal and renal Doppler ultrasounds were also unremarkable.
During her hospital course, she developed recurrent fevers that were treated with acetaminophen at typical doses. In addition, she received a 1-time dose IV methylprednisolone 1 mg/kg after her battery of laboratory tests and skin biopsy.
An echocardiogram was performed to screen for intra-cardiac thrombus and assess for coronary abnormalities due to concerns for vasculitis. The echocardiogram revealed a 2.5 by 3-cm (cm) mass in the left atrium (LA), Fig. . Cardiac magnetic resonance was performed for tissue characterization of the LA mass [] and showed a 2.7 × 2.3 cm lobulated and mobile mass within the left atrium adherent to the septum (Fig. ), consistent with a left atrial myxoma.
The patient’s rash and constitutional symptoms were attributed to the myxoma. Purpura and pain in the right toe was felt to be secondary to either micro-embolic phenomenon or vasospasm. The decision was made to proceed with surgical excision of the cardiac mass. She was observed off anticoagulation given the lack of any concerning neurologic symptoms until surgery, which followed shortly thereafter.
The patient underwent an uncomplicated surgical resection and the diagnosis of cardiac myxoma was confirmed histologically (Fig. ). She had an uncomplicated post-operative course with resolution of fevers and systemic symptoms in the immediate post-operative period. At 3-week follow-up she continued to be afebrile with near complete resolution of her skin findings (Fig. ). She had no concerning symptoms at her 8-month follow up.
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pmc-6263452-1
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A 30-year-old Caucasian woman with a three-year history of arterial hypertension, who
was an irregular user of captopril, sought medical attention due to a one-week
history of dyspnea and chest pain. The patient presented with cold and clammy skin,
dyspnea, hypotension, and tachycardia and was afebrile. A resting electrocardiogram
(ECG) showed ST-segment elevation in all derivations. She was admitted for
thrombolysis with streptokinase at the original hospital and was then transferred to
the Tertiary Clinical Hospital. The patient was admitted to our emergency department
on mechanic ventilation and was hemodynamically unstable and receiving
norepinephrine.
A chest X-ray revealed cardiomegaly and pulmonary congestion; a transthoracic
echocardiogram showed mild to moderate pericardial effusion, with diffuse
hypokinesia of the left ventricle and significant systolic impairment with a left
ventricular ejection fraction of 30%, as determined by the Teichholz method; the
coronary angiography did not show any coronary lesions. Cardiac enzymes such as
troponin and CKMB were elevated.
There was no recent history of infection. Additionally, blood cultures were negative
three times, and serology for HIV was nonreactive.
The patient was diagnosed with myopericarditis, and hemodynamic support was provided
with dobutamine, norepinephrine, and an intra-aortic balloon pump (IABP). Later, on
the tenth day of hospitalization, the patient also showed signs of knee arthritis,
altered consciousness and anisocoria.
A computed tomography scan of the brain demonstrated multiple areas of cortical and
subcortical hypodensity () and a brain
arteriography showed a vasculitis pattern in the cerebral arteries. Antinuclear
(ANA) and anti-DNA antibody tests were positive.
After the diagnosis of lupus myocarditis was made, on the twelfth day of
hospitalization, the patient was started on immunosuppressive therapy with
methylprednisolone (1 g intravenously once daily for three consecutive days) and
later with cyclophosphamide (0.6 g/m2 intravenously once a month). There
was significant clinical improvement, and a repeated transthoracic echocardiogram
showed complete resolution of all changes. The patient remained asymptomatic, and on
the twenty-eighth day was discharged from the hospital for outpatient clinical
follow-up on 25 mg of captopril twice daily, 30 mg of diltiazem twice daily, 20 mg
of omeprazole once daily, 70 mg of prednisone once daily and 250 mg of chloroquine
once daily.
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pmc-6263463-1
|
A 63-year-old male, diabetic and former smoker patient was referred to the
cardiology service one year after the TTE showed an echogenic image suggestive
of a mass in the right atrium (RA) measuring 2.5 x 1.3 cm in its largest axis,
and increased thickness and density of the atrial septum, suggestive of
lipomatous infiltration. Additionally, he had a slight aortic root dilatation,
ascending aorta (3.9 cm in diameter) and signs of atherosclerotic plaque in the
aortic arch. The complementary CMR showed a solid image in the septal region of
the RA, projecting into the mediastinum in the retroaortic position and another
image in the region of the RA roof measuring 1.5 x 1.3 cm, adhered to the
interatrial septum, with the presence of perfusion and heterogeneous enhancement
suggestive of lymphoma.
The lesion biopsy was carried out; however, the diagnosis was inconclusive. He
was referred to the hematology service, where he underwent 18-FDG PET-CT, which
identified bone, CNS and skin involvement compatible with ECD. The 18-FDG PET-CT
showed a moderate / marked uptake in the RA walls, in topography coincident with
CMR alterations, were located on the RA roof (maximum standardized uptake value
- SUVmax: 6.28) and in the interatrial septal region
(SUVmax: 5.65) (Figure 1). Skin biopsy was indicated, of which
anatomopathological analysis showed accumulation of xanthomized histiocytes in
the dermis, suggestive of xanthelasma, with negative S-100, positive CD68,
negative CD1a and positive BRAF V600E staining. The patient underwent initial
treatment with interferon, but due to bone disease progression, he is currently
undergoing treatment with vemurafenib. In the follow-up 18-FDG PET-CT, RA roof
uptake (SUVmax = 5.7) was maintained.
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pmc-6263463-2
|
This was a 64-year-old female patient, with no prior comorbidities, who was
followed by the Hematology team with a diagnosis of ECD, with bone, lymph node
and cardiovascular involvement, demonstrated by 18-FDG PET-CT examination. She
showed radiotracer hyper-uptake with a heterogeneous pattern in the RA walls
(SUVmax: 5.8) and right ventricle (SUVmax: 5.8) and
discreet pericardial thickening/effusion. The TTE performed in the Cardiology
department showed atrial pseudotumor in an echogenic image in the interatrial
septum, measuring 2.2 cm x 1.2 cm, suggestive of lipomatous infiltration. The
coronary artery angiotomography showed a calcium score (Agatston) of 4, at the
58th percentile of the MESA (Multi-Ethnic Study of
Atherosclerosis) study, with no significant coronary luminal reduction. As an
additional finding, it showed a soft tissue density expansive lesion in the RA
roof related to the interatrial septum and opening into the inferior vena cava.
The sinus node artery, the right coronary artery branch, had a partial
trajectory through the mass, in addition to atheromatosis in the descending
thoracic aorta ().
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pmc-6263463-3
|
A 38-year-old male patient, with no prior comorbidities, diagnosed with ECD since
2005, identified through lung biopsy with CD68+ histiocyte, negative S-100,
started treatment with interferon and prednisone. In 2017, he developed dyspnea
at small efforts with NYHA III.
The TTE identified left ventricle (LV) with moderate systolic dysfunction (LVEF
of 40%) with diffuse hypokinesia, dilated left chambers, and preserved valvular
system. The CMR showed discrete LV dilatation, with an end-diastolic diameter of
6.7 cm and an end-systolic diameter of 5.1 cm, mild diffuse hypokinesia, mild
systolic dysfunction (LVEF of 46%) and late enhancement of the junction between
the ventricles.
Additional investigations were performed to rule out other etiologies of
ventricular dysfunction: serology for Chagas' disease was negative,
angiotomography of the coronary arteries with zero calcium score and absence of
luminal reduction. Treatment for ventricular dysfunction was started, and the
patient showed low tolerance for hypotension and cardiopulmonary rehabilitation
was indicated, with an important improvement in dyspnea.
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pmc-6263463-4
|
A 63-years-old female patient, a former smoker, with hypothyroidism, arterial
hypertension and dyslipidemia, had generalized xanthomatous skin lesions in
2001. In 2004, due to abdominal pain, she underwent a computed tomography (CT)
scan of the upper abdomen with contrast, which demonstrated hypoattenuating
tissue involving the abdominal aorta and its branches. This promoted a discrete
segmental narrowing of some of the vessels characterized by narrowing of the
aorta in the emergence region of the renal arteries and the left subclavian
artery (). Tissue biopsy showed the
presence of a pseudotumor, confirming the diagnosis of ECD. The 18-FDG PET-CT
showed signs of retroperitoneal fibrosis involving the abdominal aorta
immediately above and at the emergence region of the renal arteries.
Concomitantly, there was infiltrative tissue surrounding the aortic arch,
descending aorta and left common iliac artery. Initially, cardiac involvement
had been ruled out by CMR, which had shown normal-sized chambers and preserved
systolic function.
|
pmc-6263492-1
|
A 63-year-old female presented in 2012 for increased abdominal girth. It was associated with nausea, vomiting, constipation, and unintentional weight loss of 10 pounds. Initial abdomen-pelvic computed tomography (CT) scan showed a very large mixed cystic and solid mass process arising from the pelvis into the abdomen of suspected ovarian origin. The patient was diagnosed with primary appendiceal adenocarcinoma based on pathology evaluation obtained after total abdominal hysterectomy with bilateral salpingo-oophorectomy, omentectomy, and right hemicolectomy with appendectomy. At this point, she had evidence of stage IV appendiceal adenocarcinoma.
The patient was started on a chemotherapy regimen consisting of folinic acid, fluorouracil, and oxaliplatin for six months. After three years, follow-up CT-scan surveillance confirmed progression of retroperitoneal lymphadenopathy. A second line chemotherapy regimen of folinic acid, fluorouracil, and irinotecan plus avastin was started. She had eight courses and CT imaging showed improvement in the left retroperitoneal lymphadenopathy. Unfortunately, she developed hypertension, deep vein thrombosis, and significant nausea. These were side effects related to her chemotherapy regimen. She was given treatment holiday. On return visit, CT-scan showed advancement and burden of metastatic disease with hepatic lesions. Additionally, carcinoembryonic antigen (CEA) was elevated. She was started on a second round of folinic acid, dose reduced fluorouracil, and oxaliplatin.
While on chemotherapy, she developed new left supraclavicular lymph node, and CEA continued to increase. Genetic testing revealed a negative result for KRAS of wild-type, absence of microsatellite instability, and negative PDL-1 testing. With these findings, the patient’s medications were switched to irinotecan and vectibix. Clinical improvement started to be noticed, but the patient acquired a hypersensitivity reaction contributed to vectibix.
The patient insisted on continuing treatment. She was started on pembrolizumab, although tests did not show microsatellite instability. After the first dose of pembrolizumab, she reported resolution of her abdominal pain and experiencing regular bowel movements. CEA was reported 95 ng/mL on a test done 10 days after the first dose. The test was repeated monthly to monitor pembrolizumab benefit. Results showed a downwards trend to 80 then 43 ng/mL. CT scan was repeated two months after initiation of pembrolizumab. It showed an increase from previous left supraclavicular adenopathy (Figure ), stable retroperitoneal periaortic lymphadenopathy (Figure ), and decreased size of hepatic metastasis (Figure ). The patient continued on this medication with notable clinical improvement. The patient completed 10 doses over a period of six months. A repeat CT scan showed increased calcification in relatively similar left supraclavicular lymphadenopathy (Figure ) and retroperitoneal adenopathy (Figure ). Hepatic metastasis lesion was similar in size from previous scans. A more recent CEA test showed an astonishing result, with CEA dropping to 1.9 ng/mL.
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pmc-6263493-1
|
A 29-year-old Caucasian female with a past medical history of a migraine without aura, a left convexity arachnoid cyst (Figures -), and pituitary microadenoma presented to the emergency department with a progressive bifrontal headache. The headaches first started two weeks prior when the patient originally presented to the emergency department and her headache was treated with migraine medication. Her headache initially improved but secondarily worsened, and she started to complain of blurry vision and right arm and leg weakness. A computed tomography (CT) scan of the head was obtained that showed a 2.4 cm left cerebral convexity acute/subacute subdural hematoma (SDH) in the area corresponding to her arachnoid cyst, and associated with a mass effect upon the left frontal and parietal lobes and 6 mm of rightward subfalcine herniation (Figures -). The scan additionally showed a hemorrhage within a loculation that suggests an intra-cystic hemorrhage within the arachnoid cyst. The patient denied any history of recent trauma. Neurosurgery was consulted, and the patient was taken to the operating room for a left-sided craniotomy for SDH evacuation. The cyst appeared to be obliterated by the hematoma as there was no evidence of a double arachnoid layer. The patient tolerated the procedure well, and her postoperative head CT showed a successful evacuation of the hematoma and the arachnoid cyst (Figure ). Her right arm and right leg weakness resolved after surgery. The patient’s postoperative course was uncomplicated, and she was discharged home on postoperative day seven. The patient presented to the emergency department two months after discharge, complaining of a similar headache. Head CT was performed and did not show any re-accumulation of the subdural hematoma or recurrence of the arachnoid cyst (Figures -).
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pmc-6263494-1
|
History
A 36-year-old female presented to the Emergency Department (ED) with a persistent generalized headache, dizziness, and blurred vision in addition to diplopia. On physical exam, she had normal range of motion and strength in all extremities and no focal neurological deficit was observed other than a lagging of her left eye while testing her extraocular muscles. The patient was discharged from the ED with instruction to follow up with the neurosurgery department as an outpatient.
At her outpatient neurosurgery appointment, the patient revealed that her headache had increased in severity and had begun to localize to the bridge of her nose and medial forehead. Her headaches were accompanied by diplopia, photophobia, blurred vision, nausea, and vomiting. Of note, the patient’s past medical history was significant for obesity, smoking, and benign essential hypertension controlled with medication. Her neuro-ophthalmologic exam was notable for enlarged blind spots bilaterally with possible inferonasal and temporal field defects. Ophthalmology also noted 20/30 vision with decreased colour vision, an afferent papillary defect in the right eye, and hemorrhagic disc elevation in both eyes with the hemorrhage extending into the macula of her right eye. Ophthalmology’s recommendation was urgent decompression of the optic chiasm, which was in agreement with neurosurgery’s recommendation.
Brain magnetic resonance imaging (MRI) with and without contrast demonstrated a 1.6 x 1.8 x 2.4 centimeter multi-locular suprasellar cyst within the suprasellar cistern, originally seen on the outside computed tomography (CT) scan, with enhancement along the left lateral and superior walls of the cyst (Figures -).
A leftward deviation of the pituitary stalk and minimal spreading of the optic nerves was noted as well, given the location anterior to the optic chiasm. The pituitary gland itself, the optic chiasm, and the cavernous sinuses were grossly normal. Prior to surgery the patient also underwent CT angiography (CTA) of the head and neck due to a protrusion found on the skull. The scan revealed a bony overgrowth of the external occipital protuberance as well as a two-centimeter cystic lesion in an area of the suprasellar cistern and anterior third ventricle. Of note, the CTA also showed normal intracranial arterial and venous anatomy and the absence of any aneurysms or malformations. At this time, the differential diagnosis presented by neuroradiology included Rathke cleft cyst, neuroepithelial cyst and craniopharyngioma.
Operative and postoperative course
The patient was counseled on the risks and benefits of the operation, and consented to frameless stereotactic endoscopic endonasal extended transsphenoidal resection of her lesion with a lumbar drain and fat graft. Given the presence of hemorrhagic papilledema, the patient consented to evaluation of opening pressure via a lumbar drain given concern for pseudotumor cerebri and increased intracranial pressure. After a standard transsphenoidal opening was prepared by Otolaryngology, we proceeded to mobilize and remove the cyst from the pituitary stalk via a vertical infundibulotomy. A portion of the cyst wall was adherent to the hypothalamus bilaterally and was left in place. The patient was then transferred to the post-operative care unit in stable condition. No intraoperative complications were noted, and the patient was transferred to the neurological intensive care unit (ICU) for further post-operative management.
Postoperatively the patient’s labs and urine output were immediately suggestive of clinical diabetes insipidus (DI). The patient had increased urine output and was started on intravenous fluid replacement as well as desmopressin prior to ICU transfer. On neurological exam, her left maxillary and mandibular trigeminal nerve dermatomes had decreased sensation to light touch and transient exotropia of the left eye was noted, as was the disconjugate gaze. Improvement in disconjugate gaze was noted on post-operative day two, and was only apparent upon opening eyes from rest. The patient’s sodium levels continued to fluctuate and some bleeding from the left nostril as well as coughing up clots of blood was noted four days after the procedure.
By post-operative day seven the DI resolved and the patient discharged. Given the continued presence of bilateral hemorrhagic papilledema on exam it was recommended at the time that the patient continue treatment with acetazolamide 500 milligrams by mouth twice daily for pseudotumor cerebri. A post-operative brain MRI performed at this time showed resection of the suprasellar lesion (Figures -).
While her DI resolved, the patient continues on hormone replacement for panhypopituitarism.
|
pmc-6263517-1
|
A 72-year-old woman presented with nine months of neck pain and left upper extremity pain and numbness, three months of right upper extremity pain, and more recent weakness in the left arm. She also had a long history of urinary stress incontinence with no changes in bowel or bladder function during the nine months of symptoms preceding her presentation. Physical examination was notable for 4/5 triceps strength, effort-limited 4+/5 left grip strength and symmetric reflexes. Magnetic resonance imaging (MRI) revealed a cervical intramedullary syrinx from C5-C7 with a nodule suggestive of a hemangioblastoma (Figure ).
She underwent uncomplicated elective C5-C7 laminectomies and resection of the nodule. Pathological testing confirmed the lesion to be a hemangioblastoma.
Imaging performed seven months postoperatively revealed abnormal hyperintensity of the left posteromedial spinal cord at C6 with a small, nodular, enhancing lesion of the most posterior portion of this abnormality. Subsequent imaging showed a progressive increase in the size of this lesion, and imaging four years postoperatively revealed increased nodular enhancement and recurrence of the syrinx (Figure ). Four years postoperatively, she was also diagnosed with complex regional pain syndrome.
Four and a half years after her index surgery, increasing enhancement size prompted additional surgery, including extension laminotomies/laminectomy from C3-T1 and resection of the pathology-proven hemangioblastoma. Imaging two months after the second surgery showed a punctate focus of enhancement at the dorsal aspect of C6, suspicious for residual or recurrent tumor. Subsequent annual imaging, with the most recent scan nine years after the second operation, has shown no significant changes in the focus of enhancement at C6 (Figure ). No further interventional treatment has been performed.
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pmc-6263518-1
|
A 42-year-old male patient with a past medical history of a migraine headache presented to the emergency department after a preliminary evaluation by his primary care provider of drooping of the right upper eyelid and asymmetric pupils. The patient complained of a right-sided headache, retro-orbital pain in the right eye, and dull, aching right-sided facial pain for one day. The patient denied visual blurriness, obscurations, photophobia, or neck pain. There were no reports of recent trauma or chiropractic manipulation of his neck. On physical examination, visual acuity was 20/20 bilaterally. The ophthalmological examination was remarkable for partial ptosis and enophthalmos of the right eye (Figure ). The pupillary examination showed anisocoria with miosis in the right eye (Figure ) with the asymmetry more prominent in the dark. Extraocular movements were intact bilaterally. The rest of the ophthalmological and neurological examination was unremarkable. The patient was admitted to the hospital for further evaluation. Magnetic resonance imaging (MRI) of the neck (Figure ) and magnetic resonance angiography (MRA) of the head and neck (Figure ) revealed a dissection of the cervical and petrous segments of the right internal carotid artery. The patient was diagnosed with Horner syndrome secondary to right internal carotid artery dissection. He was then started on dual antiplatelet therapy with aspirin and clopidogrel for three months. The patient was eventually discharged after clinical improvement and asked to follow up with neurology on an outpatient basis.
|
pmc-6263537-1
|
A 25 year old man from Morocco worked in Mauritania as an engineer in a water dam for 1 year. One month after his return to Morocco, he has suffered abdominal pain and hematuria wrongly diagnosed in a local clinic as kidney stones.
He was admitted to a central hospital with progressive hematuria, he has benefited from a cystoscopy with biopsies. Histological examination of the biopsies revealed a granulomatous inflammatory reaction made of epithelioid and gigantocellular granulomas punctuated by eosinophilic polynuclear cells. These granulomas contain in their centers bilharzia eggs (Fig. ).
