Citations

Abstract Background. Pain drives disability and medication use in autoimmune rheumatic diseases (ARDs), even when inflammation is controlled. The extent of pain-related polypharmacy across ARDs and chronic overlapping pain conditions (COPCs) remains poorly characterized. We aimed to quantify first-year pain medication burden following ARD diagnosis and examine variations by disease, COPC status, and time. Methods. Using the Merative MarketScan Commercial Claims database, we identified adults newly diagnosed with rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, psoriatic arthritis, Sjögren’s disease, or systemic sclerosis (2008–2021). We analyzed pain-related medications across ten pharmacologic categories during the first year post-diagnosis. Polypharmacy measures included distinct medication counts, medication categories, ≥ 5 and ≥ 10 medication thresholds, and the Medication Quantification Scale. Findings. Among 149,742 adults with newly diagnosed ARDs, 57.6% had at least one COPC. During the first year after diagnosis, patients filled a mean of 9.0 distinct pain medications and 47.9% met criteria for ≥ 5 medications; 30.5% met criteria for ≥ 10 medications. Ankylosing spondylitis demonstrated the highest medication burden (mean 11.6 medications; 57.5% with ≥ 5 medications; 37.9% with ≥ 10 medications). Patients with fibromyalgia had consistently higher medication burden across ARDs and were the only COPC group in whom prescribing increased after 2015. Overall medication burden rose from 2008 to 2014–2015 and declined thereafter; however, absolute levels remained high. Interpretation. Pain-related polypharmacy is common early after ARD diagnosis and varies substantially by disease and pain phenotype. Despite modest declines after 2015, medication burden remains high, underscoring the need for phenotype-informed, nonpharmacologic, and deprescribing strategies in rheumatology. Funding. NIAMS (K01AR079039).

ABSTRACT Background Sodium‐glucose cotransporter‐2 (SGLT2) inhibitors improve glycemic and cardiovascular outcomes in type 2 diabetes mellitus (T2DM). However, their impact on quality of life (QoL) and patient‐reported outcomes (PROs) has not been systematically evaluated. We conducted a systematic review and meta‐analysis to assess the effect of SGLT2 inhibitors on QoL in patients with T2DM. Methods MEDLINE, Embase, Scopus, Cochrane and ClinicalTrials.gov were searched until 18 August 2025 for randomised controlled trials and post hoc analyses of SGLT2 inhibitors reporting validated QoL or PRO outcomes in adults with T2DM. A random‐effects model was used to estimate mean differences (MD) or odds ratios (OR) with 95% CIs. Subgroup analyses compared SGLT2 inhibitors with placebo and active comparators. Risk of bias was assessed using the Cochrane RoB‐2 tool. Results Ten studies including 5294 patients (SGLT2i: 2807; control: 2487) were included. SGLT2 inhibitors significantly improved: EQ‐5D Index score versus placebo (MD: 0.04, p = 0.008), DTR‐QoL against active comparators (MD: 6.99; p = 0.0006), DTSQ compared to active comparators (MD: 0.54; p = 0.006) and IWQoL (MD: 1.44; p = 0.005) versus placebo. Improvements were also observed in SHIELD WQ‐9 overall QoL (OR: 2.11; p = 0.005), emotional health (OR: 2.16; p = 0.006), self‐esteem (OR: 2.26; p = 0.006) and work performance (OR: 1.99; p = 0.04) compared with placebo. Conclusion Randomised evidence suggests SGLT2 inhibitors enhance EQ‐5D Index score, diabetes‐specific QoL and several PROs in T2DM, particularly in physical, emotional and treatment satisfaction domains, supporting their earlier use in this population.

Background Hypermobile Ehlers–Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSDs) are heritable connective tissue disorders characterized by widespread fragile soft connective tissue affecting the skin, ligaments, joints, vasculature, and internal organs. Although hEDS and HSD are autosomal-dominant conditions and would be expected to display a 1:1 sex ratio, studies report higher prevalence in women. Objectives The purpose of this exploratory study was to determine whether self-reported sexual problems differed between females and males diagnosed with hEDS or HSD compared with controls with chronic pain but no hypermobility. Methods In this exploratory retrospective study, we examined 1,407 patients diagnosed with hEDS or HSD according to the 2017 diagnostic criteria for eight indicators of sexual problems based on a validated screening tool. Results Patients in each diagnosis primarily self-reported as White, non-Hispanic females (90%). Of the 1,407 patients who attended the EDS Clinic, 976 (69%) were diagnosed with HSD, 240 (17%) with hEDS, and 191 (14%) were chronic pain controls with neither diagnosis. For HSD, 937 (96%) were females vs. 39 (4%) males (24:1 females to males), while for hEDS, 210 (88%) were females vs. 30 (13%) males (7:1 females to males), and controls were 165 (86%) females vs. 26 (14%) males (6:1 females to males). Females with hEDS reported significantly higher rates of sexual issues than chronic pain controls, including sexual problems (69%, p = 0.018), problems with sexual interest (41%, p = 0.023), sexual pain (45%, p = 0.006), and orgasm difficulty (34%, p = 0.022) compared with males with hEDS or males or females with HSD. In contrast, males diagnosed with hEDS did not report any sexual problems over controls, and males and females diagnosed with HSD reported only one issue—more problems with sexual interest—compared with controls (females p = 0.019, males p = 0.018). However, the small number of males in this study limits conclusions that can be drawn for them. Conclusions This study is unique because we examine sex differences in sexual problems in patients with hEDS and HSD. Our findings indicate a higher percentage of sexual problems in females with hEDS than chronic pain controls without hypermobility, but this was not observed for females with HSD.

