Citations

ABSTRACT Background Diagnostic interpretation of kidney allograft biopsies using the Banff classification remains variable, but the determinants of this variability are not fully defined. We performed a global, fully digital multi-reader study to identify the principal drivers of disagreement in Banff-based assessment. Methods Thirty-six kidney transplant biopsies were independently scored by 67 renal pathologists on a standardized digital platform. Readers assessed Banff lesions on hematoxylin and eosin, periodic acid–Schiff, and Jones’ silver stains; final diagnostic categories were assigned using prespecified Banff-based decision rules. Interobserver agreement was quantified with Gwet’s agreement coefficient (AC) statistics. Determinants of diagnostic agreement were evaluated using pairwise mixed-effects logistic regression, and reader similarity was examined by principal component analysis (PCA) with post hoc molecular annotation. Results Agreement for final diagnostic categories was moderate (Gwet’s AC1, 0.55; 95% CI, 0.47–0.63). Lesion-level agreement varied substantially, with lowest agreement for selected threshold-dependent inflammatory or semi-quantitative lesions, including interstitial inflammation in areas of IFTA, peritubular capillaritis and arteriolar hyalinosis. Diagnostic concordance differed markedly across biopsies, indicating strong case-level heterogeneity. In pairwise models, differences in active inflammatory and vascular lesion scoring were the strongest correlates of diagnostic disagreement; reader experience and geography contributed minimally. Principal component analysis showed reader variation was organized along two dominant axes: a rejection-calling threshold axis linked mainly to tubulointerstitial inflammatory injury, and a T cell-mediated (TCMR/TI) and antibody-mediated/microvascular (AMR/MVI) inflammation-oriented phenotypic classification axis. Conclusion Interobserver variation in Banff-based kidney transplant biopsy assessment is structured rather than random and driven mainly by how readers threshold and integrate key inflammatory lesion compartments rather than experience or geographic location.

ABSTRACT Recent advances in the diagnosis and management of reflux disease were the central focus of the inaugural Gatherings in Esophagology (GiE), which convened experts across gastroenterology, surgery, otolaryngology, pulmonology, and basic research. The sessions highlighted innovations in reflux monitoring—including high‐resolution manometry, wireless pH monitoring, and novel salivary biomarkers—while critically evaluating their diagnostic accuracy and clinical utility. Presentations explored the limitations of traditional proton‐pump inhibitor therapy, the emergence of potassium‐competitive acid blockers as a new class of acid suppressants, and the evolving role of adjunctive treatments such as mucosal protectants, reflux reducers, and neuromodulators for refractory symptoms. The discourse extended to advanced interventional procedures, including transoral incisionless fundoplication, magnetic sphincter augmentation, and the RefluxStop device, with discussion of patient selection, efficacy, and complication management. Discussants emphasized the pathophysiology and management of extraesophageal manifestations of reflux, the interplay between reflux and pulmonary disease, and the diagnostic challenges in pediatric populations. The meeting also addressed the integration of behavioral therapies, the role of the microbiome, and the application of artificial intelligence in reflux diagnostics. Collectively, these insights underscore a shift toward precision medicine in reflux disease, emphasizing individualized diagnostic strategies and tailored therapeutic approaches to improve patient outcomes.

Purpose: These consensus guidelines by the American Clinical Neurophysiology Society (ACNS) describe best practices for performing intraoperative Electrocorticography (ioECoG) using subdural or depth electrodes for adult and pediatric population. Methods: A group of ACNS members was convened to develop technical standards for performing ioECoG. PubMed searches were performed to identify pertinent peer-reviewed literature. Sections were assigned to individual authors based on expertise. Consensus was achieved during subsequent group discussions to develop evidence-based recommendations to the extent possible. Recommendations: Communication between the neurosurgical and the neurophysiology teams is essential in verifying and documenting the location of the contacts. Most authors recommend ioECoG recordings of at least 5 and up to 30 minutes in duration to allow for sufficient observation of interictal activity. The anesthesia should be adjusted to allow continuous EEG activity and to minimize the effect on the ioECoG recording during general anesthesia or awake surgery. The surgical procedure and technical report should separate ioECoG recordings to define the irritative zone from ioECoG findings during functional mapping. The neurophysiology physician’s physical presence in the operating room is required in the definition of the services. Conclusion: These consensus guidelines by the ACNS describe best practices for performing intraoperative ECoG based on published literature and expert consensus.

