A phase 1 study of IO-202, an anti-LILRB4 antibody, in chronic myelomonocytic leukemia and acute myeloid leukemia.

IO-202 is a humanized immunoglobulin G1 monoclonal antibody with high affinity and specificity for leukocyte immunoglobulin-like receptor B4 (LILRB4; ILT3), which is predominantly expressed in monocytes and monocytic blasts. IO-202 induces antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis in vitro and in patients with leukemia. Herein, we present the phase 1a dose escalation data of IO-202 as monotherapy and in combination with azacitidine (AZA) in patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) and R/R chronic myelomonocytic leukemia (CMML), and the phase 1b dose expansion data of IO-202 combined with AZA for the treatment of hypomethylating agent (HMA)-naïve CMML.

Zoonotic vascular endograft infections are rare but serious complications.

Zoonotic infections-bacterial, viral, fungal, or parasitic-can spread from domestic or wild animals to humans, either directly or via intermediate vectors. In vascular and endovascular surgery, infections are rare and usually caused by common bacteria with familiar presentations. In contrast, zoonotically transmitted, atypically behaving organisms pose diagnostic and therapeutic challenges due to their elusive nature and resistance to conventional detection methods.

A Community Effort to Develop Common Data Elements for Pre-Clinical Spinal Cord Injury Research.

For nearly 350 years, the process of disseminating scientific knowledge has remained largely unchanged. Scientists conduct experiments, analyze the data, and publish their findings in the form of scientific articles. Since the turn of the century, this process has been challenged by numerous open science and data sharing efforts to enhance transparency, reproducibility, and replicability of scientific research.

Documentation of social determinants of health for patients with type 2 diabetes in Epic Cosmos.

Objectives: Type 2 diabetes (T2D) is a growing public health burden with persistent racial and ethnic disparities. . This study assessed the completeness of social determinants of health (SdoH) data for patients with T2D in Epic Cosmos, a nationwide, cross-institutional electronic health recors (EHR) database.

Associations of adverse childhood experiences with midlife cardiovascular health in women.

Background: Cardiovascular health (CVH) may be influenced by early life factors, such as adverse childhood experiences (ACEs). Prior work suggests social stressors may particularly influence CVH trajectories across the lifecourse in women; however, this relationship remains poorly understood. We used data from a prospective longitudinal cohort study to evaluate associations of ACEs with CVH and its components among midlife women (mean 51.

Ectopic adipose tissue in subsistence populations with minimal coronary disease, large left atria, and very low rates of atrial fibrillation.

Background: Greater deposits of epicardial adipose tissue are associated with atrial fibrillation and coronary disease, but have not been studied in subsistence populations.

Methods: We performed CT imaging to measure coronary artery and thoracic aortic calcium (CAC, TAC), epicardial fat thickness (EFT), liver density, and left atrial (LA) anteroposterior diameter and, using a deep learning-enabled software program, epicardial and thoracic fat volume (EFV, TFV), in two remote Amerindian subsistence populations with minimal coronary artery calcification and virtually no atrial fibrillation. We compared 893 adult Tsimane (mean age 58.

Lipoprotein(a) at a "Tipping Point": case to move to universal screening.

Elevated lipoprotein(a) [Lp(a)] is well established as a common risk factor for atherosclerotic cardiovascular disease (ASCVD). Lp(a) levels are >90 % genetically determined. However, Lp(a) remains very underrecognized as a cardiovascular risk factor with low rates of testing.

Investigating the Effects of Meditation, Nature Sounds, and Music on the Patient Experience During Intravitreal Injections.

Introduction: The purpose of this study was to evaluate the effects of three brief interventions (spoken/guided meditation, nature sounds, or music) on patients' subjective experience with intravitreal injections (IVIs).

Methods: A total of 121 consecutive patients were randomized into four cohorts: spoken/guided meditation (n = 31), nature sounds (n = 30), music (classical or jazz, n = 30), and control (n = 30). Subjective anxiety levels were recorded prior to and following a three- to five-minute intervention in the first three study groups as well as following the IVI.

Recurrent Hemothorax and Hemoperitoneum in Endometriosis: A Case Report.