The diagnosis was confirmed by the presence of Schistosoma heamatobium eggs in direct examination of fresh urine collected (Fig. ).
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pmc-6263545-1
|
The male patient aged 60 years was hospitalized due to sudden dizziness for 3 h combined with slurred speech on May, 16, 2017. The patient had nausea, but he did not have vomiting, incontinence and unconsciousness. The patient was immediately referred to China-Japan Union Hospital of Jilin University. Head CT performed within 3 h of onset of symptoms (Fig. a) showed hemorrhage in the left temporal lobe, and the patient was admitted in our department with a clinically confirmed diagnosis of “hemorrhage in the left temporal lobe”. The patient had a previous history of hypertension for more than 10 years, and was under medication to control and maintain the blood pressure to be around 130/80 mmHg. The patient denied the history of diabetes and had no bad habits, such as smoking and drinking alcohol. Physical examination at admission revealed that his body temperature was 36.2 °C and blood pressure was 196/119 mmHg. The patient was conscious and suffered from incomplete aphemia. Bilateral pupils were of the size and round, the diameter of pupils was 3 mm, and pupils were sensitive to light reflexes. Muscular strength of the limbs was about grade 4. Bilateral pathological signs were negative, and there was no significant abnormality noticed during nervous system examination. Head MRI conducted the next day after admission indicated no significant vascular malformations (Fig. b). General consultation evaluated that bleeding sites of the patient were slightly different from hypertensive intracerebral hemorrhage. The hematoma sites were close to the middle cerebral artery and the walking areas of its branches, mainly in the temporal lobes. Therefore, cerebral vascular hemorrhage and other causes could not be excluded, and head CTA was further suggested. Head CTA performed on 17th May 2017 showed that the patient suffered from intracerebral hematoma caused by aneurysm rupture at the M1 bifurcation of the left middle cerebral artery, without any significant subarachnoid hemorrhage (Fig. a). Craniotomy and clipping of intracranial aneurysm were performed the next day after admission. During the operation, the aneurysm was found to be located in M1 bifurcation of the left middle cerebral artery, which was in cystic bulging. An asci formation with the size of 3 × 4 × 5 mm was located on the upper side of the aneurysm, and the aneurysm neck measured 4.2 mm, which was clipped successfully. There was no significant hematoma in the subarachnoid space, and the arachnoid around the aneurysm showed no obvious adhesion during the surgery. The patient successfully recovered from anesthesia after the surgery, without any significant neurological deficits. The patient was discharged after 2 weeks and Glasgow Outcome Scale (GOS) scored 5 points. Follow-up was performed for 4 months at the Outpatient Department. Head CTA (Fig. b) demonstrated that aneurysm did not relapse and GOS score was 5 points.
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pmc-6263613-1
|
A 33-year-old-man who was a nursing home resident with a significant past medical history of anoxic brain injury after a drug overdose presented to the emergency room with upper abdominal pain and black color stools for the last one week. He was refusing tube feedings. He had a PEG tube placed for five years, and it was exchanged one month ago due to malfunction. He was alert to person and place at baseline. However, he was in mild distress due to the abdominal pain. An abdominal examination showed a soft abdomen with mild epigastric tenderness to palpation and the presence of active bowel sounds. A PEG tube was noted in the epigastric area left lateral to the midline. The external bumper of the PEG tube was observed to be more than 10 cm from the skin line. The rectal exam showed melanic stool (guaiac positive). Initial laboratory findings were as follows: amylase: 500 U/L (50 – 150 U/L), lipase: 900 U/L (10 – 140 U/L), hemoglobin: 12.5 g/dL (14 – 18 g/dL), white blood cells (WBC): 4400/µL (3800 – 11000/µL), platelets: 240,000/µL (140,000-400,000/µL), aspartate transaminase (AST): 21 IU/L (10-40 U/L), alanine transaminase (ALT): 23 IU/L (7-56 IU/L), alkaline phosphatase (ALP): 72 IU/L (32-110/IU/L), blood urea nitrogen: 7 mg/dL (6-23 mg/dL), creatinine: 0.6 mg/dL (0.6-1.5 mg/dL), international normalized ratio: 1.04. A computed tomography (CT) scan with intravenous and oral contrast was performed which revealed fat-stranding around the pancreas, suggestive of pancreatitis. An abdominal ultrasonography ruled out any stone or sludge within the gallbladder or bile duct. Fluoroscopy confirmed the position of the gastrostomy tube within the stomach without any extravasations of dye into the peritoneal cavity. Esophagogastroduodenoscopy (EGD) revealed a posterior gastric wall ulcer that was caused by the inner tip of the PEG tube. The ulcer base was deep and clean with no high-risk stigmata (Figure ). The external bumper of the PEG tube was pushed down to 2 cm from the skin line. The patient was started on proton pump inhibitors (PPI). His pancreatic enzymes continued to trend downward. He was started back on tube feeds, which he tolerated well. Repeat EGD in eight weeks showed a resolution of the gastric ulcer.
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pmc-6263615-1
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A 15-year-old female with no past medical history presented to the emergency department complaining of five months of severe pain in nasal region and associated cutaneous hypersensitivity, headache, nausea, dysphagia, otalgia, strabismus of left eye with decreased visual acuity, and quadriparesis. On physical exam, she presented with horizontal nystagmus, dysarthria, quadriparesis, and a palpable mass on the right side of the neck with neck stiffness. An MRI of the brain and neck revealed an enhanced broad and destructive mass in the infrasellar region with complete destruction of the clivus, C1-C2 infiltration with compression of the occipital foramen, and a displaced pons and medulla (Figure ).
The patient underwent a two-stage procedure. The first procedure was a transoral approach with decompressive partial excision surgery. A sample biopsy of the lesion was taken, which was found to be consistent with chondroid chordoma. Further biopsies were obtained and the pathology studies resulted positive for S100, cytokeratin AE1/AE3, and epithelial membrane antigen (EMA). Microscopically polygonal cells with hyperchromatic nuclei, fine cytoplasmic vacuoles, and chondroid tissue corresponding to phisaliferous cells constituting nests and lobules infiltrated and replaced the hyaline bone cartilage and part of the soft tissue (Figure ).
The second procedure was performed one month later and consisted of maxillectomy Le-fort 1. Partial excision of residual tumor mass was successfully achieved. After three days of postoperative recovery, the patient showed signs of partial improvement. She was discharged to follow up with imaging monthly (Figure ).
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pmc-6264041-1
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The patient was an 81-year-old Japanese man. He was diagnosed with a recurrence of UC with multiple lymph node metastases, originating from the left renal pelvis, 1 year after laparoscopic radical nephroureterectomy. In addition, his renal function worsened 1 month before the above diagnosis; a shunt was created surgically for hemodialysis initiation. Thus, chemotherapy was planned while the patient continued hemodialysis.
Before the commencement of chemotherapy, the patient’s Eastern Cooperative Oncology Group performance status was 1. His height was 163.5 cm, dry weight was 51.90 kg, and body surface area (BSA) was 1.55 m2. Laboratory findings were as follows: white blood count, 3700/μL; hemoglobin, 11.0 g/dL; platelet count, 168 × 103/μL; blood urea nitrogen, 24.2 mg/dL; and creatinine, 3.38 mg/dL. The patient had residual renal function, with daily urine volume > 500 mL and a 24-h creatinine clearance of 7.3 mL/min.
The GEM dose was reduced by 25% (750 mg/m2) and was administered by intravenous infusion for 30 min on days 1 and 8 of a 21-day cycle. CBDCA was administered by intravenous infusion for 60 min on day 1, followed by infusion of GEM. The initial CBDCA dose was calculated according to the Calvert’s formula (target AUC: 5.0 mg/ml min, GFR: 6.1 mL/min). GFR was calculated based on knowledge that 24-h creatinine clearance is generally approximately 20% higher than GFR []. Therefore, the CBDCA dose was calculated as 160 mg.
Hemodialysis commenced 2 h after the end of CBDCA infusion on day 1 and was performed for 3 h, with a blood flow rate of 200 mL/min and a continuous infusion of heparin as an anticoagulant. The dialyzer membrane was made of polymethyl methacrylate, with a surface area of 1.6 m2 (BK1.6P, TORAY Inc., Tokyo, Japan). Subsequent hemodialysis was performed on days 3 and 5.
A pharmacokinetic study was performed to monitor the measured AUC of CBDCA. This study was approved by the ethical review board at Nagoya City University Graduate School of Medical Sciences. Informed consent was obtained from the patient. Blood samples were collected during the first 2 cycles of chemotherapy. Sampling points were as follows: immediately after CBDCA infusion, before starting and ending hemodialysis, and 20 and 48 h after CBDCA infusion on day 1 (Fig. ). The plasma was stored at − 80 °C until analysis. The plasma platinum level was measured by inductively coupled plasma mass spectrometry. The CBDCA level was calculated using the molar ratio of platinum: CBDCA (371.25/195.08). The measured AUC of plasma CBDCA was calculated using the trapezoidal method according to the intervals before, during, and after hemodialysis, with extrapolation to infinity.
The measured AUC of CBDCA in the first cycle was 5.96 mg/mL min, which was 19.2% higher than the target AUC (Fig. a). Consequently, grade 4 neutropenia and grade 3 thrombocytopenia were observed, according to the National Cancer Institute’s Common Toxicity Criteria for Adverse Events version 4.0 (Table ). To match the target AUC more closely in the subsequent cycle, we performed a pharmacokinetic study using parameters obtained in the first cycle. Consequently, the CBDCA dose was reduced to 135 mg, and the time interval between the CBDCA infusion and hemodialysis initiation was shortened to 1 h in the second cycle. The hemodialysis duration and conditions, such as the dialyzer and blood or dialysate flow rates, were unchanged. The measured AUC of CBDCA in the second cycle was 4.97 mg/mL min (Fig. b). The CBDCA dose and administration procedure in the third cycle were the same as that in the second cycle. In the second and third cycles, neutropenia severities were grades 2 and 3 and thrombocytopenia severities were grades 2 and 1, respectively (Table ). In addition, no other serious adverse events, including nausea and vomiting, were observed by the supportive care. Serum creatinine levels immediately prior to starting the second and third cycles were 3.12 mg/dL and 2.84 mg/dL, respectively; the 24-h creatinine clearance was only measured prior to the first cycle. The CBDCA removal rates by hemodialysis in the first and second cycles were calculated at 56.9 and 59.3%, respectively, though the redistribution phenomenon in the post hemodialysis period could not be considered due to the small number of blood sampling points. Other pharmacokinetic parameters in the first and second cycles are shown in Table . Total clearance of CBDCA was slightly higher in the second cycle than in the first cycle. Stable disease (according to Response Evaluation Criteria in Solid Tumors) was demonstrated by computed tomography after the second and third cycles.
The patient’s QOL before treatment and after 2 cycles of treatment was evaluated using the Medical Outcomes Study 36-Item Short Form Survey (SF-36, iHope International Inc., Kyoto, Japan), which is a questionnaire used to measure general health status []. Mean norm-based score (NBS) is an international common score recalculated on the basis of the score of 8 items of the SF-36. Our patient’s NBS did not significantly decrease after 2 cycles of chemotherapy compared with his NBS before treatment (Table ).
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pmc-6264594-1
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A 9-year-old Han Chinese boy presented with both lower extremity weakness of 6-month duration. Neurophysical examination revealed weakness of the lower extremities (power grade IV/V) and decreased sensation below the T10 dermatome with bilateral knee tendon hyperreflexia and Babinski sign positive. Magnetic resonance imaging (MRI) showed an well-demarcated intramedullary lesion located at the level of T8 vertebra with isointensity on T2WI (Fig. ) and hypointensity on T1WI, which was homogeneous enhanced after gadolinium injection (Fig. ). There was associated syringomyelia extending from T7 down to the level of T10. A right thoracolumbar scoliosis with a Cobb angle of 28° was also observed (Fig. ). The patient underwent a T7–8 laminectomy. Opening the dura mater revealed a well-demarcated, soft, greyish-red tumor (Fig. ). The lesion was totally resected with the help of microsurgical techniques. T7–8 laminoplasty was performed to keep the integrity of spinal structural. Histopathological findings were consistent with fibrillary schwannoma. Postoperative MRI did not reveal the presence of a residual tumor with syringomyelia reduced. By 2 weeks after treatment, the patient had experienced nearly complete recovery. Management with external bracing was performed on this patient for 3 months after surgery to prevent spinal deformity. However, a thoracic kyphotic deformity with a Cobb angle of 30° occurred 5 months after surgery (Fig. ), and a progressive postoperative spinal kyphosis with a Cobb angle of 60° was observed 3 years after surgery (Fig. ). Continued conservative management with observation was performed as there is no association with functional decline and impairment in health-related quality-of-life measures.
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pmc-6265407-1
|
Fifty-four year-old man presented with a history of 3 months of severe shuffling gait, urinary incontinence, and difficulty managing finances and keeping track of appointments. On examination a soft voice, a delay in left shoulder shrug and mild cogwheel rigidity in the left arm were noticeable. A brain MRI revealed marked ventriculomegaly (calculated Evans index = 0.42) () (Figure ). A lumbar puncture with removal of 50 ml of cerebrospinal fluid (CSF) was performed. The CSF was clear and colorless with an opening pressure of 18 cmH20. After the spinal test, Mini-Mental State Examination scored improved from 23/30 to 29/30 and the patient subjectively experienced significant relief from his gait-related symptoms, showing a 10% of increase in his walking speed. INPH was diagnosed and a ventriculoperitoneal (VP) shunt was placed (Figure ). Cognitive impairment and urinary incontinence improved, but the parkinsonian features persisted. Then treatment with levodopa was added, and the patient experienced a sustained improvement. It was thought that PD coexisted with INPH. Five years later, he presented with acute headache and cognitive impairment. Shunt obstruction which necessitated surgical intervention was diagnosed. The VP shunt was replaced and these acute symptoms resolved.
After 7 years on levodopa treatment, the patient developed gait freezing and severe levodopa-induced dyskinesia. He was treated with various combinations of trihexyphenidyl, amantadine, pramipexole, and levodopa, up to a maximum tolerated dose (1,500 mg daily), with minimal benefit to his overall functions. At an outside institution, DBS surgery was not considered due to diagnostic and technical concerns; the latter were related to the ventriculomegaly that could complicate the accurate placement of the DBS leads.
At the age of 67, the patient was subsequently referred to our institution. Motor score following a levodopa challenge decreased from 45 to 28 on UPDRS III (40% improvement). The Unified Dyskinesia Rating Scale (UDysRS) was very high (128 out of a maximum of 196). A battery of neurocognitive tests showed no signs of cognitive impairment. After a long discussion with the patient and his family on the pro and cons of the surgery, we decided to carry out DBS because the patient was suffering from medically intractable parkinsonism. The patient underwent bilateral GPi-DBS. We chose the ventral GPi in order to suppress dyskinesia and because its more lateral position compared to the subthalamic nucleus reduces the risk of breaching the ventricle walls. We used MRI/CT fusion techniques for anatomical indirect targeting with a stereotactic CT frame. Anterior and posterior commissures were identified, and the AC-PC line was 40 mm (the usual length of the AC-PC line is measured between 19 and 32 mm). The coordinates for the right GPi were 27.38 mm lateral (X), 1.85 mm anterior (Y), and −8 mm inferior (Z) to the midpoint of the intercommisural AC-PC line (10.7° from mid-sagittal plane and 53.3° from axial plane). For the left GPi the coordinates were X: −25.35 mm, Y: 3.69 mm, and Z: −8.42 mm (11.7° from mid-sagittal plane and 67.3° from axial plane). The right burr-hole placement was shifted laterally to avoid the right VP shunt and the enlarged frontal horns of the lateral ventricles (please see Additional File : CT video). The number of microelectrode trajectories was reduced to only one. Intraoperative microelectrode recording (MER) identified the neuronal firing pattern of the GPi. Recordings were performed in steps of 0.5–1 mm, from 15 mm above the presumed target until 3 mm below the target. Microstimulation with trains of high-frecuency (200 Hz) and currents from 0.5 to 5 mA was performed in order to test for proximity of the internal capsule, without any noticeable twitching or contraction coincident with stimulation. Visual evoked responses were obtained by a stimulus of light delivered as a flash and the optic tract was identified at the base of both GPi. The GPi-DBS lead placement was confirmed on a postoperative CT scan (Figure ).
Two weeks after leads placement, monopolar stimulation of the left dorsal and right ventral contacts (1-/11-) at 3.2 V in the left GPi and 3.6 V in the right GPi with a frequency of 130 Hz and pulse duration of 90 ms led to the best clinical response. There was a 71% decrease in the UPDRS III score during the on-stimulation state (28 to 8). The patient's dyskinesias resolved dramatically with a UdysRS of 15 (88% improvement) during the on-stimulation condition. The observed motor benefits and the improvement of his daily activities have persisted 10 months after surgery. (Please see Additional File : movie shows the before/after surgery; medication-off/stimulation-on condition).
The subject gave written informed consent for the publication of this case report and video files in accordance with the Declaration of Helsinki.
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pmc-6266076-1
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A 32-year-old left-handed female patient was referred to our department with an MR scan showing a right fronto-opercular diffuse low-grade glioma and performed as a diagnostic work-up for headache (). Left-handedness was confirmed with Edinburgh’s inventory. She had no preoperative language disorders.
After navigation-guided identification of the tumour boundaries, an “awake” resection was performed and intraoperative identification of Broca’s area (tag 5) with “speech arrest” and inferior fronto-occipital fascicle (IFOF) with transient fonemic paraphasia was reached (tag 8) , and . Resection was then stopped.
Histology provided evidence for isocitrate dehydrogenase 1(IDH1)-mutated, ATP-Dependent Helicase (ATRX)-wild diffuse low-grade astrocytoma. Postoperative MR showed a subtotal removal with residual disease where IFOF was intraoperatively identified (). No adjuvant therapy was then proposed, and the patient is currently fully working. If evidence of residual disease progression is observed, a new surgery will be proposed, delaying eventual adjuvant therapy as much as possible.
This may be considered an example case of the “multi-staged” approach to dealing with diffuse low-grade gliomas, making it possible to get control of the disease as much as possible, postponing chemotherapy or radiotherapy as far as possible and reserving them for when surgery can no longer be performed.
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pmc-6266232-1
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A 17-year-old woman visited her local hospital because of cough on exertion and right chest pain over the previous two months, together with bloody sputum over the previous week. At the patient’s local hospital, chest X-ray depicted an abnormal shadow; therefore, she was referred to our hospital. She was in good health and had no remarkable family history. She had not been exposed to dust or illicit drugs and was not a smoker.
Upon initial assessment, the patient seemed to be well, and her vital signs and physical examinations were normal. Serum laboratory data were normal, including tumour markers such as carcinoembryonic antigen (3.7 ng/mL), carbohydrate antigen 19–9 (16.1 U/mL), sialyl Lewisx-i antigen (28 U/mL), pro-gastrin-releasing peptide (47.8 pg/mL), and soluble interleukin-2 receptor (307 U/mL). In addition, tests for autoimmune antibodies such as myeloperoxidase-antineutrophil cytoplasmic antibodies (MPO-ANCA) and proteinase 3 ANCA were negative.
On the day of referral to our hospital, chest X-ray demonstrated a nodule measuring 3 cm in diameter in the right middle lung field (Fig. A). At this time, contrast-enhanced thoracic computed tomography (CT) depicted an inhomogeneously enhanced nodule as large as 3 cm in diameter at the right S8/S9 (Fig. B, C). No mediastinal, hilar lymphadenopathies, or other lesions in the lung parenchyma were noted. Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) depicted the nodule as having intense standardized uptake values of 11.8 (Fig. A), suggesting high probability of malignancy.
