Journal of Internal Medicine

BackgroundPatients with cirrhosis are highly susceptible to infections due to immune dysfunction and gut barrier impairment. Non-bloodstream infections frequently trigger decompensation and mortality, yet the global distribution of antimicrobial resistance (AMR) in these infections is poorly characterized. MethodsWe performed a systematic review and meta-analysis of studies reporting AMR in non-bloodstream bacterial infections among patients with cirrhosis. PubMed, Embase, and Web of Science were searched up to 15 September 2025. Pooled prevalence estimates of multidrug-resistant (MDR) and key resistant pathogens were calculated using random-effects models. Subgroup analyses were performed by country income, continent, and bacterial species. ResultsThirty-one studies including 3,162 infections were analysed. Spontaneous bacterial peritonitis predominated (79%), followed by colonisation (12%) and urinary tract infections (7%). Gram-negative bacteria accounted for 60% of infections (Escherichia coli 29%, Klebsiella pneumoniae 11%), while Gram-positive pathogens represented 39% (Enterococcus spp. 14%, Staphylococcus aureus 6%). Overall pooled MDR prevalence was 29%, with higher burdens in lower-middle-income countries (MDR 47% vs. 22-41%; ESBL 24% vs. 10%; VRE 21% vs. 3%; CRE 32% vs. 1%). Genotypic data identified 436 resistance genes with marked continental differences. ConclusionCirrhosis-associated non-bloodstream infections are dominated by Gram-negative bacteria and show high MDR, particularly in lower-middle-income countries. These findings highlight the need for integrated phenotypic and genomic surveillance of resistance patterns in these settings to guide empiric therapy.

Background and AimMASLD affects 30-38% of Indian adults, yet the contribution of genetic risk variants to disease susceptibility and fibrosis progression remains poorly characterised. We investigated the association of 12 candidate SNPs with MASLD susceptibility and fibrosis severity in North Indian patients, benchmarking allele frequencies against IndiGenomes and global populations. MethodsSixty-nine MASLD patients (75.4% male; median BMI 29.8 kg/m{superscript 2}) from a tertiary care liver clinic in New Delhi were genotyped for 12 SNPs using Illumina custom BeadChip array and Sanger sequencing. Patients were stratified by liver stiffness measurement (LSM): significant fibrosis ([&ge;]8 kPa, n=38) versus no significant fibrosis (<8 kPa, n=31). Allele frequencies were compared with IndiGenomes ([~]1,020 Indian individuals) and 1000 Genomes populations. ResultsPNPLA3 rs738409 G allele was the strongest within-cohort predictor of significant fibrosis (allelic OR 2.89, 95% CI 1.35-6.19, P=0.006; dominant model OR 3.94, P=0.008), with carriers demonstrating higher LSM (median 15.6 vs. 7.5 kPa, P=0.005). SAMM50 rs3761472 (OR 2.12, P=0.065) and FTO rs9939609 (OR 2.08, P=0.089) showed non-significant trends. In the population-level comparison, APOC3 rs2854116 T allele was the only variant significantly enriched after Bonferroni correction (64.0% vs. 47.9%; OR 1.93, 95% CI 1.35-2.77, P<0.001), followed by PNPLA3 (33.3% vs. 24.1%, OR 1.57, P=0.019) and SAMM50 (31.2% vs. 22.6%, OR 1.55, P=0.028). Notably, APOC3 showed no association with fibrosis (OR 0.96, P=1.000), suggesting a role in susceptibility rather than progression. All SNPs were in Hardy-Weinberg equilibrium. ConclusionsThis study reveals a dissociation between genetic determinants of MASLD susceptibility and fibrosis progression in North Indian patients. APOC3 rs2854116 predisposes to MASLD at the population level, while PNPLA3 rs738409 drives fibrosis severity within established disease, underscoring the need for ancestry-specific genetic risk stratification. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=112 SRC="FIGDIR/small/26347059v1_ufig1.gif" ALT="Figure 1"> View larger version (69K): org.highwire.dtl.DTLVardef@187f189org.highwire.dtl.DTLVardef@25d3borg.highwire.dtl.DTLVardef@13704e9org.highwire.dtl.DTLVardef@1238cce_HPS_FORMAT_FIGEXP M_FIG C_FIG

