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Background: We aimed to update the 2018 systematic literature review on the efficacy and safety of treatments for hand osteoarthritis (OA), which was based on 126 studies., Methods: We performed a systematic literature search on randomised controlled trials from June 2017 up to 31 December 2023. Risk of bias was assessed using the RoB2 tool. Meta-analyses of previous and new studies regarding the efficacy for pain, function, grip strength and OMERACT/OARSI responders were performed. Certainty of evidence was judged using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) tool., Results: Sixty-five new studies were included. For non-pharmacological interventions, there was low-certainty evidence for a small long-term effect of hand exercises and a moderate long-term effect of thumb orthoses for pain, and moderate-certainty evidence that assistive devices had a moderate long-term effect on function. Concerning pharmacological interventions, there was low-certainty evidence for a moderate short-term effect of oral non-steroidal anti-inflammatory drugs (NSAIDs) on pain, high- and moderate-certainty evidence for a small short-term effect of topical NSAIDs and oral glucocorticoids on function, respectively, and low-certainty evidence that oral glucocorticoids had a small short-term effect on function. Further, there was low-certainty evidence that methotrexate had a small long-term effect on pain. The heterogeneity of studies did not allow for any meta-analyses on surgery., Conclusion: The results largely support current treatment recommendations. However, there is a lack of interventions that efficiently improve grip strength, and the evidence for most current treatments is still limited. To better understand action mechanism of different treatments, future trials should include hand OA subtyping and be powered for subgroup analyses., Competing Interests: Competing interests: This study had no competing financial interests. Interests disclosed in the international Committee of Medical Journal Editors (ICMJE) conflict of interest forms are as follows: IKH has received consulting fees from Novartis and GSK and is a member of the OARSI executive committee. MK has received grants from IMI APPROACH and the Dutch Arthritis Society, royalties/licences from Wolters Kluwer and Springer Verlag, and consulting fees from AbbVie, Pfizer, Kiniksa Flexion, Galapagos, CHDR, Novartis and UCB, and she is a member of the OARSI board, the EULAR council and President of the Dutch Society for Rheumatology., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Background: Whether fibromyalgia burden is related to measures of sensitization, assessed by quantitative sensory testing (QST), is not clear. We examine the associations between sensitization and fibromyalgia disease burden as measured by the polysymptomatic sistress scale (PDS) and the fibromyalgia impact questionnaire (FIQ) (range 0-100)., Materials and Methods: Participants were recruited from referrals to a rheumatology outpatient clinic and the fibromyalgia diagnosis was verified by a rheumatologist. They completed the PDS and FIQ and underwent QST of pressure pain threshold (PPT) at five sites, temporal summation (TS), and conditioned pain modulation (CPM) estimated as post-stimuli/pre-stimuli PPT. The associations between QST and disease burden were analysed in linear regression models adjusted for age, sex, and body mass index., Results: A total of 78 individuals with clinically verified fibromyalgia (90% women, mean age 40.9 years (SD 7.3)) were recruited. Overall mean PPT was associated with the FIQ total score (β-2.1, 95% CI-4.3, -0.0) and the function component (β-2.1, (-4.3, -0.0)). When examining the associations between PPT at individual sites and fibromyalgia disease severity, PPTs at the distal interphalangeal joint and tibialis anterior muscle were associated with both FIQ total score and the FIQ fatigue component. All associations were weak and insignificant after Bonferroni corrections., Conclusion: In this cohort of individuals with fibromyalgia, sensitization was not significantly associated with self-reported disease burden. Our results point to the multifactorial nature of fibromyalgia disease severity., Significance: In patients with fibromyalgia, commonly used measures of sensitization do not explain the symptom burden or the functional impact., (© 2024 The Author(s). European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation ‐ EFIC ®.)

Objective: To assess the longitudinal stability of biomarker-based molecular endotypes of knee osteoarthritis (KOA) participants from APPROACH and to evaluate the consistency of findings in an independent KOA population., Methods: Nineteen biomarkers were measured longitudinally in 295 KOA participants from the APPROACH cohort. K-means clustering was used to identify the structural damage, inflammation, and low tissue turnover endotypes at the six-, 12-, and 24-month follow-ups. Endotype stability was defined as having the same independent endotype assignment longitudinally for patients with complete data (n = 226). Clinical and biochemical characteristics were compared between participants with longitudinally stable and unstable endotypes. The presence and longitudinal stability of the endotypes were evaluated in a different KOA population from the placebo arm of the oral salmon calcitonin trials., Results: An average overall longitudinal endotype stability of 55% (Fleiss' Kappa of 0.53; 95% confidence interval [CI]: 0.46, 0.60) was demonstrated. An average stability of 59% (range: 54-59%) was observed for the structural damage endotype (Fleiss' Kappa 0.52; 95% CI: 0.45, 0.60), 54% (52-56%) for the inflammatory (Fleiss' Kappa 0.61; 95% CI: 0.53, 0.68), and 50% (49-52%) for the low tissue turnover endotype (Fleiss' Kappa 0.46; 95% CI: 0.39, 0.54). Participants with longitudinally unstable endotypes exhibited molecular properties of more than one endotype, which were detectable already at the first visit., Conclusions: Our study showed for the first time that more than half of KOA participants exhibited a longitudinally stable endotype, highlighting the applicability of biomarker-based endotyping in a clinical trial setting., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aims: About 10%-30% of individuals with obesity are metabolically healthy, but the specific characteristics of the metabolically healthy obesity (MHO) phenotype remain unclear. We aimed to examine how physical activity, education, depressive symptoms and genetic predisposition to obesity differ between individuals with MHO and those with metabolically unhealthy obesity (MUO), and whether these factors predict stability in MHO or conversion to a metabolically unhealthy state., Materials and Methods: We retrieved data on 9809 individuals with obesity from the Health and Retirement Study collected between 2006 and 2016. We compared how physical activity, education, depressive symptoms and a polygenic score for higher body mass index (BMI) (PGS BMI ) differed cross-sectionally between MHO and MUO using logistic regression. We then examined if the same factors predict conversion to a metabolically unhealthy state over 4 years in individuals with MHO., Results: Individuals with MHO had higher physical activity (odds ratio [OR] = 0.81), higher education (OR = 0.83) and lower depressive symptoms (OR = 1.14) compared to those with MUO but did not differ in the PGS BMI . The associations were slightly attenuated in mutually adjusted models. None of the factors were associated with conversion from MHO to a metabolically unhealthy state. However, a higher PGS BMI indicated 24% lower risk of conversion to a metabolically unhealthy state (p = 0.07)., Conclusions: Physical activity, education and depressive symptoms differed between MHO and MUO, even when mutually adjusted for, but did not predict conversion from a metabolically healthy to unhealthy state. Although not statistically significant, the results indicated that those with genetically predicted high BMI are more likely to maintain MHO and not convert to a metabolically unhealthy state., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Introduction: Musculocontractural Ehlers-Danlos syndrome (mcEDS) is a rare autosomal recessive connective tissue disorder caused by systemic depletion of dermatan sulfate. Symptoms characteristic of mcEDS include multiple contractures, fragile skin with subcutaneous bleeding, and hypermobile joints, which suggest difficulty in perioperative management. However, safe surgical techniques and perioperative management of this disorder remain unknown because of its rarity. We report a patient with mcEDS who developed endometrial cancer and underwent surgery, with emphasis on perioperative management., Case Report: A female patient, who had been genetically diagnosed with mcEDS-CHST14 at the age of 25, presented with symptoms characteristic of mcEDS, including: congenital contractures of fingers and clubfeet, recurrent joint dislocation, progressive foot and spinal deformities, and large subcutaneous hematomas. At age 33, she had been diagnosed with atypical endometrial hyperplasia, and scheduled to undergo total abdominal hysterectomy. To address the risk of massive hemorrhage during the surgery due to mcEDS-related tissue fragility, plasma-derived factor VIII concentrate was prophylactically administered before surgery. During the surgery, neither fragility, hyperextensibility, nor hemorrhagic tendency of the uterus or adnexa observed was observed. The surgery was uneventful, with blood loss of 180 mL and operative time of 2 h and 54 min. However, on the sixth postoperative day, a 2.5-cm dissection was noted at the site of skin incision. Subcutaneous fluid accumulation developed under the skin incision and it persisted for 1.5 months. The postoperative pathological diagnosis was endometrioid carcinoma grade 1, stage IA., Conclusion: The present case suggested that the prophylactic use of factor VIII was effective for the prevention of hemorrhage during surgery. However, delayed wound healing of the skin and subcutaneous tissues was considered a subject for future improvement., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2025 The Authors.)

Hepatectomy is the curative treatment for hepatocellular carcinoma (HCC), with targeted therapy used when resection is difficult. In this rare case, the tumor shrank with targeted therapy, enabling radical treatment through conversion surgery. The patient, a man in his 70s, developed an 11.5-cm HCC (T3N0M0 Stage III) in the posterior hepatic zone after being virologically negative for hepatitis C. The tumor was near the right portal vein branch, making the liver lobe unresectable due to poor liver function. Upon tumor enlargement, he was treated with atezolizumab and bevacizumab. After 5 courses, the tumor significantly shrank, allowing for complete resection with posterior segment removal. The surgery revealed mostly necrotic tumors with no active cancer cells remaining., Competing Interests: No Conflict of Interest., (© The Author(s) 2024. Published by Oxford University Press.)

