Citations

Abstract Background: Rural/nonmetropolitan (nonmetro) counties face known barriers to comprehensive cancer care compared with metropolitan (metro) counties, which may impact the outcomes for lymphoma patients. We evaluated the impact metro vs nonmetro status on outcomes after a diagnosis of non-Hodgkin lymphoma (NHL) in the context of clinical, demographic, and lifestyle factors. Methods: Of 7724 participants enrolled in the prospective LEO cohort study from 2015-2020, 7610 (98.5%) had their county of residence at diagnosis assigned a RUCC (2013) code. We compared outcomes of participants from metro (defined as RUCC 1-3, which are central counties with ≥1 urban areas of ≥50,000) vs nonmetro counties (RUCC 4-9, which are counties with smaller urban areas as well as completely rural). We estimated hazard ratios (HRs) and 95% confidence intervals (CI) from univariable and multivariable Cox models for associations of metro status with overall survival (OS). Cause of death (lymphoma [including treatment related], non-lymphoma, unknown) was assessed using a competing risk approach. Results: Compared with metro counties (N=6096), LEO participants from nonmetro counties (N=1514) were older (median age 64 vs 62 years; p<0.001), more likely to be non-Hispanic white (94% vs 75%; p<0.001) and married (84% vs 75%; p<0.001), and less likely to have completed graduate or professional school education (16% vs 27%; p<0.001). There were no notable differences (>5%) by metro status for sex, employment status, NHL subtype, stage, performance status, abnormal lactate dehydrogenase (LDH), international prognostic index (IPI), number of comorbidities, time from diagnosis to treatment interval (DTI) or participation in a clinical trial. Compared with LEO participants from metro counties, those from nonmetro counties had inferior OS at 5 years (74.5% vs 78.4%; HR=1.23, CI 1.10-1.37; p<0.001). The OS association only slightly attenuated after adjustment for age, sex, race/ethnicity and NHL subtype (HR=1.20, CI 1.07-1.34; p=0.002), and held in models that adjusted for clinical prognostic factors (stage, NHL subtype, IPI, DTI), socioeconomic status (SES; education, marital status), health status (comorbidity, frailty), or lifestyle factors (smoking, body mass index). Using a competing risk model, the cumulative incidence of death at 5 years due to lymphoma (16.9% vs 14.1%; p=0.002) and non-lymphoma (5.9% vs 3.9%; p=0.002) was higher for participants from nonmetro vs metro counties, respectively. For participants <65 years, nonmetro vs metro status had inferior OS (HR=1.40, CI 1.17-1.67; p<0.001). This association remained after adjustment for age, sex, race/ethnicity and NHL subtype (HR=1.36, CI 1.14-1.63; p<0.001), as well as after adjustment for clinical prognostic, SES, health status, or lifestyle factors. The cumulative incidence of death at 5 years due to lymphoma was higher in participants from nonmetro vs metro counties (15.1% vs 11.5%; p=0.002), while there was no difference by metro status for non-lymphoma related deaths (2.1% vs 1.7%; p=0.47). In contrast, for participants age 65+ years, there was no differences by metro status for OS (HR=1.04, CI 0.91-1.20; p=0.56). After adjustment for age, sex, race/ethnicity and NHL subtype, participants from nonmetro areas had inferior OS (HR=1.12, 0.97-1.29) although this was not statistically significant (p=0.13), and was attenuated in models adjusting for clinical, health status, or lifestyle factors. The cumulative incidence of death at 5 years due to lymphoma was no different in participants from nonmetro vs metro counties (18.9% vs 18.0%; p=0.37), while non-lymphoma related deaths were higher in nonmetro counties (9.9% vs 6.8%; p=0.017). Conclusion: LEO participants from nonmetro vs metro counties had inferior OS overall, although this was predominately observed for younger (<65 years) participants. These associations did not appear to be explained by demographic, NHL subtype, clinical, SES, health status, or lifestyle factors. Of particular note, the risk of death due to lymphoma was higher in nonmetro areas for participants <65 years but not those 65+ years, while the risk of death due to other causes was higher in nonmetro areas for participants 65+ years but not those <65 years. These findings require further study, particularly related to barriers to care, and suggest the potential need for age-specific strategies to optimize outcomes for NHL patients from nonmetro/rural areas.

