RBD-specific polyclonal F(ab´)2 fragments of equine antibodies in patients with moderate to severe COVID-19 disease: A randomized, multicenter, double-blind, placebo-controlled, adaptive phase 2/3 clinical trial.

BACKGROUND: passive immunotherapy is a therapeutic alternative for patients with COVID-19. Equine polyclonal antibodies (EpAbs) could represent a source of scalable neutralizing antibodies against SARS-CoV-2. METHODS: we conducted a double-blind, randomized, placebo-controlled trial to assess efficacy and safety of EpAbs (INM005) in hospitalized adult patients with moderate and severe COVID-19 pneumonia in 19 hospitals of Argentina. Primary endpoint was improvement in at least two categories in WHO ordinal clinical scale at day 28 or hospital discharge (ClinicalTrials.gov number NCT04494984). FINDINGS: between August 1st and October 26th, 2020, a total of 245 patients were enrolled. Enrolled patients were assigned to receive two blinded doses of INM005 (n = 118) or placebo (n = 123). Median age was 54 years old, 65•1% were male and 61% had moderate disease at baseline. Median time from symptoms onset to study treatment was 6 days (interquartile range 5 to 8). No statistically significant difference was noted between study groups on primary endpoint (risk difference [95% IC]: 5•28% [-3•95; 14•50]; p = 0•15). Rate of improvement in at least two categories was statistically significantly higher for INM005 at days 14 and 21 of follow-up. Time to improvement in two ordinal categories or hospital discharge was 14•2 (± 0•7) days in the INM005 group and 16•3 (± 0•7) days in the placebo group, hazard ratio 1•31 (95% CI 1•0 to 1•74). Subgroup analyses showed a beneficial effect of INM005 over severe patients and in those with negative baseline antibodies. Overall mortality was 6•9% the INM005 group and 11•4% in the placebo group (risk difference [95% IC]: 0•57 [0•24 to 1•37]). Adverse events of special interest were mild or moderate; no anaphylaxis was reported. INTERPRETATION: Albeit not having reached the primary endpoint, we found clinical improvement of hospitalized patients with SARS-CoV-2 pneumonia, particularly those with severe disease.

[Post-neurosurgical infections. Update and intersociety recommendations]. / Infecciones postneuroquirúrgicas. Puesta al día y recomendaciones intersociedades.

Infections associated with neurosurgical procedures are serious complications that contribute to the morbidity and mortality of neurocritical patients, as well as to the prolongation of the stay in the ICU and the hospital. The diagnosis is complex since there is no gold standard, so it is based on clinical suspicion, CSF physical-chemical examination, and microbial isolation. Treatment should be initiated early, guided by local epidemiology. The duration will depend on the causative microorganism, its sensitivity and the availability of antibiotic treatments that are effective at the site of infection. The implementation of preventive measures with proven efficacy minimizes the risk of infection. This SADI-SATI intersociety update reviews relevant data recently published on this area at the national at international level regarding epidemiology, diagnostic methodologies, therapeutic approaches, and prevention guidelines.

Las infecciones asociadas a procedimientos neuroquirúrgicos son complicaciones graves que contribuyen a la morbimortalidad de los pacientes neurocríticos, así como también a la prolongación de la estancia en la UTI y/o en el hospital. El diagnóstico es complejo ya que no se dispone de gold standard y se apoya en la sospecha clínica, las alteraciones físico-químicas del líquido cefalorraquídeo y el aislamiento microbiano. El tratamiento debe ser precoz y guiado por la epidemiología local. La duración dependerá del microorganismo causal, su sensibilidad y la disponibilidad de tratamientos antibióticos efectivos en el sitio de la infección. La implementación de medidas de prevención con evidencia demostrada minimiza el riesgo de infección. Esta puesta al día intersociedades SADI-SATI presenta datos epidemiológicos (internacionales y locales), métodos diagnósticos, tratamiento, y pautas de prevención, considerando las publicaciones más relevantes de los últimos años sobre el tema.