Background: Air pollution in later life has been associated with dementia; however, limited research has investigated the association between air pollution across the life course, either at specific life periods or cumulatively. The project investigates the association of air pollution with dementia via a life-course epidemiological approach., Methods: Participants of the Lothian Birth Cohort, born in 1936, provided lifetime residential history in 2014. Participant's air pollution exposure for time periods 1935, 1950, 1970, 1980, 1990, 2001, and 2007 was modeled using an atmospheric chemistry transport model. Lifetime cumulative exposures were calculated as time-weighted mean exposure. Of 572 participants, 67 developed all-cause dementia [35 with Alzheimer's dementia (AD)] by wave 5 (~82 years). Cox proportional hazards and competing risk models assessed the association between all-cause dementia and AD with particulate matter (diameter of ≤2.5 µm) PM 2.5 and nitrogen dioxide (NO 2 ) exposure at specific life periods and cumulatively. False discovery rate (FDR) correction was applied for multiple testing., Results: The mean follow-up was 11.26 years. One standard deviation (SD) higher exposure to air pollution in 1935 (PM 2.5 = 14.03 μg/m 3 , NO 2 = 5.35 μg/m 3 ) was positively linked but not statistically significant to all-cause dementia [PM 2.5 hazard ratio (HR) = 1.16, 95% confidence interval (CI) = 0.90, 1.49; NO 2 HR = 1.13, 95% CI = 0.88, 1.47] and AD (PM 2.5 HR = 1.38, 95% CI = 1.00, 1.91; NO 2 HR = 1.35, 95% CI = 0.92, 1.99). In the competing risk model, one SD elevated PM 2.5 exposure (1.12 μg/m 3 ) in 1990 was inversely associated with dementia (subdistribution HR = 0.82, 95% CI = 0.67, 0.99) at P = 0.034 but not after FDR correction ( P FDR = 0.442). Higher cumulative PM 2.5 per one SD was associated with an increased risk of all-cause dementia and AD for all accumulation models except for the early-life model., Conclusion: The in-utero and early-life exposure to PM 2.5 and NO 2 was associated with higher AD and all-cause dementia risk, suggesting a sensitive/critical period. Cumulative exposure to PM 2.5 across the life course was associated with higher dementia risk. Midlife PM 2.5 exposure's negative association with all-cause dementia risk may stem from unaddressed confounders or bias., Competing Interests: The authors declare that they have no conflicts of interest with regard to the content of this report., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The Environmental Epidemiology. All rights reserved.)

Objectives: Fibrosis is the final common pathway for chronic kidney disease and the best predictor for disease progression. Besides invasive biopsies, biomarkers for its detection are lacking. To address this, we used hyperpolarized 13 C-pyruvate MRI to detect the metabolic changes associated with fibrogenic activity of myofibroblasts., Materials and Methods: Hyperpolarized 13 C-pyruvate MRI was performed in 2 pig models of kidney fibrosis (unilateral ureteral obstruction and ischemia-reperfusion injury). The imaging data were correlated with histology, biochemical, and genetic measures of metabolism and fibrosis. The porcine experiments were supplemented with cell-line experiments to inform the origins of metabolic changes in fibrogenesis. Lastly, healthy and fibrotic human kidneys were analyzed for the metabolic alterations accessible with hyperpolarized 13 C-pyruvate MRI., Results: In the 2 large animal models of kidney fibrosis, metabolic imaging revealed alterations in amino acid metabolism and glycolysis. Conversion from hyperpolarized 13 C-pyruvate to 13 C-alanine decreased, whereas conversion to 13 C-lactate increased. These changes were shown to reflect profibrotic activity in cultured epithelial cells, macrophages, and fibroblasts, which are important precursors of myofibroblasts. Importantly, metabolic MRI using hyperpolarized 13 C-pyruvate was able to detect these changes earlier than fibrosis-sensitive structural imaging. Lastly, we found that the same metabolic profile is present in fibrotic tissue from human kidneys. This affirms the translational potential of metabolic MRI as an early indicator of fibrogenesis associated metabolism., Conclusions: Our findings demonstrate the promise of hyperpolarized 13 C-pyruvate MRI for noninvasive detection of fibrosis development, which could enable earlier diagnosis and intervention for patients at risk of kidney fibrosis., Competing Interests: Conflicts of interest and sources of funding: This study was funded by The Lundbeck Foundation and The Karen Elise Jensen Foundation., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Cervical spinal cord injury (SCI) has a devastating effect on health and independence. Restoring upper extremity function is a top priority and can be accomplished by tendon transfer (TT) and nerve transfer (NT) surgery. The purpose of this prospective comparative study was to assess long-term changes in upper extremity function between surgical (TT or NT) and nonsurgical groups through a comprehensive mixed-methods approach., Methods: This multicenter cohort study compared data among 3 groups: those undergoing no surgery, TT surgery, or NT surgery. Quantitative data from the Spinal Cord Independence Measure (SCIM) and 36-item Short Form Health Survey were collected at baseline and long-term follow-up (6 to 24 months). Qualitative semistructured interview data were also obtained from these participants and their identified caregivers at baseline, early follow-up (1 month), and long-term follow-up (6 to 24 months)., Results: Thirty-one participants had quantitative data across all time points: no surgery ( n = 14), TT ( n = 7), and NT ( n = 10). SCIM scores improved in TT and NT groups compared with the no-surgery group ( P < 0.05). The 36-Item Short Form Health Survey scores did not differ among groups. Qualitative data analysis ( n = 168 interviews) corroborated SCIM findings: surgical participants and their caregivers reported improvement in transfers and ability to perform activities of daily living, including grooming and self-catheterization. Improved use of electronics and ability to operate a motor vehicle were also reported. Postoperative therapy was identified as a critical component of achieving gains., Conclusions: TT and NT surgery lead to quantitative and qualitative functional gains when compared to no surgery. This comparative information should be used to help surgeons discuss treatment options., Clinical Qusetion/level of Evidence: Therapeutic, II., (Copyright © 2024 by the American Society of Plastic Surgeons.)

Objective: Our primary objectives are to assess whether intraarticular corticosteroid injections are superior to saline injections with regards to thumb base pain after 4 weeks, and to compare the efficacy of steroid injections, saline injections, and an occupational therapy intervention on thumb base pain after 12 weeks in people with painful inflammatory osteoarthritis (OA) of the first carpometacarpal (CMC-1) joint., Design: In this three-armed, double-blind, randomized multicenter trial, 354 participants with painful inflammatory CMC-1 OA from six Norwegian hospitals are recruited. Participants are randomized 1:1:1 to intraarticular steroid or saline injections in the CMC-1 joint or a multimodal occupational therapy intervention. The primary outcomes are thumb base pain measured on a numeric rating scale (NRS, range: 0-10) after 4 weeks and 12 weeks. Key secondary outcomes include synovitis by Magnetic Resonance Imaging (MRI) after 4 weeks and hand function by the Measure of Activity Performance of the Hand (MAP-Hand) questionnaire after 12 and 24 weeks. Other secondary outcomes are synovitis by clinical examination and ultrasound, measures of pain, function, stiffness, and health-related quality of life, and direct and indirect costs. Adverse events are recorded at each visit. The duration of the randomized controlled trial is 24 weeks, followed by an 80-week open-label observational phase to investigate the long-term efficacy and safety of repeated steroid injections and the occupational therapy intervention., Conclusions: The results from this trial will have important clinical implications and influence future guidelines on OA management of the CMC-1 joint., Clinical Trial Registration: EU-CT 2023-505254-17-00, NCT06084364., Competing Interests: AG reports consulting fees from Pfizer, TissueGene, Formation Bio, ICM, Coval, Novartis and Medipost, and stock/stock options in BICL and LLC, outside of the submitted work. KD is part funded by the National Institute for Health and Care Research (NIHR) Applied Health Research Collaboration (ARC) West Midlands (NIHR 200165) and the Birmingham Biomedical Research Centre (BRC). KD is also an NIHR Senior Investigator (ID NIHR 205031). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. HBH reports honorarium from Abbvie, Novartis, Lily and UCB, and advisory boards for Abbvie and Novartis, outside of the submitted work. HS reports patent issued and pending for Syrigma™ (syringe cover). IKH reports personal fees from Novartis, GSK and Grünenthal, and speaker honorarium from Abbvie, outside of the submitted work. TAS reports grants and personal fees from Roche, and personal fees from AbbVie, Roche, Sanofi, Takeda, and Novartis, outside the submitted work. AK, ATT, DTF, DS, EBF, ELE, IK, IPM, JKU, JS, KBH, KL, MG, MH, MHE, MIS, MO and TA report no conflicts of interest., (© 2024 The Authors.)

Introduction: An earlier age of menopause (AOM) is hypothesized to increase vulnerability to the neuropathological processes of dementia which begin in midlife., Methods: We tested this hypothesis in a sample of 10,832 women from the Swedish Twin Registry, stratified by menopause etiology. Survival models showed that a U-shaped association was present for women whose menopause occurred spontaneously. Sensitivity analyses conducted in hormone naïve, APOE ε4+ and AOM restricted subsamples showed largely analogous patterns of results., Discussion: Supporting conclusions from basic research, our results suggest that estrogens (proxied here by AOM) interact with several biological pathways mediating dementia disease processes. In line with trends in hormone research across the past century, our findings challenge the oversimplified 'more-is-better' perspective on hormone exposure. Specifically, the non-linear association we observed between AOM and dementia risk points to the involvement of distinct and interacting biological mechanisms beyond just estrogen levels., Competing Interests: Competing Interests The authors have no competing interests to disclose.

