Faculty Bibliography

INTRODUCTION/BACKGROUND:Adjuvant chemotherapy can improve recurrence-free survival (RFS) in gastrointestinal malignancies. Previous review of phase III randomized controlled trials (RCTs) for colorectal cancer observed that RFS improvements were driven by early divergences during active chemotherapy; late recurrences were not influenced by adjuvant therapy. The broader applicability of this finding is unknown. METHODS:PubMed, Cochrane Library (CENTRAL), Embase, Scopus, and Web of Science were queried from database inception to December 31, 2025, for phase III RCTs including pancreatic, gastroesophageal, hepatocellular, and biliary tract malignancies. Trials where significant differences in RFS were observed between experimental (adjuvant chemotherapy) and control (resection alone) arms were included. Summary data were extracted from Kaplan-Meier curves using DigitizeIT, and absolute differences in RFS were compared at matched intervals using Wilcoxon matched-pairs signed rank tests. RESULTS:A total of 14 RCTs were identified, investigating periampullary (n = 4), gastroesophageal (n = 5), hepatocellular (n = 4), and biliary tract (n = 1) carcinomas. Across pooled RCTs, the highest rates of recurrence were observed in the first year following resection. Median RFS event rate was significantly higher with resection alone (0-0.5 y: resection alone 44.9 [IQR 14.2-84.1] versus adjuvant chemotherapy 26.4 [IQR 7.7-41.9], P < 0.001; 0.5-1 y: resection alone 33.2 [22.7-42.1] versus adjuvant chemotherapy 25.0 [13.8-44.5]; P = 0.007). No difference was observed during later intervals from postoperative randomization (1-2 y: P = 0.952; 2-3 y: P = 0.191; 3-4 y: P = 0.999; 4-5 y: P = 0.110). For the subset of trials where ≤6 mo of adjuvant chemotherapy was used (n = 10), improvements in RFS event rates were observed only during and immediately following the treatment interval (0-6 mo: P = 0.001; 6-12 mo: P = 0.037). CONCLUSIONS:Across multiple gastrointestinal malignancies, improvements in RFS associated with active adjuvant chemotherapy regimens are driven by early changes in recurrence dynamics. These data may provide in vivo understanding of residual tumor cell populations after curative-intent resection and how chemotherapy can be best used to prevent recurrence.

INTRODUCTION/UNASSIGNED:Autologous serum eye drops (ASEDs) are used to treat patients with dry eye syndrome. ASED is manufactured by fractionation of autologous whole blood of concerned patients and usually stored under home freezing conditions. METHODS/UNASSIGNED:We analyzed sterility, particle number, protein concentration, and stability of 14 growth factors in ASED for 148 days at -10°C. RESULTS/UNASSIGNED:Total protein concentration was constant showing no significant degradation as assessed by 1D-SDS-PAGE. Slightly increased concentrations of angiopoietin-2, vascular endothelial growth factor, platelet-derived growth factor, and hepatocyte growth factor were observed, while stem cell factor concentration showed only a modest decrease. CONCLUSION/UNASSIGNED:Our data support the feasibility to store ASED for patient use under usual home freezing conditions for up to 148 days.

BACKGROUND AND AIMS/OBJECTIVE:While inflammation and (auto-)immunity are modifiers of atherosclerosis, immunological determinants of cardiovascular risk beyond the established inflammatory markers, high-sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) remain incompletely defined in humans. This exploratory proof-of-concept study aimed to detect immunological signals enriched in patients with increased cardiovascular risk. METHODS:A nested case-control study was performed within the Ludwigshafen Risk and Cardiovascular Health (LURIC) cohort, a single-centre prospective study of 3316 patients. Forty-four individuals with and without angiographically confirmed coronary artery disease (CAD) and defined survival status were selected for comprehensive immunophenotyping employing bulk RNA, single-cell RNA (scRNA), single-cell T-cell receptor sequencing, mass cytometry, spatial imaging, and cytokine secretion in blood immune cells. Multi-omics factor analysis was applied to identify shared transcriptional programmes. Readouts were tested for their association with CAD status and cardiovascular mortality and validated in two independent cohorts. RESULTS:The integrated analysis strategy revealed immunological signals not detectable with conventional biomarkers, including a prominent signature of cellular proliferation, linked to activation, memory formation, clonal expansion, interferon signalling, and cytokine secretion in T cells. Cell types and transcriptional programmes associated with CAD status and poor long-term survival were identified. These associations were independent of established inflammatory markers, hsCRP and IL-6 that originated from myeloid cells. Key findings were replicated across independent cohorts using 136 scRNA sequencing datasets. Cellular proliferation was confirmed by protein validation in atherosclerotic plaques, and signatures were evaluated as stratification tools to predict short-term outcomes in acute coronary syndromes. CONCLUSIONS:Multi-omic profiling of blood immune cells revealed novel immune signatures associated with CAD, short- and long-term cardiovascular disease outcomes that are independent of systemic inflammation and may be used as risk stratification tools in the future.

