Citations

Abstract Background Postoperative spinal implant infections (PSIIs) are a serious complication of instrumented spinal fusion. Although debridement with implant retention is standard for early infection, the optimal duration of antimicrobial therapy remains uncertain. Methods We conducted a multicenter retrospective cohort study across 10 US academic centers, including adults with early PSII (≤90 days after fusion surgery) from 2017 to 2021. We excluded patients who experienced treatment failure within 6 weeks of debridement. The primary outcome was treatment failure. Antibiotic therapy effect was analyzed as a time-varying exposure using adjusted Cox proportional hazards models. Secondary analyses included 12-week landmark and clone-censor-weighted models to compare durations ≤ 12 weeks versus >12 weeks. Results A total of 116 patients out of 499 (23.2%) experienced treatment failure during a median follow-up of 3.2 years. Among patients who remain failure-free 6 weeks from debridement, being on antibiotics was not associated with treatment failure (adjusted hazard ratio [aHR] 0.71; 95% CI .48–1.07; P = .10). In a 12-week landmark analysis limited to 359 patients who were not on indefinite suppressive antibiotic therapy, treatment durations > 12 weeks did not significantly reduce the risk of failure (aHR 1.01; 95% CI .62–1.64; P = .99). Results were consistent in the clone-censor-weight sensitivity analysis (aHR 0.85; 95% CI .62–1.16; P = .30). Conclusions Prolonged antibiotic therapy was not associated with improved outcomes in early PSII managed with debridement and implant retention. These results support shorter, individualized antibiotic courses in patients with adequate surgical source control.

Introduction: Heart failure (HF) with preserved ejection fraction (HFpEF) is now the predominant HF subtype, largely driven by the syndemic of physical inactivity and overweight/obesity in an aging population. Deranged skeletal muscle energetics and regional ectopic adipose depots are key cardiometabolic pathways in the pathogenesis of HFpEF, both of which may be favorably modified by 1-2 hours/week of resistance exercise (RE). However, its association with HFpEF risk has not been thoroughly examined. We investigated the association between midlife RE behaviors and incident HFpEF in the Atherosclerosis Risk in Communities (ARIC) study. Hypothesis: Participation in RE at midlife is inversely associated with the risk of incident HFpEF. Methods: Our exposure (RE)—including weightlifting and bodyweight resistance exercises—was assessed using the validated Baecke questionnaire and reported weekly RE duration was averaged across Visits 1 and 3 (1987-1995). We dichotomized averaged RE as 0 hr/wk (‘No RE’, reference) and >0 hr/wk (‘Any RE’). Our outcome (incident HFpEF) was identified through committee-adjudicated HF hospitalizations (January 1, 2005 to December 31, 2023) using medical chart abstraction. Participants with prevalent HF, death, or loss to follow-up before January 1, 2005 were excluded. We constructed Cox regression models to evaluate the association between midlife RE and incident HFpEF. Model 1 adjusted for age, sex, race, field center, education, smoking status, alcohol consumption, and non-RE physical activity. Given that adiposity may lie on the causal pathway, waist-height ratio (WHtR; both measured in cm) was added in Model 2. Results: 10,751 Black and White participants (803 incident HFpEF cases) were analyzed over a median follow-up time of 14.4 years (mean±SD Visit 1 age, 53.3±5.6 years; average Visit 1 and 3 WHtR, 0.58±0.08; 24.7% Black; 57.4% female). 1,217 participants (11.3%) reported engaging in RE at Visits 1 and/or 3, with a median duration of 0.84 hr/wk (IQR, 0.50-1.61). Compared to No RE, the fully adjusted hazard ratio (HR) for Model 1 for Any RE was: 0.78 (95% CI, 0.61-1.00, P = 0.05). The association was attenuated after adjustment for WHtR: HR = 0.84 (0.65-1.07, P = 0.16). Conclusion: Participation in RE at midlife is associated with a 22% lower risk of incident HFpEF. To inform public health and clinical guidelines, further studies are needed to clarify the role of RE in HFpEF prevention.

