BACKGROUND & AIMS:The recent approval of pharmacological therapies for fibrotic metabolic dysfunction-associated steatohepatitis (MASH) has increased the need for accurate identification of treatment-eligible patients. Current recommendations increasingly rely on non-invasive tests (NITs), including vibration-controlled transient elastography (VCTE), while multiparametric ultrasound (MPUS) may provide additional opportunities for non-invasive assessment. However, agreement between histology and imaging-based approaches remains uncertain. We compared treatment eligibility based on histology, VCTE, and MPUS in two international biopsy-proven cohorts of metabolic dysfunction-associated steatotic liver disease (MASLD). METHODS:We analysed two biopsy-proven MASLD cohorts: CAP-IPDMA (n=1029), including VCTE and controlled attenuation parameter (CAP), and iLEAD (n=124), including MPUS. Treatment eligibility was assessed using histologically confirmed F2/F3 MASH and NIT-based recommendations from international expert panels. RESULTS:In CAP-IPDMA, 277/1029 patients (26.9%) met the histological definition of "at-risk MASH". Depending on the VCTE cut-off, 13.2-32.0% qualified for treatment. Overlap between histological "at-risk MASH" and VCTE thresholds was limited, reaching 27.8% when using VCTE 8-15 kPa, and decreasing when narrower or higher thresholds were applied. Among patients identified only by VCTE 8-15 kPa, males had lower median AST and ALT than those fulfilling only the histological indication (35 vs 48 IU/L p=0.034 and 45 vs 62 IU/L p=0.0072, respectively). In iLEAD, 21/124 patients (16.9%) met the histological definition, while 13.7-16.1% were eligible based on SWE thresholds, again with a similarly limited overlap. CONCLUSIONS:Histology and non-invasive tests capture partly distinct patient populations, meaning that both the number and type of patients selected for therapy depend on the chosen modality and cutoffs. As vibration-controlled transient elastography and multiparametric ultrasound become increasingly accessible in clinical practice, prospective validation is essential for establishing reliable non-invasive treatment pathways. IMPACT AND IMPLICATIONS:The current literature reflects a paradigm shift away from biopsy-based approaches toward NIT-based assessment of treatment eligibility in metabolic dysfunction-associated steatotic liver disease (MASLD), which may substantially affect which patients receive newly approved therapies. Our results are important for clinicians, researchers, and guideline developers because histology and current NIT cut-offs identify only partially overlapping patient populations, implying that different diagnostic strategies select different risk profiles. In practice, these findings support thoughtful implementation of NIT-based treatment pathways, the use of repeated measurements, and prospective validation of NIT thresholds to guide clinical care, trial design, and health policy decisions.

Roux-en-Y gastric bypass (RYGB) is one of the most commonly performed procedures in metabolic surgery, known for its beneficial effects on type 2 diabetes (T2D). However, the optimal choice of small bowel limb lengths remains a matter of debate. Recent studies suggest that a longer biliopancreatic limb (BPL) could improve T2D more effectively than a longer alimentary limb (AL). The aim of this randomized controlled trial was to compare the effects of a long BPL-RYGB to a long AL-RYGB on T2D in adults with body mass index (BMI) between 27 and 60 kg/m2. 131 patients were randomized 1:1 to long AL-RYGB (150 cm AL/50 cm BPL) or long BPL-RYGB (50 cm AL/150 cm BPL). In patients with BMI > 50 kg/m2, limb lengths were slightly longer. The primary outcome was glycated hemoglobin (HbA1c) after 12 months. Secondary outcomes were T2D remission rate, weight loss, anthropometric measures and blood parameters reflecting glycemic control, dyslipidemia and micronutrient supply. Trial registration number: DRKS00007810 (German Clinical Trials Register Freiburg). Patients in the long BPL-RYGB group showed a -0.33

