Old Therapy, New Questions: Rethinking Phlebotomy in a Pharmacologic Landscape.

Therapeutic phlebotomy remains a key intervention in the management of erythrocytosis and iron overload disorders, particularly polycythemia vera (PV) and hereditary hemochromatosis. Despite its historical origins as an ancient practice, venesection continues to be recommended in international guidelines for the reduction of hematocrit and iron burden, thereby mitigating thrombotic and organ-related complications. However, the evolving landscape of targeted pharmacologic therapies is reshaping the therapeutic paradigm.

QRISK3 score is predictive of thrombotic risk in patients with myeloproliferative neoplasms.

Thromboembolic events (TE) represent the commonest cause of morbidity and mortality in polycythemia vera (PV) and essential thrombocythaemia (ET). The QRISK3 model is a tool for predicting TE in the general population, with 7.5% recognised as a threshold to identify high-risk patients.

Synchronous detection of cosmic rays and correlated errors in superconducting qubit arrays.

Quantum information processing at scale will require sufficiently stable and long-lived qubits, likely enabled by error-correction codes. Several recent superconducting-qubit experiments, however, reported observing intermittent spatiotemporally correlated errors that would be problematic for conventional codes, with ionizing radiation being a likely cause. Here, we directly measured the cosmic-ray contribution to spatiotemporally correlated qubit errors.

Emerging Therapeutic Approaches for Anemia in Myelofibrosis.

Purpose Of Review: In this review, we highlight conventional agents and novel emerging therapeutic strategies to treat anemia in MF.

Recent Findings: Anemia is a common and challenging feature of myelofibrosis (MF). The pathobiology of anemia is multifactorial, including progressive bone marrow fibrosis, decreased erythropoiesis due to high hepcidin levels leading to iron sequestration in the reticuloendothelial system, hypersplenism, erythropoiesis inhibition by myelosuppressive JAK inhibitors (ruxolitinib, fedratinib), and others.

An 8-year retrospective review of human albumin solution use August 2015 to March 2023; Guy's and St Thomas' NHS Foundation Trust.

Objective: The objective of this study is to critically assess the diverse indications for HAS administration over the past 8 years at a prominent tertiary care institution in the United Kingdom.

Background: This is timely and relevant, given recent developments in the field. The International Collaborative Transfusion Medicine Group (ICTMG) issued updated guidance on intravenous albumin use in March 2024, reflecting a shift towards more stringent criteria for its application, which necessitates a re-evaluation of current practices.

Impact of nutritional interventions on quality of life in schizophrenia spectrum disorders: a scoping review.

Objectives: Schizophrenia is a chronic condition that requires long-term management. Quality of life is an important outcome measure for individuals diagnosed with schizophrenia; it can be tracked over time allowing evaluation of whether interventions lead to sustainable improvements. Nutrition and dietary interventions are an underutilized treatment for tackling the metabolic consequences of mental illness, which is now recognized as having increased importance in the management of schizophrenia.

Independent FDA Analyses of Nirmatrelvir/Ritonavir Resistance in the Phase 2/3 Trials EPIC-HR and EPIC-SR.

Background: PAXLOVID consists of nirmatrelvir, an inhibitor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro), copackaged with ritonavir, a pharmacokinetic enhancer. Nirmatrelvir/ritonavir received emergency use authorization in the United States in 2021 and was approved in 2023. However, there is limited published information on SARS-CoV-2 clinical resistance to nirmatrelvir/ritonavir.

Probing entanglement in a 2D hard-core Bose-Hubbard lattice.

Entanglement and its propagation are central to understanding many physical properties of quantum systems. Notably, within closed quantum many-body systems, entanglement is believed to yield emergent thermodynamic behaviour. However, a universal understanding remains challenging owing to the non-integrability and computational intractability of most large-scale quantum systems.

Biomarkers for progressive multifocal leukoencephalopathy: emerging data for use of JC virus DNA copy number in clinical trials.

