[Phosphodiesterase 5 inhibitors for the treatment of heart failure: a systematic review and meta-analysis]. / Inhibidores de la fosfodiesterasa 5 para el tratamiento de la insuficiencia cardiaca: revisión sistemática y metaanálisis de ensayos clínicos aleatorizados.

Objective: The treatment with phosphodiesterase-5 (PDE-5) inhibitors was postulated in heart failure (HF). We conducted a systematic review and a meta-analysis on their beneficial and adverse effects in patients with HF. Method: A meta-analysis of randomized trials evaluating the chronic use of PDE-5 inhibitors in patients with HF was conducted. Endpoints included death, HF hospitalizations, functional capacity, pulmonary pressures, quality of life, and adverse effects. Random-effects models were used to pool outcomes. Categorical data were summarized with relative risks (RR) and 95% confidence intervals (95%CI), and continuous data with weighted mean differences and standardized mean differences. Results: Sixteen studies (1119 participants) were included. No effect was observed on mortality (RR: 1.16; 95%CI: 0.50-2.66; I2: 0.0%) or HF hospitalizations (RR: 0.75; 95%CI: 0.41-1.37; I2: 38.7%). Treatment significantly reduced pulmonary systolic pressure (-10.64 mmHg; 95%CI: -5.14 to -16.15 mmHg; I2: 96.0%), and increased peak oxygen consumption (2.06 ml/kg/min; 95%CI: 0.40-3.72; I2: 89.6%), although with high inconsistency. There were no significant effects on quality of life (-0.15; 95%CI: -0.48-0.18; I2: 0.0%). On the other hand, the risk of headaches was increased (RR: 1.63; 95%CI: 1.11-2.39; I2: 0.0%). Publication bias was identified for HF hospitalizations. Conclusions: Current data suggest that PDE-5 inhibitors therapy does not improve prognosis or quality of life among HF patients. Hemodynamic and functional effects could be relevant, and more studies are necessary to define its role.

Objetivo: El tratamiento con inhibidores de la fosfodiesterasa 5 (iFDE-5) fue postulado en la insuficiencia cardiaca (IC). Se realizó una revisión sistemática y metaanálisis sobre sus efectos beneficiosos y adversos en pacientes con IC. Método: Metaanálisis de ensayos clínicos aleatorizados que evaluaron el uso crónico de iFDE-5 en pacientes con IC. Los criterios de valoración finales incluyeron la muerte, las hospitalizaciones por IC, la capacidad funcional, las presiones y las resistencias pulmonares, la calidad de vida y los efectos adversos. Se utilizaron modelos de efectos aleatorios para agrupar los resultados. Los datos categóricos fueron resumidos como riesgos relativos (RR) e intervalos de confianza del 95% (IC95%), y los datos continuos como diferencias de medias ponderadas y diferencias de medias estandarizadas. Resultados: Se incluyeron 16 estudios (1119 participantes). No se observaron efectos sobre la mortalidad (RR: 1,16; IC95%: 0.50-2.66; I2: 0.0%) ni sobre las hospitalizaciones por IC (RR: 0,75; IC95%: 0.41-1.37; I2: 38.7%). El tratamiento redujo significativamente la presión sistólica pulmonar (−10,64 mmHg; IC95%: −5.14 a −16.15 mmHg; I2: 96.0%) e incrementó el consumo máximo de oxígeno (2.06 ml/kg/min; IC95%: 0.40-3.72 ml/kg/min; I2: 89.6%), aunque con elevada inconsistencia. No se detectaron efectos significativos sobre la calidad de vida (−0.15; IC95%: −0.48-0.18; I2: 0.0%). Por otra parte, aumentó el riesgo de cefaleas (RR: 1.63; IC95%: 1.11-2.39; I2: 0.0%). Se identificó un sesgo de publicación para las hospitalizaciones por IC. Conclusiones: Los datos actuales sugieren que el tratamiento con iFDE-5 no mejora el pronóstico ni la calidad de vida de los pacientes con IC. Los efectos hemodinámicos y funcionales podrían ser relevantes, y son necesarios más estudios para definir su rol.

Síndrome post COVID-19. Gravedad y evolución en 4673 trabajadores sanitarios / Post COVID-19 syndrome. Severity and evolution in 4673 health care workers

Resumen Introducción : La evolución del síndrome post COVID ha sido variable y carecemos de información sobre su impacto en los profesionales de la salud. Métodos : Realizamos una encuesta a través de una red social en profesionales de la salud sobre casos de síndrome post COVID-19 confirmados con PCR. En un cuestionario web, preguntamos sobre 21 síntomas, su gravedad, duración, grado de afectación de la actividad y reincorporación al trabajo. Resultados : Respondieron 4673 profesionales sanita rios de 21 países, edad media de 47 años, 64% mujeres. El curso inicial fue asintomático en el 9%, síntomas leves en el 36%, síntomas moderados sin hospitalización en el 40% o con hospitalización en el 11%, y síntomas graves en el 1%. Los síntomas más prevalentes fueron fatiga (67%), insomnio (44%), ansiedad (42%), mialgia (41%) y anosmia (41%). La prevalencia se redujo a la mitad en los primeros 5 cinco meses, pero en muchos casos se prolongó durante más de un año. En el análisis multi variado los síntomas tendieron a agruparse en clusters (cognitivos, neuropsiquiátricos, cardiorrespiratorios, digestivos, otros). La necesidad de cambiar de área de trabajo fue del 16% y la falta de reincorporación al tra bajo del 7%, relacionadas con la mayor edad, el número de síntomas y la gravedad del curso inicial. Conclusión : En muchos casos la persistencia de los síntomas post COVID-19 puede ser prolongada y te ner un impacto laboral en los profesionales sanitarios, requiriendo la adopción de políticas específicas para reducir el daño.

