Effect of immediate initiation of invasive ventilation on mortality in acute hypoxemic respiratory failure: a target trial emulation.

PURPOSE: Invasive ventilation is a fundamental treatment in intensive care but its precise timing is difficult to determine. This study aims at assessing the effect of initiating invasive ventilation versus waiting, in patients with hypoxemic respiratory failure without immediate reason for intubation on one-year mortality. METHODS: Emulation of a target trial to estimate the benefit of immediately initiating invasive ventilation in hypoxemic respiratory failure, versus waiting, among patients within the first 48-h of hypoxemia. The eligible population included non-intubated patients with SpO2/FiO2 ≤ 200 and SpO2 ≤ 97%. The target trial was emulated using a single-center database (MIMIC-IV) which contains granular information about clinical status. The hourly probability to receive mechanical ventilation was continuously estimated. The hazard ratios for the primary outcome, one-year mortality, and the secondary outcome, 30-day mortality, were estimated using weighted Cox models with stabilized inverse probability weights used to adjust for measured confounding. RESULTS: 2996 Patients fulfilled the inclusion criteria of whom 792 were intubated within 48 h. Among the non-invasive support devices, the use of oxygen through facemask was the most common (75%). Compared to patients with the same probability of intubation but who were not intubated, intubation decreased the hazard of dying for the first year after ICU admission HR 0.81 (95% CI 0.68-0.96, p = 0.018). Intubation was associated with a 30-day mortality HR of 0.80 (95% CI 0.64-0.99, p = 0.046). CONCLUSION: The initiation of mechanical ventilation in patients with acute hypoxemic respiratory failure reduced the hazard of dying in this emulation of a target trial.

Venous thromboembolism in critically ill adult patients with hematologic malignancy: a population-based cohort study.

PURPOSE: The aim of this study was to describe the incidence of venous thromboembolism (VTE) and major bleeding among hospitalized patients with hematologic malignancy, assessing its association with critical illness and other baseline characteristics. METHODS: We conducted a population-based cohort study of hospitalized adults with a new diagnosis of hematologic malignancy in Ontario, Canada, between 2006 and 2017. The primary outcome was VTE (pulmonary embolism or deep venous thrombosis). Secondary outcomes were major bleeding and in-hospital mortality. We compared the incidence of VTE between intensive care unit (ICU) and non-ICU patients and described the association of other baseline characteristics and VTE. RESULTS: Among 76,803 eligible patients (mean age 67 years [standard deviation, SD, 15]), 20,524 had at least one ICU admission. The incidence of VTE was 3.7% in ICU patients compared to 1.2% in non-ICU patients (odds ratio [OR] 3.08; 95% confidence interval [CI] 2.77-3.42). The incidence of major bleeding was 7.6% and 2.4% (OR 3.33; 95% CI 3.09-3.58), respectively. The association of critical illness and VTE remained significant after adjusting for potential confounders (OR 2.92; 95% CI 2.62-3.25). We observed a higher incidence of VTE among specific subtypes of hematologic malignancy and patients with prior VTE (OR 6.64; 95% CI 5.42-8.14). Admission more than 1 year after diagnosis of hematologic malignancy (OR 0.64; 95% CI 0.56-0.74) and platelet count ≤ 50 × 109/L at the time of hospitalization (OR 0.63; 95% CI 0.48-0.84) were associated with a lower incidence of VTE. CONCLUSION: Among patients with hematologic malignancy, critical illness and certain baseline characteristics were associated with a higher incidence of VTE.

Incidence of venous thromboembolic disease and risk of bleeding in critically ill patients with hematologic malignancies: A retrospective study.

OBJECTIVE: Our objectives were to describe the use of thromboprophylaxis and the incidence of VTE/bleeding in critically ill patients with hematologic malignancies (HM). DESIGN: Retrospective cohort study (2014-2022). SETTING: Medic-Surgical Intensive Care Unit (ICU) in a tertiary care academic center. PATIENTS: Adult patients admitted to ICU with a concomitant diagnosis of a hematological malignancy. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: We analyzed demographic data, use of thromboprophylaxis and secondary outcomes that included incidence of VTE (venous thromboembolism), bleeding, mortality, severity scores and organ support. We applied a multivariable logistic regression model to examine the risk of thrombosis in the ICU. RESULTS: We included 862 ICU admissions (813 unique patients). Thromboprophylaxis was given during 65% of admissions (LMWH 14%, UFH 8%, and SCDs 43%); in 21% it was contraindicated due to thrombocytopenia; 14% of cases lacked documentation on prophylaxis. There were 38 unique incident cases of VTE (27 DVT, 11 PE), constituting 4.4% of ICU episodes. Most of VTE cases happened in patients with various degrees of thrombocytopenia. In the multivariable analysis, SOFA score on the first ICU day was independently associated (OR 0.85, 95% CI 0.76-0.96) with the risk of VTE. Bleeding occurred in 7.2% (minor) and 14.4% (major) of episodes; most frequent sites being CNS, abdomen/GI and pulmonary. CONCLUSIONS: In this cohort of critically ill patients with HM, there was considerable variability in the utilization of DVT prophylaxis, with predominant use of SCDs. The incidence of VTE was 4.4% and major bleeding 14%. CLINICAL TRIAL REGISTRATION: NCT05396157. Venous Thromboembolism in Hematologic Malignancy and Hematopoietic Cell Transplant Patients: a Retrospective Study (https://clinicaltrials.gov/).