BackgroundPost-viral diseases, including post-COVID-19 syndrome (PCS) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), cause substantial long-term morbidity. Persistent cardiovascular (CV) risk after acute infection highlights the need for accessible tools to quantify microvascular health. MethodsAll Eyes on PCS is a prospective, observational study investigating the retinal microcirculation using retinal vessel analysis (RVA). We compared RVA parameters in 102 PCS patients with 204 age- and sex-matched healthy controls (HC, matched from n = 303). Secondary matched analyses included never infected controls (NI, n = 96), recovered individuals (n = 102), PCS patients, and ME/CFS patients (n = 62). Laboratory variables, circulating markers of endothelial dysfunction (ED) and inflammation were compared between cohorts and their associations with RVA parameters were examined. ResultsCompared with HC, PCS patients showed reduced venular flicker-induced dilation (3.7 {+/-} 2.2% vs. 4.5 {+/-} 2.7%, p = 0.005), narrow retinal arterioles (CRAE, 178.3 {+/-} 15.5 {micro}m vs. 183.3 {+/-} 15.9 {micro}m, p = 0.009), and lower arteriolar-to-venular ratio (0.83 {+/-} 0.06 vs. 0.86 {+/-} 0.07, p = 0.004). Findings persisted after adjustment for CV factors and remained evident in an extended secondary matched analysis across NI, recovered, and PCS patients. ME/CFS patients showed the most pronounced alterations. PCS severity correlated with lower AVR (r = -0.21, p = 0.037) and reduced arteriolar FID (r = -0.21, p = 0.039), particularly for neurocognitive symptoms. IL-6, ICAM-1 and VCAM-1 were elevated in PCS and ME/CFS and lower AVR correlated with inflammatory and iron-related markers (all adjusted p < 0.01). A combined model discriminated ME/CFS patients with good accuracy (AUC = 0.80). ConclusionsPCS is associated with persistent ED, most pronounced in ME/CFS patients and linked to symptom severity and ongoing inflammation. RVA may provide a noninvasive, readout of ED in post-viral syndromes. Trial RegistrationThe All Eyes on PCS Study has previously been registered at ClinicalTrials.gov (NCT05635552). Novelty and SignificanceO_ST_ABSWhat is known?C_ST_ABS- PCS and ME/CFS are associated with persistent endothelial dysfunction and increased long-term cardiovascular risk. - Neurocognitive symptoms in post-viral syndromes have been linked to impaired neurovascular coupling. - Retinal vessel analysis provides a validated, non-invasive readout of systemic and cerebral microvascular health. What new information does this article contribute?- PCS is characterized by persistent functional and structural retinal microvascular dysfunction - Retinal endothelial dysfunction scales continuously with post-viral disease severity and is most pronounced in patients fulfilling ME/CFS criteria. - Retinal microvascular alterations are linked to inflammatory-endothelial activation and iron dysregulation, identifying a biologically coherent vascular phenotype. This study provides the first comprehensive human in vivo assessment of retinal microvascular structure and function across the full post-COVID-19 spectrum, from never infected controls to recovered individuals, PCS patients, and those fulfilling ME/CFS criteria. Using retinal vessel analysis as a surrogate of neurovascular and endothelial function, we demonstrate that endothelial dysfunction persists in patients with ongoing post-viral symptomatology. Retinal venular flicker-induced dilation, arteriolar caliber, and autoregulatory capacity decline progressively with increasing clinical severity, indicating a dose-response relationship between microvascular injury and post-infectious disease burden. Importantly, these vascular alterations are linked to sustained inflammatory and endothelial activation and to disturbances in iron homeostasis, indicating an inflammatory-endothelial axis rather than isolated cardiovascular risk. By integrating microvascular phenotyping with symptom profiles and circulating biomarkers, this work identifies retinal endothelial dysfunction as a mechanistically informative and clinically accessible marker of post-viral disease severity. These findings advance understanding of post-infectious vascular pathology and provide a translational framework for biological stratification and risk assessment in PCS and ME/CFS.

ObjectivePrevalence of anemia in persons with spinal cord injury is higher than their able-bodied counterparts at 50-80%. The etiology is multifactorial but likely related to chronic whole-body inflammation. Chronic anemia is often an indication of gastrointestinal blood loss leading to a diagnostic colonoscopy. However, colonoscopies in persons with spinal cord injury are not without complications. We tested the hypothesis that, despite a high incidence of anemia, performing a colonoscopy in persons with spinal cord injury has a high complication rate and low rate of finding high risk pathology. DesignRetrospective chart review Subjects41 persons with chronic spinal cord injury admitted for colonoscopy from 2019-2024. MethodsPercent of complications and abnormal findings were calculated. A logistic regression model determined predictors of complications and abnormal findings. ResultsAnemia prevalence was 59.1% with a complication rate of 38.6% and 59 abnormal findings in 95.2% of CSPs (n=4 (6.8%), high-risk pathology). Persons with anemia had a higher risk of complications and a decreased risk of hemorrhoids. ConclusionIn persons with spinal cord injury, given a low-rate high risk pathology in the setting of a high complication rate, especially in persons with anemia, the risk of complications should be weighed more heavily in the decision to perform a colonoscopy.

