Citations

This study presents the first in vivo intraoperative measurement of the kinetic properties of spastic human muscle. Despite slower relaxation in spastic biceps, the force-frequency relationship was similar to that of the healthy gracilis muscle. This suggests that spasticity does not substantially alter frequency-dependent force summation, possibly due to similar fiber-type compositions and limited changes in calcium handling or myosin isoforms in human spastic muscle.

Background: Although patients often aim to lose weight after total hip arthroplasty (THA) or total knee arthroplasty (TKA), long-term changes in body mass index (BMI) are unknown. We analyzed BMI at 2, 5, and 10 years after primary THA and TKA and determined predictors of BMI change. Methods: We identified patients who underwent primary THA or TKA for osteoarthritis between 2001 and 2011 and had a BMI at surgery and at 2, 5, and 10 years postoperatively. This resulted in 763 patients (310 who underwent THA and 453 who underwent TKA). The mean patient age was 66 years, and 60% of patients were female. BMI changes were analyzed with repeated-measures analysis of variance. Multinomial logistic regression determined predictors of BMI change. Results: Following THA, the mean BMI increased from 30.3 kg/m 2 at surgery to 30.9 kg/m 2 at both 2 years (p = 0.003) and 5 years (p = 0.002). Following TKA, the mean BMI increased from 32.7 kg/m 2 at surgery to 33.1 kg/m 2 at both 2 years (p = 0.053) and 5 years (p = 0.040). By 10 years, the mean BMI was 30.6 kg/m 2 (p = 0.453) for patients undergoing THA and 32.6 kg/m 2 (p = 0.947) for patients undergoing TKA, similar to the BMIs at surgery. At 10 years, 27% of patients who underwent THA and 30% of patients who underwent TKA had a BMI decrease of >5%, whereas 30% of patients who underwent THA and 32% of patients who underwent TKA had a BMI increase of >5%. Female sex among patients who underwent THA increased the odds of a >5% BMI increase at 10 years (odds ratio [OR], 2.1; p = 0.006). Older age among patients who underwent TKA decreased the odds of a >5% BMI increase at 10 years (OR per year, 0.95; p < 0.001). Conclusions: Although most patients experienced a BMI change of >5% at 10 years, the mean BMI did not meaningfully change 2, 5, or 10 years after THA or TKA. Arthroplasty should not be viewed as a gateway to BMI improvement for patients overall, but female sex and older age may predict clinically important weight changes 10 years after arthroplasty. Level of Evidence: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.

Subretinal injection of adeno-associated virus (AAV) is generally more efficacious and less inflammatory than intravitreal injection for retinal gene therapy. However, adverse events (e.g., chorioretinal atrophy) have been reported in many patients receiving subretinal injection of Luxturna (voretigene neparvovec-rzyl) and experimental gene therapies. Subretinal injection confines transduction to the treated area. To address this, we manufactured high-concentration fibrin hydrogels encapsulating AAV2–green fluorescent protein (AAV2- GFP ). Gels had homogeneous AAV distribution, desired mechanical properties, and retained infectivity. Epiretinal placement of fibrin–AAV2- GFP ( n = 11) was compared to subretinal ( n = 5) and intravitreal AAV2- GFP injection ( n = 3). The subretinal group exhibited inconsistent retinal pigment epithelium (RPE) transduction restricted to the injection region with severe atrophy in two cases. The intravitreal group had weak transduction and inflammation. In contrast, epiretinal hydrogels degraded within days and led to broad transduction of RPE without atrophy or inflammation. This technology could advance gene therapy for retinal degenerations and other ocular or systemic disorders.

The study assesses the relationship between thalamic proton-MR spectroscopy (1H-MRS) metabolites and thalamic 11C-ER176 translocator-protein positron emission tomography (TSPO-PET) standardized uptake value ratios (SUVR) to advance our understanding of thalamic involvement in multiple sclerosis (MS)-associated neurodegeneration and disability. In this prospective cross-sectional study, patients with MS (pwMS) and controls underwent 3T-MRI, 1H-MRS, and 11C-ER176-PET targeting the thalamus. MRI-derived thalamic volume was normalized by intracranial volume. 1H-MRS metabolites—N-acetylaspartate (NAA), glutamate (Glu), glutamine (Gln), total choline (tCho), and myo-inositol (mIns)—were normalized to total creatine (tCr). Clinical disability was evaluated using MS-specific tests of Expanded Disability Status Scale-EDSS and MS-functional composite-MSFC (including Paced Auditory Serial Addition Test-PASAT). Compared to controls (n = 30), pwMS (n = 21) exhibited smaller thalamic volume, higher thalamic 1H-MRS mIns/tCr (putative gliosis marker), and higher thalamic 11C-ER176-PET SUVR (glial density marker). In pwMS, higher thalamic mIns/tCr (r = −0.67) and tCho/tCr (r = −0.52) correlated with smaller thalamic volume. In pwMS, higher thalamic mIns/tCr correlated with higher thalamic 11C-ER176-PET SUVR (r = 0.48) and decreased cognitive function (PASAT, rho = −0.48). In controls, decreased thalamic NAA/tCr correlated with increased thalamic 11C-ER176-PET SUVR (r = −0.41). Thalamus, a core central nervous system relay, is affected early in MS disease course. Glial-mediated innate immune activation in the thalamus, evaluated by increased 1H-MRS mIns/tCr and 11C-ER176-PET SUVR, is associated with loss of thalamic volume and increased disability in pwMS. The multimodal imaging approach with 1H-MRS mIns/tCr and 11C-ER176-PET SUVR emerges as potential glial biomarkers, to better understand disease mechanisms and evaluate therapeutic interventions targeting glial activity in MS.

