Short Course of Antibiotic Therapy for Gram-Negative Bacilli Bacteremia in Patients with Cancer and Hematopoietic Stem Cell Transplantation: Less Is Possible.

Data about short courses of antibiotic therapy for Gram-negative bacilli (GNB) bacteremia in immunosuppressed patients are limited. This is a prospective observational study performed on adult patients with cancer and hematopoietic stem cell transplant (HSCT) who developed GNB bacteremia and received appropriate empirical antibiotic therapy (EAT), had a clinical response within 7 days and survived 48 h after the end of therapy. They received antibiotic therapy in the range of 7-15 days and were divided into short course, with a median of 7 days (SC), or long course, with a median of 14 days (LC). Seventy-four patients were included (SC: 36 and LC: 38). No differences were observed in baseline characteristics or in the presence of neutropenia: 58.3% vs. 60.5% (p = 0.84). Clinical presentation and microbiological characteristics were similar in SC and LC, respectively: clinical source of bacteremia 72.2% vs. 76.3% (p = 0.68); shock 2.8% vs. 10.5% (p = 0.35) and multidrug-resistant GNB 27.8% vs. 21.1% (p = 0.50). Overall, mortality was 2.8% vs. 7.9% (p = 0.61), and bacteremia relapse was 2.8% vs. 0 (p = 0.30). The length of hospitalization since bacteremia was 7 days (interquartile range (IQR), 6-15) for SC and 12 days (IQR, 7-19) (p = 0.021) for LC. In the case of patients with cancer or HSCT and GNB bacteremia who receive appropriate EAT with clinical response, 7 days of antibiotic therapy might be adequate.

Prevalence of Chagas Disease and Associated Factors in an Endemic Area of Northeastern Argentina.

Chagas disease caused by Trypanosoma cruzi, remains one of the leading public health problems in Latin America. The number of infections in nonendemic countries continues to rise as a consequence of migratory flows. Updated information on prevalence, especially in treatable stages, together with vector eradication programs are key factors in an attempt to control the disease. We aim to estimate the prevalence of T. cruzi infection in an endemic area of Argentina and to describe epidemiological and clinical factors related to the disease. This is a cross-sectional study in an endemic rural area of Argentina. Our target population was people between 10 and 20 years of age, collecting demographic, clinical, and electrocardiographic data and seroprevalence against T. cruzi. We included 460 subjects; 76.7% did not have drinking water; 49.3% reported the presence of Triatoma infestans at home; 79.1% had pets or birds; 72.6% lived close to a chicken coop; 24.6% lived in adobe houses; 27.8% lived in overcrowded conditions. Seroprevalence was 9.33%. In the multivariate analysis, the presence of Triatoma infestans at home (OR 2.08, P = 0.03) had an association with seropositivity. No relevant findings indicating acute or chronic organ involvement were detected. We found no correlation of right bundle branch block (RBBB) and Chagas disease in our population. None of the infected patients were previously aware of their condition, highlighting the importance of active surveillance to detect infection in a potentially treatable stage, especially in areas with difficult access to health programs.

Efficacy of a Nasal Spray Containing Iota-Carrageenan in the Postexposure Prophylaxis of COVID-19 in Hospital Personnel Dedicated to Patients Care with COVID-19 Disease.

