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Background: Patients with spina bifida are living longer and more productive lives; however, many continue to experience functional limitations in adulthood. This study evaluated long-term functional progression and ambulatory status using the combined Myelomeningocele Functional Classification (MMFC) and Functional Mobility Scale (FMS), and examined factors associated with long-term changes. Methods: A retrospective review at a tertiary care rehabilitation center identified 168 patients with spina bifida. MMFC and FMS classifications were recorded at initial and final visits. A subgroup of ambulatory patients who underwent 3D-gait analysis was analyzed to assess the relationship between MMFC, body mass index (BMI), and functional speed (FS) using multiple linear regression. Results: The average follow-up was 15±10.31 years. The mean age at final follow-up was 20 years (range, 5 to 52), with 52% of patients being male. Fifty-two percent of patients were ≥18 years of age at final follow-up. Within the MMFC1 cohort, 48% used wheelchair mobility (FMS 1,1,1) at initial presentation; this increased to 80% at final follow-up. Eighty percent of the MMFC2 patients were able to complete the 50-yard walk test at initial classification, whereas only 60% were able to complete it at final follow-up. Within the MMFC3 cohort, there was a decline in patients requiring no external support (FMS 6,6,6) from 90% to 78%. All MMFC4 patients maintained an FMS of 6,6,6. A statistically significant relationship was found between functional speed (FS) and MMFC (with MMFC4 faster than MMFC3 and MMFC2) ( P =0.01414). Conclusions: Long-term follow-up demonstrates that functional classification may decline over time in MMFC1 to 3 cohorts, whereas MMFC4 remains stable. In addition, within individual cohorts (MMFC1 to 3), there was also a decline in FMS and functional walk testing. A positive and statistically significant relationship was observed between gait analysis FS and MMFC, and a negative and statistically significant relationship was observed between BMI and MMFC. The combined use of MMFC and FMS provides a structured framework for longitudinal functional assessment in patients with spina bifida. Level of evidence: Level III.

ABSTRACT Ciltacabtagene autoleucel (cilta‐cel) has demonstrated excellent efficacy and long‐term disease control in patients with relapsed/refractory multiple myeloma (RRMM). However, a proportion of patients experience early treatment failures. We investigated clinical factors associated with early progression or death (within 12 months) in patients with RRMM receiving standard‐of‐care cilta‐cel across the three Mayo clinic centers. Patients with a follow‐up of at least 12 months or progression or death within 12 months from infusion were included. Of the patients with early treatment failure ( n = 52), 69% had progressive disease and 31% had a non‐relapse mortality (NRM) event. In patients without early treatment failure ( n = 164), 13% of events were NRM. Among pretreatment factors, prior BCMA‐directed therapy, presence of extramedullary disease and a CAR‐HEMATOTOX score of ≥ 2 were independent predictors of early progression or death. The utilization of cilta‐cel in earlier lines of treatment (1–3 vs. 4 or more) demonstrated comparable PFS (12‐month PFS 73% vs. 77%, p = 0.94). Measurable residual disease positivity in the bone marrow at 3 months (11/197 patients) identified a small but high‐risk group with an increased risk of early treatment failure (OR 5.68; p = 0.012). Patients with less than a complete response on a FDG PET/CT at 3 months also had an increased risk of early treatment failure (OR 11.8; p < 0.0001). Our findings may help identify patients at high‐risk for early adverse outcomes despite receiving highly effective therapy, and support consideration of novel therapeutic strategies within a clinical trial setting.

