Citations

Abstract The paradigm in the field of oncolytic virotherapy proposes that tumor cell killing by an oncolytic virus (OV) culminates in the priming of antitumor CD8+ T cells. However, this ignores the impact a highly immunodominant antiviral response against the OV has on the subdominant antitumor response, particularly with regard to the naturally low affinity of tumor antigens to their cognate T-cell receptors. To investigate this experimentally, we first studied the interaction between the two responses in B16 and MC38 tumor models, both expressing ovalbumin (OVA). Contrary to the accepted paradigm, the inflammatory vesicular stomatitis virus (VSV) failed to expand OVA-specific T cells in vivo unless armed with tumor-associated antigen (TAA). In fact, treatment with the control VSV led to the ablation of antitumor T cells and a shift toward dysfunction as determined by the upregulation of markers, including LAG3 and CD39, correlating with lower rates of survival. Combination with anti–PD-1 immune checkpoint blockade therapy significantly improved survival only when VSV expressed TAA. VSV-expressing altered peptide ligand variants of tumor antigens, which evade mechanisms of central tolerance, expanded near self-antigen–specific T cells with the ability to cross-react with tolerized tumor antigens, thus providing an antitumor effector population capable of proliferating in the presence of a potent antiviral response. Taken together, these findings offer a rational approach to OV design which preserves acute antitumor therapy provided by antiviral innate and T-cell responses while promoting the induction of tumor-specific T cells. Significance: Oncolytic viruses can induce an antiviral T-cell response that occludes an antitumor response, challenging the paradigm in the field and elucidating strategies to optimize the efficacy of oncolytic viroimmunotherapy.

ABSTRACT Ileus is a common gastrointestinal complication in critically ill patients, posing a unique management challenge due to its multifactorial etiology and impact on clinical stability. Standard therapeutic approaches often fail in the setting of metabolic derangement and hemodynamic instability. Prucalopride, a selective 5-HT 4 receptor agonist, has demonstrated efficacy in promoting colonic motility; however, its use in severe small bowel and colonic ileus or decompensated liver disease populations remains limited. We report the case of a 28-year-old man with decompensated alcoholic hepatitis who developed severe small bowel and colonic ileus refractory to standard management. Concerns for worsening illness prompted a trial of prucalopride, which was temporally associated with rapid resolution of the ileus and remarkable improvement in radiographic imaging and clinical phenotype. Prucalopride may be a potential therapeutic option for severe small bowel and colonic ileus in critically ill patients. Further studies are warranted to delineate its safety and efficacy.

Introduction: Limited research explores dermoscopy use among physician associates (PAs), outside of one prior study examining dermoscopy in PA student education. This study sought to investigate dermoscopy use among practicing PAs and its impact on their overall diagnostic confidence, including in darker skin tones, when differentiating between benign and malignant skin lesions. Methods: An anonymous survey was developed in 2023 with input from experts in dermoscopy and survey creation to assess PA confidence in skin lesion evaluation as well as PA dermoscopy knowledge and use, perceptions, barriers to use, and prior education. The dermoscopy survey was included as an optional module in the 2024 American Academy of Physician Associates (AAPA) Salary Survey. Results: Of 3,174 invited PAs, 995 (31.4%) responded. Most had never used dermoscopy in practice (81%) but knew or recognized the term (71%). A majority (53%) believed PAs should be trained in dermoscopy during PA school, and 26% reported no interest in future dermoscopy use. Dermatology PAs reported more frequent dermoscopy use and generally greater confidence in evaluating skin lesions, both overall and in darker skin tones, than PAs in other specialties. PAs in surgical (OR=0.2, 95% CI 0.1-0.6) and medical (OR=0.3, 95% CI 0.2-0.5) subspecialties were less likely to use dermoscopy at least annually compared with PAs in primary care. PAs in rural areas were more likely to feel confident in differentiating skin lesions than those in urban areas (OR 2.9, 95% CI 1.7-5.0). Conclusion: Dermoscopy use is associated with higher overall skin lesion assessment confidence. Wider adoption, especially outside dermatology, requires training, increased advocacy, and expanded education.

Abstract Background Ultrasound (US)‐guided hydrodissection is a minimally invasive treatment for cubital tunnel syndrome (CuTS) with promising early results. However, data on patient‐perceived outcomes, durability of relief, and impact on surgical need remain limited. Objective To assess the effectiveness of US‐guided cubital tunnel hydrodissection in improving CuTS symptoms via patient‐centered outcomes. Design Retrospective chart review with cross‐sectional telephone follow‐up. Setting Quaternary medical center multidisciplinary outpatient hand clinic. Participants Seventeen patients (19 arms) with clinical CuTS who received US‐guided hydrodissection from one physician. Interventions Patients were contacted by telephone for cross‐sectional outcome assessment. Main Outcome Measures Patient‐reported improvements in weakness, paresthesias, and/or pain, percent pain relief, symptom improvement duration, adverse events, and Patient Global Impression of Change (PGIC) scores. Results At mean 7 ± 5 month follow‐up, improvement in weakness, paresthesia, and pain was reported in 12 (63%) extremities (95% confidence interval [CI] 41%–85%; p < .001) . Pain relief ≥50% occurred in 12 (63%) and ≥75% in 8 (42%) extremities, with mean duration 4 months. PGIC scores showed 14 (74%; 95% CI 54%–94%; p < .001) at least “minimally improved” and 8 (42%) (95% CI 20%–64%; p < .001) “much improved.” No adverse events occurred. Two patients without improvement underwent surgical decompression with anterior transposition at 1 and 3 months after hydrodissection, achieving 90%–100% pain relief and “much or very much improved” PGIC scores. Of 19 extremities, 7 (37%) were McGowan Grade I and 12 (63%) Grade II; none were Grade III. Grade II extremities showed significantly greater overall symptom relief ( p = .004) and pain relief ≥50% ( p = .004). PGIC scores did not differ significantly between grades (both p > .062). Conclusion US‐guided cubital tunnel hydrodissection was associated with meaningful symptom improvement and no adverse events. Limitations include small sample size, no control group, single operator, and potentially time‐limited relief. The procedure appears safe and a potential nonoperative treatment option.

Glioblastoma is the most common form of brain cancer in adults and remains one of the most lethal forms of cancer. Treating glioblastoma is uniquely challenging due to its aggressive nature and its critical location, the brain, which must remain largely undamaged. Due to these difficulties, there is a lack of effective treatment options. Computer models simulating tumors and their response to therapy, known as digital twins, provide a promising new strategy. These model systems are mathematical equations that capture the biological knowledge of how cells interact during tumor growth and in response to treatment. By solving these equations, we can create virtual patients that provide accurate predictions of real patients’ tumor progression. This approach has the potential to improve outcomes by designing therapies for the specific needs of each patient, moving beyond the limitations of the “one-size-fits-all” approach that is currently used.