Preclinical evaluation of the efficacy and safety of AAV8-TNAP-D10 in Alpl-/- and AlplPrx1/Prx1 mouse models for the treatment of early and late-onset hypophosphatasia.

We previously documented successful resolution of skeletal and dental disease in the infantile and late-onset murine models of hypophosphatasia (HPP), with a single injection of an adeno-associated serotype 8 vector encoding mineral-targeted TNAP (AAV8-TNAP-D10). Here, we conducted dosing studies in both HPP mouse models. A single escalating dose from 4x108 up to 4x1010 (vg/b) was intramuscularly injected into 4-day-old Alpl-/- mice (an infantile HPP model) and a single dose from 4x106 up to 4x109 (vg/b) was administered to 8-week-old AlplPrx1/Prx1 mice (a late-onset HPP model).

Insomnia Prevalence and Correlates in Cancer Patients Undergoing Treatment.

Background: Insomnia is the most common sleep disturbance among cancer patients undergoing active treatment. If untreated, it is associated with significant physical and psychological health consequences. Prior efforts to determine insomnia prevalence and correlates have primarily assessed patients in clinical trials, in limited disease groups, and excluding important patient subgroups.

The association between self-reported total gestational weight gain by pre-pregnancy body mass index and moderate to late preterm birth.

Background: Inadequate and excessive gestational weight gain (GWG) defined by the Institute of Medicine (IOM) has been associated with preterm birth. However, studies demonstrate inconsistent associations.

Objectives: We examined the associations between categorical and continuous total GWG and moderate to late preterm birth (32-<37 weeks), and evaluated differences in these associations by pre-pregnancy BMI.

Young, Empowered & strong (YES): a study protocol paper for a randomized controlled trial of an mHealth symptom monitoring and self-management intervention for adolescent and young adult (AYA) breast cancer survivors.

Background: Compared to older adults with breast cancer (BC), adolescents and young adults (AYAs) develop more aggressive disease necessitating more intensive therapy with curative intent, which is disruptive to planned life trajectories. The burden of unmet needs among AYA BC survivors exists in two domains: (1) symptoms (e.g.

Clinical Outcomes of Patients With Newly Diagnosed Acute Myeloid Leukemia Receiving Treatment in a Safety-Net Hospital System.

Background: 'Standard of care' therapies for adult acute myeloid leukemia (AML) have yielded 5-year overall survival (OS) rates of 30%-45 %. Risk stratification and novel targeted therapies have improved 5-year OS rates to >75 % for certain groups in specialized centers.

Patients And Methods: This is a retrospective cohort analysis of outcomes in patients ≥18 years with newly diagnosed AML treated between 2005 and 2019 in the Harris Health County, Safety-Net Hospital System in Houston, TX.

Efficacy, safety, and target engagement of dazukibart, an IFNβ specific monoclonal antibody, in adults with dermatomyositis: a multicentre, double-blind, randomised, placebo-controlled, phase 2 trial.

Background: Dermatomyositis is a chronic autoimmune disease with distinctive cutaneous eruptions and muscle weakness, and the pathophysiology is characterised by type I interferon (IFN) dysregulation. This study aims to assess the efficacy, safety, and target engagement of dazukibart, a potent, selective, humanised IgG1 neutralising monoclonal antibody directed against IFNβ, in adults with moderate-to-severe dermatomyositis.

Methods: This multicentre, double-blind, randomised, placebo-controlled, phase 2 trial was conducted at 25 university-based hospitals and outpatient sites in Germany, Hungary, Poland, Spain, and the USA.

The climb toward intracranial efficacy: Zorifertinib in EGFR-mutant NSCLC with CNS metastases in the EVEREST trial.

The phase III EVEREST trial evaluating zorifertinib in the treatment of metastatic EGFR-mutant NSCLC was groundbreaking in its specific inclusion of patients with brain metastases. Zorifertinib prolonged systemic and intracranial progression-free survival compared with first-generation EGFR inhibitors, yet questions remain about its efficacy and toxicity compared with osimertinib.

Cervical stromal invasion and molecular characterization in stage II-IV endometrial cancers.

Objective: The optimal treatment for patients with cervical stromal invasion (CSI) in endometrial cancer (EC) remains unclear. We aimed to test the prognostic role of molecular classification in EC patients with CSI.

Methods: A retrospective, multicenter review of EC patients with CSI was performed.

Long-Term Safety and Efficacy of Bimekizumab in Axial Spondyloarthritis: 2-Year Results from Two Phase 3 Studies.

Objectives: Bimekizumab, a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)‑17F in addition to IL-17A, previously demonstrated efficacy and was well tolerated to 1 year in patients with non-radiographic (nr-) and radiographic (r-) axial spondyloarthritis (axSpA). Here, we report bimekizumab safety and efficacy to 2 years.

Methods: Patients completing week 52 in the phase 3 studies BE MOBILE 1 (nr-axSpA; NCT03928704) and 2 (r‑axSpA; NCT03928743) were eligible for an ongoing open‑label extension (OLE; NCT04436640).

The potential of antibody-drug conjugates for effective therapy in diffuse large B-cell lymphoma.

Introduction: Antibody-drug conjugates (ADCs) are a rapidly evolving class of anti-cancer drugs with a significant impact on management of hematological malignancies including diffuse large B-cell lymphoma (DLBCL). ADCs combine a cytotoxic drug (a.k.

The PERFORMANCE II Trial: A Prospective Multicenter Investigation of a Novel Carotid Stent System.

Background: Several randomized clinical trials have shown that the composite endpoint of death, stroke, and myocardial infarction (MI) is equivalent between carotid artery stenting and carotid endarterectomy. However, the risk of minor stroke has been consistently higher with carotid artery stenting.

