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Therapeutic clinical trial enrollment does not match glioma incidence across demographics. Traditional statistical methods have identified independent predictors of trial enrollment; however, our understanding of the interactions between these factors remains limited. To test the interactive effects of demographic, socioeconomic, and oncologic variables on trial enrollment, we designed boosted neural networks (BNNs) for all glioma patients ( n = 1042), women ( n = 445, 42.7%), and minorities ( n = 151, 14.5%) and externally validated these models [whole cohort, n = 230; women, n = 89 (38.7%); minority, n = 66 (28.7%)]. For the whole-cohort BNN, the most influential variables on enrollment were oncologic variables, including KPS [total effect (TE), 0.327], chemotherapy (TE, 0.326), tumor location (TE, 0.322), and seizures (TE, 0.239). The women-only BNN exhibited a similar trend. Conversely, for the minority-only BNN, socioeconomic variables [insurance status (TE, 0.213), occupation classification (TE, 0.204), and employment status (TE, 0.150)] were most influential. These results may help prioritize patient-specific initiatives to increase accrual.

ImportanceThere exists substantial heterogeneity in outcomes within T stages for patients with cutaneous squamous cell carcinoma (cSCC).ObjectiveTo determine whether a customized generative pretrained transformer model, trained on a comprehensive dataset with more than 1 trillion parameters and equipped with relevant focused context and retrieval augmented generation (RAG), could excel in aggregating and interpreting vast quantities of data to develop a novel class-based risk stratification system that outperforms the current standards.Design, Setting, and ParticipantsTo build the RAG knowledge base, a systematic review of the literature was conducted that addressed risk factors for poor outcomes in cSCC. Using the RAG-enabled generative pretrained transformer (GPT) model, we developed a novel class-based risk stratification system that assigned point values for risk factors, culminating in a GPT-based prognostication system called the artificial intelligence–derived risk score (AIRIS). The system’s performance was validated on a combined prospective and retrospective cohort of 2379 primary cSCC tumors (1996-2023) with at least 36 months of follow-up, against Brigham and Women’s Hospital (BWH) and American Joint Committee on Cancer Staging Manual, eighth edition (AJCC8) systems in stratifying risk for locoregional recurrence (LR), nodal metastasis (NM), distant metastasis (DM), and disease-specific death (DSD).Main Outcomes and MeasuresPerformance metrics evaluated included distinctiveness, homogeneity, and monotonicity, as defined by the AJCC8, as well as sensitivity, specificity, positive predictive value, negative predictive value, accuracy, the area under the receiver operating characteristic curve, and concordance.ResultsThe median age at diagnosis was 73 (IQR, 64-81) years, with 38.5% female patients and 61.5% male patients. The AIRIS prognostication system demonstrated superior sensitivity across all outcomes (LR, 49.1%; NM, 73.7%; DM, 82.5%; and DSD, 72.2%) and the highest area under the receiver operating characteristic curve values (LR, 0.69; NM, 0.81; DM, 0.85; and DSD, 0.80), indicating significantly enhanced discriminative capability compared with the BWH and AJCC8 systems. While all systems were comparably distinctive, the AIRIS prognostication system consistently demonstrated the lowest proportion of tumors exhibiting poor outcomes in low-risk categories, suggesting its improved homogeneity and monotonicity.Conclusions and RelevanceThe results of this diagnostic study suggest that the AIRIS system outperforms the existing BWH and AJCC8 prognostication systems, potentially providing a more effective tool for predicting poor outcomes in cSCC. This study illustrates the potential of large language models in refining prognostic tools, offering implications for treating patients with cancer.

Thymomas and thymic carcinomas are rare mediastinal tumors that originate in the thymus. Patients with thymoma may experience symptoms associated with autoimmune paraneoplastic diseases (such as myasthenia gravis), which typically do not occur in patients with thymic carcinoma. The NCCN Guidelines for Thymomas and Thymic Carcinomas provide guidance for the diagnosis, treatment, and surveillance of patients with thymoma and thymic carcinoma. Involvement of a multidisciplinary team with experience treating thymomas and thymic carcinomas is highly recommended.

