Citations

ABSTRACT Background Transvenous lead extraction (TLE) is a commonly performed and generally safe procedure, though procedural complexity and risk can vary based on clinical and procedural factors. Objective This study aims to identify clinical and procedural factors associated with histologic evidence of subclinical vascular injury, defined by elastin positivity on extracted leads and its clinical significance. Methods Patients undergoing TLE with a lead dwell time of ≥ 1 year were included. Extracted leads with tissue were analyzed histologically using Verhoeff–Van Gieson staining to assess the presence of elastin. Demographic data, procedural and lead characteristics, and indication for extraction were obtained. Established extraction risk scores were calculated to determine efficacy in predicting subclinical vascular injury. Results The cohort included 49 patients with 92 leads extracted. A total of 25 patients (51%) had elastin‐positive leads. Complete procedural success occurred in 95.9% of cases. The multivariate regression model did not identify any independent predictors of elastin presence, including age (OR = 1.00; 95% CI 0.95–1.05; p = 0.89), female gender (OR = 3.04; 95% CI 0.67–13.65; p = 0.14), lead dwell time (OR = 1.13; 95% CI 0.98–1.29; p = 0.07). Additionally, no scoring system, such as the CCF, EROS, MB, SAFeTY, and LECOM, predicted the presence of elastin. Conclusion Subclinical venous injury was common following TLE, yet did not predict adverse clinical outcomes, reinforcing that TLE performed in experienced centers carries a favorable safety profile. Future studies in larger cohorts are needed to further characterize the clinical utility of subclinical vascular injury.

Abstract Introduction Acute interstitial nephritis is an important differential diagnosis in patients with deteriorating kidney function. Diagnosis currently requires kidney biopsy, an invasive procedure associated with risks. We hypothesized that urinary T cells may serve as a non-invasive biomarker for acute interstitial nephritis. Methods A total of 320 patients undergoing clinically indicated kidney biopsy were enrolled in a discovery cohort at Charité Berlin (n = 80), an internal validation cohort at Charité (n = 100), and an external validation cohort at The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou (n = 140). Urinary immune cells were assessed by flow cytometry. Renal T cell infiltration was evaluated by immunofluorescence in kidney biopsy specimens from the discovery and internal validation cohorts, including 16 patients with acute interstitial nephritis and 9 patients without acute interstitial nephritis. Additionally, CXCL9 was measured by ELISA in 102 urine samples from these cohorts. Results Across all cohorts, 27 patients (8.4%) were diagnosed with acute interstitial nephritis. In the discovery cohort, multiple urinary T cell subsets were increased in acute interstitial nephritis, with activated CD4 + effector memory T cells expressing CD38 and HLA-DR showing the strongest diagnostic performance. This marker outperformed urinary monocytes, eosinophils, and CXCL9 and was validated in both independent cohorts. Across all cohorts, the area under the receiver operating characteristic curve was 0.84 and increased to 0.91 after exclusion of 8 patients receiving corticosteroids. A cutoff of 211 activated CD4 + effector memory T cells per 100 mL urine yielded a sensitivity of 78% and a specificity of 81%. Urinary activated CD4 + effector memory T cell counts correlated with renal CD4 + and CD4 + CD38 + T cell infiltration in acute interstitial nephritis. Conclusions Urinary activated CD4 + effector memory T cells expressing CD38 and HLA-DR represent a promising non-invasive biomarker for the diagnosis of acute interstitial nephritis. Lay Summary Acute interstitial nephritis is a frequent cause of acute kidney injury and is usually diagnosed by kidney biopsy, an invasive procedure that carries risks. We investigated whether immune cells in urine could help identify AIN in a less invasive manner. In this multicenter study, urine samples from 320 patients undergoing kidney biopsy in Germany and China were analyzed. We found that a specific population of activated T cells was markedly increased in the urine of patients with AIN compared with patients with other kidney diseases. This urinary marker outperformed other immune cell types and the inflammatory cytokine CXCL9 and was successfully validated in independent cohorts from both Germany and China. Importantly, urinary activated T cell counts correlated with immune cell infiltration within the kidney. These findings suggest that urinary activated T cells may serve as a non-invasive biomarker to support the diagnosis of AIN and facilitate earlier clinical decision-making.

Abstract: Heart valve abnormalities are present in 30% of congenital heart defects. Additionally, there are acquired conditions like rheumatic heart disease. They often require surgery, and in complex cases, valve replacement becomes unavoidable. The current valve replacement options, either mechanical, bioprosthetic, homografts, or autografts, lack key properties for pediatric patient needs: availability, durability, and the ability to grow. Our goal is to review 2 clinically relevant innovations: tissue-engineered heart valves (TEHVs) and partial heart transplantation (PHT). We conducted searches in electronic databases covering the past 25 years using the terms “partial heart transplantation,” “tissue-engineered heart valves,” and their combinations. Decellularized pulmonary homografts outperform cryopreserved homografts and bovine jugular vein conduits in pulmonary valve replacement, showing less stenosis and no infective endocarditis. The European Clinical Study for the Application of Regenerative Heart Valves trial confirmed decellularized pulmonary homograft safety, demonstrating 97.5% freedom from explantation at 5 years. Decellularized aortic homografts showed excellent 97.8% 5-year survival and low endocarditis rates, though increases in transvalvular gradient and regurgitation occurred. Partial heart transplantation uses living valves from donor hearts and accommodates somatic growth. Postoperative immunosuppression in PHT is required but may be limited, as children and valve tissues may possess immune privilege, as evidenced by limited valve injury even in failed orthotopic heart transplants. In a pilot study of 19 infants, with a median follow-up of 26 weeks, increases in annular diameter and leaflet length were observed. Both PHT and TEHVs are promising valve replacement options. While PHT provides a growth-adaptive capability, TEHVs hold the potential for off-the-shelf solutions with minimal immunogenicity.