A bronchoscopy was performed 10 days after the patient’s initial visit. The bronchoscopy showed a protruded white intra-bronchial tumour at the orifice of the right B8 (Fig. D). Haematoxylin and eosin (H&E) staining of the biopsied specimens obtained from the tumour (Fig. B, 40×) via endobronchial biopsy with forceps showed that a thickened stratified squamous epithelium covered the mucosal surface. However, these findings did not lead to a diagnosis. Three weeks later, she underwent a second bronchoscopy, which showed that the protruded tumour had progressed and completely occluded the lumen of the B8 (Fig. E). H&E staining of endobronchial biopsied specimens with forceps obtained from the tumour showed fragments of ciliated columnar (glandular) epithelium (Fig. C, 100×, arrow) admixed in the abundant squamous epithelium and parakeratotic debris (Fig. C, 100×, arrow head). Papanicolaou staining of the bronchial washing fluid from the right B8 demonstrated the aggregation of stratified squamous cells with orange-coloured cytoplasm (data not shown). Repeated bronchoscopy showed no evidence of malignancy or bloody phlegm irrespective of progression of the intra-bronchial tumour on thoracic CT. However, the intra-tracheal tumour was considered the source of bloody sputum. Therefore, 40 days after the patient’s first referral to our hospital, she underwent right lower lobe lobectomy via Video-assisted thoracoscopic surgery.
A resection of the right lower lobe (14 × 11 × 5 cm) indicated a white-coloured papillary tumour measuring 4 cm in diameter located at the proximal portion of the dilated bronchus (Fig. D), which consequently leads to the right B8a. H&E staining showed that the tumour was composed of thick squamous (Fig. E, 5×, arrow head) and glandular (Fig. E, 5×, arrow) epithelia, both of which proliferated in a papillary pattern along with inflamed fibrovascular cores. The former (squamous) was predominant, and neither component demonstrated malignant features (Fig. F, G 100×). Immunohistochemical staining for Ki-67 found strong positivity up to the basal half of the squamous component (Fig. H, 100×). This increase of the positive index indicated active proliferation of the tumour. Upon further histological analysis, our case showed a negative result both in polymerase chain reaction for human papillomavirus (HPV) and immunohistochemical staining with p16Ink4a
, a surrogate molecular marker of HPV. Finally, she was diagnosed with mixed squamous cell and glandular papilloma of the bronchus without HPV infection.
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pmc-6266291-1
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The second case described by Kraemer et al. [] involved a 46-year-old female patient who also prepared to refill her fireplace with bioethanol while it was still burning. With the bottle lid removed, and the bottle in her hand, she tripped and sprayed liquid onto the burning fireplace. A flash fire followed, and resulted in an explosion of the internal bottle gas volume, exposing the patient to the fire. This patient suffered partial-thickness burns to the face, left arm, both hands, and the entire right leg, affecting a TBSA of 12%. The patient was admitted to their intensive care unit for 4 days. The duration of the in-hospital stay until discharge was 2 weeks []. This burn accident also demonstrates the dangers of approaching the fireplace for refilling while it was still burning. In this case it was also evident that the container vapor phase ignition contributed to the severity of the accident.
A study by Heald and Muller [] reported on five burn victims in Australia in 2014. All incidents involved biofuel heaters and occurred while refueling the units. The first incident involved refueling a table top heater which was believed to have been extinguished for 20–30 min. During refilling, a large fireball and explosion occurred, which exposed two patients sitting opposite the table top heater. The first patient, a 28-year-old male, sustained 43% TBSA deep partial- and full-thickness burns to the face, neck, anterior and posterior trunk, arms, legs and left foot. The patient was in the intensive care unit for 26 days and was discharged from hospital after 57 days. A 22-year-old female was involved in the same incident. She sustained 31% TBSA deep partial- and full-thickness burns to the face, neck, anterior and posterior trunk, arms, and left leg. She was discharged from hospital after 78 days. This incident clearly demonstrates the dangers related to refueling a burning unit and clearly involved container vapor phase ignition and explosion.
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pmc-6266318-1
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A female patient, aged 27 years and 4 months, had the chief complaint about the “esthetic appearance of her teeth”. She reported to be ashamed of smiling because of the high and rotated maxillary canines. The facial photographs showed proportional facial thirds and straight facial profile with a concave lower facial third. A deficient and asymmetric smile was evident due to the malposition of the maxillary canines. The intraoral photographs evidenced complete Class II molar and canine relationships, 4-mm overjet, 3-mm overbite, and negative tooth-size discrepancy of 5 mm in the maxillary arch and 8.5 mm in the mandibular arch, besides 2-mm deviation of the maxillary midline to the right side. The patient also exhibited crossbite on the left side (). The panoramic radiograph exhibited all teeth except for the third molars. Also, there was significant horizontal bone loss for the age at the premolar region; endodontic treatment of tooth 46 and impairment of dental health due to large restorations in several teeth ().
Cephalometric analysis revealed skeletal Class I relationship (ANB = 1o). Considering occlusal plane angle values (SN.Ocl = 33o), mandibular plane (SN.GoGn = 42o) and Y axis (Y-axis = 62o), a hyperdivergent skeletal pattern prevailed. The maxillary incisors were buccally tipped and protruded (1-NA = 9 mm and 1.NA = 26o) and the mandibular incisors were well positioned (1-NB = 6 mm and 1.NB = 25o, IMPA = 90o). The upper lip was retruded in 4 mm and the lower, in 2 mm in relation to the S line ( and ).
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pmc-6266799-1
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A 50-year-old man was admitted to the emergency department with abdominal pain. Blood testing showed signs of inflammation. Renal function was normal. Computed tomopgraphy (CT) of the abdomen was performed after intravenous contrast injection (Figure ). No clear explanation for the abdominal pain was found. However, there was a small supernumerary kidney fused on top of a normal-sized left kidney. The upper kidney had a normal, anteromedially oriented pelvis but the lower kidney had an anterolaterally oriented pelvis (dotted arrows, Figure ) rendering an S-shaped kidney. There were two separate but closely related ureters, as shown on the three-dimensional volume rendering (3D VR) of the excretory system (Figure ). Three left renal arteries could be seen: one at the normal level supplying the upper part and two at a lower level supplying the lower kidney, best seen on the 3D VR of the renal arteries (Figure ). Multiple interconnected renal veins were seen forming three common trunks, draining into the inferior vena cava and left common iliac vein (not shown). The right kidney had a normal shape, single vascular supply and ureter.
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pmc-6266963-1
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An 18-year-old male patient was admitted to our cardiology department with shortness of breath and chest pain on exertion lasting for one year. His blood profile, biochemical analyses, and physical examination were normal. Echocardiography revealed cystic mass with internal septations in the interventricular septum protruding into the left ventricular cavity. Prospective electrocardiography (ECG) gated cardiac computed tomography (CT) and magnetic resonance imaging (MRI) was performed for further characterization of the mass. Contrast-enhanced CT of the patient demonstrated a hypodense mass with a size of 5.5 × 6 × 5.5 cm in the interventricular septum (arrow) (Figure ). The four chamber view images of the patient on steady-state free precision MRI during the diastole (Figure ) and the systole (Figure ) depicted that the lesion mostly involved the mid-ventricular and the apical parts of the interventricular septum and had hyperintense signal characteristics with internal septations (arrows). Also, the lesion substantially obliterated the left ventricular cavity during the systole (short arrow) without causing significant obstruction at the ventricular outflow tract (Figure ). On provisional diagnosis of hydatid cyst, blood serology was requested, which yielded positive results for Echinococcus granulosus. Further imaging studies, which were ordered for the possible other locations that might be involved by hydatid cysts, yielded negative results. The patient refused any medical or surgical treatment and was discharged of his own will.
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pmc-6267010-1
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A 27-year-old Hispanic man with no significant past medical history presented to an emergency department with a 5-day history of headache, pain with ocular movements, and intermittent blurred vision starting 1 day after being immunized with DTaP-IPV. Magnetic resonance imaging and a magnetic resonance venogram of his brain were unremarkable. A lumbar puncture revealed a normal opening pressure and cerebrospinal fluid studies were positive for myelin basic protein but negative for oligoclonal bands and neuromyelitis optica autoantibody serology.
On examination, his best corrected vision was 20/100 in his right eye and 20/70 in his left eye. Intraocular pressures, pupil examination, ocular alignment, and extraocular movements were normal. Confrontational visual fields were restricted in both eyes. Posterior segment examination showed optic nerve swelling and hyperemia in both eyes (Fig. ) and two microaneurysms in the mid periphery of his left eye. No evidence of vitritis, retinal vasculitis, or choroiditis was seen in either eye.
Serum laboratory testing showed elevated glycated hemoglobin (A1C) at 6.9%, aspartate aminotransferase (AST), and alanine aminotransferase (ALT). Other liver tests including bilirubin, alkaline phosphatase, and hepatitis serologies were normal. Tests for infectious and inflammatory etiologies including angiotensin-converting enzyme (ACE), lysozyme, antinuclear antibody (ANA), cytoplasmic antineutrophil cytoplasmic antibodies (c-ANCA), perinuclear antineutrophil cytoplasmic antibodies (p-ANCA), lupus panel, rapid plasma reagin (RPR), fluorescent treponemal antibody absorption (FTA-ABS), chest X-ray, and QuantiFERON Gold assay, which were normal. Over the next 5 days, his vision declined to counting fingers at 30.5 cm (1 foot) in both eyes. A relative afferent pupil defect and dyschromatopsia developed on the left. Automated Humphrey visual field (HVF) testing demonstrated global depression in both eyes (Fig. ).
He was diagnosed as having DTaP-IPV vaccination-related optic neuritis and started on intravenously administered Solu-Medrol (methylprednisolone). One week later, his headache resolved and vision improved to 20/20 in his right eye and 20/25 in his left eye with less optic nerve hyperemia and swelling. He was discharged on a prednisone taper and an orally administered diabetic medication. One month later, his vision improved to 20/20 with resolution of the optic neuritis without residual visual field deficit in both eyes.
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pmc-6267060-1
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A 56-year-old Japanese man with end-stage renal disease secondary to diabetic nephropathy visited our hospital because of abdominal pain and pus discharge from the exit site of a PD catheter. He had redness around the exit site and tenderness at the subcutaneous tunnel. The dialysis effluent was not cloudy and the effluent cell count was < 100/μL. Thus, we performed pus swab culture based on a suspicion of ESI and TI. Treatment was started using intravenous vancomycin (1.5 g/day), oral minocycline (200 mg/day), and topical gentamicin ointment, because the patient had a history of ESI caused by methicillin-resistant coagulase-negative Staphylococcus (MRCNS).
The patient was admitted to our hospital 3 days later, with the following vital signs: blood pressure of 165/104 mmHg, pulse of 86 bpm, and temperature of 36.7 °C. A physical examination revealed continued pus discharge from the exit site, as well as redness and swelling of the surrounding skin (Fig. ). No rebound tenderness or muscle guarding were observed. A complete blood count from the admission revealed a white blood cell count of 8390/μL, a red blood cell count of 380 × 104/μL, a hemoglobin level of 10.1 g/dL, and a platelet count of 21.4 × 104/μL. The blood test results revealed an albumin level of 2.9 g/dL, a blood urea nitrogen level of 54.3 mg/dL, a creatinine level of 13.95 mg/dL, and a C-reactive protein (CRP) level of 0.09 mg/dL. The white cell count in the dialysis effluent was 7/μL (mononuclear cells: 6/μL, polymorphonuclear cells: 1/μL), and the pus culture revealed the presence of MRCNS.
We continued to suspect that the ESI and TI were caused by MRCNS, and continued treatment using intravenous vancomycin (Fig. ). However, abdominal computed tomography on day 7 revealed an increased density of fatty tissue around the PD catheter (Fig. a, b). Thus, we performed simultaneous removal and reinsertion of the PD catheter at a new exit site, based on the refractory ESI and TI in the absence of peritonitis. The PD was re-started on day 12, although evaluation of the dialysis effluent on day 15 revealed that the white cell count had increased to 631/μL (mononuclear cells: 455/μL, polymorphonuclear cells: 176/μL), which supported a diagnosis of peritonitis. Negative results were obtained from Gram staining and acid-fast staining of the dialysis effluent. The dialysis effluent was then cultured in aerobic, anaerobic, and Ogawa media. Treatment was switched to intravenous meropenem (0.5 g/day) and intraperitoneal amikacin (2 mg/kg/day). On day 23, we observed a rise in the CRP level (10.1 mg/dL) and the number of white cells in the dialysis effluent (4126/μL). Therefore, the patient was converted to hemodialysis (HD) on day 24.
On day 29, gram-positive rods (GPR) were found in the aerobic culture of the dialysis effluent from day 15. These bacilli were sensitive to imipenem but resistant to meropenem and amikacin. On day 30, we noticed growth of acid-fast bacilli in Ogawa medium. The GPR from the aerobic culture were identified as M. abscessus on day 33. M. abscessus was also detected in cultures of the dialysis effluents from days 20 and 28. After switching the treatment from meropenem to imipenem, the CRP levels decreased. However, ESI and TI persisted at the reinserted catheter and wound dehiscence was detected at the old exit site (Fig. c, d). Thus, the second catheter was removed on day 37, and the patient’s condition subsequently improved. Additional susceptibility testing revealed that the M. abscessus was sensitive to clarithromycin, and oral clarithromycin was started after 4 weeks of treatment using imipenem. Cultures of the catheter tip and intraoperative ascites fluid revealed positive results for M. abscessus. In addition, pathological findings at the original exit site revealed granulomatous dermatitis and a positive result during acid-fast staining. M. abscessus was detected in the wound cultures until day 58, although negative results were observed thereafter. On day 101, the patient developed nausea and vomiting, and computed tomography revealed intestinal dilation (Fig. e, f). On day 103, the patient underwent laparoscopic adhesiolysis surgery because of adhesive ileus, and the intraoperative findings revealed adhesion of the intestinal tract near the abdominal wall site where the catheter had been placed. There were no findings of encapsulating peritoneal sclerosis, and M. abscessus was not detected during culture of the intraoperative ascites specimen. The patient was discharged on day 115, completed 6 months of treatment using clarithromycin monotherapy, and did not develop infection or ileus recurrence during the next 2 years.
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pmc-6267074-1
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A 6-month old, 7.5 kg, male baby born at 31 weeks of gestation was admitted to a local hospital with a 20-day history of cough, wheezing, 5-day history of fever and with pleural effusion indicated by chest X-ray. Detection of Bordetella pertussis by polymerase chain reaction was positive with the nasopharyngeal specimen. The child was admitted to Pediatric Intensive care unit (PICU) in Shanghai Children’s Hospital with breathless with a temperature of 37.1 °C and heart rate 170 to 190 beats/min, who developed respiratory failure requiring intubated and mechanical ventilation [positive end-expiratory pressure (PEEP) of 6 cmH2O; a pressure support of 18 cmH2O; a respiratory rate (RR) of 25 /min; and a fraction of inspired oxygen of 0.6; Peak inspiratory pressures (PIPs) were between 27 and 29 cmH2O]. Meanwhile, laboratory studies revealed the presence of leukocytosis [26,780 white blood cells (WBCs)/μL] with 1 mg/L C-reactive protein (CRP). A chest X-radiograph showed dense opacification of the right upper and right middle lobe and patchy opacification of the left upper lobe (Fig. a). Over the next 48 h, despite application of lung protective strategies and a restrictive fluid strategy, the patient deteriorated with worsening lung compliance and hypoxemia, as well as the dense opacification of the right upper and right middle lobe enlarged (Fig.b). At the same time, the tidal volume decreased from 6 mL/kg to 2.5 mL/kg, and Cdyn (Pulmonary dynamic compliance) decreased from 3.3 (0.44/kg) to 1.2 (0.16/kg). The patient’s PIPs continued to rise to 40 cmH2O with a plateau pressure of 31 cmH2O, PaO2/FiO2 dropped to 60 mmHg and oxygen index (OI) raised to 30 lasting for 6 h. Importantly, the echocardiography (performed 3rd day after admission) demonstrated PHT (46 mmHg) with a normal left ventricular function. The diameter of the pulmonary artery was 1 cm, pulmonary artery blood flow was 1.0 m/s, the tricuspid regurgitation flow was 1.5 m/s, the tricuspid annulus was 1.5 cm, and TAPSE was 18. Furthermore, septic shock occurred, norepinephrine (0.3μg/kg.min) and dobutamine (10μg/kg.min) were needed to maintain his blood pressure.
Considering in anticipation of a rapid hemodynamic collapse resulting from severe PHT in pertussis, the initiation of ECMO was performed with an arterial blood gas noted as pH 7.20, PaCO2 77.9 mmHg and PaO2 60 mmHg. The ECMO support was equipped with a centrifugal pump and an artificial lung was used (Medtronic Bio-Medicus, Minneapolis, MN, USA). The patient inserted cannula through right neck vessels, and was placed on veno-arterial (VA) ECMO support with a pump flow of 500 to 600 mL/min and FiO2 of 1.0. The 12-Fr arterial cannula (Bio-Medicus) was placed in the right common carotid artery and the 14-Fr venous cannula (Bio-Medicus) in the right internal jugular vein. (Fig. a). During ECMO support, the ventilator setting was mode with SIMV+PS, FiO2 0.4, PIP 25–26 cmH2O, PEEP 8-9cmH2O, RR 25 rpm, which ensured a 3-5 ml/kg tidal volume. During prone position ventilation, the setting was mode with SIMV+PS, FiO2 0.4, PIP 24-25cmH2O, PEEP 8cmH2O, RR 20–25 rpm.
During the first 3 days of ECMO support, the tidal volume of this patient was only 2.5 mL/kg, and lung compliance was poor. Prone position ventilation was conducted. A team requires 5 staff members participated. A doctor positioned up to the patient’s head and fixed the catheters, one nurse positioned on each side of the bed to manage the lines and tubes. We firstly placed a blanket around the patient’s arms and turned the patient toward the ventilator. Then, the doctor held the patient’s head and fixed the catheters, while two nurses turned the patient prone. Lastly, we straightened the blanket and adjusted lines and tubes, and placed the patient’s arms in the swimmers position (the arms were positioned up toward the baby’s shoulders). During this process, another doctor was responsible for monitoring the ECMO and a third nurse was responsible for administering drugs. To supine the patient, the process was performed reversely.
There was no change in cannula position shown by X-ray when changing position (Fig. a, b), and there was no malfunction of blood access due to bending or dislodgement of the cannula when changing position. At day 4 after ECMO initiation, exhaled tidal volumes were increased to 6 mL/kg and effusion in lung were improved indicated by chest radiographs (Figs. c).
During the first 5 days of ECMO support, the patient was characterized by recurrent attacks of airway spasm lasting for 20s to 2 min each time. Consequently, the airway spasm resulted in sudden declined ECMO flow (0.15 L/min), decreased blood oxygen saturation (80%), and decreased ventilator tidal volume (2 mL/kg). Except for prone position, magnesium sulfate was given and care bundles including hand washing, heightened focus on oral hygiene, closed endotracheal suctioning, prone position ventilation, appropriate sedation, reducing unnecessary stimulus (eg. assess the state of consciousness when put the position), following the nursing sequence of sputum aspiration, diapering and feeding, using full-barrier precautions during the insertion of all catheters were performed to help improving lung compliance and reduce airway spasm. The ECMO flow started around 0.55 L/min and was adjusted according to the hemodynamic status (maintained mean airway pressure [MAP] at 50–60 mmHg). The target blood flow was 80 mL/kg/min, and coagulation profile was monitored through detecting the levels of activated coagulation time (ACT) and activated partial thromboplastin time (aPTT). The values of ACT were detected once 3–4 h and aPTT were detected once per 4–6 h. According to the results of ACT and aPTT, the dose of heparin was regulated to maintain an ACT of 180–220 s or APTT with 1.5–2 fold of normal value. During ECMO therapy, ECMO flow was adjusted to keep the serum ScVO2 > 60% and lactate level < 2 mmol/L. The target oxygenation was a normal arterial partial pressure of carbon dioxide (PaCO2) and partial pressure of oxygen (PaO2) (Fig. ).
From the 6th day of ECMO therapy, the clinical feature of airway spasm was improved. And ventilator setting was gradually reduced. After 297-h of ECMO support, the patient was weaned off V-A ECMO. During the period of ECMO therapy, respiratory mechanical parameters were monitored as shown in Fig. . And the ECMO flow dropped with the occurrence of airway spasm, the relationship between tidal volume and ECMO flow were shown in Fig. , which represented the onset and impact of airway spasm, as well as the duration of prone position. The enteral nutrition (Infatrini, Nutricia) was conducted through nasogastric tube which provided 80-100 kcal/kg.d.