Long-term survival and functional outcomes of critically ill patients with hematologic malignancies: a Canadian multicenter prospective study.

PURPOSE: Patients with hematologic malignancy (HM) commonly develop critical illness. Their long-term survival and functional outcomes have not been well described. METHODS: We conducted a prospective, observational study of HM patients admitted to seven Canadian intensive care units (ICUs) (2018-2020). We followed survivors at 7 days, 6 months and 12 months following ICU discharge. The primary outcome was 12-month survival. We evaluated functional outcomes at 6 and 12 months using the functional independent measure (FIM) and short form (SF)-36 as well as variables associated with 12-month survival. RESULTS: We enrolled 414 patients including 35% women. The median age was 61 (interquartile range, IQR: 52-69), median Sequential Organ Failure Assessment (SOFA) score was 9 (IQR: 6-12), and 22% had moderate-severe frailty (clinical frailty scale [CFS] ≥ 6). 51% had acute leukemia, 38% lymphoma/multiple myeloma, and 40% had received a hematopoietic stem cell transplant (HCT). The most common reasons for ICU admission were acute respiratory failure (50%) and sepsis (40%). Overall, 203 (49%) were alive 7 days post-ICU discharge (ICU survivors). Twelve-month survival of the entire cohort was 21% (43% across ICU survivors). The proportion of survivors with moderate-severe frailty was 42% (at 7 days), 14% (6 months), and 8% (12 months). Median FIM at 7 days was 80 (IQR: 50-109). Physical function, pain, social function, mental health, and emotional well-being were below age- and sex-matched population scores at 6 and 12 months. Frailty, allogeneic HCT, kidney injury, and cardiac complications during ICU were associated with lower 12- month survival. CONCLUSIONS: 49% of all HM patients were alive at 7 days post-ICU discharge, and 21% at 12 months. Survival varied based upon hematologic diagnosis and frailty status. Survivors had important functional disability and impairment in emotional, physical, and general well-being.

Association between arterial oxygen and mortality across critically ill patients with hematologic malignancies: results from an international collaborative network.

PURPOSE: Patients with hematological malignancies are at high risk for life-threatening complications. To date, little attention has been paid to the impact of hyperoxemia and excess oxygen use on mortality. The aim of this study was to investigate the association between partial pressure of arterial oxygen (PaO2) and 28-day mortality in critically ill patients with hematologic malignancies. METHODS: Data from three international cohorts (Europe, Canada, Oceania) of patients who received respiratory support (noninvasive ventilation, high-flow nasal cannula, invasive mechanical ventilation) were obtained. We used mixed-effect Cox models to investigate the association between day one PaO2 or excess oxygen use (inspired fraction of oxygen ≥ 0.6 with PaO2 > 100 mmHg) on day-28 mortality. RESULTS: 11,249 patients were included. On day one, 5716 patients (50.8%) had normoxemia (60 ≤ PaO2 ≤ 100 mmHg), 1454 (12.9%) hypoxemia (PaO2 < 60 mmHg), and 4079 patients (36.3%) hyperoxemia (PaO2 > 100 mmHg). Excess oxygen was used in 2201 patients (20%). Crude day-28 mortality rate was 40.6%. There was a significant association between PaO2 and day-28 mortality with a U-shaped relationship (p < 0.001). Higher PaO2 levels (> 100 mmHg) were associated with day-28 mortality with a dose-effect relationship. Subgroup analyses showed an association between hyperoxemia and mortality in patients admitted with neurological disorders; however, the opposite relationship was seen across those admitted with sepsis and neutropenia. Excess oxygen use was also associated with subsequent day-28 mortality (adjusted hazard ratio (aHR) [95% confidence interval (CI)]: 1.11[1.04-1.19]). This result persisted after propensity score analysis (matched HR associated with excess oxygen:1.31 [1.20-1.1.44]). CONCLUSION: In critically-ill patients with hematological malignancies, exposure to hyperoxemia and excess oxygen use were associated with increased mortality, with variable magnitude across subgroups. This might be a modifiable factor to improve mortality.