ABSTRACT Background Cytomegalovirus (CMV) infection remains one of the most prevalent and consequential post solid organ transplant (SOT) infections. Treatment is often challenging, especially when dealing with refractory and resistant CMV infections. Methods We performed a retrospective multicenter cohort study of SOT recipients with clinically significant CMV infection (csCMVi) during 2010–2016. The primary outcome was early refractory CMV infection and secondary outcomes were drug resistance, CMV recurrence, and mortality. Analysis was done with Kaplan‐Meier, univariable logistic regression analysis, and multivariable Cox regression. Results We included 145 SOT recipients with csCMVi, majority were liver transplant (49%). Most common induction was an anti‐IL‐2 antibody (43.9%). The majority ( n = 82; 56.5%) were CMV D+/R‐ mismatch and presented asymptomatic infection (50.3%). After the initial 3 weeks of antiviral therapy, 13 (8.9%) patients had probable refractory csCMVi; most of them (10 [76.9%]) were CMV D+/R‐ mismatch. Longer time after transplant had lower risk (OR 0.68; CI 0.48–0.95, p = 0.029) while lower absolute lymphocyte count (ALC) had a higher risk of early refractory csCMVi (OR 1.54; CI 1.01–2.44, p = 0.048). Drug‐resistant csCMVi occurred in 7 patients (4.8%); a high initial CMV DNA level was associated with resistant csCMVi (OR 2.00; CI 1.08–3.93, p = 0.031). 25 patients (17.2%) experienced recurrent csCMVi within 6 months. 30 patients (20.7%) died; refractory, resistant or recurrent CMV infections were not associated with mortality. Conclusion Refractory csCMVi is associated with a low ALC and an earlier onset after transplant. Resistant csCMVi is associated with high initial CMV DNA levels. Recurrence of csCMVi is common and potentially associated with low ALC at the end of antiviral treatment.

ABSTRACT Our study aimed to develop a novel, reproducible, minimally invasive turkey knee osteoarthritis (OA) model and evaluate whether intra‐articular hyaluronan (HA) alone or combined with purified exosome product (PEP) attenuates OA‐related functional and structural deterioration. OA was induced arthroscopically by transection of the anterior and posterior cruciate ligaments with resection of the anterior horn of the medial meniscus. Animals received intra‐articular injections of saline, HA, or PEP + HA at postoperative 2–5 weeks. Gait was assessed at 4, 8, and 12 weeks, and cartilage degeneration, subchondral bone sclerosis, osteophyte formation, synovial fibrosis, heterotopic ossification, and meniscal integrity were evaluated by quantitative CT and histology at week 12. Compared with saline, HA improved lameness, preserved cartilage glycosaminoglycan content, and reduced meniscal rupture, subchondral bone sclerosis, and periarticular heterotopic ossification. PEP + HA provided additional benefits, including prolonged stance phase, reduced synovial fibrosis, and greater chondroprotection than HA alone, while plantar pressure variables, subchondral bone remodeling, and patellar osteophytes did not differ between HA and PEP + HA. This turkey model reliably produces human‐like OA changes and enables longitudinal functional and structural assessment. Intra‐articular HA mitigated OA progression, and the addition of PEP conferred incremental joint protection.

