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BACKGROUND: Residency programs are required to incorporate simulation into their training program. Ideally, simulation provides a safe environment for a trainee to be exposed to both common and challenging clinical scenarios. The purpose of this review is to detail the current state of the most commonly used laparoscopic, endoscopic, and robotic surgery simulation programs in general surgery residency education, including resources required for successful implementation and benchmarks for evaluation. MATERIALS AND METHODS: Members of the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) Resident and Fellow Task Force (RAFT) Committee performed a literature review using PubMed and training websites. Information regarding the components of the most commonly used laparoscopic, endoscopic, and/or robotic simulation curriculum, including both formal and informal benchmarks for evaluating training competence, were collected. RESULTS: Laparoscopic simulation revolves around the Fundamentals of Laparoscopic Surgery (FLS). Proficiency-based as well as virtual simulation have been utilized for FLS training curricula. Challenges include less direct translation to the technical complexities that can arise in laparoscopic surgery. Endoscopic simulation focuses on the Fundamentals of Endoscopic Surgery. There are virtual reality simulation platforms that can be used for skills assessment and training. Challenges include simulator types and access, as well as structured mentoring and feedback. Robotic simulation training curricula have not been standardized. Simulation includes one primary technology, which can be prohibitive based on cost and requirements for onboarding. CONCLUSIONS: While surgical simulation seems to be a fundamental and integrated part of surgical training, it requires a significant number of resources, which can be daunting for residency training programs. Regardless of the barriers outlined, the need for surgical simulation in laparoscopy, endoscopy, and robotics at surgical education training programs is clear.
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Competência Clínica , Currículo , Internato e Residência , Treinamento por Simulação , Internato e Residência/métodos , Treinamento por Simulação/métodos , Humanos , Laparoscopia/educação , Cirurgia Geral/educação , Procedimentos Cirúrgicos Robóticos/educação , Endoscopia/educaçãoRESUMO
Sacrificial dilemmas such as the trolley problem play an important role in experimental philosophy (x-phi). But it is increasingly argued that, since we are not likely to encounter runaway trolleys in our daily life, the usefulness of such thought experiments for understanding moral judgments in more ecologically valid contexts may be limited. However, similar sacrificial dilemmas are experienced in real life by animal research decision makers. As part of their job, they must make decisions about the suffering, and often the death, of many non-human animals. For this reason, a context-specific investigation of so-called "3R dilemmas" (i.e., dilemmas where there is a conflict between the principles of replacement, reduction, and refinement of the use of animals in research) is essential to improve the situation of both non-human animals and human stakeholders. An approach well suited for such investigation is experimental philosophical bioethics ("bioxphi"), which draws on methods similar to x-phi to probe more realistic, practical scenarios with an eye to informing normative debates and ethical policy. In this article, we argue for a need to investigate 3R dilemmas among professional decision-makers using the tools of bioxphi. In a first step, we define 3R dilemmas and discuss previous investigations of professionals' attitudes in such cases. In a second step, we show how bioxphi is a promising method to investigate the whys and hows of professional decision-making in 3R dilemmas. In a last step, we provide a bioxphi template for 3R dilemmas, give recommendations on its use, explore the normative relevance of data collected by such means, and discuss important limitations.
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OBJECTIVE: Determine the sensitivity and specificity of the ESBP for diagnosis in patients with intermediate risk of choledocholithiasis, referred to the specialized surgical Gastroenterology center of Unión de Cirujanos SAS - Oncologists of the West Zentria group - Manizales - Colombia between March 01, 2020 to January 31, 2022. MATERIALS AND METHODS: Retrospective cross-sectional study in patients with intermediate risk for choledocholithiasis. The diagnostic performance of ESBP was calculated and confirmed with ERCP. Negative ESBPs were followed up by telephone. RESULTS: 752 cases with ESBP were analyzed, of which 43.2% (n=325) were positive and 56.8% (n=427) were negative. ERCP was performed in positive cases who accepted the procedure (n=317); 73.5% (n:233) were positive for choledocholithiasis, 25.8% (n=82) tumors and 0.6% (n=2) biliary roundworms. Patients with positive ESBP underwent ERCP. S= 98.3% (95% CI: 95.7-99.5) was obtained; E= 88.1% (95% CI: 79.2-94.1); PPV = 95.8% (95% CI: 92.4-98.0); NPV = 94.9% (95% CI: 87.4-98.7). The AUC of ESBP was 0.9319 (95% CI 0.8961-0.967). CONCLUSION: In patients with intermediate risk for choledocholithiasis, ESBP is a useful diagnostic option in the study of pancreatic pathologies, extrahepatic biliary tree, and the identification of biliary microlithiasis; Therefore, it also allows us to complement it with a therapeutic intervention such as ERCP in a single time.
