Citations

Abstract Myelodysplastic syndromes/neoplasms (MDSs) are heterogeneous stem cell malignancies characterized by poor prognosis and no curative therapies outside of allogeneic hematopoietic stem cell transplantation. Despite some recent approvals by the US Food and Drug Administration, (eg, luspatercept, ivosidenib, decitabine/cedazuridine, and imetelstat), there has been little progress in the development of truly transformative therapies for the treatment of patients with MDS. Challenges to advancing drug development in MDS are multifold but may be grouped into specific categories, including criteria for risk stratification and eligibility, response definitions, time-to-event end points, transfusion end points, functional assessments, and biomarker development. Strategies to address these challenges and optimize future clinical trial design for patients with MDS are presented here.

Purpose In lymphomas, the Deauville score (DS) standardizes 18F-FDG PET treatment response assessments. We assessed interobserver agreement of the DS and developed a quantitative PET-based parameter to minimize subjectivity of response assessments. Methods PET scans performed within the Children’s Oncology Group AHOD0831 study were analyzed. One hundred one scans obtained after the first cycle of chemotherapy (PET1) and 83 obtained after the second cycle (PET2) were eligible for inclusion. Each scan was assigned a DS by 2 nuclear medicine radiologists and a Hodgkin lymphoma index (HLI), defined as the ratio of the tumor’s SUVmax or SUVpeak to the liver’s SUVmean. Cohen κ coefficient measured the rate of agreement of the DS assigned by the 2 radiologists. Receiver operating characteristic curves and the Youden index were used with the consensus DS to identify an optimal HLI cutoff value to distinguish PET-negative from PET-positive images. For each HLI cutoff value, sensitivity, specificity, and accuracy were calculated. Results Interobserver agreement in DS was moderate (PET1: κ = 0.480, P < 0.001; PET2: κ = 0.428, P < 0.001). On PET1, the optimal cutoff values for HLImax were 1.19 for DS2/DS3 and 1.78 for DS3/DS4, and for HLIpeak were 1.19 for DS2/DS3 and 1.44 for DS3/DS4. On PET2 images, the corresponding values were 1.18, 1.58, 0.94, and 1.26. The most accurate predictor was HLImax on PET2 when scans were dichotomized as DS1–DS3 versus DS4–DS5 (accuracy, 92.8%; sensitivity, 100%; specificity, 91.8%). Conclusion The HLI provides an objective, quantitative measure of disease response and thus may improve interreader agreement for lymphoma response assessments.

AbstractAs rates of obesity rise worldwide, incidence of metabolic dysfunction‐associated steatotic liver disease (MASLD), formerly referred to as nonalcoholic fatty liver disease, is increasing, worsening the burden of healthcare systems. The council of the Federation of International Societies for Pediatric Gastroenterology, Hepatology, and Nutrition (FISPGHAN) identified the topic of MASLD epidemiology, treatment, and prevention as a global priority issue to be addressed by an expert team, with the goal to describe feasible and evidence‐based actions that may contribute to reducing MASLD risk. The FISPGHAN member societies nominated experts in the field. The FISPGHAN council selected and appointed members of the expert team and a chair. The subtopics included in this manuscript were chosen through a consensus of the experts involved. We review the epidemiology, natural history, and screening and management. We further expand to relevant public health measures aimed at MASLD prevention, including identifying interventions that could reduce risk factors (environmental and iatrogenic), optimize maternal and newborn health, and support healthier lifestyles for older children and adolescents on a local, national, and international scale. While recognizing that various aspects of population health and public policy can shape MASLD risk, we also review what we can do on an individual level to support our patients to reduce the significant burden of this ever rising disease in pediatrics.

Esophageal squamous cell carcinoma (ESCC) remains a significant global health challenge, being the sixth leading cause of cancer mortality with pronounced geographic variability. The incidence rates range from 125 per 100,000 in northern China to 1–1.5 per 100,000 in the United States, driven by environmental and lifestyle factors such as tobacco and alcohol use, dietary habits, and pollution. Major modifiable risk factors include tobacco and alcohol consumption, with a synergistic risk increase when combined. Nonmodifiable risk factors include previous diagnoses of head and neck squamous cell carcinoma (H&N SCC), achalasia, and prior radiotherapy. Prevention strategies must be tailored to specific regional burdens to efficiently allocate medical and financial resources. Gastrointestinal endoscopy is crucial in reducing ESCC burden through early detection and characterization of neoplastic changes, such as high‐grade dysplasia. Early diagnosis significantly improves survival rates, while endoscopic resection of noninvasive dysplasia can prevent ESCC onset, reducing treatment burden for advanced disease. Postresection surveillance can detect high‐risk metachronous lesions. Despite these benefits, endoscopic prevention faces challenges, including the lack of high‐level evidence supporting its efficacy, opportunity costs, the need for specialized training and techniques, and the requirement for advanced technology investments. This Position Statement from the World Endoscopy Organization (WEO) aims to address these challenges, supplying recommendations for the exploitation of endoscopic resources regarding the possible role of screening, quality, and training for the detection, characterization, resection, and surveillance of ESCC.