Objective: This single institutional analysis explored outcomes and factors associated with local control and survival in pediatric patients with nonrhabdomyosarcoma soft tissue sarcoma (NRSTS). Methods: Patients 18 years of age or younger diagnosed between October 1990 and November 2021 who received external beam radiotherapy (EBRT) were retrospectively identified. Overall survival (OS) and disease-free survival (DFS) were analyzed using Kaplan-Meier methods and univariate Cox models. Results: Among 51 included patients, there were 33 extremity tumors (65%), with 80% T1/T2 and 90% M0. Surgery in 49/51 (96%) resulted in 32 (65%) R0 resections. All received EBRT, with brachytherapy or intraoperative radiotherapy boosts in 21/51 (41%). Thirty-four (66.7%) received chemotherapy. With 5.7 years median follow-up, 5-year OS and DFS were 70.7% and 67.9%, respectively. Positive margins were significantly associated with worse OS. Two-year local failure incidence was 18.1% for EBRT versus 5.3% for EBRT+boost (HR 3.67, P =0.24). Among 6 local failures, 5 received EBRT alone, including 3 with positive margins. Two treated with EBRT+boost had positive margins, neither with local recurrence. Conclusion: Multimodality treatment of pediatric NRSTS results in 5-year OS and DFS around 70%. Although complete resection remains essential, and the modern incidence of R1 resection has declined, IORT/brachytherapy boost may continue to have a role in selected patients with a high local recurrence risk.

Abstract Background Lysosomal dysfunction plays a crucial role in the pathogenesis of Parkinson’s disease (PD), particularly among GBA1 mutation carriers. Beyond GBA1 , genes such as TMEM175 , SCARB2 , and CTSB identified in genome-wide association studies (GWAS) are also implicated in lysosomal pathways contributing to PD risk, although their functional effects in patients remain unclear. Proteins encoded by these lysosome-related genes have been explored as potential therapeutic targets in experimental models. Biomarker profiles, including clinical measures, α-syn seeding activity, lysosomal proteins, and sphingolipids, may facilitate patient stratification and support therapeutic monitoring in future clinical trials. Aim The aim of this study is to investigate the impact of genetic variants of three lysosomal-related genes ( TMEM175 , SCARB2 , and CTSB ) on biomarker profiles in PD with and without GBA1 variants. Cross-sectional data from two German cohorts: the Tuebingen Parkinson Cohort (TUEPAC) and the DESCRIBE PD cohort of the German Center for Neurodegenerative Diseases were used as explorative cohorts, and data from Accelerating Medicines Partnership® Parkinson’s Disease (AMP-PD) were used as a validation cohort. The ultimate goal is to provide new data for patient stratification based on genetics, which might serve as a readout for target engagement and treatment efficiency assessment. Methods Three cohorts were analyzed: TUEPAC, DESCRIBE PD, and AMP-PD. TUEPAC and DESCRIBE PD were combined into a single German discovery cohort (TUEPAC-DESCRIBE-PD), while AMP-PD served as an independent validation cohort. Within each cohort, for subgroup analyses, PD patients were classified as the overall PD cohort (PD all ), and further stratified by GBA1 mutation status into PD patients without GBA1 mutations (PD GBA1 _wildtype ), and PD patients carrying GBA1 mutations (PD GBA1 ). We evaluated cognitive and motor function, as well as depression using the Montreal Cognitive Assessment (MoCA), Unified Parkinson Disease Rating Scale-part I II (UPDRS III), and Beck Depression Inventory-II(BDI-II) scales. Analyzed biomarkers included CSF α-syn seeding activity using seed amplification assay (SAA), CSF lysosomal protein levels of lysosomal integral membrane protein 2 (LIMP2), also known as SCARB2, cathepsin B (CTSB) and lysosome-associated membrane protein 2 (LAMP2), blood-based enzyme activity of the lysosomal glucocerebrosidase (GCase), and CSF sphingolipid profiles. PD patients carrying risk alleles in TMEM175 , SCARB2 , and CTSB were compared to non-carriers. Results Genotype-phenotype correlation analysis in TUEPAC-DESCRIBE-PD and AMP-PD revealed: (1) In PD all , the TMEM175 p.M393T risk variant was nominally associated with decreased cognitive function when adjusted for GBA1 mutation status in TUEPAC-DESCRIBE-PD; this