Purpose Hip arthroscopy is a minimally invasive procedure which has been increasingly used among athletes for several hip joint related pathologies as it allows for a faster recovery. However, objective return to sport criteria have not been described previously among this population. Objective To systematically review the literature to evaluate and describe the objective return-to-sport (RTS) criteria to release patients back to sport following hip arthroscopy. Methods We conducted a comprehensive literature search according to the PRISMA guidelines. Studies were included in the review if patients underwent a hip arthroscopy procedure and the study described criteria for their patients to RTS. Two independent reviewers selected studies for inclusion and extracted study characteristics and objective RTS criteria. Results Of the 306 that were a part of our original search, 6 studies fit our inclusion criteria. There were 250 athletes (average age: 26.1) and 263 hips which underwent hip arthroscopy surgery. Of these athletes, the cohort was on average 46.5% female and an average of 91.2% of athletes returned to sport about 6 months following surgery. The primary sports these athletes participated in were soccer, swimming, skiing/snowboarding, and hockey. The objective RTS measures that were generally described included sport specific tests, range-of-motion, hip strength, and performance-based criteria. Conclusion There are minimal studies who described objective RTS criteria to release patients back to sport following hip arthroscopy procedures. Sports specific tests, hip strength, and performance-based criteria were mentioned as objective criteria to release patients back to sport.

Background Converging evidence hints at neurodevelopmental effects in people at risk of genetic frontotemporal dementia (FTD). Objective We investigated total intracranial volume (TIV), a neuroimaging marker of neurodevelopment, and years of education differences between adult mutation carriers and familial non-mutation carriers, as measures of the structural and functional neurodevelopmental effects of FTD-causing genetic mutations. Methods This cross-sectional cohort study, facilitated through the FTD Prevention Initiative (FPI), included 902 adult pathogenic mutation carriers of GRN , MAPT , or C9orf72 , and 532 familial non-carriers. ANCOVAs were computed to compare TIV and education between groups per gene. Pearson's correlations were used to examine associations between TIV and education. Results Mutation carriers (mean ± SD age = 50.0 ± 13.2 years, sex = 55% female, n ( GRN ) = 298, n( MAPT ) = 187, n ( C9orf72 ) = 417) were compared to familial non-carriers (age = 48.0 ± 12.9 years, sex = 58% female, n ( GRN ) = 201, n( MAPT ) = 114), n ( C9orf72 ) = 217). Consistent with prior findings in young adults, GRN carriers showed larger TIV, on average by 20531 mm 3 , compared to familial non-carriers (95% CI [85.4, 40977], p = 0.049, η 2 p = 0.008). Larger TIV correlated with higher years of education in GRN carriers (95% CI [0.01, 0.24], r (295) = 0.12, p = 0.03) and GRN non-carriers (95% CI [0.08, 0.34], r(198) = 0.21, p = 0.002). MAPT carriers demonstrated smaller TIV than non-carriers, on average by 29896 mm 3 (95% CI [–58248, −1545], p = 0.039, η 2 p = 0.02). Models with C9orf72 and education as outcome variables did not reveal significant differences. Conclusions In support of the neurodevelopmental hypothesis of FTD, GRN and MAPT mutations are linked to structural neurodevelopmental changes in TIV. Further research is needed to identify mechanisms underlying neurodevelopmental influences of FTD mutations and ascertain their suitability as intervention targets.

ABSTRACT Background We recently published the first real‐world multicenter and multi‐institutional study of cisplatin, gemcitabine, and durvalumab in patients with advanced biliary tract cancer (BTC). Here we present an expanded patient cohort with an increased sample size and longer median follow‐up. Methods The study population included patients with advanced BTC, who received cisplatin/gemcitabine plus durvalumab at 55 centers across 12 countries in Europe, the United States, and Asia. The primary endpoints of the study were progression‐free survival (PFS) and overall survival (OS). Secondary endpoints were overall response rate (ORR) and safety. Results Overall, 1358 patients were enrolled. Median PFS was 7.6 months (95% CI: 7.2–8.1), and median OS was 15.6 months (95% CI: 14.8–16.5). ORR was 35.6%, and DCR was 82.7%. Any grade AEs occurred in 1213 patients (89.3%). Grade 3–4 AEs occurred in 597 patients (43.2%). The rate of immune‐related AEs (irAE) was 20.3%. Grade 3–4 irAE occurred in 3.0% of patients. At the multivariate analysis for OS, normal albumin level (HR 0.68, 95% CI 0.57–0.81, p < 0.0001), CEA levels within normal ranges (HR 0.68, 95% CI 0.57–0.82, p < 0.0001), NLR < 3 (HR 0.62, 95% CI 0.52–0.74, p < 0.0001), ECOG PS 0 (HR 0.51, 95% CI 0.42–0.61, p < 0.0001), and prior surgery (HR 0.80, 95% CI 0.65–0.99, p = 0.036) were positive prognostic factors. Conclusion The updated findings, derived from an expanded cohort, further support the adoption of durvalumab in combination with gemcitabine and cisplatin in routine clinical practice, reinforcing the efficacy and safety outcomes demonstrated in the phase III TOPAZ‐1 trial.