Objectives: The authors sought to evaluate the safety and effectiveness of a novel carotid stent system comprised of a stent, an adjustable integrated embolic filter and a postdilation balloon, in patients at elevated risk for adverse events from carotid endarterectomy.

CAR/CSACI Practice Guidance for Contrast Media Hypersensitivity.

Contrast media, including iodinated contrast media and gadolinium-based contrast agents, are commonly administered pharmaceuticals with excellent safety profiles. However, a minority of the population may experience a hypersensitivity reaction following intravenous administration. Hypersensitivity reactions can be immediate or delayed, and range from mild, such as urticaria, to severe, including anaphylaxis.

Neonatal Feeding Practices and SARS-CoV-2 Transmission in Neonates with Perinatal SARS-CoV-2 Exposure: A Systematic Review and Meta-Analysis.

The risk of neonatal SARS-CoV-2 infection from the mother's own milk (MoM) in neonates who are exposed to maternal SARS-CoV-2 during the perinatal period remains unclear. We conducted a systematic review to assess the association between MoM feeding and neonatal SARS-CoV-2 infection in neonates who were born to SARS-CoV-2-positive pregnant persons. PubMed Central and Google Scholar were searched for studies published by 14 March 2024 that reported neonatal SARS-CoV-2 infection by feeding type.

Recent Advances and Future Directions in Extracorporeal Carbon Dioxide Removal.

Extracorporeal carbon dioxide removal (ECCOR) is an emerging technique designed to reduce carbon dioxide (CO) levels in venous blood while enabling lung-protective ventilation or alleviating the work of breathing. Unlike high-flow extracorporeal membrane oxygenation (ECMO), ECCOR operates at lower blood flows (0.4-1.

Fertility Sparing in Endometrial Cancer: Where Are We Now?

Endometrial cancer is the most common gynecological neoplasm with an increased incidence in the premenopausal population in recent decades. This raises the problem of managing endometrial cancer in fertile women who have not yet achieved pregnancy. In these women, after careful selection, hysterectomy may be postponed in favor of conservative management if specific requirements are met.

Exploring the Link Between Obligate Anaerobe-Related Dysbiosis and Prostate Cancer Development: A Pilot Study.

Background/objectives: Several independent studies have associated prostate cancer (PCa) with specific groups of bacteria, most of them reporting the presence of anaerobic or microaerophilic species such as (). Such findings suggest a prostate cancer-related bacterial dysbiosis, in a manner similar to the association between infection and gastric cancer. In an earlier exploratory study looking for such dysbiosis events, using a culturomics approach, we discovered that the presence of obligate anaerobes (OAs) along with was associated with increased prostate-specific antigen (PSA) levels in 39 participants.

Cost-Effectiveness of PARP Inhibitors for Patients with BRCA1/2-Positive Metastatic Castration-Resistant Prostate Cancer-The Canadian Perspective.

Background/objectives: Through phase III clinical trials, PARP inhibitors have demonstrated outcome improvements in mCRPC patients with alterations in BRCA1/2 genes who have progressed on a second-generation androgen receptor pathway inhibitor (ARPI). While improving outcomes, PARP inhibitors contribute to the ever-growing economic burden of PCa. The objective of this project is to evaluate the cost-effectiveness of PARP inhibitors (olaparib, rucaparib, or talazoparib) versus the SOC (docetaxel or androgen receptor pathway inhibitors (ARPI)) for previously progressed mCRPC patients with BRCA1/2 mutations from the Canadian healthcare system perspective.

Preclinical Models for Functional Precision Lung Cancer Research.

Patient-centered precision oncology strives to deliver individualized cancer care. In lung cancer, preclinical models and technological innovations have become critical in advancing this approach. Preclinical models enable deeper insights into tumor biology and enhance the selection of appropriate systemic therapies across chemotherapy, targeted therapies, immunotherapies, antibody-drug conjugates, and emerging investigational treatments.

A Randomized Pilot Study of Time-Restricted Eating Shows Minimal Microbiome Changes.

Objective: TRE is an emerging approach in obesity treatment, yet there is limited data on how it influences gut microbiome composition in humans. Our objective was to characterize the gut microbiome of human participants before and after a TRE intervention. This is a secondary analysis of a previously published clinical trial examining the effects of time-restricted eating (TRE).

Nutrient Intake and Dietary Adequacy Among Rural Tanzanian Infants Enrolled in the Mycotoxin Mitigation Trial.

Background: The Mycotoxin Mitigation Trial (MMT) was a community-based cluster-randomized trial designed to assess the effect of dietary aflatoxin (AF) on linear growth. Similar dietary intake between arms was an important component of the trial's program theory and essential for the trial's internal validity and interpretation.

Objective: This analysis assessed and compared dietary intake by arm within a sub-sample of infants enrolled in the MMT.

Postprandial Vascular Effects of a High Potassium Meal in Patients with Treated Hypertension.

Background: There is compelling evidence of an inverse association between potassium intake and blood pressure (BP). A potential mechanism for this effect may be dietary potassium-mediated augmentation of endothelium-dependent relaxation. To date, studies have investigated potassium intake supplementation over several weeks in healthy volunteers with variable results on vascular function.

Redosing with Intralymphatic GAD-Alum in the Treatment of Type 1 Diabetes: The DIAGNODE-B Pilot Trial.

Immunotherapies aimed at preserving residual beta cell function in type 1 diabetes have been successful, although the effect has been limited, or raised safety concerns. Transient effects often observed may necessitate redosing to prolong the effect, although this is not always feasible or safe. Treatment with intralymphatic GAD-alum has been shown to be tolerable and safe in persons with type 1 diabetes and has shown significant efficacy to preserve C-peptide with associated clinical benefit in individuals with the human leukocyte antigen DR3DQ2 haplotype.