Abstract Background : The evolution of post COVID-19 syn drome has been variable and we lack information on its impact on healthcare professionals. Methods : We conducted a survey through a social network in health professionals on post COVID-19 syn drome cases confirmed with PCR. In a web-based ques tionnaire, we asked about 21 symptoms, their severity, duration, degree of activity impairment and return to work. Results : 4673 health professionals from 21 countries responded, mean age of 47 years, 64% women. The initial course was asymptomatic in 9%, mild symptoms 36%, moderate symptoms without hospitalization 40% or with hospitalization 11%, and severe symptoms 1%. The most prevalent symptoms were fatigue (67%), insomnia (44%), anxiety (42%), myalgia (41%) and anosmia (41%). Prevalence dropped by half in the first 5 five months, but in many cases, it lasted for more than a year. In the mul 670 tivariate analysis, symptoms tended to be grouped into clusters (cognitive, neuropsychiatric, cardiorespiratory, digestive, others). The need to change the work area was 16% and lack of return to work 7%, related to older age, number of symptoms and severity of the initial course. Conclusion : in many cases the persistence of post- COVID symptoms can be prolonged and have an occu pational impact on healthcare professionals, requiring the adoption of specific policies to reduce harm.

Post COVID-19 syndrome. Severity and evolution in 4673 health care workers.

BACKGROUND: The evolution of post COVID syndrome has been variable and we lack information on its impact on healthcare professionals, particularly in Latin America. METHODS: We conducted a survey through a social network in health professionals on post COVID-19 syndrome cases confirmed with PCR. In a web-based questionnaire, we asked about 21 symptoms, their severity, duration, degree of activity impairment and return to work. RESULTS: 4673 health professionals from 21 countries responded, mean age of 47.8 years, 64.2% women. The initial course was asymptomatic in 9.1%, mild symptoms 36.8%, moderate symptoms without hospitalization 40.8% or with hospitalization 11.7%, and severe symptoms with respiratory assistance 1.6%. The most prevalent symptoms were fatigue (67%), insomnia (44.2%), anxiety (42.3%), myalgia (41.9%) and anosmia (41.2%). Considering only severe symptoms (grades 3-4 on a subjective index from 1 to 4), the most prevalent were slowness (36.3%), impaired concentration (33.1%), anosmia (20.4%), fatigue (19.1%), impaired memory (18.1%) and dyspnea (15.9%). Prevalence dropped by half in the first 5 five months, but in many cases, it lasted for more than a year. In the multivariate analysis, symptoms tended to be grouped into clusters (cognitive, neuropsychiatric, cardiorespiratory, digestive, others). The need to change the work area was 16% and lack of return to work 7.8%, related to older age, number of symptoms and severity of the initial course. CONCLUSION: In conclusion, in many cases the persistence of post-COVID symptoms can be prolonged and have an occupational impact on healthcare professionals, requiring the adoption of specific policies to reduce harm.

Introducción: La evolución del síndrome post COVID ha sido variable y carecemos de información sobre su impacto en los profesionales de la salud. Métodos: Realizamos una encuesta a través de una red social en profesionales de la salud sobre casos de síndrome post COVID-19 confirmados con PCR. En un cuestionario web, preguntamos sobre 21 síntomas, su gravedad, duración, grado de afectación de la actividad y reincorporación al trabajo. Resultados: Respondieron 4673 profesionales sanitarios de 21 países, edad media de 47 años, 64% mujeres. El curso inicial fue asintomático en el 9%, síntomas leves en el 36%, síntomas moderados sin hospitalización en el 40% o con hospitalización en el 11%, y síntomas graves en el 1%. Los síntomas más prevalentes fueron fatiga (67%), insomnio (44%), ansiedad (42%), mialgia (41%) y anosmia (41%). La prevalencia se redujo a la mitad en los primeros 5 cinco meses, pero en muchos casos se prolongó durante más de un año. En el análisis multivariado los síntomas tendieron a agruparse en clusters (cognitivos, neuropsiquiátricos, cardiorrespiratorios, digestivos, otros). La necesidad de cambiar de área de trabajo fue del 16% y la falta de reincorporación al trabajo del 7%, relacionadas con la mayor edad, el número de síntomas y la gravedad del curso inicial. Conclusión: En muchos casos la persistencia de los síntomas post-COVID puede ser prolongada y tener un impacto laboral en los profesionales sanitarios, requiriendo la adopción de políticas específicas para reducir el daño.