Abstract Background: With over 1 billion individuals affected globally, obesity and obesity related diseases is now a leading cause of death. Metabolic and bariatric surgery (MBS) has emerged as a cornerstone intervention for severe obesity and its associated comorbidities. Despite its efficacy, postoperative care and follow-up after MBS remains highly variable worldwide. Objective: The PARTNER study aimed to evaluate global clinical practices in the postoperative management following MBS by surveying multidisciplinary healthcare professionals . Methods: This study was an international online survey conducted between October 2024 and January 2025. A multidisciplinary team developed the questionnaire based on existing literature and international guidelines. The survey assessed five domains: follow-up care, postoperative treatment, dietary management, patient support, and measurement of surgical outcomes. Responses were analysed descriptively. Results: A total of 262 responses were received from 62 countries. Most respondents were bariatric surgeons (72.1%) working in public healthcare systems (73.3%). While 78.7% reported conducting three-month postoperative reviews, only 23.7% offered indefinite follow-up. Hybrid models of care (virtual and in-person) were common (56.9%). VTE prophylaxis and postoperative PPI use were recommended by 64.1% and 84.3% respectively. Nearly all respondents (98.1%) provided dietary advice, with protein and micronutrient supplementation widely endorsed. Only 56.1% routinely referred patients for psychological follow-up. Definitions of surgical success and failure varied widely, with inconsistent objective outcome measures. Conclusion: The PARTNER study reveals significant international variation in postoperative management practices following MBS. These findings underscore the need for more standardized, evidence-based guidelines to improve long-term outcomes and equity of care worldwide.

Abstract Apathy is a prevalent and persistent neuropsychiatric syndrome across many neurological disorders, significantly impacting both patients and caregivers. We systematically quantified discrepancies between self- and caregiver-reported apathy in 335 patients with a variety of diagnoses, such as frontotemporal dementia (behavioural variant and semantic dementia subtypes), Parkinson’s disease, Parkinson’s disease dementia, dementia with Lewy bodies, Alzheimer’s disease dementia, mild cognitive impairment, small vessel cerebrovascular disease, subjective cognitive decline and autoimmune encephalitis. Using the Apathy Motivation Index (AMI) and its analogous caregiver version (AMI-CG), we found that caregiver-reported apathy consistently exceeded self-reported levels across all conditions. Moreover, self-reported apathy accounted for only 14.1% of the variance in caregiver ratings. This apathy reporting discrepancy was most pronounced in conditions associated with impaired insight, such as behavioural variant frontotemporal dementia, and was significantly correlated with cognitive impairment. Deficits in memory and fluency explained an additional 11.2% of the variance in caregiver-reported apathy. Specifically, executive function deficits (e.g. indexed by fluency) and memory impairments may contribute to behavioural inertia or recall of it. These findings highlight the need to integrate patient and caregiver perspectives in apathy assessments, especially for conditions with prominent cognitive impairment. To improve diagnostic accuracy and deepen our understanding of apathy across neurological disorders, we highlight the need for adapted apathy assessment strategies that account for cognitive impairment particularly in individuals with insight or memory deficits. Understanding the cognitive mechanisms underpinning discordant apathy reporting in dementia might help inform targeted clinical interventions and reduce caregiver burden.