Abstract BACKGROUND Post-operative prognostication in glioma patients remains a clinical challenge, particularly given the heterogeneity in tumor biology and patient outcomes. We evaluated whether image-derived features from post-operative imaging improve survival modeling beyond established clinicopathologic factors. METHODS We analyzed a cohort of 71 post-surgical glioma patients treated at Princess Margaret Cancer Centre with known clinicopathologic features including age, histological classification, IDH mutation status, MGMT methylation status, extent of resection, and performance status. A baseline Cox proportional hazards model was fit to clinical variables. Radiomic features were extracted using PyRadiomics from post-operative CT and MRI across three regions of interest: whole brain, tumor bed, and peritumoral ring. Features underwent stepwise unsupervised reduction (variance filtering, exclusion of volume-correlated features, and removal of remaining collinear features), followed by dimensionality reduction via principal component analysis. Combined clinical and imaging models were evaluated in the overall cohort and stratified by IDH mutation status. RESULTS In the overall cohort, the clinical model was highly prognostic (C-index 0.74, p ~ 3.2×10⁻⁶). Adding imaging features improved performance (C-index 0.79) but was not significant (p ~ 0.31). Subset analysis revealed differential effects by IDH status. In IDH-mutant gliomas (n=24), neither clinical nor combined models were significant. In IDH wild-type glioblastoma (n=47), the clinical model achieved C-index 0.75 (p=0.04). The addition of imaging features significantly improved model performance (C-index 0.83, p=0.03), with selected imaging components contributing independent prognostic value after adjustment for clinical variables. Post-hoc analysis of radiomic feature importance (random forest ranking) revealed that top contributing features were drawn from both CT and MRI modalities, with most sourced from the whole brain region. CONCLUSIONS In post-surgical patients with IDH wild-type glioblastoma, image-derived features from post-operative imaging can significantly enhance prognostic modeling beyond known clinicopathologic factors. These preliminary findings support the potential role of radiomic biomarkers in refining risk stratification for this patient subgroup.

Background: Biobanks often lack standard mechanisms to keep donors connected to their biospecimens, reflecting a broken feedback loop that compromises trust, engagement, and scientific progress. Decentralized biobanking empowers patients to track their donations throughout the research journey, supporting personalized feedback and research collaboration via a privacy-preserving blockchain network. This case study explores operational feasibility of implementing decentralized biobanking for a large breast cancer biobank at a US academic medical center. Methods: A mixed-methods case study of the groundwork, implementation, and stakeholder feedback for a real-world decentralized biobanking app pilot was conducted. Biobank members were recruited from February to April 2023. Operational feasibility was assessed via analysis of institutional stakeholder perspectives, pilot engagement, and de-bi app activity. Findings: Physicians and other biobank stakeholders surfaced challenges surrounding managing expectations, balancing empowerment with clinical and research workflows, and navigating power dynamics between patients, physicians, scientists, and leadership. A total of 1080 participants enrolled over 10 weeks, including nearly 10% of the biobank with about 4000 biospecimens. During the pilot, biobank enrollment increased 65% versus the prior year, and there were no biobank withdrawals during or within 1 year following the pilot ( p < 0.001 for both). The app, which facilitated biospecimen tracking and research engagement, was downloaded by 405 users. A total of 140 users tested the blockchain component, with 89% successfully claiming a nonfungible token representing their unique, immutable connection and access to donated biospecimens. Feedback was solicited to inform potential process improvements and risk assessments related to public relations, systems infrastructure, and ethical governance, illuminating next steps. Conclusions: We established operational feasibility for the first step toward decentralized biobanking, informed by requirements to manage expectations, workflows, and power dynamics. Our technical solution demonstrated robust participant engagement and compatibility with established biobanks, suggesting potential to build trust and align incentives and identifying next steps for communications, sustainability, and governance.

Migraine is one of the most disabling diseases worldwide, especially when it transforms into chronic migraine, which is often associated with medication overuse and can become resistant or even refractory to treatments. Molecular, neuroimaging and neurophysiological changes have been described in chronic migraine, some of which might not be fully reversible with preventive treatment. For these reasons, we should aim to prevent this transition, and initiate preventive treatment before disease becomes refractory and burden increases. Preventive migraine treatments are often delayed because of access to care, stigma leading to undertreatment and patients’ reluctance as a result of fear of side effects and, in some cases, fear of being labeled as chronically ill. With the availability of effective and well-tolerated preventive treatments, we must shift our mindset and take advantage of new opportunities to initiate preventive treatment earlier. In this International Headache Society position statement, we propose a migraine preventive strategy under the idea of shifting from reactive treatment once disability is established (prevention of attacks), to proactive, individualized prevention initiated early with safe, effective and tolerable therapies (prevention of disease progression). This approach is based on 1) promoting the early initiation of effective and tolerable preventive therapies, starting from two to four monthly migraine days in line with the majority of current guidelines and recommendations and 2) fostering longitudinal studies to gather more evidence on the potential benefit of early prevention, with the final goal of improving patient outcomes, promoting excellent migraine care, enhancing individual and social well-being, and, ultimately, preventing migraine progression and preserving brain health.

