Jacksonville College

Objective.The dose-weighted linear energy transfer (LETd) increases significantly at the distal edge of the proton Bragg peak, leading to distinct biological responses compared to proximal regions of the depth-dose profile. Normal tissue complications have been linked to composite LETd distributions from clinical treatment plans, but the associations between LETd and complications remain inconclusive. This study introduces a field-by-field analysis method to provide more detailed insights into these relationships.Approach. LETd in composite plans was reformulated to account for weighted contributions from individual fields. Dose and LETd distributions for each field were calculated using the MCsquare Monte Carlo code. Field-specific dose volume histograms and LETd volume histograms (LETdVHs) were generated for regions with elevated LETd in 101 pediatric craniopharyngioma cases treated with two-field plans (n= 98) or three-field plans (n= 3).Main results.Individual fields contribute high LETd at the distal edge of the spread-out Bragg peak (SOBP) and lateral field edges. High LET particles delivered physical doses of several Gy exceeding the threshold for non-stochastic acute and late effects. Composite LETd distributions, however, show lower LET at the SOBP distal edge due to contributions from low LET particles in opposing fields. Information about high LET dose deposited by individual beams is diluted in composite plan LETd distributions.Significance.Evaluating LETd distributions based solely on composite plans can obscure the contribution of high-LET regions from individual fields to the biological response of tissues. A field-by-field assessment may provide a more accurate understanding of LETd's role in normal tissue effects and may improve the prediction of complications in proton therapy.

We evaluated the prevalence, predictors, and survival impact of positive margins in localized invasive vulvar squamous cell carcinoma. Patients with localized invasive (pT1-T4, N0, M0) vulvar squamous cell carcinoma undergoing surgical excision were identified from the National Cancer Database (2004-2023). Margin status reflects the final pathologic assessment recorded as positive (microscopic or macroscopic residual tumor) or negative. Multivariable logistic regression was used to identify factors associated with positive margins. Overall survival was estimated using Kaplan-Meier and multivariable Cox models. Among 32,341 patients, 4,249 (13.1%) had positive margins. Factors independently associated with margin positivity included older age, later year of diagnosis, Black race, higher comorbidity burden, larger tumor size, higher grade, advanced T stage, treatment at non-academic centers, organ-sparing surgery. Positive margins were associated with worse overall survival (5-year: 59.6% vs 72.5%) and remained associated with increased mortality after adjustment for demographic, tumor, treatment, facility-related factors (aHR 1.30, 95% CI 1.23-1.37). Positive margins remain common in localized vulvar squamous cell carcinoma and are associated with worse overall survival, underscoring the need to optimize margin clearance, particularly in organ-sparing surgical approaches, while also considering other important factors such as tumor location, multifocality, re-excision, adjuvant therapy, and surgical expertise.

The optimal long-term antithrombotic strategy after apparently successful catheter ablation of atrial fibrillation (AF) remains uncertain, particularly in patients who meet conventional guideline thresholds for oral anticoagulation (OAC). To compare continuation versus cessation strategies of long-term OAC after successful AF ablation and to quantify net clinical benefit (NCB) integrating thromboembolic and bleeding outcomes. We searched PubMed, Cochrane CENTRAL, and Embase from inception through February 2026 for randomized and comparative observational studies evaluating long-term OAC continuation versus cessation (no OAC and/or switch to aspirin) after successful AF ablation. Risk of bias was assessed using RoB2 for randomized trials and a modified Newcastle-Ottawa Scale (NOS) for observational studies. Random-effects meta-analyses used a restricted maximum likelihood estimator with Hartung-Knapp adjustment. NCB was calculated as: thromboembolic event rate - (1.5 × major bleeding rate). Six studies met the inclusion criteria (four randomized trials and two observational cohorts). Stroke/transient ischemic attack (TIA) events were reported in six studies and were not significantly different between OAC continuation and cessation strategies (OR 0.69; 95% CI 0.24-1.99; p = 0.49). Systemic embolism (three studies) did not differ between groups (p = 0.12). Major bleeding (five studies) was numerically higher with continued OAC but not statistically significant (OR 2.07; 95% CI 0.88-4.86; p = 0.09). In NCB analysis, continued OAC yielded more negative or near-neutral NCB values, whereas, the cessation strategies were less negative or marginally positive; the fixed-effect risk difference in NCB (continued OAC vs cessation) was +0.00067 (95% CI -0.00279 to +0.00413). This meta-analysis suggests that after successful AF ablation, continuing OAC does not significantly reduce stroke risk compared to cessation or switching to aspirin, but it may increase major bleeding. While NCB trends favor cessation, the low absolute event rates and the risk of silent AF recurrence necessitate caution.

