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Extracorporeal membrane oxygenation (ECMO) provides life support for severe respiratory and cardiac failure, including failure from severe infection such as sepsis and acute respiratory distress syndrome. Additionally, ECMO-acquired infections are frequent and associated with prolonged hospitalization, increased healthcare utilization, and higher mortality. This review summarizes current evidence regarding the epidemiology, pathophysiology, diagnosis, prevention, and management of infectious adverse events during ECMO. Future work should aim to refine ECMO-related infectious adverse event definitions, improve harmonized multicenter data collection, and to invest in high-quality, well-designed studies.

Abstract Alternaria spp. are dematiaceous ascomycetes that can cause opportunistic infections in immunocompromised hosts. They are challenging to identify and treat. However, optimal antifungal therapy remains undefined. We retrospectively reviewed antifungal susceptibilities (AST) of all Alternaria spp. isolates from adults at a tertiary care center between 2011 and 2025. We evaluated culture sources, minimum inhibitory concentration (MIC) and minimal effective concentration (MEC) distributions, and MIC₅₀/MIC₉₀ and MEC50/MEC90 values. Clinical characteristics, treatment measures, and outcomes of patients with clinically significant Alternaria spp. infections were described. Forty-one patients had Alternaria spp. isolated, most commonly from skin (n = 13), bone/joint (n = 5), nail (n = 3), or cornea (n = 3). Posaconazole and itraconazole demonstrated low MICs (MIC₅₀/MIC₉₀: 0.06/0.5 and 0.25/0.5 µg/mL, respectively). Voriconazole and isavuconazole showed higher MIC₅₀/MIC₉₀ (1/2 and 2/4 µg/mL). Caspofungin (0.125/0.5 µg/mL) and amphotericin B (0.25/1 µg/mL) had low MICs and MECs.s. Alternaria spp. represented clinically significant infection in 27 cases (66%); 26% were solid organ transplant recipients and 15% had hematologic malignancies. Other risk factors included preceding trauma (22%) and autoimmune disease (15%). Posaconazole was the most frequently used empiric agent (6, 32%). Following AST results, 14 patients (52%) received oral antifungal therapy; posaconazole was used in all 14. In addition, 7 patients (26%) received combination therapy with IV amphotericin B. Adjunctive surgery occurred in 14 cases (52%). Five patients (19%) died before completing therapy; Alternaria infections occurred predominantly in immunocompromised hosts and were frequently managed with posaconazole and surgery. Interpretive criteria for Alternaria spp. are needed to guide empiric and definitive therapy.

Abstract Background and Aims Exercise stress echocardiography is recommended as an alternative to invasive testing for diagnosing heart failure with preserved ejection fraction (HFpEF), but an evidence-based operational framework guiding its application is lacking. Methods Patients with chronic unexplained dyspnoea underwent invasive haemodynamic exercise testing with simultaneous echocardiography to test the hypotheses that (i) the current diagnostic algorithms (H2FPEF, HFA-PEFF, and HFpEF-ABA scores) could be enhanced when combined with exercise echocardiography; and (ii) incorporating resting left atrial (LA) compliance (LA reservoir strain divided by E/e′) could further improve diagnostic triage, using separate cut points optimizing sensitivity and specificity. Findings were then validated in an international multicentre cohort. Results Of 482 patients, HFpEF was present in 386 and non-cardiac dyspnoea in 96. Sensitivity to detect HFpEF was only 55%–60% and accuracy 61%–67% using individual diagnostic scores with currently recommended exercise echocardiography. Addition of abnormal resting LA compliance to exercise echocardiography increased sensitivity to 84%–85% but increased the false-positive rate to 31%–43%. Applying separate cut points that optimize specificity and sensitivity (either exercise E/e′ ≥ 13.8 or resting LA compliance ≤1.6% to rule-in HFpEF; both exercise E/e′ < 7.2 and resting LA compliance >4.4% to rule-out HFpEF, remaining patients indeterminate who require invasive testing) improved sensitivity to 95%–99% among definitively classified patients and reduced the number of patients that require invasive exercise testing from ∼60% to ∼30%. Findings were replicated in a multicentre, international validation cohort of patients undergoing rest–exercise echocardiography and invasive exercise testing. Conclusions Currently used non-invasive approaches to HFpEF diagnosis have inadequate sensitivity, indicating that exercise echocardiography cannot supplant invasive testing. Addition of LA strain imaging with optimized rule-in or rule-out values improves diagnostic triage by expanding non-invasive rule-in/rule-out classifications while identifying patients who still require invasive testing in the evaluation of HFpEF.

Abstract Background Optimal treatment following first-line immunotherapy for advanced hepatocellular carcinoma (HCC) remains uncertain. This study evaluated futibatinib, a pan-FGFR inhibitor, combined with pembrolizumab in previously treated patients with FGF19-expressing HCC. Methods Eligible patients were ≥18 years old with advanced HCC, prior systemic therapy, Child-Pugh A-B7 liver function, ECOG 0–2, and FGF19 overexpression. Patients received futibatinib 20 mg orally daily plus pembrolizumab 200 mg intravenously every 3 weeks. The primary endpoint was progression-free survival at 6 months (PFS6). Secondary endpoints included overall survival (OS), objective response rate (ORR), quality of life, and safety. Results Between August 2021 and March 2024, 14 patients enrolled and 13 were evaluable. Median age was 72 years (range, 60–87), 53.8% were male, 92.3% had Child-Pugh A liver function, and all had received prior immunotherapy. Median progression-free survival was 15 weeks (95% CI, 9.0–NE), with a PFS6 rate of 23.1% (95% CI, 8.6–62.3%). ORR was 0% (95% CI, 0–24.7%), while stable disease was observed in 53.9% of patients. Median OS was 55.7 weeks (95% CI, 47.3–NE). Grade ≥3 adverse events occurred in 69.2% of patients, and grade ≥4 adverse events in 15.4%. One grade 5 event (acute-on-chronic kidney injury) was deemed unrelated to treatment. Common adverse events included hyperphosphatemia, fatigue, diarrhea, elevated transaminases, dry eye, nail changes, rash, and oral mucositis. Conclusions Futibatinib plus pembrolizumab demonstrated an acceptable safety profile but did not meet efficacy thresholds supporting further study in FGF19-expressing HCC. Effective post-immunotherapy treatment strategies remain an unmet need.

