The Many Roads from Alternative Splicing to Cancer: Molecular Mechanisms Involving Driver Genes.

Cancer driver genes are either oncogenes or tumour suppressor genes that are classically activated or inactivated, respectively, by driver mutations. Alternative splicing-which produces various mature mRNAs and, eventually, protein variants from a single gene-may also result in driving neoplastic transformation because of the different and often opposed functions of the variants of driver genes. The present review analyses the different alternative splicing events that result in driving neoplastic transformation, with an emphasis on their molecular mechanisms. To do this, we collected a list of 568 gene drivers of cancer and revised the literature to select those involved in the alternative splicing of other genes as well as those in which its pre-mRNA is subject to alternative splicing, with the result, in both cases, of producing an oncogenic isoform. Thirty-one genes fall into the first category, which includes splicing factors and components of the spliceosome and splicing regulators. In the second category, namely that comprising driver genes in which alternative splicing produces the oncogenic isoform, 168 genes were found. Then, we grouped them according to the molecular mechanisms responsible for alternative splicing yielding oncogenic isoforms, namely, mutations in cis splicing-determining elements, other causes involving non-mutated cis elements, changes in splicing factors, and epigenetic and chromatin-related changes. The data given in the present review substantiate the idea that aberrant splicing may regulate the activation of proto-oncogenes or inactivation of tumour suppressor genes and details on the mechanisms involved are given for more than 40 driver genes.

BTK drives neutrophil activation for sterilizing antifungal immunity.

We describe a previously-unappreciated role for Bruton's tyrosine kinase (BTK) in fungal immune surveillance against aspergillosis, an unforeseen complication of BTK inhibitors (BTKi) used for treating B-cell lymphoid malignancies. We studied BTK-dependent fungal responses in neutrophils from diverse populations, including healthy donors, BTKi-treated patients, and X-linked agammaglobulinemia patients. Upon fungal exposure, BTK was activated in human neutrophils in a TLR2-, Dectin-1-, and FcγR-dependent manner, triggering the oxidative burst. BTK inhibition selectively impeded neutrophil-mediated damage to Aspergillus hyphae, primary granule release, and the fungus-induced oxidative burst by abrogating NADPH oxidase subunit p40phox and GTPase RAC2 activation. Moreover, neutrophil-specific Btk deletion in mice enhanced aspergillosis susceptibility by impairing neutrophil function, not recruitment or lifespan. Conversely, GM-CSF partially mitigated these deficits by enhancing p47phox activation. Our findings underline the crucial role of BTK signaling in neutrophils for antifungal immunity and provide a rationale for GM-CSF use to offset these deficits in susceptible patients.

hcHCR: High-Throughput Single-Cell Imaging of RNA in Human Primary Immune Cells.

Functional genomics and chemical screens can identify and characterize novel cellular factors regulating signaling networks and chemical tools to modulate their function for the treatment of disease. Screening methods have relied primarily on immortalized and/or transformed cancer cell lines, which can limit the generalization of results to more physiologically relevant systems. Most have also relied on immunofluorescence, or on stably expressed recombinant fluorescent proteins, to detect specific protein markers using high-content imaging readouts. In comparison, high-throughput methods to visualize and measure RNA species have been less explored. To address this, we have adapted an isothermal signal amplification chemistry for RNA FISH known as hybridization chain reaction (HCR) to an automated, high-content imaging assay format. We present a detailed protocol for this technique, which we have named high-content HCR (hcHCR). The protocol focuses on the measurement of changes in mRNA abundance at the single-cell level in human primary cells, but it can be applied to a variety of primary cell types and perturbing agents. We anticipate that hcHCR will be most suitable for low- to medium-throughput screening experiments in which changes in transcript abundance are the desired output measure.

Protective effect of sucrose esters from cape gooseberry (Physalis peruviana L.) in TNBS-induced colitis.

Phytotherapy is an attractive strategy to treat inflammatory bowel disease (IBD) that could be especially useful in developing countries. We previously demonstrated the intestinal anti-inflammatory effect of the total ethereal extract from the Physalis peruviana (Cape gooseberry) calyces in TNBS-induced colitis. This work investigates the therapeutic potential of Peruviose A and B, two sucrose esters that constitute the major metabolites of its calyces. The effect of the Peruvioses A and B mixture on TNBS-induced colitis was studied after 3 (preventive) and 15-days (therapy set-up) of colitis induction in rats. Colonic inflammation was assessed by measuring macroscopic/histologic damage, MPO activity, and biochemical changes. Additionally, LPS-stimulated RAW 264.7 macrophages were treated with test compounds to determine the effect on cytokine imbalance in these cells. Peruvioses mixture ameliorated TNBS-induced colitis in acute (preventive) or established (therapeutic) settings. Although 3-day treatment with compounds did not produce a potent effect, it was sufficient to significantly reduce the extent/severity of tissue damage and the microscopic disturbances. Beneficial effects in the therapy set-up were substantially higher and involved the inhibition of pro-inflammatory enzymes (iNOS, COX-2), cytokines (TNF-α, IL-1ß, and IL-6), as well as epithelial regeneration with restoration of goblet cells numbers and expression of MUC-2 and TFF-3. Consistently, LPS-induced RAW 264.7 cells produced less NO, PGE2, TNF-α, IL-6, and MCP-1. These effects might be related to the inhibition of the NF-κB signaling pathway. Our results suggest that sucrose esters from P. peruviana calyces, non-edible waste from fruit production, might be useful as an alternative IBD treatment.