Hippocampal circuits are composed of cells that exhibit heterogeneity in gene expression, connectivity, and intrinsic properties. This diversity arises during embryonic development, which produces parallel subcircuits along the trisynaptic pathway. To examine how these subcircuits support spatial memory, we combined embryonic birthdating of interconnected CA3-CA1 neurons with electrophysiology in a place-reward association task. Learning reorganized correlation patterns near rewarded locations, which were reactivated during sleep and predicted memory retrieval. Neurons born on the same day exhibited correlated activity across brain states and hippocampal subfields. Throughout learning, same-birthdate CA1 neurons coordinated their activity to encode the rewarded locations, but CA3 cells did not. These regional differences were mirrored by distinct patterns of connectivity between same-birthdate pyramidal cells and inhibitory interneurons. In particular, same-birthdate neurons converged onto parvalbumin-expressing CA1 interneurons, which were modulated by spatial learning. Together, our results demonstrate that development-defined subcircuits in the hippocampus are preconfigured to encode new memories.

Tumor vaccines represent promising strategies for cancer immunotherapy. However, their application remains restricted in HER2-positive breast cancer due to poor immunogenicity and inefficient antigen presentation. Herein, a multitargeting HER2 nanoparticle vaccine, HER2_aHPF, is developed by co-displaying the HER2 extracellular domain and AE37 T-cell epitope on a Helicobacter pylori ferritin nanoparticle via SpyTag/SpyCatcher conjugation. The nanoparticle vaccine exhibits structural homogeneity, enhanced lymphatic drainage, and high stability during freeze-thaw cycles and long-term storage, with retained immunogenicity after repeated freeze-thaw treatment. WH peptide-mediated DC targeting, in combination with the ferritin scaffold, enhances antigen uptake and DC maturation. In BALB/c mice, CpG and fullerenol dual-adjuvanted HER2_aHPF elicits robust HER2-specific humoral and cellular immunity, characterized by high-titer antibodies, polyfunctional CD4⁺ and CD8⁺ T cells, and expanded effector-memory T cells. Prophylactic and therapeutic vaccination markedly inhibits primary tumor growth and lung metastasis in mouse and human HER2-positive 4T1 models. Mechanistically, HER2_aHPF reduces myeloid-derived suppressor cells and regulatory T cells, increases cytotoxic T-cell infiltration, and maintains a favorable in vivo safety profile. Combination with anti-PD-1 and anti-CD47 antibodies further enhances T-cell activity and tumor control, demonstrating strong synergy between active vaccination and dual immune checkpoint blockade. These findings establish HER2_aHPF as a versatile nanoparticle vaccine platform with clinical translation potential for HER2-positive cancer immunotherapy.

Epilepsy is a common neurological disorder in the United States that disproportionately affects African Americans. Religious and spiritual practices are important coping mechanisms that may influence health beliefs and healthcare decisions, yet their influence on epilepsy outcomes in this population remains understudied. This narrative review examines how religious and spiritual practices contribute to health decision making behaviors among African Americans living with epilepsy. A literature search was conducted using PubMed, Google Scholar, Connected Papers, and the New York University Library system, focusing on religiosity and spirituality in chronic illness, epilepsy outcomes, racial disparities, stigma in faith-based settings, and church-based health interventions. Across the reviewed literature, findings showed that religiosity and spirituality were associated with coping, finding purpose, social support, and quality of life. In epilepsy-specific studies, positive religious and spiritual coping associated with better well-being, lower anxiety and depressive symptoms, and higher quality of life, while negative religious coping was associated with poorer psychosocial outcomes. Direct evidence among African Americans with epilepsy was limited; however, available findings suggest that Black patients relied more on religion, emotional support, positive reframing, and denial as coping strategies compared to White patients. Overall, this review highlights the need to better understand how African Americans with epilepsy use religious and spiritual frameworks to manage living with a chronic neurological condition.