Background/Objectives: This study aims to evaluate the quality of life (QoL) and oncological outcomes in premenopausal women diagnosed with hormone receptor-positive breast cancer who are receiving either bilateral oophorectomy (BO) or gonadotropin-releasing hormone agonist (GnRH) therapy. Both methods serve to inhibit ovarian function, which is essential for the management of estrogen-dependent tumors; however, their effects on QoL have yet to be fully clarified. Methods: Data were analyzed from the Mayo Clinic Breast Disease Registry, focusing on women under 55 diagnosed with estrogen receptor-positive breast cancer who received either BO or GnRH within one year of diagnosis. QoL was assessed using the Patient-Reported Outcomes Measurement Information System Global-10 (PROMIS-10) at baseline and annually for five years. Results: A total of 181 patients were enrolled in the study; 40 into the BO group and 141 to the GnRH group. Both groups exhibited similar levels of sexual dysfunction after a one-year period; however, the BO group stated a higher frequency of hot flashes. PROMIS-10 scores improved in both mental and physical health over time, with no significant differences between the groups. Within the BO group, one recurrence was observed, in contrast to the GnRH group, which had six events. Nonetheless, the difference in recurrence rates did not reach statistical significance. Conclusions: The long-term QoL and oncologic outcomes for premenopausal women with hormone receptor-positive breast cancer were similar for BO and GnRH therapy. These findings emphasize the need for individualized treatment decisions, considering patient preferences and side effects.

Importance In the literature, there is a lack of data reporting tumor control rates after radiotherapy in actively growing vestibular schwannomas (VS). Data for this rarely studied population are needed. Objective To estimate tumor control rates in radiologically growing VS treated with first-line radiotherapy. Design, Setting, and Participants This international, multicenter cohort study used prospectively collected data from patients with growing unilateral VS treated first-line with radiotherapy between January 2000 and December 2023 from 8 tertiary referral skull base units. The data were analyzed in June 2025. Exposures Radiotherapy as an initial treatment for VS. Main Outcomes and Measures The primary outcome was treatment failure, ie VS growth postradiotherapy, which was predefined as an increase in maximum intracranial tumor diameter (ICTD) of 3 mm or greater within the first 2 years after radiotherapy or 2 mm or greater thereafter. Secondary outcomes were treatment failure based on different definitions of VS growth: (1) an increase in ICTD of 2 mm or greater, (2) an increase in ICTD of 3 mm or greater, and (3) conversion to surgery. Results A total of 1883 patients (975 female individuals [51.8%]; median age at diagnosis, 63 years [IQR, 53-71 years]) were included in the study. Using the primary definition of treatment failure (an increase in ICTD of ≥3 mm within the first 2 years postradiotherapy or ≥2 mm thereafter), the Kaplan-Meier estimate yielded a 10-year tumor control rate of 76.1% (95% CI, 72.7%-79.2%). For secondary outcome definitions, 10-year tumor control rates were 60.1% (95% CI, 57.5%-64.3%) for an ICTD increase of 2 mm or greater, 78.3% (95% CI, 75.0%-81.2%) for an increase of 3 mm or greater, and 92.6% (95% CI, 90.4%-94.3%) for conversion to surgery. Neither pretreatment tumor size nor tumor location (intracanalicular vs extracanalicular) were significantly associated with treatment failure. Conclusions and Relevance The results of this cohort study provide tumor control outcomes for radiologically growing VS treated with radiotherapy using several clinically relevant definitions of growth. By focusing exclusively on this rarely isolated subgroup, the findings offer targeted data to potentially inform treatment expectations and future research.

ABSTRACT Anaplastic lymphoma kinase‐positive large B‐cell lymphoma (ALK+ LBCL) is a rare, aggressive subtype of diffuse large B‐cell lymphoma with poor outcomes using standard chemotherapy. In this multi‐institutional retrospective study, we analyzed 39 cases of ALK+ LBCL identified at six US academic centers from 2002 to 2024, with treatment including conventional cytotoxic regimens in frontline and biologically informed and nonchemotherapy‐based strategies in the relapsed setting. Ninety‐two percent of patients received frontline anthracycline‐based chemotherapy; 43% received intensified regimens, and 15% underwent upfront autologous stem cell transplantation (ASCT). Despite these approaches, outcomes remained poor. At a median follow‐up of 5.4 years, median event‐free survival (EFS) was 0.6 years (95% CI, 0.4–0.9), and median overall survival (OS) was 1.5 years (95% CI, 1.3–NR). One‐ and five‐year EFS rates were 28% and 17%, while corresponding OS rates were 72% and 42%, respectively. Advanced stage and high IPI scores were associated with inferior outcomes. Twelve patients received ALK inhibitors, with alectinib showing more durable responses than crizotinib. Lenalidomide and immune checkpoint inhibitors also demonstrated activity, including durable complete responses. Five patients underwent allogeneic stem cell transplantation, with three achieving sustained remission. In conclusion, our findings highlight the limited benefit of chemotherapy, even when intensified or followed by ASCT, and support the integration of biologically targeted therapies, which may have contributed to improved OS in our cohort compared to historical outcomes. Prospective, collaborative studies are needed to better understand disease biology and define optimal use of modern therapies in this rare lymphoma.

