Risk prediction for clonal cytopenia: multicenter real-world evidence.

Clonal cytopenia of undetermined significance (CCUS) represents a distinct disease entity characterized by myeloid-related somatic mutations with a variant allele fraction of ≥2% in individuals with unexplained cytopenia(s) but without a myeloid neoplasm (MN). Notably, CCUS carries a risk of progressing to MN, particularly in cases featuring high-risk mutations. Understanding CCUS requires dedicated studies to elucidate its risk factors and natural history.

Strengthening the use of artificial intelligence within healthcare delivery organizations: balancing regulatory compliance and patient safety.

Objectives: Surface the urgent dilemma that healthcare delivery organizations (HDOs) face navigating the US Food and Drug Administration (FDA) final guidance on the use of clinical decision support (CDS) software.

Materials And Methods: We use sepsis as a case study to highlight the patient safety and regulatory compliance tradeoffs that 6129 hospitals in the United States must navigate.

Results: Sepsis CDS remains in broad, routine use.

XPO1 Enables Adaptive Regulation of mRNA Export Required for Genotoxic Stress Tolerance in Cancer Cells.

Unlabelled: Exportin-1 (XPO1), the main soluble nuclear export receptor in eukaryotic cells, is frequently overexpressed in diffuse large B-cell lymphoma (DLBCL). A selective XPO1 inhibitor, selinexor, received approval as single agent for relapsed or refractory (R/R) DLBCL. Elucidating the mechanisms by which XPO1 overexpression supports cancer cells could facilitate further clinical development of XPO1 inhibitors.

Management of pouch neoplasia: consensus guidelines from the International Ileal Pouch Consortium.

Surveillance pouchoscopy is recommended for patients with restorative proctocolectomy with ileal pouch-anal anastomosis in ulcerative colitis or familial adenomatous polyposis, with the surveillance interval depending on the risk of neoplasia. Neoplasia in patients with ileal pouches mainly have a glandular source and less often are of squamous cell origin. Various grades of neoplasia can occur in the prepouch ileum, pouch body, rectal cuff, anal transition zone, anus, or perianal skin.

Relevance of Bone Marrow Biopsies for Response Assessment in US National Cancer Institute National Clinical Trials Network Follicular Lymphoma Clinical Trials.

Purpose: Bone marrow biopsies (BMB) are performed before/after therapy to confirm complete response (CR) in patients with lymphoma on clinical trials. We sought to establish whether BMB add value in assessing response or predict progression-free survival (PFS) or overall survival (OS) outcomes in follicular lymphoma (FL) subjects in a large, multicenter, multitrial cohort.

Methods: Data were pooled from seven trials of 580 subjects with previously untreated FL through Alliance for Clinical Trials in Oncology (Alliance) and SWOG Cancer Research Network (SWOG) completing enrollment from 2008 to 2016.

Mobile Stroke Units: Evidence, Gaps, and Next Steps.

Mobile stroke units (MSUs) are specialized ambulances equipped with the personnel, equipment, and imaging capability to diagnose and treat acute stroke in the prehospital setting. Over the past decade, MSUs have proliferated throughout the world, particularly in European and US cities, culminating in the formation of an international consortium. Randomized trials have demonstrated that MSUs increase stroke thrombolysis rates and reduce onset-to-treatment times but until recently it was uncertain if these advantages would translate into better patient outcomes.

Clinical Pharmacokinetics and Pharmacodynamics of Lefamulin.

Lefamulin (Xenleta) has been approved by the US FDA for the treatment of community-acquired bacterial pneumonia (CABP). It may be taken intravenously or orally and has activity against a broad range of pulmonary pathogens, including Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, Legionella pneumophila, and Chlamydophila pneumonia, as well as methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium. Lefamulin has an adverse effect profile that is similar to other antimicrobial agents commonly used to treat CABP.

Bariatric and metabolic endoscopy: impact on obesity and related comorbidities.

The global obesity pandemic is among the most significant public health crises today. Furthermore, obesity remains a major risk factor for many weight-related comorbid conditions including cardiovascular disease, type 2 diabetes mellitus, liver disease, and cancer. Endoscopic bariatric therapies are currently on the rise as a new tool in the fight against the obesity epidemic, offering patients an alternative to more invasive surgery and a more effective option than diet and lifestyle modifications.

Diagnostic Coding of Elder Mistreatment: Results From a National Database of Medicare Advantage and Private Insurance Patients, 2011-2017.

Health care providers may play an important role in detection of elder mistreatment, which is common but underrecognized. We used the Health Care Cost Institute insurance claims database to describe elder mistreatment diagnosis among Medicare Advantage (MA) and private insurance patients in the United States from 2011 to 2017. We used International Classification of Diseases (ICD) coding to identify cases, examining the impact of transition from ICD-9 (Ninth Revision) to ICD-10 (Tenth Revision), which occurred in October 2015 and added 14 new codes for "suspected" mistreatment.

Tumor subtype defines distinct pathways of molecular and clinical progression in primary prostate cancer.

