Adjuvant Atezolizumab for Early Triple-Negative Breast Cancer: The ALEXANDRA/IMpassion030 Randomized Clinical Trial.

Importance: Triple-negative breast cancer is an aggressive subtype with a high incidence in young patients, a high incidence in non-Hispanic Black women, and a high risk of progression to metastatic cancer, a devastating sequela with a 12- to 18-month life expectancy. Until recently, one strategy for treating early-stage triple-negative breast cancer was chemotherapy after surgery. However, it was not known whether the addition of immune therapy to postsurgery chemotherapy would be beneficial.

Recent progress in xenotransplantation and its application to pediatric kidney disease.

Patients with kidney failure require dialysis or kidney transplantation. Kidney transplantation offers great benefits, including reduced mortality; however, many patients who wish to undergo kidney transplantation are unable to do so due to a shortage of donor organs. This shortage is a global issue, and xenotransplantation has emerged as a potential solution.

Generalizability of Randomized Controlled Trials to Routine Clinical Care in Ulcerative Colitis.

Background: Historically, randomized controlled trials (RCTs) have been criticized for being poorly generalizable to patients with ulcerative colitis (UC) evaluated in routine care. We aimed to evaluate the proportion of patients with UC starting an advanced therapy who would be eligible to participate in phase 3 registrational UC RCTs.

Methods: We conducted a retrospective cohort analysis of UC patients starting vedolizumab, ustekinumab, or tofacitinib at 2 IBD clinics at the University of Calgary.

Inactivation of CaV1 and CaV2 channels.

Voltage-gated Ca2+ channels (VGCCs) are highly expressed throughout numerous biological systems and play critical roles in synaptic transmission, cardiac excitation, and muscle contraction. To perform these various functions, VGCCs are highly regulated. Inactivation comprises a critical mechanism controlling the entry of Ca2+ through these channels and constitutes an important means to regulate cellular excitability, shape action potentials, control intracellular Ca2+ levels, and contribute to long-term potentiation and depression.

Sickle Cell Trait Does Not Cause "Sickle Cell Crisis" Leading to Exertion-Related Death: A Systematic Review.

Globally, an estimated 300 million individuals have sickle cell trait (SCT), the carrier state for sickle cell disease. While sickle cell disease (SCD) is associated with increased morbidity and shortened lifespan, SCT has a lifespan comparable to that of the general population. However, "sickle cell crisis" has been used as a cause of death for decedents with SCT in reports of exertion-related death in athletes, military personnel, and individuals in police custody.

Associations of Traumatic Brain Injury and Mild Behavioral Impairment With Cognitive Function and Dementia.

Objective: Traumatic Brain Injury (TBI) may contribute additional complexity to the clinical picture of mild behavioral impairment (MBI). MBI, a behavioral analog to mild cognitive impairment (MCI), is comprised of five neuropsychiatric domains: decreased motivation, affective dysregulation, impulse dyscontrol, social inappropriateness, and abnormal perception/thought content. We investigated (1) if cross-sectional associations of cognitive status with MBI symptoms differ by TBI status and (2) if prospective associations of MBI domain positivity with incident dementia risk differ by TBI status.

Ventral Rectopexy: An International Expert Panel Consensus and Review of Contemporary Literature.

Background: Ventral rectopexy has become increasingly utilized in the surgical management of rectal prolapse. There is a need for a contemporary evaluation of the role of the procedure and description of its use in clinical practice.

Objective: To create an international consensus on ventral rectopexy.

Validation of a Novel MRI Biomarker of Infarct Severity to Predict Functional Outcome After Endovascular Thrombectomy.

Endovascular thrombectomy (EVT) dramatically improves clinical outcomes, but the final infarct volume (FIV) on MRI only accounts for a minority of the treatment effect. An imaging biomarker that more strongly correlates with post-EVT functional outcome would be helpful for clinical prognosis and serve as a surrogate outcome measure in trials of EVT-adjuvant therapies. Here, we aimed to validate a novel MRI-based metric, infarct density, which leverages post-EVT apparent diffusion coefficient (ADC) as a marker of infarct severity.