BACKGROUND: Iota-Carrageenan (I-C) is a sulfate polysaccharide synthesized by red algae, with demonstrated antiviral activity and clinical efficacy as nasal spray in the treatment of common cold. In vitro, I-C inhibits SARS-CoV-2 infection in cell culture. RESEARCH QUESTION: Can a nasal spray with Iota-Carrageenan be useful in the prophylaxis of COVID-19 in health care workers managing patients with COVID-19 disease? STUDY DESIGN AND METHODS: This is a pilot pragmatic multicenter, randomized, double-blind, placebo-controlled study assessing the use of a nasal spray containing I-C in the prophylaxis of COVID-19 in hospital personnel dedicated to care of COVID-19 patients. Clinically healthy physicians, nurses, kinesiologists and other health care providers managing patients hospitalized for COVID-19 were assigned in a 1:1 ratio to receive four daily doses of I-C spray or placebo for 21 days. The primary end point was clinical COVID-19, as confirmed by reverse transcriptase polymerase chain reaction testing, over a period of 21 days. The trial is registered at ClinicalTrials.gov (NCT04521322). RESULTS: A total of 394 individuals were randomly assigned to receive I-C or placebo. Both treatment groups had similar baseline characteristics. The incidence of COVID-19 differs significantly between subjects receiving the nasal spray with I-C (2 of 196 [1.0%]) and those receiving placebo (10 of 198 [5.0%]). Relative risk reduction: 79.8% (95% CI 5.3 to 95.4; p=0.03). Absolute risk reduction: 4% (95% CI 0.6 to 7.4). INTERPRETATION: In this pilot study a nasal spray with I-C showed significant efficacy in preventing COVID-19 in health care workers managing patients with COVID-19 disease. CLINICAL TRIALS REGISTRATION: NCT04521322.

[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.

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.

Corrigendum to Antiviral effect of high-dose ivermectin in adults with COVID-19: A proof-of-concept randomized trial [EClinicalMedicine 37 (2021) 100,959]".

[This corrects the article DOI: 10.1016/j.eclinm.2021.100959.].

Antiviral effect of high-dose ivermectin in adults with COVID-19: A proof-of-concept randomized trial.

BACKGROUND: There are limited antiviral options for the treatment of patients with COVID-19. Ivermectin (IVM), a macrocyclic lactone with a wide anti-parasitary spectrum, has shown potent activity against SARS-CoV-2 in vitro. This study aimed at assessing the antiviral effect of IVM on viral load of respiratory secretions and its relationship with drug concentrations in plasma. METHODS: Proof-of-concept, pilot, randomized, controlled, outcome-assessor blinded trial to evaluate antiviral activity of high-dose IVM in 45 COVID-19 hospitalized patients randomized in a 2:1 ratio to standard of care plus oral IVM at 0·6 mg/kg/day for 5 days versus standard of care in 4 hospitals in Argentina. Eligible patients were adults with RT-PCR confirmed SARS-CoV-2 infection within 5 days of symptoms onset. The primary endpoint was the difference in viral load in respiratory secretions between baseline and day-5, by quantitative RT-PCR. Concentrations of IVM in plasma were measured. Study registered at ClinicalTrials.gov: NCT04381884. FINDINGS: 45 participants were recruited (30 to IVM and 15 controls) between May 18 and September 9, 2020. There was no difference in viral load reduction between groups but a significant difference was found in patients with higher median plasma IVM levels (72% IQR 59-77) versus untreated controls (42% IQR 31-73) (p = 0·004). Mean ivermectin plasma concentration levels correlated with viral decay rate (r: 0·47, p = 0·02). Adverse events were similar between groups. No differences in clinical evolution at day-7 and day-30 between groups were observed. INTERPRETATION: A concentration dependent antiviral activity of oral high-dose IVM was identified at a dosing regimen that was well tolerated. Large trials with clinical endpoints are necessary to determine the clinical utility of IVM in COVID-19. FUNDING: This work was supported by grant IP-COVID-19-625, Agencia Nacional de Promoción de la Investigación, el Desarrollo Tecnológico y la Innovación, Argentina and Laboratorio ELEA/Phoenix, Argentina.

Budget impact analysis of using procalcitonin to optimize antimicrobial treatment for patients with suspected sepsis in the intensive care unit and hospitalized lower respiratory tract infections in Argentina.

