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Neuropilin-1 acts as a coreceptor with vascular endothelial growth factor receptors to facilitate binding of its ligand, vascular endothelial growth factor. Neuropilin-1 also binds to heparan sulfate, but the functional significance of this interaction has not been established. A combinatorial library screening using heparin oligosaccharides followed by molecular dynamics simulations of a heparin tetradecasaccharide suggested a highly conserved binding site composed of amino acid residues extending across the b1 and b2 domains of murine neuropilin-1. Mutagenesis studies established the importance of arginine513 and lysine514 for binding of heparin to a recombinant form of Nrp1 composed of the a1, a2, b1, and b2 domains. Recombinant Nrp1 protein bearing R513A,K514A mutations showed a significant loss of heparin-binding, heparin-induced dimerization, and heparin-dependent thermal stabilization. Isothermal calorimetry experiments suggested a 1:2 complex of heparin tetradecasaccharide:Nrp1. To study the impact of altered heparin binding in vivo, a mutant allele of Nrp1 bearing the R513A,K514A mutations was created in mice (Nrp1D) and crossbred to Nrp1+/- mice to examine the impact of altered heparan sulfate binding. Analysis of tumor formation showed variable effects on tumor growth in Nrp1D/D mice, resulting in a frank reduction in tumor growth in Nrp1D/- mice. Expression of mutant Nrp1D protein was normal in tissues, suggesting that the reduction in tumor growth was due to the altered binding of heparin/heparan sulfate to neuropilin-1. These findings suggest that the interaction of neuropilin-1 with heparan sulfate modulates its stability and its role in tumor formation and growth.
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Heparitina Sulfato , Neuropilina-1 , Neuropilina-1/metabolismo , Neuropilina-1/genética , Neuropilina-1/química , Animais , Heparitina Sulfato/metabolismo , Camundongos , Melanoma Experimental/metabolismo , Melanoma Experimental/patologia , Ligação Proteica , Sítios de Ligação , Camundongos Endogâmicos C57BL , Heparina/metabolismo , Heparina/química , Simulação de Dinâmica Molecular , MutaçãoRESUMO
OBJECTIVE: To assess clinical outcomes of lung lobectomies in dogs and cats using either self-ligating loops (SLLs) or thoracoabdominal (TA) staplers, aiming to inform sample size calculations for future superiority trials. STUDY DESIGN: Retrospective study. ANIMALS: A total of 72 dogs and 15 cats. METHODS: Records from January 2003 to October 2023 at a single institution were reviewed. Cases with lung lobectomy performed via TA stapler or SLL with a minimum 14-day postoperative follow-up were included. Pre-, intra-, and postoperative data were collected, with outcomes of interest including the frequency of intra- and postoperative complications. Outcome comparisons between techniques were performed to inform sample size calculations. RESULTS: A total of 101 lung lobectomies were performed. The TA stapler was used in 83 (82.2%) and the SLL in 18 (17.8%) lung lobectomies. Intraoperative complications were identified in 14/101 lung lobectomies (13.9%), including intraoperative hemorrhage in 12/101 lobectomies (11.8%) and air leakage in 2/101 lobectomies (1.9%). Postoperative complications were identified in 12/87 cases (13.8%), including 4 (4.6%) catastrophic complications and 5 (5.8%) major complications. All intra- and postoperative complications occurred in cases having undergone stapled lung lobectomy; however, no differences were identified between surgical technique and either intraoperative (p = .069) or postoperative complications (p = .112). A sample size of 103 lobectomies per technique group would be required for appropriate evaluation. CONCLUSION: Lung lobectomy using either surgical technique provided a good short-term outcome in this population. CLINICAL SIGNIFICANCE: Self-ligating loop lung lobectomy provided a comparable alternative to stapled lung lobectomy. Further studies are needed to assess technique superiority.