Impaired Exercise Capacity in High-Risk Diabetic Cardiomyopathy: The ARISE-HF Cardiopulmonary Exercise Testing Subanalysis.

Background: Objective indices of functional capacity in patients with diabetic cardiomyopathy and stage B heart failure (HF) have not been comprehensively defined. We sought to characterize the cardiopulmonary exercise characteristics of individuals with diabetic cardiomyopathy at high risk for overt HF.

Methods: The relationships from cardiopulmonary exercise testing with clinical and laboratory characteristics of participants with diabetic cardiomyopathy were evaluated using baseline data from the ARISE-HF trial (Aldose Reductase Inhibition for Stabilization of Exercise Capacity in Heart Failure).

Impaired Resting State Functional Connectivity in CADASIL Mutant Mice.

Cerebral autosomal-dominant arteriopathy, subcortical infarcts, and leukoencephalopathy (CADASIL) is the most prevalent monogenic inherited cause of cerebral small-vessel disease. Despite its prevalence, there is currently no proven therapy to prevent or reverse the progression of the disease. This study aimed to characterize the functional integrity of long white matter tracts in CADASIL transgenic mice, both with and without focal white matter lesions in the corpus callosum added on, utilizing optical resting-state functional connectivity imaging alongside behavioral examinations.

Predicting Atrial Fibrillation After Stroke by Combining Polygenic Risk Scores and Clinical Features.

Since treatment with anticoagulants can prevent recurrent strokes, identification of patients at risk for incident AF after stroke is crucial. We aimed to investigate whether the addition of AF polygenic risk scores (PRS) to existing clinical risk predictors could improve prediction of AF after stroke. Patients diagnosed with ischemic stroke at Massachusetts General Hospital between 2003-2017 were included.

Characterization of LTBP2 mutation causing mitral valve prolapse.

Aims: Mitral valve prolapse (MVP) is a common valvular disorder associated with significant morbidity and mortality, with a strong genetic basis. This study aimed to identify a mutation in a family with MVP and to characterize the valve phenotype in LTBP2 knockout (KO) mice.

Methods And Results: Exome sequencing and segregation analysis were performed on a large family with MVP.

Optimizing Clinical Postgraduate Training: Perspectives of Postgraduate Alumni Regarding Their Residency Training at Mbarara University of Science and Technology, Uganda.

Background: Understanding alumni satisfaction and the competencies gained during university training can guide improvements in education quality, particularly in higher education institutions. This study at Mbarara University of Science and Technology (MUST) explored the factors influencing alumni decisions, their residency experiences, and their levels of satisfaction. Additionally, it provided recommendations for improving graduate training programs.

Developing a Novel Integrative Health Equity and Anti-racism Tool (IHEART) for Pilot Application in a Multicenter Integrative Health Elective for Medical Students and Resident Physicians: A Study Protocol.

Background: This study protocol introduces the Integrative Health Equity and Anti-Racism Tool (IHEART), an innovative instrument designed to infuse equity, diversity, and inclusion (EDI) into Integrative Health (IH) education. Recognizing the gaps in current IH training that fail to address social and systemic inequities adequately, the IHEART is intended to respond to the growing need for inclusivity in IH practices and educational materials. The tool is mainly focused on addressing issues such as accessibility of complementary and integrative health (CIH) therapies, cultural misappropriation, anti-racism, gender diversity, disability justice, trauma-informed care, weight inclusivity, and planetary health, which are currently inconsistently covered in IH training.

Adult onset wilms tumor.

Wilms tumor (WT) is the most common primary renal malignancy in the pediatric population and has very good overall survival with contemporary treatment protocols. In contrast, WT in adults is extremely rare and is associated with a poorer prognosis. The clinical presentation and imaging features of WT in adults are nonspecific and overlap with other more common forms of renal cancer, often leading to a delay in diagnosis.

