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PMC11277838_p14
|
PMC11277838
|
sec[5]/sec[1]/p[1]
|
6.2. Studies in Compensated Heart Failure
| 4.136719 |
biomedical
|
Study
|
[
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[
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The study conducted by Holst et al. compared the effects of two different fluid intake regimens: a daily maximum fluid intake of 1.5 L and a liberal fluid intake of 30 mL/kg body weight/day, in patients who had improved from New York Heart Association classification (NYHA) III-IV to stable HF predominantly experiencing mild symptoms (n = 74). This investigation employed a randomized cross-over study design, and the total study duration was 32 weeks, with each intervention period lasting 16 weeks. The study did not provide specific recommendations regarding salt intake. Upon analyzing the end-of-intervention data comparing the prescribed fluid intake of 1.5 L/day and the liberal fluid intake of 30 mL/kg body weight/day, no significant differences were observed in body weight, diuretic usage, other cardiovascular medication, quality of life, physical capacity assessed via the six-minute walk test, or hospitalization rates under the less strict fluid prescription. However, it is noteworthy that sense of thirst [median = 51 vs. 23, p < 0.001] and difficulty adhering to the fluid prescription [median = 23 vs. 6, p < 0.001] were significantly reduced at the end of the 30 mL/kg/day intervention compared to the end of the 1.5 L/day intervention.
|
[
"Naoko P. Kato",
"Yuji Nagatomo",
"Fujimi Kawai",
"Takeshi Kitai",
"Atsushi Mizuno"
] |
https://doi.org/10.3390/jpm14070741
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11277838_p15
|
PMC11277838
|
sec[5]/sec[1]/p[2]
|
6.2. Studies in Compensated Heart Failure
| 4.109375 |
biomedical
|
Study
|
[
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Paterna et al. evaluated the effects of different therapeutic strategies (diuretic doses, sodium diets, and fluid intakes) on hospitalizations after a 6-month follow-up in patients with recently compensated HF who were hospitalized within 30 days. A total of 410 patients with compensated HF (NYHA II) were divided into eight groups according to fluid restriction , sodium consumption (120 or 80 mmol/day), and furosemide doses (125 or 250 mg twice daily). In their multivariate analysis, a maximum fluid intake of 2000 mL/day was significantly associated with an increased risk of hospital admissions (adjusted odds ratio = 3.82, 95%CI = 2.84–5.14, p < 0.01). They also found that a normal-sodium diet (120 mmol sodium/day) with limited fluid intake associated with high doses of loop diuretics (250 mg furosemide bid) could be the most effective treatment compared to other combinations.
|
[
"Naoko P. Kato",
"Yuji Nagatomo",
"Fujimi Kawai",
"Takeshi Kitai",
"Atsushi Mizuno"
] |
https://doi.org/10.3390/jpm14070741
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11277838_p16
|
PMC11277838
|
sec[6]/sec[0]/p[0]
|
7.1. Systematic Reviews and Meta-Analyses
| 4.117188 |
biomedical
|
Study
|
[
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To explore the influence of fluid restriction on both clinical outcomes and patient-reported outcomes among HF patients, we searched for systematic reviews focused on fluid restriction in HF patients using the following search terms in PubMed in October 2023: “heart failure” [MeSH] AND (“Water restriction” OR “fluid restriction”) AND (“systematic” [Filter] OR “Meta-Analysis” [Publication Type]). These search terms were identified using a priori PICOTS-SD (population, intervention, comparator, outcome, setting, and study design) guidelines to refine the search and decrease noise . The publication period was between 2013 and 2023. As a result, eight systematic reviews were identified. One paper was excluded, as it was written in Spanish. Among the seven remaining systematic reviews and meta-analyses of randomized controlled trials, most focused on dietary interventions, including sodium and fluid restriction , or on cardiac rehabilitation, emphasizing adherence to diet, physical activity, and fluid restriction . Only two systematic reviews included analyses to investigate the impacts of fluid restriction alone on clinical outcomes and patient-reported outcomes in HF patients . We also checked the Cochrane Database of Systematic Reviews, but we could not find any additional systematic reviews.
|
[
"Naoko P. Kato",
"Yuji Nagatomo",
"Fujimi Kawai",
"Takeshi Kitai",
"Atsushi Mizuno"
] |
https://doi.org/10.3390/jpm14070741
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11277838_p17
|
PMC11277838
|
sec[6]/sec[0]/p[1]
|
7.1. Systematic Reviews and Meta-Analyses
| 4.0625 |
biomedical
|
Study
|
[
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In a meta-analysis conducted by Stein et al. , 331 HF patients were included from three randomized controlled studies . They demonstrated that fluid restriction alone significantly reduced the relative risk of both all-cause mortality (relative risk = 0.32, 95% CI = 0.13–0.82, I 2 = 0%) and hospitalization (relative risk = 0.46, 95% CI = 0.27–0.77, I 2 = 37%) compared to usual care. Conversely, the combination of sodium and fluid restriction did not exhibit any benefit in terms of mortality (relative risk = 0.92, 95% CI = 0.49–1.73, I 2 = 7%) or hospitalization (relative risk = 0.94, 95% CI = 0.75–1.19, I 2 = 0%) compared to usual care. Li et al. also conducted a meta-analysis encompassing five studies, which demonstrated that fluid restriction offers no benefit compared to liberal fluid intake concerning mortality, hospital admission, or thirst in patients with HF. However, it is to be noted that this meta-analysis included two studies in which the intervention comprised both sodium and fluid restriction. Therefore, this study did not clearly evaluate the effects of fluid restriction alone.
|
[
"Naoko P. Kato",
"Yuji Nagatomo",
"Fujimi Kawai",
"Takeshi Kitai",
"Atsushi Mizuno"
] |
https://doi.org/10.3390/jpm14070741
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277838_p18
|
PMC11277838
|
sec[6]/sec[0]/p[2]
|
7.1. Systematic Reviews and Meta-Analyses
| 4.140625 |
biomedical
|
Study
|
[
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[
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Regarding the outcome of “thirst”, two studies utilized a visual analog scale (VAS) to compare a fluid restriction group with usual care . In the meta-analysis by Stein et al. , the VAS was standardized as a 10-point scale, and they found that fluid restriction significantly increased thirst sensation (weighted mean difference = −2.08, 95% CI = −3.81–0.34, I 2 = 54%). In contrast, another meta-analysis conducted by Simão did not find significant mean differences in thirst sensation compared with the usual-care group . The mean difference between groups was 9.84 points [95% CI = −27.36–47.04, I 2 = 90%, p < 0.01]. The inconsistencies in the results of these two meta-analyses may be attributed to methodological differences between the studies. However, it is noteworthy that both analyses included the same two studies by Holst et al. and Albert et al. . Holst et al. demonstrated that compensated HF patients (NYHA II) experienced significantly stronger thirst sensation with a 1500 mL/day fluid restriction in a randomized cross-over study (n = 64, median = 51 vs. 23, p < 0.001). Conversely, Albert et al. reported no significant differences in the sense of thirst among patients hospitalized for ADHF between a 1000 mL/day fluid restriction group and a usual-care group at 30-day follow-up (median = 50 and 50, p = 0.77) nor at 60-day follow-up (40 vs. 50, p = 0.60). The inconsistency in the results of these two studies may be attributed to several factors, including variations in the HF status of the participants (compensated or decompensated), differences in study design (such as cross-over design or randomized controlled trial), varying follow-up lengths, and small sample sizes. Therefore, further, larger randomized controlled trials are necessary to comprehensively investigate the impacts of fluid restriction on thirst sensation.
|
[
"Naoko P. Kato",
"Yuji Nagatomo",
"Fujimi Kawai",
"Takeshi Kitai",
"Atsushi Mizuno"
] |
https://doi.org/10.3390/jpm14070741
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11277838_p19
|
PMC11277838
|
sec[6]/sec[0]/p[3]
|
7.1. Systematic Reviews and Meta-Analyses
| 4.066406 |
biomedical
|
Study
|
[
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[
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Albert et al. demonstrated that 1000 mL/day fluid restriction resulted in better quality-of-life scores for symptom burden (median = 83.3 vs. 50, p = 0.018), overall QoL summary score (median = 72.6 vs. 51.0, p = 0.038) and clinical QoL score (median = 75.5 vs. 59.1, p = 0.039) at 60 days post-discharge.
|
[
"Naoko P. Kato",
"Yuji Nagatomo",
"Fujimi Kawai",
"Takeshi Kitai",
"Atsushi Mizuno"
] |
https://doi.org/10.3390/jpm14070741
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11277838_p20
|
PMC11277838
|
sec[6]/sec[1]/p[0]
|
7.2. Methodological Quality
| 4.078125 |
biomedical
|
Study
|
[
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[
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In recent years, there has been an increasing focus on the significance of quality in systematic reviews. A recent meta-analysis conducted by Stein et al. is, to our knowledge, the first study to have demonstrated the positive impacts of fluid restriction on hospitalization and mortality through meta-analysis. These results could potentially trigger a re-evaluation of current recommendations in HF guidelines. However, there is a risk in uncritically accepting the results of a single systematic review. Therefore, it is essential to first evaluate its quality. The quality of the systematic review was therefore independently assessed by three researchers (AM, YN, and NPK) using the AMSTAR 2 tool , which is a commonly used instrument for critically appraising systematic reviews including randomized or non-randomized studies of healthcare interventions. The three researchers concurred that a weakness of this systematic review was the authors’ failure to assess the potential impact of bias risk in individual studies on the results of the meta-analysis. Despite the fact that the majority of studies used for the analysis were flagged as having high levels of overall bias, this aspect remained unaddressed. Another weakness was the review’s failure to assess publication bias, which was attributed to the small number of included studies. Thus, it may be prudent to wait for further evidence before concluding whether fluid restriction reduces the risk of hospitalization and mortality.
|
[
"Naoko P. Kato",
"Yuji Nagatomo",
"Fujimi Kawai",
"Takeshi Kitai",
"Atsushi Mizuno"
] |
https://doi.org/10.3390/jpm14070741
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11277838_p21
|
PMC11277838
|
sec[7]/p[0]
|
8. Limitations of Current Evidence
| 4.066406 |
biomedical
|
Review
|
[
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[
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One major limitation of the current evidence on fluid restriction in HF is the scarcity of randomized controlled trials, with studies yielding mixed results. This variability might partly stem from factors such as suboptimal methodological quality, concurrent administration of treatments, small sample sizes, disparate follow-up durations, and climatic differences between regions. Additionally, the current randomized controlled studies were conducted over 10 years ago, primarily in Western countries. Current HF treatments and other differences, including racial and ethnic differences, could influence fluid prescriptions and outcomes. Furthermore, given the aging population, there has been a significant increase in patients with HF with preserved ejection fraction (HFpEF) over the past decade, and these patients often have multiple comorbidities. Aging and multiple comorbidities can influence the effectiveness of fluid restriction, as well as adherence to fluid restriction. Previous randomized controlled trials on fluid restriction for HF primarily focused on patients with HF and reduced ejection fraction (HFrEF), and the effectiveness of fluid restriction for patients with HFpEF remains unclear. Therefore, further studies including patients with preserved ejection are necessary.
|
[
"Naoko P. Kato",
"Yuji Nagatomo",
"Fujimi Kawai",
"Takeshi Kitai",
"Atsushi Mizuno"
] |
https://doi.org/10.3390/jpm14070741
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11277838_p22
|
PMC11277838
|
sec[7]/p[1]
|
8. Limitations of Current Evidence
| 2.917969 |
biomedical
|
Study
|
[
0.99560546875,
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[
0.64501953125,
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In terms of racial and regional disparities, non-Western countries exhibit distinct dietary cultures, climates, and body types. For instance, many Asian countries experience hot climates, and their populations generally have smaller physiques compared to Western individuals. These physical, cultural, and environmental differences could influence the recommended fluid intake and adherence to it. Therefore, studies conducted in non-Western countries are essential for understanding optimal fluid intake and fluid management strategies tailored to these unique demographics.
|
[
"Naoko P. Kato",
"Yuji Nagatomo",
"Fujimi Kawai",
"Takeshi Kitai",
"Atsushi Mizuno"
] |
https://doi.org/10.3390/jpm14070741
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11277838_p23
|
PMC11277838
|
sec[7]/p[2]
|
8. Limitations of Current Evidence
| 3.851563 |
biomedical
|
Study
|
[
0.9990234375,
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[
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Moreover, there are still fewer studies assessing patient-reported outcomes. In addition to clinical adverse events, it is crucial to evaluate patient-reported outcomes such as quality of life and thirst sensation. Given the inconsistent results from prior studies regarding the impacts of fluid restriction on quality of life and thirst sensation , it is essential to assess both outcomes. A scale to assess thirst distress was recently developed which could provide valuable insights into the impacts of fluid restriction in patients with HF.
|
[
"Naoko P. Kato",
"Yuji Nagatomo",
"Fujimi Kawai",
"Takeshi Kitai",
"Atsushi Mizuno"
] |
https://doi.org/10.3390/jpm14070741
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11277838_p24
|
PMC11277838
|
sec[8]/p[0]
|
9. The Potential Associations of Novel Therapeutics with Fluid Management in Heart Failure
| 3.890625 |
biomedical
|
Review
|
[
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[
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The advancements over the past decade in pharmacological and non-pharmacological treatments have been remarkable. Not only have novel therapeutics been introduced, but the importance of optimizing HF therapeutics has also been recognized. These treatments may potentially alleviate the need for fluid restriction or impact its effectiveness. These novel therapeutics were shown to have favorable effects on hemodynamics and cardiac function. Further, some of them exert these effects without detrimental effects on RAAS or SNS activity.
|
[
"Naoko P. Kato",
"Yuji Nagatomo",
"Fujimi Kawai",
"Takeshi Kitai",
"Atsushi Mizuno"
] |
https://doi.org/10.3390/jpm14070741
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277838_p25
|
PMC11277838
|
sec[8]/p[1]
|
9. The Potential Associations of Novel Therapeutics with Fluid Management in Heart Failure
| 4.273438 |
biomedical
|
Review
|
[
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[
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Sodium–glucose cotransporter 2 inhibitors (SGLT2is) are shown to improve cardiovascular outcomes and are recommended for patients with HF, irrespective of LVEF . SGLT-2is cause diuresis and show a significant synergistic effect on natriuresis under co-administration of loop diuretics , although some studies have suggested that the change in plasma volume caused by SGLT-2is might not be sustained in the long term . Due to these effects, SGLT-2is can cause significant dehydration . As a result, the dose of diuretics was reported to be reduced or subsequent initiation of diuretics occurred less often after SGLT-2i administration . SGLT-2is also showed protective effects on the kidneys, such as inhibition of temporal decline in estimated glomerular filtration rate in patients with chronic kidney disease . Of note, the SNS and the RAAS are not activated or may be inhibited after administration of SGLT-2is . These properties of SGLT-2is may have the potential to alleviate the need for sodium and/or fluid restriction in patients with HF.
|
[
"Naoko P. Kato",
"Yuji Nagatomo",
"Fujimi Kawai",
"Takeshi Kitai",
"Atsushi Mizuno"
] |
https://doi.org/10.3390/jpm14070741
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277838_p26
|
PMC11277838
|
sec[8]/p[2]
|
9. The Potential Associations of Novel Therapeutics with Fluid Management in Heart Failure
| 4.105469 |
biomedical
|
Study
|
[
0.99853515625,
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[
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Sacubitril/valsartan showed significant improvement of cardiovascular outcomes compared to enalapril in patients with HFrEF . Sacubitril increases natriuretic peptide levels by inhibiting the enzyme neprilysin, which may result in a natriuretic effect . Sacubitril/valsartan significantly reduced the dose of diuretics compared to the enalapril arm in patients with HFrEF in the PARADIGM-HF trial . In the post hoc analysis of the PARADIGM-HF and PARAGON trials , renal outcome (>50% decline in estimated glomerular filtration rate or progression to end-stage renal disease) was also improved by sacubitril/valsartan compared to comparators (enalapril or valsartan) . These findings suggest that sacubitril/valsartan helps diuresis and exerts renoprotective effects and potentially reduces the need for sodium and fluid restriction in patients with HF.
|
[
"Naoko P. Kato",
"Yuji Nagatomo",
"Fujimi Kawai",
"Takeshi Kitai",
"Atsushi Mizuno"
] |
https://doi.org/10.3390/jpm14070741
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277838_p27
|
PMC11277838
|
sec[8]/p[3]
|
9. The Potential Associations of Novel Therapeutics with Fluid Management in Heart Failure
| 4.160156 |
biomedical
|
Review
|
[
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[
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Vericiguat has emerged as a novel drug for the treatment of HF. Previous studies showed that vericiguat administration did not affect renal function , dose of loop diuretics , or plasma levels of neurohormonal components, including aldosterone and norepinephrine . Irrespective of its neutral effect on these, vericiguat was shown to cause significant improvement of hemodynamics, including reduced pulmonary artery wedge pressure , and was shown to be effective in reducing cardiovascular death or ADHF hospitalization of patients with HFrEF . As a novel non-pharmacological therapy, cardiac contractility modulation (CCM) therapy was found to improve cardiac function without increasing myocardial oxygen consumption through the improvement of calcium handling and facilitate reverse remodeling in patients with HFrEF . Randomized control trials demonstrated that CCM therapy improved the 6 min walk distance, quality of life, and functional status of HF patients who remained symptomatic despite GDMT without an indication for cardiac resynchronization therapy . Although there has been no evidence regarding the effect of these novel therapeutics on fluid management, they may have a potential to favorably affect fluid management in patients with HF.
