Gastritis inducida por pembrolizumab con expresión histológica de PDL1 / Pembrolizumab-induced gastritis with PDL1 histological expression

Resumen La gastritis inmunomediada es un efecto adverso raro en pacientes bajo tratamiento con inhibidores del punto de control inmunitario; se presenta el caso de una pa ciente con carcinoma de cuello uterino bajo tratamiento con pembrolizumab que ingresa con náuseas, vómitos y pérdida de peso. La endoscopía demostró una lesión ulcerada cubierta por moco en antro y cuerpo gástrico. La biopsia reveló una extensa denudación de la muco sa gástrica con material fibrinoleucocitario. La lámina propia presentó incremento del infiltrado inflamatorio linfocitario y polimorfonuclear. La inmunohistoquímica confirmó positividad para PDL1 (clon SP2630) y un score positivo combinado (CPS) del 35%, con una contribución relativa de células epiteliales de 25% y de células infla matorias de 10%. Luego de tres semanas de tratamiento con 30 mg de meprednisona, la endoscopía constató un estómago con contenido mucoso claro; fundus y cuerpo sin lesiones, antro con mucosa congestiva y múltiples úlceras extensas y superficiales cubiertas por fibrina. Se describen los aspectos diagnósticos y terapéuticos de la gastritis inmunomediada.

Abstract Immune-mediated gastritis is a rare adverse effect in patients treated with immune checkpoint inhibitors. We present a patient with a diagnosis of cervical carcinoma under treatment with pembrolizumab who was admitted with nausea, vomiting and weight loss; an endoscopy revealed a ulcerated lesion covered by mucus in the antrum and gastric body. The biopsy revealed extensive denudation of the gastric mucosa with fibrin leukocyte reaction. Into the lamina propria, an increased lymphocytic and polymorphonuclear inflammatory infiltrate was ob served. Immunohistochemistry confirmed positivity for PDL1 (clone SP2630) and combined positive score of 35%, with a relative contribution of epithelial cells of 25% and inflammatory cells of 10%. After three weeks with 30 mg meprednisone, a new endoscopy revealed a stomach with clear mucus content; fundus and body without lesions, and an antrum with congestive mucosa and multiple su perficial ulcers covered by fibrin. Diagnostic and therapeu tic aspects of immune-mediated gastritis are described.

[Pembrolizumab-induced gastritis with PDL1 histological expression]. / Gastritis inducida por pembrolizumab con expresión histológica de PDL1.

Immune-mediated gastritis is a rare adverse effect in patients treated with immune checkpoint inhibitors. We present a patient with a diagnosis of cervical carcinoma under treatment with pembrolizumab who was admitted with nausea, vomiting and weight loss; an endoscopy revealed a ulcerated lesion covered by mucus in the antrum and gastric body. The biopsy revealed extensive denudation of the gastric mucosa with fibrin leukocyte reaction. Into the lamina propria, an increased lymphocytic and polymorphonuclear inflammatory infiltrate was observed. Immunohistochemistry confirmed positivity for PDL1 (clone SP2630) and combined positive score of 35%, with a relative contribution of epithelial cells of 25% and inflammatory cells of 10%. After three weeks with 30 mg meprednisone, a new endoscopy revealed a stomach with clear mucus content; fundus and body without lesions, and an antrum with congestive mucosa and multiple superficial ulcers covered by fibrin. Diagnostic and therapeutic aspects of immune-mediated gastritis are described.

La gastritis inmunomediada es un efecto adverso raro en pacientes bajo tratamiento con inhibidores del punto de control inmunitario; se presenta el caso de una paciente con carcinoma de cuello uterino bajo tratamiento con pembrolizumab que ingresa con náuseas, vómitos y pérdida de peso. La endoscopía demostró una lesión ulcerada cubierta por moco en antro y cuerpo gástrico. La biopsia reveló una extensa denudación de la mucosa gástrica con material fibrinoleucocitario. La lámina propia presentó incremento del infiltrado inflamatorio linfocitario y polimorfonuclear. La inmunohistoquímica confirmó positividad para PDL1 (clon SP2630) y un score positivo combinado (CPS) del 35%, con una contribución relativa de células epiteliales de 25% y de células inflamatorias de 10%. Luego de tres semanas de tratamiento con 30 mg de meprednisona, la endoscopía constató un estómago con contenido mucoso claro; fundus y cuerpo sin lesiones, antro con mucosa congestiva y múltiples úlceras extensas y superficiales cubiertas por fibrina. Se describen los aspectos diagnósticos y terapéuticos de la gastritis inmunomediada.