Enhancing transcranial ultrasound stimulation planning with MRI-derived skull masks: a comparative analysis with CT-based processing.

Transcranial ultrasound stimulation (TUS) presents challenges in ultrasound wave transmission through the skull, affecting study outcomes due to aberration and attenuation. While planning strategies incorporating 3D computed tomography (CT) scans help mitigate these issues, they expose participants to radiation, which can raise ethical concerns. A solution involves generating skull masks from participants' anatomical magnetic resonance imaging (MRI).

The role of renal dual-energy computed tomography in exploring the gouty kidney: the RENODECT study.

Objective: The objective of this study was to explore the ability of dual-energy computed tomography (DECT) to detect monosodium urate (MSU) crystal deposits in the kidneys and renal artery walls, and uric acid urolithiasis, in patients with gout and chronic kidney disease (CKD).

Methods: Patients with gout and with stage 2-4 CKD were prospectively included in this cross-sectional study. Patients underwent renal, knee and feet DECT scans.

Subtypes A1 and D, and recombinant HIV-1 natural polymorphisms associated with lenacapavir drug resistance in Uganda.

Background: Lenacapavir, a novel HIV-1 capsid inhibitor, shows promise for treating MDR HIV-1, as well as for pre-exposure prophylaxis (PrEP) in prevention of HIV infection. Its unique mechanism and lack of cross-resistance with other antiretroviral classes make lenacapavir a significant addition to HIV therapy. The clinical trials CALIBRATE and CAPELLA have demonstrated high viral suppression rates in both ART-naive individuals and individuals with MDR HIV-1.

Health-Related Social Needs Intervention for Adolescents and Young Adults With Type 2 Diabetes and Their Caregivers: An Exploratory Study Using Human-Centered Design.

Youth-onset type 2 diabetes (T2D) is increasingly common and projected to impact over 200,000 adolescents and young adults by 2060. Youth with T2D frequently experience health-related social needs (HRSN) that increase their risk for poor outcomes. Using human-centered design methodology, we explored how best to address HRSN in pediatric endocrinology clinics.

Ultrasound-guided intraoperative liver ablation - retrospective review of indications and outcomes.

Aim: To define the indications and outcomes of intraoperative ablation of hepatic malignancies.

Materials And Methods: This retrospective study comprises 27 patients (male/female: 19/8; mean age: 56 ± 13) undergoing intraoperative ablation (IOA) of liver tumours between July 2001 and August 2021 for 42 tumours, including colorectal liver metastasis (CRLM) (n = 27), hepatocellular carcinoma (HCC)(n = 14), and ovarian cancer metastasis (n = 1). The mean tumour diameter was 2.

Positive STEPS: Enhancing Medication Adherence and Achieving Viral Load Suppression in Youth Living with HIV in the United States - Results from a Stepped-Care Randomized Controlled Efficacy Trial.

Background: In the U.S. and worldwide, there is a significant number of young people acquiring and living with HIV.

Medical management pathways for Cushing's disease in pituitary tumors centers of excellence (PTCOEs).

Purpose: A recent update of consensus guidelines for the management of Cushing's disease (CD) included indications for medical therapy. However, there is limited evidence regarding their implementation in clinical practice. This study aimed to evaluate current medical therapy approaches by expert pituitary centers through an audit conducted to validate the criteria of Pituitary Tumors Centers of Excellence (PTCOEs) and provide an initial standard of medical care for CD.

APOE4 and sedentary lifestyle synergistically impair neurovascular function in the visual cortex of awake mice.

Reduced cerebral blood flow occurs early in the development of Alzheimer's disease (AD), but the factors producing this reduction are unknown. Here, we ask whether genetic and lifestyle risk factors for AD-the ε4 allele of the Apolipoprotein (APOE) gene, and physical activity-can together produce this reduction in cerebral blood flow which leads eventually to AD. Using in vivo two-photon microscopy and haemodynamic measures, we record neurovascular function from the visual cortex of physically active or sedentary mice expressing APOE3 and APOE4 in place of murine APOE.