Tomas Urbina

Enterococcal infections represent 10% of intensive care unit (ICU)-acquired infections and are associated with adverse outcomes, particularly in the case o

Purpose Invasive meningococcal disease (IMD) is a rare but potentially fatal infection caused by Neisseria meningitidis. In adults requiring admission to intensive care unit (ICU), IMD typically presents with two distinct clinical presentations: neurological (meningitis) and hemodynamic (sepsis). These presentations are often conflated, despite the differences in pathophysiology and outcome. Methods RETRO-MENINGO is a nationwide, multicentre, retrospective cohort study conducted in 102 French ICUs between January 1, 2016, and December 31, 2024. Adults (≥ 18 years) admitted to the ICU with a microbiologically confirmed IMD were categorised as having either a neurological or a hemodynamic presentation according to the main reason for ICU admission. The primary outcome was day-60 mortality in each presentation. Results Of 654 patients (median age 33 years [IQR 21–56]; 63.5% without comorbidities), 407 (62%) had a neurological and 247 (38%) a hemodynamic presentation at ICU admission. Hemodynamic presentation was associated with older age (39.0 vs. 30.0 years; p = 0.001), immunosuppression (17.0% vs. 7.1%; p < 0.001), purpuric rash (55.9% vs. 43.7%; p = 0.003), earlier ICU admission (1 vs. 2 days; p = 0.001) and more frequent bacteremia (83.8% vs. 35.6%; p < 0.001). Serogroup B was predominant in neurological presentation, whereas serogroup W135 was more common in hemodynamic presentation. Compared to neurological presentation, hemodynamic presentation required more organ support (vasopressors, invasive mechanical ventilation, transfusions, renal replacement therapy) and had a significantly higher day-60 mortality (25.5% vs. 4.7%; p < 0.001). Hemodynamic presentation (aOR 4.33, 95% CI 2.26–8.62; p < 0.001), absence of comorbidities (aOR 2.21, 95% CI 1.19–4.23; p = 0.014), age > 35 years (aOR 3.65, 95% CI 1.73–6.07; p < 0.001), arterial lactate level > 5 mmol/L (aOR 2.60, 95% CI 1.43–4.77; p = 0.002) and symptom onset < 24 h (aOR 1.90, 95% CI 1.00–3.55; p = 0.040) were independently associated with day-60 mortality, while early administration of a parenteral third-generation cephalosporin prior to ICU admission was strongly protective (aOR 0.31, 95% CI 0.18–0.55; p < 0.001). Conclusion Neurological and hemodynamic presentation of IMD are clinically and prognostically distinct. Recognition of these phenotypes is critical for appropriate management and prediction of outcome.

Current triplet regimens associating therapeutic plasma exchange (TPE), immunosuppression with corticosteroids and rituximab, and caplacizumab have dramatically improved the outcome of immune‐mediated thrombotic thrombocytopenic purpura (iTTP). However, nearly half of the patients require extended caplacizumab treatment (i.e., > 30 days) due to persistent ADAMTS13 deficiency, raising cost and tolerance concerns. Therefore, we investigated whether anti‐ADAMTS13 antibodies titer and their trajectory during the acute phase of the disease could predict ADAMTS13 improvement (i.e., activity ≥ 20% before day‐30 post‐TPE). From a cohort of 286 patients receiving the triplet regimen, we identified on diagnosis a cut‐off value for anti‐ADAMTS13 IgG antibodies of 90.5 U/mL, with a modest discriminating ability (AUC: 0.57) for predicting long‐term response, precluding its use to guide therapeutic strategies. Nonetheless, the analysis of anti‐ADAMTS13 IgG antibodies titer trajectory from diagnosis revealed that the proportion of iTTP patients with ADAMTS13 activity improvement was higher in patients who decreased (Dec+) their antibodies titer within the 7–14 days interval post‐TPE compared to those without decrease (Dec−) (65% vs. 25% of cases, respectively, p < 0.001), a finding confirmed in a validation cohort ( N = 51). These results highlight the possibility of intensifying immunosuppression in an early period post‐TPE to shorten time to ADAMTS13 activity recovery. Close monitoring of anti‐ADAMTS13 antibodies titer may guide immunomodulation strategies, including additional courses of B‐cell depleting agents when appropriate.