|
[
"Naoko P. Kato",
"Yuji Nagatomo",
"Fujimi Kawai",
"Takeshi Kitai",
"Atsushi Mizuno"
] |
https://doi.org/10.3390/jpm14070741
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277838_p28
|
PMC11277838
|
sec[9]/p[0]
|
10. Future Directions
| 4.136719 |
biomedical
|
Study
|
[
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Considering the mixed results and the limitations of the systematic reviews, future studies are necessary to determine whether fluid restriction provides beneficial impacts for patients with HF. Several randomized controlled trials such as the FRESH-UP trial are either currently underway or planned . The FRESH-UP study is a randomized, controlled, open-label, multicenter trial designed to investigate the effects of a 3-month period of liberal fluid intake versus fluid restriction on the quality of life of outpatients with chronic HF, specifically those classified as NYHA II–III patients. The study aims to randomize 506 patients into two groups of 253 each. The primary outcome is quality of life after three months, assessed using the Overall Summary Score of the Kansas City Cardiomyopathy Questionnaire. Secondary outcomes include measures of thirst distress, clinical summary scores, and safety outcomes such as death and HF hospitalizations. This study will provide crucial insights into the effects of fluid restriction on quality of life and other patient-reported outcomes.
|
[
"Naoko P. Kato",
"Yuji Nagatomo",
"Fujimi Kawai",
"Takeshi Kitai",
"Atsushi Mizuno"
] |
https://doi.org/10.3390/jpm14070741
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999999 |
PMC11277838_p29
|
PMC11277838
|
sec[10]/p[0]
|
11. Conclusions
| 4.007813 |
biomedical
|
Review
|
[
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While fluid restriction has been deemed conceptually important in the management of HF, the evidence supporting its effectiveness is not as robust as that for pharmacological treatments like GDMT, making it challenging to establish recommendations for fluid intake in patients with HF. While a recent meta-analysis demonstrated the beneficial effects of fluid restriction on both all-cause mortality and hospitalization compared to usual care, several weaknesses were identified in the assessment of the methodological quality of the meta-analysis. Further randomized controlled trials with larger sample sizes and consideration of cultural and societal contexts are needed. Additionally, the impacts of fluid restriction should be assessed not only with respect to clinical outcomes, but also with respect to patient-reported outcomes such as thirst and quality of life. Managing fluid intake poses challenges for patients with HF. To ensure successful fluid intake, self-care education addressing both the quantity of fluid intake and adjustment of fluid intake based on self-care monitoring is necessary.
|
[
"Naoko P. Kato",
"Yuji Nagatomo",
"Fujimi Kawai",
"Takeshi Kitai",
"Atsushi Mizuno"
] |
https://doi.org/10.3390/jpm14070741
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11277851_p0
|
PMC11277851
|
sec[0]/p[0]
|
1. Introduction
| 4.101563 |
biomedical
|
Study
|
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The medial longitudinal arch (MLA) of the foot has important functions in both standing and walking and shows variations in its height . A high MLA is less flexible than a standard arch and is associated with varus and supination of the rearfoot . Individuals with a high MLA of the foot have reduced foot mobility , greater leg stiffness , reduced shock absorption and increased peak plantar pressure . These individuals with cavus foot have lower plantar pressure at the MLA and increased plantar pressure at the forefoot and heel compared to those with normal or low MLA of the foot . High MLA of the foot also affects the kinematics of the lower limb during walking and running; it is associated with lower knee flexion excursion , smaller peak knee abduction movements , shorter contact times, and smaller centre of pressure excursion .
|
[
"Juan Carlos Zuil-Escobar",
"José Antonio Martín-Urrialde",
"Antonia Gómez-Conesa",
"Carmen Belén Martínez-Cepa"
] |
https://doi.org/10.3390/jcm13144049
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277851_p1
|
PMC11277851
|
sec[0]/p[1]
|
1. Introduction
| 4.148438 |
biomedical
|
Study
|
[
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[
0.76904296875,
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Variations in the alignment are risk factors for lower limb injuries and changes in the height of the foot’s MLA are associated with a greater prevalence of injuries , including plantar fasciitis , knee flexor injuries , triceps surae injuries , non-contact anterior cruciate ligament injuries , lateral ankle sprains , foot pain and bony injuries . Feet with a high MLA are more likely to suffer stress fractures, particularly in the tibia, femur and fifth metatarsal . Although both increased and decreased arches are associated with lower limb injury; the strength of this relationship is weak . In addition, a high MLA of the foot affects muscle function. The strength of the ankle dorsiflexion muscles is lower in participants with cavus foot compared to controls and high-arch runners show significantly earlier electromyographic onset of vastus lateralis (VL) compared to low-arch runners . However, the height of the MLA does not affect both the vertical jump and the standing long jump . An increased MLA, therefore, makes the foot a stiffer structure, which, as mentioned above, may be associated with the development of injury and may also affect gait and running.
|
[
"Juan Carlos Zuil-Escobar",
"José Antonio Martín-Urrialde",
"Antonia Gómez-Conesa",
"Carmen Belén Martínez-Cepa"
] |
https://doi.org/10.3390/jcm13144049
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11277851_p2
|
PMC11277851
|
sec[0]/p[2]
|
1. Introduction
| 4.140625 |
biomedical
|
Review
|
[
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[
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There are different methods to evaluate the height of the MLA of the foot, including radiographic parameters, footprint angles, or indexes and clinical tests. Although the radiography evaluation is the gold standard for assessing the medial longitudinal arch, its negative side effects, such as ionizing radiation, make its use impractical and unjustified . Clinical tests include the navicular drop test (NDT) , described by Brody , which assesses the excursion of the navicular tuberosity in the sagittal plane in two positions: the subtalar neutral position unloaded and the relaxed position under load. The NDT is an inexpensive method of assessing the height of the MLA and has shown high reliability in both healthy individuals and those with lower limb injuries, such as patellofemoral syndrome or rheumatoid arthritis . In addition, the NDT has shown significant correlations with footprint parameters . Values between 5 and 9 mm are usually considered normal, with higher values associated with low MLA and lower values associated with high MLA . NDT has been used to assess the height of the MLA, including in both high and low arches , showing significant effect sizes in identifying both high and low MLA .
|
[
"Juan Carlos Zuil-Escobar",
"José Antonio Martín-Urrialde",
"Antonia Gómez-Conesa",
"Carmen Belén Martínez-Cepa"
] |
https://doi.org/10.3390/jcm13144049
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11277851_p3
|
PMC11277851
|
sec[0]/p[3]
|
1. Introduction
| 4.105469 |
biomedical
|
Review
|
[
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[
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A myofascial trigger point is a hyperirritable focus in a taut band of muscle that is painful when the muscle is compressed, stretched, or overstretched . They can be classified as active trigger points (ATrPs) or latent trigger points (LTrPs) depending on the presence or absence of spontaneous pain, respectively . LTrPs cause changes in ultrasound imaging , biochemical changes , and spontaneous electrical activity , in addition to affecting reciprocal inhibition and causing muscle spasm . They also decrease strength , reduce the range of motion (ROM) , and affect muscle activation patterns . In addition, LTrPs can become ATrPs . Therefore, both assessment and treatment of LTrPs may be necessary in clinical practice. They can be present in both patients with myofascial pain syndrome and pain-free subjects . For example, 77.7% of pain-free subjects have at least one LTrP in the lower limb muscles , with a prevalence ranging from 13% to 37.4% .
|
[
"Juan Carlos Zuil-Escobar",
"José Antonio Martín-Urrialde",
"Antonia Gómez-Conesa",
"Carmen Belén Martínez-Cepa"
] |
https://doi.org/10.3390/jcm13144049
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277851_p4
|
PMC11277851
|
sec[0]/p[4]
|
1. Introduction
| 4.082031 |
biomedical
|
Study
|
[
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There are many causes associated with the development of LTrPs, and changes in posture and joint alignment have been suggested as one of these factors . Therefore, previous studies have associated the presence of trigger points with head extension and reduction in cervical lordosis in migraineurs patients , as well as forward head posture . With regard to changes in lower limb alignment and the presence of LTrPs, it has previously been shown that people with a reduced internal longitudinal arch have a greater number of LTrPs than people with a normal-height MLA . However, the relationship between a higher MLA and LTrPs has not been investigated, and no previous studies have compared the prevalence of LTrPs in subjects with a high MLA to controls. Our hypothesis is that the presence of a high MLA is associated with a higher prevalence of latent trigger points.
|
[
"Juan Carlos Zuil-Escobar",
"José Antonio Martín-Urrialde",
"Antonia Gómez-Conesa",
"Carmen Belén Martínez-Cepa"
] |
https://doi.org/10.3390/jcm13144049
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277851_p5
|
PMC11277851
|
sec[0]/p[5]
|
1. Introduction
| 4.0625 |
biomedical
|
Study
|
[
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[
0.99951171875,
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The primary objective of this study was to assess the prevalence of LTrPs in several lower limb muscles in participants with a high MLA of the foot compared to controls. Secondly, the intra-rater reliability of the navicular drop test (NDT) and the diagnosis of LTrPs were calculated.
|
[
"Juan Carlos Zuil-Escobar",
"José Antonio Martín-Urrialde",
"Antonia Gómez-Conesa",
"Carmen Belén Martínez-Cepa"
] |
https://doi.org/10.3390/jcm13144049
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11277851_p6
|
PMC11277851
|
sec[1]/sec[0]/p[0]
|
2.1. Study Design
| 1.897461 |
biomedical
|
Study
|
[
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A cross sectional study was carried out.
|
[
"Juan Carlos Zuil-Escobar",
"José Antonio Martín-Urrialde",
"Antonia Gómez-Conesa",
"Carmen Belén Martínez-Cepa"
] |
https://doi.org/10.3390/jcm13144049
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11277851_p7
|
PMC11277851
|
sec[1]/sec[1]/p[0]
|
2.2. Sample Size
| 3.777344 |
biomedical
|
Study
|
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The first 40 participants (20 with a high MLA of the foot and 20 controls) were used to calculate the sample size of the study and the intra-rater reliability of the procedures. The prevalence of the LTrPs located in the ankle dorsiflexors and VL was used to calculate the sample size. The Ene programme (version 3.0) was used with a precision level of 5% and 80% power. The sample size obtained was 37 participants per group.
|
[
"Juan Carlos Zuil-Escobar",
"José Antonio Martín-Urrialde",
"Antonia Gómez-Conesa",
"Carmen Belén Martínez-Cepa"
] |
https://doi.org/10.3390/jcm13144049
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277851_p8
|
PMC11277851
|
sec[1]/sec[2]/p[0]
|
2.3. Intra-Rater Reliability
| 2.291016 |
biomedical
|
Study
|
[
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[
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] |
With regard to the intra-rater reliability of the NDT and LTrPs diagnosis, a test-rest was carried out, with a period of 48 h between assessments ; the rater was a physiotherapist with 20 years’ experience.
|
[
"Juan Carlos Zuil-Escobar",
"José Antonio Martín-Urrialde",
"Antonia Gómez-Conesa",
"Carmen Belén Martínez-Cepa"
] |
https://doi.org/10.3390/jcm13144049
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11277851_p9
|
PMC11277851
|
sec[1]/sec[3]/p[0]
|
2.4. Participants and Settings
| 4.003906 |
biomedical
|
Study
|
[
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[
0.99951171875,
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Pain-free volunteers who responded to an e-mail campaign were included in the study. A convenience sampling method was used. This sample has some limitations: it may not be representative of the population as a whole, and the results cannot be extrapolated to the general population, which limits its external validity . Participants were recruited from the staff and students at the University of San Pablo-CEU. The project observed the principles outlined in the Declaration of Helsinki of 1975, revised in 1983, and it was evaluated by the Research Ethics Committee of the CEU-San Pablo University. All participants were informed of the aims and procedures of the study and completed an informed consent form before being included in the research. Inclusion criteria included an NDT ≤ 4 mm in the high MLA of the foot group and an NDT between 5 and 9 mm in the control group . Participants were excluded if they had undergone lower limb surgery, had acute lower limb injuries, had lower limb deformities, had systemic or neurological conditions that could affect pain perception, and/or had a reduction in lower limb ROM compared to normal. The ball kick test was used to determine lower limb dominance .
|
[
"Juan Carlos Zuil-Escobar",
"José Antonio Martín-Urrialde",
"Antonia Gómez-Conesa",
"Carmen Belén Martínez-Cepa"
] |
https://doi.org/10.3390/jcm13144049
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11277851_p10
|
PMC11277851
|
sec[1]/sec[4]/p[0]
|
2.5. Variables
| 2.912109 |
biomedical
|
Study
|
[
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[
0.99365234375,
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0.0002651214599609375
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The variables assessed were: Demographics: sex, height, weight, and body mass index. Type of MLA: standard (NDT from 5 to 9 mm) or high (NDT ≤ 4 mm) . Total number of LTrPs in all muscles assessed. Prevalence of LTrPs in each of the muscles assessed.
|
[
"Juan Carlos Zuil-Escobar",
"José Antonio Martín-Urrialde",
"Antonia Gómez-Conesa",
"Carmen Belén Martínez-Cepa"
] |
https://doi.org/10.3390/jcm13144049
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277851_p11
|
PMC11277851
|
sec[1]/sec[5]/p[0]
|
2.6. Measurement
| 4.085938 |
biomedical
|
Study
|
[
0.994140625,
0.005279541015625,
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[
0.994140625,
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The assessment of the MLA was performed prior to the assessment of LTrPs by a physiotherapist with more than 20 years of experience in using the test. A modification of the Brody procedure was used: with the subject standing barefoot on the floor, the navicular tuberosity was marked. The examiner palpated the medial and lateral aspects of the talar dome, with the thumb over the talar sinus and the index finger over the anteromedial portion. The foot was then slowly inverted and everted until the depressions felt under both fingers were equal. With the subtalar joint in neutral position, the distance between the navicular tuberosity and the ground was measured (in millimeters) using a ruler. The height of the navicular tuberosity was then measured again with the foot in a relaxed position. The NDT was the difference between the two measurements . The procedure was repeated three times, and the average was recorded .
|
[
"Juan Carlos Zuil-Escobar",
"José Antonio Martín-Urrialde",
"Antonia Gómez-Conesa",
"Carmen Belén Martínez-Cepa"
] |
https://doi.org/10.3390/jcm13144049
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11277851_p12
|
PMC11277851
|
sec[1]/sec[5]/p[1]
|
2.6. Measurement
| 3.849609 |
biomedical
|
Study
|
[
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[
0.9833984375,
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Palpation techniques were used to assess the prevalence of LTrPs . The identification of a LTrP was considered positive if 2 or more of the following criteria were present: A palpable taut band in skeletal muscle. A hypersensitive tender spot. The reproduction of referred pain in response to compression. The jump sign. A local twitch response provoked by palpation of the taut band.
|
[
"Juan Carlos Zuil-Escobar",
"José Antonio Martín-Urrialde",
"Antonia Gómez-Conesa",
"Carmen Belén Martínez-Cepa"
] |
https://doi.org/10.3390/jcm13144049
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11277851_p13
|
PMC11277851
|
sec[1]/sec[5]/p[2]
|
2.6. Measurement
| 4.148438 |
biomedical
|
Study
|
[
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[
0.9951171875,
0.003681182861328125,
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The following muscles were assessed : gastrocnemius (GM) (LTrP1 and LTrP2), soleus (LTrP1), peroneus longus (PL), peroneus brevis, tibialis anterior (TA), extensor digitorum longus (EDL), flexor digitorum longus, rectus femoris (RF), vastus medialis (VM) (LTrP1 and LTrP2), and VL (LTrP1 and LTrP2). Flat palpation was used on the quadriceps muscles, with the participant in the supine position. For palpation of the VL, the knee was extended. For the palpation of the RF, the lower limb was placed in moderate abduction with the knee extended, while for the VM, the knee was flexed 90°. Flat palpation in the supine position was also used to examine the TA, EDL, and both peroneals. The flexor digitorum longus was assessed by flat palpation with the patient in a side-lie position. Pincer palpation was used to assess the GM, with the participant in the lateral decubitus position. Flat palpation was used for the soleus, with the participant in the lateral decubitus position with the knee flexed. The order in which the LTrPs were assessed was randomized for each subject. The LTrPs were assessed by a physiotherapist with 20 years’ experience in the management of myofascial pain syndrome. Participants were blinded to the results of both the NDT and LTrPs assessments.
|
[
"Juan Carlos Zuil-Escobar",
"José Antonio Martín-Urrialde",
"Antonia Gómez-Conesa",
"Carmen Belén Martínez-Cepa"
] |
https://doi.org/10.3390/jcm13144049
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11277851_p14
|
PMC11277851
|
sec[1]/sec[6]/p[0]
|
2.7. Statistical Methods
| 4.054688 |
biomedical
|
Study
|
[
0.99951171875,
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[
0.9990234375,
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0.0003731250762939453,
0.00006598234176635742
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Statistical analysis was performed using IBM SPSS 24, with an alpha level of 0.05 for all the tests performed. The Kolmogorov–Smirnov test was used to assess the normal distribution of the quantitative variables; in this case, parametric tests were performed. Descriptive analysis was performed using means and standard deviations for quantitative variables, and frequencies and percentages for qualitative variables. The intra-rater reliability of the NDT (continuous variable) was assessed using the intraclass correlation coefficient (ICC), and Cohen’s kappa was used to assess the diagnosis of the LTrPs (non-continuous variable). The ICC was determined by using mixed-effect and absolute agreement or consistency 2-factor alpha models. Differences in quantitative demographic variables and the number of LTrPs between the two groups were assessed using the unpaired Student t test. The chi-squared test was used to assess the difference in qualitative demographic variables and the prevalence of LTrPs in each muscle between the two groups.
|
[
"Juan Carlos Zuil-Escobar",
"José Antonio Martín-Urrialde",
"Antonia Gómez-Conesa",
"Carmen Belén Martínez-Cepa"
] |
https://doi.org/10.3390/jcm13144049
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11277851_p15
|
PMC11277851
|
sec[2]/sec[0]/sec[0]/p[0]
|
3.1.1. Participants and Descriptive Data
| 2.201172 |
biomedical
|
Study
|
[
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The high MLA foot group included 21 women (56.8%) and 16 men (43.2%), whereas the control group included 22 women (59.5%) and 15 men (40.5%). Table 1 shows the characteristics of the participants. There were no statistically significant differences ( p > 0.05) in demographic variables between the groups.