Long-Term Outcomes of the Altis® Single-Incision Sling: Up to 10 Years' Follow-up.

INTRODUCTION AND HYPOTHESIS: Single-incision slings (SIS) have emerged as a less invasive alternative to conventional slings for stress urinary incontinence (SUI) treatment. However, long-term efficacy and safety results remain uncertain owing to a lack of studies. MATERIAL AND METHODS: A retrospective review of 155 patients treated with Altis® for SUI between February 2012 and June 2017, held in 2022, as a continuation of a prospective study in which all patients (197) were reviewed for 2 years after surgery (1, 6, 12, and 24 months). Preoperative demographic data, comorbidities, and pressure-flow studies were also recorded. Continence status and satisfaction rates were assessed using the International Consultation on Incontinence Questionnaire-short form (ICIQ-SF) and the Patient Global Impression of Improvement (PGI-I) respectively. The assessment in the 2022 retrospective review was performed via a telephone survey. RESULTS: Mean follow-up time after surgery was 85.3 months (82.5-88.1). In 2022, complete continence was present in 75.4% of the patients. The presence of urinary urgency conditioned the ICIQ-SF score (10.9 vs 1.7 points, p < 0.01), with the ICIQ-SF = 0 in 84.5% of the patients with no associated urgency. Satisfaction assessed by the PGI-I was high, with 84.6% of the patients showing improvement. De novo urgency was present in 37,9% of the patients by 2022. Urinary tract infections were the most frequent complication (9.7%), with only 5 documented cases of mesh erosion. CONCLUSIONS: Altis® SIS is a safe and effective device for SUI treatment, with satisfaction rates comparable with those of the conventional slings. Persistence or development of urinary urgency influences the results.

Transapical Mitral Valve Replacement: 1-Year Results of the Real-World Tendyne European Experience Registry.

BACKGROUND: Early studies of the Tendyne transcatheter mitral valve replacement (TMVR) showed promising results in a small selective cohort. OBJECTIVES: The authors present 1-year data from the currently largest commercial, real-world cohort originating from the investigator-initiated TENDER (Tendyne European Experience) registry. METHODS: All patients from the TENDER registry eligible for 1-year follow-up were included. The primary safety endpoint was 1-year cardiovascular mortality. Primary performance endpoint was reduction of mitral regurgitation (MR) up to 1 year. RESULTS: Among 195 eligible patients undergoing TMVR (median age 77 years [Q1-Q3: 71-81 years], 60% men, median Society of Thoracic Surgeons Predicted Risk of Mortality 5.6% [Q1-Q3: 3.6%-8.9%], 81% in NYHA functional class III or IV, 94% with MR 3+/4+), 31% had "real-world" indications for TMVR (severe mitral annular calcification, prior mitral valve treatment, or others) outside of the instructions for use. The technical success rate was 95%. The cardiovascular mortality rate was 7% at 30 day and 17% at 1 year (all-cause mortality rates were 9% and 29%, respectively). Reintervention or surgery following discharge was 4%, while rates of heart failure hospitalization reduced from 68% in the preceding year to 25% during 1-year follow-up. Durable MR reduction to ≤1+ was achieved in 98% of patients, and at 1 year, 83% were in NYHA functional class I or II. There was no difference in survival and major adverse events between on-label use and "real-world" indications up to 1 year. CONCLUSIONS: This large, real-world, observational registry reports high technical success, durable and complete MR elimination, significant clinical benefits, and a 1-year cardiovascular mortality rate of 17% after Tendyne TMVR. Outcomes were comparable between on-label use and "real-world" indications, offering a safe and efficacious treatment option for patients without alternative treatments. (Tendyne European Experience Registry [TENDER]; NCT04898335).

Transcatheter edge-to-edge repair in papillary muscle injury complicating acute myocardial infarction.