BACKGROUND:Guidelines recommend catheter ablation for symptom relief in patients with atrial fibrillation. The aim of this trial was to ascertain whether catheter ablation improves atrial fibrillation-related quality of life more than a sham procedure. METHODS:PVI-SHAM-AF was a double-blind, multicentre, randomised trial conducted at nine study sites in Germany and Poland. Patients aged 18 years or older with symptomatic paroxysmal or persistent atrial fibrillation were randomly assigned in a 2:1 ratio to catheter ablation or a sham procedure using an automated online randomisation system with variable block sizes, stratified by trial site. The primary endpoint was the between-group difference in change from baseline to 6 months in the Atrial Fibrillation Effect on the Quality-of-life Questionnaire (AFEQT) summary score. The prespecified primary analysis was done in the intention-to-treat population and included all randomly assigned patients, with missing data handled by multiple imputation. This trial is registered with ClinicalTrials.gov (NCT05119231) and 12-month follow-up is ongoing. FINDINGS:Between Nov 12, 2021, and Nov 3, 2025, 1199 patients were invited to participate in the study and 262 patients consented and were randomly assigned: 173 patients to catheter ablation and 89 to sham. The median age was 67 years (IQR 62-73); 134 (51%) were female and 128 (49%) were male. Median follow-up was 184 days (IQR 181-191). At 6 months, the mean AFEQT summary score had increased from 61·3 (SD 20·1) to 81·1 (16·6) in the catheter ablation group and from 59·2 (19·0) to 74·9 (19·5) in the sham control group. The Hodges-Lehmann estimate of the between-group difference in change was 2·6 (95% CI -2·7 to 8·0; p=0·36). One death occurred in each group; neither was considered related to the study procedure. Serious adverse events adjudicated as related or possibly related to the study procedure occurred in ten unique patients: six patients in the catheter ablation group and four patients in the sham control group. One of these was an ischaemic stroke occurred in the sham control group. INTERPRETATION:Catheter ablation did not demonstrate superiority over a sham procedure for improving atrial fibrillation-related quality of life at 6 months. FUNDING:Helios Gesundheit (Förderung Leipziger Herzmedizin).

INTRODUCTION:Rapid sequence induction (RSI) is widely used in patients at risk of pulmonary aspiration but may be associated with haemodynamic instability and intubation difficulties. It remains unclear whether patients with moderately increased risk of aspiration benefit from RSI compared with standard induction including mask ventilation. METHODS AND ANALYSIS:This multicentre, randomised, controlled, parallel-group, patient-blinded trial will enrol 792 adult surgical patients with moderately increased risk of aspiration. Participants will be randomised 1:1 to RSI (no mask ventilation, rocuronium 1.0-1.2 mg/kg) or standard induction (mask ventilation with rocuronium 0.5-0.6 mg/kg until adequate neuromuscular blockade before intubation). The primary outcome is clinically relevant hypotension within 15 min after induction (peri-induction period), defined as mean arterial pressure <65 mm Hg for >1 min, a decrease >20% from baseline or vasopressor administration. Secondary outcomes include oxygen desaturation, pulmonary aspiration, intubation difficulty (first-pass success and Cormack-Lehane grade), residual neuromuscular blockade and postoperative sore throat. Recruitment is planned over approximately 3 years and is ongoing. All analyses will follow the intention-to-treat principle. ETHICS AND DISSEMINATION:The study has been approved by the Ethics Committee of the Medical Faculty, University of Leipzig, Germany (reference number: 193/23-ek). Results will be disseminated through peer-reviewed publications and presented at scientific conferences. TRIAL REGISTRATION NUMBER:DRKS00031940.

To examine the effects of differently structured exercise programs (strength training (ST) vs endurance training (ET) vs a control group (CG)) on glucose metabolism and weight loss following Roux-en-Y Gastric Bypass (RYGB). After RYGB, patients were randomized to a standardized ST or ET program or a control group, the intervention started within 28 days. Outcomes at 6 months were glucose and lipid metabolism, anthropometrics, inflammation, and quality of life. 93 patients were randomized (30 in ST and 31 in ET, 32 in CG; 28

