University of Alabama at Birmingham

Our visual abstract highlights the primary question of our work, which was to evaluate the outcomes of patients who received talimogene laherparepvec (T-VEC), an oncolytic herpes virus, for advanced Merkel cell carcinoma (MCC) and squamous cell carcinoma (SCC). While T-VEC has been approved for use in melanoma, it is currently only being used in the off-label setting for nonmelanoma skin cancer (NMSC). In addition, many of our patients received T-VEC with concurrent immune therapy, which is a patient population that has not been thoroughly studied. Data were obtained through a retrospective chart review of patients with MCC or SCC who received T-VEC at our NCI-designated comprehensive cancer center. The cohort included ten patients with MCC and three with SCC; six patients received T-VEC alone and seven received T-VEC with concurrent immune therapy. Of note, all three patients who had SCC also received immune therapy. The overall response rate (ORR) of the cohort, defined as the percentage of complete and partial responses to therapy, was 53.8%, with six complete responses and one partial response. Of the six complete responses, four patients were disease-free at their date of last follow-up, which was an average of 25 months from completion of T-VEC treatment. Our work highlights the fact that durable response to T-VEC for patients with advanced NMSC is possible in the setting of a high rate of concurrent immune therapy administration. Further work should more rigorously explore the role that T-VEC may play in NMSC, with particular attention to its use with immune therapy ( https://doi.org/10.1245/s10434-026-19182-3 ).

Artificial intelligence-derived macular thinning patterns were associated with central visual field progression in glaucoma and outperformed global thickness metrics in predicting progression across disease severities. To provide spatial patterns of ganglion cell complex thickness and assess their associations with central visual field progression in glaucoma. Macular patterns from the ganglion cell complex were determined using an artificial intelligence algorithm termed archetypal analysis (AA). The diagnostic accuracy of spatial patterns for detecting 10-2 central visual field progression in eyes with at least five 10-2 visual field tests was calculated and compared with the mean global ganglion cell complex thickness. Eyes with progression on either of 2 trend-based methods (significant MD slope less than -0.5dB/y or clustered pointwise linear regression) were classified as "progressors." A total of 4031 macular scans of 1093 eyes (611 patients) were included, with a mean (SD) age of 67.8 (12.7) years. Eleven distinct spatial patterns were identified. While the macular vulnerable zone was preferentially affected in 4 patterns, most of the less vulnerable zones were preserved. The AA models at baseline achieved AUROC [0.73 (95% CI, 0.62-0.84)] and outperformed global ganglion cell complex thickness [0.55 (95% CI, 0.46-0.61), P =0.01] for predicting central VF progression in eyes with early disease at baseline. The AA models AUROC [0.70 (95% CI, 0.59-0.80)] also outperformed ganglion cell complex thickness [0.55 (95% CI, 0.48-0.60), P =0.02] for predicting central VF progression across all severities. Using unsupervised artificial intelligence, characteristic patterns of macular thinning were identified and associated with progression in the central visual field. Spatial macular pattern analysis may enhance individualized care and improve risk stratification for those at risk of central VF damage.

High levels of l- and d-2-hydroxyglutarate (2HG), the reduced forms of α-ketoglutarate (αKG), are implicated in neurodevelopmental disorders and cancer by modulating αKG-dependent dioxygenases involved in histone, DNA, and RNA demethylation. L-2HG dehydrogenase (L2HGDH) deficiency, a rare autosomal recessive inborn error of metabolism associated with systemic L-2HG elevation, causes progressive neurological disability and increased brain tumor risk of unclear mechanism. Using an isogenic, patient-derived induced pluripotent stem cell system, we examined the impact of L2HGDH deficiency on neural progenitor cell (NPC) function and neuronal differentiation. L2HGDH deficiency caused L-2HG accumulation, NPC hyperproliferation, increased clonogenicity, and defective neuronal differentiation in 2D cultures and cortical spheroids. Editing the L2HGDH locus to WT reversed these effects. Inhibiting glutaminase reduced L-2HG levels and induced neuronal differentiation. L-2HG–dependent inhibition of KDM5 histone demethylases led to widespread retention of H3K4me2/3, markers of active gene expression, with prominent enrichment at the MYC locus and elevated MYC expression across multiple neural cell types. Despite broadly altered histone methylation, genetically or pharmacologically normalizing MYC completely restored neuronal differentiation. These data indicated that a primary metabolic disturbance activated MYC to favor self-renewal and suppress neuronal lineage commitment.