Decline in Ventilatory Ratio as a Predictor of Mortality in Adults With ARDS Receiving Prone Positioning.

BACKGROUND: Prone positioning reduces mortality in patients with moderate/severe ARDS. It remains unclear which physiological parameters could guide clinicians to assess which patients are likely to benefit from prone position. This study aimed to determine the association between relative changes in physiological parameters at 24 h of prone positioning and ICU mortality in adult subjects with ARDS. METHODS: We conducted a cohort study using the VENTILA database, including adults with ARDS receiving prone positioning. We used multivariable logistic regression to assess the association between relative changes in physiological parameters (PaO2 /FIO2 , dynamic driving pressure, PaCO2 , and ventilatory ratio defined as [minute ventilation [mL/min] × PaCO2 [mm Hg]]/[predicted body weight × 100 [mL/min] × 37.5 [mm Hg] with ICU mortality) (primary outcome). We report adjusted odds ratios with 95% CI as measures of association. RESULTS: We included 156 subjects of which 82 (53%) died in the ICU. A relative decline in the ventilatory ratio at 24 h was associated with lower ICU mortality (odds ratio 0.80 [95% CI 0.66-0.97], every 10% decrease). Relative changes in PaO2 /FIO2 (odds ratio 0.89 [95% CI 0.77-1.03], every 25% increase), PaCO2 (odds ratio 0.97 [95% CI 0.82-1.16], every 10% decrease), and dynamic driving pressure (odds ratio 0.98 [95% CI 0.89-1.07], every 10% decrease) were not associated with ICU mortality. CONCLUSIONS: In subjects with ARDS receiving prone positioning, a relative decline in the ventilatory ratio at 24 h was associated with lower ICU mortality.

Características clínicas de la enfermedad por Coronavirus 2019 en un centro de Argentina. Cohorte retrospective / Clinical characteristics of Coronavirus Disease 2019 in a single center of Argentina. Retrospective cohort

Resumen La enfermedad por coronavirus (COVID-19) es un problema prioritario de salud. El objetivo del trabajo fue evaluar las características clínicas, evolución y gravedad de COVID-19 en un centro hospitalario de tercer nivel de la provincia de Buenos Aires, Argentina. Se realizó un estudio de cohorte retrospectiva de pacientes con COVID-19, entre el 3 de marzo y 21 de junio de 2020. Se evaluaron las características en función de la presencia o ausencia de neumonía y de la gravedad de la enfermedad. Se incluyeron 101 pacientes, la mediana de edad fue de 42 años y el 53% mujeres. Los síntomas más frecuentes fueron: fiebre 66% y tos 57%. La disnea y la fiebre se asociaron a la presencia de neumonía. Las comorbilidades más prevalentes fueron: hipertensión 22%, obesidad 18%, enfermedad cardiovascular 7% y enfermedad respiratoria crónica 7%. Los hallazgos de laboratorio más comunes fueron: linfopenia 55%, dímero-D elevado 38% y plaquetopenia 20%. El 26% presentó neumonía y el 24% fue personal de salud. En el 24% de los casos se necesitó más de una muestra de RT-PCR para el diagnóstico. Un valor moderado-alto del Índice de severidad de neumonía (PSI) fue más frecuente en la neumonía grave que en la leve (63 contra 17%, p 0.032). Se registró una mortalidad del 5%. Las características clínicas, la gravedad y evolución fueron similares a las descritas a nivel mundial. Destacamos la proporción elevada del personal de salud infectado, la tasa de falsos negativos de la RT-PCR y la utilidad del PSI para discriminar la gravedad de la neumonía.