One week later, the child was successfully extubated. After a 7-day high flow nasal cannula oxygen therapy, he was transferred to the escort ward on 26 days after PICU admission, and eventually discharged with a near normal neurologic examination. The time line of this case can be consulted in the Additional file .
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pmc-6267130-1
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A 23-year-old male was presented at the emergency department following a direct trauma to the knee during a football match when another player fell on his extended knee. An evident deformity was present in the knee suggesting a lateral displacement of patella. The main symptoms were pain and limited range of motion; however, there was no neurovascular damage. The knee was locked in almost complete extension.
Radiological examination of the knee was conducted confirming a lateral displaced patella without any other apparent lesion. It also showed that the patella was not laterally rotated, as is common in most of the cases of patellar dislocation [], but maintained a correct coronal alignment (Fig. ).
A closed reduction with hyperextension and manipulation of the patella towards medial was attempted first in the emergency department, followed by a second attempt under general anaesthesia in the operation room; both attempts were unsuccessful.
Due to persistent irreducibility, a knee arthroscopy was performed in order to reduce the locked patellar dislocation. With the patient lying supine with a thigh tourniquet, standard anterolateral and anteromedial plus supra-lateral portals were performed with the knee in extension. Inflation of the knee joint with saline solution did not result reduction of the patellar dislocation. Arthroscopic inspection revealed a lateral extra-articular dislocated patella. The patella was folded in a pocket-like structure made from the lateral retinaculum that was hindering reduction. By applying lateral leverage with a tissue elevator the patella was relocated (like using a shoehorn). Further arthroscopic inspection revealed no other lesions within the joint except for the lesion of medial patellar retinaculum (Fig. ).
Normal patellar tracking was confirmed arthroscopically. An extension splint was applied during 2 weeks allowing full weight bearing. Then a hinged brace was applied with weekly progressive flexion (30°–45°–60°–75°–90°) until complete ROM.
At final follow-up (6 months), the patient was able to return to all sport activities without limitations.
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pmc-6267439-1
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Case-ZIKV01 is a 32-year-old woman who presented with a maculopapular rash on her trunk and upper limbs associated with abdominal pain and diarrhea. Two to four days after symptom onset, the exanthema became pruriginous and reached the lower limbs with the appearance of petechiae. She experienced intense epigastralgia that resolved after the fifth day. Arthralgia on ankles and edema of fingers were noticed on day 4 and lasted until day 7. No other symptoms, including fever, were reported. No significant laboratory findings were noted. The patient was subsequently followed for 78 days with no additional complications. The patient, who lives in São Paulo state, reported a trip to Espirito Santo state two weeks before the onset of symptoms.
Case-ZIKV17 is a 33-year-old man who initially reported a fever lasting 2 days, followed by headache and retro-orbital pain (days 2–3). On day 4 he reported a maculopapular rash accompanied by intense itching and diffuse arthralgia. All symptoms cleared up by day 5. The patient was subsequently studied for 298 days. He experienced pain and edema of his right testicle at 25 days post-symptomatic onset. Orchitis due to ZIKV infection was diagnosed after confirmation through serology and qRT-PCR. No other potential agents were identified.
Further monitoring of ZIKV shedding was conducted, with express patient consent, since he was planning to conceive a baby with his partner. During the study period, the patient underwent two prostate ultrasounds (USG prostate) and two spermograms. The patient presented with prostatitis at 71 days post symptoms onset, which normalized by 218 days post symptoms onset. The spermograms were normal at days 100 and 223 post symptoms onset. The couple adopted strict preventive measures with daily use of insect repellent and barrier contraception during sexual intercourse for the entire period of confirmed virus shedding. After the first negative semen sample (day 168), the patient provided weekly samples (day 174) for 2 consecutive weeks, followed by two more biweekly collections (day 200) and finally a monthly collection (day 235), totaling 67 days with negative qRT-PCR results for all tested samples. At 235 days post symptoms onset the patient and his wife began actively trying to conceive. After two months (day 298) the patient’s wife confirmed pregnancy. At the time, and further during pregnancy, she was monitored for ZIKV infection by qRT-PCR, IgG and IgM. She remained negative.
Cases-ZIKV18 and -ZIKV19 are a husband and wife who experienced ZIKV-like illness in close succession. ZIKV19 is a 64-year-old man, who reported lumbar pain, fever and malaise at onset. After 3 days of symptoms a macular rash appeared which resolved after 6 days. The patient was subsequently studied for 155 days.
ZIKV18 is a 68-year-old woman who began experiencing symptoms of malaise five days after her husband. Three days after onset, a macular rash appeared on the face, body and limbs and erythematous plaque in the right leg, accompanied by fever, headache, ocular hyperemia and articular edema. On the fourth day the exanthema became more intense, followed by somnolence, chills and tiredness. The articular edema remained for 5 weeks. The patient was subsequently studied for 108 days. There were no other reports of complications during the study period.
Timelines for all four patients with the principle clinical events and laboratorial results are shown in .
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pmc-6267613-1
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Case 1: Infected Achilles Wound
A 62-year-old female presented with a left Achilles wound in the context of severe peripheral vascular disease status-post revascularization of bilateral lower extremities. Comorbid conditions included obesity, insulin-dependent diabetes, and heart failure. She presented with severe pain, redness, and swelling of her lower extremity and a 4 x 4 x 0.5 cm wound on her left Achilles, probing along the tendon for over 15 cm. She was taken to the operating room (OR) immediately, and under local anesthesia, a large abscess extending to the mid-portion of the gastrocnemius muscles was drained. She returned to the OR two additional times where the V.A.C. VERAFLO™ was placed and the wound subsequently surgically closed. The foam was instilled with normal saline, 20 cc every two hours, which was allowed to dwell for 10 minutes. This case demonstrates how the bacterial load was reduced and the wound optimized, allowing for wound closure (Figures -).
Dilution of inflammatory and cytotoxic macromolecules
Wound healing typically follows a highly regulated, predictable pattern that is usually characterized by overlapping phases. These include hemostasis, inflammation, proliferation, and remodeling. Chronic, non-healing wounds do not follow this pattern of normal healing, and prior studies have elucidated these mechanisms, including elevated levels of inflammatory cytokines and proteases with low levels of growth factors [-]. Specifically, these wounds show elevated levels of metalloproteinases (MMP) which have been suggested to play a key role in poor wound healing []. One of the key proposed mechanisms of NPWT is the removal of fluid and, in the case of NPWTi-d, dilution of cytotoxic and inflammatory molecules. Studies have shown wounds treated with NPWT to have lower levels of MMPs and increased expression of leukocyte chemoattractants [].
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pmc-6267613-2
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Case 2: Upper Extremity Necrotizing Soft Tissue Infection
A 31-year-old male with poorly controlled type I diabetes mellitus and a history of intravenous drug abuse presented with a necrotizing soft tissue infection following an upper extremity trauma from a work injury. This was aggressively debrided, leaving him with a grossly swollen and inflamed extremity with a large open wound and exposed brachial vessels. A V.A.C. VERAFLO™ device was placed with a double layer of Adaptic™ non-adhering dressing (Systagenix Wound Management, Acelity, San Antonio, TX ) covering the vessels. This was instilled with 40 cc of normal saline every two hours and allowed to dwell for 10 minutes. Three days later, he presented with massive bleeding for which he was emergently returned to the OR for a saphenous vein patch angioplasty, a biceps brachii muscle flap, a skin graft, and a conventional V.A.C. device. Three days later, he bled a second time requiring an additional saphenous vein patch angioplasty. Six weeks after the injury, his wound had closed and the inflammation had resolved. This case demonstrates how substantial inflammation resolves in association with the use of NPWTi-d (Figures -).
Additional wound hydration
It is widely accepted that moist wounds epithelialize faster than dry wounds. A key property of NPWT is the removal of fluid and optimizing the wound microenvironment through thermal insulation and prevention of evaporative losses []. NPWTi-d harnesses the known benefits of wound irrigation and allows for the targeted and repeated even delivery of topical solutions to the wound bed. This additional capacity of NPWTi-d is thought to assist with wound healing.
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pmc-6267613-3
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Case 3: Infected Total Knee
A 58-year-old male with chronic obstructive pulmonary disease (COPD) and non-insulin-dependent diabetes suffered a fall resulting in a complex left lower extremity compound fracture three years prior. He was treated with an external fixator placement that was complicated by pin site osteomyelitis. Two years later, he developed post-traumatic osteoarthritis of the left knee and underwent left total knee arthroplasty (TKR) and removal of the tibial plate. Approximately three weeks following the TKR, he suffered massive loss of the anterior skin with exposure of the prosthesis. He had multiple previous scars on his legs from his injury and prior surgeries, complicating the flap design, in addition to a tight skin envelope around his knee; his gastrocnemius muscle was also atrophied due to disuse. He was not a free tissue transfer candidate; therefore, we placed him in a V.A.C. VERAFLO™ device and performed a large reverse anterior thigh transposition flap based on a geniculate perforator. This was delayed and transferred in place. The donor site was treated with an Integra® Dermal Regeneration Template (Integra LifeScience Corp., Plainsboro, NJ) with a conventional V.A.C. placement. He developed an additional exposure of his patellar component that required removal, exchange of the polyethylene components, and re-transposition of the flap and skin grafts. Five months following his TKR, he remains in a post-acute care facility. He has a persistent sinus tract below the reconstruction with an otherwise closed wound and continues on suppressive antibiotics. This case illustrates the benefit of maintaining a moist wound, as well as the powerful pro-angiogenic role present with NPWTi-d device (Figures -).
Enhanced angiogenesis and intermittent application
Erba and colleagues showed that NPWT stimulates angiogenesis through several mechanisms, including microdeformation, removal of factors inhibiting angiogenesis, and through the creation of a hypoxia gradient []. This gradient in tissue hypoxia upregulates hypoxia-inducible factor-1α and vascular endothelial growth factor (VEGF) expression which ultimately drives microvessel density and directionalized vessel sprouting []. Most NPWT systems use continuous suction at 125 mmHg [-]. One distinct and potentially important aspect of NPWTi-d is the use of intermittent suction applied after the period of instillation and dwell. In pre-clinical studies, the use of intermittent NPWT was shown to promote more robust granulation tissue and achieve faster wound closure rates []. Recent pre-clinical studies investigating these effects in NPWTi-d have also suggested similar findings compared to NPWT continuous and dynamic pressure control (DPC) applications, although robust comparative effectiveness studies are lacking.
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pmc-6267613-4
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Case 4: Radiated Pelvic Exenteration Defect
A 59-year-old female underwent radical vulvectomy and sentinel lymph node biopsy for poorly differentiated squamous cell carcinoma. Her pathology revealed positive margins treated with adjuvant radiation, receiving a total dose of 5,940 cGy. All lymph nodes were negative. One year after completing radiation, she presented with pain along the vulva and gluteal region showing recurrent squamous cell carcinoma.
She underwent a pelvic exenteration, leaving a large surgical wound measuring 30 x 30 cm. Her thigh skin could not mobilize to fill this massive defect, and urinary and colonic diversion precluded the abdomen as a donor site. She was not a free tissue transfer candidate primarily due to her morbid obesity. We, therefore, mobilized the omentum into the pelvis and a large VAC VERAFLO™ device was fit to size. We instilled 100 cc of saline every two hours, allowing it to dwell for 10 minutes. Three days later, the patient returned to the OR where an abdominal advancement flap was created covering 10 cm over the pelvic inlet. The omental flap was found to be viable, and a Polyglactin 910 mesh (Ethicon, Sommerville, NJ) was sutured over the omentum connecting it to the soft tissues over the pelvic opening. The skin in the area was further advanced, substantially reducing the size of her wound. A V.A.C. VERAFLO™ device was again placed. The patient was returned to the OR twice weekly for two weeks for subsequent standard V.A.C. changes and further advancement of local tissues to close her wound. She eventually underwent a large left anterolateral thigh musculocutaneous flap for definitive closure.
Unfortunately, approximately six months following pelvic exenteration, she was diagnosed with recurrent inoperable disease. She passed away 11 months following her surgery (Figures -).
Complications encountered
Bleeding
Use of NPWT open reticulated polyurethane foams directly on exposed vessels or at sites at risk of increased bleeding is contraindicated. We followed the recommendation in the literature and our own experience in using a non-adherent layer as a protective barrier over the vessels. As reported in Case 2, despite covering the exposed brachial vessels with two layers of Adaptic™ and placing a lower suction setting of 75 mm Hg, our patient had a major, life-threatening bleeding episode. He did have a second bleeding episode following muscle flap coverage, suggesting that the bleeding was likely due to an inherent infection in the arterial wall.
Maintaining a Seal
Our transition to instillation was notable for several issues, including leakage of the fluid and the ability of the fluid to disperse throughout the foam. The manufacturer (Acelity, San Antonio, TX) has made important changes in product design (V.A.C. Ulta™ System with VERAFLO™), including a skin prep and drape modifications to improve the seal, as well as to create a more hydrophilic foam (polyurethane ester rather than polyurethane ether foam). This foam comes in two varieties with the black foam having a similar pore structure as the classic Granufoam™ foam (Acelity, San Antonio, TX) and a grey foam that is a reticulated open cell foam dressing (ROCF-CC) (V.A.C. VERAFLO Cleanse Choice™ Dressing) that has a variable pore size and a contact layer with multiple 1.0 cm holes spaced at 0.5 cm in a honeycomb array []. These changes have mitigated prior frustrations and shortcomings. Clinicians continue to be challenged by placing NPWT devices in areas of irregular skin contour or near mucous membranes.
Pain
Patients with large complex wounds can have significant pain. Many have some degree of discomfort during the fluid instillation and evacuation phases of this therapy. Some patients have reported difficulty with sleeping. We have discontinued instillation therapy during sleep in some cases.
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pmc-6267707-1
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A 51-year-old female with a history of stage 1 hypertension was admitted to the hospital post cardiac arrest. She had a significant family history of premature coronary artery disease. Her father had a coronary artery disease diagnosed in his 40’s, her mother had a pacemaker inserted, and she had two first degree relatives diagnosed with an early cardiac disease. She is a nonsmoker, nonalcoholic drinker and denied recreational drug use. She was in her usual state of health and functionally active until her husband noticed her moaning and eventually unresponsive in the middle of the night. Prior to this, the patient did not complain of any chest pain, dyspnea, dizziness, lightheadedness or any other constitutional symptoms. Her husband started cardiopulmonary resuscitation and was taken over by the emergency medical staff (EMS). She was intubated and defibrillated five times by EMS for ventricular fibrillation then was given a bolus of amiodarone. She eventually had a return of spontaneous circulation and was transported to the hospital in which she was noted to have decorticate posturing with no purposeful movements. Electrocardiogram (ECG) during this time showed sinus rhythm (Figure ). She was admitted to the coronary care unit and was placed on targeted temperature management and was maintained on amiodarone drip. Transthoracic echocardiogram showed no valvular abnormalities, normal left atrium and left ventricular cavity size but with borderline concentric left ventricular hypertrophy with an ejection fraction of 56% and note of subtle regional wall motion abnormalities. About 12 hours after initiating the targeted temperature management, the patient was in severe bradycardia in the mid 30’s and a decision was made to hold the amiodarone at that point. The patient completed the targeted temperature management protocol and eventually had a full neurologic recovery thereafter.
She was extubated and subsequently transferred to the floor. She was scheduled for cardiac catheterization; however, she had witnessed ventricular fibrillation arrest on the floor (Figure ). Advanced cardiopulmonary resuscitation was initiated and she was revived immediately after defibrillation. A total of three minutes of resuscitation was performed and she was following commands afterwards. She was also given an amiodarone bolus and transferred back to coronary care unit. ECG did not show any ST elevations at this time. Subsequently, she had 23 more episodes of ventricular fibrillation arrest (Figure ) over a six-hour period which were intervened by timely defibrillation and administration of antiarrhythmic medications and inotropic agents. The antiarrhythmic medications administered were amiodarone and lidocaine boluses and drips. Intravenous magnesium was also given during the resuscitation course. Emergent cardiac catheterization showed minimal coronary artery disease. A transvenous pacemaker wire was placed due to bradycardia during a code in the catheterization laboratory, although the bradycardia did not initiate the arrest. An intra-aortic balloon pump was placed. Subsequently the balloon pump and temporary pacemaker wire were removed after she eventually became more hemodynamically stable. She once again had a full neurologic recovery and underwent an uneventful implantation of a dual-chamber implantable cardiac defibrillator (ICD). She was discharged from the hospital on amiodarone therapy and was closely followed up in the cardiology outpatient clinic. Cardiac magnetic resonance imaging was done which showed mild biventricular enlargement but with normal regional systolic function, no late gadolinium enhancement consistent with the absence of myocardial inflammation, infiltration or infarction and with no imaging features of ARVC. She eventually had a targeted genetic testing for idiopathic ventricular fibrillation and was found to have a mutation in the desmoglein-2 (DSG2) gene (c.338T > C, pVal1113Ala), which is a gene typically involved in ARVC.
She had been readmitted several times to the hospital due to palpitations, dizziness, lightheadedness, and defibrillator shocks. Her defibrillator had been interrogated as well as her antiarrhythmic medication had been adjusted which improved her symptoms and reduced defibrillator discharge. Because of intermittent episodes of defibrillator firing due to ventricular fibrillation despite antiarrhythmic medications and intracardiac device, a ventricular fibrillation radiofrequency catheter ablation was performed successfully. Thereafter, she had no repeated episodes of palpitations, dizziness, lightheadedness, and defibrillator shocks.
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pmc-6267826-1
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A 35-year-old woman was referred to the Department of Gastrointestinal Surgery of The University of Tokyo Hospital for evaluation of a gastric lesion in August 2005. During esophagogastroduodenoscopy, a 30-mm flat and depressed lesion was identified at the anterior wall of the upper gastric body and was diagnosed as Type 0-IIc gastric cancer (Fig. ). A pathological analysis of the biopsy specimen determined a moderately differentiated tubular adenocarcinoma (tub2). The patient underwent laparoscopic-assisted total gastrectomy (LATG) with Roux en-Y reconstruction and lymph node dissection (D1 + No. 7) in accordance with the Japanese Gastric Cancer Treatment Guidelines []. A pathological analysis of the specimen revealed the depth of the lesion remaining in mucosal layer, without any lymph node metastasis. The patient showed good progress after the operation and did not receive any further treatment including chemotherapy. She was only instructed to continue oral iron supplementation for postoperative chronic anemia after discharge. She became pregnant 1 year and 8 months after the operation. After her pregnancy, radiographic examinations were excluded during the follow-up period while oral iron supplements were continued. In addition, 500 μg of methylcobalamin (MeCbl), an active form of vitamin B12, was intramuscularly injected once a month for a potential vitamin B12 deficiency, although her serum vitamin B12 level was within normal range. No pregnancy-associated discomfort or illness was observed including hyperemesis gravidarum during her pregnancy while the fetus was developing normally. In May 2008, the baby was born by vaginal delivery at 41 weeks of gestation. Delivery time was 4 h and 20 min, and the baby was delivered as a healthy normal child weighing 3076 g. The mother’s weight change and the uterus height change of the fetus are shown in Fig. a–c.
After delivery, she continued to take oral iron supplements and vitamin B12 intramuscular injection and had kept exclusively breastfeeding without any problems until her first postpartum check-up. However, during the blood examination after her postoperative follow-up, 2 months after her delivery, the serum AST (aspartate transaminase) and ALT (alanine transaminase) levels of the patient were found to be elevated. We presumed that excessive oral food intake influenced gastrointestinal absorption leading to liver dysfunction. After changing exclusively breastfeeding into the combination of formula and breastfeeding, the serum AST and ALT levels were restored within the normal range (Fig. a, b). The patient has been followed-up for 10 years and has not shown recurrence of gastric cancer. Also, the child showed a good progress.
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pmc-6267840-1
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A 50-year-old woman presented with an episode of hemoptysis. She also reported low grade fevers, night sweats and chest discomfort. Her past medical history was notable for allergic rhinitis/sinusitis and asthma, and she experienced recurring upper respiratory tract infections, sinusitis, and bronchitis approximately three times per year. Chest computed tomography imaging revealed left upper lobe consolidation with a central cavitary lesion, adjacent scattered consolidation, ground-glass opacities and tree-in-bud markings (Fig. ). She subsequently underwent bronchoscopy, and bronchoalveolar lavage grew Mycobacterium avium complex (MAC). Consequently, she underwent cavitary MAC treatment with rifampin, ethambutol, erythromycin, and intravenous amikacin with improvements in low-grade fever, night sweats, and chest discomfort.
