Citations

Abstract Introduction Despite regulatory mandates for advanced therapy (AT) washout periods of up to 5 drug half-lives before enrolling patients in inflammatory bowel disease (IBD) trials, the evidence base for these requirements is largely empirical, and whether shorter intervals independently increase the risk of serious infections in real-world practice remains unknown. Methods Using the OptumLabs Data Warehouse, we identified adult patients with IBD who initiated a new AT (tumor necrosis factor antagonists, vedolizumab, interleukin (IL)-12/23 or IL-23 antagonists, or Janus kinase inhibitors) between 2018 and 2023 using a class-specific new-user design. We examined whether exposure to AT within the preceding 12 months (vs no exposure to AT within that window) and timing of discontinuation (≤1 month, 1-<3 months, or 3-12 months) were associated with risk of serious infections using multivariable Cox proportional hazards regression. Results Among 21 564 AT initiators (47 ± 18 years; 52% female; 57% Crohn’s disease), 7490 (34.7%) had AT exposure within the preceding 12 months. Over a mean follow-up of 1.6 ± 0.9 y, 1955 (9.1%) experienced a serious infection. Prior AT exposure was associated with higher infection risk (hazard ratio [HR]: 1.19, 95% confidence interval [CI]: 1.07-1.33), consistent in inverse probability of treatment-weighted analyses (HR, 1.20 [1.06-1.37]). Among patients with prior exposure, timing of discontinuation was not associated with infection risk (HR, 1.17 [0.95-1.43] for ≤1 month vs 3-12 months; HR, 1.01 [0.83-1.22] for 1-<3 months), with no dose–response relationship on continuous modeling. Discussion AT exposure within the preceding 12 months is associated with modestly higher risk of serious infection after initiating a new AT in IBD, but timing of discontinuation does not independently influence this risk.

Abstract Background Data describing the incidence and clinical outcomes of respiratory syncytial virus (RSV) infection among patients with inflammatory bowel disease (IBD) are limited. Methods We conducted a nationwide retrospective cohort study using the Veterans Health Administration (VHA) database. Adults with IBD were identified using a previously validated algorithm and matched 1:2 to non-IBD controls using propensity score matching. Laboratory-confirmed RSV infections that occurred between January 1, 2021, and December 31, 2024, were identified using standardized laboratory codes and confirmed by manual chart adjudication. Primary outcomes included RSV incidence and hospitalizations. Secondary outcomes included intensive care unit (ICU) admission and patient outcomes stratified by IBD medication class. Results After propensity score matching, 52 740 IBD patients and 104 997 non-IBD controls were included. Infection with RSV occurred in 219 patients with IBD and 426 non-IBD patients. Incidence rates of RSV were similar between cohorts across all years in our study period. Hospitalization related to RSV occurred in 18.26% of IBD-RSV patients compared with 13.15% of non-IBD patients (P = .08). ICU admission was rare in both groups (<1%). Among patients with IBD, RSV-related hospitalization did not differ significantly by medication class, when comparing biologic therapy (8.93%) with 5-aminosalicylic acid monotherapy (17.58%) (P = .15). Conclusions In this nationwide cohort, patients with IBD, with predominantly lower exposure to advanced therapies, did not have higher rates of RSV infection or worse clinical outcomes compared with matched non-IBD controls. RSV outcomes were similar across IBD medication classes. These findings support current vaccination recommendations and provide reassurance regarding RSV risk among patients with IBD.

Background Gastro-oesophageal reflux disease (GORD) occurs in most (∼75%) patients with systemic sclerosis (SSc) and significantly impacts quality of life. Current recommendations lack depth and therefore our aim was to produce practical, consensus-based recommendations for refractory SSc-related GORD. Methods An international, multidisciplinary steering board (SB) was assembled (n=19) consisting of clinicians (rheumatologists, gastroenterologists, gastrointestinal surgeons), an expert methodologist and patient representation. After reviewing the latest definitions of GORD and refractory GORD in the published literature, the SB collectively devised a practical definition of SSc refractory-GORD. Initial recommendations were drafted/agreed on by the SB based on review of the existing guidelines, published literature and expert opinion. Two online voting rounds were conducted to determine whether items should be accepted, with >75% and >60% SB agreement required for first and second rounds, respectively. Results There was a good response/completion rate for the initial (74%) and final (84%) voting rounds. The SB agreed on all 36 draft recommendations. The majority (n=34) were approved in the first round. Recommendations were organised according to the following categories: general approach to management (n=5), assessment (n=6), non-pharmacological (n=2) and pharmacological (n=10) management, endoscopic and surgical treatment (n=3), and special circumstances including refractory GORD and SSc-interstitial lung disease (n=3), myositis and SSc connective tissue disease-overlap (n=3) and perilung transplant (n=4). Conclusion The group of experts has drafted extended and practical recommendations for the management of SSc refractory-GORD. The necessity of a structured approach and a patient assessment is highlighted in order to provide a multidisciplinary approach to the tailored choice of the treatment. Our work also has also identified significant unmet needs and has provided a research agenda to advance the field.