Behavior of Endotracheal Tube Cuff Pressure During a Routine Control Maneuver With Different Manometers.

BACKGROUND: The main functions of the endotracheal tube (ETT) cuff are to prevent aspiration and to allow pressurization of the respiratory system. For this purpose, it is essential to maintain adequate pressure inside the cuff, thus reducing the risks for the patient. It is regularly checked using a manometer and is considered the best alternative. The objective of this study was to evaluate the cuff pressure behavior of different ETTs during the simulation of an inflation maneuver using different manometers. METHODS: A bench study was performed. Four brands of 8-mm internal diameter single lumen with a Murphy eye ETT with cuff and 3 different brands of manometers were used. In addition, a pulmonary mechanics monitor was connected to the inside of the cuff through the body of the distal end of the ETT. RESULTS: A total of 528 measurements were made on the 4 ETTs. During the complete procedure (connection and disconnection), there was a significant pressure drop of 7 ± 1.4 cm H2O from the initial pressure (Pinitial) (P < .001), of which 6 ± 1.4 cm H2O was lost during connection (difference between Pinitial and Pconnection). The Preconnection value was 19.1 ± 1.6 cm H2O, showing a significant total pressure drop of 11 ± 1.6 cm H2O (difference between Pinitial and Preconnection) (P < .001). The Pfinal mean was 29.6 ± 1.3 cm H2O. Significant differences were found between manometers according to the time of measurement. A similar phenomenon was evidenced when analyzing different ETTs. CONCLUSIONS: Significant pressure changes occur secondary to ETT cuff measurement, which has important implications for patient safety.

[Time of ethics review of research proposals: results of an observational study]. / Tiempos de evaluación ética de protocolos de investigación: resultados de un estudio observacional.

The review of research protocols by Research Ethics Committees (RECs), essential to ensure the protection of participants, has been managed in the City of Buenos Aires through the PRIISA.BA electronic platform since January 2020. The aim of the present study was to describe ethical review times, their temporal evolution, and predictors of their duration. We conducted an observational study that included all the protocols reviewed between January 2020 and September 2021. Times to approval and to first observation were calculated. Temporal trends in times, and the multivariate association between these and protocol and IRB characteristics were evaluated. 2,781 protocols reviewed in 62 RECs were included. The median time to approval was 29.11 (RIQ 11.29 to 63.35) days, and time to first observation was 8.92 (RIQ 2.05 to 18.18) days. The times were significantly reduced throughout the study period. We detected as variables independently associated with shorter time to approval to be a COVID proposal, having funding and the number of centers to perform the study and having been reviewed by an RECs with more than 10 members. Making observations to the protocol was associated with more time. The results of the present work suggest that ethical review times were reduced during study period. In addition, variables associated with time were identified that could be the object of interventions to improve the process.

Prevalence of non-alcoholic fatty liver disease and liver fibrosis in a general population cohort from Argentina.

INTRODUCTION AND OBJECTIVES: South America is one of the regions with the highest rates of non-alcoholic fatty liver disease (NAFLD). This study aimed to assess the prevalence and severity of NAFLD in suburban Argentina. PATIENTS AND METHODS: The study involved a general community cohort of 993 subjects evaluated sequentially with a comprehensive lifestyle questionnaire, laboratory testing, abdominal ultrasound (US) and transient elastography with XL probe. NAFLD was diagnosed according to standard criteria. RESULTS: The prevalence of NAFLD by the US was 37.2% (326/875) overall, 50.3% in subjects with overweight/obesity, 58.6% with hypertriglyceridemia, 62.3% with diabetes/hyperglycemia and 72.1% with all three risk factors. Male gender (OR 1.42, 95% CI 1.03-1.47, p = 0.029), age (50-59 years: OR 1.98, 95 CI 1.16-3.39, p = 0.013 and ≥60 years: OR 1.86, 95% CI 1.13-3.09, p = 0.015), BMI (25-29: OR 2.87, 95% CI 1.86-4.51, p<0.001 and ≥30: OR 9.57, 95% CI 6.14-15.20, p<0.001), diabetes/hyperglycemia (OR 1.65, 95% CI 1.05-2.61, p = 0.029) and hypertriglyceridemia (OR 1.73, 95% CI 1.20-2.48, p = 0.002) were independent predictors of NAFLD. Among patients with steatosis, 22.2% (69/311) had ≥F2 fibrosis (overweight 25%, hypertriglyceridemia 32%, diabetes/hyperglycemia 34%). BMI (OR 5.22, 95% CI 2.64-11.74, p<0.001), diabetes/hyperglycemia (OR 2.12, 95% CI 1.05-4.29, p = 0.04) and hypertriglyceridemia (OR 1.94, 95% CI 1.03-3.68, p = 0.040) were independent predictors of liver fibrosis. CONCLUSIONS: This general population study from Argentina showed a high prevalence of NAFLD. Significant liver fibrosis was present in 22% of subjects with NAFLD. This information adds to the existing knowledge of NAFLD epidemiology in Latin America.

