Philadelphia-like B-cell acute lymphoblastic leukaemia: Disease features and outcomes in the era of immunotherapy.

Philadelphia chromosome (Ph)-like acute lymphoblastic leukaemia (ALL) is a high-risk subtype with a gene expression profile similar to Ph-positive ALL, due to activation of tyrosine kinase signalling. To understand the clinical implications of Ph-like ALL, this single-centre retrospective study evaluates outcomes in 268 adults, largely Hispanic ALL patients treated between 2013 and 2024, with a subgroup analysis of 139 haematopoietic stem cell transplantation (HSCT) patients. ALL subtypes included 68 (25.

Balancing innovation and affordability in anti-obesity medications: the role of an alternative weight-maintenance program.

Despite remarkable clinical advances in highly effective anti-obesity medications, their high price and potential budget impact pose a major challenge in balancing equitable access and affordability. While most attention has been focused on the amount of weight loss achieved, less consideration has been paid to interventions to sustain weight loss after an individual stops losing weight. Using a policy simulation model, we quantified the impact of a weight-maintenance program following the weight-loss plateau from the initial full-dose glucagon-like peptide 1 (GLP-1) receptor agonists or incretin mimetic use.

Safety and Efficacy of Intramuscular Tixagevimab-Cilgavimab in Prevention of COVID-19 in Patients Who Are Immunocompromised.

Introduction: Patients who are immunocompromised face an increased chance of severe COVID-19 infection compared with patients who are immunocompetent. However, vaccine efficacy for COVID-19 appears to be lower in patients who are immunocompromised. Tixagevimab-cilgavimab are monoclonal antibodies designed to enhance immune defense against COVID-19.

Impact of Berberine or Berberine Combination Products on Lipoprotein, Triglyceride and Biological Safety Marker Concentrations in Patients with Hyperlipidemia: A Systematic Review and Meta-Analysis.

Monoclonal antibody Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) inhibitors reduce total cholesterol (TC), low density lipoproteins (LDL), high density lipoproteins (HDL), and triglycerides (TG). We assessed the ability of berberine, a natural PCSK9 inhibitor, to reduce lipid concentrations either alone or combined with other nutraceuticals. We searched PubMed, Scopus and EMBASE from inception to September 30, 2022 for randomized controlled trials (RCTs) assessing 8-18 wk of berberine therapy on.

Into the Unknown: Characterizing Fellow Uncertainty During the Transition to Unsupervised Practice.

Background: Helping fellows confront and manage uncertainty in the course of diagnosis and treatment of patients has been a growing focus of medical education. How these same fellows confront uncertainty as they make a transition in their professional development is less commonly a focus of training programs. Better understanding of how fellows experience these transitions will allow fellows, training programs, and hiring institutions to navigate transitions more easily.

Primary Palliative Care for Pediatric Residents: A Curricular Framework and Pilot.

Problem: Palliative care (PC) is high-value, holistic care for a child and their family across the entire arc of an illness. All physicians should be competent in symptom management and providing goal-concordant care that acknowledges the quality of life; however, there is insufficient education in pediatric residency to develop competence in basic or ..

Incidence, Risk Factors, and Outcomes of COVID-19 Infection in a Large Cohort of Solid Organ Transplant Recipients.

Background: Solid organ transplant recipients (SOTr) are at increased risk for severe disease from coronavirus disease 2019 (COVID-19) compared with non-SOTr.

Methods: We performed a retrospective cohort study between March 1, 2020, and March, 30, 2021, in an integrated healthcare system with 4.3 million members aged ≥18 y including 5126 SOTr.

Review of Urate-Lowering Therapeutics: From the Past to the Future.

We reviewed all currently available ULT, as well as any medications in development using following databases: United States Food and Drug Administration (FDA), European Medicines Agency (EMA), Japanese Pharmaceutical and Medical Devices Agency (PMDA), and ClinicalTrials.gov. We identified a total of 36 drugs, including 10 approved drugs, 17 in clinical testing phases, and 9 in preclinical developmental phases.

Introduction of an Electronic Clinical Decision Support Tool to Inform Prescribing for Pediatric Diarrhea in Bangladesh and Mali: Do Provider Expectations Predict Experiences?

Nonindicated antibiotics for childhood diarrhea is a major contributor to global antimicrobial resistance. Electronic clinical decision support tools (eCDSTs) may reduce unnecessary antibiotics. This study examined how providers' expectations of an eCDST to predict diarrhea etiology compared with their experiences using the tool.

Efficacy of Xanthine Oxidase Inhibitors in Lowering Serum Uric Acid in Chronic Kidney Disease: A Systematic Review and Meta-Analysis.

Objective: Current guidelines for gout recommend a treat-to-target approach with serum uric acid (SUA). However, there is little evidence for the dose-dependent effects of urate-lowering therapy (ULT). Herein, we analyzed the reported SUA-lowering effect and SUA target achievement differences for various doses of xanthine oxidase inhibitors.

GPC2-CAR T cells tuned for low antigen density mediate potent activity against neuroblastoma without toxicity.

Pediatric cancers often mimic fetal tissues and express proteins normally silenced postnatally that could serve as immune targets. We developed T cells expressing chimeric antigen receptors (CARs) targeting glypican-2 (GPC2), a fetal antigen expressed on neuroblastoma (NB) and several other solid tumors. CARs engineered using standard designs control NBs with transgenic GPC2 overexpression, but not those expressing clinically relevant GPC2 site density (∼5,000 molecules/cell, range 1-6 × 10).

Acral lentiginous melanoma-Population, treatment, and survival using the NCDB from 2004 to 2015.