Four months later, her symptoms returned, and chest imaging revealed a new right basilar lung infiltrate, with increased ground-glass and consolidative focal patchy disease, as well as bronchiectasis. Repeat bronchoscopy revealed a positive fungal culture for Aspergillus and she was subsequently started on voriconazole. Upon re-evaluation, the patient exhibited oral ulcers, purpuric skin lesions, and new onset peripheral neuropathy and was referred for an additional opinion.
Pertinent laboratory findings included a complete blood count with a total white cell count of 11,000 cells per microliter with marked hypereosinophilia at 5200 eosinophils per microliter. Erythrocyte sedimentation rate was elevated at 92 mm/hr., and C-reactive protein was elevated at 1.154 mg/dL (normal less than 0.4). Quantitative serum immunoglobulin E (IgE) was also elevated at 520 international units/mL (normal 0 to 11). Patient was negative for ANCA, hepatitis B or C, PR3 antibody and MPO antibody.
Pulmonary function testing demonstrated normal total lung capacity (TLC) and thoracic gas volume but an elevated residual volume at 2.93 L (154% of predicted) suggesting mild air trapping. Airflows were normal, with a forced expiratory volume in one second (FEV1) of 2.67 L (90% of predicted) and forced vital capacity (FVC) was 3.23 L (86% of predicted) with no significant bronchodilator response. Diffusing capacity of the lungs for carbon monoxide (DLCO) was mildly reduced at 20.97 or 77% of predicted, but when corrected for alveolar volume (VA), corrected to normal with a DLCO/VA of 4.59 or 86% of predicted. The VA was significantly less than the TLC, suggesting gas mal-distribution.
Repeat bronchoscopy was performed with transbronchial biopsies. Histopathology showed acute and chronic inflammation, scattered eosinophils (42 eosinophils per 60 × high power field), fresh hemorrhage and tissue eosinophilia most prominently in the bronchial wall and adjacent alveolated lung parenchyma. There was no evidence of granuloma formation or necrotizing vasculitis (Figs. , and ).
The constellation of compelling clinical, radiographic, laboratory, and pathologic findings believed to suggest GPA/EGPA overlap syndrome included a cavitary pulmonary lesion unresponsive to anti-microbial therapy, oral ulcers, purpuric skin lesions, peripheral neuropathy, long-standing asthma, chronic sinusitis, one or more episodes of alveolar hemorrhage, migratory pulmonary infiltrates on chest imaging, peripheral hypereosinophilia, a markedly elevated IgE level, elevated inflammatory markers and eosinophilic inflammation in the pulmonary parenchyma on histopathologic examination.
In addition to the very complex clinical picture most suggestive of EGPA/GPA overlap syndrome, there was compelling evidence for a concomitant aspergillus pulmonary infection, and the patient also met criteria for a diagnosis of allergic bronchopulmonary aspergillosis. There is a possibility that the aspergillus pulmonary infection may have complicated our patient’s clinical picture as it may have contributed to her pulmonary cavitation and sinusitis.
While the patient had been previously treated with oral corticosteroids and anti-fungal therapy for a prolonged period of time with little improvement, with the addition of anti-interleukin (IL)-5 therapy and cytotoxic therapy (azathioprine) to the oral corticosteroids and anti-fungal therapy, the patient had dramatic improvement in her disease manifestations.
Between 1986 and 2017, we identified 15 cases that described an overlap syndrome involving both GPA and EGPA (Table ). Patients ranged in age between 21 and 78. Of those whose sexes were identified, 80 % of cases described were female. All cases described involved the lungs, 60 % described sinus involvement, and over half had displayed renal involvement. An overwhelming majority of patients were positive for c-ANCA and demonstrated eosinophilia (peripheral or tissue involvement). A preponderance of the cases described were treated with systemic corticosteroids combined with cytotoxic/immunosuppressive agents.
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pmc-6267888-1
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A 30-year old male patient was referred to our tertiary retina clinic at the University of California Irvine for evaluation of a macular lesion and long-standing vision drop in his left eye. He had a diagnosis of PWS. He was on insulin therapy for type 2 diabetes mellitus, amlodipine for hypertension and testosterone replacement therapy for hypogonadism. He had a history of strabismus surgery in his left eye at the age of 2 years.
His best-corrected visual acuity (BCVA) was 20/20 in his right eye and 20/150 in his left eye. Intraocular pressure was 16 mmHg in both eyes. He had full visual fields on confrontation. His eyes were orthophoric with full ocular motility in all cardinal directions and no nystagmus. Anterior segment examination was unremarkable. No iris transillumination was noted.
Fundus examination of both eyes revealed mild hypertensive retinopathy and mild nonproliferative diabetic retinopathy (NPDR). His left fundus showed a subfoveal disciform scar surrounded by a large area of pigmentary disturbance and mottling.
Green (532 nm) fundus autofluorescence (FAF) imaging revealed normal FAF in the right eye, while the left eye showed an area of central decreased FAF surrounded by a ring of increased FAF, which was, in turn, surrounded by an area of decreased FAF. This triple zone corresponds to the disciform scar and surrounding areas of retinal pigment epithelial disturbance and atrophy. There was a large area of mildly increased FAF surrounding the triple zone and occupying almost the entire macula. The latter area most likely corresponded to diseased retinal pigment epithelium (RPE) and is suggestive of prior presence of subretinal fluid.
Fluorescein angiography (FA) of both eyes showed scattered microaneurysms. The left eye showed staining of the disciform scar, but no leakage was detected.
Spectral-domain OCT (SD-OCT) of the right eye showed a shallow rudimentary foveal depression, incursion of inner retinal layers, widening of outer nuclear layer (ONL) and lengthening of outer segments; consistent with grade 1 foveal hypoplasia (fovea plana). The left eye had dome-shaped subretinal hyperreflective material (SHRM) beneath the fovea, causing disorganization of the overlying retinal layers. A few tiny cysts were noted overlying the SHRM.
SD-OCT angiography (OCTA) imaging of the right eye demonstrated a very small foveal avascular zone (FAZ) area and the presence of macular foveal capillaries (MFC) crossing the FAZ on the superficial capillary plexus (SCP) slab, and a slightly wider, but still reduced, FAZ on the deep capillary plexus (DCP) slab. OCTA of the left eye showed a type 2 macular neovascular lesion.
Figures and show multimodal imaging findings in the right and left eyes, respectively.
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pmc-6269334-1
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A 37-year-old man underwent contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI) to evaluate hepatic nodules incidentally detected in ultrasonography. The CT and MRI results revealed portal vein ramification of a Shindoh’s independent right lateral type []. The first branch of the portal vein issued into the right lateral branch and then formed the trunk of the left portal vein and right paramedian portal veins. The right paramedian portal pedicle then formed the right umbilical segment of the portal vein and joined with the right-sided ligamentum teres (RSLT) (Figs. and ). The middle hepatic vein (MHV) was located to the left of the RSLT, which is one of the characteristic imaging features of RSLT [] (Fig. ). The gallbladder lay with its cholecystic axis to the left of the umbilical fissure (Fig. a, b). The hepatic nodules were radiologically diagnosed as hemangiomas.
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pmc-6269334-2
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A 42-year-old man with choroidal malignant melanoma underwent a regular MRI examination for possible distant metastasis. The MRI revealed portal vein ramification of a Shindoh’s independent right lateral type [], with the umbilical portion of the portal vein tilting to the right and joining with the RSLT and the MHV running to the left of the RSLT (Figs. and ). The diverging point of the dorsal branch of the right anterior portal vein (PA–D) was distal to that of the left lateral portal vein (PLL), which is the opposite of normal anatomy and one of the axial imaging features described by Yamashita et al. [] for identifying RSLT (Fig. ). The gallbladder had a normal cholecystic axis to the right of the umbilical fissure (Fig. a, b). Magnetic resonance cholangiopancreatography (MRCP) revealed right anterior hepatic duct confluence with the left hepatic duct before draining into the common bile duct (CBD), whereas the right posterior hepatic duct drained into the CBD directly, just following the portal ramification. The gallbladder was in its normal right-sided position (Fig. ).
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pmc-6269334-3
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A 72-year-old woman with rectal cancer underwent a regular dynamic contrast-enhanced CT survey for possible distant metastasis. The CT images revealed portal vein ramification of a Shindoh’s independent right lateral type [], with the umbilical portion of the portal vein tilting to the right and joining with the RSLT and the MHV running to the left of the RSLT (Fig. ). The gallbladder had a normal cholecystic axis to the right of the umbilical fissure (Fig. ).
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pmc-6273428-1
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A 76-year-old woman presented with the chief complaint of a non-healing ulcer on the left leg, with pain and swelling. The ulcer had not responded to consistent conventional treatment for more than one year. The patient was a non-smoker and non-dinker. There was no history of trauma, varicose veins, or calf pain, but a history of vascular disease. Physical examination revealed a single shallow, irregular, large, almost rectangular shaped, about 6.8 × 4.3 cm ulcer on her lower left leg. The surface of the ulcer demonstrated shiny granulation tissue (a). There were mild eczematous changes of the surrounding skin. There was a purulent foul smelling moderate amount of discharge from the wound, with surrounding edema. The patient reported pain at the affected area while walking and was referred to the angiology service for wound management. Despite rigorous medical measures in the form of frequent use of anabolic and topical antimicrobial agents (clostebol, neomycin, gentamicin and silver sulphadiazine), topical corticosteroids (betamethasone dipropionate), debridement, and dressing for the ulcer, the subject had a recurrent chronic wound on the left leg with an area measuring 23.52 cm2. The ulcer was in stage II, with not well defined wound margins. The angiologist prescribed a magistral formulation of a 2% (w/w) Punica granatum peel ethanolic extract (PGMF) based on a hydrophilic cream and zinc oxide. PGMF was applied to the ulcer once a day and the physician’s decision of application was taken with the written informed consent of the patient. Oral iron therapy, diuretics and other supplementary treatment were initiated. Tramadol was prescribed as pain reliever and no antibiotics were given during this course of treatment. After application, the ulcer was dressed with cotton gauge. Within six weeks, the ulcer had decreased to one quarter of its original size and had completely healed six weeks later (b–d). A total of 90 applications were needed for complete healing. No adverse effects of PGMF were observed.
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pmc-6274901-1
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A 43 years old woman, born from non-consanguineous parents and with no documented developmental structural or mental defects, presented in February 2014 a progressive dysarthria, motor slowness, and changes of behavior, becoming listless and aggressive. In April 2014 she presented a sudden aphasia and right hemiparesis for which she was hospitalized elsewhere. The acute phase cerebral Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) scan showed acute cortico-subcortical left fronto-parietal and left internal capsule acute lesions. Cerebral Computed Tomography Angiography (CTA) scan detected a bilateral stenosis of internal carotid arteries (ICAs), middle cerebral arteries (MCAs), and anterior cerebral arteries (ACAs). Coagulation and autoimmunity screening were normal, as well as electrocardiography (ECG) monitoring and echocardiography. Aspirin therapy was introduced, and the patient was addressed to a rehabilitation course. After an initial improvement of the right hemiparesis, her clinical status worsened, and she developed a vertical ophthalmoparesis and dystonic movements in the left arm. For these symptoms, a biochemistry examination was performed, which resulted in being normal, as well as an abdominal ultrasound examination showing liver steatosis. A new cerebral MRI did not show any changes and detected the previously observed left frontal and insular lesions, as well as new right frontal and parietal lesions. Cerebral MRA confirmed the severe stenosis of the ICAs, MCAs, and ACAs, mostly in the left side (). Thus, a suspicion of moyamoya angiopathy was posed, and in June 2015, she was addressed to our center. The neurological evaluation, performed at that time, showed the presence of severe attention deficit, orofacial apraxia, dysarthria, slight left hemianopia, and right hemiparesis with bilateral coreoatetosic movements and Babinski sign. Peculiar characteristics were a long narrowing face with bifrontal prominence, a low frontal hairline, arched eyebrows, downslanting palpebral fissures, hypertelorism, broad nasal tip, upturned nares, and large and low-set ears. Digital subtraction angiography (DSA) revealed stenosis of the ICAs with apex occlusion in the right one and hypertrophic aspects of lenticulostriate arteries with leptomeningeal anastomosis from ophthalmic artery and frontal artery to provide blood flow to the frontal regions. Blood flow in the temporal, parietal, and occipital regions was supported by posterior cerebral artery. Electroencephalography revealed left temporal epileptic activity. Perfusion MRI showed a decreased relative cerebral blood flow (rCBF) and cerebral blood volume (rCBV) into ischemic areas, as well as a bilateral increased time to peak (rTTP) and mean transit time (rMTT). A diagnosis of MA was confirmed, and given the somatic peculiar characteristics and the cognitive impairment associated with the MA, the patient underwent an array-comparative genomic hybridization (aCGH), after informed consent.
In September 2016 and in May 2017, the patient underwent a direct (STA-MCA) and indirect revascularization (encephalo-duro-arterio-synangiosis (EDAS)) surgery in the left and right hemispheres, respectively. The post-surgical clinical course was regular, and the post-surgery DSA confirmed the by-pass perviety. A few months later, she presented focal seizures for which she performed a new electroencephalogram showing left parietotemporal sharp waves and started treatment with levetiracetam, with complete resolution of seizures. At the two-year follow-up evaluation, she did not refer to any other symptoms, and we did not detect any other signs of cerebral or systemic involvement.
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pmc-6275155-1
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A 13-year-old girl visited our department with complaints of swelling and facial asymmetry on the left side of the face. The patient was first diagnosed as craniofacial monostotic FD involving the left maxilla, subnasal, and zygoma. The patient underwent primary bone contouring surgery under general anesthesia. At age 18, the patient presented with a swelling on the left side of the mid face region, suggesting lesion re-growth. On clinical extra-oral examination, a significant facial asymmetry was present. Computed tomographic (CT) images showed a typical dysplastic dense mass affecting the maxillary and zygomatic bones. The preoperative cephalometric analysis showed canting of 5.5 mm downwards. After confirming the cessation of the growth, presurgical orthodontic treatment was continued for 14 months. At age 20, final surgical treatment objectives were established. The patient exhibited severe maxillary occlusal canting with gummy smile and compensatory mandibular occlusal canting, but showed a relatively symmetrical outline of the mandible. Le Fort I osteotomy was performed to correct occlusal canting, and the dysplastic bone obliterating the maxillary sinus was also removed. Concomitantly, a massive amount of friable dysplastic bone from the maxillary alveolar bone to the zygoma and infraorbital areas was extensively removed. Mandibular sagittal split ramus osteotomy (BSSRO) was performed to correct compensatory mandibular occlusal canting. To adjust the mandibular chin and body contour, Triaca style mandibular wing osteotomy [] was also performed. Osteotomized maxilla was rigidly fixed with four 1.5-mm-thick microplates whereas BSSRO was fixed with two 2-mm-thick miniplates (Fig. , ). The fixation of the screws was slightly weaker at the FD-involved side than the contralateral normal maxillary bone.
The postoperative course was uneventful, and postoperative orthodontic treatment was started 4 weeks after the surgery. There was no evidence of skeletal relapse at the postoperative 2-year follow-up (Fig. ). The coronal and sagittal views of the CT showed that the bone union at the osteotomized bone was composed of dysplastic bone, and the maxillary sinus was obliterated again. The plates were covered by the newly formed dysplastic bone (Fig. ). However, slightly expanded external cortex of the left zygoma and maxilla on the left side did not influence the facial symmetry. The patient did not want further surgery and was satisfied with the final outcome.
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pmc-6275155-2
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A 29-year-old woman complained of swelling on the left side of the face. CT images showed a radiodense network of the expanded dysplastic bone lesion involving maxilla, zygoma, ethmoid bones, orbit, cranial base, and hemimandible. Therefore, the patient was diagnosed as polyostotic craniofacial FD. The patient did not exhibit visual disorders. The preoperative cephalometric analysis showed canting of 5 mm downwards. An orthognathic surgical procedure was planned. Le Fort I osteotomy, sagittal split ramus osteotomy, and genioplasty were performed under general anesthesia (Fig. ). To ensure maxillary impaction to correct occlusal canting, the FD lesion was extensively removed during the Le Fort I osteotomy. After removal of the dysplastic bone on the maxilla and debulking at the zygomaticomaxillary region, rigid internal fixation was performed with miniplates (2 mm thick). BSSRO was performed to improve mandibular occlusal canting and remove the dysplastic bone. Additional body shaving and genioplasty were performed to improve esthetics. The postoperative recovery was uneventful. The occlusion was stable after 18 months postoperatively, and there was no evidence of recurrence or relapse. At the time of plate removal, 2 years after the initial surgery, the site of maxillary Le Fort I osteotomy was examined and a significant osseous union was noted between the osteotomized segments (Fig. ). However, slight expansion of the external cortex of the left maxilla was noted, which did not influence facial symmetry. Four years after the initial surgery, the patient did not show further expansion or re-growth of the dysplastic lesion (Fig. ).
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pmc-6275160-1
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A 71-year-old man, known with polycythemia vera and aortastenosis, sustained a wound laterally on his right mid lower leg when he fell and struck a hospital bed, which failed to heal over a 2-year period. The patient was referred 2 years post trauma to a wound centre as the wound had failed to heal after 6 months of treatment by his General Practitioner.
At the wound centre the patient received treatment for a non-healing ulcer by means of various ointments, honey and dressings, with a view to referral for skin transplantation if the wound did not heal satisfactorily. It is noted that the patient was not diabetic and did not have any cardiovascular risk factors but was undergoing follow-up for aortastenosis and polycythemia vera. There was initially improvement in the wound over an approximately six-month period, but due to the return of hypergranulation tissue, increasing size of the wound and a request from the patient, a punch biopsy of the wound was taken which confirmed basal cell carcinoma. The patient was referred to The Department of Plastic Surgery and Breast Surgery, Roskilde Hospital for excision of the carcinoma. The ulcer, approximately 4 cm in diameter (), was surgically excised with a 5 mm margin, without the use of frozen sections, and covered with a split thickness skin transplant. The histology showed an ulcerated basal cell carcinoma of nodular type, with growth deep into the dermis, but not involving the subcutaneous tissue. Histology also showed that the BCC was radically removed. Post-operative control included follow up in the Plastic Surgery clinic for approximately one month. After the skin transplant healed the patient was discharged from follow up in our clinic to yearly control at his Dermatologist. There has been no local recurrence of the BCC. The patient was subsequently diagnosed, with diabetes mellitus type two (DMT2) and started treatment with dietary changes and exercise.
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pmc-6275162-1
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A 36-year-old female presented to the emergency department two months post caesarean section with a sudden onset of severe abdominal pain for 6 h. The pain was associated with two episodes of vomiting, abdominal distension and constipation. The patient underwent MGB 2 years prior to presentation. In addition, she was complaining of severe dyspepsia and unsatisfactory weight loss following her MGB. She has no known chronic medical illnesses. She had undergone open cholecystectomy 12 years ago.
On physical examination, she was afebrile, tachycardic with normal blood pressure. Abdominal examination showed right-sided abdominal fullness and tenderness and empty rectum on digital rectal examination.
Radiological studies including abdominal X-ray () and computed tomography (CT) scan () revealed a 14-cm dilatation of the cecum occupying the left upper quadrant of the abdomen with the swirling appearance of the mesentery. These findings were confirmed through emergency exploratory laparotomy. Intraoperatively, the cecum was still viable but severely dilated and twisted (). An incarcerated Petersen’s hernia was found with no signs of strangulation. At laparotomy, she underwent a right hemicolectomy, reduction of Petersen’s hernia, and conversion of MGB to a conventional retrocolic Roux-en-Y gastric bypass with closure of the mesentric defect. The post-operative period went uneventful and she was discharged from the hospital in good condition. Post-operative follow-up at 24 months showcased satisfactory weight loss and improvement of dyspepsia symptoms with no recurrence of bowel obstruction symptoms.