Infecciones postneuroquiróºrgicas: Puesta al día y recomendaciones intersociedades / Post-neurosurgical infections. Update and intersociety recommendations

Las infecciones asociadas a procedimientos neuroquiró;ºrgicos son complicaciones graves que contribuyen a la morbimortalidad de los pacientes neurocríticos, así como tambín a la prolongació;n de la estancia en la UTI y/o en el hospital. El diagnó;stico es complejo ya que no se dispone de gold standard y se apoya en la sospecha clínica, las alteraciones físico-químicas del líquido cefalorraquídeo y el aislamiento microbiano. El tratamiento debe ser precoz y guiado por la epidemiología local. La duració;n dependerá del microorganismo causal, su sensibilidad y la disponibilidad de tratamientos antibió;ticos efectivos en el sitio de la infecció;n. La implementació;n de medidas de prevenció;n con evidencia demostrada minimiza el riesgo de infecció;n. Esta puesta al día intersociedades SADI-SATI presenta datos epidemioló;gicos (internacionales y locales), mó;©todos diagnó;sticos, tratamiento, y pautas de prevenció;n, considerando las publicaciones más relevantes de los ó;ºltimos aó;±os sobre el tema.

Infections associated with neurosurgical procedures are serious complications that contribute to the morbidity and mortality of neurocritical patients, as well as to the prolongation of the stay in the ICU and the hospital. The diagnosis is complex since there is no gold standard, so it is based on clinical suspicion, CSF physical-chemical examination, and microbial isolation. Treatment should be initiated early, guided by local epidemiology. The duration will depend on the causative microorganism, its sensitivity and the availability of antibiotic treatments that are effective at the site of infection. The implementation of preventive measures with proven efficacy minimizes the risk of infection. This SADI-SATI intersociety update reviews relevant data recently published on this area at the national at international level regarding epidemiology, diagnostic methodologies, therapeutic approaches, and prevention guidelines.

[An update on catheter-associated urinary tract infection. Inter-Society recommendations]. / Infección del tracto urinario asociada a sonda vesical. Actualización y recomendaciones intersociedades.

Representatives of the Argentine Society of Infectious Diseases (SADI) and the Argentine Society of Intensive Therapy (SATI) issued the present recommendations on diagnosis, treatment, and prevention of catheter associated urinary tract infection (CA-UTI). Articles published during 2006-2016 were analyzed in the light of experts' opinion and local data. This document aims to offer basic strategies to optimize the diagnosis based on clinical and microbiological criteria, provide guidance in empirical and targeted antibiotic schemes, and promote effective measures to reduce the risk of CA-UTI. The joint work of both societies highlights the experts' concern about the mismanagement of CA-UTI, which is associated to the indiscriminate use of antimicrobials, and the importance of improving daily practices of CA-UTI management. Through these recommendations, local guidelines are established to optimize the diagnosis, treatment and prevention of CAUTI in order to reduce morbimortality, days of hospitalization, costs and antibiotic resistance due to the misuse of antimicrobials.

Infección del tracto urinario asociada a sonda vesical: Actualización y recomendaciones intersociedades / An update on catheter-associated urinary tract infection. Inter-Society recommendations

Representantes de la Sociedad Argentina de Infectología (SADI) y la Sociedad Argentina de Terapia Intensiva (SATI) acordaron la elaboración de recomendaciones de diagnóstico, tratamiento y prevención de la infección del tracto urinario asociada a sonda vesical (ITU-SV). La metodología utilizada fue el análisis de la bibliografía publicada en 2006-2016, complementada con la opinión de expertos y datos epidemiológicos locales. En este documento se pretende ofrecer herramientas básicas de optimización de diagnóstico en base a criterios clínicos y microbiológicos, orientación en los esquemas antibióticos empíricos y dirigidos, y promover las medidas efectivas para reducir el riesgo de ITU-SV. Se destaca la preocupación por el control y tratamiento inadecuados de la ITU-SV, en particular el uso indiscriminado de antimicrobianos y la importancia de garantizar la mejora en las prácticas diarias. Se establecen pautas locales para mejorar la prevención, optimizar el diagnóstico y tratamiento de la ITU-SV, y así disminuir la morbimortalidad, los días de internación, los costos y la resistencia a antibióticos debidos al mal uso de los antimicrobianos.