Abstract Adipose‐derived cellular therapies (AD‐CTs) are increasingly used in orthopedics, yet the field lacks a standardized framework for classifying these heterogeneous products. Although prior efforts have standardized platelet‐rich plasma and bone marrow‐derived mesenchymal stromal cells, AD preparations remain inconsistently defined and poorly characterized. AD‐CTs encompass a range of products including enzymatically derived stromal vascular fraction, culture‐expanded adipose‐derived mesenchymal stromal cells (AD‐MSCs), and mechanically processed adipose tissue (AD‐MPT),each with distinct regulatory, cellular, and structural profiles. Unlike stromal vascular fraction and AD‐MSCs, which can be quantified using conventional assays, the intact extracellular matrix in AD‐MPTs complicates objective characterization. This paper introduces the Mechanical Processing (Harvesting) of Adipose Tissue classification system as a novel framework for standardizing the reporting of AD‐MPT harvesting and processing techniques that provides a structured approach to nomenclature and reporting. The system aims to enhance study comparability, facilitate research replication, and support the responsible advancement of adipose‐based therapies in musculoskeletal medicine.

ABSTRACT In normal health, the liver and lungs enjoy a close anatomic, physiologic, and functional relationship. In the context of pulmonary vascular disease, however, there is accumulating evidence that the interplay between the gut microbiome, hepatic system, and pulmonary vasculature (so‐called “gut‐liver‐lung” axis) plays an important role in driving disease pathogenesis and determining clinical outcomes. Despite recognizing the importance of the gut‐liver‐lung axis in pulmonary vascular disease however, little is known about the clinical characteristics, circulating factors, and physiologic pathways that mediate this important axis of communication. In this clinical and translationally focused review, we provide an overview of liver‐lung communication in normal physiology, and contrast this with gut‐liver‐lung derangements in pulmonary arterial hypertension, portopulmonary hypertension, and hepatopulmonary syndrome. We conclude with identifying key gaps in knowledge that will need to be addressed in order to manipulate the gut‐liver‐lung axis to prevent worsening pulmonary vascular disease, develop novel therapeutics, and improve patient outcomes.

Abstract Methods that map genetic risk to cells do not directly test whether spatially organized ligand–receptor (LR) gene annotations carry conditional heritability association. Here we introduce EdgeMap, which scores each gene by the spatial activity of its LR contexts in spatial transcriptomics data, maps these scores alongside cell-intrinsic annotations to SNP-level LD scores, and tests both jointly against GWAS summary statistics. Across 17 traits and five human tissues, edge z -scores are systematically higher in biologically matched tissues: all 15 traits with both matched and unmatched tissue classes show this ordering (median Δ z = 1.51 ; sign P = 3.1 × 10 −5 ), and 11 of 13 nominal-positive associations concentrate in the biologically matched set ( P = 1 × 10 −4 ). The pattern survives broad LR-gene-class and cell-type composition controls. Donor-level cross-section summaries, independent GWAS replication for LDL and CAD, and cell-segmented Visium HD liver data provide convergent support. A secondary analysis prioritizes constituent genes within active LR contexts; sixteen of 31 prioritized genes are absent from standard gene-level methods. These results establish spatially weighted LR-gene annotations as a complementary layer for interpreting complex-trait genetic architecture.