Rheumatological adverse events secondary to immune checkpoint inhibitors.

The first experiences with a group of drugs called immune checkpoint inhibitors for the treatment of cancer were described in 2010. They are currently used in many tumours, with successful survival outcomes but a new profile of adverse events. This new spectrum of immune-mediated toxicities includes an exaggerated inflammatory response of T lymphocyte and the development of autoimmune diseases or similar pathologies. Of these, of particular note are the rheumatological toxicities. This review aims to alert internists and rheumatologists to their recognition and clinical management.

Determinants of the clinical presentation of acute coronary syndromes / Determinantes de la presentación clínica de los síndromes coronarios agudos

Abstract Introduction: Two clinical presentations of acute coronary syndrome (ACS) have been defined: ST- segment elevation ACS (STEACS) or non-ST-segment elevation ACS (NSTEACS). The mecha nism that determines the clinical presentation of ACS is not clearly understood. The aim of this study was to define the association between cardiovascular risk factors and other clinical variables with the clinical presentation of ACS as STEACS or NSTEACS. Methods: We analyzed data of patients prospectively included in the Epi-Cardio Registry with a diagnosis of ACS from April 2006 to April 2018. A total of 10 019 patients were included in the study. Results: In the multivariate analysis, male sex (OR 1.5) and active smoking (OR 1.71) were positively associated with STEACS presentation. Conversely, hypertension (OR 0.71), dyslipidemia (OR 0.74), age (OR 0.97 per quintile), history of myocardial infarction (OR 0.57), chronic angina (OR 0.44), presence of comorbidities (OR 0.64), and extension of coronary heart disease (OR 0.84) were negatively associated with STEACS. Women differed from men by presenting a higher incidence of NSTEACS, due to a greater proportion of ACS without obstructive coronary heart disease. Conclusion: Some cardiovascular risk factors and other clinical variables are independently associated with the presentation of ACS as ST EACS or NSTEACS. These findings confirm the influence of risk factors and clinical history on the pathophysiology, clinical and electrocardiographic presentation of ACS.

Resumen Introducción: Existen dos formas de presentación clínica de los síndromes coronarios agudos (SCA): con elevación del segmento ST (SCACEST) y sin elevación (SCASEST). Los mecanismos que determi nan ambas presentaciones no se conocen completamente. El objetivo del estudio fue definir la asociación entre factores de riesgo cardiovascular y otras variables clínicas con la presentación de los SCA como SCACEST o SCASEST. Métodos: Analizamos información de pacientes incluidos prospectivamente en el Registro Epi-Cardio con diagnóstico de SCA desde abril de 2006 a abril de 2018.Se incluyeron un total de 10 019 pacientes. Resul tados: En el análisis multivariado, el sexo masculino (OR 1.5) y el tabaquismo activo (OR 1.71) se asociaron positivamente con el SCACEST. Contrariamente, la hipertensión (OR 0.71), las dislipidemias (OR 0.74), la edad (OR 0.97 por quintilo), historia de infarto (OR 0.57), angina crónica (OR 0.44), presencia de comorbilidades (OR 0.64), y la extensión de enfermedad coronaria (OR 0.84) se asociaron negativamente con el SCACEST. Las mujeres presentaron mayor incidencia de SCASEST, debido a una mayor proporción de SCA sin obstrucción coronaria significativa. Conclusión: Concluimos que algunos factores de riesgo cardiovascular y otras variables clínicas se asociaron independientemente con la presentación clínica como SCACEST o SCASEST, confirmando su influencia en la fisiopatología y en la presentación clínica y electrocardiográfica de los SCA.

