Critically Ill Patients with Visceral Nocardia Infection, France and Belgium, 2004-2023.

We studied 50 patients with invasive nocardiosis treated during 2004-2023 in intensive care centers in France and Belgium. Most (65%) died in the intensive care unit or in the year after admission. Nocardia infections should be included in the differential diagnoses for patients in the intensive care setting.

Carfilzomib-associated thrombotic microangiopathy: clinical features and outcomes.

BACKGROUND AND HYPOTHESIS: Carfilzomib, a new proteasome inhibitor indicated for patients with relapsed/refractory myeloma, has been associated with cases of thrombotic microangiopathy (CFZ-TMA). The role of variants in the complement alternative pathway and therapeutic potential of complement blockade with eculizumab remain to be determined. METHODS: We report 37 cases of CFZ-TMA recorded in the French reference center for TMA with their clinical characteristics, genetic analysis and outcome according to treatments. RESULTS: A trigger was identified in more than half of cases, including 8 influenza and 5 SARS-CoV-2 cases. All patients presented with acute kidney injury (AKI) (KDIGO stage 3 in 31 (84%) patients) while neurological (n=13, 36%) and cardiac damage (n=7, 19%) were less frequent. ADAMTS13 and complement activity were normal (n= 28 and 18 patients tested) and no pathogenic variant in the alternative complement pathway was found in 7 patients tested.TMA resolved in most (n=34, 94%) patients but 12 (44%) still displayed stage 3 AKI at discharge. Nineteen (51%) patients were treated with therapeutic plasma exchange, 14 (38%) patients received corticosteroids and 18 (50%) were treated with eculizumab. However none of these treatments demonstrated a significant impact on outcomes. CONCLUSION: This study is the largest case series of CFZ-TMA since its approval in 2012. Patients present with severe AKI and experience frequent sequelae. Complement variants and blockade therapy do not seem to play a role in the pathophysiology and prognosis of the disease.

Severe Community-Acquired Pneumonia in Immunocompromised Patients.

Due to higher survival rates with good quality of life, related to new treatments in the fields of oncology, hematology, and transplantation, the number of immunocompromised patients is increasing. But these patients are at high risk of intensive care unit admission because of numerous complications. Acute respiratory failure due to severe community-acquired pneumonia is one of the leading causes of admission. In this setting, the need for invasive mechanical ventilation is up to 60%, associated with a high hospital mortality rate of around 40 to 50%. A wide range of pathogens according to the reason of immunosuppression is associated with severe pneumonia in those patients: documented bacterial pneumonia represents a third of cases, viral and fungal pneumonia both account for up to 15% of cases. For patients with an undetermined etiology despite comprehensive diagnostic workup, the hospital mortality rate is very high. Thus, a standardized diagnosis strategy should be defined to increase the diagnosis rate and prescribe the appropriate treatment. This review focuses on the benefit-to-risk ratio of invasive or noninvasive strategies, in the era of omics, for the management of critically ill immunocompromised patients with severe pneumonia in terms of diagnosis and oxygenation.

Acute kidney injury after CAR-T cell therapy: exploring clinical patterns, management, and outcomes.

Background: Acute kidney injury (AKI) has been reported after CAR-T cells, but available data are limited. We sought to describe the incidence of AKI in a cohort of patients hospitalized in the intensive care unit (ICU) following CAR-T cell reinjection, identify the primary factors linked to the onset of AKI, and ascertain the key determinants associated with kidney outcomes and mortality. Methods: We retrospectively analyzed 119 patients hospitalized in ICU after CAR-T cell therapy between 2017 and 2023. Factors associated with AKI, mortality, and kidney sequelae were identified using multivariate analyses. Results: Of the 119 patients, 41 patients fulfilled diagnostic criteria of AKI (34%). By multivariate analysis, grade ≥3 cytokine release syndrome (CRS) [OR = 1.20 CI95% (1.01-1.43)] and elevated lactate dehydrogenase (LDH) levels at admission [OR = 1.44 CI95% (1.04-1.99)] were significantly associated with the occurrence of AKI during ICU stay. AKI KDIGO ≥2 was an independent risk factor for hospital mortality [OR = 1.50 (1.22-1.85), P < 0.001]. Nine out of 12 (75%) and 6/9 (67%) patients who had experienced AKI and survived had chronic kidney disease (CKD) at 6 months and 1 year, respectively. We did not identify any specific factor associated with kidney recovery. Conclusion: AKI may occur in ICU patients receiving CAR-T cell therapy, especially those who experience CRS and exhibit elevated LDH levels. Early recognition of AKI is of utmost importance as it substantially compromises survival in these patients. Future studies should aim to elucidate the underlying pathophysiological mechanisms of AKI in this context and pinpoint predictive factors for long-term risks of CKD.