association could not be replicated, although a similar trend was observed in the slightly smaller, but multicentric AMP-PD cohort; TMEM175 p.M393T was not significantly associated with BDI-I I or UPDRS-III scores in either cohort. (2) In PD GBA1 _wildtype , GCase activity was significantly lower in PD patients with SCARB2 rs6812193 risk allele in TUEPAC-DESCRIBE-PD, while a similar but non-significant trend was observed in AMP-PD; (3) In PD all , CSF levels of CTSB were nominally lower in carriers of CTSB rs1293298 risk allele compared to carriers of CTSB rs1293298 protective allele in TUEPAC-DESCRIBE-PD; in PD GBA1 _wildtype , LAMP2 was significantly lower in carriers of CTSB rs1293298 risk allele compared to carriers of CTSB rs1293298 protective allele in TUEPAC-DESCRIBE-PD; (4) In PD all , TMEM175 p.M393T risk allele was nominally associated with altered sphingolipid profiles across both TUEPAC-DESCRIBE-PD and AMP-PD cohorts. Conclusion These findings demonstrate that genetic variants in lysosomal-related genes ( TMEM175 , SCARB2 , and CTSB ) have a functional impact on biomarker profiles in PD patients. Integrating genetic characterization with biochemical profiling provides a framework for patient stratification and may serve as a translational strategy to monitor target engagement and evaluate treatment efficacy in future clinical trials.

Abstract Background Cardiovascular implantable electronic device (CIED)-associated infective endocarditis with large vegetations carries substantial morbidity and a high risk of embolization during transvenous lead extraction (TLE). Purpose To evaluate procedural outcomes, microbiological clearance, and embolic risk in patients undergoing percutaneous aspiration of vegetations in the setting of CIED-associated infective endocarditis prior to TLE. Methods Between January 2023 and October 2025, patients with confirmed CIED-associated infective endocarditis and echocardiographic evidence of vegetations on transvenous leads or cardiac valves were included. Mechanical aspiration was performed at the operator’s discretion for vegetation size &gt; 20 mm, multiple vegetations, prior or potential embolization risk, or ongoing sepsis. All patients underwent percutaneous aspiration using the AngioVac or Penumbra system, followed by TLE either during the same session or in a staged procedure. Baseline clinical characteristics, microbiologic data, procedural details, and outcomes were reviewed. Results Our cohort comprised five patients (60% male) with a median age of 56.8 years (IQR 49.4–66.1). Median lead dwell time was 6.1 years (IQR 3.9–14.8). Median vegetation size was 12.5 mm (IQR 8–17). Two patients had prior septic pulmonary emboli. Microbiology identified Staphylococcus aureus in 2, Streptococcus spp. in 2, and Salmonella spp. in 1. The tricuspid valve and lead were involved in 4 patients, the mitral valve in 2, and the aortic valve in 1. The AngioVac system was used in 4 cases and Penumbra in 1. Successful aspiration (≥70% reduction in vegetation size of the targeted valve) was achieved in all cases. Two patients underwent staged extraction and three underwent concomitant TLE with complete removal of the transvenous system. A total of 8 leads were extracted (median 1, IQR 1–2.5); 4 patients had ICD leads, 2 with dual coil. No clinically significant embolic events occurred during the procedures. Among two patients with persistent infection, blood cultures cleared within 24 hours in one and 96 hours in the other. There were no major procedural complications or in-hospital or 30-day mortality. One patient with multivalvular involvement (aortic, mitral, tricuspid) subsequently underwent valve replacement surgery after blood cultures became sterile post-aspiration and TLE. Conclusion Percutaneous mechanical aspiration of vegetations prior to TLE was feasible and safe, resulting in effective microbiological clearance without periprocedural embolic events or major complications. This approach provides a viable alternative to surgical extraction in selected high-risk patients with large vegetations and device-related infective endocarditis and helps control sepsis.TEE images of the TV vegetationMacroscopic image of the vegetation