Tiempos de evaluación ética de protocolos de investigación: resultados de un estudio observacional / Time of ethics review of research proposals: results of an observational study

La evaluación de protocolos de investigación por Comités de Ética en Investigación (CEI), esencialpara garantizar la protección de los participantes, se gestiona en la Ciudad de Buenos Aires a través laplataforma electrónica PRIISA.BA desde enero del 2020. El objetivo del presente estudio fue describirlos tiempos de evaluación ética, su evolución temporal, y los predictores de su duración. Se realizóun estudio observacional que incluyó todos los protocolos evaluados entre enero de 2020 y septiem-bre de 2021. Se calcularon los tiempos al dictamen final y a la primera observación. Se evaluaron lastendencias temporales de los tiempos, y la asociación multivariada entre éstos y características de losprotocolos y de los CEI. Se incluyeron 2781 protocolos evaluados en 62 CEI. La mediana de tiempo aldictamen final fue de 29.11 (RIQ 11.29 a 63.35) días, y del tiempo a la primera observación de 8.92(RIQ 2.05 a 18.18) días. Los tiempos se redujeron significativamente a lo largo del período de estudio.Detectamos como variables independientemente asociadas a menor tiempo a la temática COVID, tenerfinanciamiento y el número de centros a realizarse el estudio y haber sido evaluado en un CEI con másde 10 miembros. La realización de observaciones al protocolo se asoció a mayor tiempo. Los resultadosdel presente trabajo sugieren que los tiempos de evaluación ética se redujeron durante el período deestudio. Además, se identificaron variables asociadas con los tiempos, que podrían ser objeto de inter-venciones para mejorar el proceso.(AU)

The review of research protocols by Research Ethics Committees (RECs), essential to ensure theprotection of participants, has been managed in the City of Buenos Aires through the PRIISA.BA elec-tronic platform since January 2020. The aim of the present study was to describe ethical review times,their temporal evolution, and predictors of their duration. We conducted an observational study thatincluded all the protocols reviewed between January 2020 and September 2021. Times to approvaland to first observation were calculated. Temporal trends in times, and the multivariate associationbetween these and protocol and IRB characteristics were evaluated. 2,781 protocols reviewed in 62RECs were included. The median time to approval was 29.11 (RIQ 11.29 to 63.35) days, and time to firstobservation was 8.92 (RIQ 2.05 to 18.18) days. The times were significantly reduced throughout thestudy period. We detected as variables independently associated with shorter time to approval to bea COVID proposal, having funding and the number of centers to perform the study and having beenreviewed by an RECs with more than 10 members. Making observations to the protocol was associatedwith more time. The results of the present work suggest that ethical review times were reduced duringstudy period. In addition, variables associated with time were identified that could be the object ofinterventions to improve the process.(AU)

Estudio preliminar de correlación fenotipo-genotipo en miocardiopatías de pacientes derivados a un centro de alta complejidad del conurbano bonaerense / A Preliminary Study of the Phenotype-Genotype Correlation in Cardiomyopathies in Patients Referred to a Tertiary Healthcare Center in the Suburbs of Buenos Aires

RESUMEN Introducción : Las miocardiopatías se definen como un trastorno del miocardio en el que el músculo cardíaco es estructural y funcionalmente anormal, en ausencia de enfermedad arterial coronaria, hipertensión arterial (HTA), enfermedad valvular y enfermedad cardíaca congénita. Estas enfermedades son relativamente frecuentes, y suponen una importante causa de morbimortalidad a nivel global. Aunque el estudio genético se recomienda para el cribado familiar, la falta de datos robustos sobre asociaciones genotipo-fenotipo específicas ha reducido su impacto en el manejo clínico. Objetivos : El objetivo de este estudio es analizar la frecuencia de mutaciones en una población de pacientes con miocardiopatía derivados a un centro de alta complejidad y el análisis de la correlación genotipo-fenotipo en las mutaciones identificadas. Material y métodos: Se estudiaron en forma prospectiva 102 pacientes con sospecha de miocardiopatía hipertrófica (MCH) familiar, de los cuales 70 constituían casos índices, de una cohorte ambispectiva de pacientes con miocardiopatías controladas en un hos pital público de alta complejidad de tercer nivel de atención de la provincia de Buenos Aires, desde enero 2012 al 30 agosto 2022. Resultados : De 102 pacientes 83 fueron considerados afectados. De eelos, 31 eran MCH y 52 fenocopias, sin diferencia en el pronóstico. Se realizó estudio genético en 77 pacientes, de los cuales 57 presentaron mutaciones reconocibles, en el 80% de los casos coincidentes con un Score de Mayo ≥3. Se detectaron 28 variantes de significado incierto. Conclusiones : Se comprobó que realizar estudio molecular guiado por el Score de Mayo permitió obtener un alto grado de probabilidad de detectar mutaciones. Se evidenció la importancia del estudio molecular debido a la existencia de solapamiento fenotípico y genotípico de las miocardiopatías. El conocimiento de la variante genética causal actualmente no afecta el manejo clínico de la mayoría de los pacientes con MCH, pero es de ayuda ante un pequeño grupo de genes que tienen opciones de tratamiento.