AIMS: Acute mitral regurgitation (MR) in the setting of myocardial infarction (MI) may be the result of papillary muscle rupture (PMR). This condition is associated with high morbidity and mortality. We aim to evaluate the feasibility of transcatheter edge-to-edge mitral valve repair (TEER) in this acute setting. METHODS AND RESULTS: We analysed data from the International Registry of MitraClip in Acute Mitral Regurgitation following acute Myocardial Infarction (IREMMI) of 30 centres in Europe, North America, and the middle east. We included patients with post-MI PMR treated with TEER as a salvage procedure, and we evaluated immediate and 30-day outcomes. Twenty-three patients were included in this analysis (9 patients suffered complete papillary muscle rupture, 9 partial and 5 chordal rupture). The patients' mean age was 68 ± 14 years. Patients were at high surgical risk with median EuroSCORE II 27% (IQR 16, 28) and 20 out of 23 (87% were in cardiogenic shock). All patients were treated with vasopressors, and 17 out of 23 patients required mechanical support. TEER procedure was performed on the median 6 days after the index MI date IQR (3, 11). Procedural success was achieved in 87% of patients. The grade of MR was significantly decreased after the procedure. MR reduction to 0 or 1 + was achieved in 13 patients (57%), to 2 + in 7 patients (30%), P < 0.01. V-Wave was reduced from 49 ± 8 mmHg to 26 ± 10 mmHg post-procedure, P < 0.01. Sixteen out of 23 patients (70%) were discharged from hospital and 5 of them required reintervention with surgical mitral valve replacement. No additional death at 1 year was documented. CONCLUSIONS: TEER is a feasible therapy in critically ill patients with PMR due to a recent MI. TEER may have a role as salvage treatment or bridge to surgery in this population.

TransCatheter aortic valve implantation and fractional flow reserve-guided percutaneous coronary intervention versus conventional surgical aortic valve replacement and coronary bypass grafting for treatment of patients with aortic valve stenosis and multivessel or advanced coronary disease: The transcatheter valve and vessels trial (TCW trial): Design and rationale.

BACKGROUND: Patients with severe aortic stenosis (AS) frequently present with concomitant obstructive coronary artery disease (CAD). In those, current guidelines recommend combined coronary artery bypass grafting (CABG) and surgical aortic valve replacement (SAVR) as the preferred treatment option, although this surgical approach is associated with a high rate of clinical events. Combined transcatheter aortic valve implantation (TAVI) and percutaneous coronary intervention (PCI) with or without FFR have evolved as a valid alternative for cardiac surgery in patients with AS and multivessel or advanced CAD. To date, no dedicated trial has prospectively evaluated the outcomes of a percutaneous versus surgical treatment for patients with both severe AS and CAD. AIMS: To investigate whether fractional-flow reserve (FFR)-guided PCI and TAVI is noninferior to combined CABG and SAVR for the treatment of severe AS and multivessel or advanced CAD. METHODS: The Transcatheter Valve and Vessels (TCW) trial (clinicaltrial.gov: NCT03424941) is a prospective, randomized, controlled, open label, international trial. Patients ≥ 70 years with severe AS and multivessel (≥ 2 vessels) or advanced CAD, deemed feasible by the heart team for both; a full percutaneous or surgical treatment, will be randomised in a 1:1 fashion to either FFR-guided PCI followed by TAVI (intervention arm) vs. CABG and SAVR (control arm). The primary endpoint is a patient-oriented composite of all-cause mortality, myocardial infarction, disabling stroke, unscheduled clinically-driven target vessel revascularization, valve reintervention, and life threatening or disabling bleeding at 1 year. The TCW trial is powered for noninferiority, and if met, superiority will be tested. Assuming a primary endpoint rate of 30% in the CABG-SAVR arm, with a significance level α of 5%, a noninferiority limit delta of 15% and a loss to follow-up of 2%, a total of 328 patients are needed to obtain a power of 90%. The primary endpoint analysis is performed on an intention-to-treat basis. SUMMARY: The TCW Trial is the first prospective randomized trial that will study if a less invasive percutaneous treatment for severe AS and concomitant advanced CAD (i.e., FFR-guided PCI-TAVI) is noninferior to the guidelines recommended approach (CABG-SAVR).

Métricas de los artículos publicados en la revista científica Finlay, 2011-2022 / Metrics of the articles published in the Finlay journal, 2011-2022