BACKGROUND: Inappropriate antibiotic use represents a major global threat. Sepsis and bacterial lower respiratory tract infections (LRTIs) have been linked to antimicrobial resistance, carrying important consequences for patients and health systems. Procalcitonin-guided algorithms may represent helpful tools to reduce antibiotic overuse but the financial burden is unclear. The aim of this study was to estimate the healthcare and budget impact in Argentina of using procalcitonin-guided algorithms to guide antibiotic prescription. METHODS: A decision tree was used to model health and cost outcomes for the Argentinean health system, over a one-year duration. Patients with suspected sepsis in the intensive care unit and hospitalized patients with LRTI were included. Model parameters were obtained from a focused, non-systematic, local and international bibliographic search, and validated by a panel of local experts. Deterministic and probabilistic sensitivity analyses were performed to analyze the uncertainty of parameters. RESULTS: The model predicted that using procalcitonin-guided algorithms would result in 734.5 [95% confidence interval (CI): 1,105.2;438.8] thousand fewer antibiotic treatment days, 7.9 [95% CI: 18.5;8.5] thousand antibiotic-resistant cases avoided, and 5.1 [95% CI: 6.7;4.2] thousand fewer Clostridioides difficile cases. In total, this would save $422.4 US dollars (USD) [95% CI: $935;$267] per patient per year, meaning cost savings of $83.0 [95% CI: $183.6;$57.7] million USD for the entire health system and $0.4 [95% CI: $0.9;$0.3] million USD for a healthcare provider with 1,000 cases per year of sepsis and LRTI patients. The sensitivity analysis showed that the probability of cost-saving for the sepsis patient group was lower than for the LRTI patient group (85% vs. 100%). CONCLUSIONS: Healthcare and financial benefits can be obtained by implementing procalcitonin-guided algorithms in Argentina. Although we found results to be robust on an aggregate level, some caution must be used when focusing only on sepsis patients in the intensive care unit.

Early High-Titer Plasma Therapy to Prevent Severe Covid-19 in Older Adults.

BACKGROUND: Therapies to interrupt the progression of early coronavirus disease 2019 (Covid-19) remain elusive. Among them, convalescent plasma administered to hospitalized patients has been unsuccessful, perhaps because antibodies should be administered earlier in the course of illness. METHODS: We conducted a randomized, double-blind, placebo-controlled trial of convalescent plasma with high IgG titers against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in older adult patients within 72 hours after the onset of mild Covid-19 symptoms. The primary end point was severe respiratory disease, defined as a respiratory rate of 30 breaths per minute or more, an oxygen saturation of less than 93% while the patient was breathing ambient air, or both. The trial was stopped early at 76% of its projected sample size because cases of Covid-19 in the trial region decreased considerably and steady enrollment of trial patients became virtually impossible. RESULTS: A total of 160 patients underwent randomization. In the intention-to-treat population, severe respiratory disease developed in 13 of 80 patients (16%) who received convalescent plasma and 25 of 80 patients (31%) who received placebo (relative risk, 0.52; 95% confidence interval [CI], 0.29 to 0.94; P = 0.03), with a relative risk reduction of 48%. A modified intention-to-treat analysis that excluded 6 patients who had a primary end-point event before infusion of convalescent plasma or placebo showed a larger effect size (relative risk, 0.40; 95% CI, 0.20 to 0.81). No solicited adverse events were observed. CONCLUSIONS: Early administration of high-titer convalescent plasma against SARS-CoV-2 to mildly ill infected older adults reduced the progression of Covid-19. (Funded by the Bill and Melinda Gates Foundation and the Fundación INFANT Pandemic Fund; Dirección de Sangre y Medicina Transfusional del Ministerio de Salud number, PAEPCC19, Plataforma de Registro Informatizado de Investigaciones en Salud number, 1421, and ClinicalTrials.gov number, NCT04479163.).

Coagulopatía y Covid-19. Recomendaciones para una realidad cambiante / Coagulopathy and COVID-19. Recommendations for a changing reality

La pandemia COVID-19 provocada por el betacoronavirus SARS-CoV-2 exige rápidas respuestas desde el campo de la medicina. El riesgo de tromboembolismo venoso y arterial está aumentado durante la infección, especialmente en pacientes críticos. En ese contexto se destaca una coagulopatía caracterizada por niveles elevados de dímero D, con tendencia a la falla multiorgánica, y aumento de la mortalidad. Esas anormalidades de la hemostasia responden a varios mecanismos que deben tenerse en cuenta para la toma de decisiones terapéuticas. Analizamos la evidencia científica disponible en la que se fundamenta el enfoque terapéutico de la coagulopatía descripta y sus complicaciones, con el objetivo de diseñar recomendaciones terapéuticas realistas tendientes a disminuir la morbilidad y la mortalidad en pacientes con COVID-19