Right ventricular injury in patients with COVID-19-related ARDS eligible for ECMO support: a multicenter retrospective study.

BACKGROUND: Coronavirus disease 2019 (COVID-19)-related acute respiratory distress syndrome (ARDS) is associated with high mortality. Extracorporeal membrane oxygenation (ECMO) has been proposed in this setting, but optimal criteria to select target patients remain unknown. Our hypothesis is that evaluation of right ventricular (RV) function could be helpful. The aims of our study were to report the incidence and outcomes of patients eligible for ECMO according to EOLIA criteria, and to identify a subgroup of patients with RV injury, which could be a target for ECMO. METHODS: Retrospective observational study involving 3 French intensive care units (ICUs) of teaching hospitals. Patients with confirmed SARS-CoV-2 infection between March 2020 and March 2021, presenting ARDS and with available echocardiography, were included. Patients were classified in three groups according to whether or not they met the EOLIA criteria and the presence of RV injury (RVI) ("EOLIA -", "EOLIA + RVI -" and "EOLIA + RVI + "). RVI was defined by the association of RV to left ventricular end-diastolic area ratio > 0.8 and paradoxical septal motion. Kaplan-Meier survival curves were used to analyze outcome as well as a Cox model for 90 day mortality. RESULTS: 915 patients were hospitalized for COVID-19, 418 of them with ARDS. A total of 283 patients with available echocardiography were included. Eighteen (6.3%) patients received ECMO. After exclusion of these patients, 107 (40.5%) were classified as EOLIA -, 126 (47.5%) as EOLIA + RVI -, and 32 (12%) as EOLIA + RVI + . Ninety-day mortality was 21% in the EOLIA-group, 44% in the EOLIA + RVI-group, and 66% in the EOLIA + RVI + group (p < 0.001). After adjustment, RVI was statistically associated with 90-day mortality (HR = 1.92 [1.10-3.37]). CONCLUSIONS: Among COVID-19-associated ARDS patients who met the EOLIA criteria, those with significant RV pressure overload had a particularly poor outcome. This subgroup may be a more specific target for ECMO. This represented 12% of our cohort compared to 60% of patients who met the EOLIA criteria only. How the identification of this high-risk subset of patients translates into patient-centered outcomes remains to be evaluated.

Environmental measures to improve pedestrian safety in low- and middle-income countries: a scoping review.

OBJECTIVES: This scoping study aims to identify environmental road safety measures implemented in low- and middle-income countries (LMICs) to reduce pedestrian injuries from collisions with motor vehicles. METHODS: This review followed Arksey and O'Malley's approach and reported results using the PRISMA-SCR 2018 checklist. A literature review was conducted in Medline, Google Scholar, and the Transport Research International Documentation database using keyword-derived medical subject heading terms. A total of 14 articles met the pre-established inclusion criteria and were analyzed using a data extraction matrix. The findings were categorized methodically into three prominent themes: (1) methods for reducing pedestrian exposure, (2) traffic calming strategies, and (3) measures for enhancing pedestrian visibility. RESULTS: Traffic calming strategies, including vehicular speed reduction, roadway contraction, and vertical and horizontal diversionary tactics, emerged as the most effective interventions for reducing pedestrian injuries within LMICs. Conversely, interventions geared towards minimizing pedestrian exposure, such as zebra crossings, crosswalks controlled by traffic signals, underpasses, or overpasses, often produced minimal effects, and occasionally exacerbated the risk of pedestrian accidents. Lack of pedestrian visibility due to density of street vendors and parked vehicles was associated with a higher risk of injuries, while billboards impaired drivers' attention and increased the likelihood of collisions with pedestrians. DISCUSSION: In LMICs, the effectiveness of environmental measures in reducing vehicle-pedestrian crashes varies widely. In the face of resource constraints, implementing interventions for pedestrian safety in LMICs necessitates careful prioritization and consideration of the local context.