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OBJECTIVE: To analyze the prevalence of no-reflow and the 30-day mortality in a university center in a middle-income country. METHOD: We analyzed 2463 patients who underwent primary PCI from January 2006 to December 2021. The outcome measure was 30-day mortality. RESULTS: Of a total of 2463 patients, no-reflow phenomenon was found in 413 (16.8%) patients, 30-day mortality was 16.7 vs. 4.29% (p < 0.001). Patients with no-reflow were older 60 (53-69.5) vs. 59 (51-66) (p = 0.001), with a higher delay in onset of symptom to emergency department arrival 270 vs. 247 min (p = 0.001). No-reflow patients also had had fewer previous myocardial infarction, 11.6 vs. 18.4 (p = 0.001) and a Killip class > 1, 37 vs. 26% (p < 0.001). No-reflow patients were more likely to have an anterior myocardial infarction (55.4 vs. 47.8%; p = 0.005) and initial TIMI flow 0 (76 vs. 68%; p < 0.001). CONCLUSION: No-reflow occurred in 16.8% of STEMI patients undergoing primary PCI and was more likely with older age, delayed presentation, anterior myocardial infarction and Killip class > 1. No-reflow was associated with a higher mortality at 30-day follow-up.
OBJETIVOS: Analizar la prevalencia de no reflujo y la mortalidad a 30 días en un centro universitario de un país de ingresos medios. MÉTODO: Analizamos 2,463 pacientes que se sometieron a ICP primaria desde enero de 2006 hasta diciembre de 2021. La medida de resultado fue la mortalidad a los 30 días. RESULTADOS: Del total de 2,463 pacientes, se encontró fenómeno de no reflujo en 413 (16.8%), la mortalidad a los 30 días fue del 16.7 vs. 4.29% (p < 0.001). Los pacientes sin reflujo tenían mayor edad 60 (53-69.5) vs. 59 (51-66) (p = 0.001), con mayor retraso del inicio de los síntomas a la llegada a urgencias, 270 vs. 247 min (p = 0.001). Los pacientes sin reflujo también tenían menos infarto de miocardio previo, 11.6 vs. 18.4 (p = 0.001), y una clase Killip > 1, 37 vs. 26% (p < 0.001). Los pacientes sin reflujo tenían más probabilidades de tener un infarto de miocardio anterior (55.4 vs. 47.8%; p = 0.005) y flujo TIMI inicial 0 (76 vs. 68%; p < 0.001). CONCLUSIÓN: Ocurrió ausencia de reflujo en el 16.8% de los pacientes con IAMCEST sometidos a ICP primaria y fue más probable con la edad avanzada, presentación tardía, infarto de miocardio anterior y clase Killip > 1. El no reflujo se asoció con una mayor mortalidad a los 30 días de seguimiento.
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Fenômeno de não Refluxo , Intervenção Coronária Percutânea , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/métodos , Prevalência , Idoso , Prognóstico , Fenômeno de não Refluxo/epidemiologia , Infarto do Miocárdio/epidemiologia , Estudos Retrospectivos , Fatores de Tempo , Fatores Etários , Hospitais Universitários , Infarto do Miocárdio com Supradesnível do Segmento ST/mortalidade , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Infarto do Miocárdio com Supradesnível do Segmento ST/epidemiologia , Infarto do Miocárdio com Supradesnível do Segmento ST/terapiaRESUMO
A 48-year-old woman presented to the emergency department with a one-week history of progressive dyspnea. During her hospitalization, the diagnosis of diffuse alveolar hemorrhage was made. She subsequently developed respiratory failure and acute right ventricular failure. Despite medical treatment, she continued to experience distributive shock due to a generalized inflammatory response. Circulatory support with ECMO was needed. We opted for triple cannulation to manage the multiorgan failure as a bridge to recovery. We describe our experience with an uncommon cannulation technique: veno-pulmonary-arterial cannulation, which enabled us to address cardiogenic shock, refractory hypoxemia, and distributive shock, leading to the successful recovery of the patient.
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Glycosylation is described as a non-templated biosynthesis. Yet, the template-free premise is antithetical to the observation that different N-glycans are consistently placed at specific sites. It has been proposed that glycosite-proximal protein structures could constrain glycosylation and explain the observed microheterogeneity. Using site-specific glycosylation data, we trained a hybrid neural network to parse glycosites (recurrent neural network) and match them to feasible N-glycosylation events (graph neural network). From glycosite-flanking sequences, the algorithm predicts most human N-glycosylation events documented in the GlyConnect database and proposed structures corresponding to observed monosaccharide composition of the glycans at these sites. The algorithm also recapitulated glycosylation in Enhanced Aromatic Sequons, SARS-CoV-2 spike, and IgG3 variants, thus demonstrating the ability of the algorithm to predict both glycan structure and abundance. Thus, protein structure constrains glycosylation, and the neural network enables predictive in silico glycosylation of uncharacterized or novel protein sequences and genetic variants.