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pmc-6275170-1
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This is a case of 36-year-old man who presented with features of intestinal obstruction to our institution. He was diagnosed in Egypt as a case of intestinal Schistosomiasis one year prior to admission and received treatment. However, follow up investigation to confirm eradication of the disease was not done. The patient presented to our surgical department complaining of absolute constipation, abdominal pain, abdominal distention and vomiting. On examination the abdomen was distended and bowel sounds were absent. There was tenderness in the lower part of the abdomen and digital rectal examination revealed collapsed rectum. Computed tomography (CT) scan of the abdomen revealed dilated bowel loops (). The patient was resuscitated adequately and exploratory laparotomy was done through infra-umbilical midline incision. There was localized turbid fluid collection, dilated small and large bowel loops due to paralytic ileus and gangrenous appendix. Appendectomy was done () followed by lavage and closure. The patient received antibiotics and passed through a smooth postoperative period and was discharged home after one week approximately. The appendix specimen was sent for histopathology and the result came back as extensive necrosis of the appendix with multiple viable Schistosomal ova (). Subsequent stool analysis revealed no ova. Despite of that the patient received a single dose of praziquantel therapy and he is quite well now.
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pmc-6275210-1
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A 17 years old girl was admitted to the emergency department (ED) with history of epigastric pain for 9 months duration along with severe symptoms of vomiting (undigested food and bloody content), drastic weight loss (around 4 kg over 4 months). Patient was not having any urinary symptom or any altered bowel habit.
-Past medical history: Instances of eating hair years ago.
-And no history of previous surgery.
-On Examination:
Temperature: 36.8 °C, Pulse rate: 125 beat per minute, Breathing rate: 22 breaths per minute and Blood pressure: 119/65 mmHg.
Abdomen: There was tenderness and hard mass over epigastria area extending towards the right hypochondrial area. Bowel sound was sluggish.
CBC, LFT, RFT was within normal limit.
CT scan of abdomen was performed at another Hospital: The stomach was grossly distended, compressed with displacement of the transverse colon. The colon was filled of intra-luminal abnormal mass like contents with mottled air pattern extended to fill the pylorus and first part of duodenum. Findings were the proofs for possible trichobezoar.
Endoscopic removal of hair was failed and the patient was prepared for the operation.
Upper midline incision was performed and was deepened using electrocautery. After entering the abdominal cavity, distended stomach with firm content was observed. Vertical gastrostomy was done using electrocautery of about 10–14 cm in length. The stomach was found with full of ingested hair, occupying most of the stomach. Ball of hair were then retrieved and removed (A and B). Suction and irrigation were done. Negative suction tube was inserted and the position was adjusted intra-operatively. The stomach was then closed in two layers at continuous manner. First layer was closed with full-thickness using 3-0 PDS and the other layer with Lembert technique using 3-0 PDS. Then the small bowel series or test relatively collapsed with no evidence of any distal obstruction. After suction and irrigation, homeostasis was achieved and then the abdominal wall was closed by using Loop PDS. Staplers were used in surgery in place of sutures to close the skin. The patient tolerated the procedure, recovered smoothly and then was sent to the recovery room with general stable condition.
Day 4: Post operation nasogastric tube (NGT) was removed and on the next day, the patient was discharged with outpatient clinic follow up (next week in 07/06/2017).
In clinic, the surgical wound was found to be infected with pus, but there was no sign of cellulites and dressing was done.
13/06/2017: Vacuum (VAC) dressing was applied.
22/06/2017: The wound was cleaned and VAC dressing was removed.
31/07/2017: Patient had an appointment at the psychiatric clinic and she was found stable with no active psychiatric complains.
20/09/2017: The wound was completely healed and the patient was discharged from the General Surgery Clinic.
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pmc-6276154-1
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A 17-year-old otherwise healthy Chinese female presented with tender skin lesion on her left ankle for almost three months. The lesion initially presented as an indurated erythema with central dusky necrosis, mimicking insect bites (Fig. a). She didn’t recall any evident history of trauma. During the same period, she developed extensive petechiae on both lower extremities and was diagnosed as Henoch-Schӧnlein purpura in local hospital. Subsequently she was treated with systemic corticosteroids (maximum dosage 30 mg/d) for two months. While the petechiae subsided, the ankle erythema ulcerated with suppurative discharge. She was then admitted to our hospital in March, 2017. Physical examination revealed a 3.5 cm*2.5 cm demarcated ellipsoidal ulceration covered with thick black crust and purulent discharge (Fig.b). Regional lymph nodes were not palpable. Except for these lesions, the girl was generally in good health.
Histological examination of biopsied tissue revealed multiple branching, septate hyphae and moniliform fungal elements in the dermis (Fig. a), which were positive with periodic acid–Schiff and Gomori-Grocott methenamine silver staining (Fig. b).
Tissue culture was performed and incubated at both 26 °C and 35 °C on Sabouraud’s dextrose agar (SDA) and yielded restricted, white to grey and velvety colony at 4 weeks (Fig. a). With extended incubation, the colony turned brownish at 8 weeks (Fig. b). Slides culture revealed filamentous and septate hyphae with intercalary and ballooned, chlamydospore-like structures, as well as annellidic and ampulliform conidiogenous cells along with truncated, bullet-shaped, smooth conidia (Fig. c), which resembled those found in Scopulariopsis species. Within 5 weeks, small black fruiting structures were growing on the surface of the colony, resulting in observance of globose perithecial ascomata with cylindrical necks, and a dark peridium (Fig. d). Fungal culture was identified as M. cirrosus based on the morphological features and confirmed by the molecular sequencing of internal transcribed spacer (ITS) region gene and β-tubulin gene. Comparison of the ITS (642 bp) (Genbank accession number MF450505) and β-tubulin (501 bp) (Genbank accession number MF455507) sequence with the Genbank database revealed 100% similarity with M. cirrosus reference strain CBS 116405 and CBS 115860, respectively.
In vitro susceptibility was tested according to the guidelines presented in document M38-A2 of the Clinical and Laboratory Standards Institute (CLSI) []. The minimum inhibitory concentration (MIC) was determined visually as the concentration that resulted in 100% inhibition []. The minimal effective concentration (MEC) endpoint was taken as the lowest concentration at which the visual growth pattern change from granular to filamentous growth was detected, microscopically seen as restricted hyphal growth. The results revealed that multiple antifungal agents were inactive against the isolate, with MIC value of 4 μg/ml for voriconazole (VRC), 8 μg/ml for caspofungin (CAS), >64 μg/ml for fluconazole (FLZ), >16 μg/ml for itraconazole (ITC), posaconazole (POS), amphotericin B (AMB) and terbinafine (TRB), and MEC value of > 16 μg/ml for micafungin (MCF). Due to the patient’s economic condition, itraconazole was applied. However, despite the discouraging result of in vitro susceptibilities, significant improvement of skin lesions was achieved after 10 weeks treatment with itraconazole 200 mg per day (Fig. c). No adverse event was reported.
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pmc-6276199-1
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A 42-year-old Chinese woman with good past health presented to our hospital on March 26, 2013, with bilateral progressive blurring of vision for approximately 8 days. She had no redness or photophobia, nor did she have pain at rest or upon eye movement. She did not experience headache, nausea, or vomiting or have any recent history of head trauma. Furthermore, she had no recent flulike illness, upper respiratory tract symptoms, fever, chills, or rigor. Physical examination revealed visual acuity (VA) down to hand movements only on the right eye and finger-counting on the left, as well as bilateral red color desaturation. Pupillary light reflexes were present but sluggish, with a right relative afferent pupillary defect detected. Extraocular movements were full, and intraocular pressure was normal in both eyes. Slit-lamp examination revealed normal anterior segments with no evidence of inflammation. Dilated fundal examination showed pink discs with sharp margins and cup-to-disc ratios of 0.3 bilaterally. Bilateral retinas were normal with dry maculas. Neurological examination revealed intact cranial nerves, normal limb power and sensation, generalized brisk but symmetrical jerks with downgoing plantar reflexes, and absence of cerebellar signs. No changes in sensorium or psychotic features were noted.
Magnetic resonance imaging (MRI) of the brain with contrast the next day revealed radiological evidence of bilateral optic neuritis (ON), limbic and cortical encephalitis, subcortical and pontine myelitis, and leptomeningitis (Fig. ). Blood tests revealed normal white blood cell counts, liver and renal function, and inflammatory markers, including C-reactive protein and erythrocyte sedimentation rate. The patient’s Venereal Disease Research Laboratory (VDRL) test result was nonreactive, and her test result for Lyme disease was negative. An extensive panel of autoimmune antibodies was negative, including antinuclear antibody, anti-double-stranded DNA antibody, anti-extractable nuclear antigen, and rheumatoid factor. Results of testing for specific antibodies for autoimmune encephalitis were also negative, including anti-aquaporin 4 antibody, anti-myelin oligodendrocyte glycoprotein, anti-voltage-gated potassium channel antibody, and anti-N-methyl-d-aspartate receptor antibodies. Antibodies against paraneoplastic antigens were screened, including anti-neuronal nuclear antibody type I, anti-neuronal nuclear antibody type II (anti-Ma2), anti-CRMP5 antibody, anti-Yo, anti-Ri, and anti-Hu, and all results were negative. Tumor markers, including cancer antigens CA 15-3 and CA 19-9 as well as carcinoembryonic antigen, and α-fetoprotein were all within normal limits. A lumbar puncture was performed, showing normal opening pressure of 12 mmHg, normal cerebrospinal fluid (CSF) cell count and biochemistry, and absence of oligoclonal proteins, as well as negative microbiological findings for bacterial, mycobacterial, and fungal growth; cryptococcal antigen; herpes simplex virus; and Mycobacterium tuberculosis complex PCR; and VDRL. Positron emission tomography-computed tomography (PET-CT) revealed no hypermetabolic lesion or tumor focus. Optical coherence tomography of the nerve fiber layer showed bilateral nasal thinning, consistent with myopic eyes with tilted disc configuration. In view of a likely underlying autoimmune etiology, a negative lumbar puncture microbiological workup, and evidence of limbic involvement found upon neuroimaging, a presumptive diagnosis of autoimmune limbic encephalitis was made. The patient was started on high-dose pulsed steroid therapy (intravenous methylprednisolone 1 g/day over four divided doses) 3 days after admission for 72 hours, followed by switching to oral steroids with gradual tapering according to the Optic Neuritis Treatment Trial protocol []. Over the next few months, the patient’s VA and color vision slowly improved from hand movement to 0.7 bilaterally.
MRI of the cervical and thoracic spine, with and without contrast, in July 2013 showed no evidence of myelitis or demyelinating lesions. On follow-up in August 2013, however, the patient reported cognitive slowing, new-onset facial asymmetry, slurring of speech, right upper limb weakness, and unsteady gait. Physical examination revealed right upper limb power 4/5, brisk reflexes throughout, and right lower limb ataxia. The patient’s VA had decreased to 20/200 bilaterally, with persistent sluggish pupil response. Repeat MRI of the brain with contrast in September 2013 showed resolution of previous white matter lesions but new periventricular and subcortical white matter of bilateral cerebral hemispheres, left-sided corpus callosum, bilateral internal capsules, left thalamus, bilateral hippocampal tails, left brainstem, and right cerebellar peduncle (Fig. ). Lumbar puncture and whole-body PET-CT were repeated, which showed no abnormalities. In view of relapse, the patient was restarted on intravenous methylprednisolone, followed by maintenance therapy with oral prednisolone with the aim of tapering the steroid over time. She was also started on azathioprine 25 mg/day beginning 30 September 2013, with the aim of increasing the dosage over time in order to replace oral prednisolone.
VA improved back to 0.7 bilaterally after initiation of immunosuppressant therapy. Limb power returned to full strength by November 2013. Throughout the next 2 years, the patient had slow improvement of VA back to 0.7 bilaterally and color vision recovering bilaterally. She was tapered off oral steroids by March 2016, and she was found to have stable VA at her last follow-up in July 2016. She is currently being followed with annual PET-CT imaging for tumor surveillance as well as annual serological surveillance.
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pmc-6276240-1
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We present a 69-year-old woman with a history of metastatic leiomyosarcoma, for which pazopanib treatment was initiated at the standard dose of 800 mg QD, after she progressed upon first-line chemotherapy with doxorubicin. During the first month of treatment pazopanib was temporarily withheld twice due to significant toxicities, including fatigue, nausea, vomiting and syncope. Pazopanib plasma concentrations were measured and Cmin was calculated using the formula proposed by Wang et al [], showing high pazopanib trough levels (36.1 mg/L and 41 mg/L). Pazopanib treatment was resumed after sequential dose reductions to 600 mg QD and 200 mg QD. The last dose was well tolerated despite mild liver enzyme disorders and hypertension. During the following months, the patient developed diarrhea and hypothyroidism, after which pazopanib was further reduced to 200 mg every other day. Pazopanib Cmin remained adequate at this eight times lower than standard dose at first, although the last two measurements were below the efficacy-threshold (Fig. ). Unfortunately, 14 months after start of treatment, progressive disease was observed, after which chemotherapy with trabectedin was started.
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pmc-6276240-2
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The second case is a 50-year-old male with metastatic angiosarcoma and a history of Gilbert syndrome, previously treated with 6 cycles of doxorubicin in combination with ifosfamide. Pazopanib treatment was started at the standard dose of 800 mg QD. Shortly hereafter, total bilirubin increased to twice the upper limit of normal with only minimal elevation of direct bilirubin, after which pazopanib was halted. Upon normalization of bilirubin, pazopanib treatment was resumed at a reduced dose of 400 mg QD and later 200 mg QD 1-week-on – 1-week-off. At the end of the on-treatment week pazopanib Cmin was 29.9 mg/L (Fig. ). The patient is still on treatment now, nine months after pazopanib initiation, with a partial remission.
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pmc-6276387-1
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A 50-year-old Caucasian woman with no previous ocular pathologies was admitted to our department in 2011 presenting with reduced vision and metamorphopsia in her right eye. Her best corrected visual acuity (BCVA) was 2/10 (6/30) in the right eye and 10/10 (6/6) in the left eye. A clinical examination revealed branch retinal vein occlusion (BRVO) in the inferotemporal vein with secondary MO. Over the course of the subsequent 6 months, anti-VEGF (ranibizumab) treatment was administered, resulting in improved visual acuity without complete resolution of the MO. We then opted to treat the patient with dexamethasone intravitreal implant injection. The procedure was performed in the operating room under topical anaesthesia and sterile conditions. Povidone-iodine periocular scrub and 10% solution were applied to the eyelids, followed by 5% solution to the ocular surface for 3 min. The eye was then draped, and a sterile speculum was used to perform the dexamethasone intravitreal implant injection. After implantation, moxifloxacin 0.5% drops were administered four times daily for 1 week. The patient responded well to the dexamethasone implant and showed BCVA improvement to 9/10 (6/7) and MO resolution lasting for >4 months. Six months after implantation, MO was again present, and BCVA had reduced to 6/9.5. Dexamethasone implant was applied for the second time in the same manner as previously described. On the fourth day after implantation, the patient was admitted to our department with acute pain, redness, and vision loss in her right eye. The right BCVA at that point was 1/20 (6/120). Ophthalmic examination revealed conjunctival injection, mild corneal oedema, grade 3+ anterior chamber cells, hypopyon (1 mm), and an IOP of 8 mmHg. A posterior chamber investigation revealed reduced red reflex and vitreous haze that made observation of retinal detail difficult. The implant was located inferiorly, and fibrous membranes were present in the vitreous cavity with attachment to the retinal tissue. A diagnosis of acute endophthalmitis post implantation was made. On the same evening, a 23G pars plana vitrectomy was performed, and a vitreous tap was acquired at the beginning of the procedure for cultures, sensitivity, and polymerase chain reaction (PCR). We planned to remove the dexamethasone implant using a vitrectome and 23G forceps during the vitrectomy, but this was not possible due to dense membrane formation and low visualisation of the retina at the implantation site. For safety reasons, we opted to leave the implant in place, and at the end of the procedure, we injected vancomycin (1 mg/0.1 ml) and amikacin (0.4 mg/0.1 ml) into the vitreous cavity. Postoperatively, the patient received topical treatment with norfloxacin 0.3% and vancomycin (50 mg/ml) fortified antibiotic drops hourly, atropine drops three times daily, and systemic corticosteroids (8 mg methylprednisolone) daily. Vitreous cultures were positive for Staphylococcus epidermidis, and PCR was negative for Streptococcus spp., Haemophilus influenzae, Staphylococcus aureus, Pseudomonas aeruginosa, Neisseria meningitidis, Streptococcus pneumoniae, and Listeria monocytogenes. The patient responded well to treatment, with a gradual reduction in inflammation and hypopyon as well as an improved vision at 48 h after surgery. One week after treatment, a tapering regimen of drops and steroids was initiated. Three months later, the patient's BCVA was 3/10 (6/19), and a third dexamethasone implantation was performed 6 months after the onset of endophthalmitis, resulting in a BCVA of 8/10 (6/7.5) after 4 months. At the time of writing, 5 years after the onset of endophthalmitis, the patient's VA is 10/10 (6/6, after phacoemulsification) in the right eye, and she requires a dexamethasone implantation once a year.
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pmc-6276388-1
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An 87-year-old Asian woman who fell from a 4-meter height and hit her head was transferred to our emergency room. It was difficult to conduct a detailed neurological examination due to her severe dementia, but she had no obvious neurological symptoms upon arrival at our hospital. Computed tomography of her cervical spine showed a left nondisplaced impaction OCF with an occipital condyle-C1 interval of 2.5 mm and a 5 mm translation of C1-C2 (). The fracture pattern itself, classified as Anderson and Montesano type 1 and Tuli type 1, was considered stable. However, as a craniocervical misalignment and C1-C2 translation were present, the patient was placed in a halo device temporarily before surgery. We decided to perform reduction prior to surgery; thus, while we applied rotational traction force, we adjusted the halo ring position. After reduction, computed tomography was performed and we confirmed the complete reduction of both the atlantooccipital joint and the atlantoaxial joint (). We proceeded to internal segmental fixation with an occipital bone plate and bilateral pedicle screws for C2 (). An autologous iliac crest bone graft was used in an augmented posterior fusion. The halo vest was removed immediately after surgery. The patient's clinical status improved, and she was discharged to a rehabilitation facility.
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pmc-6276391-1
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An 82-year-old man who lived alone was brought to a regional hospital from his home after being found by his family in a confused state. His past medical history was significant for DM2, hypertension, dyslipidemia, benign prostatic hyperplasia, and chronic back pain. His medications consisted of metformin 1000 mg p.o. BID, sitagliptin 50 mg p.o. BID, ramipril 10 mg p.o. daily, tamsulosin 0.4 mg p.o. daily, hydrochlorothiazide 25 mg p.o. daily, and meloxicam 7.5 mg p.o. daily. He had no known prior history of cardiac or renal disease, and baseline serum creatinine [Cr] was 79 μmol/L.
On initial assessment, the patient was in no acute distress, although he was disoriented and confused [Glasgow Coma Scale 14]. He complained of mild nausea with recent decreased oral intake, but there was no history of diarrhea. He had no history of infectious symptoms, toxic ingestions, recent medication changes, or witnessed seizure activity. On physical examination he had normal cardiorespiratory findings and no focal neurologic signs. His initial vital signs were blood pressure 150/83 mm Hg, heart rate 124/min, respiratory rate 33/min, oxygen saturation 100% on room air, and temperature 34.9° Celsius. His initial bloodwork results revealed a profound metabolic acidosis and acute kidney injury [].
A chest X-ray was unremarkable, and his electrocardiogram showed a wide QRS complex, prolonged PR interval, and peaked T waves.
He was initially treated with intravenous [i.v.] dextrose, a crystalloid bolus, and calcium gluconate, and his potassium was shifted intracellularly with inhaled salbutamol and i.v insulin. He also received one ampule of i.v. sodium bicarbonate. Given his profound metabolic disturbances, he was urgently transferred by ambulance to the local tertiary care centre for expedited management and consideration of dialysis. Upon arrival to the Emergency Department of the tertiary care hospital, he was oriented to person and place but not time, and vital signs were: blood pressure 110/80 mm Hg, heart rate 80/min, respiratory rate 20/min, and oxygen saturation 100% on room air. Within 30 minutes of arrival his mean arterial pressure [MAP] dropped to <65 mm Hg, and he required norepinephrine and vasopressin infusions as well as consultation with the intensive care unit [ICU]. At this time he also received a bolus of 1.5 litres of normal saline, and his axillary temperature was measured as 32.1° Celsius. An arterial blood gas [ABG] revealed profound metabolic acidemia ().