Extra-pelvic endometriosis, defined as the presence of endometrial tissue or stroma outside of the pelvic cavity, is a rare cause of hemothorax and hemoperitoneum. Here, we present a case of a 34-year-old woman with a history of endometriosis who experienced recurrent, cyclical episodes of hemorrhagic pleural effusions and ascites. Despite multiple surgeries to address the ectopic endometrial implants, her symptoms persisted for years without definitive resolution, illustrating the challenges of treatment even after the diagnosis has been established.

Pathogen reduction diminishes the protective effects of platelets on endothelial barrier permeability in vitro.

Platelet transfusion not only attenuates bleeding and promotes hemostasis but also plays a critical role in vascular stability and endothelial barrier integrity. Under amotosalen-UVA pathogen reduction of platelets, pathogen nucleic acids undergo adduction, which prevents their replication and greatly reduces the risk of transfusion-transmitted infections. Although pathogen-reduced (PR) platelets are increasing in clinical use, the physiologic effects of pathogen reduction on platelets, particularly its impact on platelet-endothelial interactions, have yet to be described.

Inhibitor development and clinical characteristics in children with severe hemophilia A in the ATHN 8 US cohort study.

Clotting factor concentrate (CFC), used to treat and prevent bleeding in hemophilia, is rendered ineffective if clotting factor neutralizing antibodies (inhibitors) develop. Inhibitors occur most often in children, early in treatment. The American Thrombosis and Hemostasis Network (ATHN) 8: US Cohort Study of Previously Untreated Patients (PUPs) with Congenital Hemophilia, conducted in children born in 2010 to 2020 with severe or moderate hemophilia, was designed to determine the percentage of participants who developed a confirmed, clinically significant inhibitor within the first 50 CFC exposure days (EDs).

Sex and racial disparities in clinical outcomes and healthcare costs among hospitalized older adult fall patients: A nationwide analysis.

Background: The impact of patient sex and race on clinical in-hospital outcomes and expenditures of falls in older adults remain underexplored. This study examines sex- and race-based disparities of fall-related hospitalizations.

Study Design: All hospitalizations for adults (≥65 years) from falls were identified (National Inpatient Sample, 2017-2021).

Innovative Development of Research Engagement Manual: Strategies to Enhance Recruitment and Retention of Black Individuals in Clinical Trials for Substance Use Disorders.

Background: The participation of Black individuals in clinical trials remains lower than that of other racial and ethnic groups. Substance abuse adds additional barriers to recruitment and retention. While significant attention has been devoted to identifying barriers to recruitment/retention, efforts have been largely unsuccessful in increasing the participation of Black individuals in clinical trials.

Pragmatic Comparative Effectiveness Trials in Rheumatoid Arthritis-Associated Interstitial Lung Disease: A Multiperspective Qualitative Study.

Background: Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) portends a devastating prognosis for patients, with survival typically being < 5 to 8 years after diagnosis. Limited clinical trial data exist to guide treatment strategies, and the efficacy of current strategies-immunomodulation and antifibrotics-remains uncertain. Large randomized controlled trials are costly, but pragmatic trial designs could reduce expenses.

Correction: Exploring the gut microbiome: probiotics, prebiotics, synbiotics, and postbiotics as key players in human health and disease improvement.

[This corrects the article DOI: 10.1007/s10068-024-01620-1.].

Alternating 2D and 3D culture reduces cell size and extends the lifespan of placenta-derived mesenchymal stem cells.

Background: Mesenchymal stem cells (MSCs) hold great promise for treating a variety of human diseases; however, their clinical translation is hindered by challenges in large-scale expansion while preserving therapeutic potency and maintaining small cell size. Conventional 2D culture on rigid substrates induces MSC senescence and enlargement, compromising their function and biodistribution.

Methods: We present an alternating 2D/3D culture strategy that combines adherent monolayer expansion with transient spheroid formation to mitigate these limitations.

Imagining Indigenized Futures: Multi-Eyed Seeing and Decolonialism in Integrative Health Equity.

Background: Integrative health efforts typically offer clinical services of Western and non-Western origin in a biomedical context. Indigenous communities and other minoritized populations would benefit from improved equity efforts in integrative healthcare.

Objective: As an approach to improve healthcare for Kānaka 'Ōiwi (Native Hawaiians), we explore multi-eyed seeing, an elaboration on two-eyed seeing, emphasizing decolonialism and adaptive use of healing traditions from multiple cultural backgrounds.