Background: Hepatocellular carcinoma (HCC) has a poor long-term prognosis due to high recurrence and cirrhosis-related mortality, even after potentially curative treatments such as liver transplantation (LT), surgical resection, or ablation. This study aimed to identify factors associated with ≥10-year survival in HCC patients. Methods: A retrospective cohort study was conducted among HCC patients diagnosed between 2004 and 2022 using the National Cancer Database. Multivariable Cox regression was used to identify predictors of overall survival, and logistic regression was used to identify predictors of ≥10-year survival. Results: Among 249,600 HCC patients, 177,585 (71.2%) died within 5 years, 8613 (3.5%) died at 5–10 years, 54,988 (22.0%) were alive with <10 years of follow-up, and 8219 (3.3%) survived ≥10 years. LT, resection, and ablation were performed in 6.6%, 9.3%, and 11% of patients, respectively. Compared with ablation as the reference group, LT [adjusted odds ratio (aOR) 11.96, 95% confidence interval (CI): 11.27–13.29] and resection (aOR: 2.83, 95% CI: 2.57–3.08) increased the odds of ≥10-year survival, while non-curative treatments reduced the odds compared with ablation (aOR: 0.50, 95% CI: 0.47–0.55). Cox regression results were consistent with the logistic model, confirming the association. Decision tree analysis confirmed LT as the dominant determinant of long-term survival. Black individuals were associated with lower odds of ≥10-year survival (aOR: 0.88, 95% CI: 0.820–0.96) and decreased likelihood of receiving LT (aOR: 0.73, 95% CI: 0.55–0.96). Conclusions: LT offers the best chance of ≥10-year survival in HCC. Ensuring equitable access is essential, especially for Black patients who have lower transplant rates and worse outcomes.

Abstract Carpal fractures are uncommon, representing a small proportion of hand fractures. This study aimed to determine the incidence, injury mechanisms, treatment patterns, and complication rates of carpal fractures in Olmsted County, Minnesota, United States. A retrospective review was performed using the Rochester Epidemiology Project registry to identify carpal fractures between 2013 and 2023. Fractures were confirmed by radiographs, computed tomography, or radiology reports. Demographic data, injury mechanism, fracture laterality, and fracture characteristics were recorded. A total of 699 carpal fractures were identified. Most patients were men (57%) with a mean age of 43 years. The most common fracture was the scaphoid (44%), followed by the triquetrum (31%), hamate (9%), and trapezium (3%). The overall incidence was 53.6 per 100,000 person-years. Concomitant wrist fractures occurred in 22%, and multiple ipsilateral carpal fractures in 4.6%. Patients with triquetrum fractures had the highest mean age (54 years) and low surgical rates (2%), whereas hamate and trapezoid fractures occurred at younger ages (39 and 38 years) and had the highest surgical rates (28 and 33%, respectively). The most common injury mechanism was a fall onto an outstretched hand (n = 438). Overall, 14% (n = 98) of patients underwent surgery, of whom 77% were men. The highest nonunion rate was seen in hamate fractures (10.9%), followed by scaphoid waist and proximal pole fractures (10.5%). Nonscaphoid carpal fractures occur more frequently than previously reported and demonstrate variable age distribution, treatment rates, and nonunion risks. Understanding these patterns can improve diagnosis, guide treatment planning, and inform patient expectations. IV.

Background/Objectives: Characterizing spinal cord multiple sclerosis (MS) lesions in MRI is critical for diagnosis, monitoring, and treatment evaluation. However, current automated approaches for lesion detection and segmentation are typically designed for specific MRI contrasts or acquisition sites, limiting their generalizability in real-world clinical settings where imaging protocols vary widely. This work proposes a robust multi-site, multi-contrast segmentation framework for spinal cord lesions. Methods: The segmentation model was trained and evaluated on a large-scale dataset comprising 4428 annotated images from 1849 persons with MS across 23 imaging centers, encompassing six MRI contrasts (T1w, T2w, T2*w, PSIR, STIR, and UNIT1) acquired at 1.5 tesla (T), 3 T, and 7 T. Results: Likert-type assessment performed by neuroradiologist ratings demonstrated superior generalization of the model compared to existing contrast-specific pipelines ( p < 0.01). Additional experiments evaluated robustness across spinal levels, acquisition resolutions, binarization thresholds, and quantitative evaluation on external labeled datasets. Conclusions: The proposed model can achieve accurate and reliable spinal cord MS lesion segmentation across heterogeneous MRI data, addressing a key barrier to clinical translation. The model is available in the Spinal Cord Toolbox v7.2 and higher. Code repository: https://github.com/ivadomed/seg-sc-ms-lesion-multicontrast