Representatives of the Argentine Society of Infectious Diseases (SADI) and the Argentine Society of Intensive Therapy (SATI) issued the present recommendations on diagnosis, treatment, and prevention of catheter associated urinary tract infection (CA-UTI). Articles published during 2006-2016 were analyzed in the light of experts' opinion and local data. This document aims to offer basic strategies to optimize the diagnosis based on clinical and microbiological criteria, provide guidance in empirical and targeted antibiotic schemes, and promote effective measures to reduce the risk of CA-UTI. The joint work of both societies highlights the experts' concern about the mismanagement of CA-UTI, which is associated to the indiscriminate use of antimicrobials, and the importance of improving daily practices of CA-UTI management. Through these recommendations, local guidelines are established to optimize the diagnosis, treatment and prevention of CAUTI in order to reduce morbimortality, days of hospitalization, costs and antibiotic resistance due to the misuse of antimicrobials.

[Embolism predictors of infective endocarditis]. / Variables predictoras de embolias en endocarditis infecciosa.

The embolic event (EE) increases the morbidity and mortality of infective endocarditis (IE). Prevalence of EE ranges between 22% and 50%, death rates being up to 25% of patients. EE may occur prior to diagnosis, during treatment or afterwards. The objective of this study was to evaluate the demographic, clinical, microbiological, echocardiographic and therapeutic characteristics in patients suffering from IE (with or without emboli) in order to determine predictors for EE. A descriptive study based on observations of patient population diagnosed with IE was conducted at the Hospital Italiano of La Plata during the period March 1996 - December 2004. Fifty-three patients with IE were analyzed (35 without EE and 18 with EE) in retrospect. We found that the presence of vegetations in the transthoracic (TTE) and/or transesophagic (TEE) echocardiographies at the time of diagnosis, the size > or = 10 mm and the compromise of the native mitral valve were the variables that showed significant statistical association with EE to be considered as predictors. The size _ 10 mm was the only variable associated with EE in the logistic regression analysis. During the elective antibiotic treatment, there was a reduction in EE, without their being present from the second week onwards.

Variables predictoras de embolias en endocarditis infecciosa / Embolism predictors of infective endocarditis

El evento embólico (EE) aumenta la morbi-mortalidad de la endocarditis infecciosa (EI). La prevalencia de EE oscila entre 22% y 50%, pudiendo ocasionar hasta el 25% de las muertes de los pacientes que lo presentan. El EE puede ocurrir previamente al diagnóstico, durante el tratamiento o bien posteriormente al mismo. Nuestro objetivo fue analizar las características demográficas, clínicas, microbiológicas, ecocardiográficas y terapeúticas, de pacientes con EI (con y sin embolias) para tratar de establecer variables predictoras del EE. Se realizó en el Hospital Italiano de La Plata, desde marzo de 1996 hasta diciembre de 2004, un estudio descriptivo observacional de una cohorte de pacientes con diagnóstico de EI. Se analizaron en forma retrospectiva 53 pacientes con EI (35 sin EE y 18 con EE). La presencia de vegetación (en el ecocardiograma transtorácico (ETT) y/o en el transesofágico (ETE) al momento del diagnóstico, el tamaño ³ 10 mm y el compromiso de la válvula mitral nativa, fueron las variables en las que existió una asociación estadísticamente significativa con el EE para ser consideradas como predictoras. El tamaño ³ 10 mm fue la única variable asociada a EE en el análisis de regresión logística. Durante el tratamiento antibiótico electivo hubo una reducción de EE, no observándose a partir de la segunda semana.