Purpose The purpose of this study was to compare graft failure and clinical outcomes following primary anterior cruciate ligament reconstruction (ACLR) using quadriceps tendon autograft (QA), with or without a modified Lemaire lateral extra‐articular tenodesis (LET). Methods Patients with ACL deficiency who underwent primary QA ACLR with or without LET and completed at least 2‐year follow‐up were included. Patients with a Beighton score ≥4, a preoperative pivot shift grade ≥2, or an intention to return to cutting and pivoting sports were offered LET. The primary outcome variable assessed was graft failure as defined by graft rupture or grade ≥2 pivot shift at any point postoperatively. Secondary outcomes included return to sport clearance rates, the International Knee Documentation Committee and Lysholm scores and postoperative complications. Results There were 122 undergoing QA ACLR with LET (QA + LET group) and 152 undergoing isolated QA ACLR (QA group). The QA + LET group had a significantly lower failure rate of 14.8% versus 29.6% in the QA group ( P = .02). In addition, the QA + LET group had a lower residual pivot shift rate compared with the QA group (11.3% vs. 26.3% respectively; P = .01). There was no difference in graft retear rates between the 2 groups ( P = .37). The QA + LET returned to sport significantly faster at 8.8 months compared with 9.7 months in the QA group ( P = .038). Conclusions The addition of LET to QA ACLR was associated with a significantly lower overall graft failure rate and lower percentage of patients with residual pivot shifts after ACLR compared with QA alone at 2‐year follow up. However, there was no difference between the 2 groups with regard to graft retear rates. The addition of an LET to QA ACLR also allowed athletes to return to sports faster compared with QA alone. Level of Evidence Level III, retrospective comparative study.

ABSTRACT Introduction Chronic gastroduodenal disorders remain challenging to manage, and new diagnostic approaches are needed to better delineate underlying causes and guide therapeutic decisions. Body Surface Gastric Mapping (BSGM) technologies combine high‐resolution gastric myoelectrical activity measurements with symptom and psychological profiling to provide mechanistic insights into gastric motor and sensory dysfunction. An International Working Group convened to derive the first consensus classification of BSGM phenotypes (the “Auckland Classification”). Methods A Technical Group conducted a systematic literature and clinical database review to identify objective test biomarkers and candidate disease mechanisms. Evidence was synthesized across 50 studies (primarily in gastroparesis, chronic nausea and vomiting, and functional dyspepsia), and BSGM phenotypes were mapped to existing treatment guidelines. Subsequently, iterative review and development of consensus was performed by a Consensus Group composed of international clinical experts familiar with BSGM. Eleven statements underlying the classification were then derived and circulated as a final survey to establish agreement. Results Six BSGM phenotypes were endorsed: three defined by myoelectrical abnormalities (Dysrhythmic, High Frequency, and Low Meal Response) and three by characteristic symptom associations (Sensorimotor, Continuous, and Delayed Onset Symptoms). Published studies plausibly linked these phenotypes to mechanisms including interstitial cell of Cajal depletion, vagal impairment, hypomotility, visceral hypersensitivity, gut‐brain dysregulation, and small bowel dysfunction. Phenotypes were also mapped to existing mechanism‐based treatment guidelines. Ten out of the eleven statements had > 80% agreement. Conclusions The Auckland Classification, derived by international consensus, presents a structured framework for BSGM‐defined patient phenotypes. Evidence and mechanism‐based treatment options are suggested for each phenotype to provide a foundation for research, further validation, and a pathway for integrating BSGM into clinical care.

