Citations

BACKGROUND: Social determinants of health (SDOH) are associated with adverse cancer outcomes, yet the prevalence and impact of SDOH screening across Commission on Cancer (CoC)-accredited programs are unknown. We evaluated national SDOH screening practices and their association with adherence to CoC quality measures. STUDY DESIGN: A cross-sectional survey of 1,445 CoC-accredited programs (October to December 2024) was linked to National Cancer Database data (2020 to 2022). Adult patients treated at 435 responding hospitals (30.1%) were included. Programs were categorized by routine outpatient SDOH screening status. Multivariable logistic regression assessed associations between screening and receipt of quality measure–concordant care, adjusting for screening duration, age, race, ethnicity, Charlson Comorbidity Index, insurance status, rurality, and program type or case count. RESULTS: Of 435 programs, 165 (37.9%) reported routine SDOH screening. Screening programs more frequently treated ≥10% Medicaid or uninsured patients (29.1% vs 19.6%, p = 0.023). Mean performance was higher at screening hospitals for breast radiation within 60 days (66.6% vs 64.6%, p = 0.046), colon adjuvant chemotherapy within 120 days (84.6% vs 81.9%, p = 0.018), and lung systemic therapy within 90 days (77.2% vs 75.4%, p = 0.043). On adjusted analysis, screening for more than 3 years was independently associated with timely colon adjuvant chemotherapy (odds ratio 1.05; 95% CI 1.01 to 1.07; p = 0.033). Findings persisted after excluding safety net hospitals. CONCLUSIONS: Only one-third of responding CoC programs routinely screen for SDOH. Sustained screening was independently associated with improved adherence to time-sensitive colon cancer chemotherapy, supporting integration of patient-level SDOH assessment into oncology care delivery.

ABSTRACT Background and Aims Pruritus is a frequent and debilitating symptom in primary biliary cholangitis (PBC), substantially impairing sleep, mood and quality of life. Peroxisome proliferator‐activated receptor (PPAR) agonists are promising second‐line therapies for patients with an inadequate response to ursodeoxycholic acid (UDCA). We conducted a systematic review and meta‐analysis to evaluate the efficacy of PPAR agonists on pruritus and health‐related quality of life (HRQoL) in PBC. Methods We systematically searched for randomised placebo‐controlled trials (RCTs) of PPAR agonists in PBC through December 2025. Eligible studies reported validated pruritus or HRQoL outcomes. Main outcomes were NRS and PBC‐40 total score. Pooled estimates were calculated using random‐effects models and expressed as mean differences (MD) with 95% confidence intervals (CI). Results Five RCTs evaluating bezafibrate, elafibranor and seladelpar ( n = 660; 390 PPAR agonist; 270 placebo) met the inclusion criteria. For pruritus intensity analyses, data were restricted to participants with moderate‐to‐severe baseline symptoms (NRS ≥ 4) when available. PPAR agonists significantly reduced NRS scores at 3 months (MD, −1.39; 95% CI: −2.49 to −0.29), 6 months (MD, −1.17; 95% CI: −1.96 to −0.38) and 12 months (MD, −1.73; 95% CI, −3.00 to −0.46); in individual agent analyses, bezafibrate and seladelpar reached statistical significance at two or more time points. While improvements were also noted in PBC‐40 itch‐domain and 5D‐itch score, an impact on overall HRQoL as reflected by PBC‐40 total score could not be demonstrated, with a lower level of certainty. Conclusions PPAR agonists, notably bezafibrate and seladelpar, reduce pruritus severity in PBC patients with moderate‐to‐severe symptoms and consistently improve itch‐specific outcomes. However, effects on global HRQoL remain uncertain. These findings underscore the incorporation of validated, symptom‐focused endpoints in future PBC trials.

Epilepsy-related mortality, including Sudden Unexpected Death in Epilepsy and suicide, is a crucial topic within the interdisciplinary scope of caring for people with epilepsy (PWE). This review highlights best practices that emphasize proactive education for patients, caregivers, and communities, as well as evidence-based strategies and interventions for seizure management aimed at reducing mortality risk. It further underscores the essential contribution of the multidisciplinary care team in managing epilepsy-related mortality, highlighting considerations such as comorbid behavioral health conditions, challenges with treatment adherence, the use of the ketogenic diet, and the impact of social determinants of health and health disparities on historically marginalized populations. The authors provide actionable insights to address these challenges and barriers and enhance the outcomes and quality of life for PWE and their loved ones.