Parkinson’s disease (PD) represents a growing global health challenge, with prevalence doubling from 2.5 million cases in 1990 to 6.1 million in 2016, and projections suggesting it will exceed 12 million by 2040. This exponential growth has been termed the “Parkinson’s pandemic.” China and the United States, which together account for nearly half of the global PD population, have developed markedly different approaches to end-of-life (EOL) care, shaped by their distinct healthcare systems and cultural contexts. Understanding these differences is crucial for developing effective global strategies. This systematic review and meta-analysis comprehensively compares advanced-stage PD care between these two nations to quantify disparities and inform evidence-based policy interventions. We conducted a rigorous systematic review following PRISMA 2020 guidelines, searching six databases (PubMed, Embase, Scopus, Web of Science, CNKI, Wanfang) from January 2015 to October 2025. The timeframe was selected to capture contemporary care patterns following major healthcare reforms in both countries (Affordable Care Act implementation in the US; Healthy China 2030 initiative). Inclusion criteria encompassed peer-reviewed studies reporting on advanced PD (Hoehn-Yahr stage ≥ 3) with outcome measures including survival, quality of life (QoL), palliative care access, caregiver burden, rehabilitation utilization, or healthcare costs. The sample size threshold (n ≥ 100) balanced statistical power with inclusivity. Two independent reviewers screened 3,847 records with excellent agreement (Cohen’s κ = 0.82–0.89). Quality assessment employed the Newcastle-Ottawa Scale (NOS ≥ 8 indicating high quality) for observational studies and the Cochrane Risk of Bias 2.0 tool (RoB 2) for randomized controlled trials, with GRADE criteria determining evidence certainty. Meta-analyses utilized random-effects models with comprehensive heterogeneity assessment (I² statistics, meta-regression) and publication bias evaluation (Egger’s test, trim-and-fill analysis). Sensitivity analyses included high-quality studies only and examined the influence of large database studies. Our analysis of 42 high-quality studies encompassing over 125,000 patients revealed profound and systematic cross-national disparities across multiple domains. In terms of care access, US patients demonstrated significantly higher hospice enrollment rates (28–35% vs. <1% in China, p < 0.001; HIGH certainty evidence) and greater access to specialized neuropalliative programs (15% of US centers vs. <1% in China). These differences translated into measurable quality of life disparities, with Chinese patients scoring 17.6 points worse on the PDQ-39 scale (95% CI 14.8–20.4; MODERATE certainty, I²=64%), a difference exceeding the minimal clinically important difference nearly four-fold. The burden on families showed equally striking patterns: Chinese families provided 94% of EOL care compared to 61% in the US, resulting in significantly higher caregiver depression rates (47% vs. 32%, OR = 1.89, 95% CI 1.45–2.47) and burden scores (Zarit difference: 10.2 points, 95% CI 7.8–12.6). Access to interventions revealed additional gaps, with only 9.2% of Chinese patients receiving physical therapy versus 14.4% in the US (OR = 0.61, 95% CI 0.49–0.76), and a 5.25-fold disparity in deep brain stimulation access (4.2% vs. 0.8%). Economic analysis demonstrated substantial out-of-pocket burden differences: Chinese families paid 58% of total costs ($4,200 annually) versus 12% for US families ($2,800). Meta-regression identified healthcare system characteristics as the primary driver of these disparities (R²=0.42, p < 0.001). This comprehensive analysis reveals that systematic differences in healthcare infrastructure, insurance coverage, and cultural care models are associated with markedly divergent EOL experiences for PD patients in China versus the United States. These findings have policy implications. For China, our findings suggest consideration of: (1) establishing pilot neuropalliative programs in tertiary centers with phased national expansion; (2) developing caregiver support infrastructure including respite care and training programs; (3) leveraging telemedicine platforms to address urban-rural disparities. For the United States, priorities may include: (1) addressing racial disparities in rehabilitation access through culturally competent outreach; (2) expanding Medicare coverage for maintenance therapy; (3) earlier integration of neuropalliative care. Implementation science research would strengthen the evidence base for culturally adapted interventions. As global PD prevalence accelerates, lessons from this bilateral comparison provide a framework for other nations confronting similar challenges in neurological care delivery.