Abstract Coronavirus disease (COVID-19) became a priority health problem. The objective was to evaluate the clinical characteristics, evolution and severity of COVID-19 in a third-level hospital, in the province of Buenos Aires, Argentina. We conducted a retrospective cohort of 101 patients with COVID-19 from March 3 to June 21, 2020. The patients were divided according to the presence or absence of pneumonia and the severity of the disease. The median age was 42 years and 53% were women. The most common symptoms were fever 66% and cough 57%. Dyspnea and fever were associated with the presence of pneumonia. The most prevalent comorbidities were: hypertension 22%, obesity 18%, cardiovascular disease 7% and chronic respiratory disease 7%. The presence of any comorbidity and hypertension were more common in severe cases. The most frequent laboratory findings were: lymphopenia 55%, elevated D-dimer 38%, and thrombocytopenia 20%. In severe diseases, the level of C-reactive protein and D-dimer were higher. Twenty six patients had pneumonia and 24% were healthcare workers. For diagnosis, more than one reverse transcriptase polymerase chain reaction (RT-PCR) sample was needed in 24% of cases. A moderate-high value of the Pneumonia Severity Index (PSI) was more prevalent in severe than mild pneumonia (63% vs. 17%, p 0.032). A mortality of 5% was registered (95% CI 1-11%). The clinical characteristics, severity and prognosis were similar to those described worldwide. We highlight a high proportion of healthcare workers were SARS-CoV-2 positive, the false negative rate of the RT-PCR and the usefulness of the PSI to discriminate the severity of pneumonia.

Variables clínicas asociadas al diagnóstico de meningo-encefalitis herpética en pacientes adultos: un estudio anidado de casos y controles / Clinical characteristics of adult patients with herpetic meningoencephalitis: a nested case control study

Introduction: Herpes simplex virus (HSV) is the most common etiology of sporadic encephalitis and presents with an estimated mortality of 50-70%. Objective: To describe baseline characteristics of patients with herpetic encephalitis admitted to a tertiary teaching hospital and their difference with patients with non herpetic encephalitis. Materials and Methods: Nested case control study using a retrospective cohort of patients with suspected encephalitis admitted to the Hospital Italiano de Buenos Aires (2006-2013). Adult patients included had a lumbar puncture with a positive or negative polimerase reaction for HSV. A case of herpetic encephalitis was defined as a positive polimerase reaction in spinal fluid. For each case, 5 controls were randomly selected. Results: There were no baseline differences present between cases and controls. The only covariate associated with herpetic encephalitis was an abnormal brain magnetic resonance imaging (MRI) (OR: 5.37, IC 95% 1.42-20.38, p < 0.01). The most frecuent alterations in the MRI were extratemporal lesions or temporal ones with or without haemorrhage. Discussion: There are no apparent baseline clinical differences between patients with or without herpetic encephalitis. A positive finding in a brain MRI should be taken into account during clinical workup.

Introducción: El virus herpes simplex (VHS) es la causa reportada más común de encefalitis esporádica con una mortalidad estimada de 50 a 70%. Objetivo: Describir las características de los pacientes con encefalitis herpética (EH) en nuestro medio y sus variables clínicas asociadas. Materiales y Métodos: Estudio anidado de casos y controles sobre una cohorte retrospectiva en el Hospital Italiano de Buenos Aires (2006-2013). Se incluyeron pacientes adultos con sospecha de encefalitis a quienes se les realizó una punción lumbar con posterior reacción de polimerasa en cadena para VHS en líquido cefalorraquídeo. Por cada caso (reacción positiva para VHS) se tomaron cinco controles aleatoriamente seleccionados. Resultados: No se observaron diferencias significativas en las características demográficas y clínicas entre los casos de EH y los controles. La única variable clínica asociada al diagnóstico de EH fue la alteración en la resonancia magnética (RM) de cerebro (OR: 5,37, IC 95% 1,4220,38; p < 0,01). Los patrones más comunes de alteración en la RM fueron las lesiones extra-temporales o lesiones temporales con o sin hemorragia. Discusión: Este hallazgo nos hace jerarquizar el hallazgo de un resultado positivo en la RM durante la valoración inicial de un paciente con clínica compatible de EH.

Evaluación de percepciones de residentes de Medicina Interna sobre las instancias de aprendizaje durante la Residencia: un estudio de corte transversal / Internal Medicine residents´ perceptions of education in the Residency Program: a cross-sectional study