The coronavirus disease 2019 (COVID-19) pandemic requires rapid medical responses. The risk of venous and arterial thromboembolism increases in critically ill patients with SARS-CoV-2 infection. There is a hypercoagulable state that includes elevated levels of D-dimer, with an increased risk of organ failure and increased mortality. The abnormalities described in hemostasis should be considered for therapeutic decision making. We analyzed the available scientific evidence for the therapeutic approach of coagulopathy in the course of the disease with the objective of designing realistic therapeutic recommendations aimed at reducing morbidity and mortality in patients with COVID-19

Plasma de convalecientes como terapia para la neumonía por COVID-19 grave / Convalescent plasma as a therapy for severe COVID-19 pneumonia

Resumen La pandemia de COVID-19, presentó desde su inicio elevada mortalidad, sin tratamiento efectivo para pacientes graves. Basados en experiencia previa con plasma de convaleciente en fiebre hemorrágica Argentina, incorporamos a un estudio multicéntrico 90 pacientes con COVID-19 de los que 87 fueron evaluables. Colectamos 397 donaciones de plasma de 278 convalecientes. El plasma fue suministrado con una concentración de IgG de 0.7-0.8 (medidos por quimioluminiscencia Abbott) por cada 10 kg/ peso. La supervivencia a 28 días fue la variable de resultado primario. El 77% fueron varones, edad 54 ± 15.6 años (rango: 27-85); índice de masa corporal de 29.7 ± 4.4; tenían hipertensión 39%, diabetes 20.7%; 19.5% tenían alguna condición de inmunosupresión, y el 23% era personal de salud. Se administró plasma a 55 (63%) en respiración espontánea con oxígeno (con máscara reservorio en 80%), y a 32 (37%) en ventilación mecánica. La supervivencia global a 28 días fue del 80%; 91% en quienes recibían oxígeno suplementario y 63% en los que permanecían en ventilación mecánica (p = 0.0002). Hubo mejora significativa en la escala clínica de neumonía de la OMS a los 7 y a los 14 días. La ferritina, LDH y PaO /FiO, mejoraron en la semana post-infusión. Observamos un episodio de sobrecarga de volumen circulatorio y una reacción febril, leves. Las infusiones de plasma de convaleciente son factibles, seguras y potencialmente efectivas, especialmente antes de requerir ventilación mecánica. Constituyen una opción clínica atractiva para tratar formas graves de COVID-19 hasta que estén disponibles otras terapias eficaces.

Abstract The COVID-19 pandemic presented high mortality from its beginning, without effective treatment for seriously ill patients. Build on the experience in Argentine hemorrhagic fever with convalescent plasma, we incorporated 90 patients with COVID-19, of which 87 were evaluable, into a multicenter study. We collected 397 plasma donations from 278 convalescent donors. Patients received plasma with an IgG concentration of 0.7-0.8 (measured by Abbott chemiluminescence) for every 10 kg of body weight. Survival during the first 28 days was the primary objective; 77% were male, age 54 ± 15.6 y/o (range 27-85), body mass index 29.7 ± 4.4; hypertension 39% and diabetes 20.7%; 19.5% had an immunosuppressive condition, 23% were health workers. Plasma was administered to 55 (63%) on spontaneous breathing with oxygen supplementation (mainly oxygen mask with reservoir bag in 80%), and to 32 patients (37%) on mechanical ventilation. The 28-day survival rate was 80%; 91% in patients infused on spontaneous breathing and 63% in those on mechanical ventilation (p = 0.0002). There was a significant improvement in the WHO pneumonia clinical scale at 7 and 14 days, and in PaO / FiO , ferritin and LDH, in the week post-infusion. We observed an episode of circulatory volume overload and a febrile reaction, both mild. Convalescent plasma infusions are feasible, safe, and potentially effective, especially before requiring mechanical ventilation. They are an attractive clinical option for treating severe forms of COVID-19 until other effective therapies become available.