A key ingredient for realizing a magnetically confined tritium-deuterium plasma fusion reactor is plasma heating by fusion-born high-energy helium ions, as a chained cycle of "nuclear burning." Efficient collisionless plasma heating by high-energy particles is anticipated when their energy is directly transferred to the plasma through waves. Those processes often involve nonlinear structure formations in phase-space, spanned by real-space and velocity-space coordinates, that significantly influence heating efficiency. To date, experimental knowledge of phase-space structure formation physics is severely limited, due to lack of experimental diagnostic schemes. Here, state-of-the-art hardware and software approaches for phase-space perturbative structure detection are introduced. A bifurcation in the phase-space structure formation is found, which affects the plasma heating efficiency. A confinement magnetic field structure is shown to be a potential knob for nuclear-burning control through phase-space manipulation., Competing Interests: Competing interests statement:The authors declare no competing interest.

Background: The JPLT3-S (Japanese Study Group for Pediatric Liver Tumors-3) study, conducted cisplatin (CDDP) monotherapy for young children (<3 years old) with standard-risk hepatoblastoma (HB) using a central review system in Japan. In the previous JPLT2 study, cases with resectable tumors without any annotation factors in the PRETEXT (PRETreatment EXTent of disease) classification (standard-risk HB) showed favorable outcomes with treatment consisting of CDDP and pirarubicin, but showed toxicities and late complications. In the JPLT3-S trial, a less intense regimen consisting of CDDP alone was evaluated., Methods: Patients who were less than 3 years of age and with PRETEXT I, II, or III HB without any annotation factors (e.g., E1, E1a, E2, E2a, H1, N1, P2, P2a, V3, and V3a) were eligible for inclusion in this study. In this trial, the central radiological and pathological features of all patients were reviewed. The primary outcome was the 3-year progression-free survival (PFS)., Results: A total of 38 patients (23 female) were included. The median patient age was 12 months (range: 2-34). Two patients discontinued treatment because of progressive disease, and five patients discontinued treatment for other reasons. The 3-year PFS rate was 93.9% (95% confidence interval [CI]: 86.4%-100%). All 38 patients survived (follow-up period 38-98 months), and the OS rate was 100% (CI: 100). Eighteen of the 38 patients (47.4%) experienced ototoxicity as a late complication., Conclusion: CDDP monotherapy regimen is feasible in young patients with localized HB, as classified by a central review., (© 2024 The Author(s). Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Objective: To assess whether change of semiquantitatively magnetic resonance imaging (MRI)-defined bone marrow lesions (BMLs) and inflammatory markers is associated with change in quantitatively-assessed cartilage loss in the femorotibial joint (FTJ) in knees with radiographic osteoarthritis (OA) over 24 months., Design: Participants were included from the IMI-APPROACH and the Osteoarthritis Initiative FNIH studies. Semiquantitative MRI assessment was performed for BMLs, Hoffa- and effusion-synovitis. Quantitative cartilage thickness measurements were performed manually. Definitions of change included number of subregions with BMLs, change in sum and change in maximum increase in size. Change in Hoffa-synovitis and effusion-synovitis was categorized in addition. Between-group comparisons regarding cartilage loss in the FTJ, medial and lateral compartments were performed using analysis of variance (ANOVA)., Results: A total of 629 participants were included. Knees without any BMLs at baseline (BL) and follow-up (FU) had significantly less cartilage loss compared to the other subgroups. Change in both directions in the sum score of BMLs was associated with increased rates of cartilage loss. Maximum increase in size of BMLs was associated with increased rates of cartilage loss (FTJ increase by 2 grades -0.183 mm, 95% CI [-0.335, -0.031], by 3 grades -0.306 mm, [-0.511, -0.101]). Worsening of Hoffa-synovitis was associated with increased rates of cartilage loss., Conclusion: Knees without BMLs at BL and FU showed lowest rates of cartilage loss. Knees with an increase in BML size showed increased rates of concurrent cartilage loss. Approaches with the aim to inhibit BML development, avoidance of increase in size and avoidance of Hoffa-synovitis worsening may have beneficial effects on cartilage loss., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Scientific and financial support for the FNIH OA Biomarkers Consortium are made possible through grants, direct and in-kind contributions provided by: AbbVie; Amgen Inc.; Arthritis Foundation; Bioiberica S.A.; DePuy Mitek, Inc.; Flexion Therapeutics, Inc.; GlaxoSmithKline; Merck Serono; Rottapharm | Madaus; Sanofi; Stryker; The Pivotal OAI MRI Analyses (POMA) Study, NIH HHSN2682010000. We thank the Osteoarthritis Research Society International (OARSI) for their leadership and expertise on the FNIH OA Biomarker Consortium project. The OAI is a public-private partnership comprised of five contracts (N01-AR- 2-2258; N01-AR-2-2259; N01-AR-2-2260; N01-AR-2-2261; N01-AR-2-2262) funded by the National Institutes of Health. Funding partners include Merck Research Laboratories; Novartis Pharmaceuticals Corporation, GlaxoSmithKline; and Pfizer, Inc. Private sector funding for the Consortium and OAI is managed by the FNIH.The IMI-APPROACH study consortium received support from the Innovative Medicines Initiative Joint Undertaking under Grant Agreement no 115770, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007–2013) and EFPIA companies’ in kind contribution. See www.imi.europa.eu and www.approachproject.eu. The funding sources had no role in the design of this study.

Objectives: The objective of this study is to develop classification criteria for overall hand osteoarthritis (OA), interphalangeal OA and thumb base OA based on self-reported data and radiographic features., Methods: The classification criteria sets were developed in three phases. In phase 1, we identified criteria that discriminated hand OA from controls. In phase 2, we used a consensus-based decision analysis approach to derive a clinician-based evaluation of the relative importance of the criteria. In phase 3, we refined the scoring system, determined the cut-offs for disease classification and compared the sensitivity and specificity of the European Alliance of Associations for Rheumatology (EULAR) criteria with the 1990 American College of Rheumatology (ACR) criteria., Results: In persons with hand symptoms and no other disease (including psoriasis) or acute injury that can explain the hand symptoms (mandatory criteria), hand OA can be classified based on age, duration of morning stiffness, number of joints with osteophytes and joint space narrowing, and concordance between symptoms and radiographic findings. Using a sum of scores based on each diagnostic element, overall hand OA can be classified if a person achieves 9 or more points on a 0-15 scale. The cut-off for interphalangeal OA and thumb base OA is 8 points. While the EULAR criteria demonstrated better sensitivity than the ACR criteria in the phase 1 data set, the performance of the two criteria sets was similar in two external cohorts., Conclusions: International experts developed the EULAR criteria to classify overall hand OA, interphalangeal OA and thumb base OA in clinical studies using a rigorous methodology., Competing Interests: Competing interests: IKH reports personal fees from Novartis and GSK; research grants from Pfizer and IMI-APPROACH (both paid to the institution); and unpaid role as secretary general of OARSI, all outside of the submitted work. AA reports institutional research grants from AstraZeneca and Oxford Immunotech; and personal fees from UpToDate (royalty), Springer (royalty), Cadilla Pharmaceuticals (lecture fees), NGM Bio (consulting), Limbic (consulting) and Inflazome (consulting), all outside of the submitted work. FB reports shares of 4P Pharma and 4Moving Biotech; personal fees from Boehringer Ingelgeim, Galapagos, Gilead, GSK, Merck Sereno, MSD, Novartis, Pfizer, Roche, Sanofi, Servier and Viatris; and research grant from TRB Chemedica, all outside the submitted work.Sita Bierma-Zeinstra reports research grants from Dutch Arthritis Association, EU Horizon, EU ERC and ZonMW (paid to institution), personal fees from Pfizer, Infirst healthcare, and paid role as deputy editor of Osteoarthritis and Cartilage, all outside of the submitted work.Krysia Dziedzic reports research grants from National Institute for Health and Care Research (NIHR); royalty/licence for Textbook for Rheumatology Therapists; payment for lecture at Australian Rheumatology Association Conference in May 2022; Implementation Advisor Fellows and Scholars Programme National Institute for Health and Care Excellence (UK 2019-22), Steering group member of NICE Implementation subgroup and Steering group member of OARSI Joint Effort initiative, all paid to institution and outside of the submitted work.Martin Englund reports personal fees from Cellcolabs AB (Sweden) and Key2 Compliance (Sweden), outside of the submitted work. Ying Ying Leung reports grants from National Medical Research Council (NMRC/CSA-INV/0022/2017), and personal fees from AbbVie, DKSH, Janssen, Novartis and Pfizer, outside of the submitted work. EM reports personal fees from Expanscience, Keyrus Life Science, Pierre Fabre, Rottapharm, MEDA-Mylan, Sublimed, TRB Chemedica, outside the submitted work. RR reports personal fees from from Novartis, AbbVie, Pfizer, MSD, Janssen, Lilly; support for attending EULAR, ACR and SIR; advisory board for Janssen, Novartis and Abbvie, outside of the submitted work. TAS reports grants and personal fees from AbbVie and Roche, and personal fees from Sanofi, Takeda and Novartis, outside the submitted work. ZS reports personal fees from AbbVie, Pfizer, Roche, Novartis, Lilly, Gedeon Richter, Sobi/Galapagos, outside of the submitted work. RW reports institutional research grants from Pfizer and Amgen, unrelated to this work, and is a Senior Clinical Investigator of the Research Foundation Flanders (Belgium) (FWO) (1803023N). MK reports consulting fees from Abbvie, Pfizer, Kiniksa, Flexion, Galapagos, Jansen, CHDR, Novartis and UCB (all paid to institution), outside of the submitted work. DF, JJE, MH-E, GH-B, CH, MLI, HJ, TK, CDM, MM, RHM, VR, MJPFR, FVG, LAS, CM, EG and HL report no conflicts of interest., (© European Alliance of Associations for Rheumatology, EULAR 2024. Re-use permitted under CC BY-NC-ND. No commercial re-use. No derivatives. See rights and permissions. Published by BMJ on behalf of EULAR.)