Introducción: la Residencia de Medicina Interna del Hospital Italiano de Buenos Aires posee una larga trayectoria en la formación de médicos clínicos e internistas. Existe bibliografía que sugiere que las percepciones de los residentes no son consistentes con las de aquellos encargados de organizar y evaluar los programas de residencia. Nuestro objetivo es conocer las percepciones de los residentes acerca de cuáles son las instancias formativas que mejor contribuyen a la generación de conocimiento. Materiales: estudio de corte transversal utilizando una encuesta virtual que fue enviada a todos los Residentes de Medicina Interna del Hospital Italiano de Buenos Aires. Se recolectaron datos generales de los residentes y año de residencia. Posteriormente se evaluaron las diferentes instancias involucradas en el aprendizaje: pases de guardia, recorrida de internación, pases de ambulatorio, pases de internación, ateneos y, por último, los cursos superiores universitarios. Resultados: la actividad individual más reconocida por su papel en el aprendizaje fue la discusión de los pacientes durante la recorrida (18% de los residentes). En contrapartida, la participación en cursos superiores universitarios no fue elegida como estrategia útil desde el punto de vista individual. Específicamente respecto de la utilidad de los pases de guardia (realizados por los residentes de primer año y los jefes de residentes), gran parte de los participantes optó por el pase de la tarde como el momento de mayor utilidad para el aprendizaje. Conclusión: los residentes consideran que los pases de guardia de la tarde, los pases de internación y ambulatorios y los ateneos de internación son los momentos más propicios y eficaces para la adquisición de nuevo conocimiento. Dichos datos pueden resultar de utilidad en la planificación de diversas instancias educativas y servir como base para estudios similares en poblaciones disímiles. (AU)

Introduction: the Internal Medicine Program at the Hospital Italiano de Buenos Aires has long term experience in training medical physicians. There is mounting evidence suggesting that residents' perceptions about their education are not consistent with the ones of who are responsible for designing and evaluating residency programs. Our goal is to evaluate residents' perceptions on the instances that contribute the most to their training. Methods: we conducted a cross-sectional study using an online survey offered to all Internal Medicine Residents at Hospital Italiano de Buenos Aires, Argentina. Baseline characteristics of each resident were collected. We subsequently assessed residents' perceptions of different instances of the residency program: residents´ morning and evening rounds, patients´ rounds, case discussions with staff physicians, grand rounds and postgraduate courses. Results: overall, the activity that was perceived as the most relevant for their education was the residents' evening rounds (18% of the residents). Conversely, participation in postgraduate courses was not selected as an important learning resource individually. Most residents highlighted the importance of patient discussion with their chief resident during morning and evening rounds. Conclusion: residents systematically prefer patient discussion on medical rounds rather than lectures and courses. This information might prove useful in the future so as to improve Internal Medicine residency programs. (AU)

Malformaciones arteriovenosas pulmonares y complicaciones embólicas en pacientes con telangiectasia hemorrágica hereditaria / Pulmonary Arteriovenous Malformations and Embolic Complications in Patients With Hereditary Hemorrhagic Telangiectasia

Los pacientes con telangiectasia hemorrágica hereditaria (THH) y malformación arteriovenosa pulmonar (MAVP) afrontan un riesgo más elevado de complicaciones embólicas. No está claro si la mala evolución clínica está relacionada con la gravedad de la MAVP o con los síntomas pulmonares. Además, en la actualidad no disponemos de datos de pacientes con THH en Argentina. Llevamos a cabo un estudio transversal en un hospital universitario de Buenos Aires, Argentina. Describimos aquí las características basales de la THH y comparamos la prevalencia de complicaciones embólicas en pacientes con una MAVP significativa frente a la de los pacientes sin una MAVP significativa. Un total de 108 pacientes consecutivos fueron incluidos en el estudio. La MAVP significativa se definió de la siguiente forma: ecocardiografía con contraste de grado 2 o superior; MAVP bilateral o aferencia de más de 3 mm, o tratamiento previo de la MAVP. La variable de valoración combinada primaria se definió como: accidente cerebrovascular, absceso cerebral o embolia periférica. Un 20% de los participantes presentó complicaciones embólicas, la más frecuente de las cuales fue el ictus. Las complicaciones embólicas se asociaron a una MAVP significativa y síntomas respiratorios

Patients with hereditary hemorrhagic telangiectasia (HHT) and pulmonary arteriovenous malformation (PAVM) face higher risk of embolic complications. It is not clear whether poor outcomes are related to PAVM severity or pulmonary symptoms. Furthermore, there are currently no available data on HHT patients in Argentina. We conducted a cross sectional study in a teaching hospital in Buenos Aires, Argentina. We describe baseline characteristics of HHT and compare the prevalence of embolic complications in patients with significant PAVM compared to patients without significant PAVM. One hundred and eight consecutive patients were included. Significant PAVM was defined as: contrast echocardiography grade 2 or greater; bilateral PAVM or feeding artery bigger than 3 mm; or previous PAVM treatment. Primary composite outcome was defined as: cerebrovascular accident, cerebral abscess or peripheral embolism. 20% of the participants had embolic complications, and the most frequent one was stroke. Embolic complications were associated with significant PAVM and respiratory symptoms