Background: Cefazolin is used as a prophylactic antibiotic to reduce surgical site infections (SSIs). Obesity has been identified as a risk factor for SSIs. Cefazolin dosing recommendations and guidelines are currently inconsistent for obese patients. As plasma and target-site exposure might differ, pharmacokinetic data from the sites of SSIs are essential to evaluate treatment efficacy: these data can be obtained via tissue microdialysis. This analysis was designed to evaluate the need for dosing adaptations in obese patients for surgical prophylaxis. Methods: Data from 15 obese (BMImedian = 52.6 kg m(-2)) and 15 age- and sex-matched nonobese patients (BMImedian = 26.0 kg m(-2)) who received 2 g cefazolin i.v. infusion for infection prophylaxis were included in the analysis. Pharmacokinetic data from plasma and interstitial space fluid (ISF) of adipose tissue were obtained and analysed simultaneously using nonlinear mixed-effects modelling. Dosing regimens were evaluated by calculating the probability of target attainment (PTA) and the cumulative fraction of response (CFR) for plasma and ISF using unbound cefazolin concentration above minimum inhibitory concentration 100% of the time as target (fT(>MIC) = 100%). Dosing regimens were considered adequate when PTA and CFR were >= 90%. Results: Evaluation of cefazolin doses of 1 and 2 g with redosing at either 3 or 4 h by PTA and CFR in plasma and ISF found 2 g cefazolin with redosing at 4 h to be the most suitable dosing regimen for both obese and nonobese patients (PTA >90% and CFR >90% for both). Conclusions: This model-based analysis, using fT>(MIC) = 100% as a target, showed that cefazolin dosing adaptations are not required for surgical prophylaxis in obese patients.

BACKGROUND:Catheter ablation by pulmonary vein isolation (PVI) has a class IA recommendation for patients with atrial fibrillation (AF) resistant or intolerant to antiarrhythmic drug therapy to reduce symptoms, recurrence and progression of AF. However, the symptomatic effect of catheter ablation is difficult to quantitate in the absence of a double-blind trial with a sham procedure control. The PVI-SHAM-AF trial aims to compare the effects of catheter ablation versus a sham procedure on patient-reported outcomes using standardized AF questionnaires. STUDY DESIGN:The PVI-SHAM-AF trial is a multicentre, prospective, randomized, sham-controlled, double-blinded clinical trial. The trial plans to enrol 260 patients. Patients eligible for PVI are randomly assigned in a 2:1 ratio to receive either PVI or a sham procedure. The Sham procedure involves introducing a venous sheath under deep analgosedation, maintained for at least 60 minutes; electrical cardioversion is performed if atrial fibrillation is present. Follow-up assessments are planned at 3-, 6-, and 12-months postbaseline, focusing on AF symptoms, quality of life assessments assessed by the AFEQT, SF-36, EQ-5D questionnaires, and clinical outcomes such as AF burden and NT-proBNP levels. The primary objective is the change in quality of life (measured by a standardized questionnaire) from baseline to 6 months of follow-up, compared to the sham procedure. CONCLUSION:The PVI-SHAM AF trial will assess the true (sham-controlled) effect of catheter ablation for AF on quality of life.

Guidelines on primary biliary cholangitis (PBC) recommend therapy with 13–15 mg/kg ursodeoxycholic acid (UDCA) and assessment of treatment response after 12 months. We evaluated to which extent these recommendations are followed in newly diagnosed patients. The German PBC Registry recruited three subgroups: Adequate or inadequate UDCA treatment responders (Paris II criteria) and newly diagnosed patients (<6 months prior to recruitment). We focus on newly diagnosed patients with UDCA monotherapy. 82 patients were recruited (43 at 12 tertiary and 39 at 9 secondary centers) thereof 22% with cirrhosis. Individuals with cirrhosis were older (71 ± 9 vs. 55 ± 14 years, p<0.001) and presented more frequently with diabetes mellitus (44% vs. 13%, p=0.0054) and arterial hypertension (78% vs. 42%, p=0.0076) compared to cases without cirrhosis. 12 months follow-up data were available in 62 patients. UDCA underdosing (<13 mg/kg/d) occurred in 47% and 74% of cases (p=0.013) at tertiary and secondary care at treatment initiation and in 29% and 73% (p=0.002) after 12 months, respectively. Paris II criteria were achieved in 74% and a deep UDCA response (alkaline phosphatase < ULN and bilirubin < 0.6 × ULN) in 32% of cases. Newly diagnosed PBC patients include a substantial proportion of late presenters with cirrhosis. UDCA dosage is suboptimal in many cases. Time point of diagnosis and UDCA dosage should be improved.