Eventos adversos reumatológicos secundarios al uso de inhibidores de punto de control inmunitario / Rheumatological adverse events secondary to immune checkpoint inhibitors

En 2010 se conocieron las primeras experiencias con un grupo de medicamentos denominados inhibidores de los puntos de control inmunitario (IPCI) para el tratamiento del cáncer. Actualmente se utilizan en diferentes tumores y estadios, mejorando la sobrevida de los pacientes pero generando un nuevo perfil de toxicidad. Este nuevo espectro de toxicidades inmunomediadas (irAE) es generado por una exagerada respuesta inflamatoria de linfocitosT que puede desarrollar enfermedades autoinmunes o patologías similares. Entre ellas se hallan las toxicidades reumatológicas. Esta revisión se propone alertar a los internistas y reumatólogos a reconocer las irAE reumatológicas y conocer su manejo clínico.(AU)

The first experiences with a group of drugs called immune checkpoint inhibitors for the treatment of cancer were described in 2010. They are currently used in many tumours, with successful survival outcomes but a new profile of adverse events. This new spectrum of immune-mediated toxicities includes an exaggerated inflammatory response of Tlymphocyte and the development of autoimmune diseases or similar pathologies. Of these, of particular note are the rheumatological toxicities. This review aims to alert internists and rheumatologists to their recognition and clinical management.(AU)

Determinants of the clinical presentation of acute coronary syndromes.

INTRODUCTION: Two clinical presentations of acute coronary syndrome (ACS) have been defined: ST- segment elevation ACS (STEACS) or non-ST-segment elevation ACS (NSTEACS). The mechanism that determines the clinical presentation of ACS is not clearly understood. The aim of this study was to define the association between cardiovascular risk factors and other clinical variables with the clinical presentation of ACS as STEACS or NSTEACS. METHODS: We analyzed data of patients prospectively included in the Epi-Cardio Registry with a diagnosis of ACS from April 2006 to April 2018. A total of 10 019 patients were included in the study. RESULTS: In the multivariate analysis, male sex (OR 1.5) and active smoking (OR 1.71) were positively associated with STEACS presentation. Conversely, hypertension (OR 0.71), dyslipidemia (OR 0.74), age (OR 0.97 per quintile), history of myocardial infarction (OR 0.57), chronic angina (OR 0.44), presence of comorbidities (OR 0.64), and extension of coronary heart disease (OR 0.84) were negatively associated with STEACS. Women differed from men by presenting a higher incidence of NSTEACS, due to a greater proportion of ACS without obstructive coronary heart disease. CONCLUSION: Some cardiovascular risk factors and other clinical variables are independently associated with the presentation of ACS as ST EACS or NSTEACS. These findings confirm the influence of risk factors and clinical history on the pathophysiology, clinical and electrocardiographic presentation of ACS.

Introducción: Existen dos formas de presentación clínica de los síndromes coronarios agudos (SCA): con elevación del segmento ST (SCACEST) y sin elevación (SCASEST). Los mecanismos que determinan ambas presentaciones no se conocen completamente. El objetivo del estudio fue definir la asociación entre factores de riesgo cardiovascular y otras variables clínicas con la presentación de los SCA como SCACEST o SCASEST. Métodos: Analizamos información de pacientes incluidos prospectivamente en el Registro Epi-Cardio con diagnóstico de SCA desde abril de 2006 a abril de 2018.Se incluyeron un total de 10 019 pacientes. Resultados: En el análisis multivariado, el sexo masculino (OR 1.5) y el tabaquismo activo (OR 1.71) se asociaron positivamente con el SCACEST. Contrariamente, la hipertensión (OR 0.71), las dislipidemias (OR 0.74), la edad (OR 0.97 por quintilo), historia de infarto (OR 0.57), angina crónica (OR 0.44), presencia de comorbilidades (OR 0.64), y la extensión de enfermedad coronaria (OR 0.84) se asociaron negativamente con el SCACEST. Las mujeres presentaron mayor incidencia de SCASEST, debido a una mayor proporción de SCA sin obstrucción coronaria significativa. Conclusión: Concluimos que algunos factores de riesgo cardiovascular y otras variables clínicas se asociaron independientemente con la presentación clínica como SCACEST o SCASEST, confirmando su influencia en la fisiopatología y en la presentación clínica y electrocardiográfica de los SCA.

Impact of high neutrophil-to-lymphocyte ratio on survival in hospitalized cancer patients with COVID-19.

Neutrophil-to-lymphocyte ratio (NLR) has been studied as a prognostic factor for mortality in COVID-19 patients. Our study aimed to evaluate the association between NLR at COVID-19 diagnosis and survival during the following 90 days in hospitalized patients with solid cancer. Between May 2020 and June 2021, 120 patients were included in a retrospective cohort study. Univariable analysis showed patients with an NLR > 8.3 were associated with an increased risk of death (HR: 4.34; 95% CI: 1.74-10.84) compared to patients with NLR < 3.82 and with NLR ≥3.82 and ≤8.30 (HR: 2.89; 95% CI: 1.32-6.36). Furthermore, on multivariable analysis, NLR > 8.30 independently correlated with increased mortality. In patients with solid malignancies with COVID-19, an NLR > 8.3 is associated with an increased risk of death.