Importance Recent case reports suggest that B antigen–containing blood products may be associated with anaphylactic transfusion reactions in recipients with preformed immunoglobulin E to galactose- α -1,3-galactose (alpha-gal). Objective To test the association of local alpha-gal syndrome (AGS) prevalence and allergic transfusion reaction (ATR) in patients with blood type O. Design, Setting, and Participants In this international, multicenter, retrospective cohort study at academic medical centers, sites were assigned to AGS high- or low-prevalence clusters based on the known geographic distribution of AGS. Data were collected on platelet or plasma transfusions and ATRs during 2020 to 2024. Consecutive patients receiving platelet or plasma transfusions were included. Exposures Patients with blood type O who received B or AB units and patients with blood type O who received O units (reference group) in AGS high- and low-prevalence clusters were compared. Main Outcomes and Measures Before data collection, the hypothesis was that if transfusion-related alpha-gal syndrome (TRAGS) is a true clinical entity, excess ATRs to group B or AB units would be detected in AGS high-prevalence regions exclusively. The main measure was the overall risk ratio (RR) for ATRs to B or AB plasma or platelets in AGS high- vs low-prevalence clusters. Results In total, 558 823 platelet and plasma transfusions at 40 sites in 5 countries were analyzed, of which ATRs occurred in 1744 transfusions (0.3%). In the US AGS high-prevalence cluster (9 sites), significantly more ATRs of any severity occurred among patients with blood type O who received B or AB units vs patients with blood type O who received O units (overall RR, 3.93; 95% CI, 2.96-5.21; P < .001). In contrast, in the primary analysis of the AGS low-prevalence cluster (15 sites), excess ATRs to B or AB units were not detected. In subgroup analyses among patients with blood type O receiving B units, the RR for moderate to severe ATRs was 9.14 (95% CI, 5.39-15.52; P < .001) in the AGS high-prevalence cluster vs 2.15 (95% CI, 1.34-3.47; P = .002) in the AGS low-prevalence cluster. Outside the US, a signal consistent with TRAGS was not detected. Conclusions and Relevance This cohort study provides provocative epidemiologic evidence that TRAGS may be a unique manifestation of AGS and a previously unrecognized risk associated with transfusion. In AGS high-prevalence regions, blood collectors and hospital transfusion services should consider approaches to preventing severe ATRs from B or AB plasma or platelet units.

ABSTRACT Background With increasing use of donation after circulatory death (DCD) donor grafts, the need for accurate risk‐stratification tools in liver transplantation has become critical. Machine perfusion has been shown to improve both graft and patient survival. However, existing prediction models were developed in the static cold storage (SCS) era and their accuracy when using machine perfusion remains unknown. Our study aims to study if current scoring systems can predict graft and patient survival for DCD livers preserved using normothermic machine perfusion (NMP). Methods This was a retrospective study of patient and graft survival in a two‐center U.S. DCD NMP cohort ( n = 532) between January 2022 and December 2024. Predicted graft and patient survival rates were obtained from established risk scoring systems, including the United Kingdom DCD risk score (UK‐DCD), Early Allograft Dysfunction (EAD) Olthoff score, Liver Graft Assessment Following Transplantation (L‐GrAFT 7 ) score, Donor Risk Index (DRI), Balance of Risk (BAR) score, and Survival Outcomes Following Liver Transplant (SOFT) score. Model discrimination was assessed using receiver operating characteristic (ROC) curves (C‐statistics). Survival outcomes across risk strata were estimated and compared using Kaplan‐Meier (KM) analysis. Results Across scoring systems, predicted survival consistently underestimated actual graft and patient survival in the NMP DCD cohort. The DRI, SOFT, EAD and L‐GrAFT 7 did not demonstrate predictive value. UK‐DCD predicted ≤85% and <40% 1‐year graft survival for its high‐risk and “futile” groups, whereas observed rates were 93.7% and 86.8%. BAR low‐risk predicted >60% 5‐year survival but 94.2% was observed; the high‐risk group predicted <60% and observed was 53.3%. Despite underestimations and generally poor C‐statistics, in KM stratification, high‐risk groups still showed statistical differences in the UK‐DCD categories ( p = 0.007), and in SOFT score groups ( p < 0.001). No statistical difference was seen in BAR ( p = 0.36), DRI ( p = 0.36), EAD ( p = 0.12), or L‐GrAFT 7 ( p = 0.75). Conclusion Existing liver transplant risk scores show limited predictive value for donor‐related risk factors in the NMP era, whereas recipient‐related factors remain somewhat predictive, despite overestimating risk. Early allograft dysfunction metrics were not reliable predictors of short or long‐term outcomes. Future risk models should integrate machine‐perfusion parameters and refined donor variables to reflect outcomes more accurately in contemporary DCD liver transplantation.