Acyl-CoA binding protein for the experimental treatment of anorexia.

Extracellular acyl-coenzyme A binding protein [ACBP encoded by diazepam binding inhibitor (DBI)] is a phylogenetically ancient appetite stimulator that is secreted in a nonconventional, autophagy-dependent fashion. Here, we show that low ACBP/DBI plasma concentrations are associated with poor prognosis in patients with anorexia nervosa, a frequent and often intractable eating disorder. In mice, anorexia induced by chronic restraint stress (CRS) is accompanied by a reduction in circulating ACBP/DBI concentrations. We engineered a chemical-genetic system for the secretion of ACBP/DBI through a biotin-activatable, autophagy-independent pathway. In transgenic mice expressing this system in hepatocytes, biotin-induced elevations in plasma ACBP/DBI concentrations prevented anorexia induced by CRS or chemotherapeutic agents including cisplatin, doxorubicin, and paclitaxel. ACBP/DBI reversed the CRS or cisplatin-induced increase in plasma lipocalin-2 concentrations and the hypothalamic activation of anorexigenic melanocortin 4 receptors, for which lipocalin-2 is an agonist. Daily intravenous injections of recombinant ACBP/DBI protein or subcutaneous implantation of osmotic pumps releasing recombinant ACBP/DBI mimicked the orexigenic effects of the chemical-genetic system. In conclusion, the supplementation of extracellular and peripheral ACBP/DBI might constitute a viable strategy for treating anorexia.

COVID-19 associated pulmonary aspergillosis in critically-ill patients: a prospective multicenter study in the era of Delta and Omicron variants.

BACKGROUND: During the first COVID-19 pandemic wave, COVID-19-associated pulmonary aspergillosis (CAPA) has been reported in up to 11-28% of critically ill COVID-19 patients and associated with increased mortality. As new SARS-CoV-2 variants emerged, the characteristics of critically ill COVID-19 patients have evolved, particularly in the era of Omicron. The purpose of this study is to investigate the characteristics of CAPA in the era of new variants. METHODS: This is a prospective multicenter observational cohort study conducted in France in 36 participating intensive care units (ICU), between December 7th, 2021 and April 26th 2023. Diagnosis criteria of CAPA relied on European Confederation of Medical Mycology (ECMM)/International Society for Human & Animal Mycology (ISHAM) consensus criteria. RESULTS: 566 patients were included over the study period. The prevalence of CAPA was 5.1% [95% CI 3.4-7.3], and rose to 9.1% among patients who required invasive mechanical ventilation (IMV). Univariable analysis showed that CAPA patients were more frequently immunosuppressed and required more frequently IMV support, vasopressors and renal replacement therapy during ICU stay than non-CAPA patients. SAPS II score at ICU admission, immunosuppression, and a SARS-CoV-2 Delta variant were independently associated with CAPA in multivariable logistic regression analysis. Although CAPA was not significantly associated with day-28 mortality, patients with CAPA experienced a longer duration of mechanical ventilation and ICU stay. CONCLUSION: This study contributes valuable insights into the prevalence, characteristics, and outcomes of CAPA in the era of Delta and Omicron variants. We report a lower prevalence of CAPA (5.1%) among critically-ill COVID-19 patients than previously reported, mainly affecting intubated-patients. Duration of mechanical ventilation and ICU stay were significantly longer in CAPA patients.

Analysis of implementation outcomes of quality improvement initiatives in Haiti: the fingerprint initiative / Análisis de los resultados de la puesta en práctica de iniciativas para la mejora de la calidad en Haití: la iniciativa de la huella dactilar / Análise dos resultados da implantação de iniciativas para melhoria da qualidade no Haiti: iniciativa de leitura da impressão digital