Invasive group A streptococcus (iGAS) infection incidence is rising. These infections have been studied as a whole but can be associated with critical illness in a population with a wide array of underlying conditions, sites of infection and clinical presentations. Using an unsupervised clustering approach, we aimed to identify specific clinical phenotypes regarding presentation, management and outcome. This was a retrospective multicentric study including all patients admitted to one of 9 ICUs of Paris University Hospitals for an iGAS infection between 01/03/2018 and 01/08/2023. iGAS infection was defined as GAS growth in any microbiological sample from a sterile site. Patients were grouped according to a clustering algorithm (k-prototypes) using a comprehensive set of clinical and biological variables available upon ICU admission. Clusters were described and clinical presentation, management and outcome were compared. 148 patients were included. According to the Silhouette criterion, patients were grouped in 3 clusters, and 7 patients remained unclassified. Cluster 1 (n = 73) comprised a greater proportion of less severely-ill female patients with painful skin and soft tissue infections, a quarter of whom had taken non-steroidal anti-inflammatory drugs. Cluster 2 (n = 42) was characterized by a high rate of respiratory infections with frequent viral co-infections. Cluster 3 (n = 26) included mostly socially deprived patients with high rates of chronic alcohol consumption and psychiatric illness, with severe organ dysfunction related to otherwise pauci-symptomatic skin and soft tissue infections. There was no significant difference in time to source control across clusters (0 [0–0] vs 0 [0–0] vs 0 [0–1] days, p = 0.12). Patients included in cluster 2 less frequently received antitoxin antibiotics than patients from clusters 1 and 3 (79% vs 45% vs 69%, p < 0.001) and tended to more frequently require ECMO support (3% vs 12% vs 0%, p = 0.07), while those from cluster 1 were less likely to receive invasive mechanical ventilation (48% vs 74% vs 77%, p = 0.005). There was no difference in ICU-mortality between clusters (19% vs 29% vs 31%, p = 0.32). Based on simple and readily available clinical admission characteristics of critically ill patients with iGAS, unsupervised clustering analysis identified three specific patient populations that differed regarding ICU management. Whether tailoring management would affect outcome warrants further research.

Article: Corticosteroids induce an early but limited decrease in IL-6 dependent pro-inflammatory responses in critically ill COVID-19 patients - Minerva Anestesiologica 2024 Jan 29 - Minerva Medica - Journals

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare disease characterized by arteriolar and capillary microthrombosis precipitating organ failure. However, the contribution of endothelial dysfunction on impaired microvascular blood flow in iTTP patients has been poorly explored. This pilot observational study aimed to explore endothelial-mediated vasoreactivity in iTTP patients at admission and its changes after plasma exchange therapy (PE). We conducted a prospective observational study in patients (> 18-year old) admitted in ICU for iTTP. Using laser Doppler flowmetry and acetylcholine (Ach) iontophoresis in the forearm, we recorded the skin microvascular blood flow and the endothelium-mediated vasoreactivity at admission and after PE. Demographics, biological, clinical courses, and outcomes were also collected. As a control group, we used a previously published cohort of young diabetic patients after correction of ketoacidosis. Eighteen confirmed iTTP patients and 34 controls were included in the study, mainly female (72%) aged 43 ± 16-year-old. At admission, 55% had neurological abnormalities, 50% cardiac issues and 27.8% an acute kidney injury. Median platelet count was 19 G/mL [10–37]. Baseline microvascular blood flow was decreased in iTTP patients when compared to controls (5.97 ± 4.5 vs. 10.1 ± 6.3 PU, P = 0.03), associated with markedly impaired endothelial-mediated skin microvascular reactivity (AUC: 9627 ± 8122 vs. 16,475 ± 11,738, P = 0.03). Microvascular reactivity improved after the first PE session (AUC: 9627 ± 8122 vs 16,558 ± 10,699, P = 0.007, respectively, baseline and post-PE1) and much more after the second session (26,431 ± 23,181, P = 0.04 post-PE1 vs post-PE2). Hemolysis biomarkers (LDH and bilirubin) negatively correlated with skin microvascular flow and vasoreactivity. We highlighted a marked yet reversible skin endothelium-mediated microvascular hyporeactivity in iTTP patients that could participate in organ injury pathophysiology.

The SARS-CoV-2 variant of concern, α, spread worldwide at the beginning of 2021. It was suggested that this variant was associated with a higher risk of mortality than other variants. We aimed to characterize the genetic diversity of SARS-CoV-2 variants isolated from patients with severe COVID-19 and unravel the relationships between specific viral mutations/mutational patterns and clinical outcomes. This is a prospective multicenter observational cohort study. Patients aged ≥18 years admitted to 11 intensive care units (ICUs) in hospitals in the Greater Paris area for SARS-CoV-2 infection and acute respiratory failure between 1 October 2020 and 30 May 2021 were included. The primary clinical endpoint was day-28 mortality. Full-length SARS-CoV-2 genomes were sequenced by means of next-generation sequencing (Illumina COVIDSeq). In total, 413 patients were included, 183 (44.3%) were infected with pre-existing variants, 197 (47.7%) were infected with variant α, and 33 (8.0%) were infected with other variants. The patients infected with pre-existing variants were significantly older (64.9 ± 11.9 vs. 60.5 ± 11.8 years; p = 0.0005) and had more frequent COPD (11.5% vs. 4.1%; p = 0.009) and higher SOFA scores (4 [3–8] vs. 3 [2–4]; 0.0002). The day-28 mortality was no different between the patients infected with pre-existing, α, or other variants (31.1% vs. 26.2% vs. 30.3%; p = 0.550). There was no association between day-28 mortality and specific variants or the presence of specific mutations. At ICU admission, the patients infected with pre-existing variants had a different clinical presentation from those infected with variant α, but mortality did not differ between these groups. There was no association between specific variants or SARS-CoV-2 genome mutational pattern and day-28 mortality.