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Colangiopancreatografia Retrógrada Endoscópica , Coledocolitíase , Endossonografia , Sensibilidade e Especificidade , Humanos , Coledocolitíase/diagnóstico por imagem , Coledocolitíase/diagnóstico , Estudos Transversais , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Endossonografia/métodos , Adulto , Idoso de 80 Anos ou maisRESUMO
ABSTRACT: We report the case of a young female that died due to systemic amyloidosis.
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Amiloidose , Amiloidose de Cadeia Leve de Imunoglobulina , Humanos , Feminino , Amiloidose/complicações , Morte Súbita/etiologiaRESUMO
The prognosis of patients with microvascular lesions remains poor because vascular remodeling eventually obliterates the lumen. Here we have focused our efforts on vessel dysfunction in two different organs, the lung and brain. Despite tremendous progress in understanding the importance of blood vessel integrity, gaps remain in our knowledge of the underlying molecular factors contributing to vessel injury, including microvascular lesions. Most of the ongoing research on these lesions have focused on oxidative stress but have not found major molecular targets for the discovery of new treatment or early diagnosis. Herein, we have focused on elucidating the molecular mechanism(s) based on two new emerging molecules NRF1 and ID3, and how they may contribute to microvascular lesions in the lung and brain. Redox sensitive transcriptional activation of target genes depends on not only NRF1, but the recruitment of co-activators such as ID3 to the target gene promoter. Our review highlights the fact that targeting NRF1 and ID3 could be a promising therapeutic approach as they are major players in influencing cell growth, cell repair, senescence, and apoptotic cell death which contribute to vascular lesions. Knowledge about the molecular biology of these processes will be relevant for future therapeutic approaches to not only PAH but cerebral angiopathy and other vascular disorders. Therapies targeting transcription regulators NRF1 or ID3 have the potential for vascular disease-modification because they will address the root causes such as genomic instability and epigenetic changes in vascular lesions. We hope that our findings will serve as a stimulus for further research towards an effective treatment of microvascular lesions.
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Proteínas de Ligação a DNA , Fator 1 Nuclear Respiratório , Ciclo Celular , Proliferação de Células , Proteínas de Ligação a DNA/genética , Humanos , Fator 1 Nuclear Respiratório/genética , Fator 1 Nuclear Respiratório/metabolismo , Fatores de Transcrição/genéticaRESUMO
(1) We investigated the involvement of serum magnesium level in early alcoholic liver disease (ALD), gut barrier dysfunction, and inflammation in alcohol use disorder (AUD) patients; and lastly, the efficacy of 2-week abstinence and medical management to alleviate hypomagnesemia. (2) Forty-eight heavy drinking AUD patients (34 males (M)/14 females (F)) participated in this study. Patients were grouped by serum alanine aminotransferase (ALT) level (a marker of liver injury) as group 1 (Group 1 (Gr.1); ALT ≤ 40 U/L, 7M/8F, without any indication of early-stage ALD) and group 2 (Group 2 (Gr.2); ALT > 40 U/L, 27M/6F or early-stage ALD). These patients were sub-divided within each group into patients with normal magnesium (0.85 and more mmol/L) and deficient magnesium (less than 0.85 mmol/L) levels. All participants were assessed at baseline (BL) and received standard medical management for 2 weeks with reassessment at the treatment end (2w). (3) Female participants of this study showed a significantly lower baseline level of magnesium than their male counterparts. Gr.2 patients showed a greater propensity in the necrotic type of liver cell death, who reported higher chronic and recent heavy drinking. Magnesium level improved to the normal range in Gr.2 post-treatment, especially in the hypomagnesemia sub-group (0.77 ± 0.06 mmol/L (BL) vs. 0.85 ± 0.05 mmol/L (2w), p = 0.02). In Gr.2, both apoptotic (K18M30) and necrotic (K18M65) responses were significantly and independently associated with inflammasome activity comprising of LBP (Lipopolysaccharide binding-protein) and TNFα (Tumor necrosis factor -α), along with serum magnesium. (4) In AUD patients with liver injury, 2-week medical management seems to improve magnesium to a normal level. This group exhibited inflammatory activity (LBP and TNFα) contributing to clinically significant hypomagnesemia. In this group, the level of magnesium, along with the unique inflammatory activity, seems to significantly predict apoptotic and necrotic types of hepatocyte death.