RESUMEN Objetivo: Caracterizar los artículos publicados en la revista científica Finlay durante el periodo 2011-2022. Materiales y métodos: Se realizó un estudio observacional, descriptivo, bibliométrico sobre los artículos publicados en la revista científica Finlay. El universo estuvo conformado por 525 artículos. No se aplicó técnicas de muestreo. Las variables analizadas fueron cantidad de artículos, año de publicación, cantidad y procedencia de los autores, tipo, temática central de los artículos, tipo de estudios, cantidad de referencias y referencias con cinco años de antigüedad, cantidad de citas por artículos y recibidas por la revista por años. Se aplicó la estadística descriptiva e indicadores bibliométricos. Resultados: Destacó el año 2021, con 60 investigaciones (11,38 %). Predominaron los artículos con tres autores (155; 29,52 %); sobresalió Cienfuegos, con 1074 autores (59,40 %), y prevalecieron los artículos originales (AO) (243; 46,28 %). El mayor índice de Price (IP) (0,80) lo presentaron las imágenes en la medicina (IM). Dentro de los AO, sobresalieron las investigaciones con metodología de enfoque observacional-descriptivo (225 artículos publicados, equivalente a un 92,59 % respecto al total de AO). Destacaron investigaciones relacionadas con enfermedades cardiovasculares (116; 22,09 %). Se recibieron 4870 citas, con predominio del año 2017, con un número de citas corregidas (NCC) de 38,3; mientras que, en el año 2020, hubo 3,27 de factor de impacto (FI). Conclusiones: La revista Finlay constituye un órgano científico para la difusión de resultados investigativos con amplios logros y experiencias en la gestión editorial. Su crecimiento ha sido exponencial en cuanto a la cantidad de artículos publicados, con predominio en el año 2021. En sus números se recogen investigaciones que muestran la colaboración entre autores tanto nacionales como extranjeros, y en donde se resalta los resultados de los investigadores del territorio. Al respecto, las temáticas son referentes a problemas de salud que se recogen en los programas de salud prioritarios para el sector, fundamentados en investigaciones originales en mayor medida, y aparejado a un crecimiento de las citas recibidas en especial en el 2017.

ABSTRACT Objective: To characterize the articles published in the Finlay journal during the period between 2011 and 2022. Materials and methods: An observational, descriptive, bibliometric study was carried out on the articles published in the Finlay journal. The universe consisted of 525 articles. Sampling techniques were not used. The analyzed variables were number of articles, year of publication, number of authors, origin of the authors, type of article, main theme of the articles, type of study, number of references, number of 5-year-old references, number of citations per article and number of citations received by the journal per year. A descriptive statistics and bibliometrics were used. Results: The year 2021 stood out with 60 research works (11.38 %). Articles with three authors prevailed (155; 29.52 %), Cienfuegos stood out with 1,074 authors (59.40 %) and original articles (OA) predominated (243; 46.28 %). Images in medicine (IM) had the highest Price's Index (0.80). Among the OA, research works with an observational-descriptive approach prevailed (225 published articles, which accounted for 92.59 % out of the total number of OA). Research related to cardiovascular diseases predominated (116; 22.09 %). A total of 4,870 citations were received, most of them from 2017, with a number of corrected citations (NCC) of 38.3. Meanwhile, the year 2020 had an impact factor (IF) of 3.27. Conclusions: The Finlay journal is a scientific body for the dissemination of research results with extensive achievements and experiences in editorial management. Its growth has been exponential in terms of the number of articles published, prevailing the year 2021. Its issues include research works that show the collaboration between national and foreign authors, highlighting the results of the Cienfuegos province's researchers. In this regard, the topics focus on health problems that are included in the sector's priority health programs, based on original research to a greater extent and coupled with a higher number of citations received especially in 2017.

TRI-SCORE and benefit of intervention in patients with severe tricuspid regurgitation.

BACKGROUND AND AIMS: Benefit of tricuspid regurgitation (TR) correction and timing of intervention are unclear. This study aimed to compare survival rates after surgical or transcatheter intervention to conservative management according to a TR clinical stage as assessed using the TRI-SCORE. METHODS: A total of 2,413 patients with severe isolated functional TR were enrolled in TRIGISTRY (1217 conservatively managed, 551 isolated tricuspid valve surgery, and 645 transcatheter valve repair). The primary endpoint was survival at 2 years. RESULTS: The TRI-SCORE was low (≤3) in 32%, intermediate (4-5) in 33%, and high (≥6) in 35%. A successful correction was achieved in 97% and 65% of patients in the surgical and transcatheter groups, respectively. Survival rates decreased with the TRI-SCORE in the three treatment groups (all P < .0001). In the low TRI-SCORE category, survival rates were higher in the surgical and transcatheter groups than in the conservative management group (93%, 87%, and 79%, respectively, P = .0002). In the intermediate category, no significant difference between groups was observed overall (80%, 71%, and 71%, respectively, P = .13) but benefit of the intervention became significant when the analysis was restricted to patients with successful correction (80%, 81%, and 71%, respectively, P = .009). In the high TRI-SCORE category, survival was not different to conservative management in the surgical and successful repair group (61% and 68% vs 58%, P = .26 and P = .18 respectively). CONCLUSIONS: Survival progressively decreased with the TRI-SCORE irrespective of treatment modality. Compared to conservative management, an early and successful surgical or transcatheter intervention improved 2-year survival in patients at low and, to a lower extent, intermediate TRI-SCORE, while no benefit was observed in the high TRI-SCORE category.