ABSTRACT Background : Cardiomyopathies are defined as a disorder of the myocardium in which the heart muscle is structurally and functionally abnormal, in the absence of coronary artery disease, hypertension (HT), valvular heart disease and congenital heart disease. These diseases are relatively common and a major cause of morbidity and mortality worldwide. Although genetic testing is recommended for family screening, lack of solid data on specific genotype-phenotype associations has reduced its impact on clinical management. Objectives : This study aims to analyze the frequency of mutations in a population of patients with cardiomyopathy referred to a tertiary healthcare center and to analyze the genotype-phenotype correlation of the identified mutations. Methods : We prospectively included 102 patients with suspected familial hypertrophic cardiomyopathy (HCM), 70 of which were index cases, from an ambispective cohort of patients with cardiomyopathies treated in a tertiary healthcare public hos pital in the province of Buenos Aires, from January 2012 to August 30, 2022. Results : Of 102 patients, 83 were considered affected. Of these, 31 were HCM and 52 were phenocopies, with no difference in prognosis. A genetic study was carried out in 77 patients, of whom 57 presented recognizable mutations, in 80% of the cases coinciding with a Mayo Score ≥3. Twenty-eight variants of uncertain significance were detected. Conclusions : It was confirmed that molecular testing guided by the Mayo Score provided high probability of detecting mutations. Molecular testing proved to be important due to the phenotypic and genotypic overlap in cardiomyopathies. Understanding the causative genetic variant, nowadays, does not affect the clinical management of most HCM patients, but is helpful in a small group of genes with treatment options.

Assessment of an electronic system for research ethics committees document management: An observational study.

Since 1 January 2020, the Central Research Ethics Committee of the Health Ministry implemented PRIISA.BA, an in-house developed electronic system for online submission of health research applications to the 63 public and private research ethics committees (RECs) of Buenos Aires City, Argentina. This study though to compare the times to first review and the time to approval among applications submitted prior to PRIISA.BA and thereafter, across public RECs. All public RECs of the city were invited to participate. Overall, 453 applications from 10 RECs (242 pre- and 211 post-PRIISA.BA) were available for the analyses. There was a decrease in the time to first review and an increase in the time to approval after PRIISA.BA implementation. The increase in time to approval was transient and limited to the first three months. The results were consistent with analyses limited to non-COVID applications. Our results show an increase in the times to approval after the implementation of an electronic system for online submission of health research applications that, although transient, was significant. These data could be relevant to other RECs implementing this technology since it emphasizes the need of monitoring potential unnecessary delays in reviews during the critical initial period.

Variability in Ethics Review for Multicenter Protocols in Buenos Aires, Argentina. An Observational Study.

It has been reported that significant variability in the ethics review process affects multisite studies. We analyzed 1,305 applications for multicenter studies (409 unique protocols), from 1st January 2020 to 20th September 2021. We examined the variability in the times to approval and the first observation and the variation in the level of risk assigned. The median [IQR] variabilities were 42.19 [15.23-82.36] days and 8.00 [3.12-16.68] days, for the times to approval and to the first observation, respectively. There was disagreement in the level of risk assigned by the Research Ethics Committee (REC) in 24.0% of cases. Independent predictors of variability included the number of REC members. In our study, we found substantial variability in the ethics review process among health research protocols. Also, we describe methods to readily measure the delays and the variations in the ethics review process.

Circulating microRNAs as biomarkers of Chagas cardiomyopathy.

Background: Chagas cardiomyopathy (CHCM) is the most important clinical manifestation of Chagas disease. The analysis of cardiac miRNAs may contribute to predicting the progression to CHCM in Chagas indeterminate phase and/or to the differential diagnosis for cardiomyopathy. Methods: We carried out a case-control study to identify circulating miRNAs associated with CHCM. We assigned 104 participants to four groups: healthy controls (HC), Chagas non-cardiomyopathy controls, CHCM cases, and ischemic cardiomyopathy controls. We performed a clinical, echocardiographic, and laboratory evaluation and profiled circulating miRNA in the serum samples. Results: Differences between groups were observed in clinical variables and in the analysis of miRNAs. Compared to HC, CHCM participants had 4 over-expressed and 6 under-expressed miRNAs; miR-95-3p and miR-130b-3p were upregulated in CHCM compared with controls, Chagas non-cardiomyopathy and ischemic cardiomyopathy participants, suggesting that might be a hallmark of CHCM. Analysis of gene targets associated with cardiac injury yielded results of genes involved in arrhythmia generation, cardiomegaly, and hypertrophy. Conclusions: Our data suggest that the expression of circulating miRNAs identified by deep sequencing in CHCM could be associated with different cardiac phenotypes in CHCM subjects, compared with Chagas non-CHCM, ischemic cardiomyopathy controls, and healthy controls.

Intramyocardial Dissecting Hematoma: A Mechanical Complication Needing Surgical Therapy?

Intramyocardial dissecting hematoma is a form of cardiac rupture caused by myocardial infarction, percutaneous coronary intervention, or trauma. It is a cavity between myocardial fibers caused by partial rupture of the ventricular wall. Therapeutic management, including the timing for surgical approach, has not been standardized. We present a case series describing 4 patients. (Level of Difficulty: Intermediate.).

