Citations

ABSTRACT HLA‐DRB1*03:234 differs from HLA‐DRB1*03:01:01:01 by two adjacent nucleotide substitutions in exon 2.

Abstract Purpose Bibliometric indicators are widely used to evaluate faculty productivity, yet these metrics change with career stage, evolving authorship practices, and technological shifts in how science is produced. This study examines patterns of scholarly output among radiation therapy medical physics faculty at leading cancer centers and provides a framework and quantitative metrics for managing career age‐ and era‐based effects. Methods Peer‐reviewed articles (1969–2025) were collected from Scopus for 397 Ph.D. medical physics faculty at the 20 U.S. cancer centers most highly ranked by US News and World Report in 2025. The bibliometric measures included annual rates of authorships (), first/last authorships (), monograph‐equivalents (), as well as the cumulative h‐index and contribution‐normalized ha‐index. Career age was defined by year of first publication. Productivity distributions were evaluated by career age using empirical cumulative distribution functions derived from 2016–2025 data. Era‐dependent fluctuations (1990–2025) were examined using age‐normalized metrics and trends in authorship team size. Tabulated bibliometrics as a function of career age are provided for evaluation of individual performance. Results Productivity increased substantially with career age, peaking in late career. Senior faculty produced approximately two‐fold higher annual output than early‐career peers. At career ages of 1, 10, 20, 30, and 40 years, the median bibliometric rates were = (1.2, 1.6, 2.5, 2.5,1.8) year −1 , = (0.4, 0.4, 0.5, 0.5,0.2) year −1 , = (0.2, 0.2, 0.3, 0.3,0.3) year −1 , h‐index = (0, 7, 15, 23,43), and ha‐index = (0, 3.3, 6.0, 9.4,15.0). Era‐based effects were substantial. Between 1990 and 2025, median authors per paper increased from 4 to 10, inflating authorship‐based metrics. In contrast, contribution‐weighted measures (FL, ME, ha‐index) demonstrated greater temporal stability. Conclusions Scholarly productivity in radiation therapy medical physics is strongly dependent on career age, with peak output occurring near the end of a typical career before declining modestly near retirement. Career‐age‐based percentile benchmarks provide a more balanced framework for evaluating academic performance than unadjusted bibliometric comparisons, especially for early‐career investigators. Due to changes in authorship norms over time, first/last authorships, monograph equivalents, and ha‐index may provide more accurate and equitable assessments of research performance than authorships or h‐index.

Abstract Varlilumab is a monoclonal antibody with agonistic activity on CD27. The efficacy of single-agent PD-1 inhibitors on aggressive B-cell non-Hodkin lymphoma is limited. Preclinical and phase 1 data suggest that Varlilumab is safe and may have synergistic activity with PD-1 inhibitors. In the DIAL study, we explored whether dual immunomodulatory therapy with Varlilumab and Nivolumab in patients with relapsed/refractory aggressive B-NHL was safe and effective. We conducted a randomized phase II clinical trial on adult patients with relapsed/refractory aggressive B-NHL. Patients were randomized to receive Nivolumab monotherapy in the control group and Varlilumab combined with Nivolumab in the experimental group. Crossover to the experimental group was allowed upon progression in the control group. The primary endpoint was the overall response rate based on the Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC). 54 patients underwent randomization, and 51 received assigned intervention and were included in the intention-to-treat analysis. Objective response was observed in 6 out of 51 patients (ORR 12%). There were 4 responders (ORR 16%) in the Nivolumab group and 2 responders (ORR 7.6%) in the Nivolumab and Varlilumab combination group (p = 0.3). None of the 7 patients that crossed over to the experimental group responded to the addition of Varlilumab. The ORR of patients who were previously exposed to CAR-T cell therapy was 13% (5 out of 39) compared to 8.3% (1 out of 12) in the unexposed patients (p > 0.99). The rate of treatment emergent adverse events was similar between groups, and there was no fatal TEAE in the study. The addition of Varlilumab to Nivolumb did not improve outcomes in patients with aggressive B-NHL. Even though this trial was not designed to evaluate immunotherapy as a rescue therapy after CAR-T failure, most patients (76%) had previously received CAR-T therapy, and their outcomes were equally poor.