Blood cultures and serum toxicology screen for ethanol, methanol, isopropanol, acetone, ethylene glycol, acetaminophen, salicylates, and tricyclic antidepressants were negative. His remaining metabolic workup, including plasma thyroid stimulating hormone and plasma cortisol, was normal. Computerized tomography of the head, abdomen, and pelvis were negative for acute findings with no evidence of urinary obstruction or hydronephrosis. An assay for serum metformin level was unfortunately not available at our institution.
The patient's level of consciousness remained stable, and he consistently protected his airway. He required infusion of vasoactive agents for approximately 20 hours to maintain adequate blood pressure. He was heated externally using warming blankets, and his urine output during the first 24 hours of admission was 205 mL. In addition to treatment with i.v. crystalloid and bicarbonate, he underwent urgent hemodialysis treatment [dialysate HCO3− concentration of 36 mEq/L] via central venous access, which was repeated the next day. After two days he was transferred out of the ICU and went on to achieve renal recovery [serum Cr 95 μmol/L on day 8 of hospitalization] with restoration of urine output, acid-base and electrolyte balance. His functional status at the time of discharge was at his baseline. The metformin was discontinued from the day of admission, and he was prescribed a new regimen of oral antihyperglycemic medications for his diabetes.
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pmc-6276405-1
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A 44-year-old male with no significant past medical history presented to us with the complaint of lower back pain radiating to both groins for the last 2 months. Vitals at presentation were BP of 120/70 mm Hg, pulse of 82, RR of 18/minute, and T of 98.9°F. Physical exam and lab work were unremarkable. CT scan showed a sclerotic and lytic lesion in T12 (). Further investigation with CT scan of chest revealed multiple bilateral pulmonary nodules along with mediastinal and hilar lymphadenopathy suggestive of a metastatic malignant process (). CT-guided biopsy of a pulmonary nodule showed malignant neoplasm with spindle cells (). Immunohistochemical stains showed tumor cells positive for Bcl-2, vimentin, EMA, CD56, CD99, and TLE-1 and negative for CD34, CD10, P63, cytokeratin, S100, desmin, and synaptophysin. Interphase FISH was performed and was positive for a rearrangement involving SYT gene (18q11) consistent with a synovial sarcoma. Biopsy of the T2 lesion showed exactly the same IHC and FISH findings. The whole-body CT scan for extrathoracic disease was negative. The patient was referred to another facility for further management.
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pmc-6276406-1
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A medically free 14-year-old male who was obese sustained an injury to his left knee after jumping from 3 stairs. The patient mentioned that he predominantly landed on his left lower limb with his left knee in full extension and in external rotation. The patient started complaining of left knee pain limiting his range of motion and ability to bear weight immediately after the fall. He was brought to the Emergency Department (ER) of King Saud Medical City (KSMC) by his parents immediately after the injury. On physical examination, the left knee was profoundly swollen and bruised. There was tenderness over the tibial tuberosity and lateral joint line. He was unable to actively move the knee joint. The passive range of motion was painful. There were no signs indicating compartment syndrome or neurological or vascular injury. X-ray radiographs revealed a Watson-Jones type IIIB avulsion fracture of the tibial tuberosity apophysis (). A CT scan showed a step of the articular surface more than 2 mm extending to the posterior-lateral epiphyseal part of the proximal tibia (lateral tibial plateau) ().
The patient was admitted and was prepared for operative management. A procedure was planned and done on a radiolucent table under general anesthesia. A tourniquet was used to avoid excessive bleeding during the procedure. The tourniquet was inflated after pulling down the quadriceps to avoid blocking the reduction due to the extensor mechanism. The leg is prepped and draped according to the standard orthopedic protocol. Anterolateral approach of the knee was used with an incision starting from the lateral upper border of the patella to 10 cm down. Deep fascia was opened anterior to the iliotibial tract. The fracture line was identified; the reduction of the articular step was done using a reduction clamp and assured using a portable image intensifier on flexion and extension of the knee without arthrotomy. We avoided arthrotomy of the joint to not make it vulnerable to infection and possible scarring. Stabilization of the reduction was maintained using a k-wire. Definitive fixation was achieved with three 3.5 mm partially threaded cancellous screws placed under fluoroscopic guidance for the tibial tuberosity fracture. A proximal tibial plate was slid laterally and was used to buttress the lateral tibial column. Careful placement of the screws was done to not cross the physis with the help of a C-arm (). After fixation, good hemostasis was achieved, drain was placed, and the range of motion was assessed which was full. Closure was done layer by layer, then dressing after. The postoperative plan was to immobilize the knee in a cylindrical cast for 3 weeks with no weight bearing on the left lower limb with the use of crutches for ambulation.
Postoperative knee CT scan is requested to ensure that the fracture is anatomically reduced. The patient received analgesia and antibiotics, and drain was removed 24 hours post-op. The patient was seen in an orthopedic clinic after 3 weeks, there were no signs of surgical site infection, and the clips were removed. The controlled range of motion was advised using a hinged knee brace throughout the day for 4 weeks. A follow-up X-ray () shows that the fracture is aligned with no loss of reduction or displacement. Physiotherapy is advised 7 weeks postoperative management focusing on the range of motion and strengthening. The patient was seen 6 weeks later, he had full range of motion with no deformity, and there were no complaints reported by the patient like locking or pain.
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pmc-6276408-1
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A 49-year-old man presented to our hospital with a history of night sweats, left-sided abdominal pain, weight loss, and recurrent episodes of streptococcal pharyngitis. He reported first noticing the left-sided abdominal pain about 8 months prior to presenting to our hospital, but it worsened over the past two months.
On examination, the patient was found to have cervical, supraclavicular, and inguinal lymphadenopathy as well as splenomegaly. He had a white blood cell count of 200,400/μL, with a left shift and 3% blasts. The hemoglobin, platelet count, and chemistries were all within normal limits. The imaging revealed multiple enlarged lymph nodes in the neck, mesentery, retroperitoneum, and inguinal as well as a massive splenomegaly (28 cm).
Peripheral blood analysis for BCR-ABL1 by PCR revealed the presence of p210 (b3a2) transcript at 24.991%. The bone marrow biopsy showed hypercellular marrow with striking granulocytic and megakaryocytic hyperplasia with atypical megakaryocytes and moderate reticulin fibrosis (–). Left-shifted myeloid maturation with 1.5% blasts was detected by flow cytometry. Fluorescent in situ hybridization (FISH) analysis and karyotyping () confirmed presence of BCR-ABL1 translocation. We started the patient on hydroxyurea for cytoreduction, with a plan to initiate a tyrosine kinase inhibitor (TKI) therapy. However, given the generalized lymphadenopathy, we were concerned about extramedullary (lymph node) blast crisis and included a cervical lymph node biopsy in his work up. This showed diffuse nodal effacement by blasts that were positive for CD3 and negative for CD20, CD34, and myeloperoxidase by immunostaining (Figures and ). The flow cytometry analysis detected an abnormal T-cell phenotype expressing CD45, cCD3, bright surface CD7, CD43, partial CD2, two myeloid markers (CD13 and CD33), dim/partial TdT, and, to a lesser extent, CD1a, while lacking sCD3, CD4, CD8, CD5, and defining markers for myeloid, monocytic, and B-lymphoid lineage (MPO-, CD14-, CD64-, CD11b-, CD19-, and CD20-) (). The blasts were positive for BCR-ABL1 by FISH and karyotyping (Figures and ), with additional chromosomal abnormalities indicating clonal evolution of CML with T-cell blast crisis. T-cell gene rearrangement on the lymph node was negative; however, that did not rule out T-cell blast crisis.
The patient was transferred to a higher-care facility with initiation of dasatinib and hyper-CVAD chemotherapy regimen. He completed 3 cycles of hyper-CVAD and underwent sibling-donor stem cell transplant and is on maintenance dasatinib. He is 5 months from diagnosis and is in hematological and cytogenetic remission but has minimal residual disease.
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pmc-6276409-1
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A 53-year-old Hispanic man with past medical history significant for coronary artery disease, habitual intravenous heroin abuse, chronic untreated hepatitis C without cirrhosis, bipolar disorder, tobacco abuse of 80 pack-year, and degenerative disc disease presented from home to our hospital with chief complaint of left scrotal pain, diffuse abdominal pain, back pain, and chest pain. Four days prior to presentation, he was seen in the emergency department for chronic back pain and was discharged with naproxen and instruction to follow up with his primary care physician. Since then, he developed acute onset of sharp constant pain of his left testicle and his abdomen. He admitted to using ten bags of heroin intravenously daily. He underwent an incision and drainage one month prior for a skin abscess. He reported no new sexual partner and is only sexually active with his current girlfriend. Family history was significant for heart disease in both his parents and maternal grandparents. His vital signs on admission were within the normal range. Physical exam revealed a man, with cachexia and temporal muscle wasting, in moderate distress from pain. He had jaundice with icteric sclera. His lungs were clear to auscultation. His heart sounds had regular rate and rhythm without any audible murmur. He had a soft abdomen that was mildly distended and tender in all four quadrants. His genitourinary exam was significant for bilateral scrotal erythema and swelling, which was worse on the left and was tender to light touch. He had diffuse tenderness to his back including paraspinal muscles, but no tenderness to the spinal processes. He was alert and oriented to person, time, and place and could answer questions appropriately. He had no facial asymmetry or deviated tongue, and he displayed normal proximal and distal strength. Laboratory findings were significant for WBC of 12.1 K/mm3 with a neutrophil predominance of 90%, microcytic anemia with hemoglobin 7.7 g/dL and MCV 75.6 fL, and thrombocytopenia of 47 K/mm3. His direct bilirubin level was elevated (3.0 mg/dL), as were his alkaline phosphatase (282 U/L), AST (87 U/L), ALT (33 U/L), and LDH (393 U/L). His albumin was 1.7 g/dL and lactic acid was normal at 1.2 mmol/L. His HIV-screening test was negative, as were his gonorrhea and chlamydia molecular amplification tests. He was subsequently admitted to internal medicine service/floor for further management.
His initial work up included a urinalysis that was significant for 10–20 RBC per HPF, 5–10 WBC per HPF, and positive urine nitrite; an EKG that showed normal sinus rhythm; and a chest X-ray which was negative for cardiomegaly, pleural effusions, or lung consolidations. A computed tomography (CT) of his head did not show any intracranial abnormalities. A CT of his abdomen and pelvis without contrast was performed which revealed hepatosplenomegaly with multiple large wedge-shaped areas of hypoperfusion in the spleen, concerning splenic infarctions (). The scrotal ultrasound showed no torsions, but revealed left epididymo-orchitis, large complex left scrotal hydrocele, and bilateral testicular microlithiasis. A limited bedside transthoracic echocardiogram by the emergency department physicians revealed a small pericardial effusion with no observable valvular vegetations. Blood and urine cultures were collected, and he was initially started on the broad-spectrum antibiotics of vancomycin, piperacillin-tazobactam, and azithromycin considering his risk factors and clinical presentation.
Overnight, he remained afebrile, but his leukocytosis worsened to 14.6 K/mm3, and he developed dyspnea and tachypnea with 24 breaths per minute. He became disoriented and was not answering questions appropriately. On exam, new findings of splinter hemorrhages, toe infarctions, and subconjunctival hemorrhaging were noted. Urine culture grew Serratia marcescens 50,000–100,000 CFU. Blood cultures also later grew the same organism, susceptible to all tested antibiotics including amikacin, aztreonam, cefepime, ceftriaxone, ciprofloxacin, gentamicin, ertapenem, piperacillin/tazobactam, and trimethoprim/sulfamethoxazole. On hospital day 2, a formal transthoracic echocardiogram (TTE) revealed an ejection fraction of 60% (unchanged from three years prior) with a large echodensity on the aortic valve consistent with vegetation. Mild aortic regurgitation, mild mitral regurgitation, and mild tricuspid regurgitation were also noted. Antibiotics were subsequently changed toertapenem 1 g daily and ciprofloxacin 750 mg twice daily in consultation with infectious disease.
The patient continued to deteriorate the following day. He became more disoriented and agitated. He remained afebrile, but his tachypnea worsened to 30 breaths per minute, and new rales were now audible on lung auscultation. An arterial blood gas (pH 7.51; pCO2 21 mmHg; pO2 70 mmHg; HCO3 16 mmol/L; O2 saturation 93%) showed a respiratory alkalosis. A repeat chest X-ray showed new interstitial pulmonary edema and vascular congestion. A CT of the head without contrast was performed due to his altered mental status, which showed two areas concerning embolic infarcts in the left parietal lobe and the left cerebellum (), compared to the one obtained on admission. On hospital day 4, an urgent transesophageal echocardiogram (TEE) was performed which again demonstrated the large aortic valve vegetations (), but it now demonstrated acutely deteriorating moderate to severe aortic regurgitation, which was different from the TTE findings a few days prior that only showed mild-moderate aortic insufficiency. In addition, it also revealed a mildly dilated left ventricle. The aortic valve leaflet had prolapsed motion. Due to the presence of large aortic valve vegetations, multiple embolic phenomena, and a progressively worsening of his clinical condition, decision was made to perform an urgent aortic valve replacement.
Postoperatively, he was managed in the surgical intensive care unit, where he developed a moderate-sized left pneumothorax requiring a chest tube placement. Slowly, his mental and clinical status began to improve. By hospital day 19, the patient was no longer agitated or disoriented. He displayed good appetite, and his chest tube was removed. His leukocytosis significantly improved to 8.0 K/mm3, and his repeat blood cultures did not grow any organisms for 5 days. Throughout his hospital course, he remained afebrile and did not receive any antipyretics. The lack of fever was concerning for an immunocompromised state, but he tested negative for HIV. He was ultimately discharged to a skilled nursing facility to complete his antibiotics, ertapenem 1 g daily with ciprofloxacin 750 mg twice daily, for a total course of 6 weeks, and to continue physical therapy.
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pmc-6276428-1
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The patient reported is a 59-year-old man with a past medical history of seizure disorder and multiple inpatient psychiatric hospitalizations for manic and depressive episodes of bipolar disorder. During these prior hospitalizations, no coprophagia was reported. He was admitted to the inpatient service for an acute episode of psychotic depression with complaints of a depressed mood. He exhibited psychomotor retardation, impoverished thought content, anhedonia, and a disheveled malodorous appearance but was oriented to person, place, and time.
In the course of index hospitalization, coprophagia was noted during his first day of admission, with staff observing him defecating and consuming his feces multiple times during the day despite being placed on urgent 1:1 constant observation. Initial assessment was limited as the patient had impoverished speech and was unable to communicate possible reasons for his behavior. Laboratory work-up for possible organic etiology was only significant for a slightly low total iron binding capacity as he had an otherwise normal metabolic panel and complete blood count. Urine toxicology was negative for alcohol and illicit drugs. A brain computed tomography (CT) scan was normal showing only minimal periventricular and subcortical white matter lucencies, compatible with minimal chronic microvascular ischemic changes.
He was commenced on risperidone 2 milligrams twice daily. There was a slight improvement within the first week as he was better at communicating, but his coprophagic behavior continued unabated. The slight improvement in thought content and process enabled him to express the symptoms associated with his coprophagia. He reported command auditory hallucinations resulting in the urge to consume feces, followed by the release of guilt and tension after consumption. In addition, he expressed excessive guilt in regard to his forensic history, being a registered sexual offender, with prior incarceration for lewd conduct with three female minors. He believed his consumption of feces was a necessary retribution for his behavior, to prevent “god and society from imposing worse punishments” on him. Over the next few days on the inpatient unit, risperidone was cross-tapered with clozapine which was started at 25 mg and titrated to 125 mg per day over 12 days. Cognitive therapy was also used to explore his automatic feelings associated with his forensic history during this time period. He was compliant with both interventions. Over the course of the cross-taper and cognitive therapy, the patient reported resolution of the command hallucinations to consume feces and his excessive guilty feelings. This was accompanied by an improvement in his coprophagic behavior.
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pmc-6276428-2
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The patient reported is a 32-year-old man with a past medical history of seizure disorder and a known psychiatric history of bipolar disorder with multiple inpatient hospitalizations for manic episodes during which he exhibited agitated and violent behavior. The patient has a comorbid use of synthetic cannabinoids. He was admitted to the acute inpatient service for a recurrent episode of agitation and threatening behavior in the community in the context of medication nonadherence and continuous use of synthetic cannabinoids. In the course of index hospitalization, the patient self-reported his coprophagic behavior during his initial psychiatric assessment. The patient stated that he believed that the consumption of feces was preventing him from going to jail and facing the death penalty for a murder that he claimed he committed in the past. He was unable to describe any specifics for his murder but felt that he deserved unusually cruel and harsh punishment from law enforcement that could only be prevented by consuming feces. This feeling of guilt and continued belief that he was deserving of cruel and harsh punishment induced his coprophagic behavior. He did not report any associated command auditory hallucinations but expressed depressed mood as he discussed his reasons for feeling guilty. His affect was however incongruent with his stated depressed mood. He was oriented to person, place, and time. Laboratory work-up was within normal limits and a urine toxicology panel (which does not detect synthetic cannabinoids) was also negative for illicit substances. He declined brain imaging for unclear reasons.
The patient was started on a course of risperidone 2 mg twice daily, by mouth, and divalproex sodium 750 mg orally twice a day for mood stabilization. He continued to display mood instability with multiple periods of agitation and aggression, as well as coprophagic behavior. His expressed reasons for coprophagia remained the same. He declined any psychotherapeutic interventions to address his excessive guilt and automatic negative cognitions. Over the course of a few days, risperidone was titrated to 6 mg daily in divided doses, with augmentation of his treatment with 200 mg every eight hours orally for mood stabilization/impulsivity in addition to divalproex sodium. The patient's mood symptoms improved after a few days on the current regimen; he became less irritable and easily redirectable, exhibited less impulsivity, and expressed more logical thinking process. His activities of daily living also improved, as he was less malodorous and exhibited improved grooming and hygiene. The patient's coprophagic behavior, however, did not resolve. He continued to express the same guilt and desire of unusually cruel and harsh punishments for his previous transgressions. He was discharged on the twenty-sixth day of admission with resolution of his acute manic episode. His coprophagic behavior and feelings of guilt did not show any resolution.
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pmc-6276432-1
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A 71-year-old male presented to cardiology clinic with a 3-week history of worsening dyspnea, night sweats, and subjective fevers. Of note, he underwent an ischemic evaluation one week prior that was significant for newly identified left pleural effusion, moderate pericardial effusion, and mild pericardial thickening on chest CT ().
Initial physical exam was significant for a heart rate of 107 beats per minute and relative hypotension at 98/61 mmHg. Additionally, heart sounds were distant but jugular venous distention was absent. Later appreciated to have potential relevance, he was noted to have facial acne. Electrocardiogram revealed sinus tachycardia. Transthoracic echocardiogram (TTE) was performed which revealed that the effusion increased by greater than one centimeter since the most recent echocardiogram nine days prior and was now large and circumferential with early right ventricular diastolic collapse concerning for tamponade physiology (Figures and ). However, it also noted a nonplethoric inferior vena cava (IVC) and a lack of exaggerated respiratory inflow variability.
Urgent pericardiocentesis was performed with removal of 370 mL of nonclotting serosanguinous fluid with immediate hemodynamic and symptomatic improvement. Gram stain of pericardial fluid demonstrated microscopic purulence with mixed inflammatory cells. Empiric broad-spectrum antibiotic therapy with vancomycin was initiated. Both 72-hour aerobic cultures and anaerobic cultures held for six days were negative. Full laboratory data from before and after the pericardiocentesis can be found in the table below ().