Liquid biopsy for KRAS, NRAS and BRAF mutation testing in advanced colorectal cancer patients: the Argentinean experience.

Objective: To analyze the frequency of KRAS, NRAS and BRAF hotspot mutations in circulating tumor DNA (ctDNA) from patients with metastatic colorectal cancer (mCRC). Methods: Observational, descriptive and retrospective study in mCRC patients with available ctDNA-based genotype of KRAS, NRAS and BRAF. Results: The frequencies of plasma mutations for KRAS, NRAS and BRAF were 34% (± 7), 4% (± 3) and 4% (± 3), respectively. Median overall survival of plasma-tested RAS/BRAF-mutated patients was 26.6 months (95% CI: 14.4-not estimable [NE]), while RAS/BRAF wild-type patients did not reach the median survival during follow-up. Median progression-free survival for RAS/BRAF wild-type and RAS/BRAF-mutated patients was 12 (95% CI: 7-NE) and 4 months (95% CI: 4-NE), respectively. Conclusion: Our work supports the utility of KRAS, NRAS and BRAF analysis in liquid biopsy from mCRC patients.

Sex Differences in the Clinical Presentation of Acute Coronary Syndromes.

The clinical presentation of acute coronary syndromes (ACS) as ST-elevation ACS (STEACS) or non-ST-elevation ACS (NSTEACS) differs between women and men. The aim of this study was to describe the difference in the clinical presentation of ACS between sexes. A total of 10,019 patients included in the Epi-Cardio Registry were analyzed. A higher proportion of women than men presented with NSTEACS (60.3% vs 46.7%; P <0.001). The difference between sexes was driven by a higher prevalence of ACS with non-obstructive coronary arteries (20.9% vs 6.6%) mainly in young women, since ACS without coronary lesions were mostly NSTEACS (77.7% vs 22.3%). In patients with obstructive coronary heart disease, there were no differences in the clinical presentation between sexes. In conclusion, younger women are more likely than men to present ACS with non-obstructive coronary arteries, whereas no significant difference exists between sexes regarding the prevalence of ACS with obstructive coronary artery disease.

High-dose vitamin D versus placebo to prevent complications in COVID-19 patients: Multicentre randomized controlled clinical trial.

BACKGROUND: The role of oral vitamin D3 supplementation for hospitalized patients with COVID-19 remains to be determined. The study was aimed to evaluate whether vitamin D3 supplementation could prevent respiratory worsening among hospitalized patients with COVID-19. METHODS AND FINDINGS: We designed a multicentre, randomized, double-blind, sequential, placebo-controlled clinical trial. The study was conducted in 17 second and third level hospitals, located in four provinces of Argentina, from 14 August 2020 to 22 June 2021. We enrolled 218 adult patients, hospitalized in general wards with SARS-CoV-2 confirmed infection, mild-to-moderate COVID-19 and risk factors for disease progression. Participants were randomized to a single oral dose of 500 000 IU of vitamin D3 or matching placebo. Randomization ratio was 1:1, with permuted blocks and stratified for study site, diabetes and age (≤60 vs >60 years). The primary outcome was the change in the respiratory Sepsis related Organ Failure Assessment score between baseline and the highest value recorded up to day 7. Secondary outcomes included the length of hospital stay; intensive care unit admission; and in-hospital mortality. Overall, 115 participants were assigned to vitamin D3 and 105 to placebo (mean [SD] age, 59.1 [10.7] years; 103 [47.2%] women). There were no significant differences in the primary outcome between groups (median [IQR] 0.0 [0.0-1.0] vs 0.0 [0.0-1.0], for vitamin D3 and placebo, respectively; p = 0.925). Median [IQR] length of hospital stay was not significantly different between vitamin D3 group (6.0 [4.0-9.0] days) and placebo group (6.0 [4.0-10.0] days; p = 0.632). There were no significant differences for intensive care unit admissions (7.8% vs 10.7%; RR 0.73; 95% CI 0.32 to 1.70; p = 0.622), or in-hospital mortality (4.3% vs 1.9%; RR 2.24; 95% CI 0.44 to 11.29; p = 0.451). There were no significant differences in serious adverse events (vitamin D3 = 14.8%, placebo = 11.7%). CONCLUSIONS: Among hospitalized patients with mild-to-moderate COVID-19 and risk factors, a single high oral dose of vitamin D3 as compared with placebo, did not prevent the respiratory worsening. TRIAL REGISTRATION: ClincicalTrials.gov Identifier: NCT04411446.