Importance: Dermoscopy is increasingly recognized by skin cancer experts and professional leaders as an essential skill for physicians in dermatology and primary care. A substantial number of patients in both settings also receive care from physician assistants (PAs), who provide additional opportunities to evaluate patients with concerning skin lesions. Earning dermatology-specific credentials from the National Commission on Certification for PAs requires passing a written exam with dermoscopic content, and 77% of practicing PAs (all specialties) believe dermoscopy should be a standard element of their formal education. No published studies have identified precise learning objectives that would represent appropriate foundational proficiency in dermoscopy for PAs. Objective: We sought to identify common diagnoses with distinct dermoscopic features and delineate which of these represent appropriate proficiency expectations for early-career PAs in primary care and dermatology. Design, setting, and participants: A panel of 14 dermoscopists was assembled (8 dermatologists; 6 PAs), reflecting contributors to existing consensus statements on physician dermoscopy proficiency benchmarks, dermatologist-recommended competencies for PAs, and/or standardized test content for dermatology PAs. Panelists completed a modified Delphi consensus process involving electronic surveys and roundtable discussions. Main outcomes and measures: Consensus on which specific dermoscopic diagnoses reflect appropriate foundational proficiency expectations for PAs in both primary care and dermatology. Results: Twelve of 14 panelists (86%) reported using dermoscopy for over 12 years (mean: 15.5 y). All panelists completed 2 iterations of an electronic survey regarding 54 diagnoses, with 39 (72%) reaching a final consensus for inclusion in PA curricula and 15 (28%) being identified as non-priority items for early-career PAs. Panelists recommended 14 conditions for primary care PAs and 25 conditions for dermatology PAs. Conclusions and Relevance: Consensus achieved in this modified Delphi process identified diagnoses that represent pragmatic learning objectives to achieve foundational proficiency in dermoscopy for PAs in both primary care and dermatology. This list of validated objectives provides a consensus-based guide to help educators, supervising physicians, and professional leaders to cultivate specialty-appropriate dermoscopic proficiency among early-career PAs.

AbstractBackgroundThe clinical significance of natural and treatment‐emergent antibodies specific for amustaline/glutathione pathogen‐reduced red blood cells (PRRBCs) is not known.Study Design and MethodsA Phase 3, randomized clinical trial of PRRBCs (ReCePI) compared PRRBCs with conventional RBCs in cardiac or thoracic‐aorta surgery. Subjects transfused during and for 7 days after surgery were screened for PRRBC‐specific antibodies at baseline, 28 and 75 days post‐surgery. Subjects with treatment‐emergent antibodies were assessed for evidence of hemolysis. Cryopreserved subject RBC samples were assayed by flow cytometry for circulating PRRBCs using an acridine‐specific (2S197‐2M1) monoclonal antibody, and for human IgG‐coated RBCs. RBC‐surface acridine density was quantitated using a commercial calibrated phycoerythrin (PE)‐bead panel.ResultsFive of 159 (3.1%) PRRBC and zero of 162 conventional RBC recipients developed treatment‐emergent PRRBC‐specific IgG, low titer antibodies detected 26–80 days post‐surgery after exposure to 1–3 PRRBC units, without clinical evidence of hemolysis. DAT and eluate were weak (w+) positive and PRRBC‐specific in one subject. A monocyte monolayer assay (MMA) was non‐reactive in the three subjects with an interpretable result. Flow cytometry demonstrated circulating PRRBCs in all five subjects expressing surface acridine concentrations at the limit of detection (approximately 150–301 PE molecules/RBC) compared with freshly transfused PRRBCs (approximately 7500 PE molecules/RBC). In some samples, loss of surface acridine expression could not be distinguished from clearance of the PRRBCs.DiscussionTreatment‐emergent PRRBC‐specific antibodies with the characteristics of nonclinically significant antibodies were detected in five subjects transfused with PRRBCs. Flow cytometry demonstrated persistent circulating PRRBCs with minimal surface acridine expression. (www.ClinicalTrials.gov Identifier NCT03459287).

Abstract INTRODUCTION Psychotropic medication (PM) use in behavioral‐variant frontotemporal dementia (bvFTD) is higher than in other dementias. However, no information exists on whether PM use differs between sporadic and genetic bvFTD. METHODS We analyzed data from sporadic and genetic bvFTD participants with PM prescriptions in the Advancing Research and Treatment in Frontotemporal Lobar Degeneration/Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects study. We estimated ordinal odds ratio (OOR) of having more PM comparing sporadic and genetic bvFTD. Finally, we explored the neuropsychiatric symptom (NPS) combinations using classification and regression trees (CART). RESULTS We included 263 with sporadic and 193 with genetic bvFTD. The OOR for sporadic bvFTD to be on PM was 1.75 (95% confidence interval: 1.21 to 2.53) for the fully adjusted model. CART revealed the most common NPS combination was apathy + personality changes in 18% of participants. DISCUSSION Participants with sporadic bvFTD were twice as likely to be on PM compared to genetic bvFTD. The reason for increased PM usage in sporadic bvFTD participants should be further investigated. Highlights We report on patients with behavioral variant frontotemporal dementia (bvFTD). We evaluated the psychotropic medication (PM) prescription at baseline in the cohort. Patients with sporadic bvFTD had more prescriptions for PM than genetic patients. The frequency of symptoms combination was different in sporadic and genetic bvFTD.