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.

[Clinical outcomes in cancer patients hospitalized with COVID-19]. / Evolución clínica de pacientes internados con cáncer e infección por COVID-19.

Cancer patients are exposed to more complications from COVID-19 than non-cancer patients. We report a cohort of 74 cancer patients (87.8% with solid neoplasia and 12.2% with hematological diseases) with COVID-19 infection admitted to a tertiary medical cancer center in Argentina. Pulmonary infiltrates were diagnosed at admission in 78.3% (N = 58) of the cases. COVID-19 infection was hospital-acquired in 20 (27.0%) patients. Thirty-nine patients (52.7%) received anticancer therapy within the 30 days prior to COVID-19 diagnosis; one was on radiation therapy. Twenty-four (32.4%) patients were admitted in the intensive care unit (ICU) and 18 (75.0%) required mechanical ventilation. All cause in-hospital mortality was 32.4% (N = 24) and ICU mortality was 62.5% (N = 15). Mortality under mechanical ventilation was 72.2% (N = 13). In the univariate analysis age, neutrophil count, neutrophil/lymphocyte index, D-dimer, ferritin, smoking, and nosocomial acquired infection were associated with in-hospital mortality. There were no statistically significant differences in mortality related to disease stage for solid tumors, neither cancer treatment within 30 days of COVID-19 diagnosis. Age and smoking were associated with mortality in the multivariate analysis. The adjusted odds ratios (95 CI) for age = 65 years and smoking were 8.87 (1.35-58.02) and 8.64 (1.32 - 56.64), respectively. Our experience can be useful for other institutions that assist cancer patients during the pandemic.

Los pacientes con cáncer y COVID-19 tienen más complicaciones que la población general. Comunicamos una cohorte de 74 pacientes con cáncer y COVID-19 internados en una institución oncológica. El 87.8% tenía diagnóstico de tumores sólidos y 12.2% oncohematológicos. Entre los tumores sólidos, el 61.5% presentó enfermedad metastásica. El 78.3% (N = 58) tenía infiltrados pulmonares al diagnóstico de COVID-19. La infección fue intrahospitalaria en 20 pacientes. Habían recibido tratamiento antineoplásico dentro de los 30 días anteriores al diagnóstico 39 pacientes (52.7%); uno se encontraba recibiendo radioterapia. Veinticuatro pacientes (32.4%) se derivaron a terapia intensiva (UTI) y 18 (75%) de ellos requirieron asistencia respiratoria mecánica (ARM). La mortalidad general durante la internación fue 32.4% (N = 24). La mortalidad en UTI fue 62.5% (N = 15). La mortalidad en ARM fue 72.2% (N = 13). La edad, recuento de neutrófilos, índice neutrófilo/linfocito, dímero D, ferritina, tabaquismo y haber adquirido la infección durante la internación resultaron estadísticamente significativos en el análisis univariado para mortalidad. No hallamos diferencias en mortalidad por estadio de enfermedad, en los pacientes con tumores sólidos, ni por haber recibido tratamiento antineoplásico dentro de los 30 días del diagnóstico de COVID-19. En el análisis multivariado con el modelo de regresión logística, solo la edad y el tabaquismo fueron predictores de mortalidad. Los odds ratios (IC 95) ajustados para la edad =65 años y el tabaquismo fueron 8.87 (1.35-58.02) y 8.64 (1.32-56.64), respectivamente. Este trabajo puede resultar de utilidad para instituciones polivalentes que asistan pacientes oncológicos durante la pandemia.

[Descriptive analysis of 4776 patients admitted to medical clinic services for COVID-19. Results of the Argentine Multi-Center Registry - REMA-COVID-19]. / Análisis descriptivo de 4776 pacientes internados en servicios de clínica médica por COVID-19. Resultados del Registro Multicéntrico Argentino - REMA-COVID-19.

