Invasive Pulmonary Aspergillosis in Critically Ill Patients with Hantavirus Infection, Austria.

We investigated a cohort of 370 patients in Austria with hantavirus infections (7.8% ICU admission rate) and detected 2 cases (cumulative incidence 7%) of invasive pulmonary aspergillosis; 1 patient died. Hantavirus-associated pulmonary aspergillosis may complicate the course of critically ill patients who have hemorrhagic fever with renal syndrome.

Pulmonary manifestations of VEXAS syndrome with acute interstitial pneumonia and diffuse alveolar hemorrhage: a case report and literature review.

Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is an emerging adult-onset systemic autoinflammatory disorder affecting multiple organ systems. While lung involvement is common in this syndrome, literature regarding specific patterns is sparse. In this report, we present a case description of a patient with VEXAS syndrome who presented at the emergency department on two separate occasions with acute interstitial pneumonia (AIP) and diffuse alveolar hemorrhage (DAH). A literature review with a comparison of our observed findings to the general findings of VEXAS syndrome, AIP, and DAH is provided. This report underscores the rarity of specific pulmonary manifestations associated with VEXAS syndrome, contributing valuable insight to the limited literature available on this topic.

Ruxolitinib, IV Immunoglobulin, and High-Dose Glucocorticoids for Critically Ill Adults With Secondary Hemophagocytic Lymphohistiocytosis: A Single-Center Observational Pilot Study.

OBJECTIVES: Secondary hemophagocytic lymphohistiocytosis (sHLH) is a cytokine-driven inflammatory syndrome that is associated with substantial morbidity and mortality and frequently leads to ICU admission. Overall survival in adults with sHLH remains poor, especially in those requiring intensive care. Classical chemotherapeutic treatment exhibits myelosuppression and toxicity. Recently, inhibition of Janus kinase signaling by ruxolitinib has shown efficacy in pediatric HLH. We therefore aimed to determine the activity and safety of a ruxolitinib-based regimen, in critically ill adults with sHLH. DESIGN: Observational pilot study. SETTING: Single-center tertiary academic ICU. PATIENTS: Nine adults (≥ 18 yr) who fulfilled at least five of the eight HLH-2004 criteria. INTERVENTION: Triplet regimen combining: 1) ruxolitinib, 2) polyvalent human IV immunoglobulins (IVIG) at a dose of 1 g/kg bodyweight for 5 days, and 3) high-dose corticosteroids (CSs, dexamethasone 10 mg/m² body surface area, or methylprednisolone equivalent) with subsequent tapering according to the HLH-2004 protocol. MEASUREMENT AND MAIN RESULTS: Nine patients (median age: 42 yr [25th-75th percentile: 32-54]; male: n = 6 males, median H-score: 299 [255-304]) were treated with the triplet regimen. The median Sequential Organ Failure Assessment score at HLH diagnosis was 9 (median; 25th-75th percentile: 7-12), indicating multiple-organ dysfunction in all patients. Within 10 days a significant decrease of the inflammatory parameters soluble interleukin-2 receptor and ferritin as well as a stabilization of the blood count could be shown. All patients were alive at ICU discharge (100% ICU survival), 1 patient died after ICU discharge because of traumatic intracerebral hemorrhage that might be related to HLH or treatment, corresponding to an overall survival of 86% in a 6 months follow-up period. CONCLUSION: In this small case series, a triplet regimen of ruxolitinib in combination with IVIG and CS was highly effective and save for treating critically ill adults with sHLH.

Biomarkers of alcohol abuse potentially predict delirium, delirium duration and mortality in critically ill patients.

Carbohydrate-deficient transferrin (CDT) and the γ-glutamyltransferase-CDT derived Anttila-Index are established biomarkers for sustained heavy alcohol consumption and their potential role to predict delirium and mortality in critically ill patients is not clear. In our prospective observational study, we included 343 consecutive patients admitted to our ICU, assessed the occurrence of delirium and investigated its association with biomarkers of alcohol abuse measured on the day of ICU admission. 35% of patients developed delirium during ICU stay. We found significantly higher CDT levels (p = 0.011) and Anttila-Index (p = 0.001) in patients with delirium. CDT above 1.7% (OR 2.06), CDT per percent increase (OR 1.26, AUROC 0.75), and Anttila-Index per unit increase (OR 1.28, AUROC 0.74) were associated with delirium development in adjusted regression models. Anttila-Index and CDT also correlated with delirium duration exceeding 5 days. Additionally, Anttila-Index above 4, Anttila-Index per unit increase, and CDT per percent increase were independently associated with hospital mortality.

ERG status is unrelated to PSA recurrence in radically operated prostate cancer in the absence of antihormonal therapy.

PURPOSE: About 50% of prostate cancers have TMPRSS2-ERG fusions with concurrent ERG overexpression. The aim of this study was to determine whether clinical differences exist between ERG-positive and ERG-negative cancers in surgically treated patients not exposed to antihormonal therapy. A secondary aim was to search for differences between these tumor classes. EXPERIMENTAL DESIGN: A tissue microarray containing samples from more than 2,800 prostate cancers with clinical data was analyzed for ERG alterations by immunohistochemistry and FISH. Results were compared with tumor phenotype, biochemical recurrence, and molecular features considered important for prostate cancer. The effect of ERG on androgen receptor (AR)-dependent transcription was analyzed in cell lines. RESULTS: ERG expression was found in 52.4% of 2,805 cancers with a 95% concordance between ERG expression and ERG gene rearrangement detected by FISH. ERG expression was unrelated to clinical outcome and tumor phenotype. Differences in AMACR, Annexin A3, Bcl2, CD10, ALCAM, chromogranin A, epidermal growth factor receptor, HER2, mTOR, p53, and synaptophysin status were significant but minimal in absolute numbers. The most striking difference was found for AR expression, which was markedly higher in ERG-positive cancers. In vitro studies showed ERG-dependent impairment of AR-mediated transcriptional activity. CONCLUSIONS: The striking similarities between these two types of prostate cancers rules out a major impact of ERG on tumor aggressiveness in early, not hormonally treated cancer. The marked difference in AR levels between ERG-positive and -negative cancers supports a systematic difference in potential response to hormonal therapy as previously observed in clinical trials.