Background: Provoked vestibulodynia (PVD) is a common pain condition, negatively impacting the relationships and sexual lives of sufferers. Women's coping behaviour has been associated with psychosexual outcomes, yet coping patterns in clinical PVD samples are unexplored, and it is not known how women's coping relates to their relational context., Method: Women (N = 128) with PVD answered questionnaires about psychosexual function, pain coping (avoidance and endurance), relational- and pain catastrophizing, sexual goals and perceived partner responses. Cluster analysis was used to explore coping patterns; clusters were validated on measures of pain and psychosexual function and compared on catastrophizing, sexual goals and partner responses using multivariate analyses of variance., Results: The analysis yielded four clusters: endurance; combined high avoidance and endurance; avoidance; and combined low. The group with high levels of both avoidance and endurance coping displayed the worst psychosexual outcomes and high levels of pain- and relational catastrophizing, approach and avoidance goals and perceived negative partner responses., Conclusion: There are distinct patterns of coping among women with PVD, and these coping patterns are associated with psychosexual outcomes and relational cognitions and goals, and perceived partner responses. Women who alternate between avoidance and endurance are more distressed and report worse psychosexual functioning. This pattern needs to be identified and addressed in the treatment of PVD., Significance Statement: This study extends previous findings on vulvar pain coping patterns to a clinical population of women with PVD. It is further the first study to address the relationship between relational variables, such as partner responses and relational catastrophizing and different coping patterns. Thus, the contribution of this study is the contextualizing of coping patterns among women with PVD. The results showed that a combined pattern of avoidance and endurance coping is associated with high distress, poor psychosexual outcomes, and indications of insufficient relational coping, highlighting the need for clinical assessment and intervention to target both women's individual coping patterns and their relational context., (© 2024 The Author(s). European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation ‐ EFIC ®.)

Background: DNA methylation-derived epigenetic clocks and frailty are well-established biological age measures capturing different aging processes. However, whether they are dynamically linked to each other across chronological age remains poorly understood., Methods: This analysis included 1 309 repeated measurements in 524 individuals aged 50-90 years from the Swedish Adoption/Twin Study of Aging. Frailty was measured using a validated 42-item frailty index (FI). Five epigenetic clocks were calculated, including 4 principal component (PC)-based clocks trained on chronological age (PCHorvathAge and PCHannumAge) and aging-related physiological conditions (PCPhenoAge and PCGrimAge), and a pace of aging clock (DunedinPACE). Using dual change score models, we examined the dynamic, bidirectional associations between each of the epigenetic clocks and the FI over age to test for potential causal associations., Results: The FI exhibited a nonlinear, accelerated increase across the older adulthood, whereas the epigenetic clocks mostly increased linearly with age. For PCHorvathAge, PCHannumAge, PCPhenoAge, and PCGrimAge, their associations with the FI were primarily due to correlated levels at age 50 but with no evidence of a dynamic longitudinal association. In contrast, we observed a unidirectional association between DunedinPACE and the FI, where a higher DunedinPACE predicted a subsequent increase in the FI, but not vice versa., Conclusions: Our results highlight a temporal order between epigenetic aging and frailty such that changes in DunedinPACE precede changes in the FI. This potentially suggests that the pace of aging clock can be used as an early marker of the overall physiological decline at system level., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Diabetes mellitus type 2 (T2D) is associated with accelerated biological aging and the increased risk of onset of other age-related diseases. Epigenetic changes in DNA methylation levels have been found to serve as reliable biomarkers for biological aging. This study explores the relationship between various epigenetic biomarkers of aging and diabetes risk using longitudinal data. Data from the Swedish Adoption/Twin Study of Aging (SATSA) was collected from 1984 to 2014 and included 536 individuals with at least one epigenetic measurement. The following epigenetic biomarkers of aging were employed: DNAm PAI-1, DNAmTL, DunedinPACE, PCHorvath1, PCHorvath2, PCHannum, PCPhenoAge, and PCGrimAge. Firstly, longitudinal analysis of biomarker trajectories was done. Secondly, linear correlations between the biomarkers and time to diabetes were studied within individuals developing diabetes. Thirdly, Cox proportional hazards (PH) models were used to assess the associations between these biomarkers and time of diabetes diagnosis, with adjustments for chronological age, sex, education, smoking, blood glucose, and BMI. The longitudinal trajectories of the biomarkers revealed differences between individuals with and without diabetes. Smoothened average curves for DunedinPACE and DNAm PAI-1 were higher for individuals with diabetes around the age 60-70, compared to controls. Likewise, DunedinPACE and DNAm PAI-1 were higher closer to diabetes onset. However, no significant associations were found between the epigenetic biomarkers of aging and risk of diabetes in Cox PH models. Our findings suggest the potential value of developing epigenetic biomarkers specifically tailored to T2D, should we wish to model and explore the potential for predicting the disease., (© 2024. The Author(s).)

Introduction/objectives: Among people with or without hand osteoarthritis, we aimed to identify characteristics of people (e.g., age and gender) with marginal erosions (MEs). We also examined changes in MEs during 48 months. We described radiographic severity and progression among joints with MEs, changes in MEs, or central erosions (CEs)., Design: We studied participants from the Osteoarthritis Initiative with baseline and 48-month hand radiographs. A radiologist and rheumatologist evaluated the radiographs for disease severity (Kellgren-Lawrence grades) and erosions (central or marginal), respectively. We used descriptive statistics to characterize participants and calculated frequencies at the joint level., Results: Of the 3558 participants, 89 had a ME at baseline. People with MEs were more often male, older, and ever (former and current) smokers than those without a ME. There was no difference in inflammatory biomarkers or the presence of hand pain between individuals with and without a baseline ME. Almost all hands had only one ME (80%), whereas only 50% of individuals with CEs had only one CE at baseline. Compared to CEs, MEs appeared more frequently in joints without osteoarthritis (54% vs. < 1%). Approximately 18% of joints with an ME progressed in Kellgren-Lawrence grade versus 4% without ME. Among the joints with an ME at baseline, 10% resolved by 48 months. Less than 0.1% of joints developed a new ME., Conclusion: MEs appear to be distinct from CEs. MEs are predominantly present in males, isolated to one specific joint without osteoarthritis within a hand, and possibly predictive of radiographic progression. Key Points • Marginal erosions appear to be distinct from central erosions. • Most marginal erosions occur in joints without radiographic osteoarthritis. • Radiographic progression but not hand pain is more common in joints with a marginal erosion than without one., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Background: Psychological resilience refers to an individual's ability to cope with and adapt to challenging life circumstances and events., Objective: This study aims to explore the association between psychological resilience and all-cause mortality in a national cohort of US older adults by a cross-sectional study., Methods: The Health and Retirement Study (2006-2008) included 10 569 participants aged ≥50. Mortality outcomes were determined using records up to May 2021. Multivariable Cox proportional hazards models were used to analyse the associations between psychological resilience and all-cause mortality. Restricted cubic splines were applied to examine the association between psychological resilience and mortality risk., Findings: During the follow-up period, 3489 all-cause deaths were recorded. The analysis revealed an almost linear association between psychological resilience and mortality risk. Higher levels of psychological resilience were associated with a reduced risk of all-cause mortality in models adjusting for attained age, sex, race and body mass index (HR=0.750 per 1 SD increase in psychological resilience; 95% CI 0.726, 0.775). This association remained statistically significant after further adjustment for self-reported diabetes, heart disease, stroke, cancer and hypertension (HR=0.786; 95% CI 0.760, 0.813). The relationship persisted even after accounting for smoking and other health-related behaviours (HR=0.813; 95% CI 0.802, 0.860)., Conclusions: This cohort study highlights the association between psychological resilience and all-cause mortality in older adults in the USA., Clinical Implications: Psychological resilience emerges as a protective factor against mortality, emphasising its importance in maintaining health and well-being., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Progressive familial intrahepatic cholestasis (PFIC) is a liver disease that occurs during childhood and requires liver transplantation. ABCB4 is localized along the canalicular membranes of hepatocytes, transports phosphatidylcholine into bile, and its mutation causes PFIC3. Abcb4 gene-deficient mice established as animal models of PFIC3 exhibit cholestasis-induced liver injury. However, their phenotypes are often milder than those of human PFIC3, partly because of the existence of large amounts of less toxic hydrophilic bile acids synthesized by the rodent-specific enzymes Cyp2c70 and Cyp2a12. Mice with double deletions of Cyp2c70/Cyp2a12 (CYPDKO mice) have a human-like hydrophobic bile acid composition. PFIC-related gene mutations were induced in CYPDKO mice to determine whether these triple-gene-deficient mice are a better model for PFIC. To establish a PFIC3 mouse model using CYPDKO mice, we induced abcb4 gene deletion in vivo using adeno-associated viruses expressing SaCas9 under the control of a liver-specific promoter and abcb4-target gRNAs. Compared to Abcb4-deficient wild-type mice, Abcb4-deficient CYPDKO mice showed more pronounced liver injury along with an elevation of inflammatory and fibrotic markers. The proliferation of intrahepatic bile ductal cells and hematopoietic cell infiltration were also observed. CYPDKO/abcb4-deficient mice show a predominance of taurine-conjugated chenodeoxycholic acid and lithocholic acid in the liver. In addition, phospholipid levels in the gallbladder bile were barely detectable. Mice with both human-like bile acid composition and Abcb4-defect exhibit severe cholestatic liver injury and are useful for studying human cholestatic diseases and developing new treatments., Competing Interests: Conflicts of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper: The author, Akira Honda, is an Editorial Board Member for Journal of Lipid Research and was not involved in the editorial review or the decision to publish this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Left ventricular assist devices (LVAD) improve survival for patients with cardiac failure, but LVAD-specific infection (VSI) remains a challenge with poorly understood predictive risk factors. The indications and use of escalating medical treatment to surgical debridement and potential flap reconstruction are not well characterized., Study Design: A retrospective review of consecutive patients undergoing primary LVAD implantation at a tertiary academic center was performed. The primary outcome measures were 90-day and overall mortality after VSI. Cox proportional hazards regression was used to generate a risk prediction score for mortality., Results: Of the 760 patients undergoing primary LVAD implantation, 255 (34%) developed VSI; of these patients, 91 (36%) were managed medically, 134 (52%) with surgical debridement, and 30 (12%) with surgical debridement and flap reconstruction. One-year survival after infection was 85% with median survival of 2.40 years. Factors independently associated with increased mortality were diabetes (hazard ratio [HR] 1.44, p = 0.04), MRSA infection (HR 1.64, p = 0.03), deep space (pump pocket or outflow cannula) involvement (HR 2.26, p < 0.001), and extracorporeal membrane oxygenation after LVAD (HR 2.52, p < 0.01). Factors independently associated with decreased mortality were flap reconstruction (HR 0.49, p = 0.02) and methicillin-sensitive Staphylococcus aureus infection (HR 0.63, p = 0.03). A clinical risk prediction score was developed using these factors and showed significant differences in median survival, which was 5.67 years for low-risk (score 0 to 1), 3.62 years for intermediate-risk (score 2), and 1.48 years for high-risk (score ≥3; p < 0.001) patients., Conclusions: We developed a clinical risk prediction score to stratify patients with VSI. In selected cases, escalating surgical treatment was associated with increased survival. Future work is needed to determine whether early surgical debridement and flap reconstruction can alter outcomes in select cases of VSI., (Copyright © 2024 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: To investigate the barriers and facilitators to rehabilitation experienced by individuals with cervical SCI after upper limb (UL) reconstructive surgery., Methods: We conducted a prospective cohort study with a follow-up period of up to 24 months. Data collection occurred at two academic and two Veterans Affairs medical centers in the United States. Participants were purposively sampled and included 21 adults with cervical SCI (c-SCI) who had received nerve or tendon transfer surgeries and 15 caregivers. We administered semi-structured interviews about participants' experiences of accessing rehabilitation services after surgery., Results: Four themes emerged from the data: (1) participants encountered greater obstacles in accessing therapy as follow-up time increased; (2) practical challenges (e.g., insurance coverage, opportunity costs, transportation) limited rehabilitation access; (3) individuals with c-SCI and their caregivers desired more information about an overall rehabilitation plan; and (4) external support systems facilitated therapy access., Conclusion: Individuals with c-SCI experience multilevel barriers in accessing rehabilitation care after UL reconstructive surgeries in the United States. This work identifies areas of focus to mitigate these challenges, such as enhancing transparency about the overall rehabilitation process, training providers to work with this population, and developing, testing, and disseminating rehabilitation protocols following UL reconstruction among people with c-SCI., (© 2024 American Spinal Injury Association.)

