Citations

Abstract Anaplastic large cell lymphomas (ALCLs) are CD30+ T-cell lymphomas that share pathologic features but differ in presentation, outcome, and genetics. Current classification incorporates clinical presentation and anaplastic lymphoma kinase (ALK) status but inadequately addresses molecular heterogeneity and therapeutic vulnerabilities. We studied 689 patients with ALCL in the LLMPP (Lymphoma/Leukemia Molecular Profiling Project) and performed expert consensus review, genetic subtyping (ALK, DUSP22, TP63, and triple negative), and immunohistochemistry for phosphorylated STAT3Tyr705. RNA sequencing with unsupervised gene expression profiling in 393 patients identified 2 main molecular types of ALCL that could be predicted with 91% accuracy based on the presence (type I) or absence (type II) of phosphorylated STAT3Y705 expression. Type I ALCLs included ALK+ ALCL and a subset of triple-negative ALCLs (TN-I); type II ALCLs included tumors with DUSP22 and/or TP63 rearrangements and the remaining triple-negative ALCLs (TN-II). Type I ALCLs were enriched for JAK-STAT3, whereas type II ALCLs were enriched for non–tyrosine kinase pathways, particularly epigenetic regulators such as EZH2. Immunohistochemistry showed overexpression of EZH2 and its trimethylated substrate H3K27. Prognosis in systemic ALCL was favorable for DUSP22-rearranged ALCL (5-year overall survival, 95%) and ALK+ ALCL (88%), intermediate for triple-negative ALCL (TN-I, 52% and TN-II, 37%), and poor for TP63-rearranged ALCL (0%). We introduce an integrated molecular classification that preserves currently diagnosed ALCL entities but identifies 4 molecularly distinct ALK− ALCL subtypes (DUSP22-rearranged, TP63-rearranged, TN-I, and TN-II). This classification can be easily implemented on paraffin tissue in routine practice or clinical trials, and stratifies ALCL into diagnostically, prognostically, biologically, and potentially therapeutically relevant subtypes.

Objective: To review the pharmacology, usage, efficacy, and safety of fenfluramine in treating seizures in pediatric patients with Lennox-Gastaut syndrome or Dravet syndrome. Data sources: The PubMed database was searched for studies using the search terms “Lennox-Gastaut Syndrome,” “Dravet Syndrome,” “fenfluramine,” and “Fintepla©.” Study selection and data extraction: Articles were selected based on the following criteria: published in English, published between January 1950 and September 2025, and included clinical relevancy for pharmacology, efficacy, and adverse events. Data synthesis: In a phase 3 trial, patients with Lennox-Gastaut syndrome experienced a median 26.5% decrease in frequency of drop seizures when taking the 0.7 mg/kg/d dose. In a 2-part phase 2 trial, 54% of patients with Dravet syndrome concurrently taking stiripentol experienced a >50% decrease in monthly seizures at a dosage of 0.4 mg/kg/d; 72.9% of patients with Dravet syndrome not concurrently taking stiripentol experienced a >50% decrease in monthly seizures at a dosage of 0.7 mg/kg/d. Most common adverse effects in both trials included lethargy, decreased weight, and decreased appetite. Relevance to patient care and clinical practice: Fenfluramine’s dual mechanism of action makes it uniquely suited to reduce seizure activity after previous failures in treatment. Some providers are hesitant to prescribe fenfluramine due to its historical association with severe cardiovascular risks. However, proper dosage and titration, as well as adherence to the Risk Evaluation and Mitigation Strategy program can sufficiently mitigate risk for the outcome of seizure reduction and increased quality of life. Conclusions: As seen through the results of multiple clinical trials, fenfluramine can provide significant seizure reduction for Lennox-Gastaut and Dravet patients with treatment-resistant seizures. Risks can be mitigated through adherence to proper programs and schedules, and can provide enough benefits to outweigh risks in patients with particularly resistant epilepsies.

Aims Data on revision of unicompartmental knee arthroplasty (UKA) to total knee arthroplasty (TKA) are limited by low patient numbers and short-term follow-up. This study evaluated the mid-term outcomes of revision of UKA to TKA focusing on implant survival, radiological results, and clinical outcomes in a large series. Methods We identified 235 revisions of UKA to TKA performed between 1995 and 2022 utilizing our institutional total joint registry. The mean age was 65 years (SD 10), mean BMI was 32 kg/m 2 (SD 6), and 50% were female (n = 118). The most common indications for revision were aseptic loosening (37%; n = 83), progression of arthritis in adjacent compartments (35%; n = 81), and unexplained pain (20%; n = 47). The mean time from UKA to revision to a TKA was four years (26 days to 15 years). Posterior-stabilized constructs were used in 78% of the revisions (n = 184), varus-valgus constrained implants in 14% (n = 33), and cruciate-retaining implants in 7% (n = 16). Metaphyseal fixation devices were used in 8% of cases (n = 18) and augments in 31% (n = 73). Kaplan-Meier implant survival analyses were performed, radiographs reviewed, and clinical outcomes were measured with Knee Society Scores (KSSs). Mean follow-up was eight years (2 to 25). Results The five-year survival free of any re-revision was 93% (95% CI 89 to 97). There were 17 further re-revisions with femoral and/or tibial aseptic loosening (n = 7), periprosthetic joint infection (n = 4), and stiffness (n = 2) being the most common indications. The five-year survival free of any reoperation was 87% (95% CI 83 to 92). Stiffness (n = 7) and unresurfaced patellar clunk/crepitus (n = 4) were the most common indications for reoperations without implant exchange. There were 25 nonoperative postoperative complications, most commonly stiffness (n = 5), flexion instability (n = 4), and haematoma (n = 4). No unrevised TKAs showed signs of radiological loosening. KSS function score improved from 54 (SD 18) to 69 (SD 26; p = 0.003). Conclusion In this large series of 235 revisions of UKA to TKA, the five-year survival of the TKAs free of re-revision was good. Our data suggest that the implant survival and clinical outcomes were inferior to primary TKA. Tibial component aseptic loosening was the most common reason for re-revision. Cite this article: Bone Joint J 2025;107-B(12):1281–1287.