BACKGROUND Acral lentiginous melanoma (ALM) is a biologically distinct, inherently aggressive, and understudied melanoma subtype without a unified surgical approach. OBJECTIVE To provide an updated review of ALM and offer practical, surgeon-focused guidance on diagnosis, biopsy, margin-controlled excision, and Mohs micrographic surgery (MMS)-based management of ALM. METHODS & MATERIALS A PubMed/MEDLINE search of ALM, with an emphasis on articles published after 2015. RESULTS ALM demonstrates inherent biological aggressiveness characterized by extensive subclinical spread, delayed diagnosis, and higher stage-adjusted recurrence compared with nonacral cutaneous melanomas. Anatomic constraints additionally necessitate specialized surgical approaches, although current management is extrapolated from nonacral melanoma data. Retrospective data support MMS and margin-controlled excision and tissue preservation in ALM, with the benefit of digit-sparing surgery and functional preservation. No randomized trials have included ALM, highlighting a key evidence gap. CONCLUSION Margin-controlled approaches such as MMS may improve local control and tissue preservation in select ALM patients. Prospective ALM-specific research and standardized diagnostic and surgical protocols are strongly needed.

Abstract Post-traumatic headache (PTH) is the most common consequence of mild traumatic brain injury (mTBI) and often resembles migraine. In 20% to 30% of migraine patients, headaches are preceded by aura, transient visual or sensory disturbances, which are caused by cortical spreading depression (CSD) that can induce headache pain. However, whether mTBI promotes the development of aura and CSD and their possible contributions to PTH remains unclear. We examined the incidence of new-onset aura in individuals with PTH who had no history of aura. Thirty-two percent (35/108) developed new aura symptoms within 60 days of injury, suggesting that mTBI can sensitize the cortex to the induction of CSD. To test this, we combined electrophysiology, neuroimaging, and behavioral assays in a mouse model of mTBI-induced PTH. After closed-head mTBI, injured mice exhibited a 160% increase in CSD induction probability (ie, lowered threshold) and became sensitized to CSD induction by brief exposure to stress, a common headache trigger. When evoked optogenetically, CSD produced prolonged periorbital and hind paw allodynia, consistent with headache-like pain. Subcutaneous onabotulinumtoxinA administered to the scalp after mTBI did not alter CSD susceptibility but completely abolished optogenetic CSD-induced allodynia. These findings suggest that mTBI elicits sensitization to CSD induction and promotes the emergence of aura in humans, likely contributing to PTH. It is important that, even after mTBI-induced sensitization, onabotulinumtoxinA decoupled CSD from pain behaviors, suggesting efficacy in treating PTH associated with aura.

Importance Recent case reports suggest that B antigen–containing blood products may be associated with anaphylactic transfusion reactions in recipients with preformed immunoglobulin E to galactose- α -1,3-galactose (alpha-gal). Objective To test the association of local alpha-gal syndrome (AGS) prevalence and allergic transfusion reaction (ATR) in patients with blood type O. Design, Setting, and Participants In this international, multicenter, retrospective cohort study at academic medical centers, sites were assigned to AGS high- or low-prevalence clusters based on the known geographic distribution of AGS. Data were collected on platelet or plasma transfusions and ATRs during 2020 to 2024. Consecutive patients receiving platelet or plasma transfusions were included. Exposures Patients with blood type O who received B or AB units and patients with blood type O who received O units (reference group) in AGS high- and low-prevalence clusters were compared. Main Outcomes and Measures Before data collection, the hypothesis was that if transfusion-related alpha-gal syndrome (TRAGS) is a true clinical entity, excess ATRs to group B or AB units would be detected in AGS high-prevalence regions exclusively. The main measure was the overall risk ratio (RR) for ATRs to B or AB plasma or platelets in AGS high- vs low-prevalence clusters. Results In total, 558 823 platelet and plasma transfusions at 40 sites in 5 countries were analyzed, of which ATRs occurred in 1744 transfusions (0.3%). In the US AGS high-prevalence cluster (9 sites), significantly more ATRs of any severity occurred among patients with blood type O who received B or AB units vs patients with blood type O who received O units (overall RR, 3.93; 95% CI, 2.96-5.21; P < .001). In contrast, in the primary analysis of the AGS low-prevalence cluster (15 sites), excess ATRs to B or AB units were not detected. In subgroup analyses among patients with blood type O receiving B units, the RR for moderate to severe ATRs was 9.14 (95% CI, 5.39-15.52; P < .001) in the AGS high-prevalence cluster vs 2.15 (95% CI, 1.34-3.47; P = .002) in the AGS low-prevalence cluster. Outside the US, a signal consistent with TRAGS was not detected. Conclusions and Relevance This cohort study provides provocative epidemiologic evidence that TRAGS may be a unique manifestation of AGS and a previously unrecognized risk associated with transfusion. In AGS high-prevalence regions, blood collectors and hospital transfusion services should consider approaches to preventing severe ATRs from B or AB plasma or platelet units.