Purpose: To determine the causes of benign hepaticojejunostomy strictures (BHSs) after pancreaticoduodenectomy (PD) and the outcome of endoscopic retrograde cholangiography (ERC) treatment for BHSs., Methods: A total of 175 patients who underwent PD between January 2013 and December 2020 and who were followed up for at least 1 year were included. Preoperative data, operative outcomes, and postoperative courses were compared between the BHS group and the group of patients who did not develop stenosis during follow-up (non-BHS group). The course of treatment in the BHS group was also examined., Results: BHS occurred in 13 of 175 patients (7.4%). Multivariate analysis of the BHS and non-BHS groups revealed that male sex (OR; 3.753, 95% CI; 1.029-18.003, P = 0.0448) and a preoperative bile duct diameter less than 8.8 mm (OR; 7.51, 95% CI; 1.75-52.40, P = 0.0053) were independent risk factors for the development of BHS. In the BHS group, all patients underwent ERC using enteroscopy. The success rate of the ERC approach to the bile duct was 92.3%. Plastic stents were inserted in 6 patients, and metallic stents were inserted in 3 patients. The median observation period since the last ERC was 17.9 months, and there was no recurrence of stenosis in any of the 13 patients., Conclusions: Patients with narrow bile ducts are at greater risk of BHS after PD. Recently, BHS after PD has been treated with ERC-related procedures, which may reduce the burden on patients., (© 2024. The Author(s).)

Objective: Hand osteoarthritis (OA) pain is characterized as heterogeneous and multifactorial. Differences in pain may be explained by underlying phenotypes, which have not been previously explored DESIGN: Latent class analysis determined classes of participants with hand OA from the Nor-Hand study baseline examination (2016-17) based on a biopsychosocial framework. Outcomes were hand and overall bodily pain intensity (Numeric Rating Scale, 0-10) at baseline and follow-up (2019-21), The relations of the classes to pain outcomes at baseline, follow-up, and change over time were analysed in separate models by linear regression, using the overall healthiest class as reference., Results: Five classes differing in radiographic hand OA burden and OA burden in the lower extremities by ultrasound, demographic factors, psychosocial burden and pain sensitization was identified. Persons with the least severe OA but higher burden of biopsychosocial factors reported the most hand pain (beta 3.65, 95% CI 2.53, 4.75). Pain was less pronounced in persons with the most severe hand OA but low burden of biopsychosocial factors (beta 1.03, 95% CI 0.41, 1.65). Results were similar for overall bodily pain and at follow-up. Changes in pain were small, but the association between a separate class defined by higher levels of biopsychosocial burden and pain changes was significant., Conclusion: The five hand OA phenotypes were associated with pain at baseline and 3.5 years later. The phenotype with the least OA severity, but higher burden of biopsychosocial factors reported more pain than the phenotype with the most severe OA, reflecting the symptom-structure discordance of the hand OA pain experience., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

This paper presents an overview of recent hardware extensions and data analysis developments to the Wendelstein 7-X visible core spectroscopy systems. These include upgrades to prepare the in-vessel components for long-pulse operation, nine additional spectrometers, a new line of sight array for passive spectroscopy, and a coherence imaging charge exchange spectroscopy diagnostic. Progress in data analysis includes ion temperatures and densities from multiple impurity species, a statistical comparison with x-ray crystal spectrometer measurements, neutral density measurements from thermal passive Balmer-alpha emission, and a Bayesian analysis of active hydrogen emission, which is able to infer electron density and main ion temperature profiles., (© 2024 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/).)

A preparatory study is underway to investigate the feasibility study of high-energetic, non-thermal electron distribution function measurements using a vertical-viewing electron cyclotron emission (ECE) diagnostic on JT-60SA. The system is designed to detect broad ECE spectra (70-260 GHz) due to the second, third, and fourth harmonics using a focusing optics system with four quasi-optical mirrors in the upper port of JT-60SA. A Gaussian beam optics design is performed in vacuum, and ray tracing calculations are performed in plasma using the TRAVIS code to investigate density characteristics. A ceramic viewing dump is also designed to reduce the effects of multiple reflections from the opposing vacuum vessel surface., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Lobular endocervical glandular hyperplasia (LEGH) may be a precursor lesion of gastric-type adenocarcinoma of the uterine cervix (GAS). However, the genetic mechanisms underlying its carcinogenesis remain unclear. To elucidate the oncogenic process from LEGH to GAS, we compared gene mutations in early-stage GAS and adjacent LEGH in the same case. Fresh-frozen tissue sections were obtained from a patient with Stage IB3 GAS and adjacent LEGH who had undergone hysterectomy. Using laser microdissection, we harvested the LEGH and GAS portions separately from these sections and extracted the genomic DNA. Somatic variant analysis using whole-exome sequencing used DNA from the normal myometrium as a reference sequence. Somatic variants involving amino acid substitutions were detected in 61 and 125 locations in LEGH and GAS, respectively. Seven variants were common in both lesions, of which the pathogenic variant was GNAS only (c.2531G>A, p.R844H), a mutation frequently reported in pancreatic and colorectal cancers. LEGH had no other pathogenic variants; another pathogenic variant in GAS was found only at the same amino acid site as GNAS (c.2530C>T, p.R844C). In the present case, LEGH and GAS shared the same pathogenic variant of GNAS, indicating that both lesions had a common origin. Furthermore, the current results showed that the second GNAS variant is associated with the progression of LEGH to GAS. Further studies are required to elucidate GAS's pathogenesis and biological characteristics., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 by the International Society of Gynecological Pathologists.)