Background: Acute myeloid leukemia (AML) with CBFB::MYH11 fusion and myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions (MLN-TK) are genetically defined and typically mutually exclusive entities. Case Presentation: We report a unique case of de novo AML harboring two clonal, transcriptionally active class-defining fusions: CBFB::MYH11 and GOLGA4::PDGFRB. A 61-year-old woman presented with leukocytosis with neutrophilia, eosinophilia, and monocytosis; circulating blasts; and a markedly hypercellular marrow. Cytogenetic analysis revealed inv(16)(p13.1q22) and t(3;5)(p21;q32) in all 20 metaphases, and RNA sequencing confirmed expression of both CBFB::MYH11 and GOLGA4::PDGFRB fusions. In addition, an oncogenic WT1 frameshift variant was identified. Hematopathologic findings were largely consistent with AML with CBFB::MYH11 fusion but exhibited features reminiscent of PDGFRB-rearranged MLN-TK. The patient achieved complete remission following the standard 7 + 3 induction chemotherapy regimen for AML with gemtuzumab ozogamicin. Conclusions: This case illustrates the diagnostic challenges posed by concomitant class-defining alterations in hematologic neoplasms and underscores the importance of integrated genomic assessment.

ABSTRACT Background A rare autosomal recessive disorder known as hyperphosphatasia with impaired intellectual development syndrome (HPMRS), also referred to as Mabry syndrome, is caused by a deficiency in glycosylphosphatidylinositol (GPI). Elevated blood alkaline phosphatase (ALP) levels, cognitive impairment, and epileptic seizures are among its key features. These pathways are involved in the synthesis of GPI and the transfer of GPI anchor to the proteins, fatty acid remodeling, and transport of GPI‐anchored proteins (GPI‐APs). Methods Using exome sequencing (ES), the cause of hyperphosphatasia and ID of an 11‐year‐old girl from non‐consanguineous parents was solved, and the results confirmed by direct Sanger sequencing method. Results ES identified a novel homozygous pathogenic variant, PGAP3 (NM_033419.5: c.202dupT, p.Cys68fs*2) that segregated within the family members. To the best of our knowledge at the time of writing this manuscript, this variant has not been reported in HPMRS in the literature. Conclusion Our findings indicate that the p.Cys68fs*2 variant may disrupt normal protein function and likely disrupt its interaction with its associated partner proteins, potentially leading to disruption of GPI biosynthesis. We present a novel pathogenic variant thus expanding the phenotypic and mutational spectrum of this extremely rare disorder. Elevated ALP assays and ES are valuable diagnostic tools for HPMRS. Additionally, a comprehensive literature review was conducted to expand the phenotypic and genotypic spectrum within the PGAP3 gene responsible for HPMRS.

Abstract Models that estimate the probability of an adverse clinical outcome require an operational cutoff to translate continuous estimated probabilities into discrete labels that can trigger clinical action. Although statistical methods identify ‘optimal’ cut-offs, threshold selection ultimately reflects value judgments regarding harm tolerance, resource allocation, and workflow feasibility. We describe a governance-informed approach to selecting a deployment threshold for an asthma exacerbation (AE) prediction model integrated into clinical workflows. Using prevalence-adjusted performance metrics and real-world provider capacity modeling, we evaluated multiple candidate thresholds and quantified downstream workload and missed-event trade-offs. We demonstrate that statistically optimal thresholds may produce operationally infeasible alert volumes or unacceptable miss rates. We propose a structured threshold governance framework integrating statistical performance, clinical utility, stakeholder input, and human oversight safeguards. This case illustrates how threshold decisions should be treated as organizational governance processes rather than purely technical optimizations.

Abstract Lichen Planopilaris (LPP) is a lymphocyte-mediated scarring alopecia characterized by progressive follicular destruction and fibrosis. In this clinical trial, patients with biopsy proven LPP were treated with deucravacitinib (an oral inhibitor of tyrosine kinase 2 (TYK2)) 6 mg BID for 24 weeks (NCT-06091956). Bulk and single-cell RNA sequencing was performed on paired pre- and post-treatment scalp biopsies from baseline and week 4. Patients (N=10) demonstrated improvements in PGA (88.9%, p=0.008), LPPAI (−2.3 points, SD 1.1, p=0.002) and Skindex-16 (−21.0 points, SD 22.1, p=0.014) scores at week 24. Bulk transcriptomic analysis of untreated LPP revealed upregulation of type I Interferon (IFN)-stimulated genes and pathways related to inflammation, immune activation, keratinization, and extracellular matrix remodelling, with downregulation of immune and inflammatory pathways following treatment. Single-cell RNA-seq of LPP was characterized by enrichment of CD8+GZMK+ T cells which showed downregulation of T-cell receptor signaling as well as antiviral pathways with treatment. Basal keratinocytes exhibited reduced cytokine and interferon signaling and decreased communication with NK cells following treatment. CCL19+ fibroblasts were prominent in untreated disease was attenuated after treatment, with downregulation of type I IFN signaling. Selective TYK2 inhibition with deucravacitinib effectively suppresses these inflammatory circuits in LPP and represents a promising therapeutic strategy.