IntroductionHyperferritinemia is a prognostic marker in critical illness, but its role in postoperative outcomes of pediatric congenital heart defects remains poorly defined, especially in resource-limited settings. This study evaluated early serum ferritin as a predictor of outcomes after congenital heart surgery and its association with the PIM 3 score. MethodsA single-center, prospective cohort study was conducted from April 2023 to October 2024 at a tertiary referral center in southeastern Brazil. Patients aged 29 days to 18 years, of both sexes, admitted to the PICU after congenital heart surgery were included and categorized as cyanotic or acyanotic. Statistical significance was defined as two-sided p < 0.05. ResultsA total of 105 patients were included. Median ferritin was higher in patients with PICU stays < 7 days (183 ng/mL; p = 0.004) and was significantly associated with a PIM 3 score [&ge;] 5% (642 ng/mL; p < 0.006). Cyanotic patients had longer PICU stays (11.0 vs. 7.2 days; p = 0.02), longer use of vasoactive drugs (3.8 vs. 2.6 days; p = 0.01), and accounted for all deaths (p < 0.001). Hemoglobin and hematocrit were also significantly higher in cyanotic patients (14 vs. 13 g/dL and 40% vs. 37%; p < 0.001). ConclusionsSerum ferritin may serve as a marker of secondary outcomes and aid early risk stratification in congenital heart defects patients in the PICU.

BackgroundDynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) enables non-invasive characterization of carotid atherosclerotic plaque. PurposeTo evaluate the performance and reproducibility of a simplified DCE-MRI quantification method for carotid plaque assessment. MethodsT1-weighted black-blood DCE-MRI of the carotid arteries at 3T was performed at baseline and after six months in patients with mild-to-moderate atherosclerotic lesions in a pilot placebo-controlled randomized trial evaluating the effects of low-dose (0.5mg daily) colchicine therapy on carotid plaque volume. DCE-MRI signal intensity was measured in manually drawn regions of interest in the plaque core, remote non-atherosclerotic vessel wall, and skeletal muscle. Peak signal intensities were normalized to skeletal muscle signal in the same slice. ResultsIn patients (n=28, median [interquartile range] age 72 [64-74] years, 36% female, n=13/15 colchicine/placebo), normalized peak signal intensity was higher in the plaque core than in the remote vessel wall at both baseline (3.5 [2.3-4.1] vs 2.1 [1.7-2.5], p<0.001) and follow-up (3.2 [2.5-4.4] vs 2.0 [1.7-2.5], p<0.001). Measurements did not differ between baseline and follow-up for all patients (0.7{+/-}0.7 for plaque core, 0.6{+/-}0.4 for remote vessel wall, p>0.80 for both) nor between colchicine intervention and placebo control (p>0.35 for either region). ConclusionsNormalised peak signal intensity on DCE-MRI was consistently higher in the carotid plaque core than in the remote vessel wall, showed excellent reproducibility in both regions over six months, and was not altered by colchicine treatment. This simplified, muscle-normalised approach may facilitate future studies exploring DCE-MRI measures potentially related to plaque vulnerability.

BackgroundAlthough ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) are very similar regarding pathophysiology and clinical treatments, especially NSTEMI comprises a much more heterogenic group of patients and underlying diseases. We therefore aimed to assess the treatments and outcomes of both entities in a large contemporary cohort. MethodsPatients with STEMI and NSTEMI between 01/2010 to 12/2018 were identified from the largest German Health Insurance (AOK, {approx}26 million members). Patient demographics, their hospital course, adherence to guideline-directed drug therapy and overall survival were assessed. ResultsIn total 544,529 patients (mean age 74, IQR 62-82), one third of whom had a STEMI. Chronic kidney disease, peripheral arterial disease, and heart failure were more common in patients with NSTEMI. Patients with STEMI were more likely to get coronary angiograms and percutaneous coronary interventions. Although STEMI more frequently led to cardiogenic shock, the rate of serious cardiac events was lower. Mortality was higher for STEMI only within the first 30 days, whereas long-term survival rates were better. The combination of statins, angiotensin converting enzyme inhibitors /angiotensin receptor blockers, beta blockers, and oral anticoagulants or antiplatelet agents was associated with higher overall survival in patients with STEMI (hazard ratio [HR] 0.20; 95% confidence interval [95%CI] 0.18 - 0.24; p<0.001) or NSTEMI (HR 0.30; 95%CI 0.28 - 0.33; p<0.001). Nevertheless, the prescription rates decreased over time, particular in patients with NSTEMI. ConclusionClear differences between STEMI and NSTEMI were observed regarding short-and long-term survival. Guideline-recommended therapy improved long-term survival, but decreased during the follow-up period.