Background and Objectives: Observational studies have demonstrated an increased amyotrophic lateral sclerosis (ALS) risk among professional athletes in various sports. For moderately increased levels of physical activity and fitness, the results are diverging. Through a cohort study, we aimed to assess the relationship between indicators of physical activity and fitness (self-reported physical activity and resting heart rate) and long-term ALS risk., Methods: From a large Norwegian cardiovascular health survey (1985-1999), we collected information on self-reported physical activity in leisure time, resting heart rate, and other cardiovascular risk factors. Patients with ALS were identified through health registries covering the whole population. We fitted Cox proportional hazard models to assess the risk of ALS according to levels of self-reported physical activity in 3 categories (1: sedentary; 2: minimum 4 hours per week of walking or cycling; 3: minimum 4 hours per week of recreational sports or hard training), and resting heart rate modeled both on the continuous scale and as quartiles of distribution., Results: Out of 373,696 study participants (mean 40.9 [SD 1.1] years at inclusion), 504 (41.2% women) developed ALS during a mean follow-up time of 27.2 (SD 5.0) years. Compared with participants with the lowest level of physical activity, the hazard ratio was 0.71 (95% CI 0.53-0.95) for those with the highest level. There were no clear associations between resting heart rate and ALS in the total sample. In men, the hazard ratio of ALS was 0.71 (95% CI 0.53-0.95) for those reporting moderate levels of physical activity and 0.59 (95% CI 0.42-0.84) for those reporting high levels, compared with those reporting low levels. Men with resting heart rate in the lowest quartile had 32% reduced risk of ALS (hazard ratio 0.68, 95% CI 0.49-0.94) compared with those in the second highest quartile. In women, no association was detected between neither self-reported levels of physical activity nor resting heart rate and ALS risk., Discussion: Indicators of high levels of physical activity and fitness are associated with a reduced risk of ALS more than 30 years later in men, but not in women.

Background and Objectives: Some researchers are concerned that the performance of pancreatic resection in cases of low malignancy with distal localization will increase, resulting in the occurrence or worsening of post-operative glucose intolerance. Herein, we retrospectively investigated the relationship between the pancreatic resection ratio and post-operative glucose intolerance in distal pancreatectomy (DP)., Methods: Total 135 patients who underwent DP at our hospital and were followed up for > 12 months between January 2013 and December 2022 were included. Of these, 52 patients were included, excluding those with pre-operative diabetes and those who underwent pancreatectomy using other than a stapling device. The pancreatic resection ratio (%) was measured using pancreatic volumetry by manually tracing the pancreatic area on computed tomography images obtained before and after surgery and the relationship with post-operative glucose intolerance was investigated., Results: Among the 52 patients, 13 (25.0%) showed post-operative worsening of glucose tolerance (impaired glucose tolerance [IGT] group). The pancreatic resection ratios were 51.1% and 34.8% in the IGT (13 patients) and non-IGT groups (39 patients), respectively (p = 0.0027). The cut-off value for the IGT group was 46.5%. The resection site was divided into two groups as follows. One group was resected near the portal vein (portal group) and the other group was resected more caudally (caudal group). Mean pancreatic resection ratios were 46.5% and 28.5% in cases of resection of the portal group (30 patients) and caudal group (22 patients), respectively (p < 0.0001). The thickness of the pancreas at the resection site was 13.1 mm in the portal group and 17.7 mm in the caudal group (p < 0.0001) and the incidence of pancreatic fistula was 6.7% and 9.1%, respectively (p = 0.7472). The incidence of post-operative glucose intolerance was 40.0% (12/30) in the portal group and 4.5% (1/22) in the caudal group (p = 0.0016)., Conclusion: In cases of low-grade tumors and benign disease, pancreatic resection with preservation of the remaining pancreatic volume should be considered whenever possible., (© 2024. Indian Society of Gastroenterology.)

Inherited antithrombin deficiency is an autosomal dominant thrombophilia, resulting from genetic variations in the serpin family C member 1 (SERPINC1) gene. Antithrombin deficiency increases the risk of venous thromboembolism (VTE) compared to the general population. In this report, a novel missense variant of SERPINC1 , c.40A>G, p.Arg14Gly that predicts to cause secretion defect of antithrombin, was identified in two related patients: a 65-year-old man with chronic thromboembolic pulmonary hypertension (CTEPH) after acute pulmonary embolism, and his son with early onset of VTE. Treatment with direct oral anticoagulants and catheter interventions led to successful outcomes for both patients. These cases highlight the importance of screening testing for inherited antithrombin deficiency and intrafamilial survey in patients with VTE and CTEPH., Learning Objectives: Inherited antithrombin deficiency is associated with a strong risk of venous thromboembolism (VTE). However, the relationship between inherited antithrombin deficiency and chronic thromboembolic pulmonary hypertension (CTEPH) remains unclear. The influence of antithrombin deficiency on developing CTEPH following acute pulmonary embolism requires further investigation. This report emphasizes the importance of screening for thrombophilic factors in cases of VTE and CTEPH., Competing Interests: The authors declare that there is no conflict of interest., (© 2024 Japanese College of Cardiology. Published by Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Objectives: We aimed to determine whether hand OA is characterized by systemic cartilage loss by assessing if radiographically normal joints had greater joint space width (JSW) loss over 4 years in hands with incident or prevalent OA elsewhere in the hand compared with hands without OA., Methods: We used semi-automated software to measure JSW in the distal and proximal IP joints of 3368 participants in the Osteoarthritis Initiative who had baseline and 48-month hand radiographs. A reader scored 16 hand joints (including the thumb base) for Kellgren-Lawrence (KL) grade. A joint had OA if scored as KL ≥2. We identified three groups based on longitudinal hand OA status: no hand OA (KL <2 in all 16 joints) at the baseline and 48-month visits, incident hand OA (KL <2 in all 16 joints at baseline and then one or more joints with KL ≥2 at 48 months) and prevalent hand OA (one or more joints with KL ≥2 at baseline and 48 months). We then assessed if JSW in radiographically normal joints (KL 0) differed across these three groups. We calculated unpooled effect sizes to help interpret the differences between groups., Results: We observed small differences in JSW loss that are unlikely to be clinically important in radiographically normal joints between those without hand OA (n = 1054) and those with incident (n = 102) or prevalent hand OA (n = 2212) (effect size range -0.01-0.24). These findings were robust when examining JSW loss dichotomized based on meaningful change and in other secondary analyses., Conclusions: Hand OA is not a systemic disease of cartilage., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Synthesis of the A/D/E-ring core compounds of maoecrystal V was achieved. The key Diels-Alder reactions between tricyclic α-methylene lactones and Kitahara-Danishefsky dienes afforded the spirocyclic core compounds in a regioselective and stereoselective manner., (© The Author(s) 2024. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

In this study, we discovered a turbulence transition in a large helical device. The turbulence level and turbulence-driven energy transport decrease to a specific transition density and increase above it. The ruling turbulences below and above the transition density were ion-temperature gradient (ITG) and resistive-interchange (RI) turbulences, consistent with the predictions of gyrokinetic theory and two-fluid MHD model, respectively. Isotope experiments on hydrogen (H) and deuterium (D) clarified the role of transitions. In the ITG regime, turbulence levels and energy transport were comparable in the H and D plasmas. In contrast, in the RI regime, they were clearly suppressed in the D plasma. The results provide crucial knowledge for understanding isotope effects and future optimization of stellarator and heliotron devices.

The experimental findings from the Large Helical Device have demonstrated a fast, nondiffusive behavior during the propagation of heat pulses, with an observed increase in speed with reduction in their temporal width. Concurrent propagation of the temperature gradient and turbulence, in a timeframe spanning from a few milliseconds to tens of milliseconds, aligned with the avalanche model. These results indicate that the more spatiotemporally localized the heat and turbulence pulses are, the greater the deviation of the plasma from its equilibrium state, coupled with faster propagation velocity. This insight is pivotal for future fusion reactors, which necessitate the maintenance of a steady-state, non-equilibrium condition., (© 2024. The Author(s).)