Abstract Topic Benign Disease: Eosinophilic Esophagitis Background Active inflammation in eosinophilic esophagitis (EoE) disrupts the mucosal barrier, leading to dilated intercellular spaces and decreased transepithelial electrical resistance. Mucosal impedance (MI) has been used to assess mucosal integrity in EoE. We evaluated whether baseline MI measured by high-resolution impedance manometry (HRIM) distinguishes active and inactive EoE. Methods We retrospectively reviewed data from patients with EoE who underwent endoscopic esophageal biopsies within three months of HRIM from 2018-2026 at our tertiary referral center and had no treatment changes between studies. We excluded patients with a history of foregut surgery, erosive esophagitis, or Barrett’s esophagus. Demographics, endoscopy and pathology results were collected by chart review. Active EoE was histologically defined as ≥15 eosinophils per high-power field. Esophageal baseline MI was measured in the 30-second landmark period for the whole esophagus (from 2 cm above LES to 2 cm below UES), distal esophagus (from 2–7 cm above LES), and mid/proximal esophagus (from 10 cm above LES to 2 cm below UES). Mann–Whitney U or T tests were used for comparisons . Optimal MI thresholds were identified by Youden index with 10,000 bootstrap validations, and interrater reliability was assessed using two-way mixed effects intraclass correlation coefficients. Results Seventy-three patients were included: 37 (51%) female, median age 52 years, median BMI 27.2 kg/m2. Fifty-seven patients (78%) had atopic history, including seasonal allergies (38, 52%), asthma (31, 42%), eczema (21, 29%), and food allergies (19, 26%). Thirty-nine patients (53%) were receiving proton pump inhibitors, 25 (34%) were not on EoE therapy, 5 (6.8%) were on swallowed topical steroids, 3 (4.1%) were on dupilumab, and 1 (1.4%) was on an elimination diet. Esophageal strictures were present in 23 patients (32%), and 45 (62%) had active EoE. Baseline MI measurement showed high interrater reliability (n=50, 2 raters; intraclass correlation coefficient 0.937–0.963, p<0.001). Basal mean and minimal impedance were significantly lower in active EoE across all segments, greatest in the distal esophagus (all p<0.05; Figure 1). ROC analysis showed high discrimination of distal mean MI, with a cutoff ≤1.91 kΩ (AUC=0.837, sensitivity 67.9%, specificity 86.7%, Youden 0.545; Figure 2). Conclusion Baseline mucosal impedance during HRIM distinguishes active from inactive EoE, with strongest discrimination in the distal esophagus, supporting MI as a potential, minimally-invasive physiologic marker of mucosal inflammation and disease activity. Clinically, MI may serve as an adjunct tool in dysphagia evaluation, prompting EoE-directed biopsy when abnormal, aiding management in biopsy–symptom discordance, and potentially supporting disease monitoring in selected patients. Larger prospective studies are warranted.

PURPOSE EA1181 (ClinicalTrials.gov identifier: NCT04266249 ) is a single-arm trial evaluating neoadjuvant taxane, trastuzumab, and pertuzumab (THP) in patients with clinical stage II/IIIa human epidermal growth factor receptor 2 (HER2)–positive breast cancer. This report focuses on the secondary end points of pathologic complete response (pCR) rates and associated factors. The primary end point—3-year recurrence-free survival among patients achieving a pCR (ypT0/Tis, ypN0)—will be reported when data mature. METHODS Patients received four cycles of trastuzumab and pertuzumab (HP) with either once per week paclitaxel (12 weeks) or docetaxel (every 3 weeks for four cycles), followed by surgery. Clinicopathologic characteristics were assessed in all patients. The HER2DX pCR score was determined using diagnostic biopsy samples in a representative subset. Logistic regression models identified factors associated with pCR. RESULTS A total of 2,175 patients were enrolled (781 HER2+/estrogen receptor‑negative [ER–]; 1,394 HER2+/ER+). Of 2,141 patients who initiated THP, the overall pCR rate was 43.8%: 63.7% in HER2+/ER– and 32.4% in HER2+/ER+ tumors. Higher pCR rates were observed in tumors that were ER-negative or low ER expressing, progesterone receptor-negative or low expressing, HER2 immunohistochemistry (IHC) 3+, and in patients treated with once per week paclitaxel. T3 disease was associated with a lower pCR rate in HER2+/ER– tumors; otherwise, tumor (T) and nodal (N) stage did not significantly affect pCR. Among 569 patients assessed for HER2DX pCR scores, a high score was independently associated with higher pCR rates, after adjustment for clinicopathologic variables. CONCLUSION Neoadjuvant THP achieved pCR in nearly two-thirds of patients with HER2+/ER– and one third with HER2+/ER+ breast cancer. Low hormone receptor expression, HER2 IHC 3+ status, once per week paclitaxel use, and a high HER2DX pCR score were independent predictors of pCR. These findings should help optimize risk stratification and treatment personalization for patients with HER2-positive breast cancer.