BACKGROUND/UNASSIGNED:Diffuse unpatterned alopecia (DUPA) is an uncommon and incompletely characterized variant of androgenetic alopecia (AGA) marked by diffuse follicular miniaturization across the entire scalp, including the occipital region, which distinguishes it from classic patterned AGA and often precludes hair transplantation. SUMMARY/UNASSIGNED:In this review of the available literature on DUPA, we discuss its clinical presentation, diagnostic features, competing pathophysiologic hypotheses, and management considerations. Current evidence suggests DUPA typically presents with diffuse thinning across all scalp regions, with trichoscopy demonstrating widespread follicular miniaturization without features of scarring alopecia. Diagnosis remains clinical because histopathologic criteria and standardized trichometric thresholds have not been established. Important mimickers include telogen effluvium and diffuse alopecia areata, requiring careful history, examination, trichoscopy, and occasional scalp biopsy. Management is primarily medical, emphasizing stabilization rather than regrowth, and includes topical or oral minoxidil with consideration of adjunctive therapies in selected patients. KEY MESSAGES/UNASSIGNED:DUPA is a diffuse, non-patterned hair loss condition affecting the entire scalp, including the occipital region, for which medical management remains the cornerstone of treatment. DUPA remains poorly defined and further clinicopathologic, trichometric, and longitudinal studies are needed to clarify major knowledge gaps, including epidemiology, pathology, diagnostic criteria, and treatment-specific outcomes.

BackgroundHyaluronic acid (HA) has emerged as a potential biologic adjunct in the management of various foot and ankle pathologies due to its viscoelastic, anti-inflammatory, and chondroprotective properties.MethodsA scoping review of the currently available literature evaluating HA use in foot and ankle pathology was performed, with emphasis on osteoarthritis (OA), osteochondral lesions of the talus (OLTs), and soft tissue disorders.ResultsCurrent evidence suggests that HA injections may provide pain relief and functional improvement across multiple foot and ankle conditions. The most consistent evidence supports potential HA use in soft tissue disorders, including Achilles tendinopathy, plantar fasciitis, and acute lateral ankle injuries. HA may be used as an adjunct in OLT and selected OA applications, although outcomes remain heterogeneous across studies.ConclusionAlthough HA demonstrates a favorable safety profile and potential clinical benefit in selected foot and ankle conditions, currently available evidence remains limited by heterogeneous study designs, inconsistent treatment protocols, and short-term follow-up. Additional high-quality, comparative, and long-term studies are warranted to better define the role of HA in foot and ankle pathology.Level of Evidence:Level V, Scoping Review.

Long-term studies on safety of beta-blockers in pediatric heart failure (HF) are scant. We describe the safety profile, dose ranges, and tolerability of carvedilol in pediatric dilated cardiomyopathy (DCM). The Pediatric Cardiomyopathy Registry (PCMR) was used to identify patients with DCM, treated with carvedilol from 1997 to 2005. Descriptive statistics were analyzed and echocardiographic parameters were compared longitudinally using ANOVA. Total 118 patients were included with median age 4.4 years (interquartile range (IQR) 1.0-13.3). The etiology of DCM was idiopathic (66%), myocarditis (14%), familial DCM (21%). Majority (63%) had symptoms of HF at diagnosis and were on an angiotensin-converting enzyme inhibitor (ACEi) (95%) at carvedilol initiation. The mean ± standard deviation (SD) carvedilol dose at 1 year was 0.38 ± 0.44 mg/kg/dose. The median duration of carvedilol therapy studied was 361 days (IQR 101-958) with 18% of the patients treated for > 3 years. Few patients (< 10%) had blood pressure or heart rate below safety thresholds with no admission for hypotension or bradycardia. Only 4 patients discontinued carvedilol for bradycardia (n = 1), fatigue (n = 1), poor LV function (n = 1) and worsening renal function (n = 1). Mean left ventricular shortening fraction (LVFS) was 16% ± 8 at carvedilol initiation (n = 98), 21% ± 9 at 1 year (n = 49) and 23% ± 9 at 2 years (n = 20) post-carvedilol initiation, suggesting a possible clinical benefit (p < 0.01). These results provide safety data for chronic carvedilol use in children and show a low prevalence of discontinuation for adverse events. Further study of the long-term remodeling effects of chronic beta-blocker use in pediatric HF is required.