BackgroundEarly lactate is widely used to risk-stratify septic shock, yet clinically actionable cut-offs for 28-day mortality remain uncertain. MethodsIn a single-centre study conducted across two intensive care units, we analysed 84 adults with septic shock identified within 24 hours of intensive care unit admission. The primary endpoint was 28-day mortality. Four lactate metrics obtained during the first 24 hours were evaluated: first (admission) lactate, last lactate, peak lactate, and lactate clearance from first to last. Associations were tested using logistic regression with and without adjustment for the Simplified Acute Physiology Score 3; discrimination was assessed by area under the receiver-operating characteristic curve (AUROC), and optimal cut-offs were defined by the Youden index. ResultsThirty-nine of 84 patients (46.4%) died by day 28. Higher absolute lactate values were independently associated with death (adjusted odds ratio (OR) per 1 mmol/L increase: First 1.47, p<0.001; Last 1.41, p=0.002; Peak 1.39, p<0.001), whereas Lactate clearance was not (OR 0.65, p=0.202). Discrimination was moderate to good for peak (AUROC 0.817), first (0.791), and last (0.757) lactate, and poor for clearance (0.577). Youden-derived thresholds provided pragmatic trade-offs: First 3.55 mmol/L (sensitivity 0.821, specificity 0.689), Last 3.15 mmol/L (0.567, 0.864), and Peak 3.55 mmol/L (0.973, 0.556). Kaplan-Meier curves using these cut-offs showed early and sustained separation. ConclusionsIn adults with septic shock, simple early lactate thresholds around 3.3- 3.6 mmol/L (first/peak) and approximately 3.15 mmol/L (last) identify 28-day mortality risk and outperform lactate clearance.

BackgroundSepsis is a major public health challenge, and reliable biomarkers are essential for distinguishing sepsis from other conditions. Neutrophil Gelatinase-Associated Lipocalin (Neutrophil gelatinase-associated lipocalin (NGAL)) has shown promise as a diagnostic marker due to its role in the immune response. This study evaluates plasma NGAL as a diagnostic tool at the time of ICU admission. MethodsWe analysed plasma NGAL and C-reactive protein (CRP) levels in 4732 adult patients admitted to four ICUs between 2015 and 2018. All patients were retrospectively screened for Sepsis-3 criteria at ICU admission. The discriminative performance of NGAL and CRP for sepsis was assessed using receiver operating characteristic (ROC) analysis, with NGAL levels adjusted for Chronic kidney disease (CKD) and age. Patients were stratified by renal function. ResultsPlasma NGAL levels were significantly higher in septic patients (p<0.001). For the whole cohort, NGAL alone yielded an Area under the curve (AUC) of 0.67 (Confidence interval (CI) 0.66-0.69), CRP yielded an AUC of 0.72 (CI 0.71-0.73, p<0.001), and combining NGAL with CRP nominally improved discriminative performance (AUC 0.74 vs 0.72, p<0.001). Stratified analyses indicated that NGAL, together with CRP, significantly outperformed CRP alone in patients with no kidney injury and those with Acute Kidney Injury (AKI) only. In contrast, differences were not significant in patients with CKD only or CKD and AKI. ConclusionIn this large cohort, NGAL showed modest discrimination for sepsis, with a nominal improvement when combined with CRP. These findings do not indicate that NGAL meaningfully improves sepsis diagnosis in the ICU.

ObjectiveTo assess whether focal and non-focal COVID-19 ARDS exhibit different respiratory mechanics and arterial blood gas (ABG) trajectories during the first extended prone positioning (PP) session. DesignPost-hoc analysis of a previously published retrospective monocentric cohort study. SettingA university-affiliated intensive care unit in Paris (France) between March 2020 and April 2021. PatientsSeventy-four adult patients with moderate-to-severe COVID-19 ARDS who underwent extended prone positioning (PP) and had chest imaging (CT or X-ray) performed within five days before the first PP session. InterventionsNone MeasurementsChanges in compliance, driving pressure, PaO2/FiO2 ratio, and ventilatory ratio between pre-PP and end-of-PP; chest X-rays and CT scans diagnostic agreement between reviewers assessed by crude agreement and Cohens kappa coefficient. Main resultsDiffuse ARDS predominated, identified in 91% by the intensivist and 86% by the radiologist. Crude diagnostic agreement was 89% (95% CI 79.8-95.2), while interrater reliability was only fair ({kappa} = 0.44, 95% CI 0.08-0.81). Discrepancies mainly involved focal classifications on chest X-rays, whereas agreement was perfect when CT scans were available. The small number of focal cases precluded comparative analysis of PP trajectories. ConclusionsPP indication or duration should probably not be based on ARDS phenotypes and when differentiating focal from diffuse COVID ARDS is necessary, chest CT scans should be preferred to ensure accurate and reproducible phenotyping.