Introduction: ECG-monitoring covering several days is recommended by current guidelines to detect atrial fibrillation (AF) and other arrhythmias in stroke patients. In practice, the extent of rhythm monitoring varies. Here, we use data from the 24-hour screening-Holter-ECGs of the ongoing randomized multicenter trial Find-AF 2 to assess the rate of AF and other arrhythmias. Methods and Results: Find-AF 2 (NCT04371055) is a randomized and controlled open-label parallel multicenter trial with central AF adjudication (intervention arm) and blinded endpoint assessment. Patients ≥60 years with recent (≤30 days) ischemic strokes according to the AHA/ASA definition of any etiology are screened for eligibility. All eligible patients receive a 24-hour Holter-ECG prior to randomization. Holter ECG data are analyzed by the core laboratory using dedicated analysis software and following a predefined standard operation procedure. In this analysis, we included all 24-hour Holter-ECGs up to June 1, 2023. We analyzed 3742 24-hour-Holter-ECGs from 51 different centers and found new arrhythmias in 120 patients (3.2%). AF was detected in 61 patients (1.6%) with a median duration of the longest episode of 730 minutes [interquartile range (IQR) 220;1180] (see Figure 1). This led to the initiation of anticoagulation in all 61 patients (100%). In 47 patients (1.3%), pauses >2.5 s (mean 3.1s±0.5s; longest pause 4.8s) or relevant bradycardias <40 bpm were diagnosed. This resulted in the implantation of pacemakers in six patients. Finally, we found regular supraventricular tachycardias in 25 patients (0.7%; median duration 7.0 min [IQR 1.0;21.3]) - 24 of them had focal atrial tachycardias and one an AVNRT. Conclusion: Overall, 3.2% of ischemic stroke patients had pathological ECG findings, leading to a therapeutic change in 56%, most commonly anticoagulation for AF detection The number needed to screen for a change in medical management was 56.

In the Find-AF 2 randomised controlled trial, we investigate whether a risk-adapted intensified heart rhythm monitoring with subsequent initiation of oral anticoagulation in ischaemic stroke patients leads to a reduction of recurrent ischaemic stroke and systemic embolism. The objective of this analysis is to present baseline characteristics of the overall Find-AF 2 study population and stratified by low or high risk for developing AF. The Find-AF 2 trial included acute ischaemic stroke patients ≥ 60 years of age within 30 days of ischaemic stroke of any cause. Before randomisation, patients received a 24-h Holter-ECG to exclude those with easily detectable AF and to determine the presence or absence of enhanced supraventricular ectopic activity (ESVEA), used as a marker indicating high or low risk for developing AF. Those without AF were randomly assigned 1:1 to either usual care diagnostics for AF detection (control group) or enhanced, prolonged and intensified ECG monitoring (intervention group). In the intervention group, patients with ESVEA received an implantable cardiac monitor (ICM), whereas those without ESVEA received repeated annual 7-day Holter ECGs. We present baseline characteristics of the overall Find-AF 2 population and stratified by ESVEA. Between July 2020 and July 2024, 5227 patients (mean age 72.3 ± 7.5 years, 40

The THR-β agonist resmetirom is the first treatment approved for metabolic dysfunction-associated steatohepatitis (MASH) in the US so far. It can be prescribed given MASH and F2/F3-fibrosis (“at-risk MASH”). We analyzed how many patients qualify for resmetirom in a recently recruited Steatotic Liver Disease-cohort involving both tertiary and secondary care centers, the German SLD-Registry. Indication for resmetirom was assessed by three different approaches: (i) biopsy-proven MASH with F2/3 fibrosis and NAS-score ≥ 4; (ii) FibroScan-AST (FAST) score ≥ 0.67 and vibration controlled transient elastography (VCTE) < 15 kPa; (iii) US expert recommendations with VCTE 10–15 kPa and platelets ≥ 140×109/L or VCTE 8–15 kPa. 1113 patients were recruited across 8 tertiary and 12 secondary care centers. NAS grading and staging were available for 180 cases (16%) with 179/180 conducted at tertiary care level. Of these, 61 (34%) qualified for resmetirom. FAST score without histologic assessment was available for 638 cases (57.3%), of which 612 (87%) were from tertiary and 26 (11%) from secondary care centers. Based on approach (ii), 41 (6%) of these individuals qualified for resmetirom compared to 117 (18.3%) using approach (iii). Combining approach (iii) with FAST ≥ 0.67 leads to 191 (30.0%) eligible patients. Using VCTE 8–15 kPa results in 182 (28.5%) eligible patients. Eligibility for resmetirom treatment depends on the available method used to identify “at-risk MASH”. Availability of VCTE was highest among different levels of care.