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Alcoolismo , Hepatopatias Alcoólicas , Alanina Transaminase , Alcoolismo/complicações , Feminino , Humanos , Inflamassomos , Inflamação/complicações , Lipopolissacarídeos , Hepatopatias Alcoólicas/terapia , Magnésio , Masculino , Fator de Necrose Tumoral alfaRESUMO
An increased risk of slow gait speed (GS) has been reported among older adults with decreased muscle strength, coupled with a concomitant increase in body fat known as dynapenic obesity (DO); however, these two conditions together have rarely been studied. The objective of this study was to determine the association between GS and DO in older Mexican ambulatory adults. A cross-sectional study was conducted; body fat percentage, and muscle strength and GS using EWGSOP criteria, were measured in 126 older ambulatory Mexican adults, with a mean age of 71 years old. The association was evaluated using controlled logistic regression models. Among ambulatory older adults with slow GS, the risk of DO was 3.4 times higher than among those without, controlling for age and sex (p<0.01). In conclusion, slow GS in ambulatory older adults can be a useful indicator for the early identification of DO.
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Força Muscular , Velocidade de Caminhada , Tecido Adiposo , Idoso , Estudos Transversais , Marcha/fisiologia , Força da Mão/fisiologia , Humanos , Força Muscular/fisiologia , Obesidade/complicaçõesRESUMO
Perivascular epithelioid cell tumour (PEComa) is a rare mesenchymal tumour made up of clear perivascular cells with epithelioid characteristics, which co-expresses muscle and melanocytic markers with a component of spindle cells, like sarcoma and variety of other tissues. This time, we present the case of a young patient with a tumour in the dorsal region of progressive growth, compatible with PEComa of soft tissue after histopathological and immunohistochemical analysis.
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Neoplasias de Células Epitelioides Perivasculares , Humanos , Neoplasias de Células Epitelioides Perivasculares/diagnóstico , Neoplasias de Células Epitelioides Perivasculares/cirurgiaRESUMO
The proteasome is a vital cellular machine that maintains protein homeostasis, which is of particular importance in multiple myeloma and possibly other cancers. Targeting of proteasome 20S peptidase activity with bortezomib and carfilzomib has been widely used to treat myeloma. However, not all patients respond to these compounds, and those who do eventually suffer relapse. Therefore, there is an urgent and unmet need to develop new drugs that target proteostasis through different mechanisms. We identified quinoline-8-thiol (8TQ) as a first-in-class inhibitor of the proteasome 19S subunit Rpn11. A derivative of 8TQ, capzimin, shows >5-fold selectivity for Rpn11 over the related JAMM proteases and >2 logs selectivity over several other metalloenzymes. Capzimin stabilized proteasome substrates, induced an unfolded protein response, and blocked proliferation of cancer cells, including those resistant to bortezomib. Proteomic analysis revealed that capzimin stabilized a subset of polyubiquitinated substrates. Identification of capzimin offers an alternative path to develop proteasome inhibitors for cancer therapy.