BackgroundCarbohydrate-restricted diets are gaining popularity, including among lean individuals. In these populations, a lipid phenotype often emerges comprising elevated LDL cholesterol (LDL-C), alongside elevated HDL-C and low triglycerides, termed the lean mass hyper-responder (LMHR). ObjectiveTo evaluate one-year coronary plaque progression in LMHRs and near-LMHRs. MethodsThis prospective study followed 100 participants who developed the triad of high LDL-C, high HDL-C, and low triglycerides after adopting a ketogenic diet over one year. Coronary plaque changes were assessed using coronary CT angiography and analyzed using the prespecified QAngio(R) methodology (Leiden, the Netherlands), with AI-enabled coronary plaque analysis (AI-CPA; HeartFlow(R) Inc., Mountain View, CA) used as an independent, blinded confirmatory analysis. Plaque burden and plaque progression predictors were examined using linear regression. ResultsAll 100 participants with elevated LDL-C and a mean BMI of 22.5 {+/-} 2.7 kg/m2 completed the study. At baseline, 57 (57%) had zero CAC. After follow-up, most participants remained with low-risk plaque burden markers: 81% of participants had a CAC score <100, and 54% had a CAC of 0. The median increase in non-calcified plaque volume was 5.6 mm3 (37% relative increase). Notably, 15% of participants exhibited plaque regression despite sustaining elevated LDL-C (mean 242 mg/dL) and ApoB (mean 180 mg/dL). Additionally, 78% had percent atheroma volume (PAV) below the high-risk threshold of 2.6%, and 93% had total plaque volume (TPV) below the high-risk threshold of 254 mm3. Baseline plaque metrics were consistently predictive of plaque progression. By contrast, neither ApoB levels nor cumulative LDL-C exposure predicted plaque progression in this population of LMHR and near-LMHR individuals. ConclusionThese findings suggest that over one year, progression was modest and heterogeneous in this population, with baseline coronary plaque emerging as the strongest predictor of subsequent plaque progression in LMHRs, whereas traditional lipid markers such as ApoB and LDL are not.

BackgroundCirculating lipoprotein(a) [Lp(a)] levels are highly heritable and linked to atherosclerotic cardiovascular disease, yet clinical measurement rates remain low (<1%) in the United States. The high heritability of Lp(a) across populations makes genetic prediction an attractive approach for closing this testing gap, but existing polygenic scores transfer poorly across populations. Haplotype-based prediction models, which use standard genome-wide genotype data to capture common-, rare-, and structural-variation at the LPA locus, could bridge this gap, enabling opportunistic identification of individuals with elevated Lp(a) levels across diverse populations within existing large, genotyped cohorts. ObjectivesThis study sought to develop and validate a haplotype-based prediction model using genome-wide genotype data to identify individuals with elevated Lp(a) levels across diverse populations. MethodsWe developed an LPA-haplotype model using data from the All of Us Research Program and validated it in the Penn Medicine BioBank (PMBB), Mass General Brigham Biobank (MGBB), and Mount Sinai BioMe cohorts. Primary outcomes included model performance for predicting continuous Lp(a) concentrations (r{superscript 2}) and identifying elevated Lp(a) levels (>125 nmol/L) through positive predictive value (PPV) and number needed to test (NNT). ResultsAmong PMBB (n = 1856), MGBB (n = 1401), and BioMe (n = 1686) participants with available genotype and Lp(a) measurements, average age was 60 years, and 51% were female. Overall r{superscript 2} of the haplotype model was 0.46 (95% Credible Interval [CrI] 0.32 to 0.6), with similar performance across genetically inferred ancestries and cohorts. For identifying elevated Lp(a) levels >125 nmol/L the overall PPV was 0.81 (95% CrI 0.6 to 0.89), corresponding to a NNT of 1.2 (95% CrI 1.1 to 1.7) individuals predicted to have elevated levels needing to undergo clinical testing to identify one true elevation. In the full PMBB cohort (n = 49310), the haplotype model identified elevated Lp(a) at a rate of 128 per 1000 (95% CrI 125 to 130), corresponding to an estimated 14.4-fold improvement (95% CrI 13.1 to 15.9; P(improvement) = 1) in identification rate compared with the existing rate of clinical assessment. ConclusionsA haplotype-based genetic model effectively identified individuals with elevated Lp(a) levels across diverse populations, with potential utility for opportunistic screening among cohorts where genotype data is available, but Lp(a) testing rates are low.

BackgroundClonal hematopoiesis of indeterminate potential (CHIP) is associated with cardiovascular disease (CVD) in the general population and is more common among people with HIV (PWH). The mechanisms by which CHIP contributes to atherosclerosis in PWH are unknown. We hypothesized that CHIP is associated with carotid atherosclerosis, arterial inflammation, and hematopoietic activity among PWH. MethodsIn a cohort study, we studied PWH ages 31-74 years. CHIP mutations were detected with a validated targeted sequencing assay. Carotid intima-media thickness (IMT) was measured longitudinally with ultrasound. Aortic inflammation and lymph node activity were assessed cross-sectionally using 18F-FDG-PET. Inflammatory biomarkers were measured using multiplex electrochemiluminescence assay. Linear regression was employed, with adjustments for traditional and HIV-related factors. ResultsWe included 230 PWH (52{+/-}9 years, 7% female); 32 (14%) had CHIP with median variant allele fraction of 2.8%. Common mutations were in DNM3TA (n=21) and TET2 (n=6). Age was associated with CHIP (OR 2.0 per decade older, 95% CI 1.3-3.01; p=0.002). Among 166 participants with IMT measurements (CHIP=23), CHIP was not associated with IMT (p=0.21; unchanged after adjustment). Among 80 with FDG-PET, CHIP (n=12) was not associated with arterial inflammation (p=0.89), but was associated with higher lymph node metabolic activity (p=0.03) that was attenuated in reference to background activity and adjusted for risk factors. CHIP was not associated with soluble inflammatory markers or viral persistence markers. ConclusionsAmong PWH, CHIP mutations were not associated with subclinical atherosclerosis, arterial inflammation, or soluble inflammatory markers but were related to hematopoietic activity. The mechanism by which CHIP increases HIV-associated atherosclerosis may preferentially involve lymph nodes and merits additional evaluation.