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Objectives: The aim of our study was to investigate whether TNFAIP3, PTPN22, and TRAF1-5 single nucleotide polymorphisms (SNPs) are associated with susceptibility, severity, or serological markers in primary Sjögren's syndrome (pSS). Patients and methods: The cases and controls study was conducted between December 2021 and June 2022. TNFAIP3 rs10499194C/T, rs6920220G/A, and rs2230926T/G, PTPN22 rs2476601C/T and rs33996649G/A, and TRAF1-C5 rs10818488G/A polymorphisms were genotyped in 154 female pSS patients (mean age: 45.2±6.8 years) and 313 female control subjects (mean age: 50.3±7.5 years) using the TaqMan® SNP genotyping assay. An association analysis between TNFAIP3, PTPN22, and TRAF1-C5 SNPs and susceptibility, clinical characteristics, and serological markers of pSS was performed. Interactions between TNFAIP3, PTPN22, and TRAF1-C5 SNPs were also evaluated in patients and controls. Results: The genotype and allele frequencies showed no association with susceptibility, severity, or serological markers of pSS. Nevertheless, several interactions between TNFAIP3 and TRAF1-C5 or TNFAIP3, PTPN22, and TRAF1-C5 genotypes were associated with susceptibility to pSS (p<0.01). Conclusion: Individual TNFAIP3, PTPN22, and TRAF1-C5 SNPs are not associated with susceptibility, severity, or serological markers of pSS. However, genetic interactions between TRAF1-C5 and TNFAIP3 or TNFAIP3, PTPN22, and TRAF1-C5 SNPs are risk factors for pSS.
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The literature mostly has addressed the determinants of entrepreneurial intention in general and social entrepreneurship, without focusing specifically on sustainable entrepreneurial intention despite it has become highly relevant in addressing environmental degradation and social challenges. This study aims to contributes to the understanding of psychological and social factors that influence sustainable business, evaluating the effect of resilience, subjective norms, and perceived social support on sustainable entrepreneurial intention. We analysed the online survey responses of 433 students from Chile and Ecuador enrolled in business and engineering programs using Partial Least Squares Structural Equation Models (PLS-SEM), moreover, a multi-group analysis (MGA) has been conducted to assess gender differences. The findings have supported the positive effect of psychological resilience and subjective norms on perceived social support, besides, an important effect of social support on sustainable entrepreneurial intention was found. These results offer new evidence regarding the significance of the social environment, support networks, and resilience of university students in fostering the establishment of sustainable businesses with a focus on social well-being and environmental protection in Latin America. This is particularly pertinent as the countries in this region are grappling with social and environmental challenges that could be addressed through sustainable entrepreneurship.
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Resiliência Psicológica , Humanos , Intenção , Universidades , Meio Social , EstudantesRESUMO
Chronic thromboembolic pulmonary hypertension (CTEPH) is a subtype of pulmonary hypertension characterized by the obstruction of pulmonary arteries secondary to chronic thromboembolism. Pulmonary thromboendarterectomy surgery (PTE) is the main treatment for patients with CTEPH, as it removes the chronic thrombi from the pulmonary arteries. Pulmonary reperfusion syndrome is a common complication of the surgery, which involves the development of pulmonary edema in the area where blood perfusion improves after the surgery. The incidence of this syndrome varies from 8 to 91% depending on the criteria used for diagnosis, and it is one of the most serious complications of pulmonary thromboendarterectomy. In such cases, circulatory support with extracorporeal membrane oxygenation (ECMO) has become a valuable therapeutic modality. We present the case of a 60-year-old woman with a history of acute pulmonary embolism due to deep vein thrombosis of the right pelvic limb who was diagnosed later with CTEPH who was admitted for scheduled surgical treatment involving bilateral PTE. However, during the immediate postoperative period, she developed cardiogenic shock and refractory hypoxemia secondary to pulmonary reperfusion syndrome following the surgical procedure. As a result, she required veno-venous ECMO circulatory support for 6 days, leading to resolution of the pulmonary condition and clinical improvement.