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Inibidores de Proteassoma/farmacologia , Quinolinas/farmacologia , Transativadores/antagonistas & inibidores , Relação Dose-Resposta a Droga , Humanos , Estrutura Molecular , Complexo de Endopeptidases do Proteassoma/metabolismo , Inibidores de Proteassoma/química , Quinolinas/química , Relação Estrutura-Atividade , Transativadores/metabolismoRESUMO
The folding dynamics of riboswitches are central to their ability to modulate gene expression in response to environmental cues. In most cases, a structural competition between the formation of a ligand-binding aptamer and an expression platform (or some other competing off-state) determines the regulatory outcome. Here, we review single-molecule studies of riboswitch folding and function, predominantly carried out using single-molecule FRET or optical trapping approaches. Recent results have supplied new insights into riboswitch folding energy landscapes, the mechanisms of ligand binding, the roles played by divalent ions, the applicability of hierarchical folding models, and kinetic vs. thermodynamic control schemes. We anticipate that future work, based on improved data sets and potentially combining multiple experimental techniques, will enable the development of more complete models for complex RNA folding processes. This article is part of a Special Issue entitled: Riboswitches.
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Riboswitches are motifs in the untranslated regions (UTRs) of RNA transcripts that sense metabolite levels and modulate the expression of the corresponding genes for metabolite import, export, synthesis, or degradation. All riboswitches contain an aptamer: an RNA structure that, upon binding ligand, folds to expose or sequester regulatory elements in the adjacent sequence through alternative nucleotide pairing. The coupling between ligand binding and aptamer folding is central to the regulatory mechanisms of thiamine pyrophosphate (TPP) riboswitches and has not been fully characterized. Here, we show that TPP aptamer folding can be decomposed into ligand-independent and -dependent steps that correspond to the formation of secondary and tertiary structures, respectively. We reconstructed the full energy landscape for folding of the wild-type (WT) aptamer and measured perturbations of this landscape arising from mutations or ligand binding. We show that TPP binding proceeds in two steps, from a weakly to a strongly bound state. Our data imply a hierarchical folding sequence, and provide a framework for understanding molecular mechanism throughout the TPP riboswitch family.
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Aptâmeros de Nucleotídeos/química , Conformação de Ácido Nucleico , Riboswitch , Tiamina Pirofosfato/química , Sequência de Bases , Cinética , Dados de Sequência MolecularRESUMO
Infection is the most serious complication of arthroplasty. It's a rare event usually caused by Staphylococcus spp. Prosthetic tuberculosis is rarely reported. We report the case of a 41 year-old patient who underwent a hip replacement for osteoarthritis and after multiple procedures an infection caused by Mycobacterium tuberculosis was documented. We review the literature of previously reported cases.
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Prótese de Quadril/efeitos adversos , Infecções Relacionadas à Prótese/diagnóstico , Tuberculose Osteoarticular/diagnóstico , Adulto , Feminino , Humanos , Mycobacterium tuberculosis/isolamento & purificação , Infecções Relacionadas à Prótese/microbiologiaRESUMO
In this article, we describe and analyse the Swiss legislation relating to animal dignity. We conclude that previous criticisms of the law do not go far enough: far from protecting animal dignity, the Swiss law not only undermines such dignity but itself serves as a means to ensure that animals can be used merely as a means, and not treated with respect. As such, the Swiss Animal Welfare Act is deeply unethical and undermines the constitutional requirement to treat animals with dignity.