Abstract Objectives This study aimed to investigate the procedural characteristics, efficacy, and safety of atrioventricular junction (AVJ) ablation for atrial tachyarrythmia (AT) in patients with congenital heart disease (CHD). Background Although AVJ ablation is an established treatment option for intractable AT in the general population, there is no existing data on this treatment in patients with CHD. Methods Data were analyzed from an observational, retrospective, multicenter cohort, initiated jointly by the Pediatric and Congenital Electrophysiology Society and the International Society of Adult Congenital Heart Disease. Eleven centers contributed baseline, procedural and longitudinal data, including vital status, echocardiographic data, QRS duration, and NYHA class. Outcomes were assessed at early (3 months-1 year), and late follow-up (≥2 years) after AVJ ablation. Results A total of 66 patients (46.7 ± 20.2 years) underwent 71 AVJ ablations. In total, 58.5% had moderate or complex CHD, including 17.1% patients with a systemic RV or single ventricular circulation. The cumulative AVJ ablation success rate was 98.5%. An abnormal location of the atrioventricular conduction pathway was successfully targeted in 20.0% of the patients, which was significantly more common in patients with complex CHD compared to moderate or mild CHD (44.4%, 15.8%, and 3.6%, respectively; both P&lt;0.05). Thirty-six patients (54.5%) underwent primary pacemaker implantation as part of the ‘pace and ablate’ strategy; final pacing modes were VVI pacing in 60.9%, and CRT/CSP in 39.1%. The transplant-free survival rates at 2, 5 and 10 years after AVJ ablation were 91.5%, 84.3%, and 69.0%, respectively. The acute and long-term complication rates were 3.0% and 13.6%, respectively. Conclusions AVJ ablation can be successfully performed in CHD patients with a high acute success rate and low complication rate. Anatomical challenges were common, which underscores the need for careful planning and operator experience. Given the acceptable long-term survival, these findings support the consideration of a ‘pace and ablate’ strategy in CHD patients with intractable AT.

Abstract Background Arrhythmogenic mitral valve prolapse (AMVP) is increasingly recognized as a cause of sustained ventricular arrhythmias (VA) and sudden cardiac death. Although prior studies have identified clinical and imaging risk markers in AMVP, it remains unclear whether the arrhythmogenic phenotype differs between women and men. Purpose To investigate sex-specific differences in clinical profiles, structural substrates, and arrhythmia presentations in patients with AMVP who experienced sustained VA. Methods We conducted a sex-based sub-analysis of a multicenter cohort (35 centers from 15 countries) of patients with AMVP and sustained VA. Participants were grouped by sex and by initial arrhythmia type (sustained monomorphic ventricular tachycardia [SMVT] vs ventricular fibrillation [VF]). Data collected included clinical history, ECG findings, echocardiographic measurements, and cardiac MRI (CMR) markers, such as late gadolinium enhancement (LGE) patterns and mitral annular disjunction (MAD). These factors were compared across groups. Results The study comprised 129 women (57%) and 96 men (43%). Women were diagnosed at younger ages (39±16 years vs. 49±16 years, p&lt;0.03) and had more frequently a family history of MVP (22% vs 10%, p=0.027). MAD was significantly more common in women (66% vs 48%, p=0.015) while LGE was more frequently observed in men than women (N=39 (72%) vs N=41 (53%), p=0.028), with no significant regional patterns (myocardial and/or papillary muscle). ECG T-wave inversion (p=0.627), PVC burden (p&gt;0.03) and arrhythmia types were similar in men and women. However, stress was a more often commonly recognized as the initiating trigger for VA in men than in women (38% [N=24] vs. 18% [N=18], p&lt;0.05). The overwhelming majority of VA were initiated by PVCs in both sexes with no differences in the initiating mechanisms. Conclusion In patients with AMVP presenting with sustained VA, the arrhythmic phenotype and initiating mechanisms are similar between sexes, although stress was a significantly stronger trigger for VA in men. Women more often exhibited MAD, whereas LGE was more frequent in men. These findings suggest that structural and tissue-based markers, rather than sex alone, contribute to the development of malignant arrhythmias in AMVP.