White matter hyperintensities (WMHs) are common MRI findings and established markers of cerebral small-vessel disease associated with stroke, cognitive decline, and vascular risk factors. Several studies have suggested that individuals with migraine, particularly migraine with aura (MA), may have an increased burden of WMHs compared with individuals without migraine. Early population-based studies and meta-analyses reported a higher prevalence of WMHs in migraine, whereas more recent large neuroimaging cohorts have reported conflicting findings or no association. Differences in study design, migraine ascertainment, MRI acquisition parameters, WMH quantification methods, and adjustment for vascular risk factors complicate interpretation of the existing literature. An updated systematic review focusing on methodologically comparable population-based cohorts is therefore warranted. The primary objective of this systematic review and meta-analysis is to determine whether adults with migraine have a higher prevalence or burden of WMHs on MRI than non-migraine controls. Secondary objectives include evaluating associations according to migraine subtype (MA vs. migraine without aura and episodic vs. chronic migraine), sex, WMH location, age, and MRI acquisition or WMH quantification methods, as well as examining longitudinal WMH progression where available. We will include population-based cross-sectional or longitudinal cohort studies of adults undergoing brain MRI with sequences suitable for WMH detection. Migraine exposure may be defined using International Classification of Headache Disorders criteria, structured interviews, validated questionnaires, physician diagnosis, or ICD codes. Controls must originate from the same source population. Searches will be conducted in PubMed/MEDLINE, EMBASE, Web of Science, and Scopus. Study selection, data extraction, and risk-of-bias assessment will be performed independently by two reviewers using Covidence, and risk of bias will be evaluated using the ROBINS-E tool. Because WMH burden is reported using heterogeneous metrics across studies, the primary synthesis will use a precision-weighted direction-of-effect approach, in which each study contributes the direction of the association, weighted by statistical precision. Where sufficiently comparable outcomes are available, random-effects meta-analysis will be performed. Sensitivity analyses will explore the influence of diagnostic criteria, MRI field strength, and confounder adjustment. This review will provide an updated and methodologically rigorous synthesis of the evidence on the association between migraine and WMHs.

Abstract Introduction: Erythromelalgia is a descriptive term for burning pain and erythema in distal extremities, often worsened by heat and improved by cold. Inherited erythromelalgia has been primarily linked to gain-of-function variants in SCN9A , encoding voltage-gated sodium channel NaV1.7. However, approximately 65% to 85% of patients with erythromelalgia do not have pathogenic SCN9A variants. Objectives: The objective of this study was to uncover and assess gene variants potentially associated with pediatric-onset erythromelalgia. Methods: With IRB approval and informed consent, probands and families with erythromelalgia underwent next-generation sequencing. A list of genes of interest was produced based on Mendelian inheritance models. Selected gene candidates were assessed using the Sequence Kernel Association Test-Optimal (SKAT-O). Results: Sixty-two probands with erythromelalgia and their relatives were included in Mendelian analysis, which identified variants in PR domain zinc finger protein 12 ( PRDM12 ) and dihydropyrimidinase-like protein 2 ( DPYSL2 ). In a targeted 12-gene rare-variant set analysis using SKAT-O, zinc finger homeobox protein 2 ( ZFHX2 ) showed evidence of association ( P = 6.9 × 10 −4 ), surpassing Bonferroni correction for 12 tests (α = 4.17 × 10 −3 ), whereas KIF1B showed only a nominal association signal ( P = 0.03) that did not survive multiple-testing correction. Conclusion: Genes associated with both increased and decreased pain sensitivity are of considerable interest for elucidating pain mechanisms and analgesic development. As rare variants in PRDM12 and DPYSL2 were identified in a pediatric erythromelalgia cohort and a gene-based rare-variant association signal for ZFHX2 was identified, replication and functional validation are needed.