Objective: To evaluate the current literature on the role of collagen peptide supplementation in bone health, focusing on changes in bone turnover markers (BTMs) and bone mineral density (BMD). Data Sources: A search was conducted following PRISMA guidelines in the databases Academic Search Premier, APA PsychInfo, CINAHL Plus, GreenFILE, MEDLINE, and SPORTDiscus. Keywords included “collagen supplementation,” “bone turnover,” and “bone structure.” Studies published between January 2000 and March 2024 were included if they involved human subjects, oral collagen supplementation, and skeletal-related outcomes (BTMs or BMD). Risk of bias was assessed using the modified Physiotherapy Evidence Database (PEDro) scale. Main Results: Fifteen studies met the inclusion criteria. Collagen supplementation was associated with improvements in BTMs such as procollagen type I N-terminal propeptide and C-terminal telopeptide of type I collagen, as well as increases in BMD at whole body, femoral neck, and lumbar spine sites, particularly in postmenopausal women. However, neutral findings and substantial heterogeneity in study design, population characteristics, and dosing protocols were also observed. Conclusions: Collagen supplementation shows promise for supporting bone health, particularly in postmenopausal women, but the evidence remains inconsistent. Future research should address these gaps by focusing on premenopausal populations, standardizing dosing protocols, and exploring broader orthopedic applications, such as reducing stress fractures and enhancing recovery from musculoskeletal injuries.

Fetal repair of myelomeningocele remains an effective intervention to decrease hindbrain herniation and reduce the need for postnatal CSF shunting. Effectiveness depends on a watertight closure; however, there are challenges to achieving such. Often, a separate, watertight dural closure is difficult due to the thinness and fragility of the dural membrane. This video demonstrates the approach utilizing a previously described myofascial rotation of the bilateral paraspinal muscles to construct a robust closure even without the need for a separate dural closure or patch reinforcement. This method has been associated with improved primary closure rates and fewer postnatal procedures. The video can be found here: https://stream.cadmore.media/r10.3171/2026.1.FOCVID25235

OBJECTIVE Anterior cervical discectomy and fusion (ACDF) is commonly performed in both inpatient and outpatient settings. In this study, the authors evaluate the influence of surgical setting on patient-reported outcome measures (PROMs), satisfaction, dysphagia, and complications following ACDF. METHODS A prospectively collected, multi-institutional quality improvement registry was retrospectively reviewed. Patients eligible for study inclusion were those who underwent ACDF without corpectomy or arthroplasty between 2016 and 2023. The patients were stratified by surgery setting, with same-day discharge indicating outpatients and an overnight stay indicating inpatients. PROMs were collected preoperatively and at 3 and 12 months postoperatively. Patient satisfaction was measured using the North American Spine Society (NASS) outcome assessment questionnaire, and dysphagia was measured using the 10-item Eating Assessment Tool (EAT-10). Propensity score overlap weighting (average treatment effect in the overlap population) was used to balance baseline covariates. RESULTS Of the 1514 patients who underwent ACDF, 462 were inpatients and 1052 were outpatients. The outpatient cohort was younger (55.1 ± 10.7 vs 60.5 ± 11.0 years, p < 0.001), had higher rates of private insurance (73% vs 52%, p < 0.001), had a lower mean American Society of Anesthesiologists (ASA) physical status (2.3 ± 0.6 vs 2.6 ± 0.6, p < 0.001), and underwent more single-level surgeries (53% vs 33%, p < 0.001). Propensity weighting resulted in comparable mean ages (58.9, p > 0.9) and ASA classes (2.5, p = 0.8) as well as private insurance rates (56%, p > 0.9) between the cohorts. After weighting, the inpatient cohort had a higher share of single-level fusions (46% vs 37%, p = 0.007). An outpatient status was associated with significantly better 12-month numeric rating scale (NRS) scores for neck pain (2.4 ± 2.7 vs 3.1 ± 3.0, p = 0.006), NRS scores for arm pain (1.7 ± 2.6 vs 2.2 ± 3.0, p = 0.047), and Neck Disability Index (NDI; 7.7 ± 7.8 vs 9.8 ± 9.4, p = 0.004) and greater improvement from baseline to 12 months on the NDI (−12.5 ± 9.7 vs −10.8 ± 10.5, p = 0.017), EQ-5D (0.242 ± 0.220 vs 0.209 ± 0.226, p = 0.047), and EQ visual analog scale (10.6 ± 21.6 vs 7.1 ± 20.8, p = 0.012). Fewer outpatients reported dysphagia at 3 months postoperatively (31% vs 40%, p = 0.010). No differences were observed in readmissions or revision procedures, although fewer outpatients experienced new neurological deficits (1.0% vs 2.6%, p = 0.032) and pneumonia (< 0.1% vs 0.9%, p < 0.001). In terms of the 12-month NASS outcome assessment, a smaller proportion of the outpatient cohort reported the lowest satisfaction score (3.9% vs 8.0%, p = 0.019). CONCLUSIONS Outpatient setting was associated with better PROMs at the 12-month follow-up when patients were weighted by baseline health status. These findings support the efficacy of outpatient ACDF in appropriately selected patients.