Neuronal intranuclear inclusion disease (NIID) is a neurodegenerative condition characterized by the presence of intranuclear inclusions in neuronal and visceral cells. Patients with NIID can present respiratory symptoms; however, data on pulmonary functions in NIID are lacking. This study investigated the respiratory conditions in NIID patients diagnosed with histopathological and genetic studies. We conducted two spirometries before and after administrating the bronchodilator in NIID patients with asthmatic histories or symptoms. We statistically compared pre- and post-measured values including forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and peak expiratory flow (PEF). Before two spirometries, we also measured fractional concentration of exhaled nitric oxide (FeNO), if possible. Of the 51finally enrolled patients, 17 (33.3%, 95% CI 20.8% to 47.9%) patients had asthmatic histories or symptoms, and 14 patients received two spirometries. After administrating the bronchodilator, FEV1 and PEF significantly increased by 150 mL (6.01%, p = 0.002) and 260 mL/s (6.72%, p = 0.017), respectively. The median (interquartile range) of FeNO measured in nine patients was 15 (10-21) ppb. Patients with NIID have airflow reversibility like asthma. Airway inflammation is less associated with this condition; thus, immunomodulators such as corticosteroid may not improve respiratory symptoms in NIID.

PurposePortal hypertension, a major complication of chronic liver disease, leads to significant morbidity and mortality. While portal vein diameter measured on imaging has long been proposed as a non-invasive marker of portal hypertension, normative CT-based reference values and population-level associations remain incompletely characterized. Here, we aim to define contemporary reference values for portal vein diameter on clinically obtained CT and evaluate its associations with demographic, clinical, and imaging factors, as well as its diagnostic performance for portal hypertension. MethodsWe conducted a retrospective analysis of 20,225 clinically obtained CT scans at a single academic medical center. The main portal vein was automatically segmented using Total Segmentator, and maximum diameter extracted using the Vascular Modeling Toolkit. Associations with demographic and imaging factors were evaluated using linear mixed-effects models; prevalent liver disease and portal hypertension using logistic regression; risk of incident ascites and esophageal varices among participants with liver disease using Cox regression; and invasive hepatic venous pressures using correlation analysis and linear regression. ResultsThe mean portal vein diameter was 12.4 mm (95% CI, 12.37-12.45). Larger diameter was independently associated with male sex (+1.4 mm), higher BMI (+0.11 mm/kg/m2), greater height (+0.04 mm/cm), and older age (+0.05 mm/10 years) (all p <0.001), and was substantially larger on contrast-enhanced abdomen/pelvis CT (+2.4 mm, p <0.001). Each 1-mm increase in portal vein diameter was associated with higher odds of prevalent liver disease (OR 1.06; 95% CI, 1.04-1.08) and portal hypertension (OR 1.18; 95% CI, 1.12-1.28). Among individuals with liver disease, greater diameter predicted higher risk of incident esophageal varices (baseline diameter HR 1.50; 95% CI, 1.14-2.08) and ascites (HR per mm increase in diameter 1.06; 95% CI, 1.003-1.12). However, portal vein diameter demonstrated weak to no association with invasively measured hepatic venous pressures. ConclusionIn this large, EHR-linked imaging cohort, the mean portal vein diameter on CT was 12.4 mm and varied with demographic and imaging factors. Larger diameter was associated with liver disease, portal hypertension, and subsequent development of varices and ascites, supporting use of portal vein diameter as a pragmatic screening or enrichment tool within multimodal clinical frameworks. Key ResultsO_LIMean portal vein diameter on routine clinical CT was 12.4 mm (95% CI, 12.37-12.45) and varied with sex, height, BMI, exam type, contrast use, and clinical setting. C_LIO_LIEach 1-mm increase in portal vein diameter was associated with higher odds of prevalent liver disease (OR 1.06) and portal hypertension (OR 1.18). C_LIO_LIAmong individuals with liver disease, larger portal vein diameter predicted higher risk of incident esophageal varices and ascites, independent of demographic and imaging factors. C_LI

