Citations

Importance Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis characterized by sterile ulcerative skin lesions. Multiple comorbidities and clinical features have been associated with PG, but no standardized guidelines exist for classifying PG phenotypes. Objective To develop an expert-established classification framework for PG phenotypes to inform treatment guidelines and future research endeavors. Evidence Review In this modified Delphi consensus study that included 23 board-certified dermatologists and Medical Dermatology Society members with expertise in PG, panelists completed 5 rounds of anonymous, iterative online surveys that were administered from December 2023 through July 2025. Before the beginning of the consensus exercise, a literature review was performed by nonvoting researchers to summarize existing data on PG clinical associations and comorbidities. A PubMed search from inception to September 2023 identified observational studies, narrative reviews, systematic reviews, and meta-analyses describing PG clinical associations and comorbidities that were published in English. Experts indicated their agreement with proposed PG phenotypes and disease modifiers with a consensus threshold of 70% or greater. Anonymous comments and aggregated results were presented in each subsequent round. In the final round, a framework of PG phenotypes and disease modifiers was proposed for agreement. Findings Twenty-three board-certified dermatologists and Medical Dermatology Society members with expertise in PG completed 5 rounds of iterative surveys. Consensus was reached on the final set of PG phenotypes and disease modifiers, with 83% of experts in agreement. PG phenotypes were overall classified into 2 major groups: PG with autoinflammatory syndromes and nonsyndromic PG. Nonsyndromic PG included 4 phenotypes: inflammatory bowel disease–associated PG, PG in association with hematologic cancers and blood dyscrasias, drug-induced PG, and other (including idiopathic) PG. Disease modifiers of PG phenotype presentations included involvement of special sites (head/neck, genitals, or peristomal skin) and extracutaneous manifestations. Conclusions and Relevance This expert-established, descriptive framework provides a standardized classification system for distinct PG phenotypes and its modifiers. This nomenclature may inform upcoming clinical guidelines and allow for consistency in reporting epidemiological research and outcomes among patients with PG.

Abstract Objective Epilepsy duration is a modifiable risk factor in the outcome of definitive epilepsy surgery; however, an analogous effect in palliative procedures has not been shown. We reviewed the Pediatric Epilepsy Surgery Database data for an association between epilepsy duration and seizure reduction in palliative procedures. Methods Patients enrolled between January 2018 and April 2025 who underwent their first epilepsy surgery with palliative intent with 6 months of follow‐up were included. Procedures included neuromodulation, corpus callosotomy, hemispherotomy, lesionectomy, and lobectomy where surgical intent was not seizure freedom. Outcomes of seizure freedom, 90% seizure reduction, and 50% seizure reduction were considered at 6–12 months and >12 months from surgery. Duration from epilepsy onset to surgery was compared for patients above and below each outcome threshold at each time point. Logistic regression analysis for the association between epilepsy duration and seizure reduction adjusted for potential confounders including procedure type, etiology, and other clinical factors. Logistic regression analysis was performed on the overall cohort and subgroups of patients with each procedure. Results A total of 588 patients were included. Initial univariate analysis suggested that epilepsy duration at time of surgery was significantly associated with seizure freedom and 90% seizure reduction at both 6–12 months and >12 months. After adjusting for confounders, only seizure freedom at >12 months was significantly associated with duration of epilepsy. When individual procedures were considered, only lobectomy was sensitive to duration of epilepsy in multivariate analysis, with significant impacts on >50% and >90% seizure reduction at >12 months. Lesional epilepsy predicted seizure freedom at >12 months. Neuromodulation and corpus callosotomy were less likely to achieve seizure reduction than other procedures. Significance We did not find an association between early epilepsy surgery and seizure reduction. This reflects the heterogeneity of our population, including different types of surgical procedures and lesional and nonlesional epilepsies.

ABSTRACT The recent inclusion of the Merlin clinicopathologic–gene expression profile (CP‐GEP) assay in the National Comprehensive Cancer Network (NCCN) Melanoma Guidelines represents an important milestone in the clinical integration of molecular testing for cutaneous melanoma. Unlike earlier melanoma gene expression profile (GEP) assays, which focused primarily on prognostic risk stratification, CP‐GEP was specifically developed to predict sentinel lymph node (SLN) metastasis risk by identifying early metastatic competence within primary melanomas, with additional prognostic utility. This review discusses the biological evidence supporting CP‐GEP and examines how unbiased transcriptomic discovery converged with established insights from cancer cell biology, integrin signaling, focal adhesions, and extracellular matrix (ECM) remodeling to shape its conceptual framework. We further discuss how CP‐GEP captures a transformation‐associated biological state centered on an integrin‐ and TGF‐β–dependent signaling axis ( ITGB3 , TGFBR1 ) that promotes pericellular proteolysis and ECM remodeling ( PLAT , SERPINE2 , LOXL4 ), inflammatory and angiogenic signaling ( CXCL8 , GDF15 ), and melanocytic lineage identity ( MLANA ). Collectively, these genes identify a dissemination‐competent phenotype that is detectable within primary tumors before clinically apparent metastasis. Overall, the biological framework supporting CP‐GEP reinforces the concept that altered adhesion signaling and ECM remodeling are central drivers of early melanoma metastasis and represent clinically actionable biomarkers for individualized melanoma management. image