Shear wave elastography generates shear waves with an acoustic radiation force to obtain estimates of the shear wave speed. Shear wave elastography often utilizes time-of-flight calculations that apply cross-correlations or time-to-peak methods to obtain estimates of the shear wave speed in the time-domain. However, these time-domain methods fail to consider the effect of dispersion caused by the shear viscosity, which can introduce substantial errors into estimates of the shear wave speed. To solve this problem, a new viscoelastic method for estimating shear wave parameters in the time-domain is introduced. The performance of the new method, which is applied to shear wave particle velocity waveforms, is established by evaluating a simulated three-dimensional viscoelastic Green's function model for shear waves in the time-domain. Results show that the new viscoelastic time-domain method is applicable to locations outside of the push beam region at the focal depth and throughout a two-dimensional plane. The results also indicate that estimates of the shear wave speed are either comparable to or significantly improved relative to values obtained from cross-correlations while simultaneously providing estimates of the shear viscosity in the time-domain.

BACKGROUND AND OBJECTIVES: Pediatric large-volume brain arteriovenous malformations (AVMs) carry a substantial lifelong hemorrhage risk, neurological symptoms, and treatment morbidity. Single-session stereotactic radiosurgery (SRS) is often unsuitable due to constraints on dose-volume toxicity. Volume-staged SRS (VS-SRS) enables sequential dosing of large nidus volumes, potentially enhancing safety while maintaining efficacy. Evidence in children remains limited. We aimed to evaluate outcomes of VS-SRS for large AVMs in pediatric patients. METHODS: A multicenter retrospective cohort was assembled from 21 centers, including patients aged younger than 21 years treated with VS-SRS for AVMs >10 cm 3 . Clinical and radiological end points included obliteration, hemorrhage, and permanent symptomatic radiation-induced changes (RIC). RESULTS: A total of 103 patients were included (median age 14 years; IQR, 12-17). The median nidus volume at first stage was 18.2 cm 3 (IQR, 12.3-25.6). Median prescription dose per stage was 17 Gy (IQR, 16-18). The median clinical follow-up from the first stage was 57.5 months (IQR, 25-138). Obliteration occurred in 42 of 103 patients (40.8%), with actuarial rates of 6.9% (95% CI: 2.8-14) at 3 years and 29% (95% CI: 20-39) at 5 years. Hemorrhage occurred in 17 of 103 patients (16.5%) during follow-up, and permanent RIC was observed in 9 of 103 patients (8.7%). CONCLUSION: VS-SRS is a reasonably safe, selected option for pediatric large-volume AVMs when microsurgical or endovascular cure is not feasible or prudent. Delivering ≥17 Gy per stage while limiting each treatment volume to <15 cm 3 supports durable nidus control with acceptable toxicity. VS-SRS represents a key modality in multidisciplinary management of this historically difficult-to-treat population.