|
[
"Juan Carlos Zuil-Escobar",
"José Antonio Martín-Urrialde",
"Antonia Gómez-Conesa",
"Carmen Belén Martínez-Cepa"
] |
https://doi.org/10.3390/jcm13144049
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277851_p16
|
PMC11277851
|
sec[2]/sec[0]/sec[1]/p[0]
|
3.1.2. Main Results
| 4.0625 |
biomedical
|
Study
|
[
0.9990234375,
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[
0.99951171875,
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In the high MLA group, twenty-nine (78.4%) participants had at least 1 LTrP, compared to 62.2% (twenty-three participants) in the control group. Although the high MLA foot participants had more LTrPs (mean: 4.46 ± 3.8) than the controls (mean: 3.24 ± 3.9), no statistical difference was found in the unpaired Student t test ( p > 0.05).
|
[
"Juan Carlos Zuil-Escobar",
"José Antonio Martín-Urrialde",
"Antonia Gómez-Conesa",
"Carmen Belén Martínez-Cepa"
] |
https://doi.org/10.3390/jcm13144049
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999994 |
PMC11277851_p17
|
PMC11277851
|
sec[2]/sec[0]/sec[1]/p[1]
|
3.1.2. Main Results
| 4.007813 |
biomedical
|
Study
|
[
0.99951171875,
0.0002570152282714844,
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] |
[
0.99951171875,
0.0002789497375488281,
0.00022912025451660156,
0.00005322694778442383
] |
The Chi-squared test showed statistically significant differences ( p < 0.05) in the prevalence of LTrPs in the TA, EDL, and both VLs (LTrP1 and LTrP2). The high MLA group had a higher number of LTrPs in these muscles than the control group. Table 2 and Figure 2 show the prevalence of each LTrP.
|
[
"Juan Carlos Zuil-Escobar",
"José Antonio Martín-Urrialde",
"Antonia Gómez-Conesa",
"Carmen Belén Martínez-Cepa"
] |
https://doi.org/10.3390/jcm13144049
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11277851_p18
|
PMC11277851
|
sec[2]/sec[1]/p[0]
|
3.2. Intra-Rater Reliability
| 4.070313 |
biomedical
|
Study
|
[
0.99853515625,
0.0009784698486328125,
0.0005674362182617188
] |
[
0.99951171875,
0.0003981590270996094,
0.00016057491302490234,
0.00007277727127075195
] |
There were 11 women (55.5%) in the high MLA foot group and 10 (50%) in the control group. Both groups showed excellent intra-rater reliability for the NDT. The ICC (2,1) was 0.957 (95% confidence interval, 0.895–0.983) in the control group and 0.959 (95% confidence interval, 0.899–0.983) in the high MLA group. The intra-reliability of the diagnosis of LTrPs was excellent in both the control group (0.828–1) and the high MLA group (0.828–1). Table 3 shows all the values.
|
[
"Juan Carlos Zuil-Escobar",
"José Antonio Martín-Urrialde",
"Antonia Gómez-Conesa",
"Carmen Belén Martínez-Cepa"
] |
https://doi.org/10.3390/jcm13144049
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11277851_p19
|
PMC11277851
|
sec[3]/p[0]
|
4. Discussion
| 4.089844 |
biomedical
|
Study
|
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[
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0.00007826089859008789
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The main objective of this study was to assess the prevalence of LTrPs in different muscles of the lower limbs in subjects with an increased MLA compared to controls. Although no significant differences were found in the total number of LTrPs between the groups, participants with increased MLA had a higher number of LTrPs in the TA, ED, and VL. The secondary objective was to assess the intra-observer reliability of the NDT and the diagnosis of LTrPs, both of which were excellent.
|
[
"Juan Carlos Zuil-Escobar",
"José Antonio Martín-Urrialde",
"Antonia Gómez-Conesa",
"Carmen Belén Martínez-Cepa"
] |
https://doi.org/10.3390/jcm13144049
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11277851_p20
|
PMC11277851
|
sec[3]/sec[0]/p[0]
|
4.1. Intra-Rater Reliability
| 4.085938 |
biomedical
|
Study
|
[
0.9990234375,
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[
0.99853515625,
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The reliability of clinical tests is important to researchers and clinicians , as it is important for the interpretation of the measurements, whereas low reliability may be a source of bias. In this study, the intra-rater reliability for the NDT was excellent in both the control and high MLA groups. Good to excellent reliability, both intra-rater and inter-rater , has been demonstrated previously. In participants with a low foot MLA, the intra-rater reliability for the NDT was also excellent . The intra-rater reliability of the LTrP diagnosis was excellent (0.828–1). The reliability of the LTrP diagnosis in the lower limb muscles has been previously studied and ranged from moderate to excellent . Palpation techniques are currently the preferred method for the clinical diagnosis of LTrPs, and reliable palpation is required for a diagnosis to be considered valid . Reliability is related to the experience of the rater , palpatory skills , and the location of the muscles .
|
[
"Juan Carlos Zuil-Escobar",
"José Antonio Martín-Urrialde",
"Antonia Gómez-Conesa",
"Carmen Belén Martínez-Cepa"
] |
https://doi.org/10.3390/jcm13144049
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277851_p21
|
PMC11277851
|
sec[3]/sec[1]/p[0]
|
4.2. Prevalence of LTrPs
| 4.164063 |
biomedical
|
Study
|
[
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[
0.99853515625,
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0.00007021427154541016
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The main goal of this study was to evaluate and compare the prevalence of LTrPs in the lower limb muscles in both participants with high MLA of the foot and controls. There are no previous studies that have evaluated this. Although participants with high MLA had a higher number of LTrPs (mean: 4.46 ± 3.8) than controls (mean: 3.24 ± 3.9), there was no statistical difference. However, significant differences were found in some of the muscles examined. The high MLA group showed a higher prevalence of LTrPs ( p < 0.05) in the TA, EDL, and VL (LTrP1 and LTrP2) compared to the control group. Previous researchers have compared the prevalence of LTrPs in controls and participants with other clinical characteristics. Zuil-Escobar et al. compared participants with low MLA of the foot (n = 82) and controls (n = 82), and found no statistical differences in the total number of LTrPs between the two groups. However, the low MLA foot group showed a higher prevalence of LTrPs than the control group ( p < 0.05) in the TA, FLD, and VM. In the first group, the prevalence of LTrP in these muscles ranged from 38% to 43%, whereas in the control group, it ranged from 18% to 26%. Torres-Chica et al. evaluated the prevalence of both ATrPs and LTrPs in post-meniscectomy pain participants and controls in the GM, RF, VM, and VL. They found no statistical difference in the total number of LTrPs between the groups. The prevalence of LTrPs ranged from 3% to 63.3% in the control group and from 15.2% to 51.5% in the post-meniscectomy pain group. In both groups, the highest prevalence was found in the GM and the lowest in the RF. Bajab et al. compared the prevalence of both ATrP and LTrP in the quadriceps, triceps surae, and the peronei in osteoarthritis participants (n = 14) and controls (n = 14). The osteoarthritis group had a higher prevalence of LTrPs than controls ( p < 0.05), with LTrPs present in all muscles examined (7.1%-64.3%). In participants with knee osteoarthrosis, Sánchez-Romero et al. found a prevalence of LTrPs ranging from 12% to 50% in different lower limb muscles, including quadriceps and gastrocnemius. Rozenfeld et al. found differences in the prevalence of both ATrPs and LTrPs in the VM, VF, and RF in military personnel with anterior knee pain (n = 65) and controls (n = 24). While only 6.3% of controls had at least 1 ATrP or LTrP, 78.8% of the participants with anterior knee pain had at least 1 ATrP or LTrP. In addition, other studies have shown that LTrPs in the lower limb are common in pain-free subjects .
|
[
"Juan Carlos Zuil-Escobar",
"José Antonio Martín-Urrialde",
"Antonia Gómez-Conesa",
"Carmen Belén Martínez-Cepa"
] |
https://doi.org/10.3390/jcm13144049
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11277851_p22
|
PMC11277851
|
sec[3]/sec[1]/p[1]
|
4.2. Prevalence of LTrPs
| 4.378906 |
biomedical
|
Study
|
[
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[
0.9990234375,
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Several factors associated with the presence of myofascial trigger points have been hypothesised. One of them may be mechanical dysfunctions . A lower MLA of the foot and subtalar pronation could be an activating or perpetuating factor for LTrPs located in the VM, PL, peroneus brevis, flexor digitorum longus, and tibialis posterior . Although previous research has shown a greater prevalence of LTrPs in the flexor digitorum longus, TA, and VM in participants with low MLA compared to controls , no previous studies have evaluated the relationship between a high MLA and LTrPs. Biomechanical factors may be related to the higher prevalence of LTrPs in the high MLA foot participants compared to controls. A high MLA is associated with calcaneal inversion and forefoot varus and is stiffer than a low or standard MLA . Cavus feet have reduced foot mobility and are associated with lower limb stiffness and a reduction in shock-absorbing capacity . Previously, a high MLA foot has been shown to correlate with reduced ankle dorsiflexion and a shortened Achilles tendon . It has been proposed that a low ankle ROM is associated with myofascial trigger points located in the quadriceps muscles . A decrease in ankle dorsiflexion ROM could stretch the plantar flexors, affecting the LTrPs located in the triceps surae . The TA and EDL could be affected simultaneously, as they are agonists of the triceps surae . However, our study did not assess ankle ROM, so it is not possible to conclude whether there is a relationship between ankle ROM and the prevalence of LTrPs in the muscles assessed. In addition to changes in joint biomechanics, the height of the MLA could influence muscle activity and its characteristics . Foot type explains the variation in the anteroposterior thickness of the TA tendon (7.1%), PL muscle (7.6%), and Achilles’ tendon (16%) and is correlated with toe flexor and tibialis posterior strength . These changes could be related to the presence of LTrPs in the affected muscles.
|
[
"Juan Carlos Zuil-Escobar",
"José Antonio Martín-Urrialde",
"Antonia Gómez-Conesa",
"Carmen Belén Martínez-Cepa"
] |
https://doi.org/10.3390/jcm13144049
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999999 |
PMC11277851_p23
|
PMC11277851
|
sec[3]/sec[1]/p[2]
|
4.2. Prevalence of LTrPs
| 4.371094 |
biomedical
|
Study
|
[
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[
0.99658203125,
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A high MLA of the foot also affects the gait. Therefore, a greater vertical load has been found in participants with high MLA , and the speed of the centre of pressure is also affected . During walking and running, people with high MLA of the foot have a different pattern of movement compared to those with a low or normal MLA . In addition, an earlier electromyography onset of VL has been found in participants with high MLA compared to those with low MLA during running . These changes could lead to fatigue in the affected muscles and could be a cause for the presence of LTrPs. During gait, the rotational stress in the weight-bearing lower limb is related to the supination or pronation of the foot during the stance phase, and the movement of the hip, knee, and subtalar joints during this phase is interdependent . Individuals with high MLA of the foot have altered angles in the transverse and frontal planes of the rearfoot and less ROM in the midfoot in both the sagittal and transverse planes during the initial contact and midstance phases . This may be related to the stiffness of the MLA and an increase in vertical loading. It has been suggested that small angular variations in the ROM of the foot may be critical in the development of lower limb overuse injuries ; LTrPs may be involved in these injuries. It should also be considered that the NDT may not reflect the dynamic behaviour of the navicular. The limit value for flat feet in dynamic NDT has been set at 8.5 mm , which is close to the 10 mm established for the NDT. No reference values for dynamic NDT have been found for high MLA. It should be noted that the NDT does not overestimate the walking motion of the navicular in the hypomobile feet , which corresponds to the lowest static NDT values and therefore to the MLAs catalogued as high in our research. This can be seen in the greater joint congruence and stiffness of the soft structures that appear in this type of foot . However, it should also be remembered that the foot is loaded twice as much in monopodal stance as in bipodal clinical testing . It is therefore necessary to include dynamic gait analysis and other imaging tests that can provide complementary information on the dynamic function of the foot compared to the static function assessed by NDT.
|
[
"Juan Carlos Zuil-Escobar",
"José Antonio Martín-Urrialde",
"Antonia Gómez-Conesa",
"Carmen Belén Martínez-Cepa"
] |
https://doi.org/10.3390/jcm13144049
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999994 |
PMC11277851_p24
|
PMC11277851
|
sec[3]/sec[1]/p[3]
|
4.2. Prevalence of LTrPs
| 4.308594 |
biomedical
|
Study
|
[
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[
0.9970703125,
0.0004570484161376953,
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0.00022232532501220703
] |
Our results suggest that LTrPs are common in the lower limb muscles of both participants with high MLA of the foot and controls. The high MLA group showed a higher prevalence in the ECD, TA, and VL. This high prevalence may be clinically important and the assessment and management of the height of the MLA of the foot may be important in the management of lower limb myofascial pain syndrome. The LTrPs are present in lower limb disorders such a knee osteoarthritis , post-meniscectomy pain , calf pain , patellofemoral pain syndrome , and anterior knee pain . LTrPs do not cause spontaneous pain, but they can affect multiple muscle functions. For example, they can affect muscle activity , reciprocal inhibition , and muscle activation patterns, reducing overall movement efficiency . They also increase intramuscular electromyographic activity in synergist muscles , accelerate muscle fatigability , and decrease strength . In the lower limb, they can also reduce ankle ROM and increase muscle spasm . LTrPs can easily convert into ATrPs if the underlying causes are not treated . LTrPs are common in different conditions involving biomechanical changes in the lower limb and a high MLA is associated with several injuries . In addition, the height of the MLA is associated with changes in the lower limb biomechanics . Although the mechanisms linking foot position and increased risk of lower limb injury are unclear, changes in lower limb biomechanics are considered to be among them . Changes in joint alignment may be one of the causes of the development of LTrPs in these muscles . Therefore, the mechanisms involved in the higher prevalence of LTrPs in different muscles in participants with high MLA of the foot should be investigated. Prospective research is needed to investigate the relationship between LTrPs and high MLA of the foot to determine whether the LTrPs located in these muscles are a consequence of the biomechanical changes associated with a cavus foot. Assessment and, where appropriate, control of high MLA may be useful in the management of LTrPs. Control of MLA height has previously been shown to influence the electromyographic activity of lower extremity muscles such as the tibialis anterior, tibialis posterior , peroneus longus , and medial gastrocnemius . It may also be helpful to investigate the effect of techniques to control the height of the MLA, such as orthotics or functional taping, on the presence of LTrPs, but it should be noted that there may be other factors associated with the presence of LTrPs in the lower limb musculature, so an individual assessment of each patient is required.
|
[
"Juan Carlos Zuil-Escobar",
"José Antonio Martín-Urrialde",
"Antonia Gómez-Conesa",
"Carmen Belén Martínez-Cepa"
] |
https://doi.org/10.3390/jcm13144049
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277851_p25
|
PMC11277851
|
sec[3]/sec[2]/p[0]
|
4.3. Limitations
| 4.125 |
biomedical
|
Study
|
[
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[
0.99951171875,
0.00018584728240966797,
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] |
This study has limitations. Firstly, this research includes LTrPs; future studies should include ATrPs as they could be associated with foot and ankle pathologies , and their study would be interesting. In addition, we did not include all the important muscles of the lower limb, such as the tibialis posterior, the adductors, or the hamstrings. With regard to the arch, we did not differentiate between rigid and mobile high MLA. Midfoot mobility during walking and running is thought to play a role in lower limb function, and arch mobility influences rearfoot movement . This factor may influence the development of LTrPs in lower limb muscles. The height of the MLA was assessed using the NDT. It should be noted that the gold standard for assessing MLA height is radiographic parameters . The NDT has been shown to be less reliable for inexperienced raters . This may be related to the difficulty in locating the navicular tuberosity and positioning the subtalar joint in a neutral position . However, in our study, the assessor was experienced in the use of this clinical test. We sought to limit the risk of bias inherent in the NDT as a clinical test by assessing MLA height prior to the presence of LTrPs. It should also be considered that the NDT may not reflect the dynamic behaviour of the navicular bone and that this study assessed the MLA in static rather than dynamic conditions. Future research is therefore needed to evaluate the dynamic behaviour of the MLA and its relationship to the presence of LTrPs. The use of dynamic NDT can be compromised by the need to use video systems, which can be unreliable and expensive . Finally, a cohort of pain-free young people was studied, so the results cannot be generalized to other populations. Further studies in populations with different demographic characteristics or foot pathology are needed in order to extrapolate the results of this research.
|
[
"Juan Carlos Zuil-Escobar",
"José Antonio Martín-Urrialde",
"Antonia Gómez-Conesa",
"Carmen Belén Martínez-Cepa"
] |
https://doi.org/10.3390/jcm13144049
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277851_p26
|
PMC11277851
|
sec[4]/p[0]
|
5. Conclusions
| 3.822266 |
biomedical
|
Study
|
[
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[
0.99951171875,
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No significant differences were found in the total number of LTrPs between the participants with high MLA of the foot and the control group. However, the specific prevalence of LTrPs in the TA, EDL, and VL was statistically significantly higher in the high MLA group. The reliability of both NDT and the diagnosis of the LTrPs was excellent. It is necessary to investigate whether both alignment and kinematics in the high MLA of the foot are related to the presence of LTrPs.
|
[
"Juan Carlos Zuil-Escobar",
"José Antonio Martín-Urrialde",
"Antonia Gómez-Conesa",
"Carmen Belén Martínez-Cepa"
] |
https://doi.org/10.3390/jcm13144049
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11277865_p0
|
PMC11277865
|
sec[0]/p[0]
|
Introduction
| 4.332031 |
biomedical
|
Review
|
[
0.978515625,
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[
0.0040740966796875,
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Several studies demonstrate that dysregulation of RNA metabolism by aberrant functioning of RNA-binding proteins (RBPs) plays a central role in disease pathogenesis, especially of neurodegenerative diseases. Defects in RBPs have a deleterious effect on neuron survival and functioning. Such defects are often associated with impaired RBP expression, cellular mislocalization of aggregated RBPs, dysregulation of various metabolic pathways by sequestering RNA and proteins and DNA damage caused by increased accumulation of R-loops affecting the genomic integrity. Senataxin (SETX) is one such RBP, known as a guardian of the genome, regulates diverse cellular processes linked to genomic integrity, including regulation of RNA metabolism, resolution of RNA:DNA hybrids of R-loops and DNA damage response (DDR) and repair. Interestingly, mutations in SETX with loss-of-function and gain-of-function are associated with distinct human neurodegenerative disorders. In this review, we shed light on the multifaceted role of SETX in cellular processes, its role in the pathogenesis of neurological disorders and its therapeutic implication as a potential modifier of disease phenotype.
