Long-Term Prognosis of Patients With Coexisting Obesity and Malnutrition After Acute Myocardial Infarction: A Cohort Study.

Background: The double burden of malnutrition, described as the coexistence of malnutrition and obesity, is a growing global health issue. This study examines the combined effects of obesity and malnutrition on patients with acute myocardial infarction (AMI).

Methods: Patients presenting with AMI to a percutaneous coronary intervention-capable hospital in Singapore between January 2014 and March 2021 were retrospectively studied.

The association of epicardial adipose tissue volume and density with coronary calcium in HIV-positive and HIV-negative patients.

Aims: We sought to assess and compare the association of epicardial adipose tissue (EAT) with cardiovascular disease (CVD) in HIV-positive and HIV-negative groups.

Methods And Results: Using existing clinical databases, we analyzed 700 patients (195 HIV-positive, 505 HIV-negative). CVD was quantified by the presence of coronary calcification from both dedicated cardiac computed tomography (CT) and non-dedicated CT of the thorax.

Prevalence of Potentially Clinically Significant Drug-Drug Interactions With Antiretrovirals Against HIV Over Three Decades: A Systematic Review of the Literature.

Background: Contemporary first-line antiretrovirals have considerably reduced liability for clinically significant drug-drug interactions (DDI). This systematic review evaluates the prevalence of DDI among people receiving antiretrovirals across 3 decades.

Methods: We searched 3 databases for studies reporting the prevalence of clinically significant DDIs in patients receiving antiretrovirals published between January 1987 and July 2022.

Characterization of the minimal residual disease state reveals distinct evolutionary trajectories of human glioblastoma.

Recurrence of solid tumors renders patients vulnerable to advanced, treatment-refractory disease state with mutational and oncogenic landscape distinctive from initial diagnosis. Improving outcomes for recurrent cancers requires a better understanding of cell populations that expand from the post-therapy, minimal residual disease (MRD) state. We profile barcoded tumor stem cell populations through therapy at tumor initiation, MRD, and recurrence in our therapy-adapted, patient-derived xenograft models of glioblastoma (GBM).

Pre-Clinical Evaluation of Tenofovir and Tenofovir Alafenamide for HIV-1 Pre-Exposure Prophylaxis in Foreskin Tissue.

Background: HIV-1 pre-exposure prophylaxis (PrEP) has focused predominantly on protective efficacy in receptive sex, with limited research on the dosing requirements for insertive sex. We pre-clinically assessed the ex vivo pharmacokinetic-pharmacodynamic (PK-PD) profile of tenofovir (TFV) and tenofovir alafenamide (TAF) in foreskin tissue.

Methods: Inner and outer foreskin explants were exposed to serial dilutions of TFV or TAF prior to addition of HIV-1 at a high (HVT) or a low viral titer (LVT).

Recommendations for the Management of Drug-Drug Interactions Between the COVID-19 Antiviral Nirmatrelvir/Ritonavir (Paxlovid) and Comedications.

The coronavirus disease 2019 (COVID-19) antiviral nirmatrelvir/ritonavir (Paxlovid) has been granted authorization or approval in several countries for the treatment of patients with mild to moderate COVID-19 at high risk of progression to severe disease and with no requirement for supplemental oxygen. Nirmatrelvir/ritonavir will be primarily administered outside the hospital setting as a 5-day course oral treatment. The ritonavir component boosts plasma concentrations of nirmatrelvir through the potent and rapid inhibition of the key drug-metabolizing enzyme cytochrome P450 (CYP) 3A4.

Prescribing Nirmatrelvir-Ritonavir: How to Recognize and Manage Drug-Drug Interactions.

Nirmatrelvir–ritonavir (NMV/r) is now being used to treat high-risk patients with mild to moderate COVID-19. This article provides advice to clinicians regarding recognition of medications likely to interact with NMV/r and suggests approaches to managing such drug–drug interactions. An algorithm is provided to assist in decision making.

An Open Label, Adaptive, Phase 1 Trial of High-Dose Oral Nitazoxanide in Healthy Volunteers: An Antiviral Candidate for SARS-CoV-2.