A multicenter registry that included adults hospitalized for COVID-19 was carried out in various provinces of Argentina, from March to October 2020. The objectives were to describe the epidemiological characteristics, clinical manifestations, treatments, complications and risk factors, need for admission to critical care units and mortality. The registry included information on 4776 patients in 37 health centers in Argentina. Of them, 70.2% came from the city of Buenos Aires and from Buenos Aires Province; 52.3% were men. The mean age was 56 years (SD 20.3). Of them, 13.1% stated that they were health personnel. The median time of symptoms at the time of hospitalization was 3 days (CI 1-6). The most frequent comorbidities were hypertension in 32.4% and diabetes mellitus in 15.8%. The most frequent symptoms were: cough 58%, odynophagia 23.3%, myalgia 20.5% and fever / low-grade fever 19.9%. The hospital stay had a median of 8 days (CI 4-15). A 14.8% of the patients required critical care, while 3.2% who also required it, were not transferred to a closed unit due to adequacy of the therapeutic effort. The most frequent complications in critical care were: cardiovascular events (54.1%), septic shock (33.3%), renal failure (9.7%) and pneumonia associated with mechanical ventilation (12.5%). Overall mortality was 12.3%. Old age, dementia and COPD behaved as independent predictors of mortality (p < 0.001, 0.007 and 0.002 respectively) in the multivariate analysis.

Se realizó un registro multicéntrico que incluyó personas adultas internadas por COVID-19 en varias provincias de la Argentina, desde marzo a octubre de 2020. Los objetivos fueron describir las características epidemiológicas, manifestaciones clínicas, tratamientos, complicaciones y factores de riesgo, necesidad de admisión a unidades de cuidados críticos y mortalidad. El registro incluyó información de 4776 pacientes, en 37 centros de salud de Argentina. El 70.2% provenían de la ciudad de Buenos Aires y la provincia de Buenos Aires. El 52.3% eran hombres. La media de edad fue de 56 años (DE 20.3). Un 13.1% de pacientes manifestó ser personal de salud. La mediana de tiempo de síntomas al momento de la internación fue de 3 días (IC 1-6). Las comorbilidades más frecuentes fueron hipertensión arterial en 32.4% y diabetes mellitus en 15.8%. Los síntomas más frecuentes fueron: tos 58%, odinofagia 23.3%, mialgias 20.5% y fiebre/febrícula 19.9%. La estadía hospitalaria tuvo una mediana de internación de 8 días (IC 4-15). El 14.8% de los pacientes requirió cuidados críticos, en tanto que el 3.2%, que también lo requería, no pasó a unidad cerrada por adecuación del esfuerzo terapéutico. Las complicaciones más frecuentes en cuidados críticos fueron: eventos cardiovasculares (54.1%), shock séptico (33.3%), insuficiencia renal (9.7%) y neumonía asociada a la ventilación mecánica (12.5%). La mortalidad global fue del 12.3%. La edad avanzada, demencia y EPOC se comportaron como predictores independientes de mortalidad (p < 0.001, 0.007 y 0.002 respectivamente) en el análisis multivariado.

Evolución clínica de pacientes internados con cáncer e infección por COVID-19 / Clinical outcomes in cancer patients hospitalized with COVID-19

Resumen Los pacientes con cáncer y COVID-19 tienen más complicaciones que la población general. Comunicamos una cohorte de 74 pacientes con cáncer y COVID-19 internados en una institución on cológica. El 87.8% tenía diagnóstico de tumores sólidos y 12.2% oncohematológicos. Entre los tumores sólidos, el 61.5% presentó enfermedad metastásica. El 78.3% (N = 58) tenía infiltrados pulmonares al diagnóstico de COVID-19. La infección fue intrahospitalaria en 20 pacientes. Habían recibido tratamiento antineoplásico den tro de los 30 días anteriores al diagnóstico 39 pacientes (52.7%); uno se encontraba recibiendo radioterapia. Veinticuatro pacientes (32.4%) se derivaron a terapia intensiva (UTI) y 18 (75%) de ellos requirieron asistencia respiratoria mecánica (ARM). La mortalidad general durante la internación fue 32.4% (N = 24). La mortalidad en UTI fue 62.5% (N = 15). La mortalidad en ARM fue 72.2% (N = 13). La edad, recuento de neutrófilos, índice neutrófilo/linfocito, dímero D, ferritina, tabaquismo y haber adquirido la infección durante la internación resultaron estadísticamente significativos en el análisis univariado para mortalidad. No hallamos diferencias en mortalidad por estadio de enfermedad, en los pacientes con tumores sólidos, ni por haber recibido tratamiento antineoplá sico dentro de los 30 días del diagnóstico de COVID-19. En el análisis multivariado con el modelo de regresión logística, solo la edad y el tabaquismo fueron predictores de mortalidad. Los odds ratios (IC 95) ajustados para la edad ≥65 años y el tabaquismo fueron 8.87 (1.35-58.02) y 8.64 (1.32-56.64), respectivamente. Este trabajo puede resultar de utilidad para instituciones polivalentes que asistan pacientes oncológicos durante la pandemia.