Normothermic regional perfusion (NRP) adoption for donation after circulatory death (DCD) liver transplantation in the United States has been growing, but there remains a higher rate of non-utilization of NRP DCD liver grafts as compared with donation after brain death liver grafts. Six transplant centers and 1 organ procurement organization (OPO) with substantial NRP liver procurement experience performed retrospective reviews of all NRP procurement attempts from September 1, 2021, until March 1, 2024, identifying opportunities for utilization. Five of the 6 transplant centers had prospectively collected data on all accepted livers with NRP intent. The transplant center's intention to utilize DCD donors included 329 livers accepted for transplantation before withdrawal, 252 (76.6%) potential donors expired within the hospital timeframe for donation, and 168 (66.7%) livers were transplanted. Fifty-seven opportunities for utilization were identified by transplant centers, plus 11 from the OPO: most were due to exceeding a functional warm ischemic time limit (n=26), other reasons (n=17), and functional assessment (n=16). The lessons learned by centers in this study provide guidance for newer NRP centers and for OPOs in identifying opportunities for utilization of NRP DCD grafts that have historically been declined.

Lichen Planopilaris (LPP) is a lymphocyte-mediated scarring alopecia characterized by progressive follicular destruction and fibrosis. In this clinical trial, patients with biopsy proven LPP were treated with deucravacitinib (an oral inhibitor of tyrosine kinase 2 (TYK2)) 6 mg BID for 24 weeks (NCT-06091956). Bulk and single-cell RNA sequencing was performed on paired pre- and post-treatment scalp biopsies from baseline and week 4. Patients (N=10) demonstrated improvements in PGA (88.9%, p=0.008), LPPAI (-2.3 points, SD 1.1, p=0.002) and Skindex-16 (-21.0 points, SD 22.1, p=0.014) scores at week 24. Bulk transcriptomic analysis of untreated LPP revealed upregulation of type I Interferon (IFN)-stimulated genes and pathways related to inflammation, immune activation, keratinization, and extracellular matrix remodelling, with downregulation of immune and inflammatory pathways following treatment. Single-cell RNA-seq of LPP was characterized by enrichment of CD8+GZMK+ T cells which showed downregulation of T-cell receptor signaling as well as antiviral pathways with treatment. Basal keratinocytes exhibited reduced cytokine and interferon signaling and decreased communication with NK cells following treatment. CCL19+ fibroblasts were prominent in untreated disease was attenuated after treatment, with downregulation of type I IFN signaling. Selective TYK2 inhibition with deucravacitinib effectively suppresses these inflammatory circuits in LPP and represents a promising therapeutic strategy.

Abstract Reactive arthritis is an immune-mediated arthropathy caused by a preceding remote infection. Typically, reactive arthritis affects the joints of the lower extremities but can occur in the upper extremity. There are a few case reports of reactive arthritis primarily involving the joints of the hand and wrist, necessitating surgical intervention. We describe the case of a 37-year-old, right-hand dominant female who presented with severe left wrist pain. After obtaining radiographs, she was diagnosed with severe erosive changes in the radiolunate joint and distal radioulnar joint (DRUJ) and secondary reactive gonococcal arthritis of the DRUJ. The patient failed conservative measures and ultimately underwent radioscapholunate (RSL) arthrodesis, distal ulna resection, and wrist denervation. Postoperatively, she had resolution of her pain and an excellent functional outcome. Refractory reactive arthritis of the DRUJ can cause concomitant adjacent joint erosive changes. Performing RSL arthrodesis and distal ulna resection can provide an excellent functional outcome and still allow motion to be preserved through the midcarpal joint. IV: Case report level IV or higher evidence.