Abstract Background Real-world first-line maintenance (1LM) treatment data are limited for advanced/metastatic non-small cell lung cancer (a/mNSCLC). Materials and Methods In this electronic health record-derived, deidentified database study, eligible patients (≥18 years; diagnosed with stage III/IV non-small cell lung cancer [June 1, 2017-September 30, 2021]) initiated pembrolizumab-based 1LM after 4-6 cycles of first-line (1L) platinum-based chemotherapy-pembrolizumab ± pemetrexed. Study outcomes were real-world time to next treatment or death (rwTTNTD), overall survival (rwOS), and predictors of outcomes. Results Of 1944 patients analyzed (median follow-up, 12.2 months), 51.9% received 1LM pembrolizumab-pemetrexed and 48.1% pembrolizumab monotherapy. Median rwTTNTD and rwOS were 9.2 (95% CI: 8.5-9.8) and 18.7 (95% CI: 17.7-20.3) months, respectively. In multivariable analyses, factors significantly associated with shorter rwTTNTD included 5%-<10% (hazard ratio [HR], 1.34; 95% CI: 1.17-1.54) or ≥10% (HR, 1.69; 95% CI: 1.42-2.01) weight loss during 1L versus 0% or <5% weight loss. Programmed death-ligand 1 (PD-L1) expression 1%–49% (HR, 0.81; 95% CI: 0.71-0.93) or ≥50% (HR, 0.55; 95% CI: 0.47-0.64) and female sex (HR, 0.85; 95% CI: 0.75-0.95) were significantly associated with longer rwTTNTD. These variables were also significantly associated with shorter (weight loss 5%-<10%: HR, 1.52; 95% CI: 1.30-1.77; ≥10% HR, 2.06; 95% CI: 1.71-2.48) and longer rwOS (PD-L1 expression: 1%-49% HR, 0.84; 95% CI: 0.72-0.98; ≥ 50% HR, 0.57; 95% CI: 0.48-0.68; female sex: HR, 0.81; 95% CI: 0.71-0.92). Conclusions Predictors of real-world clinical outcomes included 1L treatment, weight loss, PD-L1 status, and sex. Poor outcomes persisted despite immunotherapy-based 1LM availability, revealing an unmet need in this population.

AbstractBackgroundPrevious publications have described the presence and severity of insomnia amongst those with persistent post‐traumatic headache (PPTH), but there has been a paucity of studies investigating insomnia during the acute phase of post‐traumatic headache (APTH). The primary study objective was to investigate insomnia symptoms and their severity in individuals with APTH due to mild traumatic brain injury (mTBI), and the secondary objective was to assess how psychological factors, sensory hypersensitivities, headache burden, and cognitive performance might associate with insomnia.MethodsIn this clinic‐based, cross‐sectional study, 82 individuals with APTH due to mTBI and 82 healthy controls (HC) were included. Participants completed the Insomnia Severity Index (ISI), Trail Making Test (TMT A and B), 12‐item Allodynia Symptom Checklist (ASC‐12), State–Trait Anxiety Inventory, Photosensitivity Assessment Questionnaire (PAQ), Beck Depression Inventory (BDI), Hyperacusis Questionnaire (HQ), Rey Auditory Verbal Learning Test (RAVLT), and a detailed headache characteristics questionnaire within 59 days of their mTBI to assess insomnia severity, psychological features, sensory hypersensitivities, headache symptoms, and cognitive performance. The questionnaire and test results were compared between APTH and HC groups. Within the APTH group, ISI scores were correlated with the other assessments to determine underlying clinical relationships.ResultsParticipants with APTH, evaluated an average of 27.2 days after their mTBI, had significantly higher ISI scores (median [interquartile range, IQR] score 12 [6–17]) compared to HC (0 [1.3–6], p < 0.001). Twenty‐four (29%) individuals with APTH had ISI scores categorized as moderate clinical insomnia compared to two (2%) in the HC group. Additionally, seven (9%) in the APTH group and none of the HC had ISI scores indicative of severe clinical insomnia. Those with APTH significantly differed from the HC on the BDI (median [IQR] score APTH: 9 [5–16.8] vs. HC: 2 [0–4]; p < 0.001), state anxiety (median [IQR] score APTH: 36.5 [26–45] vs. HC: 23 [20–27.5]; p < 0.001), trait anxiety (median [IQR] score APTH: 38 [27.3–46.8] vs. HC: 26 [23–30]; p < 0.001), photosensitivity (median [IQR] PAQ score APTH: 2 [1–4] vs. HC: 0 [0–1]; p < 0.001), allodynia (median [IQR] ASC‐12 score APTH: 2 [0–5.8] vs. HC: 0 [0–0], p < 0.001), hyperacusis (median [IQR] HQ score APTH: 15.5 [7–23] vs. HC: 4 [2.3–7], p < 0.001), and RAVLT‐delayed recall (median [IQR] score APTH: −0.8 [−1.5 to 0] vs. HC: −0.1 [−0.9 to 0.7], p = 0.019). For participants with APTH, the ISI was most significantly associated with the BDI (standardized regression coefficient (RC) [95% confidence interval, CI] 0.68 [0.52–0.84], p < 0.001), followed by state anxiety (RC [95% CI] 0.60 [0.42–0.78], p < 0.001), trait anxiety (RC [95% CI] 0.56 [0.37–0.74], p < 0.001), headache severity (RC [95% CI] 0.40 [0.19–0.60], p < 0.001), HQ (RC [95% CI] 0.36 [0.16–0.57], p = 0.001), and PAQ (RC [95% CI] 0.35 [0.15–0.56], p = 0.001).ConclusionsIndividuals with APTH have more symptoms of insomnia compared to HC with 38% of individuals with APTH experiencing moderate or severe insomnia symptoms. Insomnia symptoms may be associated with more severe depression, anxiety, photophobia, hyperacusis, headache severity, and cognitive impairment. To address the overall well‐being of patients with APTH, clinicians should screen for and appropriately manage insomnia along with other symptoms following mTBI.