[Coagulopathy and COVID-19. Recommendations for a changing reality]. / Coagulopatía y COVID-19. Recomendaciones para una realidad cambiante.

The coronavirus disease 2019 (COVID-19) pandemic requires rapid medical responses. The risk of venous and arterial thromboembolism increases in critically ill patients with SARS-CoV-2 infection. There is a hypercoagulable state that includes elevated levels of D-dimer, with an increased risk of organ failure and increased mortality. The abnormalities described in hemostasis should be considered for therapeutic decision making. We analyzed the available scientific evidence for the therapeutic approach of coagulopathy in the course of the disease with the objective of designing realistic therapeutic recommendations aimed at reducing morbidity and mortality in patients with COVID-19.

La pandemia COVID-19 provocada por el betacoronavirus SARS-CoV-2 exige rápidas respuestas desde el campo de la medicina. El riesgo de tromboembolismo venoso y arterial está aumentado durante la infección, especialmente en pacientes críticos. En ese contexto se destaca una coagulopatía caracterizada por niveles elevados de dímero D, con tendencia a la falla multiorgánica, y aumento de la mortalidad. Esas anormalidades de la hemostasia responden a varios mecanismos que deben tenerse en cuenta para la toma de decisiones terapéuticas. Analizamos la evidencia científica disponible en la que se fundamenta el enfoque terapéutico de la coagulopatía descripta y sus complicaciones, con el objetivo de diseñar recomendaciones terapéuticas realistas tendientes a disminuir la morbilidad y la mortalidad en pacientes con COVID-19.

Coagulopatía y covid-19. recomendaciones para una realidad cambiante / Coagulopathy and COVID-19. Recommendations for a changing reality

Resumen La pandemia COVID-19 provocada por el betacoronavirus SARS-CoV-2 exige rápidas respuestas desde el campo de la medicina. El riesgo de tromboembolismo venoso y arterial está aumentado durante la infección, especialmente en pacientes críticos. En ese contexto se destaca una coagulopatía caracterizada por niveles elevados de dímero D, con tendencia a la falla multiorgánica, y aumento de la mortalidad. Esas anormalidades de la hemostasia responden a varios mecanismos que deben tenerse en cuenta para la toma de decisiones terapéuticas. Analizamos la evidencia científica disponible en la que se fundamenta el enfoque terapéutico de la coagulopatía descripta y sus complicaciones, con el objetivo de diseñar recomendaciones terapéuticas realistas tendientes a disminuir la morbilidad y la mortalidad en pacientes con COVID-19.

Abstract The coronavirus disease 2019 (COVID-19) pandemic requires rapid medical responses. The risk of venous and arterial thromboembolism increases in critically ill patients with SARS-CoV-2 infection. There is a hypercoagulable state that includes elevated levels of D-dimer, with an increased risk of organ failure and increased mortality. The abnormalities described in hemostasis should be considered for therapeutic decision making. We analyzed the available scientific evidence for the therapeutic approach of coagulopathy in the course of the disease with the objective of designing realistic therapeutic recommendations aimed at reducing morbidity and mortality in patients with COVID-19.

[Convalescent plasma as a therapy for severe COVID-19 pneumonia]. / Plasma de convalecientes como terapia para la neumonía por COVID-19 grave.

The COVID-19 pandemic presented high mortality from its beginning, without effective treatment for seriously ill patients. Build on the experience in Argentine hemorrhagic fever with convalescent plasma, we incorporated 90 patients with COVID-19, of which 87 were evaluable, into a multicenter study. We collected 397 plasma donations from 278 convalescent donors. Patients received plasma with an IgG concentration of 0.7-0.8 (measured by Abbott chemiluminescence) for every 10 kg of body weight. Survival during the first 28 days was the primary objective; 77% were male, age 54 ± 15.6 y/o (range 27-85), body mass index 29.7 ± 4.4; hypertension 39% and diabetes 20.7%; 19.5% had an immunosuppressive condition, 23% were health workers. Plasma was administered to 55 (63%) on spontaneous breathing with oxygen supplementation (mainly oxygen mask with reservoir bag in 80%), and to 32 patients (37%) on mechanical ventilation. The 28-day survival rate was 80%; 91% in patients infused on spontaneous breathing and 63% in those on mechanical ventilation (p = 0.0002). There was a significant improvement in the WHO pneumonia clinical scale at 7 and 14 days, and in PaO2 / FiO2, ferritin and LDH, in the week post-infusion. We observed an episode of circulatory volume overload and a febrile reaction, both mild. Convalescent plasma infusions are feasible, safe, and potentially effective, especially before requiring mechanical ventilation. They are an attractive clinical option for treating severe forms of COVID-19 until other effective therapies become available.