Background/Objectives: Novel vision-language models (VLMs) can integrate patient textual data with image data to support medical diagnosis. Recent studies reported conflicting results regarding the performance of multimodal VLMs compared to other models and physician performance. This systematic review aims to assess the diagnostic performance of multimodal VLMs integrating both patient textual and image data across diverse real-world hospital settings. Methods: We performed comprehensive searches of eight resources, including Embase, MEDLINE, and SCOPUS, on 17 December 2025. Eligible studies reporting diagnostic performance of VLMs integrating both image and patient history textual data from real-world adult patients compared to that of other models and physicians were included. The review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The Prediction model study Risk Of Bias Assessment Tool + AI (PROBAST + AI) was used to assess the quality and risk of bias. The study protocol was registered in the PROSPERO database (CRD420251244054). This review received no external funding. Results: We screened 11,026 records, of which 18 studies met the inclusion criteria. Six studies comparing multimodal and unimodal models demonstrated the consistent superiority of the multimodal models. Four studies evaluating VLM accuracy as standalone agents compared with physician performance reported conflicting evidence. One study assessing VLMs as a clinical copilot demonstrated higher accuracy from the group of physicians using VLM assistance. A meta-analysis could not be performed due to the heterogeneity across study populations and outcomes. The majority of the studies were assessed as having a high risk of bias due to dataset quality. Primary limitations identified across studies include small sample size, a lack of external validation, and the need for prospective clinical deployment studies. No study provided documented considerations regarding model safety or data security. Conclusions: This systematic review suggests that multimodal VLMs consistently outperform unimodal models with access to only image or text. While model performance as standalone agents compared to humans remains inconclusive, a copilot model has demonstrated high diagnostic accuracy. Given substantial methodological concerns across studies, cautious interpretation is required, No firm clinical recommendation can be made regarding the use of standalone VLMs. Further research employing high-quality datasets is needed to ensure the reliability and clinical applicability of future VLMs.

Abstract Extramedullary disease (EMD) is increasingly recognized in relapsed/refractory multiple myeloma (MM), with central nervous system involvement (CNS-MM) representing a rare but highly aggressive manifestation associated with dismal outcomes. Data on its incidence and optimal management, particularly in the era of cellular and bispecific therapies, remain limited. We conducted a retrospective analysis of patients with MM with pathology-confirmed EMD treated at our institution between January 2000 and December 2023. CNS-MM was defined by parenchymal or leptomeningeal involvement. Clinical features, cytogenetics, treatments, and outcomes were analyzed, with predictors of CNS involvement evaluated among patients with EMD. Among 304 patients with EMD, 20 (6.5%) had CNS-MM. CNS involvement occurred a median of 19.2 months after MM diagnosis, though 15% presented at diagnosis. CNS-MM was strongly associated with high-risk cytogenetics (odds ratio [OR], 3.7) and additional visceral EMD (OR, 4.6). Median overall survival (OS) from CNS-MM diagnosis was 4.2 months. Outcomes were significantly improved in patients receiving chimeric antigen receptor T-cell therapy or bispecific antibodies, with a median OS of 19.2 months vs 1.2 months in those who did not receive immune effector therapies. Intrathecal (IT) chemotherapy demonstrated limited and transient benefit. In conclusion, CNS-MM is an aggressive complication enriched in high-risk, multifocal EMD with extremely poor prognosis. Cellular and bispecific therapies show promising activity and may meaningfully improve survival, whereas IT therapy appears to have limited efficacy. Prospective studies are needed to define optimal treatment strategies for CNS-MM.

Abstract Background Cholangiocarcinoma (CCA) is an aggressive primary liver cancer with remarkable molecular heterogeneity. Mutations in SWI/SNF chromatin remodeling components occur in > 20% of CCA cases, with ARID1A and PBRM1 being significantly co-mutated. However, how the dual loss of these subunits reshapes chromatin architecture and drives oncogenic programs remains unclear that we aimed to address by profiling SWI/SNF redistribution, chromatin accessibility, 3D chromatin structure, and transcriptome in a dual Arid1a/Pbrm1 knockout mouse model. Methods CCA was induced in Cas9 knock-in mice via biliary instillation of myr-AKT along with sgRNAs targeting Arid1a and Pbrm1, generating APAC cell line. AC cell line was derived from mice receiving myr-AKT alone. Isogenic dual knockout (AC-sgAP) and control (AC-NT) lines were then generated from AC cells. Multi-omics profiling included ChIP-seq for SMARCA4/BRG1 and DPF2, ATAC-seq, RNA-seq, and Hi-C. Results ChIP-seq revealed that AC-sgAP cells showed decreased BRG1 binding (9,217 vs. 20,769 peaks) but increased DPF2 binding (7,527 vs. 2,068 peaks) and co-occupancy (5,037 vs. 1,888 peaks) compared to AC-NT. In contrast, APAC cells exhibited depletion of both BRG1 (12,994 peaks) and particularly DPF2 (146 peaks) with minimal overlap (68 shared peaks). Genome-wide accessibility profiling demonstrated that APAC cells had 78,582 differentially accessible regions compared to AC-NT, the majority (>70%) representing loss of accessibility, whereas AC-sgAP cells showed only 6,587 differentially accessible regions. Transcriptional profiling identified both unique and common significantly differentially expressed genes in APAC and AC-sgAP relative to AC-NT controls. Interestingly, topologically associating domains (TADs) calling revealed that AC-sgAP cells displayed approximately three-fold more differential TADs compared to AC-NT than APAC cells relative to controls. Conclusions Concurrent Arid1a/Pbrm1 loss drives extensive chromatin and transcriptional reprogramming through SWI/SNF redistribution. APAC cells achieving greater transcriptional dysregulation with fewer TAD disruptions might suggest that intra-TAD regulatory changes are critical events in SWI/SNF-mutant cholangiocarcinoma.