La hipertensión pulmonar tromboembólica crónica (HPTEC) es un subtipo de hipertensión pulmonar caracterizada por la obstrucción de las arterias pulmonares secundaria a tromboembolias crónicas. La cirugía de tromboendarterectomía pulmonar (TEAP) es el tratamiento principal para los pacientes con HPTEC, elimina los trombos crónicos de las arterias pulmonares. El síndrome de reperfusión pulmonar es una complicación común de la cirugía, se trata del desarrollo de edema pulmonar en el área en la que la perfusión sanguínea mejora después de la cirugía. La incidencia del síndrome varía del 8 al 91% según los criterios utilizados para diagnosticarlo y es una de las complicaciones más graves de la tromboendarterectomía pulmonar. En tales casos, el soporte circulatorio con oxigenación por membrana extracorpórea (ECMO) se ha convertido en una valiosa modalidad terapéutica. Presentamos el caso de una paciente de 60 años de edad con antecedente de tromboembolia pulmonar aguda secundaria a trombosis venosa profunda de miembro pélvico derecho a quien durante el seguimiento se realizó el diagnóstico de HPTEC e ingresó de manera programada para tratamiento quirúrgico con realización de TEAP bilateral, sin embargo durante el posquirúrgico inmediato presentó choque cardiogénico e hipoxemia refractaria secundarios a síndrome de reperfusión pulmonar, por lo cual requirió soporte circulatorio con ECMO venovenosa durante seis días, con resolución del cuadro pulmonar y mejoría clínica.
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Endarterectomia , Oxigenação por Membrana Extracorpórea , Complicações Pós-Operatórias , Edema Pulmonar , Embolia Pulmonar , Humanos , Feminino , Oxigenação por Membrana Extracorpórea/métodos , Endarterectomia/métodos , Pessoa de Meia-Idade , Edema Pulmonar/etiologia , Embolia Pulmonar/etiologia , Complicações Pós-Operatórias/etiologia , Hipertensão Pulmonar/etiologia , Artéria Pulmonar/cirurgiaRESUMO
We present the case of a 34-year-old male patient with a history of Marfan syndrome who was admitted to the emergency room for acute aortic regurgitation secondary to aneurysmal dilation of the ascending thoracic aorta. In the postoperative period, post-cardiotomy cardiogenic shock was documented, so circulatory support was initiated with peripheral Veno-Arterial ECMO, which developed hypoxemia due to bacterial pneumonia and data compatible with North-South syndrome. We present a review, non-conventional cannulation strategies and a diagnostic alternative for this entity.
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Introduction: Time-fixed analyses have traditionally been utilized to examine outcomes in post-infarction ventricular septal defect (VSD). The aims of this study were to: (1) analyze the relationship between VSD closure/non-closure and mortality; (2) assess the presence of immortal-time bias. Material and methods: In this retrospective cohort study, patients with ST-elevation myocardial infarction (STEMI) complicated by VSD. Time-fixed and time-dependent Cox regression methodologies were employed. Results: The study included 80 patients: surgical closure (n = 26), transcatheter closure (n = 20), or conservative management alone (n = 34). At presentation, patients without VSD closure exhibited high-risk clinical characteristics, had the shortest median time intervals from STEMI onset to VSD development (4.0, 4.0, and 2.0 days, respectively; P = 0.03) and from STEMI symptom onset to hospital arrival (6.0, 5.0, and 0.8 days, respectively; P < 0.0001). The median time from STEMI onset to closure was 22.0 days (P = 0.14). In-hospital mortality rate was higher among patients who did not undergo defect closure (50%, 35%, and 88.2%, respectively; P < 0.0001). Closure of the defect using a fixed-time method was associated with lower in-hospital mortality (HR = 0.13, 95% CI 0.05-0.31, P < 0.0001, and HR 0.13, 95% CI 0.04-0.36, P < 0.0001, for surgery and transcatheter closure, respectively). However, when employing a time-varying method, this association was not observed (HR = 0.95, 95% CI 0.45-1.98, P = 0.90, and HR 0.88, 95% CI 0.41-1.87, P = 0.74, for surgery and transcatheter closure, respectively). These findings suggest the presence of an immortal-time bias. Conclusions: This study highlights that using a fixed-time analytic approach in post-infarction VSD can result in immortal-time bias. Researchers should consider employing time-dependent methodologies.