Abstract Background/Introduction Multielectrode mapping catheters enhance the speed and accuracy of 3-dimensional data collection. However, with variable catheter configurations, data acquisition and efficiency may differ. We sought to compare the HD Grid X mapping catheter to a multi linear 8-spline catheter (spline catheter) with respect to chamber modeling speed and accuracy in in-vivo and bench setups. Methods In-vivo: In 6 pigs, 4 physicians used each catheter in a randomized order to create unedited models of the left atrium and ventricle (LA and LV) during coronary sinus atrial pacing. A sensor-enabled ablation catheter marked five locations per chamber while applying 10-15g of force. These markers, which denoted the ‘true’ location of the endocardial surface, were compared to the nearest surface location defined by each mapping catheter. Bench: In a tank setup designed to emulate an LA to pulmonary vein (PV) transition, chamber models were created during robotic manipulation of each mapping catheter. Resulting models were compared to a "gold-standard" model generated using robotic manipulation of sensor-enabled ablation catheters. Additionally, a static shape analysis was performed with each catheter held by a fixture in a deformed (HD Grid X catheter-bent 90o degrees; spline catheter-3 splines bunched) and undeformed state. Images of the physical catheters were captured to determine the true catheter shape and were compared to the renderings from the respective electroanatomical mapping systems (EnSite X v3.1 and Carto v7.2). Results In-Vivo: The mean error between the ablation catheter generated points and the models for HD Grid X trended lower than for the spline catheter by 11.7% (p=0.63; 2.57mm, 2.91mm) in the LA. In the LV, the mean error for HD Grid X was 34.4% (p=0.04; 2.04 mm, 3.67mm) less than for the spline catheter. In the LA, time for model creation for HD Grid X trended higher than for the spline catheter by 14.0% (p=0.34; 524s, 451s). However, in the LV, modeling time for HD Grid X was 22.9% (p=0.05; 368s, 478s) less than for the spline catheter. Bench: Compared to the ablation catheter created models, HD Grid X had a median bloat of 1.70mm (5.91mm max) while the spline catheter had 2.53mm (11.45mm max). The RMS error (mm) for the static shape analysis of electrode positions in an undeformed state was 0.60 for HD Grid X and 2.26 for the spline catheter. In a deformed state, the error was 0.82 for HD Grid X and 2.07 for the spline catheter. Conclusion In this translational model, the HD Grid X catheter created faster and more accurate unedited LV model geometry than the spline catheter, with no statistically significant difference noted in the LA. Bench data further supports the enhanced geometry accuracy seen in-vivo with HD Grid X, which may result in superior anatomical delineation, and faster mapping data acquisition times.

Abstract Aims Sodium–glucose co-transporter-2 (SGLT2) inhibitors improve health status and outcomes in the setting of heart failure (HF) across the range of ejection fraction (EF). Baseline kidney disease is common in HF, complicates HF management and is strongly linked to worse health status. This study aimed to assess whether the treatment effects of dapagliflozin on health status vary based on estimated glomerular filtration rate (eGFR). Methods and Results We conducted a pooled participant-level analysis of two double-blind, randomized trials, DEFINE-HF (n = 236) and PRESERVED-HF (n = 324), which evaluated dapagliflozin versus placebo. Both multicentre studies enrolled adults with HF, New York Heart Association Class II or higher, elevated natriuretic peptides, and an EF < 40% in DEFINE-HF or >45% in PRESERVED-HF. The primary exposure was eGFR. The main outcome was the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) at 12 weeks. Across both trials, there were 583 (99.3%) participants with a baseline eGFR. The median (25th, 75th) eGFR was 59 (46, 77) mL/min/1.73 m2. Dapagliflozin improved KCCQ-CSS at 12 weeks [placebo-adjusted difference, +5.0 points, 95% confidence interval (CI) 2.6–7.5; P < 0.001], and this was consistent in participants with an eGFR ≥ 60 (+6.0 points, 95% CI 2.4–9.7; P = 0.001) and eGFR < 60 (+4.1 points, 95% CI 0.5–7.7; P = 0.025) (P interaction = 0.46). The benefits of dapagliflozin on KCCQ-CSS remained robust across eGFR when modelled as a continuous variable (P interaction = 0.48). Conclusions Dapagliflozin led to early and clinically meaningful improvements in health status in HF patients, regardless of EF or baseline eGFR.

SummaryGlobal obesity rates have risen dramatically, now exceeding deaths from starvation. Metabolic and bariatric surgery (MBS), initially for severe obesity (BMI ≥35 kg/m2), is performed globally over 500 000 times annually, offering significant metabolic benefits beyond weight loss. However, varying eligibility criteria globally impact patient care and healthcare resources. Updated in 2022, ASMBS and IFSO guidelines aim to standardise MBS indications, reflecting current understanding and emphasising comprehensive preoperative assessments. Yet, clinical variability persists, necessitating consensus‐based recommendations. This modified Delphi study engaged 45 global experts to establish consensus on perioperative management in MBS. Experts selected from bariatric societies possessed expertise in MBS and participated in a two‐round Delphi protocol. Consensus was achieved on 90 of 169 statements (53.3%), encompassing multidisciplinary team composition, patient selection criteria, preoperative testing, and referral pathways. The agreement highlighted the critical role of comprehensive preoperative assessments and the integration of healthcare professionals in MBS. These findings offer essential insights to standardise perioperative practices and advocate for evidence‐based guidelines in MBS globally. The study underscores the need for unified protocols to optimise outcomes and guide future research in MBS.