ABSTRACT Objective. To assess the process and outcomes of the implementation of an electronic fingerprint initiative as part of quality improvement in three health facilities in the Northern Department of Haiti, in terms of its acceptability, adoption, feasibility, fidelity, and sustainability. In Haiti, poor attendance of the healthcare workforce is a nationwide problem, closely related to the quality of care. Three health institutions have tried to implement an electronic fingerprint system to monitor and improve attendance. Methods. An exploratory and qualitative descriptive study of the implementation outcomes of the fingerprint initiative. It was based on semi-structured interviews and one group discussion using purposeful sampling techniques to recruit participants, and an open coding system and deductive approach to analyze the data using ATLAS.ti 8. Results. The fingerprint initiative was successfully implemented in a non-governmental organization supported health facility but, despite some planning, it was never implemented in the public health facilities. The acceptability of the implementation was high in the not-for-profit organization and low in the public settings, mostly in relation to the presence of champions and the leadership at each health facility. Conclusions. We recommend more involvement of the leadership of health facilities in the different phases of the implementation process in order to guarantee acceptability, adoption, fidelity and sustainabiliy. More research is needed to articulate this technology-driven initiative in the Haitian health system.

RESUMEN Objetivo. Evaluar el proceso y los resultados de la puesta en práctica de una iniciativa de digitalización de huellas dactilares como parte de la mejora de la calidad en tres establecimientos de salud del departamento Norte de Haití, en cuanto a su aceptabilidad, adopción, viabilidad, fidelidad y sostenibilidad. En Haití, el absentismo de los trabajadores de atención de salud es un problema nacional, estrechamente relacionado con la calidad de la atención. Tres instituciones de salud han tratado de poner en práctica un sistema de huellas dactilares digitalizadas para monitorear y mejorar la asistencia. Métodos. Se ha llevado a cabo un estudio descriptivo cualitativo y exploratorio de los resultados de la puesta en práctica de la iniciativa de la huella dactilar. Este estudio empleó entrevistas semiestructuradas y una discusión de grupo mediante técnicas de muestreo con fines específicos para reclutar a los participantes, y un sistema de codificación abierta y enfoque deductivo para analizar los datos con ATLAS.ti 8. Resultados. La iniciativa de la huella dactilar se llevó a cabo satisfactoriamente en un establecimiento de salud no gubernamental; sin embargo, a pesar de cierta planificación, no llegó a ponerse en práctica en establecimientos públicos de salud. La aceptabilidad de la implementación fue alta en las organizaciones sin fines de lucro y baja en los entornos públicos, principalmente en lo que respecta a la presencia de líderes y dirigentes en cada establecimiento de salud. Conclusiones. Recomendamos una mayor participación de la gerencia de los establecimientos de salud en las diferentes fases del proceso de ejecución para garantizar aceptabilidad, adopción, fidelidad y sostenibilidad. Se necesita investigación adicional para integrar esta iniciativa impulsada por la tecnología en el sistema de salud haitiano.

RESUMO Objetivo. Avaliar o processo e os resultados da implantação de uma iniciativa de controle de ponto eletrônico por biometria para melhoria da qualidade em três serviços de saúde no Departamento Norte do Haiti quanto à aceitabilidade, adoção, viabilidade, fidelidade e sustentabilidade. A baixa assiduidade no trabalho do pessoal da saúde é um problema em todo o país e está estreitamente relacionada à qualidade da atenção. Foi feita uma tentativa de implantar um sistema de ponto eletrônico por biometria em três instituições de saúde, para monitorar e aumentar a assiduidade no trabalho. Métodos. Estudo exploratório, descritivo e qualitativo dos resultados da implantação da iniciativa de ponto eletrônico por biometria. Os dados foram coletados em entrevistas semiestruturadas e em um grupo de discussão usando técnica de amostragem intencional para recrutar os participantes. A análise de dados foi realizada por codificação aberta e enfoque dedutivo com o uso do software ATLAS.ti 8. Resultados. A iniciativa de ponto eletrônico por biometria foi implantada com êxito em um serviço de saúde apoiado por uma organização não governamental. Porém, apesar do planejamento, ela nunca foi implantada nos serviços da rede pública. A aceitabilidade foi muito boa na entidade sem fins lucrativos, mas foi baixa na rede pública, sobretudo em relação à presença de apoiadores e dirigentes no local. Conclusões. Recomenda-se maior envolvimento dos dirigentes dos serviços de saúde nas diferentes fases do processo de implantação para garantir a aceitabilidade, adoção, fidelidade e sustentabilidade da iniciativa. Mais pesquisas são necessárias para estruturar esta iniciativa com uso de tecnologia no sistema de saúde do Haiti.