Recomendaciones de manejo de los anticoagulantes orales directos (DOACs) anti Xa y anti IIa / Recommendations for the practical management of the direct oral anticoagulants anti Xa and anti IIa

Resumen Los anticoagulantes orales directos han surgido como una de las herramientas que ha cambiado el manejo de la enfermedad trombótica en los últimos 15 años. Sus ventajas, desde el punto de vista de la facilidad de uso y menor riesgo de sangrado, especialmente de sangrado cerebral, han posicionado a estos nuevos anticoagulantes como la primera alternativa de tratamiento en las dos indicaciones más frecuentes en que necesitamos estas drogas, la fibrilación auricular y la enfermedad tromboembólica venosa. Sin embargo, no todos los pacientes pueden recibir estos agentes, no todos los anticoagulantes directos tienen las mismas pro piedades y fundamentalmente, no todas las enfermedades con indicación de un anticoagulante pueden tratarse con ellos;con lo cual es necesario que todos los profesionales que están involucrados en el manejo de estos medicamentos estén obligados a conocerlos en profundidad, para poder decidir el mejor tratamiento en cada caso particular. Este documento de posición de expertos de diferentes especialidades de Argentina, presenta lineamientos para el uso correcto de los anticoagulantes directos en base a nueva evidencia y a la experiencia de uso de un amplio grupo de profesionales. La forma de relacionarnos con el tratamiento anticoagulante ha cambiado. Los médicos que trabajamos con ellos también debemos hacerlo.

Abstract Direct oral anticoagulants have emerged as the drugs that have changed the man agement of the antithrombotic treatment in the last 15 years. Their advantages, like a more friendly way of anticoagulation and their lower risk of bleeding, especially in the brain, have positioned these new anticoagu lants as the first drug of choice in the two most frequent indications of anticoagulation, atrial fibrillation, and the venous thromboembolic disease. However, not all the patients can receive these agents, not all the direct oral anticoagulants have the same characteristics, and most importantly, not all the diseases with an indication of an anticoagulant drug can be treated with them. Therefore, it is mandatory that all the faculties involved in the management of these drugs must know them in depth, to decide the best treatment for the patient. This position paper, from a group of experts in anticoagulation in Argentina, can help the general practitioner in the daily use of direct oral anticoagulants based on the new evidence and the experience of a wide group of professionals. The way we relate to the anticoagulant treatment has changed in the last years. The doctors who work with them must also do so.

[MANAGEMENT RECOMMENDATIONS FOR DIRECT ORAL ANTICOAGULANTS (DOACs) ANTI Xa AND ANTI IIa]. / RECOMENDACIONES DE MANEJO DE LOS ANTICOAGULANTES ORALES DIRECTOS (DOACS) ANTI Xa Y ANTI IIa.

Direct oral anticoagulants have emerged as the drugs that have changed the management of the antithrombotic treatment in the last 15 years. Their advantages, like a more friendly way of anticoagulation and their lower risk of bleeding, especially in the brain, have positioned these new anticoagulants as the first drug of choice in the two most frequent indications of anticoagulation, atrial fibrillation, and the venous thromboembolic disease. However, not all the patients can receive these agents, not all the direct oral anticoagulants have the same characteristics, and most importantly, not all the diseases with an indication of an anticoagulant drug can be treated with them. Therefore, it is mandatory that all the faculties involved in the management of these drugs must know them in depth, to decide the best treatment for the patient. This position paper, from a group of experts in anticoagulation in Argentina, can help the general practitioner in the daily use of direct oral anticoagulants based on the new evidence and the experience of a wide group of professionals. The way we relate to the anticoagulant treatment has changed in the last years. The doctors who work with them must also do so.

Los anticoagulantes orales directos han surgido como una de las herramientas que ha cambiado el manejo de la enfermedad trombótica en los últimos 15 años. Sus ventajas, desde el punto de vista de la facilidad de uso y menor riesgo de sangrado, especialmente de sangrado cerebral, han posicionado a estos nuevos anticoagulantes como la primera alternativa de tratamiento en las dos indicaciones más frecuentes en que necesitamos estas drogas, la fibrilación auricular y la enfermedad tromboembólica venosa. Sin embargo, no todos los pacientes pueden recibir estos agentes, no todos los anticoagulantes directos tienen las mismas propiedades y fundamentalmente, no todas las enfermedades con indicación de un anticoagulante pueden tratarse con ellos;con lo cual es necesario que todos los profesionales que están involucrados en el manejo de estos medicamentos estén obligados a conocerlos en profundidad, para poder decidir el mejor tratamiento en cada caso particular. Este documento de posición de expertos de diferentes especialidades de Argentina, presenta lineamientos para el uso correcto de los anticoagulantes directos en base a nueva evidencia y a la experiencia de uso de un amplio grupo de profesionales. La forma de relacionarnos con el tratamiento anticoagulante ha cambiado. Los médicos que trabajamos con ellos también debemos hacerlo.

¿Cuál es el impacto emocional de los resultados de estudios genéticos en pacientes oncológicos con sospecha de síndrome hereditario para cáncer? / What is the emotional impact of the genetic test results on oncologic patients with suspected hereditary cancer syndrome?