Bicaval TricValve Implantation in Patients With Severe Symptomatic Tricuspid Regurgitation: 1-Year Follow-Up Outcomes.

BACKGROUND: Several orthotopic transcatheter strategies have been developed to treat severe tricuspid regurgitation (TR); however, many patients are deemed unsuitable. Caval valve implantation with the TricValve system addresses this unmet need. OBJECTIVES: This study sought to determine the impact of TricValve on systemic congestion and quality of life (QOL) at 1 year. METHODS: The TRICUS (Safety and Efficacy of the TricValve® Transcatheter Bicaval Valves System in the Superior and Inferior Vena Cava in Patients With Severe Tricuspid Regurgitation) and TRICUS EURO studies were prospective, nonblinded, nonrandomized, single-arm trials representing the early-in-man experience of the TricValve system in NYHA functional class III or IV severe TR patients, optimally medicated and ineligible for open heart surgery, with significant caval backflow. The primary endpoint was QOL metrics and functional status. The 1-year results of the combined cohort are described here. RESULTS: Forty-four patients were included. Mean age was 76.2 ± 7.5 years, 81.0% were women, and the TRISCORE (risk score model for isolated tricuspid valve surgery) was 5.3 ± 1.3. Clinical improvement at 1 year was achieved in 42 (95.5%) patients, measured by (at least 1 of) an increase in ≥15 points from baseline in 12-item Kansas City Cardiomyopathy Questionnaire score, improvement to NYHA functional class to I or II, or an increase ≥40 m in the 6-minute walk test. There were 3 (6.8%) deaths at 1-year follow-up (1 cardiovascular), and the heart failure rehospitalization rate was 29.5%. Stent fracture, conduction system disturbances, or clinically significant leaflet thrombosis were not detected. Abolished hepatic vein backflow was achieved and persisted in 63.8% of the patients, contributing towards a reduction in congestive symptoms, N-terminal pro-B-type natriuretic peptide levels (P = 0.032), and diuretic treatment. CONCLUSIONS: Caval valve implantation with the TricValve system associated with meaningful 1-year clinical improvements in terms of QOL along with relatively low mortality rates. (TRICUS Study - Safety and Efficacy of the TricValve® Device; NCT03723239).

Grupo Científico Estudiantil Tecnología y Ciencia. Experiencias en la divulgación científica

Introducción: La divulgación científica no debe verse solo como una actividad propia del profesional de la comunicación o del periodismo. Saber divulgar una investigación científica es una forma de gestión del conocimiento adquirido. Objetivo: Describir las experiencias en la divulgación científica del Grupo Científico Estudiantil Tecnología y Ciencia. Método: Se realizó un estudio observacional, descriptivo y transversal. Durante el período comprendido de octubre de 2020 a mayo de 2023 en la Universidad de Ciencias Médicas de Cienfuegos, Cuba. La información se recopiló a partir del análisis de las evidencias de trabajo del Grupo Científico Estudiantil. Las experiencias se describieron teniendo en cuenta las acciones, actividades y espacios creados para el desarrollo de la divulgación científica. Resultados: El Grupo Científico Estudiantil está integrado por 14 estudiantes de las diferentes carreras de las ciencias médicas. De ellos: 7 son estudiantes de Medicina, 2 pertenecen a Estomatología, 3 a las Tecnologías de la Salud y 2 a la carrera de Enfermería. En cuanto al sexo el 57 % son masculinos y el 43 % femeninos. El trabajo sistemático con el Grupo Científico Estudiantil ha permitido avanzar considerablemente en cuanto a organización y desarrollo de eventos donde se socializan y divulgan resultados científicos, además la sostenibilidad del trabajo en equipo ha permitido que se publiquen en revistas científicas los aportes que se derivan de los resultados. Conclusiones: El trabajo del Grupo Científico Estudiantil Tecnología y Ciencia juega un papel decisivo en la comunidad universitaria, pues organiza actividades científicas y académicas en aras de incrementar el desarrollo científico estudiantil.

Introduction: Scientific dissemination should not be seen only as an activity of the communication or journalism professional. Knowing how to disseminate scientific research is a form of management of acquired knowledge. Objective: To describe the experiences in scientific dissemination of the Student Scientific Group: Technology and Science. Method: An observational, descriptive and cross-sectional study was carried out. During the period from October 2020 to May 2023 at the University of Medical Sciences of Cienfuegos, Cuba. The information was compiled from the analysis of the GCE's work evidence. The experiences were described taking into account the actions, activities and spaces created for the development of scientific dissemination. Results: The GCE is madeup of 14 students from different careers in medical sciences. Of them: seven are medical students, two belong to Stomatology, three to Health Technologies, and two to the Nursing career. Regarding sex, 57% are male and 43% female. The systematic work with the GCE has allowed for considerable progress in terms of organization and development of events where scientific results are socialized and disseminated, and the sustainability of team work has allowed the contributions derived from the results to be published in scientific journals. Conclusions: The work of the GCE: Technology and Science plays a decisive role in the university community, as it organizes scientific and academic activities in order to increase student scientific development.