BACKGROUNDMolecular characterization of prostate cancer (PCa) has revealed distinct subclasses based on underlying genomic alterations occurring early in the natural history of the disease. However, how these early alterations influence subsequent molecular events and the course of the disease over its long natural history remains unclear.METHODSWe explored the molecular and clinical progression of different genomic subtypes of PCa using distinct tumor lineage models based on human genomic and transcriptomic data.

Measurable residual disease as a biomarker in acute myeloid leukemia: theoretical and practical considerations.

Several methodologies that rely on the detection of immunophenotypic or molecular abnormalities of the neoplastic cells are now available to quantify measurable ("minimal") residual disease (MRD) in acute myeloid leukemia (AML). Although the perfect MRD test does not (yet) exist, the strong association between MRD and adverse patient outcomes has provided the impetus to use measures of MRD as biomarker in the routine care of AML patients and during clinical trials. MRD test results may inform the selection of postremission therapy in some patients but evidence supporting the use of MRD as predictive biomarker is still limited.

Metformin-induced weight loss in patients with or without type 2 diabetes/prediabetes: A retrospective cohort study.

It is unknown whether weight loss outcomes differ with metformin monotherapy in patients with obesity with or without type 2 diabetes (T2DM)/prediabetes (PreDM). In this retrospective study, 6- or 12-month weight loss outcomes were compared in 222 patients with or without T2DM/preDM who completed metformin monotherapy. Average weight loss was similar between groups, euglycemic vs.

Author Correction: FOXA1 mutations alter pioneering activity, differentiation and prostate cancer phenotypes.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Integrative multiplatform molecular profiling of benign prostatic hyperplasia identifies distinct subtypes.

Benign prostatic hyperplasia (BPH), a nonmalignant enlargement of the prostate, is among the most common diseases affecting aging men, but the underlying molecular features remain poorly understood, and therapeutic options are limited. Here we employ a comprehensive molecular investigation of BPH, including genomic, transcriptomic and epigenetic profiling. We find no evidence of neoplastic features in BPH: no evidence of driver genomic alterations, including low coding mutation rates, mutational signatures consistent with aging tissues, minimal copy number alterations, and no genomic rearrangements.

A phase 1/2 study of the oral FLT3 inhibitor pexidartinib in relapsed/refractory FLT3-ITD-mutant acute myeloid leukemia.

FMS-like tyrosine kinase 3 (FLT3) tyrosine kinase inhibitors (TKIs) have activity in acute myeloid leukemia (AML) patients with FLT3 internal tandem duplication (ITD) mutations, but efficacy is limited by resistance-conferring kinase domain mutations. This phase 1/2 study evaluated the safety, tolerability, and efficacy of the oral FLT3 inhibitor PLX3397 (pexidartinib), which has activity against the FLT3 TKI-resistant F691L gatekeeper mutation in relapsed/refractory FLT3-ITD-mutant AML. Ninety patients were treated: 34 in dose escalation (part 1) and 56 in dose expansion (part 2).

Machine learning of clinical variables and coronary artery calcium scoring for the prediction of obstructive coronary artery disease on coronary computed tomography angiography: analysis from the CONFIRM registry.

Aims: Symptom-based pretest probability scores that estimate the likelihood of obstructive coronary artery disease (CAD) in stable chest pain have moderate accuracy. We sought to develop a machine learning (ML) model, utilizing clinical factors and the coronary artery calcium score (CACS), to predict the presence of obstructive CAD on coronary computed tomography angiography (CCTA).

Methods And Results: The study screened 35 281 participants enrolled in the CONFIRM registry, who underwent ≥64 detector row CCTA evaluation because of either suspected or previously established CAD.

Efficacy of Surgery in the Primary Tumor Site for Metastatic Urothelial Cancer: Analysis of an International, Multicenter, Multidisciplinary Database.

Background: The effect of local treatment on survival in advanced-stage patients has gained interest in several malignancies; however, limited data exist regarding urothelial carcinoma (UC).

Objective: To test the impact of surgery of the primary tumor site on cancer-specific mortality (CSM) and overall mortality (OM) in patients affected by metastatic UC.

Design, Setting, And Participants: Individual patient-level data from a multicenter collaboration, including metastatic UC patients treated with first-line cisplatin- or carboplatin-based chemotherapy administered between January 2006 and January 2011 from hospitals in the USA, Europe, Israel, and Canada.

FOXA1 mutations alter pioneering activity, differentiation and prostate cancer phenotypes.

Mutations in the transcription factor FOXA1 define a unique subset of prostate cancers but the functional consequences of these mutations and whether they confer gain or loss of function is unknown. Here, by annotating the landscape of FOXA1 mutations from 3,086 human prostate cancers, we define two hotspots in the forkhead domain: Wing2 (around 50% of all mutations) and the highly conserved DNA-contact residue R219 (around 5% of all mutations). Wing2 mutations are detected in adenocarcinomas at all stages, whereas R219 mutations are enriched in metastatic tumours with neuroendocrine histology.