Abstract Pancreatic cancer disproportionately affects Black individuals in the United States, but they have limited representation in genetic studies of pancreatic ductal adenocarcinoma (PDAC). To address this gap, we performed admixture mapping and genome-wide association analysis (GWAS) in genetically inferred African ancestry individuals (1,030 cases and 889 controls). Admixture mapping identified three regions with a significantly higher proportion of African ancestry in cases compared to controls (5q33.3, 10p1, 22q12.3). GWAS identified a genome-wide significant association at 5p15.33 ( CLPTM1L , rs383009:T>C, T Allele Frequency=0.51, OR:1.45, P value=1.24×10 -8 ), a locus previously associated with PDAC. Known loci at 5p15.33, 7q32.3, 8q24.21 and 7q25.1 also replicated (P value <0.01). Multi-ancestral fine-mapping identified two potential causal SNPs (rs3830069 and rs2735940) at 5p15.33. Collectively these findings identified novel PDAC risk loci and expanded our understanding of this deadly cancer in underrepresented populations, emphasizing the multifactorial nature of PDAC risk including inherited genetic and non-genetic factors. Statement of Significance To understand how genetic variation contributes to PDAC risk in Black people in North American, we studied individuals of genetically-inferred African ancestry. We identified novel risk loci and differences in the contribution of known loci. This demonstrates that ancestry-informed genetic analyses improve our understanding of PDAC risk and enhances discovery.

Abstract In 2011, a workgroup of the Alzheimer's Association Research Roundtable introduced recommendations for detecting and monitoring amyloid‐related imaging abnormalities (ARIA) in Alzheimer's disease (AD) clinical trials. Since then, anti‐amyloid immunotherapies have received regulatory approval for AD treatment and are beginning to enter clinical practice, underscoring the importance of informing healthcare providers, researchers, and patients about ARIA's implications in real‐world settings. In response, the Alzheimer's Association convened a new workgroup to review current knowledge of ARIA, including underlying mechanisms, clinical presentations, associated risk factors, mitigation strategies, radiologic detection methods, patients’ perspectives in treatment decision‐making, and outstanding challenges. Here, we outline key insights from this workgroup, highlighting that effective ARIA detection and monitoring in clinical practice requires adherence to robust protocols to mitigate risks and enhance patient safety. Limited availability of clinical and pathologic data on predictors of symptomatic and severe ARIA underscores the importance of continued real‐world data collection.

Background: The National SCI Model Systems (SCIMS) Database was established in 1973 to study longitudinal data from persons with traumatic SCI (TSCI). The SCIMS provides an ideal platform to explore the feasibility of a parallel data collection effort to understand the characteristics of individuals with nontraumatic SCI (NTSCI). In the current data collection cycle (2021-2026), all SCIMS centers gathered data specific to NTSCI. Objectives: To (1) describe the demographic and injury-specific characteristics of participants with NTSCI and (2) assess neurological changes from admission to discharge. Methods: The International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) examination data of participants with NTSCI who were enrolled at an SCIMS center were extracted from the medical records at admission and discharge from inpatient rehabilitation. Data from 178 participants with NTSCI were analyzed. Results: Among the 93 participants who had adequate ISNCSCI data on admission, only 8.6% had neurological complete injuries. More participants had paraplegia ( n = 58, 62.4%) than tetraplegia ( n = 35, 37.6%). For participants with full ISNCSCI data at both admission and discharge ( n = 47), there were significant improvements in the lower extremity motor score and pinprick and light touch scores on discharge. Conclusion: On admission to acute rehabilitation, more people with NTSCI had paraplegia than tetraplegia, and neurological incomplete injuries were more common. People with NTSCI experienced significant improvement in ISNCSCI neurological variables by the time of discharge from rehabilitation.