ImportanceRecent reports have highlighted an intense influenza activity related to the circulation of the influenza A(H3N2) subclade k variant. There is no data available on the impact of the emergence of H3N2 subclade k on the severity of the 2025-2026 epidemic or on the clinical phenotype of patients requiring admission to the intensive care unit (ICU). ObjectiveTo compare the clinical presentation, hospital mortality and virological characteristics of patients with laboratory-confirmed influenza infection included in French intensive care units during the 2025-2026 epidemic season with those of patients admitted during the 2024-2025 season. We also aimed at measuring the impact of the A(H3N2) subtype on hospital mortality during the 2025-2026 season. DesignProspective, multicenter, observational SEVARVIR cohort study including patients admitted during the 2024-2025 and 2025-2025 influenza seasons. SettingForty-two French ICUs ParticipantsAdult patients with laboratory-confirmed influenza infection Interventionsnone Main Outcomes and MeasuresThe primary outcome measure was in-hospital mortality. ResultsPatients admitted in intensive care units for influenza in 2024-2025 (n=360) and 2025-2026 (n=325) were included in the French nationwide prospective multicentre SEVARVIR study. There was no significant difference in day-28 mortality between the seasons (12.7%, n=45/355 vs 16.5% n=28/170; p=0.28). In the 2025-26 season, 49% had the A(H1N1) subtype and 51% the A(H3N2) subtype (k subclade: 77%). The univariable Cox analysis revealed that patients infected with A(H3N2) viruses were at greater risk of death over time. Multivariable Cox analysis revealed that during the 2025-2026 season, age (adjusted hazard ratio, aHR=1.05 [1.00;1.11]; p=0.046) and the clinical frailty scale (aHR=1.82 [1.26;2.72]; p=0.001) were associated with an increased risk of death. The A(H3N2) subtype was not associated with an increased risk of death (aHR=1.13 [0.32;4.51]; p=0.85). Phylogenetic analyses from our ICU cohort together with 300 contextual sequences from community-acquired influenza cases collected during the same period showed no clustering according to severity. Conclusions and RelevanceThis French national prospective observational study, found that the emergence of the influenza A(H3N2) subclade K was associated with an increased risk of death in univariable but not multivariable analysis, adjusting for host-related factors. Trial RegistrationNCT051625 Key PointsQuestion: What impact did the 2025-26 influenza epidemic and the A(H3N2) variant have on the mortality of patients admitted to intensive care units? Findings: In this prospective, nationwide cohort study of 685 patients admitted to intensive care units with severe influenza during the 2024-25 or 2025-26 seasons, no difference in hospital mortality was observed between the two seasons. Patients infected with the A(H3N2) virus, 77% of which corresponded to clade k, were at higher risk of death in univariable but not in multivariable analysis after adjusting for age and clinical frailty scale. Meaning: Patients in intensive care units with severe A(H3N2) infection during the 2025/2026 season were not at higher risk of death after adjusting for confounding variables.

ImportanceBowel ultrasound (BUS) offers real-time assessment of bowel integrity and perfusion, but its clinical impact on diagnosis and management of necrotizing enterocolitis (NEC) remains unclear. ObjectiveTo evaluate whether adding BUS to standard abdominal radiography (AXR) improves diagnostic decision-making and clinical outcomes in infants evaluated for suspected NEC. DesignRandomized clinical trial. SettingLevel IV neonatal intensive care unit (NICU) of a freestanding childrens hospital (BUS-experienced) and a level III NICU of an adult hospital (BUS-naive). ParticipantsInfants undergoing imaging for suspected NEC. InterventionsInfants randomized by calendar month to AXR alone or AXR + BUS. Clinical management followed standard NICU practice. Main Outcomes and MeasuresThe primary outcome was time to full enteral feeds within 30 days of NEC concern. Secondary outcomes included duration of antibiotics and bowel rest. Analyses followed the intention-to-treat principle, with per-protocol sensitivity analyses. Post-imaging survey assessed the perceived impact of adding BUS on diagnostic and therapeutic decision-making. ResultsA total of 169 infants (199 NEC evaluations; 114 AXR, 85 AXR + BUS) were included; 84% were preterm, and 62% were from the level IV NICU. Among infants ultimately classified as extended NEC rule-out (NEC excluded after repeated imaging evaluations), BUS was associated with faster recovery to full feeds (median 4 vs 8 days; hazard ratio [HR], 1.89; 95% CI, 1.23-2.91). No differences were observed among infants with quick NEC rule-out (NEC excluded after single imaging evaluation) or confirmed NEC. BUS did not prolong antibiotic or bowel rest duration. Per-protocol analysis yielded similar results for all outcomes. Neonatologists reported greater diagnostic and therapeutic confidence with BUS. Conclusions and RelevanceIn this dual-site randomized trial, adding BUS to standard AXR accelerated feeding recovery among infants with prolonged diagnostic evaluations for suspected NEC, without increasing adverse events. BUS may enhance diagnostic confidence and streamline management in cases of diagnostic uncertainty. Larger multicenter studies are warranted to confirm these findings and guide implementation across NICU settings. Trial RegistrationClinicalTrials.gov Identifier NCT05573113 Key PointsO_ST_ABSQuestionC_ST_ABSDoes adding bowel ultrasound to standard radiography improve outcomes among infants evaluated for suspected necrotizing enterocolitis? FindingsIn this randomized diagnostic trial of 169 infants, adding bowel ultrasound shortened time to full feeds among infants with prolonged diagnostic evaluations without increasing adverse events. MeaningBowel ultrasound may enhance diagnostic confidence and expedite feeding recovery in infants with diagnostic uncertainty for NEC.