Abstract Cancer patients are exposed to more complications from COVID-19 than non-cancer patients. We report a cohort of 74 cancer patients (87.8% with solid neoplasia and 12.2% with hematological diseases) with COVID-19 infection admitted to a tertiary medical cancer center in Argentina. Pulmonary infiltrates were diagnosed at admission in 78.3% (N = 58) of the cases. COVID-19 infection was hospital-acquired in 20 (27.0%) patients. Thirty-nine patients (52.7%) received anticancer therapy within the 30 days prior to COVID-19 diagnosis; one was on radiation therapy. Twenty-four (32.4%) patients were admitted in the intensive care unit (ICU) and 18 (75.0%) required mechanical ventilation. All cause in-hospital mortality was 32.4% (N = 24) and ICU mortality was 62.5% (N = 15). Mortality under me chanical ventilation was 72.2% (N = 13). In the univariate analysis age, neutrophil count, neutrophil/lymphocyte index, D-dimer, ferritin, smoking, and nosocomial acquired infection were associated with in-hospital mortality. There were no statistically significant differences in mortality related to disease stage for solid tumors, neither cancer treatment within 30 days of COVID-19 diagnosis. Age and smoking were associated with mortality in the multivariate analysis. The adjusted odds ratios (95 CI) for age ≥ 65 years and smoking were 8.87 (1.35-58.02) and 8.64 (1.32 - 56.64), respectively. Our experience can be useful for other institutions that assist cancer patients during the pandemic.

Análisis descriptivo de 4776 pacientes internados en servicios de clínica médica POR COVID-19. Resultados del Registro Multicéntrico Argentino - REMA-COVID-19 / Descriptive analysis of 4776 patients admitted to medical clinic services for COVID-19. Results of the Argentine Multi-Center Registry - REMA-COVID-19

Resumen Se realizó un registro multicéntrico que incluyó personas adultas internadas por COVID-19 en varias provincias de la Argentina, desde marzo a octubre de 2020. Los objetivos fueron describir las características epidemiológicas, manifestaciones clínicas, tratamientos, complicaciones y factores de riesgo, necesidad de admisión a unidades de cuidados críticos y mortalidad. El registro incluyó información de 4776 pacientes, en 37 centros de salud de Argentina. El 70.2% provenían de la ciudad de Buenos Aires y la provincia de Buenos Aires. El 52.3% eran hombres. La media de edad fue de 56 años (DE 20.3). Un 13.1% de pacientes manifestó ser personal de salud. La mediana de tiempo de síntomas al momento de la internación fue de 3 días (IC 1-6). Las comorbilidades más frecuentes fueron hipertensión arterial en 32.4% y diabetes mellitus en 15.8%. Los síntomas más frecuentes fueron: tos 58%, odinofagia 23.3%, mialgias 20.5% y fiebre/febrícula 19.9%. La estadía hospitalaria tuvo una mediana de internación de 8 días (IC 4-15). El 14.8% de los pacientes requirió cuidados críticos, en tanto que el 3.2%, que también lo requería, no pasó a unidad cerrada por adecuación del esfuerzo terapéutico. Las complicaciones más frecuentes en cuidados críticos fueron: eventos cardiovasculares (54.1%), shock séptico (33.3%), insuficiencia renal (9.7%) y neumonía asociada a la ventilación mecánica (12.5%). La mortalidad global fue del 12.3%. La edad avanzada, demencia y EPOC se comportaron como predictores independientes de mortalidad (p < 0.001, 0.007 y 0.002 respectivamente) en el análisis multivariado.