Introdução: A divulgação científica não deve ser vista apenas como uma atividade do profissional de comunicação ou jornalismo. Saber divulgar pesquisas científicas é uma forma de gestão do conhecimento adquirido. Objetivo: Descrever as experiências de divulgação científica do Grupo Científico de Estudantes de Tecnologia e Ciências. Método: Foi realizado estudo observacional, descritivo e transversal. Durante o período de outubro de 2020 a maio de 2023 na Universidad de Cieências Médicas de Cienfuegos, Cuba. As informaçõ es foram compiladas a partir da análise das evidências de trabalho do Grupo Científico Estudantil. As experiências foram descritas levando em consideração as ações, atividades e espaços criados para o desenvolvimento da divulgação científica. Resultados: O Grupo Científico Estudantil é composto por 14 estudantes de diferentes carreiras das ciências médicas. Destes: 7 são estudantes de Medicina, 2 pertencem à Estomatologia, 3 às Tecnologias da Saúde e 2 à carreira de Enfermagem. Quanto ao sexo, 57% são homens e 43% mulheres. O trabalho sistemático com o Grupo Científico de Estudantes tempermitido avanços consideráveis em termos de organização e desenvolvimento de eventos onde os resultados científicos são socializados e divulgados, além disso a sustentabilidade do trabalho emequipe tem permitido que as contribuições derivadas dos estudos sejam publicadas em revistas científicas. Conclusões: A atuação do Grupo Científico de Estudantes de Tecnologia e Ciências desempenha um papel decisivo na comunidade universitária, pois organiza atividades científicas e acadêmicas com o objetivo de aumentar o desenvolvimento científico dos estudantes.

Treatment with SGLT2 Inhibitors in Patients with Diabetes Mellitus and Extensive Coronary Artery Disease: Mortality and Cardiovascular Outcomes.

INTRODUCTION: Sodium-glucose type 2 cotransporter inhibitors (SGLT2-I) have shown solid benefits in reducing cardiovascular mortality and admissions for heart failure in patients with type 2 diabetes mellitus (T2DM) and cardiovascular disease. However, no specific studies exist in patients with high-risk coronary artery disease (CAD). METHODS: Single-center, retrospective, observational study including patients with T2DM and a new diagnosis of extensive CAD (defined as left main disease or three main coronary vessel disease). Patients were recruited from 2015 until 2020, with a follow-up of at least 12 months. The primary outcome was to compare all-cause mortality in patients treated with or without SGLT2-I at discharge and adjusted by inverse probability of treatment weighting (IPTW) propensity score. RESULTS: A total of 420 patients were included: 104 (24.7%) were treated with SGLT2-I and 316 (75.3%) were not (non-SGLT2-I group). The presentation was acute coronary syndrome in 44.3%. The mean age was 71.2 ± 10.5 years. The mean left ventricular ejection fraction was 51.5 ± 12.5%, and the mean estimated glomerular filtration rate was 73.9 ± 22 ml/min. After a mean follow-up of 3 ± 1.6 years, all-cause mortality was 16.4%, and cardiovascular mortality was 9.5%. After IPTW, the risk of all-cause death was lower in the SGLT2-I group with a hazard ratio of 0.32 (95% confidence interval 0.12-0.81), p = 0.016. With regard to secondary outcomes, patients in the SGLT2-I group were associated with less renal function deterioration but an increase in unplanned revascularizations. CONCLUSIONS: In patients with T2DM and extensive CAD, treatment with SGLT2-I after discharge was associated with a reduced risk of all-cause death.

The Evolution of Triamcinolone Acetonide Therapeutic Use in Retinal Diseases: From Off-Label Intravitreal Injection to Advanced Nano-Drug Delivery Systems.

Ophthalmic drug delivery to the posterior segment of the eye has been challenging due to the complex ocular anatomy. Intravitreal injection of drugs was introduced to deliver therapeutic doses in the posterior segment. Different posterior segment diseases including age-related macular degeneration, diabetic macular edema, retinal vein occlusions, uveitis, and cystoid macular edema, among others, have been historically treated with intravitreal corticosteroids injections, and more recently with intravitreal corticosteroids drug implants. Triamcinolone acetonide (TA) is the most frequently used intraocular synthetic corticosteroid. Using nanoparticle-based TA delivery systems has been proposed as an alternative to intravitreal injections in the treatment of posterior segment diseases. From these novel delivery systems, topical liposomes have been the most promising strategy. This review is oriented to exhibit triamcinolone acetonide drug evolution and its results in treating posterior segment diseases using diverse delivery platforms.