Progressive multifocal leukoencephalopathy is a rare but devastating demyelinating disease caused by the JC virus (JCV), for which no therapeutics are approved. To make progress towards addressing this unmet medical need, innovations in clinical trial design are needed. Quantitative JCV DNA in CSF has the potential to serve as a valuable biomarker of progressive multifocal leukoencephalopathy disease and treatment response in clinical trials to expedite therapeutic development, as do neuroimaging and other fluid biomarkers such as neurofilament light chain.

Salmonellosis: An Overview of Epidemiology, Pathogenesis, and Innovative Approaches to Mitigate the Antimicrobial Resistant Infections.

is a major foodborne pathogen and a leading cause of gastroenteritis in humans and animals. is highly pathogenic and encompasses more than 2600 characterized serovars. The transmission of to humans occurs through the farm-to-fork continuum and is commonly linked to the consumption of animal-derived food products.

Polycythemia Vera: Barriers to and Strategies for Optimal Management.

Polycythemia vera (PV) is a subtype of myeloproliferative neoplasms characterized by impaired quality of life and severe complications. Despite the increasingly in-depth knowledge of this condition, it necessitates a multifaceted management approach to mitigate symptoms and prevent thrombotic and hemorrhagic events, ensuring prolonged survival. The therapeutic landscape has been revolutionized in recent years, where venesection and hydroxycarbamide associated with antiplatelet therapy have a central role and are now accompanied by other drugs, such as interferon and Janus kinase inhibitors.

Evaluation of SARS-CoV-2 RNA Rebound After Nirmatrelvir/Ritonavir Treatment in Randomized, Double-Blind, Placebo-Controlled Trials - United States and International Sites, 2021-2022.

Rebound of SARS-CoV-2 shedding or COVID-19 signs and symptoms has been described after treatment with nirmatrelvir/ritonavir (Paxlovid). The direct association of nirmatrelvir/ritonavir to COVID-19 rebound remains unclear because most reports are based on individual cases or nonrandomized studies. Viral RNA shedding data from two phase 2/3, randomized, double-blind, placebo-controlled clinical trials of nirmatrelvir/ritonavir (Evaluation of Protease Inhibition for COVID-19 in High-Risk Patients [EPIC-HR] and Evaluation of Protease Inhibition for COVID-19 in Standard-Risk Patients [EPIC-SR]) were analyzed to investigate the role of nirmatrelvir/ritonavir treatment in COVID-19 rebound.

Prediction of atrial fibrillation from at-home single-lead ECG signals without arrhythmias.

Early identification of atrial fibrillation (AF) can reduce the risk of stroke, heart failure, and other serious cardiovascular outcomes. However, paroxysmal AF may not be detected even after a two-week continuous monitoring period. We developed a model to quantify the risk of near-term AF in a two-week period, based on AF-free ECG intervals of up to 24 h from 459,889 patch-based ambulatory single-lead ECG (modified lead II) recordings of up to 14 days.

Differential inhibition of T-cell receptor and STAT5 signaling pathways determines the immunomodulatory effects of dasatinib in chronic phase chronic myeloid leukemia.

Dasatinib is a multi-kinase inhibitor with activity against the SRC kinase LCK, which plays a critical role in T-cell receptor signaling. Dasatinib, initially developed as an immunosuppressive agent, is by contrast, also noted to result in enhanced tumor immunity in a subset of patients. We studied the impact of dasatinib in chronic myeloid leukemia patients and compared it with patients taking other tyrosine kinase inhibitors (TKI) and healthy controls.

Benefit-risk assessment for brincidofovir for the treatment of smallpox: U.S. Food and Drug Administration's Evaluation.

The development and approval of brincidofovir for the treatment of smallpox, a disease that was eradicated from the world over 40 years ago, has resulted in the second antiviral approved via the Medical Countermeasure Initiative (MCMi) to combat this disease. Approval of brincidofovir required a unique regulatory approach based on the FDA Animal Rule, and development was supported by many years of research and collaboration among academic investigators, the pharmaceutical industry and multiple government agencies. This article summarizes the FDA regulatory pathway and describes the challenges involved.