Pre-treatment monocytic myeloid-derived suppressor cells as predictive biomarkers for immune checkpoint inhibitor response in clear cell renal cell carcinoma.

Background: Immune checkpoint inhibitors (ICIs) are a cornerstone of systemic therapy for clear cell renal cell carcinoma (ccRCC), yet response rates remain variable and predictive biomarkers are lacking. This study aimed to determine whether baseline levels of myeloid-derived suppressor cells (MDSCs), especially monocytic (M-MDSC) and polymorphonuclear (PMN-MDSC) subtypes, could predict ICI response in ccRCC patients.

Methods: In this prospective cohort study, 20 ccRCC patients receiving ICI-based therapy for at least 3 months were enrolled.

Reduced-dose vs full-dose direct oral anticoagulants for extended treatment of venous thromboembolism: a meta-analysis of randomized controlled trials.

Background: Venous thromboembolism (VTE) is a major cause of cardiovascular morbidity and mortality globally. Although direct oral anticoagulants (DOACs) have improved extended VTE treatment, the optimal dose for balancing efficacy and safety remains unclear.

Objectives: This systematic review and meta-analysis aimed to evaluate the efficacy and safety of reduced-dose DOACs vs full-dose regimens during extended anticoagulation for VTE.

Serially-Connected Soft Continuum Robots for Endovascular Emergencies.

Endovascular surgeries generally rely on push-based catheters and guidewires, which require significant training to master and can still result in high stress being exerted on the anatomy, especially in tortuous paths. Because these procedures are so technically challenging to perform, many patients have limited access to high-quality treatment. Although various robotic systems have been developed to enhance navigation capabilities, they can also apply high stresses due to sliding against the vascular walls, impeding movement and raising the risk of vascular damage.

Cognitive and Global Morphometry Trajectories as Predictors of Youth Persistent Distressing Psychotic-Like Experiences.

Psychotic-like experiences (PLEs) may arise from genetic and environmental risk leading to worsening cognitive and morphometry metrics over time, which in turn lead to worsening PLEs. Analyses used three waves of unique longitudinal Adolescent Brain Cognitive Development Study data (ages 9-13) to test whether changes in cognition and global morphometry metrics attenuate associations between genetic and environmental risk with persistent distressing PLEs. Multigroup univariate latent growth models examined three waves of cognitive metrics and global morphometry separately for three PLE groups: persistent distressing PLEs (n=356), transient distressing PLEs (n=408), and low-level PLEs (n=7901).

Targeting Wnt-driven metabolic adaptations in cancer: integrating glycolysis, glutaminolysis, IDO1-mediated immune evasion, and therapeutic delivery strategies.

The Wnt pathway is an evolutionarily conserved signaling cascade that regulates a wide range of fundamental cellular processes, including proliferation, differentiation, polarity, migration, metabolism, and survival. Due to its central regulatory roles, Wnt signaling is critically involved in the pathophysiology of numerous human diseases. Aberrant activation or insufficient inhibition of this pathway has been causally linked to cancer, degenerative disorders, metabolic syndromes, and developmental abnormalities.

Gender Identity and Gender-Related Medical Outcomes of Autistic Young Adults Who Experienced Transgender Identity as Adolescents.

Purpose: We examined gender identity and gender-affirming care outcomes of autistic transgender adolescents followed into young adulthood, as well as relationships between gender-related medical care receipt and mental health across time.

Methods: This longitudinal two-timepoint study was conducted between 2018 and 2024, with 4 years between timepoints. Twenty-seven autistic transgender youth participated, with one lost to follow-up.

Hematopoietic stem cell gene therapy for the treatment of X-linked agammaglobulinemia.

X-linked agammaglobulinemia (XLA) is a rare inborn error of immunity caused by loss-of-function mutations in the gene encoding Bruton's tyrosine kinase (BTK). XLA patients lack mature B cells and have negligible antibody levels, leaving them susceptible to recurrent bacterial and chronic viral infections. Autologous hematopoietic stem cell gene therapy with gene-corrected HSC may serve as a promising treatment of XLA; this therapy would provide a one-time cure and would replace lifelong immunoglobulin replacement therapy.