Improving access to transcatheter aortic valve implantation across Europe by restructuring cardiovascular services: An expert council consensus statement.

Transcatheter aortic valve implantation (TAVI) is recommended for a growing range of patients with severe aortic stenosis in the European Society of Cardiology and European Association for Cardio-Thoracic Surgery (ESC/EACTS) 2021 Guidelines update. However, guideline implementation programs are needed to ensure the application of clinical recommendations which will favorably influence disease outcomes. An Expert Council was convened to identify whether cardiology services across Europe are set up to address the growing needs of patients with severe aortic stenosis for increased access to TAVI by identifying the key challenges faced in growing TAVI programs and mapping associated solutions. Wide variation exists across Europe in terms of TAVI availability and capacity to deliver the increased demand for TAVI in different countries. The recommendations of this Expert Council focus on the short-to-medium-term aspects where the most immediate, actionable impact can be achieved. The focus on improving procedural efficiency and optimizing the patient pathway via clinical practice and patient management demonstrates how to mitigate the current major issues of shortfall in catheterization laboratory, workforce, and bed capacity. Procedural efficiencies may be achieved through steps including streamlined patient assessment, the benchmarking of standards for minimalist procedures, standardized approaches around patient monitoring and conduction issues, and the implementation of nurse specialists and dedicated TAVI coordinators to manage organization, logistics, and early mobilization. Increased collaboration with wider stakeholders within institutions will support successful TAVI uptake and improve patient and economic outcomes. Further, increased education, collaboration, and partnership between cardiology centers will facilitate sharing of expertise and best clinical practice.

Validation of the TRI-SCORE in patients undergoing surgery for isolated tricuspid regurgitation.

INTRODUCTION: Estimation of peri-procedural risk in patients with tricuspid regurgitation (TR) undergoing isolated tricuspid valve surgery (ITVS) is of paramount importance. The TRI-SCORE is a new surgical risk scale specifically developed for this purpose, which ranged from 0 to 12 points and included eight parameters: right-sided heart failure signs, daily dose of furosemide ≥125 mg, glomerular filtration rate <30 mL/min, elevated bilirubin (with a value of 2 points), age ≥70 years, New York Heart Association Class III-IV, left ventricular ejection fraction <60% and moderate/severe right ventricular dysfunction (with a value of 1 point). The objective of the study was to evaluate the performance of the TRI-SCORE in an independent cohort of patients undergoing ITVS. METHODS: A retrospective observational study was performed in four centres, including consecutive adult patients undergoing ITVS for TR between 2005 and 2022. The TRI-SCORE and the traditional risk scores used in cardiac surgery (Logistic EuroScore (Log-ES) and EuroScore-II (ES-II)) were applied for each patient, and discrimination and calibration of the three scores were evaluated in the entire cohort. RESULTS: A total of 252 patients were included. The mean age was 61.5±11.2 years, 164 (65.1%) patients were female, and TR mechanism was functional in 160 (63.5%) patients. The observed in-hospital mortality was 10.3%. The estimated mortality by the Log-ES, ES-II and TRI-SCORE was 8.7±7.3%, 4.7±5.3% and 11.0±16.6%, respectively. Patients with a TRI-SCORE ≤4 and >4 had an in-hospital mortality of 1.3% and 25.0%, p=0.001, respectively. The discriminatory capacity of the TRI-SCORE had a C-statistic of 0.87 (0.81-0.92), which was significantly higher than both the Log-ES (0.65 (0.54-0.75)) and ES-II (0.67 (0.58-0.79)), p=0.001 (for both comparisons). CONCLUSION: This external validation of the TRI-SCORE demonstrated good performance to predict in-hospital mortality in patients undergoing ITVS, which was significantly better than the Log-ES and ES-II, which underestimated the observed mortality. These results support the widespread use of this score as a clinical tool.

Mecanismos fisiopatológicos de asociación entre síndrome metabólico e hipertensión arterial: una actualización

El síndrome metabólico es una asociación de varias entidades nosológicas que se agrupan bajo dicho nombre siendo las más frecuentes: hipertensión arterial, diabetes mellitus, dislipidemia y la obesidad. Se propuso como objetivo argumentar los mecanismos fisiopatológicos de asociación entre el síndrome metabólico y la hipertensión arterial. Para ello se consultaron un total de 29 fuentes bibliográficas, entre ellas artículos de revistas científicas, 3 libros y otras accedidas a través de los principales gestores de la red informática. La hipertensión arterial y la dislipidemia a menudo aparecen juntas y también acompañan a la resistencia a la captación de glucosa estimulada por insulina; factores que suelen acompañar a la obesidad. Son criterios que ayudan al diagnóstico de síndrome metabólico. Los trastornos metabólicos asociados a la hipertensión arterial desempeñan un papel clave en su aparición y mantenimiento, y modifican el pronóstico a largo plazo en hipertensos y alteran la estrategia terapéutica.