Epigenetics plays an important role in the aging process, but it is unclear whether epigenetic factors also influence frailty, an age-related state of physiological decline. In this study, we performed a meta-analysis of epigenome-wide association studies in four samples drawn from the Swedish Adoption/Twin Study of Aging (SATSA) and the Longitudinal Study of Aging Danish Twins (LSADT) to explore the association between DNA methylation and frailty. Frailty was defined using the frailty index (FI), and DNA methylation levels were measured in whole blood using Illumina's Infinium HumanMethylation450K and MethylationEPIC arrays. In the meta-analysis consisting of a total of 829 participants, we identified 589 CpG sites that were statistically significantly associated with either the continuous or categorical FI (false discovery rate <0.05). Many of these CpGs have previously been associated with age and age-related diseases. The identified sites were also largely directionally consistent in a longitudinal analysis using mixed-effects models in SATSA, where the participants were followed up to a maximum of 20 years. Moreover, we identified three differentially methylated regions within the MGRN1, MIR596, and TAPBP genes that have been linked to neuronal aging, tumor growth, and immune functions. Furthermore, our meta-analysis results replicated 34 of the 77 previously reported frailty-associated CpGs at p < 0.05. In conclusion, our findings demonstrate robust associations between frailty and DNA methylation levels in 589 novel CpGs, previously unidentified for frailty, and strengthen the role of neuronal/brain pathways in frailty., (© 2024 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Antihypertensive, lipid-lowering, and blood glucose-lowering drugs have slowed down the aging process in animal models. In humans, studies are limited, have short follow-up times, and show mixed results. Therefore, this study aimed to estimate the effects of commonly used medications on functional aging, cognitive function, and frailty. We included information on individuals from three Swedish longitudinal population-based studies collected between 1986 and 2014. Our exposures were the 21 most used groups of medications among individuals aged 65 years and older in the Swedish population in 2022. Functional aging index (n = 1191), cognitive function (n = 1094), and frailty index (n = 1361) were the outcomes of interest. To estimate the medication effects, we used a self-controlled analysis, where each individual is his/her own control, thereby adjusting for all time-stable confounders. The analysis was additionally adjusted for time-varying confounders (chronological age, Charlson Comorbidity Index, smoking, body mass index, and the number of drugs). The participants were 65.5-82.8 years at the first in-person assessment. Adrenergics/inhalants (effect size = 0.089) and lipid-modifying agents/plain (effect size = 0.082) were associated with higher values of cognitive function (improvement), and selective calcium channel blockers with mainly vascular effects (effect size = -0.129) were associated with lower values of the functional aging index (improvement). No beneficial effects were found on the frailty index. Adrenergics/inhalants, lipid-modifying agents/plain, and selective calcium channel blockers with mainly vascular effects may benefit functional biomarkers of aging. More research is needed to investigate their clinical value in preventing adverse aging outcomes., (© 2024 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Objectives: There is no evidence linking specific osteoarthritis (OA) types, such as erosive hand OA (EHOA), with distant generalised changes in muscle composition (sarcopenia), which can potentially be modified. This study pioneers the exploration of the association between EHOA and sarcopenia, both of which are predominantly observed in the older adults., Methods: Using the Osteoarthritis Initiative cohort, we selected hand OA (modified Kellgren and Lawrence (grade ≥2 in ≥1 hand joint) participants with radiographic central erosions in ≥1 joints (EHOA group) and propensity score-matched hand OA participants with no erosion (non-EHOA group). MRI biomarkers of thigh muscles were measured at baseline, year 2 and year 4 using a validated deep-learning algorithm. To adjust for 'local' effects of coexisting knee OA (KOA), participants were further stratified according to presence of radiographic KOA. The outcomes were the differences between EHOA and non-EHOA groups in the 4-year rate of change for both intramuscular adipose tissue (intra-MAT) deposition and contractile (non-fat) area of thigh muscles., Results: After adjusting for potential confounders, 844 thighs were included (211 EHOA:633 non-EHOA; 67.1±7.5 years, female/male:2.9). Multilevel mixed-effect regression models showed that EHOA is associated a different 4-year rate of change in intra-MAT deposition (estimate, 95% CI: 71.5 mm 2 /4 years, 27.9 to 115.1) and contractile area (estimate, 95% CI: -1.8%/4 years, -2.6 to -1.0) of the Quadriceps. Stratified analyses showed that EHOA presence is associated with adverse changes in thigh muscle quality only in participants without KOA., Conclusions: EHOA is associated with longitudinal worsening of thigh muscle composition only in participants without concomitant KOA. Further research is needed to understand the systemic factors linking EHOA and sarcopenia, which unlike EHOA is modifiable through specific interventions., Competing Interests: Competing interests: AG is a shareholder of BICL and consultant to Pfizer, TissueGene, Pfizer, Novartis, Coval, ICM, TrialSpark and Medipost. FWR is shareholder of BICL, LLC and consultant to and Grünenthal. IKH has research grant from Pfizer/Lily, consultancies from Novartis, GSK and Grünenthal, and speaker honorarium from Abbvie. SD reported that he received funding from Toshiba Medical Systems (for consultation) and grants from GERRAF and Carestream Health (for a clinical trial study). None of the authors has any conflicting personal or financial relationships that could have influenced the results of this study. Other authors declare that they did not have any competing interests., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To investigate whether structural hand OA or its progression is associated with structural knee OA progression after two years in a population with symptomatic knee OA., Methods: We used baseline and two-year follow-up data from the IMI-APPROACH cohort. Symptomatic hand and knee OA were defined using ACR criteria. Radiographs of hands and knees were scored semi-quantitatively for osteophytes and joint space narrowing (JSN) following the OARSI atlas, and Kellgren-Lawrence (KL) scale. Knee images were also scored quantitatively with the Knee Image Digital Analysis (KIDA). Progression was defined as change above the minimal detectable change on patient level, except for KIDA (most affected knee compartment level). With logistic regression analyses the severity or progression of hand OA was associated with knee OA progression., Results: In 221 participants (mean age 66, 77% women, mean BMI 27.7, 19% hand OA), OA progression occurred in 18%-28%, and 9%-38% in hands and knees respectively, depending on features. Baseline structural hand OA features were not significantly associated with knee OA progression, except for hand osteophytes with KIDA osteophytes progression (odds ratio (OR) 1.03, 95% confidence interval (CI) 1.01-1.06). Progression of structural hand OA features was not significantly associated with knee OA progression, except for hand osteophyte or JSN progression, which was significantly associated with knee osteophyte progression (OR 0.44, 95%CI 0.22-0.84 and OR 0.43, 95%CI 0.18-0.94, respectively), and hand osteophyte progression for knee JSN (OR 2.51, 95%CI 1.15-5.48)., Conclusions: In patients with symptomatic knee OA, no consistent associations between baseline structural hand OA or hand OA progression and knee OA progression were shown., Competing Interests: F Berenbaum received consulting fees from Grunenthal, GSK, Eli lilly, Novartis, Pfizer and Servier, IKH received consulting fees from novartis, GSK and Grunenthal, SCM received a grant from the Dutch Arthritis Foundation, HW received financial support for the IMI-APPROACH cohort, and MK received financial support from the Dutch Arthritis Foundation, all paid to the institution. All other authors declare no competing interests., (© 2024 The Authors.)

Objective: In this study, we propose a novel framework that utilizes deep learning and attention mechanisms to predict the radiographic progression of patellofemoral osteoarthritis (PFOA) over a period of 7 years., Material and Methods: This study included subjects (1,832 subjects, 3,276 knees) from the baseline of the Multicenter Osteoarthritis Study (MOST). Patellofemoral joint regions of interest were identified using an automated landmark detection tool (BoneFinder) on lateral knee X-rays. An end-to-end deep learning method was developed for predicting PFOA progression based on imaging data in a five-fold cross-validation setting. To evaluate the performance of the models, a set of baselines based on known risk factors were developed and analyzed using gradient boosting machine (GBM). Risk factors included age, sex, body mass index, and Western Ontario and McMaster Universities Arthritis Index score, and the radiographic osteoarthritis stage of the tibiofemoral joint (Kellgren and Lawrence [KL] score). Finally, to increase predictive power, we trained an ensemble model using both imaging and clinical data., Results: Among the individual models, the performance of our deep convolutional neural network attention model achieved the best performance with an area under the receiver operating characteristic curve (AUC) of 0.856 and average precision (AP) of 0.431, slightly outperforming the deep learning approach without attention (AUC = 0.832, AP = 0.4) and the best performing reference GBM model (AUC = 0.767, AP = 0.334). The inclusion of imaging data and clinical variables in an ensemble model allowed statistically more powerful prediction of PFOA progression (AUC = 0.865, AP = 0.447), although the clinical significance of this minor performance gain remains unknown. The spatial attention module improved the predictive performance of the backbone model, and the visual interpretation of attention maps focused on the joint space and the regions where osteophytes typically occur., Conclusion: This study demonstrated the potential of machine learning models to predict the progression of PFOA using imaging and clinical variables. These models could be used to identify patients who are at high risk of progression and prioritize them for new treatments. However, even though the accuracy of the models were excellent in this study using the MOST dataset, they should be still validated using external patient cohorts in the future., Competing Interests: I.K.H. received consulting fees from Novartis, GSK, and Grünenthal. He also received honorarium from Abbvie. M.E. is a president of OARSI (Osteoarthritis Research Society International). S.S. is an Associate Editor of Associate Editor for Osteoarthritis and Cartilage Open journal. All other authors have nothing to declare., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Purpose: Advancing age is one of the strongest risk factors for osteoarthritis (OA). DNA methylation-based measures of epigenetic age acceleration may provide insights into mechanisms underlying OA., Methods: We analyzed data from the Multicenter Osteoarthritis Study in a subset of 671 participants ages 45-69 years with no or mild radiographic knee OA. DNA methylation was assessed with the Illumina Infinium MethylationEPIC 850K array. We calculated predicted epigenetic age according to Hannum, Horvath, PhenoAge, and GrimAge epigenetic clocks, then regressed epigenetic age on chronological age to obtain the residuals. Associations between the residuals and knee, hand, and multi-joint OA were assessed using logistic regression, adjusted for chronological age, sex, clinical site, smoking status, and race., Results: Twenty-three percent met criteria for radiographic hand OA, 25% met criteria for radiographic knee OA, and 8% met criteria for multi-joint OA. Mean chronological age (SD) was 58.4 (6.7) years. Mean predicted epigenetic age (SD) according to Horvath, Hannum, PhenoAge, and GrimAge epigenetic clocks was 64.9 (6.4), 68.6 (5.9), 50.5 (7.7), and 67.0 (6.2), respectively. Horvath epigenetic age acceleration was not associated with an increased odds of hand OA, odds ratio (95% confidence intervals) = 1.03 (0.99-1.08), with similar findings for knee and multi-joint OA. We found similar magnitudes of associations for Hannum epigenetic age, PhenoAge, and GrimAge acceleration compared to Horvath epigenetic age acceleration., Conclusions: Epigenetic age acceleration as measured by various well-validated epigenetic clocks based on DNA methylation was not associated with increased risk of knee, hand, or multi-joint OA independent of chronological age., (Copyright © 2024. Published by Elsevier Ltd.)