Abstract Germinal center (GC)-derived lymphomas arise within a specialized immune ecosystem, yet whether malignant cells direct its remodeling remains unclear. Integrating genomic, transcriptomic, spatial, and functional analyses across follicular lymphoma and diffuse large B-cell lymphoma, we define a developmental framework linking malignant B-cell differentiation state to tumor microenvironment (TME) organization. Rather than segregating by histology, lymphomas align along a shared differentiation continuum in which proliferative dark zone (DZ) states associate with immune-depleted TMEs, whereas post-GC/memory B-cell (MBC) states drive inflamed but immunosuppressed TMEs. Spatial profiling reveals collapse of GC architecture and emergence of suppressive myeloid niches along this trajectory. Single-cell lineage reconstruction uncovers a DZ-to-MBC developmental axis underlying lymphoma evolution. Genetic reprogramming in vivo demonstrates that malignant differentiation state is sufficient to instruct TME remodeling. Collectively, these findings establish malignant differentiation state as a causal determinant of immune architecture across GC-derived lymphomas and identify lineage-directed immune reprogramming as a potential therapeutic strategy.

Abstract Invasive lobular breast carcinoma (ILC) is the most common special histological subtype of breast cancer, which accounts for 10-15% of all cases. To study the phenotype characteristics, metastatic growth kinetic and immune microenvironment of ILC, we developed an orthotopically transplantable cell line model from the spontaneous mammary fat pad tumor of CDH1-PTEN dual knockout C57BL/6 mouse with Cre-loxP system, designated CPT6. CPT6 recapitulates single-file growth pattern of human ILC, with pleomorphic features and a high mitotic index. RNA sequencing together with whole exome sequencing reveals a luminal A subtype with targetable driver mutations such as Kras G12C. As a novel orthotopically transplantable ILC model in immune competent mice, CPT6 shows robust in vivo growth and metastatic rate, and has moderate immunogenicity which appears to be T-cell independent. We also profiled the immune microenvironment of CPT6, revealing a myeloid-rich environment with dominant M2-macrophage population, which is concordant with human ILC. In summary, this model recapitulates human ILC phenotype and represents a valuable preclinical platform for evaluating immunotherapy and other therapeutic strategies for invasive lobular breast carcinoma.

Scientific evidence regarding AKI and acute kidney care has advanced in recent years. However, a knowledge gap remains on the implementation of these evidence-based practices (EBPs) into clinical care. Implementation science (IS) is focused on ensuring that this knowledge is translated in an effective, efficient and sustainable fashion. Objectives: 1) Define the current status of IS; 2) Define a roadmap for accelerating IS with a focus on patient/care partner advocacy, digital tool application, social determinants of health, and resource-limited settings; and 3) Develop a robust and broad research agenda incorporating IS methodology into the programs. Evidence Review: ADQI XXXV was conducted through a modified Delphi process with virtual meetings preceding an in-person meeting. Five workgroups were determined a priori to focus on 1) IS definitions and methods applicable to AKI and acute kidney care; 2) IS literature in AKI and acute kidney care; 3) Innovations in IS to accelerate the adoption, adherence to, and sustainment of EBPs in AKI and acute kidney care; 4) IS methods in resource-limited settings; and 5) Recommendations to identify and evaluate EBPs that are ready for implementation or de-implementation. Prior to the in-person meeting, each workgroup met virtually to review the literature and develop framework questions to address their objectives. During the two-day in person meeting, through iterative discussions, questions and supporting statements were finalized. These questions and statements were agreed upon through voting to achieve consensus, defined as agreement of ≥80%. Conclusions and Relevance: We report a structured multidisciplinary consensus for defining the role of IS in AKI and acute kidney care. Future programs should address these consensus questions and apply these statements along with IS methodology in the translation of science into clinical practice and the implementation/de-implementation of EBPs in clinical care.

BMT CTN 1506 ("MORPHO") was a phase 3 study of post-hematopoietic cell transplantation (HCT) maintenance with gilteritinib versus placebo for patients with FLT3-ITD-mutated acute myeloid leukemia (AML) in first remission. Subgroup analysis indicated a significant benefit of post-HCT gilteritinib for participants in North America, but no benefit for those in Europe or Asia. We conducted a post-hoc analysis of the data focusing on days from AML diagnosis to HCT, pre-HCT FLT3 inhibitor use, and FLT3-ITD measurable residual disease (MRD). Participants transplanted < 120 days from AML diagnosis and/or those treated with FLT3 inhibition pre-HCT were more likely to have improved survival from post-HCT gilteritinib. Pre-HCT MRD levels were higher (P = 0.001) in participants transplanted within 120 days from diagnosis and in those treated with a FLT3 inhibitor pre-HCT and transplanted within 120 days (P = 0.008). Pre-HCT MRD was dependent on both FLT3 inhibitor use and time to HCT, as participants treated with successive courses of chemotherapy + FLT3 inhibition had successively lower MRD by the time of HCT. Time from AML diagnosis to HCT and pre-HCT FLT3 inhibitor use both appeared to impact MRD levels immediately prior to HCT, and geographic differences in these two practice patterns likely accounted for the observed regional differences in benefit from post-HCT gilteritinib. Increasing the number of courses of treatment pre-HCT may lower MRD sufficiently to eliminate the need for post-HCT inhibition, but with a presumed risk of some patients experiencing early progression. This trial was registered at www.clinicaltrials.gov as #NCT02997202.