ABSTRACT Peritoneal fibrosis is one of the main causes of peritoneal dysfunction and withdrawal of patients from peritoneal dialysis (PD). Our previous study has shown that high‐glucose dialysis solution promotes glycolysis in peritoneal mesothelial cells, leading to mesothelial‐to‐mesenchymal transition (MMT) and peritoneal fibrosis. However, the molecular mechanisms remain unclear. Using single‐cell RNA sequencing (scRNA‐seq) analysis of cells from the effluent of patients undergoing PD from our previous study, we found that pyruvate kinase isozymes M2 (PKM2), a key rate‐limiting enzyme of glucose metabolism, was significantly upregulated in the mesothelial cells of patients with long‐term peritoneal dialysis (LPD). Using co‐immunoprecipitation, chromatin immunoprecipitation assay, and gene silencing techniques, we revealed that PKM2 promotes the expression of transcription factor SNAI2 by acetylating histone H3K9 (H3K9ac), thereby promoting the occurrence of MMT and hence peritoneal fibrosis. l ‐cysteine, a known PKM2 inhibitor, blocked these responses and prevented PD‐induced peritoneal fibrosis. These results could provide a novel therapeutic strategy for treating peritoneal fibrosis.

We report a case of a triazole and echinocandin-resistant C. glabrata right shoulder prosthetic joint infection in a 60-year-old woman. The patient underwent surgery and received the novel triterpenoid antifungal agent ibrexafungerp. She initially improved, but relapsed four months post-treatment. This case highlights the potential role of ibrexafungerp in multidrug-resistant Candida infections.

Objective: To evaluate the first 3 years of compliance with the American College of Surgeons Commission on Cancer (CoC) Operative Standards. Background: CoC implemented evidence-based standards to improve the quality of sentinel lymph node biopsy and axillary lymph node dissection for breast cancer (operative standards 5.3 and 5.4), wide local excision for melanoma (5.5), colectomy for colon cancer (5.6), proctectomy for rectal cancer (5.7), and pulmonary resection for lung cancer (5.8) at ∼1400 programs treating >74% of US cancer patients. Each operative standard defines a technical element of the operation and structured documentation. Methods: Compliance data are from site visits conducted between January 1, 2022, and December 31, 2024 (implementation/site visits began in 2021/2022 for 5.7 and 5.8 and 2023/2024 for 5.3–5.6). Compliance with each operative standard was determined by evaluation of 7 operative (5.3–5.6) or pathology (5.7, 5.8) reports. Deficiency in technical performance, documentation, or both was considered noncompliance. Results: Reviewers conducted 974 site visits of Comprehensive Community (44%), Community (23%), Academic Comprehensive (16%), network (12%), NCI-Designated Comprehensive (4%), and other (1%) cancer programs. Program compliance rates ranged from 53% to 88%. Documentation noncompliance was more common for standards 5.3 to 5.6 (based on operative reports), and technical noncompliance was more common for 5.7 and 5.8 (based on pathology reports). Compliance significantly (P=0.006) varied by program type for 5.8 (highest: 66% at NCI-designated Comprehensive programs; lowest: 37% at Community Cancer programs). Conclusions: Early compliance with CoC operative standards varied, indicating local and large-scale national quality improvement efforts are needed.