Minnesota Gastroenterology

Abstract Background Approved treatment options for children and adolescents with ulcerative colitis (UC) are limited.1 The KEPLER phase 3 trial evaluated the efficacy, immunogenicity, pharmacokinetics (PK) and safety of vedolizumab (VDZ), an anti-α4β7 integrin biologic, administered as intravenous (IV) induction and maintenance therapy in children and adolescents with moderately to severely active UC. Methods This phase 3, single arm trial (NCT04779307) enrolled patients with moderate-to-severe UC (modified Mayo score of 5-9 with endoscopic subscore ≥2) aged 2-17 years and weighing ≥10kg with prior failure of conventional therapy such as steroids, immunomodulators, and/or tumour necrosis factor (TNF) antagonists. VDZ IV was administered during a 14-week, open-label induction period followed by a 40-week, randomised, double-blind maintenance period evaluating low- (LD) or high-dose (HD) VDZ (1:1) by body weight (10-15kg [100 vs 150mg]; >15-<30kg [100 vs 200mg]; ≥30kg [150 vs 300mg]) given every 8 weeks. The primary endpoint was clinical remission by modified Mayo score at Week 54 in the intention-to-treat maintenance population. Secondary endpoints included clinical remission at Week 14, sustained clinical remission (at Weeks 14 and 54), corticosteroid-free clinical remission at Week 54, immunogenicity, PK, and safety. Results The trial enrolled 121 patients (10-15kg, n = 3; >15-<30kg, n = 27; ≥30kg, n = 91), of whom 120 were dosed; 93 were subsequently randomised into LD (n = 47) or HD n = 46) groups for maintenance therapy (Table 1). Forty-four of 93 (47.3%) patients achieved the primary endpoint of clinical remission at Week 54, with similar proportions in LD and HD groups (Fig. 1A). Clinical remission rates at Week 54 for patients categorised by weight, age, anti-TNF exposure, and baseline corticosteroid use are shown in Fig. 1B-E. Forty-two of 121 (34.7%) patients achieved clinical remission at Week 14. At Week 54, 27/93 (29.0%) patients achieved sustained clinical remission. Anti-VDZ antibodies occurred in 7/120 (5.8%) VDZ-exposed patients, including neutralizing antibodies in 4 (3.3%); similar VDZ serum trough levels were observed across weight groups. In the safety population, 103/120 (85.8%) patients had treatment emergent adverse events (TEAEs), including 15/120 (12.5%) related to VDZ. Twenty-five of 468 (5.3%) TEAEs were serious. Five (4.2%) patients had serious VDZ-related TEAEs. Seven (5.8%) patients had TEAEs leading to VDZ discontinuation (most common: UC worsening, n = 3; infection, n = 3). Conclusion LD and HD VDZ IV were effective for children and adolescents with UC, including those with prior anti-TNF or corticosteroid failure. Similar rates were observed in adult patients with UC.2 VDZ was well tolerated, with no new safety signals identified.

Abstract Purpose Falls are common in adults with cerebral palsy (CP) and remain a significant concern. The study examined whether fall risk, fall incidence, and fall-related injuries differ by GMFCS level, CP type, age, and gender in adults with CP. Materials and Methods A cross-sectional, retrospective chart review was conducted for adults 18 years or older with CP who received outpatient specialty care between December 2022 to May 2023. CP diagnosis and type were determined using ICD-10 codes; GMFCS level was extracted from electronic medical record notes. Fall risk was determined using the Morse Fall Scale (MFS), with scores ≥45 indicating high fall risk. Results Among 647 adults with CP, ambulatory individuals (GMFCS II–III) had significantly higher MFS scores and fall incidence than non-ambulatory individuals (p < 0.001). CP type and gender showed significant group differences, whereas age did not. Individuals with spastic diplegia and unspecified CP showed higher fall risk. Females were twice as likely as males to report a recent fall, although MFS scores did not differ by gender. Five injuries were reported among ambulatory individuals in the past three months. Conclusions Findings highlight the importance of refining fall-risk assessment and prevention strategies for higher-risk groups.

No systematic procedures exist to ensure that differences in animal sensory capacities are accounted for in experimental design and ethical review processes. This oversight can compromise both scientific validity and animal welfare. This review presents three practical methodologies to address this gap: incorporation of specialist expertise through consultation frameworks, voluntary certification schemes modeled on Open Science practices, and mandatory sensory capacity review integrated into existing ethics committee processes. We provide a concrete tool-a sensory modality survey-that can be implemented by institutional review committees to evaluate sensory considerations in research proposals systematically. These approaches align with the 3Rs principles by enhancing experimental refinement and potentially reducing animal use through improved study design.