The embolic event (EE) increases the morbidity and mortality of infective endocarditis (IE). Prevalence of EE ranges between 22% and 50%, death rates being up to 25% of patients. EE may occur prior to diagnosis, during treatment or afterwards. The objective of this study was to evaluate the demographic, clinical, microbiological, echocardiographic and therapeutic characteristics in patients suffering from IE (with or without emboli) in order to determine predictors for EE. A descriptive study based on observations of patient population diagnosed with IE was conducted at the Hospital Italiano of La Plata during the period March 1996 - December 2004. Fifty-three patients with IE were analyzed (35 without EE and 18 with EE) in retrospect. We found that the presence of vegetations in the transthoracic (TTE) and/or transesophagic (TEE) echocardiographies at the time of diagnosis, the size ³ 10 mm and the compromise of the native mitral valve were the variables that showed significant statistical association with EE to be considered as predictors. The size ³ 10 mm was the only variable associated with EE in the logistic regression analysis. During the elective antibiotic treatment, there was a reduction in EE, without their being present from the second week onwards.

Variables predictoras de embolias en endocarditis infecciosa / Embolism predictors of infective endocarditis

El evento embólico (EE) aumenta la morbi-mortalidad de la endocarditis infecciosa (EI). La prevalencia de EE oscila entre 22% y 50%, pudiendo ocasionar hasta el 25% de las muertes de los pacientes que lo presentan. El EE puede ocurrir previamente al diagnóstico, durante el tratamiento o bien posteriormente al mismo. Nuestro objetivo fue analizar las características demográficas, clínicas, microbiológicas, ecocardiográficas y terapeúticas, de pacientes con EI (con y sin embolias) para tratar de establecer variables predictoras del EE. Se realizó en el Hospital Italiano de La Plata, desde marzo de 1996 hasta diciembre de 2004, un estudio descriptivo observacional de una cohorte de pacientes con diagnóstico de EI. Se analizaron en forma retrospectiva 53 pacientes con EI (35 sin EE y 18 con EE). La presencia de vegetación (en el ecocardiograma transtorácico (ETT) y/o en el transesofágico (ETE) al momento del diagnóstico, el tamaño ³ 10 mm y el compromiso de la válvula mitral nativa, fueron las variables en las que existió una asociación estadísticamente significativa con el EE para ser consideradas como predictoras. El tamaño ³ 10 mm fue la única variable asociada a EE en el análisis de regresión logística. Durante el tratamiento antibiótico electivo hubo una reducción de EE, no observándose a partir de la segunda semana. (AU)

The embolic event (EE) increases the morbidity and mortality of infective endocarditis (IE). Prevalence of EE ranges between 22% and 50%, death rates being up to 25% of patients. EE may occur prior to diagnosis, during treatment or afterwards. The objective of this study was to evaluate the demographic, clinical, microbiological, echocardiographic and therapeutic characteristics in patients suffering from IE (with or without emboli) in order to determine predictors for EE. A descriptive study based on observations of patient population diagnosed with IE was conducted at the Hospital Italiano of La Plata during the period March 1996 - December 2004. Fifty-three patients with IE were analyzed (35 without EE and 18 with EE) in retrospect. We found that the presence of vegetations in the transthoracic (TTE) and/or transesophagic (TEE) echocardiographies at the time of diagnosis, the size ³ 10 mm and the compromise of the native mitral valve were the variables that showed significant statistical association with EE to be considered as predictors. The size ³ 10 mm was the only variable associated with EE in the logistic regression analysis. During the elective antibiotic treatment, there was a reduction in EE, without their being present from the second week onwards.(AU)

Propafenone hepatotoxicity: report of two new cases.

Two patients developed acute cholestatic hepatitis during treatment with propafenone. Viral infections, alcohol abuse, hepatotoxicity by other drugs, and biliary obstruction were excluded as causes. In one patient, liver biopsy showed changes consistent with a drug-associated injury. Another patient had autoimmune antibodies (ANA) in the serum. Following propafenone withdrawal, the clinical and biochemical profiles of both patients improved. Hepatic toxicity from the antiarrhythmic drug propafenone is highly uncommon. Moreover, the drug produces hepatocellular injury by an unknown mechanism. Most of the seven cases reported here had acute cholestatic hepatitis after a latency period of two to four weeks.