Aims The aim of this study was to achieve consensus for important topics related to periprosthetic infection (PJI) in orthopaedic oncology, and to identify areas for future research. Methods In January 2024, the Birmingham Orthopaedic Oncology Meeting (BOOM) held in Birmingham, UK, gathered 309 delegates from 53 countries to debate 20 consensus statements on PJI in orthopaedic oncology using a modified Delphi process. Results Of 20 questions and statements on PJI in orthopaedic oncology, none achieved unanimous consensus, 18 achieved strong consensus, one achieved moderate consensus, and one achieved weak consensus. The statements that reached consensus with notable agreement were on the prophylaxis of infection, management of leaking wounds, and surgical strategies for the treatment of PJI. Short-duration antibiotic prophylaxis was deemed as effective as longer courses for lower-risk reconstructions, and aggressive management was recommended for wounds draining beyond five to seven days to prevent deep infection. Furthermore, single-stage, two-stage, and 1.5-stage revision were recognized as valid strategies, with two-stage revision remaining the most reliable. The statements that did not achieve consensus were on the role of debridement, antibiotics, and implant retention and prolonged antibiotic use post-revision. Conclusion The BOOM meeting achieved consensus for important topics on periprosthetic infection in orthopaedic oncology, but highlighted the low quality of the underlying evidence. This study has provided recommendations for the treatment of leaky wounds, duration of postoperative antibiotic prophylaxis, and choice of revision strategy. Cite this article: Bone Joint J 2025;107-B(12):1352–1359.

Abstract Objectives The primary objective of this research is to assess the content coverage of nursing data within a publicly available common data model (CDM), focusing on how nursing data, documented in flowsheets, are represented within the model. Materials and Methods This mapping study was informed by previous evaluation studies and serves as a framework for evaluating information resources, including to guide development and implementation. The overall research process consists of 4 steps: (1) identify a CDM; (2) define evaluation criteria; (3) map nursing flowsheet data; and (4) apply evaluation criteria. Results Overall, 65.5% (n = 1170) of the flowsheet concepts were mapped to Systematized Nomenclature of Medicine—Clinical Terms (SNOMED CT) and Logical Observation Identifiers Names and Codes (LOINC) target codes and 56.0% (n = 1831) of the flowsheet values were mapped to SNOMED CT and LOINC target codes. The flowsheet concepts had a higher average mapping time per concept/reviewer (1.19 min) as compared to the average mapping time per value/reviewer (0.64 min). Discussion This mapping study demonstrated the progress and ongoing challenges of mapping nursing data to a national common data model. However, the ability to use nursing data at scale in a national CDM remains limited until more comprehensive mapping is completed. Conclusion This mapping study identifies a significant gap in integrating nursing data into a national common data model, highlighting an opportunity to enhance patient care through improved real-time insights and evidence-based nursing practices. Addressing this gap can help shape policies that prioritize the inclusion of nursing data. Additionally, aligning nursing data at scale can advance research, increase efficiency, and optimize nurse-sensitive patient outcomes.

Parkinson's disease (PD) is a progressive neurodegenerative disease with multiple manifestations including both motor and non-motor symptoms. One manifestation of PD that is often overlooked is the sexual dysfunction (SD) that patients may experience. Individuals with PD can experience impairment in sexual desire, arousal or lubrication, orgasm, ejaculation, pain and the physical aspect of intimacy. This article aims to provide an overview of the current practices in the evaluation and treatment of sexual dysfunction in men in the context PD. Note that this article focuses on the male population as it reviews the available American Urology Association practice guidelines many practitioners follow, which focus on the male population. Sexual dysfunction guidelines for the female population are much more limited, and future work should review the existing literature and gaps to provide a more robust understanding of sexual dysfunction in PD. PD represents a particularly vulnerable population for development of sexual dysfunction given the multifactorial nature of its manifestations. Given its profound impact on not only the patient, but their partner, it is important to be aware of the various manifestations of SD when evaluating individuals with PD. Through thorough history taking and targeted psychosexual evaluation, we as practitioners can ensure a more holistic and comprehensive approach to caring for individuals with PD.