Metabolic syndrome is an association of several disease entities that are grouped under this name, the most frequent being: arterial hypertension, diabetes mellitus, dyslipidemia, and obesity. The objective was to argue the pathophysiological mechanisms of association between the metabolic syndrome and arterial hypertension. For this, a total of 29 bibliographic sources were consulted, including articles from scientific journals, 3 books and others accessed through the main managers of the computer network. Hypertension and dyslipidemia often occur together and also accompany resistance to insulin-stimulated glucose uptake; factors that often accompany obesity. These are criteria that help diagnose metabolic syndrome. The metabolic disorders associated with arterial hypertension play a key role in its appearance and maintenance, and modify the long-term prognosis in hypertensive patients and alter the therapeutic strategy.

Association between hormone therapy and short-term cardiovascular events in women with spontaneous coronary artery dissection.

INTRODUCTION AND OBJECTIVES: Changes in sex hormone levels are a known triggering factor for spontaneous coronary artery dissection (SCAD) in women. However, it is unknown whether exposure to exogenous hormone therapy (HT) at the time of SCAD presentation modifies the clinical course of this condition. We investigated the association between HT in female patients presenting with SCAD and short-term clinical outcomes. METHODS: We enrolled consecutive patients presenting with SCAD from the DISCO-IT/SPA (dissezioni spontanee coronariche Italian-Spanish) registry. Women on HT (estrogens, progestagens, or gonadotropins) at the time of presentation were identified, and their clinical characteristics and short-term outcomes were compared with those not receiving active HT. The outcome measure was nonfatal myocardial infarction and/or unplanned percutaneous coronary intervention during the first 28 days after the index catheterization. RESULTS: Of 224 women presenting with SCAD (mean age 52.0±10.0 years), 39 (17.4%) were currently using HT while 185 (82.6%) were not. No significant differences were noted in the baseline demographics, clinical presentation, angiographic features, or initial treatment received between the 2 groups. All patients on systemic HT (n=36, 92%) discontinued it at the time of diagnosis. The composite outcome occurred in 7 (17.9%) patients with prior HT compared with 14 (7.6%) without (P=.039). After multivariable adjustment, HT remained associated with the composite outcome recorded in the first 28 days of follow-up (HR, 3.53; 95%CI, 1.30-9.61; P=.013). CONCLUSIONS: In women with SCAD, exposure to HT at the time of clinical presentation was associated with short-term recurrent cardiovascular events such as nonfatal myocardial infarction and/or unplanned percutaneous revascularization.

Classic Versus Congruent-Arc Latarjet Procedures.

Glenohumeral instability remains a frequent pathology, specifically in athletes and active patients. As such, several treatment options have been described. In the setting of significant glenoid bone loss (i.e., >20%), off-track Hill-Sachs lesions, and failed previous soft-tissue-based repairs, glenoid bone-augmentation techniques must be considered. These techniques restore stability by a triple blocking effect of the bony graft, the capsulolabral complex repair, and the dynamic sling effect of the conjoined tendon. The classic Latarjet procedure consists in performing a coracoid osteotomy along with the conjoined tendon attachment followed by transfer and fixation to the anterior glenoid, positioning the lateral surface of the coracoid to be flush with the articular side. Then, a modification of this technique defined as "congruent-arc Latarjet" (CAL) was described. This approach involves rotating the coracoid process 90° along its longitudinal axis using the inferior surface to recreate the native glenoid arc. Biomechanical studies have discussed advantages and disadvantages of these techniques. The CAL allows a greater glenoid surface area, which may be relevant in patients with increased glenoid bone loss. However, the bone contact area is reduced, which increases the technical difficulty of screw positioning with an increased risk of graft fragmentation. The classic Latarjet technique has a greater initial fixation strength between the graft and the glenoid and a greater potential for bone consolidation due to the broader contact bone area. Excellent clinical and sports outcomes with low recurrence rates have been observed in both techniques. Imaging findings have exhibited high bone block healing and no difference in graft placement, but CAL demonstrated a greater incidence of fibrous or nonunion rates and errors in screw fixation. Finally, while similar early complications have been reported, long-term outcomes are still needed in CAL for comparing osteoarthritis progression. These results emphasize that either technique can be considered to manage glenohumeral instability when appropriately indicated.