|
[
"Annapoorna Kannan",
"Shyni Gangadharan Leela",
"Dana Branzei",
"Laxman Gangwani"
] |
https://doi.org/10.1093/braincomms/fcae239
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11277865_p1
|
PMC11277865
|
sec[1]/p[0]
|
R-loops
| 4.859375 |
biomedical
|
Study
|
[
0.99853515625,
0.0007519721984863281,
0.0005178451538085938
] |
[
0.87890625,
0.0037784576416015625,
0.11627197265625,
0.0010614395141601562
] |
R-loops are three stranded structures resulting during transcription in which the nascent RNA hybridizes to the template DNA strand forming initial RNA:DNA hybrids and displacing the non-template single-stranded DNA (ssDNA). As RNA/DNA hybrids elongate, they become R-loops. R-loops are relatively stable and account for 3–5% of the human genome. 1-3 The stability of R-loops depends on the RNA structure, size and DNA sequence. 4 The minimum length of 100 nucleotides of normal RNA is required to generate stable R-loops for quantitation. However, modification of uridines to 5-allylamine uridines (Uaa) requires only 50 nucleotides to form stable R-loops. 4 The presence of G-quadruplex (G4) structures help stabilize the R-loops and are involved in regulatory processes, including DDX1 (RNA helicase)-dependent conversion of RNA G4 structures into R-loops during immunoglobulin H (IgH) class switch recombination 5 and the CCCTC-binding factor (CTCF) binding, which plays a critical role in regulating chromatin architecture and gene expression. 6
|
[
"Annapoorna Kannan",
"Shyni Gangadharan Leela",
"Dana Branzei",
"Laxman Gangwani"
] |
https://doi.org/10.1093/braincomms/fcae239
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11277865_p2
|
PMC11277865
|
sec[1]/p[1]
|
R-loops
| 4.332031 |
biomedical
|
Study
|
[
0.99951171875,
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[
0.880859375,
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R-loops play important roles in several physiological cellular functions, which include class switch recombination of immunoglobulin G (IgG) in B cells, mitochondrial DNA replication, CRISPR-Cas9 gene edition, DNA repair and telomere homeostasis. 7-10 R-loops are found frequently at GC-rich regions, high CpG islands containing promoters, transcription termination sites with rich GC skew or G4-containing sequences. R-loops preferentially accumulate at the promoter and termination regions of highly transcribed genes, implicating their potential as regulatory steps in transcription initiation and termination sites to regulate gene expression. 11-18
|
[
"Annapoorna Kannan",
"Shyni Gangadharan Leela",
"Dana Branzei",
"Laxman Gangwani"
] |
https://doi.org/10.1093/braincomms/fcae239
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277865_p3
|
PMC11277865
|
sec[1]/p[2]
|
R-loops
| 4.839844 |
biomedical
|
Study
|
[
0.99755859375,
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[
0.759765625,
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0.23681640625,
0.0007929801940917969
] |
Several factors prevent the formation of R-loops, including RNaseH, RNA/DNA helicases topoisomerase I (TOP I) and ribonucleoproteins (RNPs) involved in RNA metabolism. There are two types of RNaseH, RNaseH1 and RNaseH2, all of which can resolve RNA:DNA hybrids and R-loops. 19-21 Regarding RNA/DNA helicases, SETX is the primary helicase that removes R-loops formed during transcription. 22-24 Aquarius intron-binding spliceosomal factor, 25 DEAD-box-like putative RNA/DNA helicase, DDX5, 26 RECQL5, 27 Pif1, 28 BLM and Sgs1 (yeast orthologue of human BLM and RECQL5), 29 , 30 DDX18, 31 FANCM, 32 , 33 Mph1 (yeast homologue of FANCM) 34 and DHX9 35 , 36 are other helicases involved in clearance of R-loops. 5 , 37 The RNA helicase DDX19, a mRNA export factor, removes R-loops formed during replication stress. 38 DDX23 is another RNA helicase that functions at the RNAPII pause site. 39 TOP I and topoisomerase II (TOP II) 40-42 relax the negative supercoiling of DNA formed behind elongating RNA polymerase II (RNAPII) and prevent R-loop formation. Moreover, topoisomerase, TOP3B, coordinates with the DEAD-box helicase DDX5 in resolution of R-loop resolution. 42 , 43 Finally, various RNPs involved in RNA processing, splicing, packaging and export prevent R-loop formation by concomitantly binding to nascent RNA transcripts. 19-21 , 44
|
[
"Annapoorna Kannan",
"Shyni Gangadharan Leela",
"Dana Branzei",
"Laxman Gangwani"
] |
https://doi.org/10.1093/braincomms/fcae239
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11277865_p4
|
PMC11277865
|
sec[1]/sec[0]/p[0]
|
R-loop accumulation and neurodegenerative diseases
| 4.597656 |
biomedical
|
Review
|
[
0.9765625,
0.0097808837890625,
0.0135650634765625
] |
[
0.028228759765625,
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0.96875,
0.0010471343994140625
] |
Accumulation of R-loops is associated with the pathogenesis of several neurodegenerative disorders. Such accumulation causes genomic instability due to DNA double-strand breaks (DSBs), hyper-mutation, hyper-recombination, transcription-associated recombination, gross chromosomal rearrangements, as reviewed in Aguilera and García-Muse, 7 Crossley et al. 8 Li and Manley, 45 RNA processing defects 44 , 46 and replication stress, 47 as well as fragile site instability and chromosome loss if not properly cleared. 48 Several neurological disorders, including ataxias, neuromuscular disorders and nucleotide repeat expansion disorders, result from mutation of genes involved in R-loop resolution. 14 , 15 , 49 , 50 Specific examples of neurological disorders include nucleotide repeat expansion disorders such as Huntington’s disease and spinocerebellar ataxia type 1, which are caused by CAG repeats in Huntingtin and ataxin 1 genes, respectively. Other neurological disorders included fragile X mental retardation or fragile X syndrome caused by CGG repeats in the fragile X mental retardation 1 gene and Friedreich’s ataxia with GAA repeats in frataxin gene. 51 , 52 R-loops formed following transcription of GC-rich trinucleotide repeats become highly stable due to the formation of G4 and triplex DNA structures in the non-transcribing DNA strand, which further stabilize the R-loops and increase the probability for DNA damage and genomic instability. 53-55 R-loop accumulation is also reported in hexanucleotide GGGGCC repeat expansion in C9ORF72 gene, which contributes to the molecular pathogenesis of amyotrophic lateral sclerosis with frontotemporal dementia (ALS-FTD). 56 R-loop accumulation is reported in cells derived from patients with ataxia with oculomotor apraxia type 2 (AOA2) caused by mutations in the SETX gene. 57-59 Recent studies have identified R-loop accumulation in neuromuscular disorders, also classified as motor neuron diseases. These include spinal muscular atrophy (SMA) caused by mutations in the survival motor neuron 1 ( SMN1 ) gene 60-62 and amyotrophic lateral sclerosis 10 (ALS10) caused by mutations in the TAR DNA binding protein or TDP-43 gene. 63
|
[
"Annapoorna Kannan",
"Shyni Gangadharan Leela",
"Dana Branzei",
"Laxman Gangwani"
] |
https://doi.org/10.1093/braincomms/fcae239
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11277865_p5
|
PMC11277865
|
sec[2]/sec[0]/p[0]
|
R-loop resolution
| 4.667969 |
biomedical
|
Study
|
[
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[
0.9892578125,
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0.0002930164337158203
] |
The human SETX gene encodes an RNA/DNA helicase of 2677 amino acids, conserved across evolution, including the budding yeast orthologue known as Splicing Endonuclease 1 ( SEN1 ) gene that encodes similar RNA/DNA helicase. 22 , 64 SETX is an ubiquitously expressed protein containing a protein–protein interaction domain in the N-terminal and a DEAD-box helicase domain, and nuclear localization signal in the C-terminal. 64 , 65 SETX helicase domain is highly conserved and shows significant homology with helicase domains of Sen1, 66 regulator of nonsense transcripts-1 and immunoglobulin mu DNA binding protein 2. SETX localizes in both the nucleus and the cytoplasm, suggesting cytoplasmic roles besides transcription-associated R-loop processing and metabolism. 67 , 68 The growing SETX protein interactome implicates a broader role of SETX in the function of RNA processing, including transcriptional termination and maintenance of genomic stability. 23 , 69-71
|
[
"Annapoorna Kannan",
"Shyni Gangadharan Leela",
"Dana Branzei",
"Laxman Gangwani"
] |
https://doi.org/10.1093/braincomms/fcae239
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277865_p6
|
PMC11277865
|
sec[2]/sec[0]/p[1]
|
R-loop resolution
| 4.617188 |
biomedical
|
Study
|
[
0.9990234375,
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[
0.92822265625,
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0.0004012584686279297
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Significant insight into the function of SETX is gained from studies of budding yeast Sen1. Sen1 is a highly conserved RNA and DNA helicase that belongs to the superfamily 1B of helicases. 72 , 73 Sen1 interacts with RNA-Pol I, RNA-Pol II and RNA-Pol III. 74 , 75 Sen1 is important for transcription termination of genes transcribed by three RNA polymerases and contributes to the processing of diverse RNAs, including tRNA, rRNA, snRNA and snoRNA. 23 , 76-84 Sen1 interacts with multiple proteins involved in RNA synthesis, processing, transcription termination, RNP assembly and maturation, as well as DNA repair. 85 , 86 Similarly, human SETX regulates gene expression by controlling transcription initiation, termination and pre-mRNA splicing. 87 SETX also interacts with several proteins involved in transcription, splicing, RNA processing and stability factors, R-loop resolution and DNA repair, including nucleolin, RNAPII, SMN, hnRNPs, poly(A)-binding proteins 1 and 2, SF3B1 and SAP155, 69 ZPR1 88 and BRCA1. 89
|
[
"Annapoorna Kannan",
"Shyni Gangadharan Leela",
"Dana Branzei",
"Laxman Gangwani"
] |
https://doi.org/10.1093/braincomms/fcae239
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277865_p7
|
PMC11277865
|
sec[2]/sec[0]/p[2]
|
R-loop resolution
| 4.789063 |
biomedical
|
Study
|
[
0.99853515625,
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[
0.96728515625,
0.001285552978515625,
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] |
The functions of SETX and Sen1 in R-loop processing and transcription termination demonstrate the conservation of R-loop metabolism among eukaryotes. 24 , 73 , 90 , 91 Both Sen1 and SETX, through their interactions with RNA polymerases, are targeted to chromatin to continuously surveil the local chromatin landscape for the presence of R-loops. When encountered, they mediate timely removal of R-loops by unwinding the nascent RNA from RNA:DNA hybrids through the highly conserved DNA/RNA helicase activity at transcriptionally active sites and stalled elongation complexes. 72 , 85 , 91-93 Mutations in the catalytic domain of Sen1 confer defective transcription termination and increased transcriptional readthrough of several transcription units on small coding and non-coding genes, rDNA and tRNA. These events cause reduced gene expression, accumulation of R-loops and increased recombination. 19 , 22 Moreover, mutations in Sen1 also cause increased transcription associated with genome instability. 22 , 94 In summary, the resolution of R-loops by SETX prevents DNA damage and chromosomal translocations and helps maintain the integrity of the genome. 87 , 90
|
[
"Annapoorna Kannan",
"Shyni Gangadharan Leela",
"Dana Branzei",
"Laxman Gangwani"
] |
https://doi.org/10.1093/braincomms/fcae239
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11277865_p8
|
PMC11277865
|
sec[2]/sec[1]/p[0]
|
Transcription termination
| 4.953125 |
biomedical
|
Study
|
[
0.99755859375,
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] |
[
0.9873046875,
0.00249481201171875,
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0.0007777214050292969
] |
Transcription termination of protein coding genes involves cleavage at the polyadenylation [poly(A)] site by the cleavage and polyadenylation factor-cleavage factor IA and IB (CPF-CF1A and CF1B) complex of the pre-mRNA transcript and addition of a poly(A) tail. 95 , 96 Yeast Sen1 is involved in poly(A)-dependent termination. 23 , 69 , 97 , 98 The C-terminal domain of Sen1 has a sequence for nuclear localization and interacts with Glc7p, a protein phosphatase subunit of the cleavage/polyadenylation factor. 74 , 99 , 100 Sen1 interacts with RBPs, Nab3 and Nrd1 to form the Nrd1–Nab3–Sen1 (NNS) complex. NNS complex comprises two RBPs, Nrd1 and Nab3, in addition to Sen1 helicase, 99 , 101 which carries out the Sen1-mediated transcription termination of non-coding RNAs (ncRNAs) in yeast. ncRNAs are polyadenylated by the Trf4, a subunit of the TRAMP complex mediating this process. Nrd1 of the NNS complex interacts with Trf4 of the TRAMP complex to promote the 3′-end trimming of ncRNAs and degradation of unstable RNAs in the nuclear exosome bearing the Rrp6 exonuclease. 83 , 101-105 The NNS complex is also required for the biogenesis of most of the snRNA and snoRNAs and their 3′-end maturation by the exosome. 79 Unlike the poly(A) pathway, the NNS pathway is not conserved in higher eukaryotes. Sen1 induces transcription termination in both cases by unwinding the RNA:DNA hybrid formed within the transcription bubble. 81 , 86 , 106
|
[
"Annapoorna Kannan",
"Shyni Gangadharan Leela",
"Dana Branzei",
"Laxman Gangwani"
] |
https://doi.org/10.1093/braincomms/fcae239
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11277865_p9
|
PMC11277865
|
sec[2]/sec[1]/p[1]
|
Transcription termination
| 4.472656 |
biomedical
|
Study
|
[
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[
0.9921875,
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] |
In eukaryotic RNAPII, the conserved C-terminal arginine residue R1810 undergoes symmetrical dimethylation (me2 s) by protein arginine methyltransferase 5. Methylation of arginine helps to recruit the SMN protein and causes the formation of a ternary complex SETX–RNAPII–SMN, required to resolve RNA:DNA hybrids in the transcription termination regions. Mutation in the RNAPII R1810 residue results in the disruption of RNAPII and SMN binding, causing the accumulation of R-loops in the transcription termination regions. 77
|
[
"Annapoorna Kannan",
"Shyni Gangadharan Leela",
"Dana Branzei",
"Laxman Gangwani"
] |
https://doi.org/10.1093/braincomms/fcae239
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11277865_p10
|
PMC11277865
|
sec[2]/sec[2]/p[0]
|
Resolution of transcription and replication collision conflicts
| 4.695313 |
biomedical
|
Study
|
[
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[
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SETX also has a role in DDR by co-localizing at transcriptionally induced DNA damage sites. SETX forms nuclear foci during the S-phase of the cell cycle. These foci represent sites of DNA polymerase/RNAPII collision and co-localize with DDR markers 53BP1 and γH2AX. SETX undergoes SUMO-2 modification specifically during the early S-phase, facilitating SETX accumulation into these foci. 23 , 66 , 75 At these nuclear foci, RNAPII collides with the replication fork and results in the halt of RNA elongation. SETX utilizes its helicase activity to unwind the R-loop formed behind the stalled RNAPII. SETX then directs incomplete RNA transcripts to the nuclear exosome for degradation through interaction with components of the nuclear exosome complex, Rrp45 and exosome component 9 (Exosc9), which require SETX SUMOylation at the N-terminus. 107 , 108 The exosome complex is the major eukaryotic 3′ → 5′ exonuclease, conferring accurate degradation of RNAs in the nucleus and cytoplasm and playing a critical role in RNA turnover and quality control. 109 The SUMOylation of SETX and the interaction of SUMOylated SETX with Rrp45 and Exosc9 are disrupted in AOA2 but not in amyotrophic lateral sclerosis 4 (ALS4). The loss of SETX, Rrp45 and Exosc9 interaction in AOA2 cells may contribute to a defective DDR and repair of DSBs, commonly present in these cells. 110
|
[
"Annapoorna Kannan",
"Shyni Gangadharan Leela",
"Dana Branzei",
"Laxman Gangwani"
] |
https://doi.org/10.1093/braincomms/fcae239
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999994 |
PMC11277865_p11
|
PMC11277865
|
sec[2]/sec[2]/p[1]
|
Resolution of transcription and replication collision conflicts
| 4.382813 |
biomedical
|
Study
|
[
0.99951171875,
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[
0.99609375,
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] |
Sen1 also binds to the replisome complex by interacting with Ctf4 and Mrc1 components of the replication fork through its N-terminal domain. Association of Sen1 to the replisome is abolished upon deletion of CTF4 or MRC1 genes. 111 The association of Sen1 with the replication fork complex is critical for the timely removal of R-loops promoting fork progression across RNAPII transcribed genes. Altogether, these results highlight a key functional role of Sen1 in replication fork progression during DNA replication and chromosome stability. 94 , 111 A recent study also shows that Sen1 acts as a key regulator in resolving transcription-driven conflicts. 112
|
[
"Annapoorna Kannan",
"Shyni Gangadharan Leela",
"Dana Branzei",
"Laxman Gangwani"
] |
https://doi.org/10.1093/braincomms/fcae239
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11277865_p12
|
PMC11277865
|
sec[2]/sec[3]/p[0]
|
Telomere stability
| 4.410156 |
biomedical
|
Study
|
[
0.99951171875,
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] |
[
0.99853515625,
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0.00011622905731201172
] |
Sub-telomeric and telomeric DNAs are transcribed by RNAPII into telomere repeat containing ncRNA (TERRA/TelRNA). 113 , 114 Transcription-dependent binding of SETX to telomeric and sub-telomeric DNA and its inhibition by amanitin suggests a possible involvement of SETX in the regulation of TERRA expression. 115 AOA2 patient cells possessing constitutively shortened telomeres show increased sensitivity with further shortening of telomere length when treated with camptothecin and X-rays, suggesting a possible involvement of SETX in maintaining the telomere length and stability via a mechanism tied to TERRA formation. 113-115
|
[
"Annapoorna Kannan",
"Shyni Gangadharan Leela",
"Dana Branzei",
"Laxman Gangwani"
] |
https://doi.org/10.1093/braincomms/fcae239
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277865_p13
|
PMC11277865
|
sec[2]/sec[4]/p[0]
|
Transcription-coupled DNA damage and repair
| 4.496094 |
biomedical
|
Study
|
[
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[
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In addition to RNA metabolism, SETX plays a crucial role in DNA integrity and genome stability. SETX associates with many DDR and repair proteins, including γH2AX, 53BP1, MDC1, XPA, FANCD2, ATRIP, BRCA1, DNA-PKCs, MRE11, RAD50 and PIAS1, involved in the repair of DNA lesions caused by oxidative DNA damage, DNA single-strand breaks (SSBs) and DNA DSBs. Loss of SETX causes increased accumulation of DNA damage, 59 , 75 , 89 , 108 , 116 potentially due to defective DNA repair. The N-terminal domain of Sen1 interacts with nucleotide excision repair factor, Rad2, a single-strand DNA endonuclease required for transcription-coupled DNA repair. 74 , 117-119
|
[
"Annapoorna Kannan",
"Shyni Gangadharan Leela",
"Dana Branzei",
"Laxman Gangwani"
] |
https://doi.org/10.1093/braincomms/fcae239
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11277865_p14
|
PMC11277865
|
sec[2]/sec[4]/p[1]
|
Transcription-coupled DNA damage and repair
| 4.800781 |
biomedical
|
Study
|
[
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[