Surgical antibiotic prophylaxis is an important measure to prevent postoperative surgical site infections. Current guideline recommendations do not treat obesity specifically, although it can affect pharmacokinetics and pharmacodynamics. The objective of this review was to synthesize current evidence on the need for obesity-related dosing adjustments in surgical antibiotic prophylaxis. MEDLINE and Cochrane Library were searched for studies investigating antibiotic prophylaxis dosing in surgical patients with obesity. Outcomes of interest were pharmacokinetic parameters such as plasma and interstitial fluid concentrations, area under the concentration time curve in plasma and in interstitial fluid, and other pharmacokinetic measures. Thirty studies investigating cefazolin, cefoxitin, cefuroxime, piperacillin/tazobactam, meropenem, ertapenem, metronidazole, vancomycin, ciprofloxacin, and gentamicin were included in this analysis. Except for metronidazole, cefoxitin, and gentamicin, there is currently no evidence suggesting the need for dosing adjustments.

easy to obtain and noninvasive reliable, reproducible, and prospectively applicable affordable Controlled attenuation parameter is a quantitative ultrasound based technique to noninvasively characterize hepatic steatosis. It is an add-on software to the fibroscan® device—the standard of care for ultrasound based noninvasive fibrosis characterization of MASLD in clinical guidelines - and quantifies attenuation of the ultrasound tracking impulses during liver stiffness measurement and delivers the attenuation slope with a range of 100–400 dB/m.5-7 CAP fulfills most of the aforementioned criteria, however, only about 140 fibroscan® devices are currently available in Germany, for example, and these are mainly restricted to secondary and tertiary care.8-10 Moreover, they are not universally equipped with the CAP software, which would be quite expensive for a stand-alone tool for quantification of steatosis. This is mitigated by the fact that the parameters liver stiffness, CAP value, and aspartate aminotransferase (AST) can be combined to the FAST score as estimation of fibrotic steatohepatitis.11 In the present issue of UEG journal, Bianco and colleagues developed the steatosis score "CAPS" to predict CAP values ≥275 dB/m, which was taken as a surrogate for hepatic fat.12 It is based on the readily available clinical parameters age, BMI, abdominal circumference, HbA1c, ALT and HDL and was derived in a cohort of blood donors with at least three items of metabolic dysfunction (overweight, hypertension, fasting glucose/diabetes/HbA1c, low HDL, or increased triglycerides). The CAPS score was validated in three additional cohorts including the general population and individuals scheduled for bariatric surgery. The AUROC to predict a CAP value ≥275 dB/m was 0.73. The authors conclude that the CAPS score is useful to identify MASLD in high-risk individuals. Investigation of the CAPS score in four different cohorts spanning a broad spectrum where MASLD is clinically important is a strength of the Bianco paper. However, the accuracy of the score is only moderate, a control with liver histology or magnetic resonance based proton density fat fraction (MR-PDFF) is missing, and prospective longitudinal data or correlation with clinical endpoints do not yet exist. The use of "healthy", middle aged blood donors for the derivation cohort led to a predominantly male (83%) population with almost no diabetes (1.5%). Furthermore, the CAPS score is not meaningfully better in performance than the established Fatty Liver Index in the validation cohorts, although the abstract implied the contrary by stating results from the derivation cohort. Nevertheless, it is important that the authors focus on the clinical relevance of steatosis in the disease continuum from MASLD and MASH to advanced stages of fatty liver disease. The community has to develop adequate noninvasive tools to screen for MASLD and longitudinally monitor treatment effects of upcoming therapeutic options like the thyroid receptor beta agonist resmetirom which has recently successfully passed phase 3 development.13 These tools finally should also predict hepatic and cardiovascular endpoints to identify patients suitable for pharmacological interventions and define a population that is not at risk and does not unnecessarily tie up scarce health care resources.