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BACKGROUND: Acute Respiratory Distress Syndrome (ARDS) due tocoronavirus disease (COVID-19) infection has a unique phenotype generating a growing need to determine the existing differences that can alter existing evidence-based management strategies for ARDS. RESEARCH QUESTION: What differences does the clinical profile of patients with ARDS due to COVID 19 and Non-COVID 19 have? STUDY DESIGN AND METHODS: We conducted a comparative, observational, retrospective study in the Intensive Care Unit (ICU)of a third-level hospital in Mexico City, from March 2020 through March 2022. Clinical, echocardiographic, and laboratory variables were compared between patients with ARDS due to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and those due to other etiologies. RESULTS: We enrolled 140 patients with a diagnosis of ARDS. The study group of COVID-19 etiology were younger males, higher body mass index, progressed to organ dysfunction, required more frequently renal replacement therapy, and higher SOFA score. There was no difference in rates of right ventricular dysfunction. INTERPRETATION: COVID-19 ARDS exhibit much greater severity that led to higher admission and mortality rates, whilst being younger and less comorbid.
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COVID-19 , Síndrome do Desconforto Respiratório , Humanos , Masculino , México , Síndrome do Desconforto Respiratório/terapia , Estudos Retrospectivos , SARS-CoV-2 , Atenção Terciária à Saúde , FemininoRESUMO
Background: Congenital heart disease (CHD) survival rate has improved dramatically due to advances in diagnostic and therapeutic techniques. However, concerning the unrepaired CHD population of moderate and severe complexity, the data regarding risk predictors and surgical outcomes are scarce. Our aim was to describe the surgical results and predictors of in-hospital outcomes in adult patients with moderate-to-severe complexity CHD that were not repaired in childhood. Methods: We conducted a retrospective cohort study that included 49 adult patients with moderate-to-complex CHD who were treated in a single medical centre. Clinical and echocardiographic variables were obtained on admission, after surgical procedures and during follow-up. Results: Most of the patients were female (66%). Left ventricular ejection fraction and right ventricular outflow tract fractional shortening were within the normal range. The median pulmonary artery systolic pressure was 37 (27-55) mm Hg. The median time was 118 (80-181) minutes for extracorporeal circulation and 76 (49-121) minutes for aortic cross-clamping. The most frequent complication was postoperative complete atrioventricular block (12.2%). In-hospital survival rate was 87.7%. The development of low cardiac output syndrome with predominant right ventricle failure in the postoperative period was the most important predictor of in-hospital death (P = 0.03). Conclusions: Deciding to treat adults with CHD is challenging in moderate and severe unrepaired cases. Adequate clinical, functional, and imaging evaluation is essential to determine each patient's suitability for surgical management and to achieve the best clinical outcome for this population.
Contexte: Grâce aux avancées réalisées en matière de techniques diagnostiques et thérapeutiques, la survie des patients atteints d'une cardiopathie congénitale s'est considérablement améliorée. Cependant, en ce qui concerne les personnes atteintes d'une cardiopathie congénitale non corrigée présentant une complexité modérée ou extrême, les données portant sur les facteurs de risque prédictifs ainsi que sur les résultats chirurgicaux sont rares. Notre objectif était de décrire les résultats chirurgicaux ainsi que les facteurs prédictifs des résultats obtenus en milieu hospitalier chez les patients adultes atteints d'une cardiopathie congénitale présentant une complexité modérée ou extrême qui n'a pas été corrigée pendant l'enfance. Méthodologie: Nous avons mené une étude de cohorte rétrospective comprenant 49 patients adultes atteints d'une cardiopathie congénitale modérée ou complexe qui ont reçu leurs traitements dans un seul centre médical. Les variables cliniques et échocardiographiques ont été obtenues au moment de l'admission, après les interventions chirurgicales et pendant la période de suivi. Résultats: Les patients étaient en majorité des femmes (66 %). La fraction d'éjection du ventricule gauche ainsi que la fraction de raccourcissement de la voie d'éjection ventriculaire droite sont demeurées dans les limites de la normale. La pression systolique médiane de l'artère pulmonaire a été de 37 mmHg (27-55 mmHg). Le temps médian écoulé pour la circulation extracorporelle a été de 118 minutes (80-181 minutes) et pour le clampage de la crosse aortique, de 76 minutes (49-121 minutes). Le bloc auriculo-ventriculaire postopératoire complet a été la complication la plus fréquente (12,2 %). Le taux de survie en milieu hospitalier a été de 87,7 %. Le développement du syndrome du faible débit cardiaque accompagné d'une insuffisance prédominante du ventricule droit durant la période postopératoire a constitué le principal facteur prédictif de décès à l'hôpital (p = 0,03). Conclusion: Il est difficile de traiter les adultes qui présentent une cardiopathie congénitale modérée ou sévère non corrigée. Il est essentiel que les évaluations cliniques, fonctionnelles et par imagerie soient réalisées de façon adéquate pour déterminer si une prise en charge chirurgicale convient aux patients et pour garantir les meilleurs résultats cliniques chez ces derniers.