Abstract Introduction Drug-coated balloons (DCBs) have reduced restenosis and reintervention of femoropopliteal lesions compared to uncoated percutaneous transluminal angioplasty (PTA). However, limited data are available on different dosages of the DCBs. Purpose We aimed to give a comprehensive analysis in this regard and update the current evidence. Methods We searched Scopus, Cochrane, PubMed, and WOS from inception till February 2024 to include all randomized controlled trials (RCTs) that addressed different dosages of DCBs in femoropopliteal lesions. The primary endpoint was all-cause death, primary patency, and amputation at six months, while the secondary outcomes were all-cause death, primary patency, and amputation at 12 months. Dichotomous data were pooled using Odds Ratio (OR) and 95% Confidence Interval (CI) in a random-effect model. Results A total of 21 studies, including 4081 patients in the analysis. Low-dose DCB was associated with high rates of primary patency compared to the standard dose at both 6 and 12 months of follow-up with the following values (OR: 2.46, 95% CI: 1.48 to 4.08, and 1.93, 95% CI: 1.5 to 2.49, receptively). Also, low-dose DCB reduced the incidence of clinically driven target lesion revascularization (CD-TLR) compared to the standard dose at 12 months (OR: 0.45, 95% CI: 0.31 to 0.65). Regarding high-dose DCB, higher primary patency rates were observed when compared to standard doses at 6 and 12 months (OR: 1.89, 95% CI: 1.19 to 2.99, and 5.47, 95% CI: 4.31 to 6.95, respectively). Moreover, high-dose DCB reduced the incidence of CD-TLR at 6 and 12 months of follow-up (OR: 0.33, 95% CI: 0.18 to 0.63, and 0.63, 95% CI: 0.48 to 0.84, respectively). Conclusion Low-dose DCBs were associated with higher primary patency without significant differences in all-cause mortality or amputation. On the other hand, high-dose DCBs were associated with a higher incidence of amputation without significant differences in other studied outcomes.Low dose Paclitaxel coated balloon vs CoHigh dose Paclitaxel coated balloon vs C

BACKGROUND: Mechanisms of benefit with SGLT2is (sodium-glucose cotransporter-2 inhibitors) in heart failure (HF) remain incompletely characterized. Dapagliflozin alters ketone and fatty acid metabolism in HF with reduced ejection fraction though similar effects have not been observed in HF with preserved ejection fraction. We explore whether metabolic effects of SGLT2is vary across the left ventricular ejection fraction spectrum and their relationship with cardiometabolic end points in 2 randomized trials of dapagliflozin in HF. METHODS: Metabolomic profiling of 61 metabolites was performed in 527 participants from DEFINE-HF (Dapagliflozin Effects on Biomarkers, Symptoms and Functional Status in Patients With HF With Reduced Ejection Fraction) and PRESERVED-HF (Dapagliflozin in PRESERVED Ejection Fraction HF; 12-week, placebo-controlled trials of dapagliflozin in HF with reduced ejection fraction and HF with preserved ejection fraction, respectively). Linear regression was used to assess changes in principal components analysis–defined metabolite factors with treatment from baseline to 12 weeks, as well as the relationship between changes in metabolite clusters and HF-related end points. RESULTS: The mean age was 66±11 years, 43% were female, and 33% were self-identified as Black. Two principal components analysis–derived metabolite factors (which were comprised of ketone and short-/medium-chain acylcarnitines) increased with dapagliflozin compared with placebo. Ketosis (defined as 3-hydroxybutyrate >500 μM) was achieved in 4.5% with dapagliflozin versus 1.2% with placebo ( P =0.03). There were no appreciable treatment effects on amino acids, including branched-chain amino acids. Increases in several acylcarnitines were consistent across LVEF ( P interaction >0.10), whereas the ketogenic effect diminished at higher LVEF ( P interaction =0.01 for 3-hydroxybutyrate). Increases in metabolites reflecting mitochondrial dysfunction (particularly long-chain acylcarnitines) and aromatic amino acids and decreases in branched-chain amino acids were associated with worse HF-related outcomes in the overall cohort, with consistency across treatment and LVEF. CONCLUSIONS: SGLT2is demonstrate common (fatty acid) and distinct (ketogenic) metabolic signatures across the LVEF spectrum. Changes in key pathways related to fatty acid and amino acid metabolism are associated with HF-related end points and may serve as therapeutic targets across HF subtypes. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique Identifiers: NCT03030235 and NCT02653482.