La pandemia de COVID-19, presentó desde su inicio elevada mortalidad, sin tratamiento efectivo para pacientes graves. Basados en experiencia previa con plasma de convaleciente en fiebre hemorrágica Argentina, incorporamos a un estudio multicéntrico 90 pacientes con COVID-19 de los que 87 fueron evaluables. Colectamos 397 donaciones de plasma de 278 convalecientes. El plasma fue suministrado con una concentración de IgG de 0.7-0.8 (medidos por quimioluminiscencia Abbott) por cada 10 kg/ peso. La supervivencia a 28 días fue la variable de resultado primario. El 77% fueron varones, edad 54 ± 15.6 años (rango: 27-85); índice de masa corporal de 29.7 ± 4.4; tenían hipertensión 39%, diabetes 20.7%; 19.5% tenían alguna condición de inmunosupresión, y el 23% era personal de salud. Se administró plasma a 55 (63%) en respiración espontánea con oxígeno (con máscara reservorio en 80%), y a 32 (37%) en ventilación mecánica. La supervivencia global a 28 días fue del 80%; 91% en quienes recibían oxígeno suplementario y 63% en los que permanecían en ventilación mecánica (p = 0.0002). Hubo mejora significativa en la escala clínica de neumonía de la OMS a los 7 y a los 14 días. La ferritina, LDH y PaO2/FiO2, mejoraron en la semana post-infusión. Observamos un episodio de sobrecarga de volumen circulatorio y una reacción febril, leves. Las infusiones de plasma de convaleciente son factibles, seguras y potencialmente efectivas, especialmente antes de requerir ventilación mecánica. Constituyen una opción clínica atractiva para tratar formas graves de COVID-19 hasta que estén disponibles otras terapias eficaces.

Gas exchange and lung mechanics in patients with acute respiratory distress syndrome: comparison of three different strategies of positive end expiratory pressure selection.

PURPOSE: The purpose of the study was to compare gas exchange and lung mechanics between different strategies to select positive end-expiratory pressure (PEEP) in acute respiratory distress syndrome (ARDS). METHODS: In 20 consecutive ARDS patients, 3 PEEP selection strategies were evaluated. One strategy was based on oxygenation using the ARDS network PEEP/fraction of inspired oxygen (Fio2) table; and two were based on lung mechanics, either PEEP titrated to reach a plateau pressure of 28 to 30 cm H2O as in the ExPress trial or best respiratory compliance method during a derecruitment maneuver. Gas exchange, airway pressures, stress index (SI), and end-expiratory transpulmonary pressure (P(tpe)) and end-inspiratory transpulmonary pressure (P(tpi)) values were assessed. Data are expressed as median (interquartile range [IQR]). RESULTS: Lower total PEEP levels were observed with the use of the PEEP/Fio2 table (8.7 [6-10] cm H2O); intermediate PEEP levels, with the Best Compliance approach (13.0 [10.2-13.8] cm H2O); and higher PEEP levels, with the ExPress strategy (16.5 [15.0-18.5] cm H2O) (P < .01). Pao2/Fio2 ratio was lower with the PEEP/Fio2 table. Oxygenation with Best Compliance approach and ExPress strategy was not different with lower plateau pressure in the former (23 [20-25] vs 30 [29-30] cm H2O; P < .01). Paco2 was slightly higher with the ExPress method than the others 2 strategies. Negative P(tpe) was observed in 35% of the patients with the PEEP/Fio2 table, in 15% applying the Best Compliance, and in only 1 case with the ExPress method. Higher SI and P(tpi), with lower lung compliance, were obtained with ExPress strategy. CONCLUSIONS: Using a best respiratory compliance approach resulted in better oxygenation levels without risk of overdistension according to SI and P(tpi), achieving a mild risk of lung collapse according to P(tpe).