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BACKGROUND: Studies had previously identified three cardiogenic shock (CS) phenotypes (cardiac-only, cardiorenal, and cardiometabolic). Therefore, we aimed to understand better the hemodynamic profiles of these phenotypes in acute myocardial infarction-CS (AMI-CS) using pulmonary artery catheter (PAC) data to better understand the AMI-CS heterogeneity. METHODS: We analyzed the PAC data of 309 patients with AMI-CS. The patients were classified by SCAI shock stage, congestion profile, and phenotype. In addition, 24 h hemodynamic PAC data were obtained. RESULTS: We identified three AMI-CS phenotypes: cardiac-only (43.7%), cardiorenal (32.0%), and cardiometabolic (24.3%). The cardiometabolic phenotype had the highest mortality rate (70.7%), followed by the cardiorenal (52.5%) and cardiac-only (33.3%) phenotypes, with significant differences (p < 0.001). Right atrial pressure (p = 0.001) and pulmonary capillary wedge pressure (p = 0.01) were higher in the cardiometabolic and cardiorenal phenotypes. Cardiac output, index, power, power index, and cardiac power index normalized by right atrial pressure and left-ventricular stroke work index were lower in the cardiorenal and cardiometabolic than in the cardiac-only phenotypes. We found a hazard ratio (HR) of 2.1 for the cardiorenal and 3.3 for cardiometabolic versus the cardiac-only phenotypes (p < 0.001). Also, multi-organ failure, acute kidney injury, and ventricular tachycardia/fibrillation had a significant HR. Multivariate analysis revealed that CS phenotypes retained significance (p < 0.001) when adjusted for the Society for Cardiovascular Angiography & Interventions score (p = 0.011) and ∆congestion (p = 0.028). These scores independently predicted mortality. CONCLUSIONS: Accurate patient prognosis and treatment strategies are crucial, and phenotyping in AMI-CS can aid in this effort. PAC profiling can provide valuable prognostic information and help design new trials involving AMI-CS.
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Select prion diseases are characterized by widespread cerebral plaque-like deposits of amyloid fibrils enriched in heparan sulfate (HS), a abundant extracellular matrix component. HS facilitates fibril formation in vitro, yet how HS impacts fibrillar plaque growth within the brain is unclear. Here we found that prion-bound HS chains are highly sulfated, and that the sulfation is essential for accelerating prion conversion in vitro. Using conditional knockout mice to deplete the HS sulfation enzyme, Ndst1 (N-deacetylase / N-sulfotransferase) from neurons or astrocytes, we investigated how reducing HS sulfation impacts survival and prion aggregate distribution during a prion infection. Neuronal Ndst1-depleted mice survived longer and showed fewer and smaller parenchymal plaques, shorter fibrils, and increased vascular amyloid, consistent with enhanced aggregate transit toward perivascular drainage channels. The prolonged survival was strain-dependent, affecting mice infected with extracellular, plaque-forming, but not membrane bound, prions. Live PET imaging revealed rapid clearance of recombinant prion protein monomers into the CSF of neuronal Ndst1- deficient mice, neuronal, further suggesting that HS sulfate groups hinder transit of extracellular prion protein monomers. Our results directly show how a host cofactor slows the spread of prion protein through the extracellular space and identify an enzyme to target to facilitate aggregate clearance.