Abstract VanZile, AW, Jones, DD, McHugh, LJ, Clickovich, GL, Morales, MA, Reimschisel, RK, Widenhoefer, TL, Baughman, JT, Urquidi, MD, Conner, DJ, Dobbs, WC, Jagim, AR, Luedke, JA, and Almonroeder, TG. Examining countermovement jump performance and dynamic balance among male high school athletes with varying levels of sports specialization. J Strength Cond Res 39(11): 1163–1168, 2025—Specializing at a young age may limit an athlete's motor development, since focusing on a single sport potentially exposes athletes to less variety of movements and neuromuscular demands. However, there are few studies examining the association between sport specialization and movement performance/control. The purpose of this study was to compare countermovement jump performance and dynamic balance among high school athletes of varying levels of sports specialization. 110 male high school athletes completed countermovement jump testing and the Y-Balance Test (YBT). Ground reaction forces were recorded during countermovement jumps and used to derive peak force, peak velocity, peak power, jump height, and the modified reactive strength index. Y-Balance Test composite scores were calculated to assess dynamic balance across multiple directions, for the dominant and non-dominant limbs. Athletes were grouped into high ( n = 46), moderate ( n = 39), and low ( n = 25) specialization groups based on their sport participation habits. There were no between-group differences for any of the countermovement jump metrics ( p > 0.05). For the YBT composite scores, there was not a group-by-limb interaction effect ( p = 0.28); however, there was a main effect of group ( p = 0.03). Post hoc tests indicated that the high specialization group exhibited lower YBT composite scores compared to the moderate specialization group ( p = 0.01) and a trend toward lower scores compared to the low specialization group ( p = 0.05). In general, highly specialized male athletes exhibited poorer dynamic balance compared to less specialized athletes.

Background: Chronic hamstring tears can result in challenging surgical repairs. Allografts may be used to augment the repair; however, there is limited clinical evidence supporting their use. Purposes: To (1) evaluate clinical outcomes of patients who underwent proximal hamstring repair with allograft augmentation or interposition and (2) compare them to matched controls who underwent primary hamstring repair. Study Design: Cohort study; Level of evidence, 3. Methods: A total of 117 patients who underwent proximal hamstring repair were included, consisting of 19 allograft augmentations, 20 allograft interpositions, and 78 primary repairs. Allograft cohorts were propensity-matched with those who underwent primary repair in a 1 to 2 ratio. Clinical outcomes were obtained at the final follow-up. Data were extracted using continuous variables, with normality reported as mean values ± standard deviation, and non-normality reported as median values with interquartile ranges (IQR). Results: The median follow-up of the augmentation cohort was 1.9 [IQR, 0.8-3.9] years, while it was 3.2 [IQR, 1.6-5.1] years ( P = .182) for the primary repair cohort. The mean follow-up for the interposition cohort was 3.5 ± 2.4 years, while it was 4.2 ± 2.5 years for the primary repair cohort ( P = .227). Forty-two percent of the augmentation cohort had undergone previous surgery, compared with 5% of the interposition cohort. The time from injury to surgery for the augmentation and primary repair cohorts was 6.4 and 1.3 months, respectively ( P < .001). For the interposition and primary repair cohorts, the durations were 17.8 and 1 months, respectively ( P < .001). Clinical outcomes, including the Tegner Activity Scale (3 vs 3), pain with activity (47.4% vs 23.7%), and muscle spasms (36.8% vs 26.3%), did not show significant differences between the augmentation and primary repair cohorts. The augmentation cohort had a significantly worse Lower Extremity Functional Scale (LEFS) score (64 vs 75; P < .001) and were more likely to experience pain with sitting (52.6% vs 21.1%; P = .034) than the primary repair cohort. There was no significant difference in clinical outcomes between the interposition and primary repair cohorts (LEFS: 69 vs 75.5, Tegner Activity Scale: 4 vs 4; pain with sitting: 26.3% vs 27.5%; pain with activity: 42.1% vs 30%; muscle spasms: 26.3% vs 30%). Revision rates were similar between cohorts ( P ≥ .255). Conclusion: Proximal hamstring repair for chronic tears with allograft augmentation or interposition is a reproducible procedure that results in satisfactory, yet poorer clinical outcomes compared with patients who underwent primary hamstring repair. These procedures should be considered in symptomatic patients with chronic tears that are not amenable to primary repair.