Objetivos: valorar el impacto emocional de recibir los resultados del estudio genético (EG) en pacientes con antecedente oncológico personal y sospecha de síndrome hereditario, aplicando el Cuestionario Multidimensional del Impacto de la evaluación de riesgo de cáncer (MICRA). Método: 219 pacientes con diagnóstico oncológico que concurrieron a la consulta de Asesoramiento Genético Oncológico en el Instituto Alexander Fleming entre 2014 y 2019, fueron evaluados aplicando el MICRA. Resultados: Edad promedio 49,84 (42,21; 62,02), 82,2% con diagnóstico de cáncer de mama. En un 16% se halló una variante patogénica (VP). La media de los puntajes obtenidos por cada subescala fue: 5,26 (DS=4,48, rango 0-22) para Malestar Emocional (ME); 12,31 (DS 7,42 rango 0-37) para Incertidumbre (I); 16,36 (DS 4.30 rango 2-20) para Experiencias Positivas (EP) y de 34,37 (DS 10,24 rango 8-62) para la puntuación global, lo que muestra un bajo nivel de ME e I y la presencia de EP entre los pacientes. Se hallaron diferencias significativas según tipo de resultado: los portadores de VP, mostraron una modesta elevación del nivel de ME y menor puntuación en EP, respecto de aquellos que tuvieron resultados no informativos o inciertos. Sin diferencias significativas según edad, pacientes con o sin hijos, o tiempo entre la realización del estudio y la aplicación del cuestionario. Conclusiones: Recibir resultados de estudio genético no produciría un impacto psicológico adverso. Las puntuaciones altas de esta escala podrían ser usadas para identificar a pacientes con malestar emocional y ofrecerles un seguimiento psicooncológico específico (AU)

Objective: The aim of our study is to assess the emotional impact of genetic test results disclosure to patients with a personal cancer history and suspected hereditary syndrome, applying the Multidimensional Impact of Cancer Risk Assessment (MICRA) Questionnaire. Methods: two hundred nineteen patients affected with cancer, referred to the Cancer Genetic Counseling department at the Alexander Fleming Institute, between 2014 and 2019, were evaluated using the MICRA questionnaire. Results: Average age 49.84 (42,21; 62,02), 82.2% presented breast cancer. In 16% a pathogenic variant (PV) was found. The mean of the scores obtained for each subscale in the questionnaire was 5.26 (0-22, SD 4.48) for Distress (D); 12.31 (0-37, DS 7.42) for Uncertainty (U); 16.36 (2-20 SD 4.30) for Positive Experiences (PE) and 34.37 (8-62 SD 10.24) for the global score, which shows a low level of D and U and the presence of PE among the patients. Significant differences were found according to the type of result: We found modestly increased distress in PV carriers compared to patients who received uninformative or negative test results. No significant differences according to age, patients with or without children, or time between the completion of the genetic test and the application of the questionnaire. Conclusion: Genetic test disclosure does not seem to produce an adverse psychological impact. High scores on this scale could be used to identify patients with emotional distress and offer them specific psycho-oncological follow-up (AU)

Immunogenicity induced by the use of alternative vaccine platforms to deal with vaccine shortages in a low- to middle-income country: Results of two randomized clinical trials.

BACKGROUND: Shortages of component two of Sputnik V vaccine (rAd5) are delaying the possibility of achieving full immunisation. The immunogenic response associated with the use of alternative schemes to complete the scheme was not explored. METHODS: We did two non-inferiority randomized clinical trials with outcomes measures blinded to investigators on adults aged 21-65 years, vaccinated with a single dose of rAd26 ≥ 30 days before screening and no history of SARS-CoV-2. Participants were assigned (1:1:1:1:1) to receive either rAd5; ChAdOx1; rAd26; mRNA-1273 or BBIBP-CorV. The primary endpoint was the geometric mean ratio (GMR) of SARS-CoV-2 anti-spike IgG concentration at 28 days after the second dose, when comparing rAd26/rAd5 with rAd26/ChAdOx1, rAd26/rAd26, rAd26/mRNAmRNA-1273 and rAd26/BBIBP-CorV. Serum neutralizing capacity was evaluated using wild type SARS-CoV-2 reference strain 2019 B.1. The safety outcome was 28-day rate of serious adverse. The primary analysis included all participants who received ≥ 1 dose. The studies were registered with NCT04962906 and NCT05027672. Both trials were conducted in Buenos Aires, Argentina. FINDINGS: Between July 6 and August 3, 2021, 540 individuals (age 56·7 [SD 7·3]; 243 (45%) women) were randomly assigned to received rAd5 (n=150); ChAdOx1 (n=150); rAd26 (N=87); mRNAmRNA-1273 (n=87) or BBIBP-CorV (n=65). 524 participants completed the study. As compared with rAd26/rAd5 (1·00), the GMR (95%CI) at day 28 was 0·65 (0·51-0·84) among those who received ChAdOx1; 0·47 (0·34-0·66) in rAd5; 3·53 (2·68-4·65) in mRNA-1273 and 0·23 (0·16-0·33) in BBIBP-CorV. The geometric mean (IU/ml) from baseline to day 28 within each group increased significantly with ChAdOx1 (4·08 (3·07-5·43)); rAd26 (2·69 (1·76-4·11)); mRNA-1273 (21·98 (15·45-31·08)) but not in BBIBP-CorV (1·22 (0·80-1·87)). INTERPRETATION: Except for mRNA-1273 which proved superior, in all other alternatives non-inferiority was rejected. Antibody concentration increased in all non-replicating viral vector and RNA platforms. FUNDING: The trials were supported (including funding, material support in the form of vaccines and testing supplies) by the Buenos Aires City Government.