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Neurônios , Doenças Priônicas , Príons , Sulfotransferases , Animais , Camundongos , Heparitina Sulfato/metabolismo , Camundongos Knockout , Neurônios/enzimologia , Doenças Priônicas/metabolismo , Proteínas Priônicas/genética , Príons/metabolismo , Sulfotransferases/genética , Sulfotransferases/metabolismoRESUMO
BACKGROUND: Evaluation of the venous system has long been underestimated as an important component of the circulatory system. As systemic venous pressure increases, the perfusion pressure to the tissues is compromised. During initial resuscitation in cardiac surgery, excessive fluid administration is associated with increased morbidity and mortality. METHODS: We conducted a cross-sectional study of 60 consecutive adult patients who underwent cardiac surgery and in whom it was possible to obtain the venous excess ultrasound (VExUS) grading system and mean systemic filling pressure (Pmsf) in the postoperative period upon admission, at 24 and 48 h. We then determined the correlation between VExUS grading and Pmsf. RESULTS: On admission, patients with VExUS grading 0 predominated, with a progressive increase in venous congestion and an increase in Pmsf over the course of the first 48 h. There was a strong positive correlation between VExUS grading and the invasive measurement of Pmsf at 24 and 48 h after arrival. The presence of grade 2 or grade 3 venous congestion in the postoperative period poses an increased risk of developing acute kidney injury. CONCLUSION: The VExUS grading system indicates a high degree of systemic venous congestion in the first 48 h of the postoperative period after cardiac surgery and correlates with the Pmsf, which is the best surrogate of stressed circulatory volume.
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Procedimentos Cirúrgicos Cardíacos , Sistema Cardiovascular , Hiperemia , Humanos , Estudos TransversaisRESUMO
Objective: The objective of the study is to identify clinical and angiographic characteristics of patients with ST-segment elevation myocardial infarction (STEMI) but without clinical manifestations of COVID-19 infection during the pandemic, compared with patients 1 year before the pandemic. Methods: Observational study that included 138 consecutive patients hospitalized with STEMI who underwent primary percutaneous coronary intervention (PCI) without COVID-19 infection during the 2020 pandemic. A group of 175 STEMI patients treated with PCI in the year before the pandemic served as the control group. Results: During the periods analyzed, compared with the control group, patients admitted during the pandemic without clinical manifestations of COVID-19 did not have significant differences in demographic characteristics, comorbidities, or delayed time and location of the acute myocardial infarction. Furthermore, there were no differences between the two groups concerning levels of CK-MB and NT-proBNP, or in inflammation markers and left ventricular ejection fraction. In patients without COVID-19 during the pandemic compared with control, we found a higher intracoronary thrombus burden (thrombus grade 5; 78.3% vs. 62.9%, respectively. p = 0.002). Accordingly, the use of glycoprotein IIB/IIIa inhibitors (37.7% vs. 26.3%, p = 0.03) was higher in these patients. Conclusions: This study demonstrates an increased thrombus burden in STEMI patients without clinical manifestation of COVID-19 during the pandemic compared with the same time period in the previous year.
Objetivo: Identificar las características clínicas y angiográficas de los pacientes con infarto agudo de miocardio con elevación del segmento ST (IAMCEST) sin manifestaciones clínicas de COVID-19 durante la pandemia y compararlos con los pacientes en el año previo. Métodos: Estudio observacional que incluyó 138 pacientes consecutivos que fueron hospitalizados por IAMCEST y que fueron tratados con angioplastía primaria (ACTP) sin manifestaciones clínicas de COVID-19 durante la pandemia de 2020. Se seleccionó a un grupo control de 175 pacientes con IAMCEST tratados con ACTP en el año previo a la pandemia. Resultados: Los pacientes atendidos durante la pandemia no tuvieron diferencias significativas en cuanto a las características clínicas, demográficas, comorbilidades, tiempo de retraso y localización del infarto. Además, no hubo diferencias entre ambos grupos en los niveles de CK-MB, NT-proBNP, marcadores de inflamación ni en la fracción de eyección del ventrículo izquierdo. En los pacientes sin COVID-19 tratados durante la pandemia encontramos mayor carga trombótica intracoronaria (trombo grado 5; 78.3% vs. 62.9%, respectivamente. p = 0.002). De igual manera, el uso de inhibidores de la glucoproteina IIB/IIIa (37.7% vs. 26.3%, p = 0.03) fue mayor. Conclusiones: Este studio demostró un aumento en la carga trombótica en los pacientes con IAMCEST sin manifestaciones clínicas de COVID-19 durante la pandemia al compararlos con los pacientes tratados por la misma patología en el año previo.