Abstract Introduction: Surveillance biopsies after kidney transplantation provide an opportunity to assess early renal disease processes, including diabetic nephropathy, before clinical manifestation. This study aimed to identify proteomic alterations in renal allografts at 5 years post-transplant (5yrPT) and their associations with histologic features in diabetic/obese (DM/OB) versus non-diabetic/non-obese (nDM/nOB) recipients. Methods: We studied protocol biopsies from 17 DM/OB and 14 nDM/nOB kidney transplant recipients at Mayo Clinic (2000–2012). Laser capture microdissection followed by mass spectrometry was used for proteomic profiling. Histologic assessment included Banff and Tervaert scoring and morphometric analysis. Statistical comparisons were performed using ANOVA with Tukey post-hoc testing. Results: DM/OB recipients demonstrated greater histologic and metabolic injury at 5yrPT. Proteomic analysis identified 101 glomerular and 86 non-glomerular proteins differentially expressed between groups. Significant alterations were observed in proteins associated with mitochondrial dysfunction, including VDAC1 (fold change [FC] 2.6, p = 0.03), NDUFB9 (FC 0.15, p = 0.009), and NDUFA9 (FC 1.72, p = 0.01). Extracellular matrix remodeling proteins COL6A1, COL6A2, and COL6A3 were upregulated (FC 1.6–1.8, p < 0.05). Immune and inflammatory markers C9 (FC 1.6, p < 0.03) and TGFBI (FC 1.7, p < 0.001), as well as oxidative stress–related CLU, were increased. GGACT showed the greatest decrease (FC 0.30, p < 0.001), implicating altered energy metabolism. Conclusion: Distinct proteomic signatures at 5yrPT in DM/OB recipients highlight early mitochondrial, metabolic, immune, and extracellular matrix pathways involved in diabetic kidney disease. These changes precede clinical disease and identify candidate biomarkers and therapeutic targets to improve graft longevity.

Objective: Percutaneous needle tenotomy (PNT) and ultrasonic debridement (UD) are minimally invasive interventions for the management of chronic tendinopathy. Despite their increasing use, no standardized, evidence-based rehabilitation guidelines currently exist to direct clinicians in post-procedural management. This systematic review aimed to characterize and synthesize reported rehabilitation protocols following PNT and UD for patellar, proximal hamstring, and gluteal tendinopathies. Design: Systematic Review Results: Twenty-seven studies met inclusion criteria, with patellar tendon procedures (n=13) being the most common, followed by gluteal (n=6), proximal hamstring (n=3), and multi-tendon protocols (n=5). Of the included studies, 21 (78%) utilized percutaneous needle tenotomy (PNT) and six (22%) used ultrasound debridement or Tenex. Exercise restrictions were mandated in 19 studies (70%), while 12 (44%) provided a detailed, structured rehabilitation program, frequently emphasizing eccentric loading for patellar and hamstring tendons. Weight-bearing limitations were uncommon, appearing in only three studies (11%). Fifteen studies (56%) combined the procedure with platelet-rich plasma (PRP). Pharmacological protocols also showed high variance, with NSAID restrictions ranging from 1 to 28 days and corticosteroid avoidance lasting between 10 days and one year. Overall, substantial variability remains regarding recommended activity progression, exercise initiation, and mechanical loading strategies across current research. Conclusion: PNT and UD appear effective for managing refractory tendinopathy, yet post-procedure rehabilitation guidelines remain inconsistent and supported by limited high-quality evidence. Future research should aim to identify key variables that guide individualized rehabilitation progressions, optimizing recovery timelines, and facilitating safe and efficient return to activity following PNT and UD procedures.

Purpose: To evaluate the diagnostic performance and limitations of a general-purpose multimodal large language model (GPT-5.4) in detecting early keratoconus (KC) using corneal tomography images. Methods: This retrospective study included 66 eyes: 15 with subclinical KC, 18 with forme fruste keratoconus (ffKC), and 33 normal controls. Control eyes were obtained from refractive surgery candidates with normal corneas. For each eye, a standardized four-map Pentacam tomography image was analyzed using GPT-5.4 (OpenAI) with a predefined prompt. Only images were provided, without clinical or demographic data. Diagnostic performance for detecting early KC was assessed using sensitivity, specificity, predictive values, accuracy, and receiver operating characteristic (ROC) analysis. Results: GPT-5.4 demonstrated low sensitivity (30.3%) and high specificity (100%) for detecting early KC, with an overall accuracy of 65.2% and an area under the ROC curve of 0.65. The model showed a strong tendency to classify eyes as normal, resulting in a high rate of false-negative classifications. Multiclass analysis revealed a stage-dependent performance pattern, with excellent classification of normal corneas (100%), moderate detection of subclinical KC (53.3%), and poor detection of ffKC (11.1%), with most ffKC cases misclassified as normal. Conclusions: GPT-5.4 demonstrates high specificity but limited sensitivity for detecting early KC using image-only input and is not a reliable diagnostic or screening tool in its current form.