Repurposing approved drugs may rapidly establish effective interventions during a public health crisis. This has yielded immunomodulatory treatments for severe coronavirus disease 2019 (COVID-19), but repurposed antivirals have not been successful to date because of redundancy of the target in vivo or suboptimal exposures at studied doses. Nitazoxanide is a US Food and Drug Administration (FDA) approved antiparasitic medicine, that physiologically-based pharmacokinetic (PBPK) modeling has indicated may provide antiviral concentrations across the dosing interval, when repurposed at higher than approved doses.

Associations of Hepatosteatosis With Cardiovascular Disease in HIV-Positive and HIV-Negative Patients: The Liverpool HIV-Heart Project.

Background: Hepatosteatosis (HS) has been associated with cardiovascular disorders in the general population. We sought to investigate whether HS is a marker of cardiovascular disease (CVD) risk in HIV-positive individuals, given that metabolic syndrome is implicated in the increasing CVD burden in this population.

Aims: To investigate the association of HS with CVD in HIV-positive and HIV-negative individuals.

Enhanced and Timely Investigation of ARVs for Use in Pregnant Women.

Background: Concerns have been voiced that the exclusion of pregnant women from clinical trials results in a lack of safety and pharmacokinetic data for antiretroviral drugs (ARVs) in pregnancy, creating clear risks to pregnant women living with HIV (PWLHIV), and their infants.

Setting: The World Health Organization convened a Paediatric Antiretroviral Drug Optimization group meeting, December 10-12, 2018, in Geneva, Switzerland.

Methods: The group, comprised of clinicians, scientists, HIV program managers, regulators, and community representatives, were tasked to consider how ARVs are studied in PWLHIV, define alternative approaches to studying ARVs in PWLHIV, identify ways to shorten the timeline to determine safe use of new agents during pregnancy, and define strategies to collaborate with regulators and industry to change longstanding practices.

Targeting Glycosylated PD-1 Induces Potent Antitumor Immunity.

Immunotherapies targeting programmed cell death protein 1 (PD-1) and programmed cell death 1 ligand 1 (PD-L1) immune checkpoints represent a major breakthrough in cancer treatment. PD-1 is an inhibitory receptor expressed on the surface of activated T cells that dampens T-cell receptor (TCR)/CD28 signaling by engaging with its ligand PD-L1 expressed on cancer cells. Despite the clinical success of PD-1 blockade using mAbs, most patients do not respond to the treatment, and the underlying regulatory mechanisms of PD-1 remain incompletely defined.

Case 237: Renal Cell Carcinoma with Osseous Metaplasia.

History A 47-year-old man presented with palpitations and decreased exercise tolerance. A peripheral blood smear revealed anemia, thrombocytopenia, and blast cells, and a diagnosis of acute myeloid leukemia was made. Immunohistochemistry revealed positivity for cluster of differentiation (or CD) markers, which have been reported to be associated with an increased risk of extramedullary leukemic involvement.

Comparison of the utility of Cocaine- and Amphetamine-Regulated Transcript (CART), chromogranin A, and chromogranin B in neuroendocrine tumor diagnosis and assessment of disease progression.

Context: Prognosis in patients with neuroendocrine tumors (NETs) is often poor, frequently reflecting delayed diagnosis. Hence, accurate and practical NET markers are needed. Cocaine- and amphetamine-regulated transcript (CART) peptide is a potential novel NET marker.

Tricuspid regurgitation in hypoplastic left heart syndrome: mechanistic insights from 3-dimensional echocardiography and relationship with outcomes.

Background: Our purpose was to test the following hypotheses: (1) patients with hypoplastic left heart syndrome who develop significant tricuspid regurgitation (TR) or require tricuspid valve (TV) surgery in the medium term have detectable TV abnormalities by 3-dimensional echocardiography (3DE) prestage 1 palliation and (2) TR is associated with reduced survival and increased TV intervention.

Methods And Results: Infants were prospectively studied with 3DE and 2DE prestage 1 and followed up for the end points of TR, TV surgery, transplantation, or death. From prestage 1 3DE, spatial coordinates of TV annulus and leaflets were extracted; annulus size, leaflet area, prolapse volume, tethering volume, bending angle, and papillary muscle angle were measured.