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In Switzerland, the importance of transparency in animal experimentation is emphasized by the Swiss Federal Council, recognizing the public's great interest in this matter. Federal reporting on animal experimentation indicates a total of 585,991 animals used in experiments in Switzerland in 2022. By Swiss law, the report enables the public to learn about many aspects such as the species and degree of suffering experienced by the animals, but some information of interest to the public is missing, such as the fate of the animals at the end of the experiment (e.g., euthanized, rehomed in a private home, reused in another experiment). When it comes to animals bred in facilities but not used in experiments, further information of interest is not required to be made public according to Swiss law, for example, the number and fate of "surplus" animals (i.e., animals bred but not used in experiments for a variety of reasons such as not carrying the phenotypical properties needed). Considering that the Swiss government has a duty to provide a full accounting of animal experimentation conducted on the public's behalf, further relevant information should be disclosed. While efforts toward transparency, such as the STAAR Agreement, have been made in the scientific community, these mostly reflect the legal requirements already in force. If Switzerland is to move toward more transparency in public information on animal experimentation, an update of the legal requirements is needed. In this article, we give recommendations for Swiss law to move toward more transparency in public information on seven aspects: (1) the fate of the animals at the end of the experiment; (2) the sources of funding for animal experimentation; (3) the harm-benefit analysis performed by researchers and ethics committees to justify an experiment using animals; (4) the number of breeding/surplus animals; (5) the fate of breeding/surplus animals; (6) the harms experienced by animals in facilities; and (7) the funding of animal facilities.
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Cerebral amyloid angiopathy (CAA) is a degenerative vasculopathy. We have previously shown that transcription regulating proteins- inhibitor of DNA binding protein 3 (ID3) and the nuclear respiratory factor 1 (NRF1) contribute to vascular dysregulation. In this study, we have identified sex specific ID3 and NRF1-mediated gene networks in CAA patients diagnosed with Alzheimer's Disease (AD). High expression of ID3 mRNA coupled with low NRF1 mRNA levels was observed in the temporal cortex of men and women CAA patients. Low NRF1 mRNA expression in the temporal cortex was found in men with severe CAA. High ID3 expression was found in women with the genetic risk factor APOE4. Low NRF1 expression was also associated with APOE4 in women with CAA. Genome wide transcriptional activity of both ID3 and NRF1 paralleled their mRNA expression levels. Sex specific differences in transcriptional gene signatures of both ID3 and NRF1 were observed. These findings were further corroborated by Bayesian machine learning and the GeNIe simulation models. Dynamic machine learning using a Monte Carlo Markov Chain (MCMC) gene ordering approach revealed that ID3 was associated with disease severity in women. NRF1 was associated with CAA and severity of this disease in men. These findings suggest that aberrant ID3 and NRF1 activity presumably plays a major role in the pathogenesis and severity of CAA. Further analyses of ID3- and NRF1-regulated molecular drivers of CAA may provide new targets for personalized medicine and/or prevention strategies against CAA.
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Doença de Alzheimer , Angiopatia Amiloide Cerebral , Feminino , Humanos , Masculino , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Apolipoproteína E4 , Teorema de Bayes , Angiopatia Amiloide Cerebral/complicações , Proteínas de Ligação a DNA , Proteínas Inibidoras de Diferenciação , Proteínas de Neoplasias , Fator 1 Nuclear Respiratório/genética , RNA Mensageiro/genéticaRESUMO
Gene function annotations enable microbial ecologists to make inferences about metabolic potential from genomes and metagenomes. However, even tools that use the same database and general approach can differ markedly in the annotations they recover. We compare three popular methods for identifying KEGG Orthologs, applying them to genomes drawn from a range of bacterial families that occupy different host-associated and free-living biomes. Our results show that by adaptively tuning sequence similarity thresholds, sensitivity can be substantially improved while maintaining accuracy. We observe the largest improvements when few reference sequences exist for a given protein family, and when annotating genomes from non-model organisms (such as gut-dwelling Lachnospiraceae). Our results suggest that straightforward heuristic adjustments can broadly improve microbial metabolic predictions.