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SETX is also recruited to DSBs induced in transcriptionally active loci where it unwinds the induced RNA:DNA hybrids. At transcriptionally active loci, DSBs induce RNAPII stalling, thereby stabilizing the R-loop formation. Genome-wide studies revealed R-loop accumulation on regions flanking DSBs, with these levels reducing upon SETX binding. 45 , 120 , 121 At DSB sites, SETX increases RAD51 recruitment and reduces illegitimate resection of broken ends, thereby preventing translocation and promoting cell viability following DSB production in transcriptionally active genes. Thus, SETX loss contributes to neuronal loss in AOA2 and ALS4 pathology. 90 SETX-associated nuclease 1 (SAN1) interacts with SETX. SETX recruits SAN1 to sites of inter-strand DNA cross-links (ICLs) and together they mediate their repair. The cascade of events here is triggered by the stalling of the transcription complex and subsequent formation of R-loops at ICL lesions. SAN1 repairs ICLs independently of the Fanconi anaemia pathway, thereby acting as a parallel pathway to protect cells from ICL lesions. SAN1–SETX interaction is crucial for SAN1-mediated repair of ICLs. 122
|
[
"Annapoorna Kannan",
"Shyni Gangadharan Leela",
"Dana Branzei",
"Laxman Gangwani"
] |
https://doi.org/10.1093/braincomms/fcae239
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277865_p15
|
PMC11277865
|
sec[2]/sec[4]/p[2]
|
Transcription-coupled DNA damage and repair
| 4.503906 |
biomedical
|
Study
|
[
0.99951171875,
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[
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SETX's DNA repair involvement also relies on its direct interaction with BRCA1, a key player in DSB repair by homologous recombination (HR). Genome-wide studies suggested that BRCA1 binds to R-loops formed at transcription termination regions of active gene loci. 89 , 123 It is proposed that BRCA1 mediates the recruitment of SETX and suppresses co-transcriptional R-loop-mediated DNA damage. Disruption of BRCA1–SETX interaction causes R-loop-induced SSBs in non-template DNA strand that are marked by the accumulation of γH2AX foci, suggesting a function of SETX–BRCA1 complexes in DNA repair. Sen1 has also been shown to play a direct role in transcription-coupled DNA repair. 124
|
[
"Annapoorna Kannan",
"Shyni Gangadharan Leela",
"Dana Branzei",
"Laxman Gangwani"
] |
https://doi.org/10.1093/braincomms/fcae239
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11277865_p16
|
PMC11277865
|
sec[3]/p[0]
|
SETX mutations and neurodegenerative disorders
| 4.648438 |
biomedical
|
Study
|
[
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[
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The role of SETX in neurodegeneration was suggested after the identification of SETX mutations in patients with neurodegenerative disorders. 66 Mutations in the SETX gene are associated with different neurodegenerative disorders such as autosomal dominant ALS4, 65 , 125-129 autosomal recessive AOA2 67 , 130-133 and autosomal dominant SMA . 134 A broad-spectrum of homozygous mutations in SETX has been identified, of which most of the missense mutations are clustered around the conserved helicase domain or the amino terminal domain. 66 Such clustered mutations in SETX cause loss of function resulting in AOA2, characterized by cerebellar ataxia with occasional oculomotor apraxia, cerebellar atrophy and peripheral neuropathy. 64 , 130 , 131 Analysis of cells derived from AOA2 patients suggests that loss of SETX function results in R-loop accumulation. 59 Studies with iPSCs and neural progenitors derived from AOA2 patient cell lines reveal increased levels of R-loop accumulation and increased sensitivity to DNA damaging agents such as H 2 O 2 , camptothecin and mitomycin C as well as high susceptibility to oxidative DNA damage-induced cell death. The abnormal expression of SOD1 in patient-derived AOA2 cells may be a cause of increased levels of H 2 O 2 , resulting in oxidative DNA damage. 59 , 110 , 115 , 116 A recent study provided insight into Sen1 structural changes responsible for the loss of SETX helicase activity and defects in RNA-binding ability of SETX mutations associated with AOA2. 73 The role of SETX in ALS4 pathogenesis has been recently reviewed. 135
|
[
"Annapoorna Kannan",
"Shyni Gangadharan Leela",
"Dana Branzei",
"Laxman Gangwani"
] |
https://doi.org/10.1093/braincomms/fcae239
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11277865_p17
|
PMC11277865
|
sec[3]/p[1]
|
SETX mutations and neurodegenerative disorders
| 4.652344 |
biomedical
|
Study
|
[
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[
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The decrease in SETX levels results in the accumulation of R-loops in cells derived from SMA patients. 61 The knockdown of SETX in mammalian cells results in accumulation of R-loops, suggesting that loss of function or decrease in SETX levels causes a disease-related phenotype of R-loop accumulation. 60 SMA is caused by homozygous mutations/deletions of the SMN1 gene resulting in low levels of the ubiquitously expressed SMN protein. 136 , 137 SMA is characterized by the progressive degeneration of motor neurons in the anterior horns of the spinal cord results in muscle weakness, respiratory failure and death. 138 Depletion of SMN results in reduced formation of snRNPs resulting in widespread splicing defects. Global splicing defects caused by chronic low levels of SMN in SMA may be a cause of splicing inefficiency of SETX pre-mRNA resulting in reduced full-length SETX transcripts, thus explaining the low levels of the SETX protein. 139-142 A decrease in SETX levels causes accumulation of R-loops and DNA damage in SMA patient fibroblasts and spinal cord motor neurons derived from SMA mice. 61
|
[
"Annapoorna Kannan",
"Shyni Gangadharan Leela",
"Dana Branzei",
"Laxman Gangwani"
] |
https://doi.org/10.1093/braincomms/fcae239
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11277865_p18
|
PMC11277865
|
sec[3]/p[2]
|
SETX mutations and neurodegenerative disorders
| 4.699219 |
biomedical
|
Study
|
[
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[
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Investigation of the molecular mechanism of motor neuron degeneration provided insight into the role of SETX in R-loop-mediated neurodegeneration in SMA. Chronic low levels of SETX in SMA resulted in a higher ∼8-fold accumulation of R-loops in neurons compared to ∼2-fold in fibroblasts indicating a greater amount of DNA damage accumulation in neurons than in fibroblasts and suggesting a higher efficiency of DNA repair is required to prevent genomic instability and neurodegeneration. 61 Because the motor neurons degenerate in SMA, these findings suggested a likely defect in the DNA repair mechanisms. DNA damage, specifically DSBs, is repaired by two main pathways in dividing cells (fibroblasts): HR and non-homologous end joining (NHEJ), with the latter further divided into canonical NHEJ (c-NHEJ) and alternative NHEJ (alt-NHEJ). 143 However, neurons rely on NHEJ for DSB repair. 144 Investigation of the activation of NHEJ in SMA neurons demonstrated that DNA-activated protein kinase catalytic subunit (DNA-PKcs), which is critical for this branch, is downregulated in SMA patient spinal cords and motor neurons from SMA mice . 61 Accumulation of SETX-dependent R-loops and DNA damage combined with inefficient NHEJ-mediated DSB repair due to DNA-PKcs deficiency leads to genomic instability and degeneration of motor neurons in SMA. 60 , 61 , 145
|
[
"Annapoorna Kannan",
"Shyni Gangadharan Leela",
"Dana Branzei",
"Laxman Gangwani"
] |
https://doi.org/10.1093/braincomms/fcae239
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11277865_p19
|
PMC11277865
|
sec[3]/p[3]
|
SETX mutations and neurodegenerative disorders
| 4.667969 |
biomedical
|
Study
|
[
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[
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ALS4 is a juvenile form of autosomal dominant neuromuscular disease characterized by progressive degeneration of upper and lower motor neurons in the brain and spinal cord and results in progressive muscle weakness, muscle wasting, atrophy and spasticity. 128 In contrast to the SETX mutations in AOA2 that cause loss of function, SETX mutations associated with ALS4 result in gain of function in SETX R-loop resolution activity leading to neurodegeneration. 65 , 125 , 146 , 147 An increase in SETX-dependent R-loop resolution activity results in fewer R-loops in ALS4 patient cells. Low levels of R-loops in promoters allow modification of regulatory regions such as DNA methylation that regulate transcription. 12 , 13 , 148 In ALS4 cells, reduced R-loops allow DNA methylation, which decreases the expression of BAMBI, a negative regulator of the transforming growth factor beta (TGF-β) pathway, therefore causing the activation of the TGF-β signalling that may mediate neurodegeneration. 149 Alteration of the TGF-β signalling pathway is just one example, but there may be several other genes or pathways altered in response to the low levels of R-loops that contribute to ALS4 pathogenesis. Thus, further investigation of the effects of reduced R-loops in neurons will provide better insight into the cause of neurodegeneration in ALS4.
|
[
"Annapoorna Kannan",
"Shyni Gangadharan Leela",
"Dana Branzei",
"Laxman Gangwani"
] |
https://doi.org/10.1093/braincomms/fcae239
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11277865_p20
|
PMC11277865
|
sec[4]/p[0]
|
Mechanism of SETX-dependent R-loop resolution
| 3.755859 |
biomedical
|
Study
|
[
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[
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Understanding the molecular mechanism of R-loop resolution will provide critical insight into modulating levels of R-loops and managing pathological conditions. The molecular mechanism of R-loop resolution is unclear. However, some progress has been made towards identifying critical steps involved in SETX-mediated R-loop resolution under normal and ALS4 disease conditions. 88 , 150
|
[
"Annapoorna Kannan",
"Shyni Gangadharan Leela",
"Dana Branzei",
"Laxman Gangwani"
] |
https://doi.org/10.1093/braincomms/fcae239
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277865_p21
|
PMC11277865
|
sec[4]/p[1]
|
Mechanism of SETX-dependent R-loop resolution
| 4.851563 |
biomedical
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Study
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The helicase activity of SETX is involved in the unwinding of RNA:DNA hybrids, 24 one of the initial steps in the resolution of R-loops. SETX interacts with RNAPII, 69 but how the helicase activity of SETX is regulated and how the protein is recruited to R-loops are still unclear. A recent study showed that the zinc finger protein 1 (ZPR1) binds to SETX and is required to recruit SETX onto R-loops. Moreover, ZPR1 may regulate the helicase activity of SETX. 88 ZPR1 is an essential protein that is evolutionarily conserved in eukaryotes. 151-153 ZPR1 is shown to be involved in the regulation of transcription, cell growth and cell cycle progression. 154 , 155 ZPR1 also interacts with RNAPII and is a part of transcription complexes. 62 In addition, ZPR1 interacts with several proteins including the EGF receptor, eukaryotic translation elongation factor 1A and SMN. 152 , 154 , 156 Notably, the interaction of ZPR1 with SMN is disrupted in SMA patients that have mutations in the SMN1 gene. 156 ZPR1 is required for the accumulation of SMN in sub-nuclear bodies, including gems (SMN containing nuclear bodies) and Cajal bodies . The disruption of ZPR1–SMN complexes causes mislocalization of SMN in SMA patient cells and motor neurons. ZPR1 plays a critical role in neuron survival. ZPR1 deficiency causes degeneration of spinal cord motor neurons and cerebellar granule neurons and results in the degeneration of nerves in the peripheral nervous system. 145 , 157-159 Although ZPR1 is essential for neuronal cell viability, the essentiality mechanism was unclear until recently. Recent studies have provided insight into the function of ZPR1 in the resolution of R-loops, which may likely be its essential cellular function because impaired R-loop resolution would result in cell death. ZPR1 deficiency causes accumulation of R-loops and DNA damage in dividing cells and neurons. 62 , 88
|
[
"Annapoorna Kannan",
"Shyni Gangadharan Leela",
"Dana Branzei",
"Laxman Gangwani"
] |
https://doi.org/10.1093/braincomms/fcae239
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11277865_p22
|
PMC11277865
|
sec[4]/p[2]
|
Mechanism of SETX-dependent R-loop resolution
| 4.78125 |
biomedical
|
Study
|
[
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[
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The core components of R-loop resolution complexes (RLRCs) bind directly to RNA:DNA hybrids. Other components critical for R-loop resolution, such as SMN, can directly bind to RNAPII, a core component of RLRC, and contribute to R-loop resolution. ZPR1 and SETX can independently bind to RNAPII and RNA:DNA hybrids. SETX interacts with ZPR1, co-localizes with ZPR1 in sub-nuclear bodies and forms in vivo complexes with R-loops. ZPR1 recruits SETX to R-loops and is critical for in vivo assembly of the RLRC comprising SETX–ZPR1–RNA:DNA–RNAPII. 88 Of interest, the interaction of SETX with ZPR1 is disrupted in fibroblasts derived from ALS4 patients with SETX (L389S) mutation. Mutation in SETX causes mislocalization of SETX, which fails to accumulate in sub-nuclear bodies and is redistributed in the nucleoplasm. However, the levels of ZPR1 and SETX are not altered in ALS4. 88 Disruption of ZPR1 interaction with SETX results in reduced recruitment of SETX onto R-loops. 88 Partial recruitment of SETX by ZPR1 onto R-loops is due to two reasons: (i) ALS4 is an autosomal dominant disease caused by heterozygous SETX mutation, and (ii) SETX forms a dimer, with its dimerization ability not affected by the L389S mutation, suggesting that the SETX can form homo and heterodimers. 71 Thus, ZPR1 may interact and recruit SETX–SETX (wild-type) homodimer and SETX–SETX* (wild-type mutant) heterodimer but fails to interact or recruit SETX*–SETX* (mutant–mutant) homodimer. 88 One of the important questions addressed by a recent study is how mutation in SETX results in gain of function leading to fewer R-loops in ALS4. The study demonstrated that ZPR1 interacts with SETX and may function as a ‘molecular brake’ to regulate the speed of SETX-dependent R-loop resolution activity . Therefore, suboptimal ZPR1 interaction with SETX may cause failure of this molecular brake, resulting in increased speed of SETX-dependent resolution of R-loops that leads to fewer R-loops in ALS4. 88
|
[
"Annapoorna Kannan",
"Shyni Gangadharan Leela",
"Dana Branzei",
"Laxman Gangwani"
] |
https://doi.org/10.1093/braincomms/fcae239
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11277865_p23
|
PMC11277865
|
sec[5]/p[0]
|
Role of SETX as a potential modifier of neurodegenerative diseases
| 4.613281 |
biomedical
|
Study
|
[
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[
0.9638671875,
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The dysregulation of R-loop metabolism as a common pathogenic mechanism in mediating neurodegeneration in neurodegenerative disorders with either increased levels of R-loop accumulation, such as in SMA and AOA2, or with reduced levels of R-loops, such as in ALS4, suggests that modulation of R-loop levels could be exploited as a potential therapeutic method. The emerging connections between R-loop levels and proteins with the potential to regulate R-loop resolution, such as SETX, ZPR1 and other components of RLRC, could be potential modifiers of neurodegenerative diseases. Initially, ZPR1 was identified as a modifier of SMA disease. However, the precise mechanism of rescue of the disease phenotype was unclear. 156-161 Recent studies demonstrated that SETX and SMN are downstream targets of ZPR1. Overexpression of ZPR1 in SMA patient cells, motor neurons and SMA mice resulted in upregulation of SMN and SETX levels that decreased pathogenic R-loop levels, reduced DNA damage and motor neuron degeneration and improved the lifespan of SMA mice. 61 , 62 Further, overexpression of SETX in SMA patient cells and motor neurons reduced R-loop levels and DNA damage and prevented degeneration of spinal cord motor neurons. 62 Together, these findings demonstrated that the R-loop-mediated toxic effects are rescued by ZPR1 and SETX, establishing their role as potential modifiers of disease severity by their ability to modulate the levels of pathogenic R-loops in SMA. 60-62 , 88 , 150
|
[
"Annapoorna Kannan",
"Shyni Gangadharan Leela",
"Dana Branzei",
"Laxman Gangwani"
] |
https://doi.org/10.1093/braincomms/fcae239
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11277865_p24
|
PMC11277865
|
sec[5]/p[1]
|
Role of SETX as a potential modifier of neurodegenerative diseases
| 4.695313 |
biomedical
|
Study
|
[
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[
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Amyotrophic lateral sclerosis 4, caused by SETX mutation, is a unique and very interesting case of neurodegenerative disease characterized by reduced levels of R-loops. More interesting and important aspects of regulating R-loop levels emerged from the recent findings that ZPR1 can regulate the activity of SETX-mediated R-loop resolution in ALS4 patient cells. ZPR1 overexpression resulted in an increase of R-loop levels in normal and ALS4 cells. ZPR1 increased the levels of SETX that elevated the recruitment of SETX onto R-loops and the formation of ZPR1–SETX complexes, which allowed ZPR1 to control SETX-dependent R-loop resolution activity and restore normal levels of R-loops in ALS4 patient cells. 88 In addition, cell models harbouring the C9ORF72 sense repeats also show accumulation of R-loops and DSBs, which can be rescued by SETX overexpression, suggesting a potential therapeutic role of SETX in overcoming R-loop-associated defects and DNA damage in nucleotide repeat-associated neurodegenerative disorders. 162 A recent study showed that SETX is a significant modifier of C9ORF72-related ALS-FTD disease severity caused by G4C2 and arginine containing dipeptide repeat toxicity. 163
|
[
"Annapoorna Kannan",
"Shyni Gangadharan Leela",
"Dana Branzei",
"Laxman Gangwani"
] |
https://doi.org/10.1093/braincomms/fcae239
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11277865_p25
|
PMC11277865
|
sec[5]/p[2]
|
Role of SETX as a potential modifier of neurodegenerative diseases
| 4.78125 |
biomedical
|
Study
|
[
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[
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Together, these findings opened the door to exploring the therapeutic potential of the SETX–ZPR1 axis in regulating pathogenic R-loops in neurodegenerative diseases subject to abnormal levels of R-loops such as SMA and ALS4. It is possible that future research in understanding pathological mechanisms of neurodegenerative disorders will reveal others with defects in R-loop resolution, including AOA2, ALS-FTD, ALS10, Huntington’s disease, spinocerebellar ataxia, fragile X mental retardation or fragile X syndrome and Friedreich’s ataxia. The role of SETX may also be examined in other cellular processes correlated with neurological disorders, such as autophagy and mitochondrial dysfunction that are associated with the pathogenesis of Alzheimer's disease and Parkinson's disease. SETX regulates the expression of different autophagy genes, and differential expression of SETX has an adverse effect on the autophagic process. 164 Defective autophagy is reported in AOA2 and ALS4 patient cells. 165 Mutant SETX also shows defective redox signalling and severe loss of mtDNA with increased ROS production in ALS-FTD caused by the C9ORF72 mutation, implicating the critical functional role of SETX in regulating redox homeostasis. 166 , 167 Notably, R-loop accumulation at microRNAs (miRNAs) plays a role in the co-transcriptional processing of primary miRNAs. 168 Of interest, there is convincing evidence of involvement of miRNAs and mitochondrial miRNAs in Alzheimer's disease pathogenesis; however, the role of R-loops in altering miRNAs in the context of Alzheimer's disease remains to be examined. 169-172 Further, reports of DNA damage and defects in DNA repair associated with reduced DNA-PKcs and the possibility of R-loops in mediating transcriptional alterations in Alzheimer's disease related gene expression and DNA damage call for further investigations. 173-176 In conclusion, SETX, a core component of the R-loop resolution machinery that functions in collaboration with other critical factors, such as ZPR1, may be a potential therapeutic target for a broad range of neurodegenerative diseases.