Abstract Background Operative notes in electronic health records contain critical information for understanding surgical care, yet manual coding is time-consuming, costly, and inconsistent. Large language models (LLMs) promise to transform this process by automatically extracting detailed procedure information — a capability with significant implications for scaling clinical registries and advancing surgical research. Methods We conducted a large-scale evaluation of state-of-the-art LLMs for zero-shot structured information extraction from orthopedic clinical notes. Fourteen open-source and proprietary models were tested on 800 real operative notes, annotated by both an orthopedic surgeon and an administrator using a curated list of 74 procedure classes. We compared model outputs to human annotations, assessing accuracy and exploring the effects of model scale, reasoning capabilities, and prompt design. Results Across models, LLMs consistently outperformed administrator-assigned labels, achieving macro-F1 scores above 0.6 and improving over administrative coding by up to 10 points. Larger models and reasoning capabilities further boosted performance, though gains plateaued beyond 30 billion parameters. Performance varied by procedure frequency, revealing clear strengths and persistent challenges for rare or complex cases. Conclusion Modern LLMs can already outperform routine administrative coding in extracting detailed surgical procedure data, pointing to a future where registry curation could be faster, cheaper, and more consistent. Yet, full alignment with surgical experts remains an open challenge—especially for rare procedures —emphasizing the need for domain adaptation and thoughtful deployment. Our findings illustrate how general-purpose LLMs can advance automated clinical data curation and inform the next generation of surgical informatics.

Kaposiform hemangioendothelioma (KHE) is a rare vascular tumor that typically presents in infancy and may be associated with the Kasabach-Merritt phenomenon (KMP). We present a challenging case of multifocal KHE on the leg of an infant, initially suspected at birth to be a reticulate port wine birthmark. Skin biopsy and imaging supported the rare diagnosis of multifocal KHE. Complicated by KMP, he was started on sirolimus monotherapy with significant improvement in his widespread disease.

Legg-Calvé-Perthes Disease (LCPD) is an idiopathic ischemic hip disorder that can lead to significant impairments in children. Despite representing a substantial portion of LCPD patients, children under 6 remain understudied. This study evaluates longitudinal PROMIS scores in children diagnosed with LCPD before age 6. This multicenter prospective cohort included children diagnosed with LCPD at age 6 or younger between February 2017 and July 2023. PROMIS T-scores (mobility, pain interference, fatigue, depression, anxiety, anger, and peer relationships) were analyzed alongside the Waldenström stage at the time of assessment using linear mixed-effects regression models, adjusting for demographics and interventions. Among 188 hips in 181 children (median age 4.6y, 81% male, 79% Caucasian) across 11 institutions, 810 PROMIS surveys were included. The mean and median follow-up was 1.9 years. At stage I, all domains showed mild impairment except depression and fatigue, which remained normal. Pain interference and anger normalized by stage iia, mobility by stage IIIa, and anxiety by stage IIIb (P<0.05). In children under 6, PROMIS T-scores showed significant improvements across domains as patients progressed through Waldenström stages. These findings provide insight into how PROMIS T-scores evolve with disease stage, helping clinicians guide families on expected outcomes and set realistic expectations. Level II-prognostic.

Sacral nerve modulation (SNM) therapy is an established treatment for pelvic floor disorders, yet its programming relies heavily on subjective patient feedback during follow-up visits. This paper introduces a non-invasive system for quantifying pelvic floor contractions, addressing the need for objective, real-time measurements to enhance clinical decision-making. The system employs a pressure-based sensor array integrated into a user-friendly design that ensures patient comfort and usability while maintaining millisecond-level temporal resolution. Initial testing with healthy volunteers demonstrated the system's ability to detect and differentiate contractions, though limitations such as movement artifacts and positioning variability were identified. Subsequent optimization reduced these challenges by refining sensor placement and signal conditioning. Future work includes clinical validation in SNM patients and integration of stimulation artifact measurement to establish a causal link between stimulation parameters and observed contractions. This system has the potential to bridge the gap between intraoperative observations and outpatient therapy programming, offering a pathway to more precise, efficient, and patient-centered SNM therapy.Clinical Relevance- The proposed system for measuring pelvic floor contractions provides a quantitative, real-time measurement for pelvic floor muscle contractions, which could address a gap in current programming paradigms that rely predominantly on subjective patient feedback. The design prioritizes patient comfort and ease of use, making it well-suited for clinical visits. With future integration of stimulation artifact measurement and validation in SNM patients, the system has the potential to enhance the precision and efficacy of therapy programming.

The purpose of this review is to explore the role of specialized pro-resolving mediators (SPMs) in the resolution of inflammation in inflammatory bowel disease (IBD) focusing on their potential therapeutic benefits in these conditions. IBD is characterized by chronic inflammation and mucosal barrier dysfunction, driven by a dysregulated immune response. SPMs, which are derived from polyunsaturated fatty acids, have been identified as active agents in resolving inflammation without impairing immune function. Preclinical studies indicate that SPMs can reduce intestinal inflammation, but clinical data are still limited. Moreover, SPMs may influence colorectal cancer (CRC) by modulating tumor-promoting inflammation and enhancing chemotherapy response. SPMs offer a promising approach to inflammation resolution and mucosal healing in IBD and CRC. However, further research is necessary to better understand their therapeutic potential and to establish their clinical applicability in these diseases.