Repeat bedside transthoracic echocardiogram on day three demonstrated resolution of the previously noted anterior effusion. With these imaging findings and with minimal pericardial drain output noted, the drain was removed. On day five, the patient experienced recurrent tachycardia to 121 beats per minute, relative hypotension at 97/64 mmHg, and tachypnea to 28 breaths per minute, prompting evaluation for pulsus paradoxus which was found to be 18 mmHg. Repeat TTE showed a large effusion and recurrent evidence of tamponade physiology (). Following a heart team discussion, subxiphoid pericardial window and left-sided chest tube for pleural effusion were performed with removal of 800 mL and 200 mL of serosanguinous output, respectively. Anterior adhesions of the pericardium as well as loculated posterior pericardial effusion requiring blunt dissection were noted intraoperatively.
Intraoperative anaerobic cultures of the pleural and pericardial fluid grew C. acnes after six and seven days, respectively, and anaerobic blood cultures from admission grew the same organism two weeks later. These results can be found in the table below (). Histopathology of operative pericardial samples showed fibrinous pericarditis with granulation tissue formation. Given the patient's history of anaphylaxis to penicillin, he was initiated on a 14-day course of parenteral vancomycin. The patient was discharged from the hospital in stable condition and his symptoms remained controlled at follow-up. Also noted on follow-up was resolution of the pericardial effusion as seen on TTE (Figures and ).
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pmc-6276437-1
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A 22-year-old male patient was referred to the Oral and Maxillo-Facial Surgery Service at Federal University of Paraná after occasional finding on a routine panoramic radiograph. The patient experienced no symptoms. A computed tomographic (CT) was requested and showed a well-defined hyperdense mass showing a hypodense center inside the left maxillary sinus measuring approximately 15 mm × 10 mm situated in a posterior position of this anatomical space (). It was observed that this calcified mass was associated with the roots of the impacted third molar. Treatment proposed was the complete excision of the lesion through an intraoral approach and Caldwell-Luc access to reach the maxillary sinus.
Under general anesthesia, an incision from the superior left first molar extending to retromolar area, with anterior and posterior relaxant incisions, was conducted to provide a sufficient access to the region of interest without causing gingival tissue tension. Osteotomy of the lateral maxillary sinus wall was conducted in order to expose its membrane. Once the sinus membrane was exposed, it was carefully detached from the bone without it disrupting until the calcified mass was reached (). The third molar with calcified mass associated with the roots was removed.
The chosen postoperative drug therapy was cefazoline-oral (500 mg) each 8 hours during 7 days, nimesulide (100 mg) each 12 hours during 5 days, and dipyrone (1 g) for each 6 hours during 3 days. Patient experienced no infection symptoms and drug therapy showed to effective in swelling and pain control.
Pathological mass removed was stored in 10% formalin and sent as excision biopsy for further histopathological investigation. It was fixed in 10% neutral formalin, subjected to decalcification in formic acid, bisected in a mesiodistal direction, and then processed for light microscopic examination. Histopathology showed that the calcified tumor mass was composed of sheets of cementum-like tissue with lack of interstitial tissue. The middle part of the tumor was found to be more mature and the peripheral part is more cellular. Multinucleated giant cells and blastic cells were found within the margins of the mineralized mass. The pathological mass was also associated with the yet not totally formed maxillary third molar root, corroborating the benign cementoblastoma diagnosis ().
Postoperative orthopantomogram radiography shows the success of the tumor removal (). One-year follow-up shows no recurrence and absence of symptoms.
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pmc-6276439-1
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62-year-old female with past medical history of anemia presented with complaint of weakness and dizziness that started a week prior to admission, associated with > 20 lbs. of weight loss over 1 year. Upon admission, no specific clinical findings were noted except for reddish annular spots on the right lower extremities. Blood pressure was 169 / 72; pulse was 102 bpm; respiratory rate was 18 breaths/ minute; temp was 98.3 F; pulse ox was 100% on R/A.
Initial laboratory data revealed the data in .
Based on the results in , the serum anion gap is 21.5. However, the delta/delta ratio is ~0.74 which indicates that the patient has mixed anion gap and non-anion gap metabolic acidosis. The positive urine anion gap (36) and urine PH > 6 in the presence of metabolic acidosis suggest a renal involvement represented as RTA. Furthermore, we calculate the urine osmolar gap (UOG) using the following formula:
UOG = measured urine osmolality - ((2 ∗ (urine Na + urine K)) + (urine urea nitrogen / 2.8) + (urine glucose / 18)) which would create a urine osmolar gap of 95.43 mOsm/kg which further suggests the distal RTA.
Additionally, the patient had a bone marrow biopsy which showed markedly hypercellular bone marrow with 70% B-lymphoblast which is consistent with B-ALL. Staining is positive for TdT, PAX5, CD79a, and CD10. Cytological studies could not be performed due to dry tap.
Peripheral blood smear showed only few target cells.
Initial CT scan of abdomen was significant for enlargements of the kidneys bilaterally (see ).
shows the hospital course for the management of lactic acidosis.
Based on , metabolic acidosis was first managed with fluid replacement and sodium bicarbonate while searching for possible causes of lactic acidosis. Lactic acidosis improved with fluids and bicarbonate replacement. However, the complete resolution was achieved only after chemotherapy with hyperfractionated chemotherapy of cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD) with intrathecal prophylaxis methotrexate was started. Patient received a total of 8 cycles of hyper-CVAD chemotherapy.
She had her bone marrow biopsy done after 6 cycles and was found to be in complete remission.
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pmc-6276441-1
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A 70-year-old man transferred to our institution with a 24-hour history of intermittent central chest pain and evidence of inferior ST elevation myocardial infarction (STEMI) on the twelve-lead electrocardiogram. He was an ex-smoker with a history of 10 pack-years without any significant past medical history and not on any regular medications.
Given his symptoms and the associated ECG findings, he was transferred to the catheterisation laboratory and an emergency coronary angiography was performed via the right radial artery access route using a 6Fr arterial sheath. The left main (LMS) and the right coronary artery (RCA) were engaged with a 5f Judkins left (JL) 3.5 diagnostic catheter and a 6f Judkins right (JR) 4.0 guiding catheter, respectively. The left coronary system revealed a patent LMS, a tubular moderate to severe stenosis extending from the proximal to the mid segment of the left anterior descending artery (LAD) (), and a minor nonobstructive atheroma in a nondominant left circumflex artery (LCx). The RCA was acutely occluded. We proceeded to primary PCI of the RCA. Using the 6Fr JR4 guiding catheter, a Sion Blue guide wire (Asahi INTECC Co., Ltd.) was passed through the occluded segment into the distal vessel. Predilatation was then performed with a 2.5 mm Trek, semicompliant, balloon (Abbott Vascular) with immediate restoration of TIMI 3 flow. This revealed a critical mid vessel stenosis, which was subsequently stented with an Orsiro (BIOTRONIK) 3.5 × 30 mm drug eluting stent (DES), deployed at 12 atmospheres and postdilated with a 3.75 × 20 mm Accuforce (Terumo) noncompliant (NC) balloon inflated to 20 atmospheres with an excellent final angiographic result.
In light of the significant bystander disease, we elected to treat the proximal-mid LAD stenosis during the index procedure. Using a 6Fr EBU 3.5 guiding catheter, the lesion was crossed with a Sion Blue guide wire and predilatation was performed with a Trek (Abbott Vascular), 2.5 × 20 mm, semicompliant balloon followed by a 3.0 × 20 mm Accuforce (Terumo) NC balloon at 12 atmospheres. Following predilatation, we could easily identify an intima flap within the stenotic lesion (). Aiming to cover the dissection flap, we deployed a 2.75 × 26 mm Orsiro (BIOTRONIK) DES at the mid segment, which was overlapped proximally with a 3.5 × 20 mm Orsiro (BIOTRONIK) DES. The overlapping part of the stents was then postdilated with the 3.5 mm stent balloon at 16 atmospheres. The succeeding cine-acquisition demonstrated a significant luminal stenosis at the outflow of the distal stent (), associated with new dynamic anterior ST elevation on the ECG and chest discomfort of the patient. The administration of two consecutive bolus 300 mcg of intracoronary nitrates failed to resolve stenosis and restore normal blood flow, a finding in keeping more likely with a plausible iatrogenic intramural haematoma rather than a coronary spasm. As the patient was clinically unstable and rapidly deteriorating, we initially opted not to perform further assessment with an intravascular ultrasound (IVUS) and quickly treat the haematoma with an additional stent implantation, but after deploying a 2.5 × 18 mm Orsiro (BIOTRONIK) DES, the subintimal haematoma was propagated more distally with further subtotal occlusion of the vessel (). At this stage, we selected to treat the haematoma with a cutting balloon inflation technique, intending to create multiple microfenestrations and relieve the excess inner luminal pressure caused by the haematoma. First, a 2.5 × 6 mm Flextome (Boston Scientific) cutting balloon was successfully delivered at the outflow of the distal stent. Then, we inflated the balloon at nominal pressure, exactly at the transition point between the distal edge of the stent and the adjacent unstented vessel wall (). Successive angiography demonstrated complete resolution of the luminal stenosis with complete restoration of TIMI 3 flow (). The patient's troponin level from a blood sample taken on admission was 4528.00 ng/L (normal range 0–14 ng/L), and an echocardiogram two days after his index procedure showed preserved left ventricular systolic function with an ejection fraction of 55–60% and regional wall motion abnormalities involving hypokinesia of the basal to mid-inferior and inferolateral wall segments. The rest of the myocardial segments had normal contractility. The patient had further follow-up in the outpatient cardiology clinic 3 months later, where he reported an excellent recovery and denied any recurrent symptoms. Additional follow-up has been scheduled for one year after his successful PCI and myocardial infarction.
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pmc-6276445-1
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A 16-year-old woman presented to her local hospital with a few-month history of right knee pain. She was in good health and had no history of direct trauma to the knee. Upon admission, her knee motion range was not restricted and other physical examinations were nonspecific. An anteroposterior plain radiograph revealed the osteolytic lesion surrounding by the bone sclerotic lesion in the lateral femoral condyle (Figures and ). On magnetic resonance imaging (MRI), the lesion exhibited an intermediate signal on T1-weighted (T1W) and T2-weighted (T2W) images (). The orthopedic physician made a diagnosis of osteochondritis dissecans. After 13 months, the patient underwent MRI of the knee once more, which demonstrated that the osteolytic lesion grew larger and now measured 16 mm × 10 mm × 10 mm (Figures –). The patient was then referred to our institution for further management. In our institution, computed tomography scans showed well-defined geographic bone destruction demarcated by the sclerotic rim. Therefore, we highly suspected the tumor of being a benign lesion, such as a fibroma. To achieve a definitive diagnosis, we attempted to perform a resection biopsy with knee arthroscopy as the epiphyseal plate did not require removal or destruction. During the surgery, anterolateral and anteromedial portals were used. Arthroscopy revealed a depressed lesion, such as the dimple at the lateral condyle of the femur (). We performed biopsy, and the tumor was removed completely with the sharp curettes and suction during arthroscopy (). The tumor tissue was macroscopically gray-white and contained yellow brown foci (). The histological specimen showed a storiform pattern with giant cells (). Immunohistochemical analyses revealed that the tumor cells were negative for SOX9 and S100. The tumor did not show nuclear Histone 3.3 G34W immunoreactivity (). The tumor occurred in an epiphysis, and the pathological findings concluded that the pathological diagnosis was BFH. Full weight-bearing was allowed soon after surgery as the tumor was located in the lateral condyle of the femur. One year after surgery, she was asymptomatic. Computed tomography revealed that the previous tumor bone cavity was filled with bone formation and no evidence of recurrence ().
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pmc-6276453-1
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A 78-year-old Caucasian female was admitted to our hospital for a four-month history of severe fatigue, anorexia, and intermittent abdominal discomfort. The patient had been in her usual state of health until four months prior to the presentation when she developed fatigue and abdominal discomfort without apparent inciting factors. She was seen by her primary care physician a week prior to the admission, when she was reportedly found to have severe renal failure; her serum creatinine was 0.74 mg/dL two months prior to the admission. A few days prior to the presentation, the patient started to note dark-colored urine. The abdominal discomfort lacked specific localization and was not postprandial. She had not had hearing loss, vertigo, alopecia, epistaxis, mucosal ulcers, photosensitive rash, pleurisy, dyspnea, hemoptysis, arthralgia, purpura, Raynaud's phenomenon, cutaneous ulcers, muscle weakness, or paresthesia. There was no history of seizures, stroke, coronary artery disease, venous thrombosis, or miscarriages. Her past medical history was only significant for hypertension. Her medications upon admission included metoprolol, losartan, and naproxen. She had no known drug allergies. There was no family history of autoimmune diseases.
On examination, the patient was in moderate distress. The temperature was 97.3°F, the blood pressure was 166/81 mmHg, the pulse was 99 beats per minute, and the oxygen saturation was 98% while she was breathing ambient air. The patient had anasarca. Conjunctivae were pale but not icteric. Her nasal and oral mucosa were normal. There was no tenderness over the sinuses. Superficial lymph nodes were not palpable. Breath sounds were clear in both lungs. There were no pericardial friction rubs. There was no abdominal tenderness or organomegaly. There was no rash. There was no joint tenderness or synovitis. The remainder of the physical as well as neurological examination was unremarkable.
Laboratory studies showed leukocyte count of 4500/μl (reference range: 4000–10,000/μl; reference range is provided in the parentheses in the following laboratory studies), hemoglobin 9.3 g/dL (13.5–18 g/dl), and platelet count 161,000/μl (150,000–400,000/μl). Her leukocyte count, hemoglobin, and platelet count subsequently dropped during her hospitalization and reached their nadirs of 3300/μl, 6.9 g/dL, and 75,000/μl, respectively. Peripheral blood smear did not show schistocytes. Her erythrocyte sedimentation rate was 7 mm/h (0–15 mm/h). Chemistries showed BUN of 54 mg/dL (8–24 mg/dL), creatinine 4.84 mg/dL (0.66–1.25 mg/dL), aspartate aminotransferase 35 U/L (11–39 U/L), alanine aminotransferase 22 U/L (12–78 U/L), alkaline phosphatase 125 U/L (45–117 U/L), albumin 2.5 g/dL (3.2–4.5 g/dL), total bilirubin 0.6 mg/dL (0–1.0 mg/dL), lactate dehydrogenase 224 U/L (84–246 U/L), and haptoglobin 214 mg/dL (30–200 mg/dL). Antinuclear antibody (ANA) indirect immunofluorescence assay was positive at 1 : 250 dilution (homogenous pattern). Solid-phase ANA assay showed positive chromatin antibody and double-stranded DNA (dsDNA) antibody at 71 IU/mL (0–4 IU/mL), while Smith, Ro, La, and RNP antibodies were negative. C3, C4, and CH50 were 46 mg/dL (90–180 mg/dL), 7 mg/dL (10–40 mg/dL), and 116 CAE units (60–144 CAE units). Anticardiolipin IgM was 69 MPL (0–12 MPL) while the remainder of cardiolipin and beta-2 glycoprotein antibodies was negative. Hepatitis B and C serologies did not suggest past exposure. Serum protein and immunofixation electrophoreses did not show paraproteins. Urinalysis showed 3–5 WBC/high-power field (hpf), 50–100 RBC/hpf, and 2+ proteins. A spot urine protein to creatinine ratio was 3.98. The chest X-ray did not show significant parenchymal disease. Based on the ANA, dsDNA antibody, antiphospholipid antibody, cytopenias, and likely GN, the patient was diagnosed with systemic lupus erythematosus (SLE) []. In particular, the presentation of her kidney disease, which was consistent with rapidly progressive GN, raised a concern for diffuse proliferative LN, and the patient was started on methylprednisolone 1 gram × 3 doses followed by prednisone 60 mg daily. On the 5th hospital day, ANCA immunofluorescence (IF) assay showed perinuclear staining pattern at 1 : 320 dilution (<1 : 20). Furthermore, myeloperoxidase (MPO) antibody was strongly positive at 147 AU/mL (0–19 AU/mL), while serine proteinase 3 (PR3) IgG was 9 AU/mL (0–19 AU/mL). Accordingly, overlapping ANCA-associated vasculitis was suspected, and she was started on plasmapheresis given its proven benefits in severe renal disease in ANCA-associated vasculitis []. However, her BUN and creatinine continued to increase up to 102 mg/dL and 6.08 mg/dL on the 7th hospital day, when she was started on hemodialysis.
Renal biopsy was done on the 4th hospital day and showed an acute necrotizing and crescentic glomerulonephritis, with ten of fourteen glomeruli showing cellular crescents, often in association with areas of fibrinoid necrosis (Figures and ). Only one glomerulus was globally sclerotic, and none showed segmental scars. The glomeruli had mild mesangial and no endocapillary hypercellularity (). Interstitial fibrosis was mild (10–15%), and there was no significant vascular disease. The electron microscopy performed on glomeruli extracted from the paraffin block showed predominantly mesangial and rare subendothelial immune-type electron dense deposits (). No tubuloreticular inclusions were observed. Immunofluorescence showed mostly mesangial and rare capillary wall weak granular positivity for IgG (1+), IgM (1+), IgA (1+), C1q (1+), and C3 (2+), with equal kappa (1+) and lambda (1+) (). There was diffuse nuclear positivity for IgM, IgM, C1q, kappa, and lambda (“tissue antinuclear antibodies” pattern), and fibrinogen highlighted segmental areas of capillary tuft fibrinoid necrosis. The final diagnosis was MPO-ANCA-associated necrotizing and crescentic glomerulonephritis on a background of mesangial proliferative glomerulonephritis consistent with class II lupus nephritis (ISN/RPS).
The patient received a total 6 sessions of plasmapheresis over two weeks. In addition, she received rituximab (375 mg/m2 body surface area once weekly) × 3 doses in the hospital and was started on mycophenolate mofetil which was titrated to 1 gram twice daily. We recommended the 4th dose of rituximab as outpatient; however, it was foregone due to difficulty obtaining vascular access. 1.5 months after the initial presentation, the patient was readmitted for severe anemia with hemoglobin of 5.2 g/dL. Her leukocyte and platelet counts were 4,100/μl and 87,000/μl. Her clinical picture did not indicate acute blood loss, and there was no evidence of hemolysis. A chest X-ray did not suggest diffuse alveolar hemorrhage. In association with the foregoing treatment, the titer of her dsDNA Ab declined to 6 IU/ml, whereas her C3 and C4 rose to 80 mg/dL and 14 mg/dL. Her ANCA was undetectable. Collectively, it was felt that SLE was not directly contributing to her anemia, and mycophenolate mofetil was suspended. The patient remained dialysis dependent and subsequently developed sepsis. Given the lack of improvement of overall clinical conditions, the patient elected to pursue comfort care and deceased one month after the second admission.
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pmc-6276461-1
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A 66-year-old female patient, who was hospitalized in a psychiatric clinic, suddenly developed dysarthria and anisocoria with subsequent loss of consciousness. Without palpable pulses immediate bystander CPR was performed and the patient was transferred to our hospital. On the way CPR of the ventilated patient was continued with a mechanical resuscitation device (LUCAS 2, Physio-Control™). After 45 minutes of CPR for pulseless electrical activity spontaneous circulation returned as assessed by a palpable carotid pulse, however femoral pulses were absent, precluding cannulation for mechanical circulatory support (MCS). ECG showed ST-segment elevation in leads II, III, aVF, and V6 (). Fast-track echocardiography demonstrated severe dysfunction of the dilated right ventricle. Pericardial effusion and severe aortic regurgitation were absent. Medical history comprised an infrarenal aortic aneurysm. Acute aortic dissection Stanford Type A, De Bakey I with involvement of the right coronary artery was suspected. As percutaneous MCS was not possible without femoral pulses and since Type-A-dissection would have prompted emergency surgery, the heart team decided for immediate computed tomography (CT), which showed no signs of Type A aortic dissection, pulmonary embolism, intracerebral bleeding, or carotid stenosis, but severe ubiquitous aortic calcification. Main findings were as follows: a large ventricular septal rupture with classical radiological signs of acute myocardial infarction (), signs of severe backward failure with contrast agent being observed in hepatic veins, renal veins (), the portal vein and the inferior vena cava (), and thrombotic occlusion of the descending aorta just distal to the left subclavian artery (). The latter was probably facilitated by massive left-to-right shunt and associated severe forward failure. Shortly after the CT scan the patient had to be resuscitated again, but due to futility with subtotal body ischemia without any option for MCS or emergent surgery resuscitation was terminated.
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