[Rapidly progressive crescentic glomerulonephritis in the elderly]. / Glomerulonefritis rápidamente progresiva en ancianos.

Rapidly progressive glomerulonephritis (RPGN) is a syndrome characterized by glomerular lesions giving rise to acute renal injury that develops within a brief period of time, usually days or a few months. It is classified according to the underlying mechanism of injury and the immunofluorescence findings into four main disorders. In the last decade, nephrologists have witnessed a steady rise in the mean age of the patients diagnosed with RPGN. This observation may reflect an increase in the incidence of this entity and also a more timely diagnosis. We present 3 cases of RPGN in elderly patients, diagnosed within a 3 month period at our institution which illustrates the spectrum of these conditions.

Glomerulonefritis rápidamente progresiva en ancianos / Rapidly progressive crescentic glomerulonephritis in the elderly

La glomerulonefritis rápidamente progresiva (GNRP) es un síndrome clínico que se caracteriza por la presencia de signos urinarios de enfermedad glomerular e insuficiencia renal de desarrollo en un lapso de días a pocos meses. La inmunofluorescencia permite clasificar a las GNRP en cuatro tipos según se identifiquen o no depósitos inmunes y, si están presentes, de acuerdo con su naturaleza. En la última década se ha demostrado un aumento constante en el promedio de edad de los pacientes con GNRP. Este fenómeno podría reflejar tanto una mayor incidencia de la enfermedad, como un incremento en la tasa de diagnóstico. Se presentan 3 casos de GNRP en adultos mayores de 65 años, diagnosticados en un periodo de 3 meses en nuestra institución.

Rapidly progressive glomerulonephritis (RPGN) is a syndrome characterized by glomerular lesions giving rise to acute renal injury that develops within a brief period of time, usually days or a few months. It is classified according to the underlying mechanism of injury and the immunofluorescence findings into four main disorders. In the last decade, nephrologists have witnessed a steady rise in the mean age of the patients diagnosed with RPGN. This observation may reflect an increase in the incidence of this entity and also a more timely diagnosis. We present 3 cases of RPGN in elderly patients, diagnosed within a 3-month period at our institution which illustrates the spectrum of these conditions.

Glomerulonefritis rápidamente progresiva en ancianos / Rapidly progressive crescentic glomerulonephritis in the elderly

La glomerulonefritis rápidamente progresiva (GNRP) es un síndrome clínico que se caracteriza por la presencia de signos urinarios de enfermedad glomerular e insuficiencia renal de desarrollo en un lapso de días a pocos meses. La inmunofluorescencia permite clasificar a las GNRP en cuatro tipos según se identifiquen o no depósitos inmunes y, si están presentes, de acuerdo con su naturaleza. En la última década se ha demostrado un aumento constante en el promedio de edad de los pacientes con GNRP. Este fenómeno podría reflejar tanto una mayor incidencia de la enfermedad, como un incremento en la tasa de diagnóstico. Se presentan 3 casos de GNRP en adultos mayores de 65 años, diagnosticados en un periodo de 3 meses en nuestra institución.(AU)

Rapidly progressive glomerulonephritis (RPGN) is a syndrome characterized by glomerular lesions giving rise to acute renal injury that develops within a brief period of time, usually days or a few months. It is classified according to the underlying mechanism of injury and the immunofluorescence findings into four main disorders. In the last decade, nephrologists have witnessed a steady rise in the mean age of the patients diagnosed with RPGN. This observation may reflect an increase in the incidence of this entity and also a more timely diagnosis. We present 3 cases of RPGN in elderly patients, diagnosed within a 3-month period at our institution which illustrates the spectrum of these conditions.(AU)