BackgroundThe role of arterial blood gas (ABG) testing in the intensive care unit (ICU) remains debated within the "less is more" paradigm. While unnecessary testing may pose risks without benefit, timely ABGs provide critical information in unstable patients. Institutional variation in early ABG utilization and its association with outcomes remains unclear. MethodsWe conducted a multicenter retrospective cohort study using the Japanese Intensive Care PAtient Database (JIPAD) between April 2015 and March 2023. Adult ICU patients with a stay [&ge;]24 h and arterial line placement were included. The standardized number of ABGs (SNABGs) within the first 24 h was calculated as the ratio of observed to expected values, where expectations were derived from a multivariable model adjusting for patient covariates. ICUs were categorized into tertiles according to SNABG utilization. The primary outcome was in-hospital mortality, analyzed using multilevel logistic regression with ICU-level random intercepts. Restricted cubic splines were used to explore non-linear associations. ResultsAmong 117,546 patients from 87 ICUs, the mean number of ABGs varied widely. After standardization, SNABGs ranged from 0.73-0.90 in the low tertile to 1.09-1.15 in the high tertile. In the multilevel model, SNABG was not significantly associated with in-hospital mortality (adjusted OR 0.942 [95% CI 0.807-1.100] for tertile 2; 0.874 [95% CI 0.751-1.017] for tertile 3). Flexible modeling suggested a non-linear trend toward better outcomes with higher utilization, but confidence intervals included unity. ConclusionEarly ABG utilization varied across ICUs, yet was not significantly associated with mortality. Sensitivity analysis suggested a non-linear relationship, with a tendency toward better outcomes at higher utilization. These findings warrant further investigation to clarify the role of early ABG utilization in critical care.

AimsThis study aimed to examine the prevalence of malnutrition and its associations with functional capacity and quality of life (QoL) in AL and ATTR cardiac amyloidosis patients. Methods and ResultsThis cross-sectional pilot study included 29 patients with confirmed CA (14 AL, 15 ATTR). Data were collected between January 2020 and September 2021. Nutritional status was assessed using body mass index (BMI), anthropometric measures, and the Subjective Global Assessment (SGA). Functional capacity was evaluated via handgrip strength and the 6-minute walk test, while QoL was assessed using the SF-36 and Kansas City Cardiomyopathy Questionnaire. Malnutrition, as determined by SGA, was present in 62% of patients, with no significant difference between AL and ATTR subtypes. In contrast, BMI according to WHO criteria failed to identify any cases of malnutrition, highlighting its limited utility in this population. These results suggest that conventional indicators may underestimate nutritional impairment in CA. Although overall QoL and functional capacity did not differ significantly between nutritional groups, malnourished AL patients showed notably lower QoL scores compared with well-nourished peers. ConclusionMalnutrition is highly prevalent in cardiac amyloidosis and seems to particularly affect the AL subtype. These findings underscore the importance of routine nutritional screening and targeted interventions, as early identification and management of malnutrition may improve patients quality of life and long-term outcomes.

BackgroundHFE p.C282Y (c.845G>A; rs1800562) is a common missense mutation in persons of European ancestry, but we found no comprehensive tabulation of p.C282Y allele frequencies in Iberia. MethodsWe performed computerized and manual searches to identify evaluable reports of p.C282Y alleles in population/control cohorts [&ge;]50 subjects in Iberia. We tabulated numbers of subjects, nominal geographic sites of cohort recruitment, cohort characteristics, corresponding latitudes and longitudes, and p.C282Y allele frequencies [95% confidence intervals]. We computed the aggregate p.C282Y allele frequencies of mainland Spain and mainland Portugal and compared the aggregate frequencies using the Chi-square test (two-tailed). Using combined mainland Spain and mainland Portugal data, we computed the aggregate p.C282Y allele frequency in Iberia. ResultsWe identified 25 cohorts in mainland Spain (12,297 subjects; 11 of the 15 autonomous communities) and nine cohorts in mainland Portugal (1,024 subjects; each of the five administrative regions). Cohorts were recruited in this region: latitude 43.4619 - 37.2299{degrees} N; longitude -9.1366 - 2.1899{degrees} W. The range of p.C282Y allele frequencies in the 34 cohorts was 0.0000 to 0.0517. The aggregate p.C282Y allele frequency in mainland Spain was 0.0291 (716/24,594) [0.0271, 0.0313] and that in mainland Portugal was 0.0303 (62/2048) [0.0237, 0.0386] (p = 0.8343). The aggregate p.C282Y allele frequency in Iberia was 0.0292 (778/26,642) [0.0272, 0.0313]. ConclusionsWe conclude that the aggregate HFE p.C282Y allele frequencies in mainland Spain and mainland Portugal do not differ significantly. The aggregate p.C282Y allele frequency of 34 population/control cohorts (13,321 subjects, 16 geographic regions) in Iberia is 0.0292.