|
[
"Annapoorna Kannan",
"Shyni Gangadharan Leela",
"Dana Branzei",
"Laxman Gangwani"
] |
https://doi.org/10.1093/braincomms/fcae239
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11277877_p0
|
PMC11277877
|
sec[0]/p[0]
|
1. Introduction
| 4.089844 |
biomedical
|
Review
|
[
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[
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The first transcatheter heart valve (THV) implantation in 2002 paved the way for the percutaneous valve therapies to witness rapid technological progress. This has generated a growing interest in valvular heart disease (VHD), which is an important group of diseases with increasing clinical reverberations and substantial financial distress . The occurrence and frequency of VHD has expanded, mostly as a result of the rising life expectancy of the population . Expansion in the surgical field of VHD, and currently in the transcatheter VHD procedures, are changing the way we treat patients at a gallop by providing less invasive treatment choices. Furthermore, advancements in imaging technology have yielded more accurate information on the structure and function of heart valves . This has facilitated superior unification of images for scheming and managing procedures . The acknowledgment of the relevance and efficacy of catheter-based treatments for VHD has also heightened enthusiasm for them and their implications .
|
[
"Nikolaos Ktenopoulos",
"Odysseas Katsaros",
"Anastasios Apostolos",
"Maria Drakopoulou",
"Grigorios Tsigkas",
"Constantinos Tsioufis",
"Periklis Davlouros",
"Konstantinos Toutouzas",
"Antonios Karanasos"
] |
https://doi.org/10.3390/life14070842
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277877_p1
|
PMC11277877
|
sec[0]/p[1]
|
1. Introduction
| 4.464844 |
biomedical
|
Review
|
[
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[
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VHD refers to a condition that affects any of the four valves of the heart. Since its inception in 2002 , transcatheter aortic valve implantation (TAVI) has significantly transformed the medical treatment of aortic stenosis (AS). Due to advancements in relevant equipment and procedural methods, TAVI has emerged as the primary treatment alternative for individuals with severe symptomatic AS , routinely performed as an elective procedure in stable patients and in some cases as an urgent one . The implementation of various advancements, including the transition from conscious sedation to a single arterial access perspective , the adoption of novel implantation methods, and the utilization of innovative technologies like intravascular lithotripsy , as well as the improvement of THV appliances, has led to a significant decrease in complications and an enhancement of related results . Evidently, recent data from important trials suggest TAVI to be on par with, or even better than surgery, paving the way for its use in younger and lower-risk patients with different AS categories . In fact, for older patients with higher surgical risks, TAVI has become the preferred choice, while for younger patients, there are still open issues, with a notable drawback being the limited lifespan of the biological material utilized for the valve leaflets, which is the same for both transcatheter and surgical valves. This raises questions regarding the long-term outcomes of these valves and a potential need for re-intervention later in a patient’s lifetime, with this being the main reason for the use of mechanical valves in younger patients undergoing aortic valve replacement (AVR). Therefore, TAVI implantation in younger patients should account for the potential need for repeat operations, which are difficult due to the presence of adhesions between the stent and tissue and entail a mortality risk of 15–20% , or the need for a transcatheter valve-in-valve (ViV) implantation. This is now a component of the discourse on the patient’s age at the first implantation of the biological valve and the subsequent long-term treatment plan derived from it.
|
[
"Nikolaos Ktenopoulos",
"Odysseas Katsaros",
"Anastasios Apostolos",
"Maria Drakopoulou",
"Grigorios Tsigkas",
"Constantinos Tsioufis",
"Periklis Davlouros",
"Konstantinos Toutouzas",
"Antonios Karanasos"
] |
https://doi.org/10.3390/life14070842
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11277877_p2
|
PMC11277877
|
sec[0]/p[2]
|
1. Introduction
| 4.050781 |
biomedical
|
Study
|
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As a result, the latest guidelines from the European Society of Cardiology (ESC) recommend TAVI as the primary treatment option for patients aged 75 years or older with severe AS . Although currently surgical aortic valve replacement (SAVR) is the preferred treatment for patients with native aortic regurgitation (AR) without AS , ongoing studies are exploring the potential use of TAVI with innovative THV systems to address the unsettled challenges, such as the JenaValve Trilogy. In the ALIGN AR trial the researchers demonstrated the safety and efficacy of this THV in high surgical risk patients with symptomatic, severe AR .
|
[
"Nikolaos Ktenopoulos",
"Odysseas Katsaros",
"Anastasios Apostolos",
"Maria Drakopoulou",
"Grigorios Tsigkas",
"Constantinos Tsioufis",
"Periklis Davlouros",
"Konstantinos Toutouzas",
"Antonios Karanasos"
] |
https://doi.org/10.3390/life14070842
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277877_p3
|
PMC11277877
|
sec[0]/p[3]
|
1. Introduction
| 4.273438 |
biomedical
|
Review
|
[
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[
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Moreover, it has been observed that mitral regurgitation (MR) is seen in more than 1% of the populace in Western countries who are over 70 years old and is linked to elevated mortality rates . Although the surgical treatment of the mitral valve (MV) accounts for 10% of all surgeries , it is still inadequate in managing the problem of transcatheter treatment of MV conditions . In addition, the prevalence of substantial tricuspid regurgitation (TR) in individuals over the age of 70 exceeds the 5% of the populace, with an accountable link between moderate or severe TR and worse long-term survival rates . However, surgical or percutaneous procedure is rarely used to treat it . It is the most frequent abnormality of the tricuspid valve (TV), and in the majority of the occasions (90–95%), TR is functional, caused by factors such as enlargement of the right ventricle or atrium, rather than by a primary cause, such as trauma, radiation, or endocarditis . The distinguished invasiveness of surgical treatment and the inadequate contemplation of MR and TR in terms of their actual effects on patient survival and symptoms might be contributing factors to the lack of effective interventional treatment. Therefore, these components are potential areas of focus for further study.
|
[
"Nikolaos Ktenopoulos",
"Odysseas Katsaros",
"Anastasios Apostolos",
"Maria Drakopoulou",
"Grigorios Tsigkas",
"Constantinos Tsioufis",
"Periklis Davlouros",
"Konstantinos Toutouzas",
"Antonios Karanasos"
] |
https://doi.org/10.3390/life14070842
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11277877_p4
|
PMC11277877
|
sec[0]/p[4]
|
1. Introduction
| 4.105469 |
biomedical
|
Study
|
[
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[
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Furthermore, in view of the pulmonary valve (PV), tetralogy of Fallot (TOF) is the predominant cyanotic congenital heart disease (CHD) and it is commonly addressed in a similar manner to other CHDs . In the past, surgery was commonly used for PV replacement (PVR) and to alleviate right ventricular (RV) outflow tract (RVOT) deterioration . In the year 2000, Bonhoeffer et al. performed the inaugural implantation of a bovine THV in an ovine model and subsequently in a 12-year-old boy . In 2010, the Melody transcatheter PV, developed by Medtronic Inc. in Minneapolis, received Food and Drug Administration (FDA) acquiescence for mercantile use in malfunctioning PV conduits in the United States. Further research led to the compliance of the Sapien XT valve (Edwards Lifesciences LLC, Irvine, CA, USA) as a THV for cases with dysfunctional PVs .
|
[
"Nikolaos Ktenopoulos",
"Odysseas Katsaros",
"Anastasios Apostolos",
"Maria Drakopoulou",
"Grigorios Tsigkas",
"Constantinos Tsioufis",
"Periklis Davlouros",
"Konstantinos Toutouzas",
"Antonios Karanasos"
] |
https://doi.org/10.3390/life14070842
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11277877_p5
|
PMC11277877
|
sec[0]/p[5]
|
1. Introduction
| 3.908203 |
biomedical
|
Review
|
[
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[
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Since the role of TAVI in the management of severe AS is established and very well studied, this review aims to provide a comprehensive summary of all currently present and developing transcatheter treatments for VHD in the MV, TV, and PV.
|
[
"Nikolaos Ktenopoulos",
"Odysseas Katsaros",
"Anastasios Apostolos",
"Maria Drakopoulou",
"Grigorios Tsigkas",
"Constantinos Tsioufis",
"Periklis Davlouros",
"Konstantinos Toutouzas",
"Antonios Karanasos"
] |
https://doi.org/10.3390/life14070842
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11277877_p6
|
PMC11277877
|
sec[1]/sec[0]/p[0]
|
2.1. The Evolving Burden of Mitral Valve Disease
| 4.375 |
biomedical
|
Study
|
[
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The predominant factor leading to mitral stenosis (MS) is mostly associated with rheumatic disease (RHD), which may develop in individuals who have had rheumatic fever, a result of an infection caused by group A beta-hemolytic streptococcus . The incidence of RHD in North America had a significant reduction in the 20th century due to a decline in occurrences of rheumatic fever and the advent of antibiotics . The RHD remains prevalent in underdeveloped nations, but there has been a global decline in its prevalence, while degenerative calcific MS is increasingly observed in the elderly population . Furthermore, MR has emerged as the prevailing manifestation of MV conditions in industrialized societies . It is linked to higher mortality rates and a higher incidence of heart failure diagnosis . Regrettably, this condition is commonly not adequately treated, resulting in just 15% of patients ultimately receiving MV surgery . According to the EuroHeart Survey, about one-third of the individuals had a native MV condition . Specifically, 9.5% of patients were diagnosed with MS and 24.8% were diagnosed with MR. Among the 5001 patients included in the survey, MR was the second most prevalent diagnosis, while the survey observed a transition in the main cause of MR from RHD, which accounted for 14.2% of cases, to degenerative valve disease, which accounted for 61.3% of cases. Ischemic or secondary MR was found in 7.3% of cases . Furthermore, this discovery was validated in a comprehensive national database in Sweden, where MR remained the second most prevalent VHD behind AS, with an occurrence rate of 21.3 per 100,000 person-years .
|
[
"Nikolaos Ktenopoulos",
"Odysseas Katsaros",
"Anastasios Apostolos",
"Maria Drakopoulou",
"Grigorios Tsigkas",
"Constantinos Tsioufis",
"Periklis Davlouros",
"Konstantinos Toutouzas",
"Antonios Karanasos"
] |
https://doi.org/10.3390/life14070842
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11277877_p7
|
PMC11277877
|
sec[1]/sec[1]/p[0]
|
2.2. Transcatheter Mitral Valve Therapy
| 4.078125 |
biomedical
|
Review
|
[
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[
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The introduction of MS treatment occurred in 1940 with the development of closed MV commissurotomy, which was characterized by Harken and Bailey as “finger-fracture valvuloplasty” . In 1970, the introduction of cardiopulmonary bypass allowed for the switch from a closed surgical commissurotomy to an open one. Furthermore, in 1984, the Japanese cardiac surgeon Kanji Inoue presented the initial attempt for percutaneous therapy of VHD . He and his colleagues presented five cases detailing the effective use of MV balloon valvuloplasty using venous access and transseptal puncture for the treatment of MS . Retrograde non-transseptal balloon mitral valvuloplasty is a method of balloon valvuloplasty, developed by Stefanadis et al., with the aim of avoiding complications associated with transseptal catheterization for patients with symptomatic MS by using a dedicated steerable catheter; however, its use has declined over time .
|
[
"Nikolaos Ktenopoulos",
"Odysseas Katsaros",
"Anastasios Apostolos",
"Maria Drakopoulou",
"Grigorios Tsigkas",
"Constantinos Tsioufis",
"Periklis Davlouros",
"Konstantinos Toutouzas",
"Antonios Karanasos"
] |
https://doi.org/10.3390/life14070842
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11277877_p8
|
PMC11277877
|
sec[1]/sec[1]/p[1]
|
2.2. Transcatheter Mitral Valve Therapy
| 4.332031 |
biomedical
|
Review
|
[
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[
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Transcatheter MV balloon valvuloplasty is a procedure that resembles the closed surgical approach, and it involves the utilization of a balloon to rupture the MV commissures and restore mobility to the MV leaflets . Randomized studies have demonstrated that compared to the surgical approach, it results in wider valve areas and improved permanence . The initial utilization of this technique sparked curiosity in identifying anatomical factors that might forecast the effectiveness of a procedure through the use of echocardiography . The outcome was the creation of the Wilkins score, which aims to assess the mobility, thickness, calcification, and sub-valvular thickening of the leaflets . This score helps identify individuals with anatomies that are more likely to have successful procedures. This started the significant collaboration between imaging and intervention in the management of MV disease . Currently, the most widely used approach for treating rheumatic MS is MV balloon valvuloplasty, which involves the use of the Inoue balloon trademarked by Toray Medical in Tokyo, Japan . Kanji Inoue pioneered the development of structural VHD procedures, initiating a transformative shift and fostering new alliances that would restructure the treatment of MV conditions .
|
[
"Nikolaos Ktenopoulos",
"Odysseas Katsaros",
"Anastasios Apostolos",
"Maria Drakopoulou",
"Grigorios Tsigkas",
"Constantinos Tsioufis",
"Periklis Davlouros",
"Konstantinos Toutouzas",
"Antonios Karanasos"
] |
https://doi.org/10.3390/life14070842
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11277877_p9
|
PMC11277877
|
sec[1]/sec[1]/p[2]
|
2.2. Transcatheter Mitral Valve Therapy
| 3.904297 |
biomedical
|
Review
|
[
0.9970703125,
0.0019359588623046875,
0.0009870529174804688
] |
[
0.0227508544921875,
0.006855010986328125,
0.9697265625,
0.0005970001220703125
] |
While percutaneous treatments for MS have been in existence and evolving for a considerable period, the development of procedural alternatives specifically for MR has only occurred in the last 20 years . This progress has been made possible by scientific expansion, which has facilitated the creation of a growing array of percutaneous MV treatment options. Currently, there are a variety of equipment alternatives available that use distinct approaches and modes of operation. These devices can be deployed based on the specific underlying pathophysiology of the MV. The new advances may be broadly classified as processes that aim to target (I) leaflet repair; (II) direct or indirect annuloplasty; (III) implantation of artificial chordae; and (IV) transcatheter MV replacement . Table 1 summarizes the currently available transcatheter treatments for MV repair.