Introduction/Objectives: Little is known about the prevalence of patient-reported social risk factors and the use of the HOUSES Index, a simple, reliable method of assessing socioeconomic status (SES) based on publicly available housing data, in a predominantly rural, primary care population. Methods: We conducted a cross-sectional analysis of adult patients paneled to family medicine clinicians in a US Midwest health system as of December 31, 2022. Patients’ listed address determined HOUSES Index as quartile rank (Q1 lowest SES) and rural/urban status. Social risk data including housing, food, transportation, finances, and violence were collected from health record questionnaires. A mixed effect model was used to assess associations between social risk, HOUSES Index, and rurality. Results: Of the 352 355 patients included, rural patients were more likely than urban patients to report all social risk factors and had lower SES as measured by HOUSES quartiles. In the mixed effects analysis, HOUSES quartile was independently predictive of reporting an at-risk social risk factor (Q1 vs Q4 OR = 2.27, 95% CI = 2.19-2.37), but rurality was not (OR = 1.02, 95% CI = 0.97-1.07) after adjusting for HOUSES. Conclusions: The increased prevalence of social risk factors among rural residents is largely explained by individual SES measured by HOUSES Index.

Abstract Aims Type 2 myocardial infarction due to myocardial oxygen supply–demand imbalance is associated with poor outcomes. There are no guidelines to inform care for these patients. The consensus on the assessment and management of type 2 myocardial infarction is gained. Methods and results An international e-Delphi study including experts in type 2 myocardial infarction identified through systematic review was conducted. Participants were asked to describe their approach to (i) definition and diagnosis, (ii) risk stratification, (iii) assessment of coronary artery disease and cardiac function, (iv) specialty management, (v) treatment and secondary prevention, and (vi) communication and rehabilitation. Statements generated in round one were circulated, with consensus defined a priori as ≥70% agreement on a 5-point Likert scale. Where no consensus was reached, statements were amended and recirculated for a final round. The response rate was 56% (38/68), 54% (37/68), and 72% (49/68) in the first, second, and third rounds, respectively. Following the first round, 67 unique statements were generated across six domains. Overall, consensus was achieved on 64% (43/67) of statements. Consensus was achieved for 42% (5/12) of statements on the diagnosis of type 2 myocardial infarction, 75% (3/4) on risk stratification, 50% (9/18) on the assessment of coronary artery disease and cardiac function, 60% (6/10), on specialty management, 100% (9/9) on treatment and secondary prevention, and 79% (11/15) on communication and rehabilitation. Conclusion Consensus was obtained across a number of domains for the assessment and management of patients with type 2 myocardial infarction. However, there was limited agreement amongst experts on the diagnostic criteria, which may benefit from refinement.

Abstract Background Physical activity (PA) is an established protective factor for colorectal cancer (CRC), but it is unclear if genetic variants modify this effect. To investigate this possibility, we conducted a genome-wide gene–PA interaction analysis. Methods Using logistic regression and two-step and joint tests, we analyzed interactions between common genetic variants across the genome and PA in relation to CRC risk. Self-reported PA levels were categorized as active (≥ 8.75 MET-h/wk) vs. inactive (< 8.75 MET-h/wk) and as study- and sex-specific quartiles of activity. Results PA had an overall protective effect on CRC (OR [active vs. inactive] = 0.85; 95%CI = 0.81–0.90). The two-step GxE method identified an interaction between rs4779584, an intergenic variant near the GREM1 and SCG5 genes, and PA for CRC risk (p-interaction = 2.6×10 − 8 ). Stratification by genotype at this locus showed a significant reduction in CRC risk by 20% in active vs. inactive participants with the CC genotype (OR = 0.80; 95%CI = 0.75–0.85), but no significant PA–CRC association among CT or TT carriers. When PA was modeled as quartiles, the 1-d.f. GxE test identified that rs56906466, an intergenic variant near the KCNG1 gene, modified the association between PA and CRC (p-interaction = 3.5×10 − 8 ). Stratification at this locus showed that increase in PA (highest vs. lowest quartile) was associated with a lower CRC risk solely among TT carriers (OR = 0.77; 95%CI = 0.72–0.82). Conclusions In summary, we identified two genetic variants that modified the association between PA and CRC risk. One of them, related to GREM1 and SCG5 , suggests that the bone morphogenetic protein (BMP)-related, inflammatory, and/or insulin signaling pathways may be associated with the protective influence of PA on colorectal carcinogenesis.