Hannah Wozniak

Background: The optimal timing of empiric antifungal therapy in patients with suspected candidemia remains uncertain. In practice, many antifungal treatments initiated empirically are eventually found to be unnecessary, exposing patients to potential toxicity, selection of non- albicans Candida species, emergence of resistance, and additional costs. The objective of the study was to evaluate whether adequate empiric antifungal therapy initiated within 2 days after blood culture draw was associated with 28-day mortality. Methods: We performed a pooled secondary analysis of two prospective worldwide observational cohorts (EUROBACT-1 and EUROBACT-2) including adult patients with Candida bloodstream infection. The exposure was defined as receipt of adequate antifungal therapy within 2 days after blood culture draw. Propensity scores for receiving early adequate antifungal therapy were estimated using prespecified covariates, and inverse probability of treatment weights were applied in a weighted Cox proportional hazards model to assess the association with 28-day mortality. Prespecified subgroup analyses were conducted according to study cohort, Candida species, and presence of hypotension at the time of bloodstream infection. As a sensitivity analysis, a frailty Cox proportional hazards model including a random center effect was performed. Results: The final study population included 272 patients with candidemia from 158 centers, including 81 from EUROBACT-1 and 191 from EUROBACT-2. One hundred and ten patients received early adequate antifungal therapy and 162 did not. Overall, 38.6% of patients (105/272) died within 28 days, including 40.9% (45/110) in the early adequate therapy group and 37.0% (60/162) in the non-early adequate therapy group. In the weighted Cox model, early adequate antifungal therapy was not significantly associated with 28-day mortality (HR 1.23, 95% CI 0.82–1.83, p = 0.314). Results were consistent across subgroup analyses according to study cohort, Candida species, the presence of hypotension at the time of bloodstream infection, as well as in the frailty Cox sensitivity analysis. Conclusions: Early adequate antifungal therapy was not independently associated with improved 28-day survival in ICU patients with candidemia. These findings support a more targeted approach to early empirical antifungal treatment and underscore the need to identify patient subgroups most likely to benefit from immediate therapy.

Background: Critical illness is known to reduce gut microbiota (GM) diversity, a change associated with adverse outcomes. Among potential mechanisms, splanchnic hypoperfusion may play a key role. Cardiac arrest (CA), characterized by transient global hypoperfusion, provides a relevant model to explore this effect. Results: We conducted a secondary, propensity score-matched analysis of a cohort study investigating GM changes during early intensive care unit stay. Stool samples were collected at ICU admission (S1) and at least 24 h later (S2). GM profiling was performed using 16S rRNA sequencing. Shannon diversity index and taxonomic composition were compared between CA and non-CA patients. Propensity score matching and generalized linear models (GLM) were used to adjust for confounding. A total of 26 patients were included in this analysis (13 CA, 13 matched controls). At S1, CA patients had significantly lower GM diversity (Shannon index: 3.6 [3.0–3.8] vs. 4.3 [3.9–4.8], p = 0.019). This was confirmed in the GLM (β = − 0.30, SE 0.12, p = 0.022). At S2, diversity remained lower (3.2 [2.7–3.8] vs. 4.0 [3.7–4.3], p = 0.064). While no global compositional shifts were observed between groups, differences in the abundance of specific taxa were noted. Conclusion: CA is associated with reduced GM diversity in the first few days of intensive care unit admission compared to non-CA patients, supporting a role for splanchnic hypoperfusion in GM modulation. Further research should investigate clinical consequences and evaluate microbiota-targeted interventions in this high-risk population.

Non-invasive ventilation (NIV) is a cornerstone in the management of acute chronic obstructive pulmonary disease (COPD) exacerbations with respiratory failure. While extensively studied in hospital settings, limited data exist on its use in the pre-hospital setting and clinical factors influencing its application. This study aimed to identify predictors of NIV use in the pre-hospital setting and to assess its association with patient-centered outcomes. This single-center retrospective cohort study analyzed data from a pre-hospital emergency medical service registry in Geneva, Switzerland. Adult patients with a presumptive diagnosis of acute COPD exacerbation were included, spanning a control period (2007–2010, before NIV implementation) and an intervention period (2013–2017, after NIV implementation). For the primary analysis, multivariable logistic regression was used to identify predictors of NIV use during the intervention period. For the secondary analysis, coarsened exact matching balanced patients treated with NIV during the intervention period with those from the control period, followed by conditional regression analyses to assess patient-centered outcomes. Among 270 included patients, 84 (46%) received NIV during the intervention period. Age ≥ 70 years (aOR 2.49, 95% CI 1.11, 5.76), female sex (aOR 2.48, 95% CI 1.13, 5.60), and systolic blood pressure (SBP) ≥ 140 mmHg (aOR 2.75, 95% CI 1.19, 6.62) were independent predictors associated with receiving NIV in the pre-hospital setting. In the matched cohort, pre-hospital NIV use was significantly associated with increased ICU admission rates, but was not associated with transport time, emergency department length of stay, hospital length of stay, or 28-day mortality. Sensitivity analyses demonstrated consistent results across different modeling approaches. Age ≥ 70 years, female sex, and SBP ≥ 140 mmHg were independent predictors associated with receiving NIV in the pre-hospital management of acute COPD exacerbation. The association between NIV use and increased ICU admissions may reflect its application in more severely ill patients. Pre-hospital NIV was not associated with short- or long-term outcomes beyond ICU admission. These findings underscore the need for prospective studies to clarify the role of pre-hospital NIV in patient outcomes.

Although a set period of abstinence is no longer a requirement for transplant consideration in many liver transplantation programs, it is imperative to use valid monitoring tools to detect ongoing alcohol use in candidates for transplant. Urinary ethyl glucuronide (EtG) is an objective measure of alcohol use. This single-center retrospective study aims to describe the psychosocial characteristics of patients with alcohol-associated liver disease (ALD) who provided positive EtG tests in the pretransplant phase. Data were collected between May 1, 2018, and November 30, 2021, for all patients with ALD referred to our transplantation program (n = 497). Psychosocial characteristics and transplant outcomes were recorded for all patients. Patients with a positive EtG test were compared to patients who did not have a positive EtG test. A backward logistic regression analysis was performed to assess the factors associated with a positive EtG test. Of the 497 patients evaluated, 40 (8%) provided a positive EtG test, including at the initial clinic visit (n = 20), during medical evaluation (n = 14), and while on the waitlist (n = 6). Severe alcohol use disorder (p < 0.01), consuming p = 0.011), and longer duration of daily alcohol use (p = 0.028) were significantly associated with a positive EtG test. Psychiatric comorbidity and previous treatment for alcohol use disorder were not significantly associated with positive tests. A minority of patients with ALD provided a positive urine EtG in the pretransplant phase. Alongside clinical interviews, biomarker testing is an objective tool to identify ongoing alcohol use in patients with ALD.