Abstract A multicenter registry that in cluded adults hospitalized for COVID-19 was carried out in various provinces of Argentina, from March to October 2020. The objectives were to describe the epidemiological characteristics, clinical manifestations, treatments, complications and risk factors, need for admission to critical care units and mortality. The registry included information on 4776 patients in 37 health centers in Argentina. Of them, 70.2% came from the city of Buenos Aires and from Buenos Aires Province; 52.3% were men. The mean age was 56 years (SD 20.3). Of them, 13.1% stated that they were health personnel. The median time of symptoms at the time of hospitalization was 3 days (CI 1-6). The most frequent comorbidities were hypertension in 32.4% and diabetes mellitus in 15.8%. The most frequent symptoms were: cough 58%, odynophagia 23.3%, myalgia 20.5% and fever / low-grade fever 19.9%. The hospital stay had a median of 8 days (CI 4-15). A 14.8% of the patients required critical care, while 3.2% who also required it, were not transferred to a closed unit due to adequacy of the thera peutic effort. The most frequent complications in critical care were: cardiovascular events (54.1%), septic shock (33.3%), renal failure (9.7%) and pneumonia associated with mechanical ventilation (12.5%). Overall mortality was 12.3%. Old age, dementia and COPD behaved as independent predictors of mortality (p < 0.001, 0.007 and 0.002 respectively) in the multivariate analysis.

Hypothyroid cardiomyopathy: A reversible phenocopy of hypertrophic cardiomyopathy.

We present the case of a 46-year-old patient with hypothyroidism secondary to Hashimoto's thyroiditis who was admitted with decompensation in the form of myxedema. A 2-D echocardiogram shows a septal asymmetric hypertrophy, with low-voltage QRS complex in the ECG and a bull's-eye map of longitudinal strain with preserved apical strain with reduction of mid and basal strain that results in "cherry on the top" pattern, similar to the most frequent phenocopy of hypertrophic cardiomyopathy, as is the cardiac amyloidosis, and that, unlike this pathology, reverted after the patient reached the euthyroid state.

Reacciones adversas a medicamentos inhibidores del punto de control inmunitario / Adverse drug reactions associated with immune checkpoint inhibitors

Resumen El manejo de las reacciones adversas inducidas por los inhibidores del punto de control inmunitario (IPCI) en cáncer, demanda un trabajo multidisciplinario. Revisamos las causas y el curso clínico de las consultas e internaciones debidas a reacciones adversas de los IPCI entre septiembre de 2015 y julio de 2019 en el Instituto Alexander Fleming. Se registraron los datos demográficos, diagnóstico oncológico, reacción adversa y su grado, requerimiento de internación, tratamiento, mortalidad y evaluación de la reexposición. Se registraron 124 reacciones adversas por IPCI en 89 pacientes. Sesenta y ocho recibían monoterapia y 21 terapia combinada. Las manifestaciones cutáneas fueron las más frecuentes, seguidas de las generales, endocrinas (con mayor frecuencia hipotiroidismo), colitis, neumonitis, neurológicas y hepatitis. Fueron graves (grado ≥ 3), 26 toxicidades en 25 pacientes. Se internaron 15, y 6 de ellos requirieron terapia intensiva. Un caso fue fatal. Recibieron glucocorticoides 34 (12 de ellos por vía intravenosa). Un paciente recibió micofenolato y uno inmuno globulina endovenosa. En 20 se discontinuó el tratamiento. Ocho se reexpusieron y uno de ellos debió suspender definitivamente. Se presenta en esta serie de casos nuestra experiencia con el diagnóstico y tratamiento de las reacciones adversas de una familia de drogas cuya utilización ha crecido en los últimos años.

Abstract The management of patients with immune-related adverse events (irAEs) frequently demands a multidisciplinary approach. We reviewed the causes and clinical course of medical visits and admissions at the Instituto Alexander Fleming due to irAEs between September 2015 and July 2019. Demographic data, diagnosis, toxicity and its severity, requirement of admission, treatment, mortality, and evaluation of the re-administration of immunotherapy were collected. We found 124 irAEs in 89 patients. Sixty-eight of them received monotherapy (76.4%) and 21 (23.6%) combination of drugs. Cutaneous manifestations were the most frequent cause of irAEs, followed by general manifestations, endocrine dysfunctions (hypothyroidism the most frequent), colitis, pneumonitis, neurologic dis orders, and hepatitis. In 26 adverse events (in 25 patients), severity grade was ≥ 3. Fifteen were admitted and 6 required ICU admission. One patient died. Thirty-four received glucocorticoids, 12 of them by intravenous route. One patient received mycophenolate and one IVIG. In 20, the treatment was discontinued; 8 were re-exposed, with definitive discontinuation in one patient. In this case series we report our experience in the diagnosis and management of adverse reactions related to a family of drugs whose use has grown in recent years.