|
[
"Nikolaos Ktenopoulos",
"Odysseas Katsaros",
"Anastasios Apostolos",
"Maria Drakopoulou",
"Grigorios Tsigkas",
"Constantinos Tsioufis",
"Periklis Davlouros",
"Konstantinos Toutouzas",
"Antonios Karanasos"
] |
https://doi.org/10.3390/life14070842
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277877_p10
|
PMC11277877
|
sec[1]/sec[2]/p[0]
|
2.3. Leaflet Repair/Edge-to-Edge Technique
| 4.136719 |
biomedical
|
Review
|
[
0.99609375,
0.003139495849609375,
0.000682830810546875
] |
[
0.1546630859375,
0.2191162109375,
0.6220703125,
0.0040435791015625
] |
MitraClip. The MitraClip (Abbott Laboratories, Menlo Park, CA, USA) is constructed using cobalt chromium and is coated with a polypropylene tissue. The MitraClip device consists of two appendages and operates by bringing the margins of the anterior and posterior fragments of the MV leaflet closer together. This approach was developed based on the surgical “edge-to-edge” repair procedure, initially introduced by Alfieri et al. . The MitraClip device obtained Conformité Européenne (CE) mark certification in Europe in 2008 and FDA clearance in the United States of America (USA) in 2013 for its application in primary MR . Subsequently, in 2019, it was also approved for use in secondary MR. Currently, the MitraClip’s third generation is available commercially. This version includes two sizes: the original NTR size and the XTR size, which has clip appendages that are 3 mm lengthier . The third generation of the MitraClip has enhanced steering, navigational, and positioning clip capabilities. These improvements make it easier to precisely place the clip and improve the accuracy of the procedure . In order to attain a high eminence rate in reducing MR, it is important to address certain structural characteristics of the MV. The following principles were shown to be anatomical features that are advantageous for a proper device implantation in MR: a leaflet coaptation length greater than 2 mm, a coaptation depth less than 11 mm, a flail gap less than 10 mm in cases of primary MR, and a flail breadth less than 15 mm . The increasing expertise in this procedure allows for the treatment of more intricate MV structures and alternations .
|
[
"Nikolaos Ktenopoulos",
"Odysseas Katsaros",
"Anastasios Apostolos",
"Maria Drakopoulou",
"Grigorios Tsigkas",
"Constantinos Tsioufis",
"Periklis Davlouros",
"Konstantinos Toutouzas",
"Antonios Karanasos"
] |
https://doi.org/10.3390/life14070842
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277877_p11
|
PMC11277877
|
sec[1]/sec[2]/p[1]
|
2.3. Leaflet Repair/Edge-to-Edge Technique
| 4.265625 |
biomedical
|
Review
|
[
0.99755859375,
0.0014333724975585938,
0.0010471343994140625
] |
[
0.455810546875,
0.0012149810791015625,
0.54248046875,
0.0006046295166015625
] |
As mentioned previously, transcatheter management of MR has lately become a significant option, particularly for individuals who have a high risk for surgery and suffer from functional MR. The initial transcatheter device offered was the transcatheter edge-to-edge repair (TEER) . The frequency of TEER operations has notably escalated in recent years, with functional MR emerging as a primary indication for TEER. Following the completion of two significant studies, namely, MITRA-FR and COAPT , a substantial debate ensued due to their contradictory outcomes. Specifically, MITRA-FR demonstrated no improvement in prognosis when compared to medical therapy . Conversely, COAPT revealed that the MitraClip operation significantly reduced the mortality and hospitalization rates . The disparities can be elucidated by the significantly elevated MR in the COAPT study. Additionally, the patients participating in the MITRA-FR study exhibited considerably worse left ventricular (LV) function, characterized by severe LV dilatation and dysfunction, in comparison to those in the COAPT trial . Felbel et al. conducted a meta-analysis that compared the short-term and one-year results in individuals with functional MR who had TEER or surgical MV repair . The researchers included 21 studies on TEER and 37 studies on surgery. They witnessed a noteworthy decrease in the in-hospital mortality with TEER, while there was no significant difference in the 1-year mortality . Furthermore, one contemporary study conducted by Stone et al. has validated the previously observed low rates of short-term death associated with TEER . Nevertheless, it has also been revealed that the long-term mortality among patients with decreased LV function and functional MR remains significant, with a 5-year mortality rate approaching 60% .
|
[
"Nikolaos Ktenopoulos",
"Odysseas Katsaros",
"Anastasios Apostolos",
"Maria Drakopoulou",
"Grigorios Tsigkas",
"Constantinos Tsioufis",
"Periklis Davlouros",
"Konstantinos Toutouzas",
"Antonios Karanasos"
] |
https://doi.org/10.3390/life14070842
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999999 |
PMC11277877_p12
|
PMC11277877
|
sec[1]/sec[2]/p[2]
|
2.3. Leaflet Repair/Edge-to-Edge Technique
| 4.261719 |
biomedical
|
Study
|
[
0.99609375,
0.0034313201904296875,
0.0002760887145996094
] |
[
0.9736328125,
0.0115966796875,
0.01373291015625,
0.0010061264038085938
] |
PASCAL transcatheter mitral valve repair (TMVr) system. The PASCAL percutaneous appliance, developed by Edwards Lifesciences in Irvine, CA, USA, obtained CE compliance in Germany in 2019. This device shares similarities with the MitraClip system, since both utilize the edge-to-edge repair procedure . The purpose of this equipment was to address certain technical limitations of the MitraClip. It was designed with wider paddles and an interior spacer to make it easier to reduce MR and decrease tension and tethering on the MV. The unconstrained motion of the paddles allows for better grappling of the leaflets, particularly in difficult structures . Additionally, the protraction of the equipment helps with its movement in the left ventricle (LV). The procedural processes are similar to those of the MitraClip . The procedure involves initiation through the right femoral vein and utilizing the transseptal route to advance the PASCAL system into the LV using a 22 F guide catheter. The clinical data supporting the PASCAL implant remains weak. It was firstly implanted in 23 individuals as part of a conservative treatment in an observational study . Excess MR of ≤2+ was reported in 96% of the participants and despite the presence of a bulky system, no significant rise in the trans-mitral gradient was identified. Furthermore, the CLASP trial assessed the safety and effectiveness of the PASCAL device in 62 individuals with moderate to severe mitral regurgitation . After a period of 30 days, the major adverse events were 6.5%, while the overall mortality rate was 1.6%, with a residual MR of ≤2 in 98% of them. These encouraging findings need to be validated in a wider group of patients and with extended follow-up . The ongoing CLASP II study will include a direct comparison between the well-established MitraClip device and the PASCAL device.
|
[
"Nikolaos Ktenopoulos",
"Odysseas Katsaros",
"Anastasios Apostolos",
"Maria Drakopoulou",
"Grigorios Tsigkas",
"Constantinos Tsioufis",
"Periklis Davlouros",
"Konstantinos Toutouzas",
"Antonios Karanasos"
] |
https://doi.org/10.3390/life14070842
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11277877_p13
|
PMC11277877
|
sec[1]/sec[3]/p[0]
|
2.4. Indirect Annuloplasty Devices
| 4.371094 |
biomedical
|
Study
|
[
0.99658203125,
0.0030956268310546875,
0.0002849102020263672
] |
[
0.970703125,
0.006320953369140625,
0.0217437744140625,
0.0009937286376953125
] |
Carillon Mitral Contour System. The Carillon Mitral Contour System (Cardiac Dimensions, Kirkland, WA, USA) is a medical device used for the treatment of patients with functional MR. It is a percutaneous indirect annuloplasty system, which comprises a self-expanding nitinol anchor at both the proximal and distal ends, which are joined by a shaping ribbon . The Carillon System is utilized via the jugular vein using a 9F delivery catheter and it is inserted into the coronary sinus. By taking advantage of the close propinquity between the coronary sinus and the MV annulus apparatus, the diameter of the MV annulus will be decreased when the device is deployed, consequently reducing the functional MR . This system has several benefits, including its user-friendly interface, unobtrusive construction, and the ability to easily retrieve and relocate the system if necessary. The earliest trials assessing this device demonstrated an amelioration of symptomatology, a decrease in MR, and an enhancement in LV remodeling metrics . Regarding the Carillon system, due to its outline and precise placement, experiencing significant tension at the proximal anchor, asymptomatic fractures of the device were seen in 25% of patients in this area. Hence, a revised apparatus was created and assessed in the prospective single-arm safety TITAN II study . The enhanced clinical and echocardiographic outcomes observed in prior investigations were validated in the TITAN II study . There was a solitary instance of device fracture, accounting for 2.8% of all cases. The primary endpoint, major adverse events at 30 days, also occurred in 2.8% of the patients. The mortality rate after twelve months was 23%, and none of the fatalities were attributed to the device . In July 2019, the Carillon System was successfully implanted in its 1000th case, which serves as evidence of its widespread use in the field of transcatheter MV replacement. A double-blind randomized study, the REDUCE-FMR trial, was conducted to objectively assess the effectiveness of this system . In this study, 87 symptomatic patients with functional mitral regurgitation under optimal medical treatment were randomized to either receive this treatment or sham and a decrease in MR and LV remodeling was demonstrated in patients treated with the Carillon System .
|
[
"Nikolaos Ktenopoulos",
"Odysseas Katsaros",
"Anastasios Apostolos",
"Maria Drakopoulou",
"Grigorios Tsigkas",
"Constantinos Tsioufis",
"Periklis Davlouros",
"Konstantinos Toutouzas",
"Antonios Karanasos"
] |
https://doi.org/10.3390/life14070842
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11277877_p14
|
PMC11277877
|
sec[1]/sec[4]/p[0]
|
2.5. Direct Annuloplasty Devices
| 4.148438 |
biomedical
|
Study
|
[
0.9892578125,
0.01041412353515625,
0.0003325939178466797
] |
[
0.9453125,
0.0440673828125,
0.008270263671875,
0.0021762847900390625
] |
Cardioband system. The Cardioband device (Edwards Lifesciences, Irvine, CA, USA) is a minimally invasive system used for the treatment of functional MR. It functions similarly to annuloplasty, a surgical technique to repair the MV and improve its performance. The device is built based on the surgical annuloplasty devices; however, it is administered using a percutaneous trans-septal technique. The Cardioband is a flexible band that is surgically inserted from the anterolateral to the posteromedial commissure, using many tiny anchors at the structure . The procedure is conducted with the assistance of continuous echocardiographic and fluoroscopic assistance. Once the band is securely attached to the annulus, the implant is used to decrease the size of the MV annulus, improve the alignment of the leaflets, and thus decrease MR . A multicenter trial including 60 patients who received the Cardioband system showed satisfactory outcomes after one year . The 1-year survival rate was 87% and moderate or less residual MR was found in 61% of the cases. Alongside, there was a considerable improvement in functional status, quality of life, and exercise ability. In the initial stage of the trial, this device encountered technical issues, where 9 out of 10 patients had anchor disengagement, resulting in an ineffective outcome for 5 patients, and as a result, it underwent modifications throughout the initial phase of the investigation .
|
[
"Nikolaos Ktenopoulos",
"Odysseas Katsaros",
"Anastasios Apostolos",
"Maria Drakopoulou",
"Grigorios Tsigkas",
"Constantinos Tsioufis",
"Periklis Davlouros",
"Konstantinos Toutouzas",
"Antonios Karanasos"
] |
https://doi.org/10.3390/life14070842
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11277877_p15
|
PMC11277877
|
sec[1]/sec[4]/p[1]
|
2.5. Direct Annuloplasty Devices
| 4.160156 |
biomedical
|
Study
|
[
0.99658203125,
0.0032978057861328125,
0.00023245811462402344
] |
[
0.9658203125,
0.0247802734375,
0.00823974609375,
0.0012350082397460938
] |
Mitralign system. The Mitralign annuloplasty system (Mitralign, Tewksbury, MA, USA) is based on the circumvolution of the posterior annulus using a device that delivers pledgets. This device is inserted through the aorta in a retrograde manner, allowing for access to both the LV and left atrium (LA). Pledgets are positioned in sets at the antithetical ends of the annulus to decrease the diameter of the annulus, which leads to a depletion in MR . The Mitralign system obtained CE mark clearance in 2016 based on the safety and effectiveness results presented in the CE mark study. The data from the prospective, multicenter, single-arm trial showed a notable enhancement in the 6 min walk test and a refinement in the size and remodeling of the LV after 6 months. MR depletion was observed in 50% of the cases, with a device success rate of 70.4%, while tamponade occurred in 8.9% of the patients, although no mortality events occurred .
|
[
"Nikolaos Ktenopoulos",
"Odysseas Katsaros",
"Anastasios Apostolos",
"Maria Drakopoulou",
"Grigorios Tsigkas",
"Constantinos Tsioufis",
"Periklis Davlouros",
"Konstantinos Toutouzas",
"Antonios Karanasos"
] |
https://doi.org/10.3390/life14070842
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999999 |
PMC11277877_p16
|
PMC11277877
|
sec[1]/sec[4]/p[2]
|
2.5. Direct Annuloplasty Devices
| 2.556641 |
biomedical
|
Other
|
[
0.99072265625,
0.004932403564453125,
0.004119873046875
] |
[
0.0233154296875,
0.97314453125,
0.001300811767578125,
0.00226593017578125
] |
Memo 3D ReChord ring. The highly stiff circular ring Memo 3D ReChord, developed in United Kingdom, is equipped with a chordal guiding system. Its purpose is to facilitate the implantation of artificial neochordae, ensuring precise and successful results without the requirement for specialized chordal measurement. There are limited data on this technique, with a Greek series of 10 patients with promising initial results .
|
[
"Nikolaos Ktenopoulos",
"Odysseas Katsaros",
"Anastasios Apostolos",
"Maria Drakopoulou",
"Grigorios Tsigkas",
"Constantinos Tsioufis",
"Periklis Davlouros",
"Konstantinos Toutouzas",
"Antonios Karanasos"
] |
https://doi.org/10.3390/life14070842
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11277877_p17
|
PMC11277877
|
sec[1]/sec[5]/p[0]
|
2.6. Chordal Replacement
| 3.626953 |
biomedical
|
Other
|
[
0.9970703125,
0.002193450927734375,
0.0008759498596191406
] |
[
0.03271484375,
0.92626953125,
0.0394287109375,
0.0014743804931640625
] |
Chordal replacement, a frequently used procedure for patients in need of cardiac operations, is yet to establish itself as a minimally invasive treatment rather than a transcatheter therapy. Being an MV treatment, it conceptually addresses the pathology of MR mainly using the transapical approach. Currently, there are two systems being utilized, namely the NeoChord DS1000 and the TSD-5 MV repair device .
|
[
"Nikolaos Ktenopoulos",
"Odysseas Katsaros",
"Anastasios Apostolos",
"Maria Drakopoulou",
"Grigorios Tsigkas",
"Constantinos Tsioufis",
"Periklis Davlouros",
"Konstantinos Toutouzas",
"Antonios Karanasos"
] |
https://doi.org/10.3390/life14070842
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277877_p18
|
PMC11277877
|
sec[1]/sec[5]/p[1]
|
2.6. Chordal Replacement
| 4.128906 |
biomedical
|
Study
|
[
0.99609375,
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] |
[
0.9375,
0.053466796875,
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0.0016803741455078125
] |
The NeoChord DS1000 device. The NeoChord device (NeoChord Inc., St. Louis Park, MN, USA) is a surgical technique used to overhaul the MV in patients suffering from degenerative MR without the need for a heart–lung machine (cardiopulmonary bypass). The surgery is conducted with the use of general anesthesia, utilizing the transapical access to insert artificial chords into the MV leaflets . Once the neochordae are secured within the specific leaflet region, the chordae will be fastened at the entry point of the LV. The outcomes of the FIH TACT study resulted in the device receiving CE mark certification in 2012. Each of the 30 participants in the study experienced a prolapse of the posterior MV leaflet accompanied by either chordal rupture or elongation and repeat procedure necessitated in six individuals . Since 2012, NeoChord devices have been utilized in over 450 cases and their data are all collected in a proceeding registry. Furthermore, a crucial study conducted by the FDA, known as the RECHORD study, has commenced with the objective of recruiting 585 patients across 20 engaged centers.
|
[
"Nikolaos Ktenopoulos",
"Odysseas Katsaros",
"Anastasios Apostolos",
"Maria Drakopoulou",
"Grigorios Tsigkas",
"Constantinos Tsioufis",
"Periklis Davlouros",
"Konstantinos Toutouzas",
"Antonios Karanasos"
] |
https://doi.org/10.3390/life14070842
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11277877_p19
|
PMC11277877
|
sec[1]/sec[5]/p[2]
|
2.6. Chordal Replacement
| 3.958984 |
biomedical
|
Other
|
[
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0.000640869140625
] |
[
0.327880859375,
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] |
TSD-5 mitral valve repair device. The TSD-5 MV repair system (Edwards Lifesciences, Irvine, CA, USA) is a homogeneous appliance to the aforementioned NeoChord, since it also utilizes the transapical approach. The manufactured cords are inserted accompanied by transesophageal echocardiography and fluoroscopic employ at the posterior MV leaflet using their specialized equipment. Once the proper length of the chordae has been confirmed, they are secured outside the LV using Teflon substance . The initial findings were presented at the Transcatheter Cardiovascular Therapeutics Conference in 2016, demonstrating a procedural success rate of 100%. However, there were two instances of repeat procedures caused by pericardial effusions and two more due to persisted MR during the follow-up . A CE mark study is now being conducted at 22 centers in five countries across the European Union.
|
[
"Nikolaos Ktenopoulos",
"Odysseas Katsaros",
"Anastasios Apostolos",
"Maria Drakopoulou",
"Grigorios Tsigkas",
"Constantinos Tsioufis",
"Periklis Davlouros",
"Konstantinos Toutouzas",
"Antonios Karanasos"
] |
https://doi.org/10.3390/life14070842
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11277877_p20
|
PMC11277877
|
sec[1]/sec[6]/p[0]
|
2.7. Transcatheter Mitral Valve Replacement (TMVR)
| 4.046875 |
biomedical
|
Study
|
[
0.99853515625,
0.0009584426879882812,
0.0002696514129638672
] |
[
0.83056640625,
0.037689208984375,
0.130615234375,
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] |
The intricate structure of the MV, characterized by its semi-circular shaped, oblique annulus, complicated sub-valvular apparatus, and vast and wavering acreage, presents significant challenges for mitral valve replacement (MVR). The primary obstacles in the creation of proper TMVR prostheses involve securely attaching them to a semi-circular shaped, native MV without calcific deposits to prevent the prosthesis from slipping into the LV . Additionally, it is important to avoid substantial paravalvular leak (PVL) and obstruction of the LV outflow tract (LVOT) by supplanting the anterior MV leaflet into the LVOT. Several prostheses outlines have been developed to tackle these obstacles, with some of them already being tested in individuals as part of initial-phase trials .