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COVID-19 , Infarto do Miocárdio , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Trombose , Humanos , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Volume Sistólico , Pandemias , COVID-19/complicações , Função Ventricular Esquerda , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/terapia , Trombose/epidemiologia , Trombose/etiologia , Resultado do TratamentoRESUMO
Background: Ventricular septal defect (VSD) complicating acute myocardial infarction (MI) represents a life-threatening condition and has a mortality of >90% if left untreated. Case summary: A 53-year-old man with a prior medical history of diabetes and hypertension presented with cardiogenic shock secondary to VSD as a mechanical complication of non-reperfused inferior MI. Discussion: The choice of mechanical support can be difficult in this type of patient. Given the risk of an increased shunt because of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and the increase in left ventricle (LV) afterload, several measures were taken to plan the best ECMO configuration. Given the absence of any real improvement in the LV and an elevated residual ratio between pulmonary and systemic flow (Qp/Qs), the final decision was to switch to left atrial VA-ECMO (LAVA-ECMO). The use of LAVA-ECMO improved the patient's haemodynamics and allowed his condition to stabilize; LAVA-ECMO is feasible and may be effective as a mechanical circulatory support (MCS) strategy for patients in cardiogenic shock due to VSD as a mechanical complication of acute MI.
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Congenitally corrected transposition of the great arteries is a rare clinical entity, which usually presents during adulthood with associated defects; atrioventricular block, heart failure, systemic valve failure, and arrhythmias usually complicate the clinical course. Even rarer is associated hypertrophic cardiomyopathy, which complicates the disease course and clinical decision-making. Herein, we present a patient with this condition who underwent heart transplantation, with adequate clinical resolution.
Assuntos
Cardiomiopatia Hipertrófica , Insuficiência Cardíaca , Transposição dos Grandes Vasos , Humanos , Adulto , Transposição das Grandes Artérias Corrigida Congenitamente/complicações , Transposição dos Grandes Vasos/complicações , Transposição dos Grandes Vasos/diagnóstico por imagem , Transposição dos Grandes Vasos/cirurgia , Ventrículos do Coração/diagnóstico por imagem , Insuficiência Cardíaca/complicações , Cardiomiopatia Hipertrófica/complicações , Cardiomiopatia Hipertrófica/diagnóstico por imagemRESUMO
BACKGROUND: Haemodynamic monitoring of patients after cardiac surgery using echocardiographic evaluation of fluid responsiveness is both challenging and increasingly popular. We evaluated fluid responsiveness in the first hours after surgery by determining the variability of the velocity-time integral of the left ventricular outflow tract (VTI-LVOT). METHODS: We conducted a cross-sectional study of 50 consecutive adult patients who underwent cardiac surgery and in whom it was possible to obtain VTI-LVOT measurements. We then determined the variability and correlations with our pulse pressure variation (PPV) measurements to predict fluid responsiveness. RESULTS: A strong positive correlation was seen between the VTI-LVOT variability index absolute values and PPV for predicting fluid responsiveness in the first hours after cardiac surgery. We also found that the VTI-LVOT variability index has high specificity and a high positive likelihood ratio compared with the gold standard using a cut-off point of ≥ 12%. CONCLUSIONS: The VTI-LVOT variability index is a valuable tool for determining fluid responsiveness during the first 6 postoperative hours in patients undergoing cardiac surgery.
RESUMO
BACKGROUND: Suicide is a leading cause of death in adolescents and adults in the US. Follow-up support delivered when patients return home after an emergency department (ED) or primary care encounter can significantly reduce suicidal ideation and attempts. Two follow-up models to augment usual care including the Safety Planning Intervention have high efficacy: Instrumental Support Calls (ISC) and Caring Contacts (CC) two-way text messages, but they have never been compared to assess which works best. This protocol for the Suicide Prevention Among Recipients of Care (SPARC) Trial aims to determine which model is most effective for adolescents and adults with suicide risk. METHODS: The SPARC Trial is a pragmatic randomized controlled trial comparing the effectiveness of ISC versus CC. The sample includes 720 adolescents (12-17 years) and 790 adults (18+ years) who screen positive for suicide risk during an ED or primary care encounter. All participants receive usual care and are randomized 1:1 to ISC or CC. The state suicide hotline delivers both follow-up interventions. The trial is single-masked, with participants unaware of the alternative treatment, and is stratified by adolescents/adults. The primary outcome is suicidal ideation and behavior, measured using the Columbia Suicide Severity Rating Scale (C-SSRS) screener at 6 months. Secondary outcomes include C-SSRS at 12 months, and loneliness, return to crisis care for suicidality, and utilization of outpatient mental health services at 6 and 12 months. DISCUSSION: Directly comparing ISC and CC will determine which follow-up intervention is most effective for suicide prevention in adolescents and adults.