Study DesignUmbrella systematic review.ObjectiveTo qualitatively synthesise systematic reviews evaluating the prevalence, correlates, and outcomes of mental illnesses in individuals with traumatic spinal cord injury (tSCI).MethodsSystematic reviews reporting on depression, anxiety, post-traumatic stress disorder (PTSD), substance use disorders (SUD), cognitive impairment, and related psychological outcomes in tSCI populations were identified and synthesized as per PRISMA guidelines. Data on prevalence, risk factors, assessment tools, and interventions were extracted. Methodological quality was appraised using AMSTAR 2, and primary study overlap was assessed.ResultsTwenty systematic reviews published between 2005 and 2025 were included. Depression was the most frequently studied condition (n = 16), followed by anxiety (n = 10), PTSD (n = 6), and SUD (n = 4), with several reviews addressing multiple conditions. Primary study sample sizes ranged from 3152 to over 50000 participants, with wide variation in injury characteristics, study design, and outcome measures. Pooled prevalence estimates indicated a substantial burden: depression affected up to 43% of community-dwelling individuals, anxiety symptoms around 27%, PTSD up to 62%, and hazardous alcohol use ≥50% in some cohorts. Common risk factors included pain, injury severity, incomplete injury, low social support, maladaptive coping, and co-occurring psychological symptoms. Evidence for effective interventions was limited, and few studies used standardised, validated tools across settings.ConclusionsMental health conditions are highly prevalent in the tSCI population, yet intervention research remains limited. Standardised assessment, longitudinal designs, and targeted, evidence-based interventions are urgently needed to address this critical but under-recognised aspect of tSCI care.

Interfacility transfers for facial trauma are common but often avoidable. However, the magnitude of these potentially avoidable interfacility transfers (PAITs), which can strain trauma systems and incur avoidable costs to the patients, remains unknown. This study aimed to quantify the burden of PAITs for isolated facial trauma in the US. A retrospective analysis using the 2022 Nationwide Emergency Department Sample was performed. Patients aged 16 years and older with isolated facial injuries were identified using ICD-10-CM codes and the Abbreviated Injury Scale. A multiple logistic regression model was developed from level I trauma center (TC) data to predict emergency department home discharge, internally validated, and applied to transfers from level III or non-TCs to identify PAITs based on high predicted discharge probabilities. Among 856,197 patients with isolated facial trauma, 661,149 were initially treated at level III or non-TCs, of whom 2.4% were transferred to higher-level facilities. Using a Youden Index-derived predicted home discharge probability of greater than or equal to 0.946, 43.2% (95% CI 40.9% to 45.4%) of these transfers were classified as potentially avoidable. These transfers were more common among younger, male individuals, White race, those with private insurance, urban residence and those injured by being struck, treated in Southern hospitals, or private not-for-profit facilities. A substantial proportion of interfacility transfers for isolated facial trauma may be avoidable when benchmarked against discharge practices at level I TCs. These findings highlight a critical opportunity to optimize secondary triage decision-making, possibly in conjunction with telehealth consultations, before patient transfer.

Anti-Inflammatory Reliever (AIR) therapy-the use of inhaled corticosteroids (ICS)/formoterol or ICS with short-acting beta-agonists as reliever therapy is guideline-recommended for mild asthma. However, its uptake remains low in community settings. To improve AIR adoption, we developed an AIR Asthma Plan (AIR-AP) and implementation strategies to support its adoption, which we then pilot-tested to assess feasibility and acceptability. Using an exploratory sequential design, we collaborated with stakeholders and pilot site providers to: (1) assess provider needs, (2) co-develop multicomponent provider support tools, (3) tailor workflows, and (4) conduct a 3-5-month pilot test of the tools and implementation strategies in three diverse community practices (pediatrics, family medicine, and allergy). We evaluated usability, acceptability, and feasibility of our implementation strategy using validated questionnaires and provider interviews. Asthma patients were asked to evaluate the usability of the AIR-AP and instructional videos. We co-developed multi-component provider support tools for adoption of AIR, including: (1) AIR-AP (patient-level), (2) instructional videos (patient-level), (3) patient selection tool (provider-level),(4) AIR implementation guide (provider-level), and (5) practice training materials (slide deck). Seven providers from three pilot sites participated. AIR provider support tools were generally feasible and acceptable; however, ongoing barriers to AIR adoption persisted, including limited visit time, unfamiliarity and communication challenges, patients' health literacy and hesitancy to change, and inadequate institutional dissemination. Based on pilot testing, co-developed tools for AIR adoption were feasible and acceptable in community settings. Future efforts should focus on evaluating the effectiveness and other implementation outcomes of these tools.