|
[
"Nikolaos Ktenopoulos",
"Odysseas Katsaros",
"Anastasios Apostolos",
"Maria Drakopoulou",
"Grigorios Tsigkas",
"Constantinos Tsioufis",
"Periklis Davlouros",
"Konstantinos Toutouzas",
"Antonios Karanasos"
] |
https://doi.org/10.3390/life14070842
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11277877_p21
|
PMC11277877
|
sec[1]/sec[6]/p[1]
|
2.7. Transcatheter Mitral Valve Replacement (TMVR)
| 3.96875 |
biomedical
|
Other
|
[
0.99072265625,
0.0083160400390625,
0.001171112060546875
] |
[
0.074951171875,
0.89013671875,
0.0318603515625,
0.00286102294921875
] |
Access site. There are two approaches available for performing TMVR: the transfemoral (TF) venous approach with transseptal (TS) puncture, and the transapical (TA) approach of the LV . The first route is considered a vaguely invasive method, especially compared to the second one, and it allows for an antegrade access to the MV. However, it might present certain difficulties due to its methodology. On the other hand, anterolateral thoracotomy is necessary for the transapical approach. This method is more invasive; nevertheless, it is a commonly performed procedure with the least possible invasiveness. The operator uses this technique to directly approach the MV, and this permits the accurate placement, securing, and insertion of any TMVR bioprosthetic valve .
|
[
"Nikolaos Ktenopoulos",
"Odysseas Katsaros",
"Anastasios Apostolos",
"Maria Drakopoulou",
"Grigorios Tsigkas",
"Constantinos Tsioufis",
"Periklis Davlouros",
"Konstantinos Toutouzas",
"Antonios Karanasos"
] |
https://doi.org/10.3390/life14070842
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277877_p22
|
PMC11277877
|
sec[1]/sec[6]/p[2]
|
2.7. Transcatheter Mitral Valve Replacement (TMVR)
| 4.308594 |
biomedical
|
Study
|
[
0.99853515625,
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0.0005288124084472656
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[
0.57421875,
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0.4208984375,
0.0008192062377929688
] |
Prostheses. Various bioprosthetic valves are accessible, each utilizing distinct techniques, anchoring, and sealing methods. The global exposure to various valves remains constrained. Every prosthesis is composed of a self-expanding frame, often made of nitinol, which includes leaflets, usually from bovine or pig pericardium, to create the bioprosthesis. The available THVs that are being tested are mentioned below ( Table 2 ) : The Intrepid TMVR system, manufactured by Medtronic in Minnesota, features a flexible dual-stent architecture that operates without the necessity for alternating alignment. The results of the Intrepid TMVR Early Feasibility Study indicate that the advantages of this THV were sustained for up to 12 months, with low mortality, low need for re-operation, and almost outright removal of the MR. These findings demonstrate a favorable safety profile and long-lasting functionality of the valve. A completely recoverable and re-adjustable TMVR system is the Tendyne, made by Abbott Vascular in California. A 34 F sheath is utilized for its implantation through the apex. It features a porcine pericardial valve with three leaflets encased in two self-expanding stents from nitinol. The Real-World Tendyne European Experience Registry outcomes indicate an elevated probability of technical success, long-lasting and thorough elimination of MR, notable therapeutic advantages, and a cardiovascular mortality rate of 17% within 12 months following the TMVR. The Tiara, developed by NeoVasc in Canada, is a device that includes bovine pericardial leaflets, and it is embedded within a self-expanding nitinol compound. The AltaValve, developed by 4C Medical in Minnesota, is a distinctive THV that is positioned in the LA. The device is composed of a nitinol body that is self-expanding with an elongated form and inside this, there is a bovine pericardial valve. The Cardiovalve, developed in Israel, is a self-expanding THV made from bovine pericardium. It consists of two segments, one for the LA and one for the LV. The product is offered in three different shapes, and it is provided using a 28 F sheath. The Cephea system, developed by Abbott Vascular, has a self-expanding structure with two plates. The inner compound contains a valve from bovine pericardium, and its layout enables the outer disk to adapt to different shapes while segregating the rest THV. The EVOQUE valve, developed by Edwards Lifesciences in California, is a self-expanding THV made of nitinol, with leaflets derived from bovine pericardium. The LV skeleton consists of nine hooks that connect to the leaflets of the MV and chords. The LA component of the device offers extra support by attaching to the annulus and it includes a skirt that prevents PVL. The initial trial conducted in the USA has shown that the transseptal TMVR system is possible, with technical success in 92.9% of the patients, while non-cardiovascular death occurred in 7.1% of cases. The system resulted in improved MR and the overall clinical state of the patients. The HighLife system, developed by HighLife Medical in France, utilizes a sub-annular ring that is attached over the MV via a TF approach. This structure functions as a stabilizing point for the self-expanding THV, which incorporates three leaflets from bovine pericardium, and it can be implanted either via the apex of the heart or through the interatrial septum. The SAPIEN M3 system (Edwards Lifesciences, Irvine, CA, USA) consists of a nitinol structure that surrounds the MV and inside is attached a balloon-expandable THV through the interatrial septum. The valve resembles the SAPIEN 3 THV; nevertheless, it features an extra skirt to assist in sealing, avoiding any PVL. The ongoing ENCIRCLE trial is designed to evaluate the safety and efficacy of the SAPIEN M3 THV in individuals with symptomatic, severe MR who are not suitable candidates for surgery or other percutaneous procedures.
|
[
"Nikolaos Ktenopoulos",
"Odysseas Katsaros",
"Anastasios Apostolos",
"Maria Drakopoulou",
"Grigorios Tsigkas",
"Constantinos Tsioufis",
"Periklis Davlouros",
"Konstantinos Toutouzas",
"Antonios Karanasos"
] |
https://doi.org/10.3390/life14070842
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999999 |
PMC11277877_p23
|
PMC11277877
|
sec[1]/sec[7]/p[0]
|
2.8. Mitral Valve-in-Valve (MVIV), Valve-in-MAC (TMVR in-MAC), and Valve-in-Ring (MVIR)
| 4.6875 |
biomedical
|
Review
|
[
0.990234375,
0.007709503173828125,
0.00212860107421875
] |
[
0.07696533203125,
0.00791168212890625,
0.912109375,
0.0029659271240234375
] |
Mitral valve replacement and repair have been the mainstay of the MV surgical treatment in recent years . Opting for MV repair is more advantageous than MVR, since it has demonstrated superior prognostic outcomes and, also, delays the necessity for MVR in comparatively younger individuals. This is crucial, as we now lack an optimal alternative for MVR, even though younger individuals are often recommended to have mechanical valves, which have a longer lifespan but necessitate anticoagulation . Conversely, older patients are advised to have a bioprosthetic valve (either pericardial or porcine) to avoid the requirement for anticoagulation. These valves degenerate over time, and their lifespan in the MV ranges from 10 to 15 years . Prior to recent advancements, repeat procedure was the sole recourse for these cases. However, the success of TAVI and valve-in-valve (VIV) procedures for damaged aortic bioprosthetic valves has introduced a new option known as MV valve-in-valve (MVIV) . In this procedure, a TAVI THV in implanted within the failing valve in the mitral position. Although MVIV shares many similarities with other procedures, it possesses distinct characteristics in terms of case screening, operation preparation, post-operative care and possible complications . Annuloplasty is a crucial component of MV repair and is executed to restructure and strengthen the MV annulus. This is accomplished by applying an annuloplasty ring or band to the atrial side of the MV annulus. Like MVIV, repair deficits have been addressed by inserting a TAVI THV within the ring, known as MV valve-in-ring (MVIR) . Furthermore, mitral annular calcification (MAC) is a gradual and degenerative process in which the MV becomes calcified and is commonly linked to MS, MR, or a combination of the two. Individuals diagnosed with MAC have limited suitability for surgical treatment due to the complex technical difficulties involved and the elevated risk of death during the peri-operative period. TMVR has become a viable choice for those individuals and is elucidated by the utilization of the transcatheter valve-in-MAC procedure . Precise anatomical evaluation is crucial in order to prevent adverse events associated with TMVR, including LVOT obstruction, THV migration, embolization, and PVL .
|
[
"Nikolaos Ktenopoulos",
"Odysseas Katsaros",
"Anastasios Apostolos",
"Maria Drakopoulou",
"Grigorios Tsigkas",
"Constantinos Tsioufis",
"Periklis Davlouros",
"Konstantinos Toutouzas",
"Antonios Karanasos"
] |
https://doi.org/10.3390/life14070842
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11277877_p24
|
PMC11277877
|
sec[1]/sec[8]/p[0]
|
2.9. Critical Appraisal of Transcatheter Mitral Valve Interventions
| 3.986328 |
biomedical
|
Review
|
[
0.990234375,
0.007678985595703125,
0.002323150634765625
] |
[
0.006137847900390625,
0.0191497802734375,
0.9736328125,
0.0011377334594726562
] |
Although currently available percutaneous MV procedures are limited to patients who are deemed inoperable or have a very high surgical risk, such patients are frequently encountered in clinical practice. Therefore, these therapies are continuously evolving and will become a mainstream therapy over the following years. Currently, devices for TEER are by far the most common transcatheter treatment, especially for patients with secondary mitral regurgitation. Despite the limited clinical experience, the newer transcatheter repair options may provide an alternative or complementary option in patients who are not anatomically ideal candidates for TEER, while developments in TMVR, especially with an eventual decrease in the profile of delivery systems, may provide a more comprehensive option for patients with MR.
|
[
"Nikolaos Ktenopoulos",
"Odysseas Katsaros",
"Anastasios Apostolos",
"Maria Drakopoulou",
"Grigorios Tsigkas",
"Constantinos Tsioufis",
"Periklis Davlouros",
"Konstantinos Toutouzas",
"Antonios Karanasos"
] |
https://doi.org/10.3390/life14070842
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11277877_p25
|
PMC11277877
|
sec[2]/p[0]
|
3. Transcatheter Interventions for Tricuspid Valve Disease
| 2.988281 |
biomedical
|
Other
|
[
0.998046875,
0.0008940696716308594,
0.0011262893676757812
] |
[
0.058563232421875,
0.8720703125,
0.0677490234375,
0.0014400482177734375
] |
Due to the unsatisfactory results of performing surgery solely on TV, researchers are currently examining various transcatheter treatments for it. The percutaneous techniques may be classified into four main categories: edge-to-edge repair, TV replacement (TVR), TV annuloplasty, and palliative TV treatment .
|
[
"Nikolaos Ktenopoulos",
"Odysseas Katsaros",
"Anastasios Apostolos",
"Maria Drakopoulou",
"Grigorios Tsigkas",
"Constantinos Tsioufis",
"Periklis Davlouros",
"Konstantinos Toutouzas",
"Antonios Karanasos"
] |
https://doi.org/10.3390/life14070842
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999999 |
PMC11277877_p26
|
PMC11277877
|
sec[2]/sec[0]/p[0]
|
3.1. Transcatheter Edge-to-Edge Repair (TEER) of the Tricuspid Valve
| 4.011719 |
biomedical
|
Other
|
[
0.98291015625,
0.016815185546875,
0.0004584789276123047
] |
[
0.442138671875,
0.5322265625,
0.007068634033203125,
0.018646240234375
] |
TriClip. The TriClip system (Abbott Cardiovascular, Plymouth, MN, USA) is a TEER device that demonstrates high efficacy in mitigating the severity of TR . The system utilizes the surgical technique of edge-to-edge valve approach using a 24 Fr TF delivery device. The system comprises a 4 mm cobalt–chromium clip and two gripper arms that can be operated separately, allowing for unrestrained opening and closing. The clip is transported via a controllable catheter, and it secures itself in position by grasping the TV leaflets. After the MitraClip proved to be successful, it was used for the first time in 2015 on three patients with severe TR. The procedure was successful in all cases, with no mortality events occurring during the procedure, demonstrating its feasibility .
|
[
"Nikolaos Ktenopoulos",
"Odysseas Katsaros",
"Anastasios Apostolos",
"Maria Drakopoulou",
"Grigorios Tsigkas",
"Constantinos Tsioufis",
"Periklis Davlouros",
"Konstantinos Toutouzas",
"Antonios Karanasos"
] |
https://doi.org/10.3390/life14070842
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11277877_p27
|
PMC11277877
|
sec[2]/sec[0]/p[1]
|
3.1. Transcatheter Edge-to-Edge Repair (TEER) of the Tricuspid Valve
| 4.128906 |
biomedical
|
Study
|
[
0.998046875,
0.001377105712890625,
0.0005497932434082031
] |
[
0.5810546875,
0.3701171875,
0.047027587890625,
0.0020084381103515625
] |
The MitraClip and TriClip platforms comprise a navigable guiding catheter and a clip delivery structure. The components of this system consist of a controllable sleeve, a catheter for delivery, and a clip with two movable arms, measuring either 4 mm (NT size) or 7 mm (XTR size) in width . The clip is designed to securely hold and pull the TV leaflets. The MitraClip XTR the platform’s 3 mm longer clips are beneficial for individuals who have bigger coaptation gaps. The clip delivery structures are advanced using the conduit given by the guiding catheter to modify the implanted clip. Unlike the conventional MitraClip system, the new TriClip design includes two knobs specifically designed for steering maneuvers . Furthermore, the steerable sleeve possesses a solitary knob for tip deflection, and its distal curvature exhibits a reduced radius. The different versions of the TriClip system enhance the ability to perform bending and directing maneuvers within the right atrium (RA) .
|
[
"Nikolaos Ktenopoulos",
"Odysseas Katsaros",
"Anastasios Apostolos",
"Maria Drakopoulou",
"Grigorios Tsigkas",
"Constantinos Tsioufis",
"Periklis Davlouros",
"Konstantinos Toutouzas",
"Antonios Karanasos"
] |
https://doi.org/10.3390/life14070842
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999994 |
PMC11277877_p28
|
PMC11277877
|
sec[2]/sec[0]/p[2]
|
3.1. Transcatheter Edge-to-Edge Repair (TEER) of the Tricuspid Valve
| 4.183594 |
biomedical
|
Study
|
[
0.984375,
0.01505279541015625,
0.00042819976806640625
] |
[
0.98876953125,
0.00780487060546875,
0.002193450927734375,
0.0010099411010742188
] |
The TV TEER has now become the most often conducted percutaneous procedure for TV globally. In 2019, the Transcatheter Tricuspid Valve Therapies (TriValve) registry published the 1-year results of 249 individuals who had attempted TEER with the TriClip . Procedural success was observed in 77% of the cases, with each patient receiving 1–3 clips. At the one-year mark, 72% of patients showed a decrease in TR and 69% showed a refinement in their New York Heart Association (NYHA) functional class, with a level of II or below .
|
[
"Nikolaos Ktenopoulos",
"Odysseas Katsaros",
"Anastasios Apostolos",
"Maria Drakopoulou",
"Grigorios Tsigkas",
"Constantinos Tsioufis",
"Periklis Davlouros",
"Konstantinos Toutouzas",
"Antonios Karanasos"
] |
https://doi.org/10.3390/life14070842
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11277877_p29
|
PMC11277877
|
sec[2]/sec[0]/p[3]
|
3.1. Transcatheter Edge-to-Edge Repair (TEER) of the Tricuspid Valve
| 4.078125 |
biomedical
|
Study
|
[
0.94384765625,
0.053955078125,
0.0020046234130859375
] |
[
0.88916015625,
0.1063232421875,
0.0022220611572265625,
0.0021877288818359375
] |
The TRILUMINATE single-arm trial subsequently evaluated the safety and effectiveness of the TriClip technology . Data were provided for the outcomes at 6 months and 1 year. After 6 months, 86% of the cases had a decrease in the intensity of TR by at least one grade, while 4% of them died during that period. After 1 year, 71% of the cases continued to see a decrease in TR severity, while 83% of them showed refinements in NYHA functional class and their all-cause mortality rate was 7% .
|
[
"Nikolaos Ktenopoulos",
"Odysseas Katsaros",
"Anastasios Apostolos",
"Maria Drakopoulou",
"Grigorios Tsigkas",
"Constantinos Tsioufis",
"Periklis Davlouros",
"Konstantinos Toutouzas",
"Antonios Karanasos"
] |
https://doi.org/10.3390/life14070842
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999999 |
PMC11277877_p30
|
PMC11277877
|
sec[2]/sec[0]/p[4]
|
3.1. Transcatheter Edge-to-Edge Repair (TEER) of the Tricuspid Valve
| 4.128906 |
biomedical
|
Study
|
[
0.99658203125,
0.003173828125,
0.0003571510314941406
] |
[
0.98583984375,
0.0113525390625,
0.0024013519287109375,
0.0003418922424316406
] |
The TRILUMINATE Pivotal study aimed to compare patients who are randomly assigned to receive medical therapy with those who receive TriClip . For that reason, 350 patients were randomized, and the results showed significant improvement in quality of life, related to accountable TR reduction, while there were no differences regarding mortality and heart failure hospitalization . TriClip technology has achieved a high level of technical success, and operators are quite experienced with it. As a result, TV TEER has become the benchmark for repairs performed by percutaneous procedures.
|
[
"Nikolaos Ktenopoulos",
"Odysseas Katsaros",
"Anastasios Apostolos",
"Maria Drakopoulou",
"Grigorios Tsigkas",
"Constantinos Tsioufis",
"Periklis Davlouros",
"Konstantinos Toutouzas",
"Antonios Karanasos"
] |
https://doi.org/10.3390/life14070842
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
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