Objective: Erosive hand osteoarthritis (eHOA) is a subtype of hand osteoarthritis (OA) that develops in finger joints with pre-existing OA and is differentiated by clinical characteristics (hand pain/disability, inflammation, and erosions) that suggest inflammatory or metabolic processes., Method: This was a longitudinal nested case-cohort design among Osteoarthritis Initiative participants who had hand radiographs at baseline and 48-months, and biospecimens collected at baseline. We classified incident radiographic eHOA in individuals with ≥1 joint with Kellgren-Lawrence ≥2 and a central erosion present at 48-months but not at baseline. We used a random representative sample (n = 1282) for comparison. We measured serum biomarkers of inflammation, insulin resistance and dysglycemia, and adipokines using immunoassays and enzymatic colorimetric procedures, blinded to case status., Results: Eighty-six participants developed incident radiographic eHOA. In the multivariate analyses adjusted for age, gender, race, smoking, and body mass index, and after adjustment for multiple analyses, incident radiographic eHOA was associated with elevated levels of interleukin-7 (risk ratio (RR) per SD = 1.30 [95% confidence interval (CI) 1.09, 1.55] p trend 0.01)., Conclusion: This exploratory study suggests an association of elevated interleukin-7, an inflammatory cytokine, with incident eHOA, while other cytokines or biomarkers of metabolic inflammation were not associated. Interleukin-7 may mediate inflammation and tissue damage in susceptible osteoarthritic finger joints and participate in erosive progression., (Copyright © 2024 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Background: The incidence rate of olecranon fractures is highest in the elderly population. The aim of this study was to determine whether patients with olecranon fractures have similar demographic and risk characteristics compared to patients with osteoporotic upper extremity fractures., Methods: A retrospective data analysis was performed with diagnoses for olecranon fracture, distal radius fracture and proximal humerus fracture between 2014 and 2016., Results: A total of 157 olecranon, 1022 distal radius and 451 proximal humerus fractures were identified. The risk of mortality after olecranon and distal radius fractures was comparable but statistically significantly higher after proximal humerus fractures (HR 1.97, 95% CI 1.19-3.27). The risk of subsequent osteoporotic fractures after an olecranon fracture was 10% at 1 year and 14% at 5 years and the risks did not differ statistically after a proximal humerus fracture, 6% and 11% (HR 0.65, 95% CI 0.40-1.06). After a distal radius fracture, the risks were statistically significantly lower: 2% and 5% (HR 0.35, 95% CI 0.22-0.56)., Discussion: Patients with olecranon fractures have essentially similar demographic characteristics compared to patients with distal radius fractures, but the probability for a subsequent fracture is significantly higher and more comparable to patients with proximal humerus fractures., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Significance Statement: Proteinuria predicts accelerated decline in kidney function in CKD. The pathologic mechanisms are not well known, but aberrantly filtered proteins with enzymatic activity might be involved. The urokinase-type plasminogen activator (uPA)-plasminogen cascade activates complement and generates C3a and C5a in vitro / ex vivo in urine from healthy persons when exogenous, inactive, plasminogen, and complement factors are added. Amiloride inhibits uPA and attenuates complement activation in vitro and in vivo . In conditional podocin knockout (KO) mice with severe proteinuria, blocking of uPA with monoclonal antibodies significantly reduces the urine excretion of C3a and C5a and lowers tissue NLRP3-inflammasome protein without major changes in early fibrosis markers. This mechanism provides a link to proinflammatory signaling in proteinuria with possible long-term consequences for kidney function., Background: Persistent proteinuria is associated with tubular interstitial inflammation and predicts progressive kidney injury. In proteinuria, plasminogen is aberrantly filtered and activated by urokinase-type plasminogen activator (uPA), which promotes kidney fibrosis. We hypothesized that plasmin activates filtered complement factors C3 and C5 directly in tubular fluid, generating anaphylatoxins, and that this is attenuated by amiloride, an off-target uPA inhibitor., Methods: Purified C3, C5, plasminogen, urokinase, and urine from healthy humans were used for in vitro / ex vivo studies. Complement activation was assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, immunoblotting, and ELISA. Urine and plasma from patients with diabetic nephropathy treated with high-dose amiloride and from mice with proteinuria (podocin knockout [KO]) treated with amiloride or inhibitory anti-uPA antibodies were analyzed., Results: The combination of uPA and plasminogen generated anaphylatoxins C3a and C5a from intact C3 and C5 and was inhibited by amiloride. Addition of exogenous plasminogen was sufficient for urine from healthy humans to activate complement. Conditional podocin KO in mice led to severe proteinuria and C3a and C5a urine excretion, which was attenuated reversibly by amiloride treatment for 4 days and reduced by >50% by inhibitory anti-uPA antibodies without altering proteinuria. NOD-, LRR- and pyrin domain-containing protein 3-inflammasome protein was reduced with no concomitant effect on fibrosis. In patients with diabetic nephropathy, amiloride reduced urinary excretion of C3dg and sC5b-9 significantly., Conclusions: In conditions with proteinuria, uPA-plasmin generates anaphylatoxins in tubular fluid and promotes downstream complement activation sensitive to amiloride. This mechanism links proteinuria to intratubular proinflammatory signaling. In perspective, amiloride could exert reno-protective effects beyond natriuresis and BP reduction., Clinical Trial Registry Name and Registration Number: Increased Activity of a Renal Salt Transporter (ENaC) in Diabetic Kidney Disease, NCT01918488 and Increased Activity of ENaC in Proteinuric Kidney Transplant Recipients, NCT03036748 ., (Copyright © 2024 by the American Society of Nephrology.)

Objective: To use the ulnar compound muscle action potential (CMAP) to abductor digiti minimi (ADM) to identify the proportion of individuals with cervical spinal cord injury (SCI) who have lower motor neuron (LMN) abnormalities involving the C8-T1 spinal nerve roots, within 3-6 months, and thus may influence the response to nerve transfer surgery., Design: Retrospective analysis of prospectively collected data. Data were analyzed from European Multicenter Study About SCI database., Setting: Multi-center, academic hospitals., Participants: We included 79 subjects (age=41.4±17.7, range:16-75; 59 men; N=79), who were classified as cervical level injuries 2 weeks after injury and who had manual muscle strength examinations that would warrant consideration for nerve transfer (C5≥4, C8<3)., Interventions: None., Main Outcome Measures: The ulnar nerve CMAP amplitude to ADM was used as a proxy measure for C8-T1 spinal segment health. CMAP amplitude was stratified into very abnormal (<1.0 mV), sub-normal (1.0-5.9 mV), and normal (>6.0 mV). Analysis took place at 3 (n=148 limbs) and 6 months (n=145 limbs)., Results: At 3- and 6-month post-injury, 33.1% and 28.3% of limbs had very abnormal CMAP amplitudes, respectively, while in 54.1% and 51.7%, CMAPs were sub-normal. Median change in amplitude from 3 to 6 months was 0.0 mV for very abnormal and 1.0 mV for subnormal groups. A 3-month ulnar CMAP <1 mV had a positive predictive value of 0.73 (95% CI 0.69-0.76) and 0.78 (95% CI 0.75-0.80) for C8 and T1 muscle strength of 0 vs 1 or 2., Conclusion: A high proportion of individuals have ulnar CMAPs below the lower limit of normal 3- and 6-month post cervical SCI and may also have intercurrent LMN injury. Failure to identify individuals with LMN denervation could result in a lost opportunity to improve hand function through timely nerve transfer surgeries., (Copyright © 2023 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Obesity and metabolic syndrome (MetS) share common pathophysiological characteristics with aging. To better understand their interplay, we examined how body mass index (BMI) and MetS jointly associate with physiological age, and if the associations changed from midlife to late-life. We used longitudinal data from 1,825 Swedish twins. Physiological age was measured as frailty index (FI) and functional aging index (FAI) and modeled independently in linear mixed-effects models adjusted for chronological age, sex, education, and smoking. We assessed curvilinear associations of BMI and chronological age with physiological age, and interactions between BMI, MetS, and chronological age. We found a significant three-way interaction between BMI, MetS, and chronological age on FI (p-interaction = 0·006), not FAI. Consequently, we stratified FI analyses by age: < 65, 65-85, and ≥ 85 years, and modeled FAI across ages. Except for FI at ages ≥ 85, BMI had U-shaped associations with FI and FAI, where BMI around 26-28 kg/m 2 was associated with the lowest physiological age. MetS was associated with higher FI and FAI, except for FI at ages < 65, and modified the BMI-FI association at ages 65-85 (p-interaction = 0·02), whereby the association between higher BMI levels and FI was stronger in individuals with MetS. Age modified the MetS-FI association in ages ≥ 85, such that it was stronger at higher ages (p-interaction = 0·01). Low BMI, high BMI, and metabolic syndrome were associated with higher physiological age, contributing to overall health status among older individuals and potentially accelerating aging., (© 2023. The Author(s).)

Objective: This perspective describes the evolution of semi-quantitative (SQ) magnetic resonance imaging (MRI) in characterizing structural tissue pathologies in osteoarthritis (OA) imaging research over the last 30 years., Methods: Authors selected representative articles from a PubMed search to illustrate key steps in SQ MRI development, validation, and application. Topics include main scoring systems, reading techniques, responsiveness, reliability, technical considerations, and potential impact of artificial intelligence (AI)., Results: Based on original research published between 1993 and 2023, this article introduces available scoring systems, including but not limited to Whole-Organ Magnetic Resonance Imaging Score (WORMS) as the first system for whole-organ assessment of the knee and the now commonly used MRI Osteoarthritis Knee Score (MOAKS) instrument. Specific systems for distinct OA subtypes or applications have been developed as well as MRI scoring instruments for other joints such as the hip, the fingers or thumb base. SQ assessment has proven to be valid, reliable, and responsive, aiding OA investigators in understanding the natural history of the disease and helping to detect response to treatment. AI may aid phenotypic characterization in the future. SQ MRI assessment's role is increasing in eligibility and safety evaluation in knee OA clinical trials., Conclusions: Evidence supports the validity, reliability, and responsiveness of SQ MRI assessment in understanding structural aspects of disease onset and progression. SQ scoring has helped explain associations between structural tissue damage and clinical manifestations, as well as disease progression. While AI may support human readers to more efficiently perform SQ assessment in the future, its current application in clinical trials still requires validation and regulatory approval., (Copyright © 2024 Osteoarthritis Research Society International. All rights reserved.)