Background: Discovering risk biomarkers in small benign breast disease (BBD) biopsies is constrained by scarce tissue and microanatomic heterogeneity of terminal duct lobular units (TDLUs). We tested whether tissue-sparing tissue microarray (TMA)–based Digital Spatial Profiling (DSP) can deliver reproducible, biologically coherent protein measurements across benign lobules and breast cancers (BCs), and how well DSP aligns with standard immunoassays. Methods: We performed a pilot using tissues from the Mayo Clinic BBD cohort using TMAs representing four contexts: terminal duct lobular units (TDLUs) from BBD biopsies preceding BC and matched BBD-controls, subsequent BCs, and BC-associated TDLUs. We profiled 79 proteins by DSP (37 retained after QC) and benchmarked against chromogenic IHC and OPAL immunofluorescence. Reproducibility was evaluated using intraclass correlation coefficients (ICCs), cross-platform agreement (weighted kappa), marker correlations, and mixed-effects models with false-discovery-rate (FDR) control. Results: We analyzed 368 BBD-TDLU cores (88 cases; 88 controls), 204 BC cores and 110 BC-associated TDLU cores. ICCs were highest in BC tissues, and lower in BC-associated TDLUs and BBD-TDLUs. Agreement was slight–to-fair in TDLUs but moderate (ER/PR) to substantial (BCL2) in BC. DSP recapitulated expected immunologic correlations (CD45 with T-cell, B-cell, and macrophage markers) and tissue-type gradients (BC > BC-associated TDLUs > BBD-TDLUs). Exploratory case–control differences in BBD-TDLUs did not persist after FDR control. Conclusions: TMA-based DSP is feasible in archival breast tissues and yields biologically coherent, cross-platform-benchmarked profiles that are particularly robust in BC, while conserving scarce TDLUS and clarifying current limits of single-marker risk stratification from benign lobules. These data provide a foundation for refined sampling and expanded panels in future TDLU-focused studies.

Goals: Describe the establishment and expansion of a global gastrointestinal (GI) partnership and its impact on the advancement of GI care in Rwanda. Background: GI disease disproportionately affects low- and middle-income countries. In Rwanda, governmental and nonprofit efforts have made significant progress in expanding access to health care in the wake of the 1994 genocide; however, specialized care remains largely unrecognized or inaccessible. In response, the Rwanda Ministry of Health established a partnership with an international gastroenterology NGO to address this critical need. Study: We present summative data generated by this partnership. To inform future global GI programs, we provide lessons learned and details about Rwanda’s successful establishment of an in-country, self-sustainable, and locally governed gastroenterology training program. Results: From 2017 to 2023, the partnership expanded the number of clinical sites receiving care from 4 to 11. Total procedural volume increased from 244 to 1069. Most common presenting upper GI symptoms included dyspepsia, reflux, and emesis, while most common lower GI symptoms included hematochezia and constipation. Since 2017, this partnership has increased the number of faculty volunteering in Rwanda (and Rwandan clinicians studying in US academic medical centers), expanded its geographical reach, assisted in the creation of a GI fellowship, and enabled Rwanda to become an East African hub for medical education. Conclusions: Lessons learned across ethical, financial, leadership, cultural, and medical domains from the successful establishment and expansion of an international GI partnership in Rwanda provides invaluable insights to guide development of future models of health care in emerging economies.

Purpose: Patients with chronic obstructive pulmonary disease (COPD) and symptoms of depression have increased health care utilization and lower quality of life. There is a knowledge gap regarding feasible and effective approaches for the management of depressive symptoms in patients with COPD. The objective of this randomized clinical trial sub-study is to determine whether 12-weeks of home-based pulmonary rehabilitation (PR) with health coaching is feasible and effective for improving depressive symptoms in patients with COPD. Methods: Patients with severe COPD and symptoms of depression (Patient Health Questionnaire-9 [PHQ-9] ≥5 points) randomized to the intervention (N = 90) or control (N = 78) groups in the parent study were included. The primary outcome of this sub-study was the 12-week change in the PHQ-9 score. Secondary outcomes included dyspnea, fatigue, emotions, and mastery (self-management) as measured by the Chronic Respiratory Questionnaire (CRQ) and daily physical activity and sleep measured by ActiGraph. Results: Home-based PR with health coaching was associated with improved measures of depression ( P = .07), dyspnea, fatigue, emotion, and mastery (self-management) ( P < .001). Being in the intervention group was associated with a higher odds of improving by the minimal clinically important difference on the PHQ-9 (OR = 2.10: 95% CI, 1.06-4.27), CRQ-Dyspnea (OR = 2.37: 95% CI, 1.11-5.26), CRQ-Fatigue (OR = 3.35: 95% CI, 1.59-7.35), CRQ-Emotions (OR = 4.59: 95% CI, 2.13-10.40), and CRQ-Mastery (OR = 3.36: 95% CI 1.60-7.28) after multivariable adjustment. The improvement in depression symptoms was maintained for 3 and 6 months after finishing the intervention. Conclusion: Home-based PR with health coaching is feasible and possibly effective in improving depressive symptoms and quality of life in patients with COPD and symptoms of depression.