Acral lentiginous melanoma (ALM) is a rare histological subtype of cutaneous malignant melanoma that typically presents on the palms and soles. To characterize the demographic and treatment characteristics of ALM, we used the National Cancer Database (NCDB) to describe a large multi-institutional cohort of ALM patients, consisting of 4,796 ALM patients from 2004 to 2015. ALM was more likely to be diagnosed at a later stage overall compared with non-ALM cutaneous melanomas, and more likely to be thicker, ulcerated, lymph node positive, and have lymphovascular invasion and positive margins.

Acute pulmonary pressure change after transition to sacubitril/valsartan in patients with heart failure reduced ejection fraction.

Aims: Sacubitril/valsartan combines renin-angiotensin-aldosterone system inhibition with amplification of natriuretic peptides. In addition to well-described effects, natriuretic peptides exert direct effects on pulmonary vasculature. The effect of sacubitril/valsartan on pulmonary artery pressure (PAP) has not been fully defined.

Family Meetings in the Intensive Care Unit During the Coronavirus Disease 2019 Pandemic.

Purpose: Visitor restrictions during the COVID-19 pandemic limit in-person family meetings for hospitalized patients. We aimed to evaluate the quantity of family meetings by telephone, video and in-person during the COVID-19 pandemic by manual chart review. Secondary outcomes included rate of change in patient goals of care between video and in-person meetings, the timing of family meetings, and variability in meetings by race and ethnicity.

Development of Subspecialty-Specific Reporting Milestones for Hospice and Palliative Medicine Fellowship Training in the U.S.

Continuing the transition to competency-based education, Hospice and Palliative Medicine (HPM) fellowship programs began using context-free reporting milestones (RMs) for internal medicine subspecialties in 2014 but quickly recognized that they did not reflect the nuanced practice of the field. This article describes the development of 20 subspecialty-specific RMs through consensus group process and vetting by HPM educators. A workgroup of content experts used an iterative consensus building process between December 2017 and February 2019 to draft new RMs and create a supplemental guide that outlines the intent of each RM, examples of each developmental trajectory, assessment methods, and resources to guide educators.

Hearing loss and speech understanding in noise in Aboriginal and Torres Strait Islander children from locations varying in remoteness and socio-educational advantage.

Objective: Otitis media resulting in conductive hearing loss is a major health issue for Aboriginal and Torres Strait Islander children, which can also lead to the child developing spatial processing disorder (SPD). This study examined the prevalence of hearing loss and deficits in speech understanding in noise, including SPD, in Aboriginal and Torres Strait Islander children from schools varying in remoteness and socio-educational advantage.

Method: 288 Aboriginal and Torres Strait Islander children aged 4-14 years from three schools varying in remoteness and socio-educational advantage completed audiological assessment and the Listening in Spatialized Noise - Sentences test to assess for hearing loss and SPD.

Integration of Pediatric Palliative Care Into Cardiac Intensive Care: A Champion-Based Model.

Integration of pediatric palliative care (PPC) into management of children with serious illness and their families is endorsed as the standard of care. Despite this, timely referral to and integration of PPC into the traditionally cure-oriented cardiac ICU (CICU) remains variable. Despite dramatic declines in mortality in pediatric cardiac disease, key challenges confront the CICU community.

Modulation of Target Antigen Density Improves CAR T-cell Functionality and Persistence.

Purpose: Chimeric antigen receptor T-cell (CART) therapy targeting CD22 induces remission in 70% of patients with relapsed/refractory acute lymphoblastic leukemia (ALL). However, the majority of post-CD22 CART remissions are short and associated with reduction in CD22 expression. We evaluate the implications of low antigen density on the activity of CD22 CART and propose mechanisms to overcome antigen escape.

Development of Curricular Milestones for Hospice and Palliative Medicine Fellowship Training in the U.S.

Context: A physician workgroup of the American Academy of Hospice and Palliative Medicine sought to define curricular milestones (CMs) for hospice and palliative medicine (HPM) Fellowship Programs. The developed list of CMs would serve as components upon which to organize curriculum and standardize what to teach during training. These would complement entrustable professional activities previously developed by this group and new specialty-specific reporting milestones (RMs) for HPM developed through the Accreditation Council for Graduate Medical Education.

Pragmatic Strategies for Shared Decision-making.

Shared decision-making (SDM) is a process that brings together clinical expertise and families' values to arrive at a treatment choice. The process is especially useful for situations with >1 reasonable option, a condition of equipoise. However, for pediatricians who want to adhere to SDM best practices, there is limited practical guidance regarding how to communicate with parents and patients.

Integrating Palliative Care Into the ICU: From Core Competency to Consultative Expertise.

Objectives: To propose a model describing levels of integration of palliative care into the care of ICU patients.

Data Sources: Literature review and author opinion.

Conclusions: All critical care team members should demonstrate and foster their core competencies in caring for patients with complex illness and uncertain prognosis, including at the end of life.

Tumor stroma-targeted antibody-drug conjugate triggers localized anticancer drug release.

Although nonmalignant stromal cells facilitate tumor growth and can occupy up to 90% of a solid tumor mass, better strategies to exploit these cells for improved cancer therapy are needed. Here, we describe a potent MMAE-linked antibody-drug conjugate (ADC) targeting tumor endothelial marker 8 (TEM8, also known as ANTXR1), a highly conserved transmembrane receptor broadly overexpressed on cancer-associated fibroblasts, endothelium, and pericytes. Anti-TEM8 ADC elicited potent anticancer activity through an unexpected killing mechanism we term DAaRTS (drug activation and release through stroma), whereby the tumor microenvironment localizes active drug at the tumor site.