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Since Russell and Burch introduced and defined the 3Rs, i.e., the replacement, reduction, and refinement of animal use in research, in 1959, different definitions have emerged and been implemented in guidelines and policies. Switzerland is known for having some of the most restrictive legislation regarding the use of animals, in which the 3Rs are also defined and implemented. To our knowledge, the purpose and definitions of the 3Rs used in the Swiss Animal Welfare Act, Animal Protection Ordinance, and Animal Experimentation Ordinance have never been compared with Russell and Burch's original purpose and definitions. In this paper we make this comparison with two aims: to reveal ethically relevant departures from the original purpose and definitions, and to provide an ethical evaluation of the current Swiss law regarding the 3Rs. In doing so, we first expose the similarity of purposes. We then identify one risky departure from the original definition of replacement in Swiss law, which shows a problematic focus on species. Finally, we address Swiss law's failure to apply the 3Rs in the most effective way. With respect to this last point, we discuss the need for 3R conflict resolution, the timing of application of the 3Rs, problematic prioritizations and choices of convenience as well as a solution to apply the 3Rs more effectively using Russell and Burch's concept of total sum of distress.
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Experimentação Animal , Alternativas aos Testes com Animais , Animais , Bem-Estar do Animal , SuíçaRESUMO
Comprehensive data on factors influencing left atrial appendage (LAA) thrombus formation, resolution and impact on survival are limited. In this single-center, retrospective study 7759 (2010-2015) patients with symptomatic ongoing atrial fibrillation (AF) on admission were screened for LAA thrombi. 450 patients had LAA thrombi. 481 patients without LAA thrombi were randomly selected as controls. We assessed clinical, echocardiographic, laboratory parameters and long-term survival of both groups. Patients with LAA thrombi compared to controls were older, had more strokes, higher CHA2DS2 -VASc scores, worse renal function, less controlled diabetes, advanced heart failure, lower LAA emptying velocities, higher levels of cardiac and inflammatory markers (all p < 0.001). 56.3% of followed-up patients (304) dissolved their LAA thrombi. Chances of thrombus resolution increased with rising LAA flow velocities (OR 1.061, p = 0.022), whereas advanced age (OR 0.950, p < 0.001) and presence of permanent AF (OR 0.354, p < 0.001) decreased chances of thrombus resolution. Presence of LAA thrombi was associated with a markedly reduced 10-year survival probability (31% versus 69%). LAA thrombus formation is promoted by advanced structural heart disease, inflammation, diabetes and impaired renal function. Younger age, non-permanent AF and higher LAA flow velocities were predictors of thrombus resolution. Thrombus formation was associated with poor prognosis.
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Apêndice Atrial , Fibrilação Atrial , Cardiopatias , Trombose , Humanos , Apêndice Atrial/diagnóstico por imagem , Fibrilação Atrial/complicações , Ecocardiografia Transesofagiana , Prognóstico , Estudos RetrospectivosRESUMO
OBJECTIVES: The PASCAL device is a transcatheter edge-to-edge repair system (TEER) for treatment of mitral regurgitation (MR). The PASCAL Ace as a newer version of the PASCAL device consists of a thinner profile without a spacer. The aim of the study was to examine the functional and hemodynamic outcome after TEER with the PASCAL Ace device in a real-world cohort. METHODS: Between September 2020 and August 2021, all consecutive patients with MR 3+/4+ treated percutaneously with PASCAL Ace were included in this study. Primary endpoints included successful device implantation, device success, improvement of exercise capacity, quality of life, and a composite of all-cause mortality, non-fatal stroke, myocardial infarction, new need for renal replacement therapy or severe bleeding at 30 days and 5 month. RESULTS: 49/66 patients had a functional etiology. Overall success rate was 98.5%. At follow-up, 84.7% of the patients had MR grade ≤ 1. TEER was associated with an improvement of LV ejection fraction (45% to 53%, p = 0.048). 86.5% were in NYHA class I or II. 6-minute-walking distance improved by 79m (p = 0.009). Kansas City Cardiomyopathy Questionnaire (KCCQ) improved by 19 points (p = 0.012). NT-proBNP levels decreased from 4832 to 2137 pg/dl (p = 0.003). Mean pulmonary capillary wedge pressures improved from 21 to 15mmHg (p = 0.001). At 5 month, a total of 3 patients died, none of cardiovascular cause. CONCLUSION: PASCAL Ace is safe and effective in treating MR, resulting in a sustained MR reduction, a reverse cardiac remodelling, improvement of exercise capacity, quality of life, NT-proBNP levels and hemodynamics at follow-up.