Abstract Cardiovascular disease remains a prominent cause of disability and premature death worldwide. Within this spectrum, carotid artery atherosclerosis is a complex and multifaceted condition, and a prominent precursor of acute ischaemic stroke and other cardiovascular events. The intricate interplay among inflammation, oxidative stress, endothelial dysfunction, lipid metabolism, and immune responses participates in the development of lesions, leading to luminal stenosis and potential plaque instability. Even non-stenotic plaques can precipitate a sudden cerebrovascular event, regardless of the degree of luminal encroachment. In this context, carotid imaging modalities have proved their efficacy in providing in vivo characterization of plaque features, contributing substantially to patient risk stratification and clinical management. This review emphasizes the importance of identifying high-risk individuals by use of current imaging modalities, biomarkers, and risk stratification tools. Such approaches inform early intervention and the implementation of personalized therapeutic strategies, ultimately enhancing patient outcomes in the realm of cardiovascular disease management.

Background Multimorbidity is common in patients with atrial fibrillation (AF), yet comorbidity patterns are not well documented. Methods The prevalence of 18 chronic conditions (6 cardiometabolic, 7 other somatic, 5 mental health) was obtained in patients with new-onset AF from 2013-2017 from a 27-county region and controls matched 1:1 on age, sex, and county of residence. For AF patients and controls separately, clustering of conditions and co-occurrence beyond chance was estimated (using the asymmetric Somers’ D statistic), overall and for ages <65, 65-74, 75-84, and ≥85 years. Results Among 16,509 patients with AF (median age 76 years, 57% men), few (4%) did not have any of the 18 chronic conditions, whereas nearly one-quarter of controls (23%) did not have any chronic conditions. Clustering of cardiometabolic conditions was common in both AF patients and controls, but clustering of other somatic conditions was more common in AF. Although the prevalence of most condition pairs was higher in AF patients, controls had a larger number of condition pairs occurring together beyond chance. In persons aged <65 years, AF patients more frequently exhibited concordance of condition pairs that included either pairs of somatic conditions or a combination of conditions from different condition groups. In persons aged 65-74 years, AF patients more frequently had pairs of other somatic conditions. Conclusion Patterns of co-existing conditions differed between patients with AF and controls, particularly in younger ages. A better understanding of the clinical consequences of multimorbidity in AF patients, including those diagnosed at younger ages, is needed.

Abstract Vasculitic neuropathy is caused by inflammatory destruction of nerve blood vessels resulting in nerve ischaemia. Nerve vasculitis can be divided into two categories based on vessel size: large-arteriole vasculitis (≥75 µm) and microvasculitis (&lt;75 µm). Herein, we characterize the clinical features of nerve large-arteriole vasculitis in comparison to nerve microvasculitis. This is a retrospective cohort study of patients evaluated and biopsied at Mayo sites between 2001 and 2020. We collected clinical and histopathological data from patients whose nerve biopsies were either diagnostic or highly suggestive of nerve vasculitis. Two hundred and seventy-eight cases were identified: 125 cases of large-arteriole vasculitis and 153 cases of microvasculitis. Nerve large-arteriole vasculitis presented with a more acute (50.4% versus 26.8%) versus chronic onset (33.6% versus 57.5%) than nerve microvasculitis (P = 0.0001). Nerve microvasculitis had longer mean time to diagnosis (10.5 versus 4.3 months; P &lt; 0.0001) and longer time to plateau (8.9 versus 3.5 months; P &lt; 0.0001). Nerve large-arteriole vasculitis typically presented as distal asymmetric polyneuropathy (48.0%), whereas nerve microvasculitis typically presented as radiculoplexus neuropathy/polyradiculoneuropathy (more proximal involvement of shoulder and thigh) (43.8%) (P &lt; 0.0001). Systemic autoimmune disease was more common in nerve large-arteriole vasculitis (70.4% versus 22.9%, odds ratio, 8.0; 95% confidence interval, 4.7–13.7; P &lt; 0.0001). Nerve microvasculitis was significantly related to non-systemic vasculitis (71% versus 23%, odds ratio, 7.9; 95% confidence interval, 4.6–13.6; P &lt; 0.0001). Nerve microvasculitis had more autonomic involvement (24.2% versus 7.2%, odds ratio, 4.1; 95% confidence interval, 1.9–8.9; P = 0.0002). Nerve large-arteriole vasculitis and nerve microvasculitis have different but overlapping clinical features. Nerve large-arteriole vasculitis usually presents with acute onset, distal asymmetric polyneuropathy, associated with other autoimmune diseases and systemic involvement. In contrast, nerve microvasculitis usually presents with a subacute/chronic onset, as radiculoplexus neuropathy/polyradiculopathy (distal and proximal pattern) with autonomic involvement, and is more often a form of non-systemic vasculitis.