How do restrictions on opioid prescribing, harm reduction, and treatment coverage policies relate to opioid overdose deaths in the United States in 2013-2020? An application of a new state opioid policy scale.

Background: Identifying the most effective state laws and provisions to reduce opioid overdose deaths remains critical.

Methods: Using expert ratings of opioid laws, we developed annual state scores for three domains: opioid prescribing restrictions, harm reduction, and Medicaid treatment coverage. We modeled associations of state opioid policy domain scores with opioid-involved overdose death counts in 3133 counties, and among racial/ethnic subgroups in 1485 counties (2013-2020).

The relationship of medical and recreational cannabis laws with opioid misuse and opioid use disorder in the USA: Does it depend on prior history of cannabis use?

Background: Wider availability of cannabis through medical and recreational legalization (MCL alone and RCL+MCL) has been hypothesized to contribute to reductions in opioid use, misuse, and related harms. We examined whether state adoption of cannabis laws was associated with changes in opioid outcomes overall and stratified by cannabis use.

Methods: Using National Survey on Drug Use and Health (NSDUH) data from 2015 to 2019, we estimated cannabis law associations with opioid (prescription opioid misuse and/or heroin use) misuse and use disorder.

A fatal case of peritonitis due to colonic localization of acute myeloid leukemia.

Myeloid sarcoma (MS) is an extramedullary localization of immature granulocyte cells that can occur in association with acute myeloid leukemia (AML). Gastrointestinal involvement is relatively common in MS, but exclusive colonic localization is a rare occurrence. Here, we report on a 53-year-old male patient affected by AML developing a severe abdominal pain caused by intestinal perforation requiring surgical intervention.

Polymer-free versus biodegradable-polymer drug-eluting stent in patients undergoing percutaneous coronary intervention: an assessor-blind, non-inferiority, randomised controlled trial.

Background: Few data are available on polymer-free drug-eluting stents in patients undergoing percutaneous coronary intervention (PCI).

Aims: We aimed to determine the efficacy and safety of a polymer-free amphilimus-eluting stent (AES), using a reservoir-based technology for drug delivery, compared with a biodegradable-polymer everolimus-eluting stent (EES).

Methods: This was a randomised, investigator-initiated, assessor-blind, non-inferiority trial conducted at 14 hospitals in Italy (ClinicalTrials.

Depression is Associated with Treatment Response Trajectories in Adults with Prolonged Grief Disorder: A Machine Learning Analysis.

Unlabelled: Although evidence-based treatments for Prolonged Grief Disorder (PGD) exist, pretreatment characteristics associated with differential improvement trajectories have not been identified. To identify clinical factors relevant to optimizing PGD treatment outcomes, we used unsupervised and supervised machine learning to study treatment effects from a double-blinded, placebo-controlled, randomized clinical trial. Participants were randomized into four treatment groups for 20 weeks: citalopram with grief-informed clinical management, citalopram with prolonged grief disorder therapy (PGDT), pill placebo with PGDT, or pill placebo with clinical management.

The sedoheptulose kinase CARKL controls T-cell cytokine outputs and migration by promoting metabolic reprogramming.

Background: Immunometabolism is a crucial determinant of immune cell function, influencing cellular activation and differentiation through metabolic pathways. The intricate interplay between metabolism and immune responses is highlighted by the distinct metabolic programs utilized by immune cells to support their functions. Of particular interest is the pentose phosphate pathway (PPP), a key metabolic pathway branching out of glycolysis that plays a pivotal role in generating NADPH and pentose sugars crucial for antioxidant defense and biosynthesis.

Age-related loss of intestinal barrier integrity plays an integral role in thymic involution and T cell ageing.

The intestinal epithelium serves as a physical and functional barrier against harmful substances, preventing their entry into the circulation and subsequent induction of a systemic immune response. Gut barrier dysfunction has recently emerged as a feature of ageing linked to declining health, and increased intestinal membrane permeability has been shown to promote heightened systemic inflammation in aged hosts. Concurrent with age-related changes in the gut microbiome, the thymic microenvironment undergoes a series of morphological, phenotypical and architectural alterations with age, including disorganisation of the corticomedullary junction, increased fibrosis, increased thymic adiposity and the accumulation of senescent cells.

Medicaid expansion and medications to treat opioid use disorder in outpatient specialty care from 2010 to 2020.

Introduction: Medications for opioid use disorder (MOUD) are considered the first line treatment for opioid use disorder. As states expanded Medicaid beginning in 2014 under the Affordable Care Act, policymakers and public health officials were interested in the potential for expansion to increase access to MOUD. This study examined whether there were changes in MOUD use within outpatient admissions to specialty treatment facilities in Medicaid expansion states beyond the initial expansion period.

The Role of Vericiguat in Early Phases of Anterior Myocardial Infarction: A Potential Game-Changer?

Anterior myocardial infarction is a critical condition with significant implications for cardiac function and patient prognosis. Despite advancements in reperfusion therapies, optimizing recovery during the early phases of myocardial infarction remains challenging. Anterior myocardial infarction can lead to substantial long-term effects on a patient's health due to extensive damage to the heart muscle, particularly the left ventricle, impacting both quality of life and overall prognosis.

PCSK9 Inhibitors: Is the Time Ripe for the "Fast Track" Use Independently on the LDL-C Baseline Values in Acute Coronary Syndrome?

The low-density lipoprotein cholesterol (LDL-C) lowering decreases the risk to develop major adverse cardiovascular events (MACE) in patients with acute coronary syndrome (ACS). Therefore, the "fast track" use of PCSK9 inhibitors (PCSK9i) has been introduced in ACS patients not achieving LDL-C target (70 mg/dl) despite an ongoing lipid lowering therapy with statin at maximum tolerated dosage plus ezetimibe or stain-naïve (LDL-C > 130 mg/dl). PCSK9i "fast track" use has shown to achieve the regression of "non-culprit" atherosclerotic plaques leading to a further MACE decrease.

The Combined Relationship of Prescription Drug Monitoring Program Enactment and Medical Cannabis Laws with Chronic Pain-Related Healthcare Visits.

Background: U.S. state electronic prescription drug monitoring programs (PDMPs) are associated with reduced opioid dispensing among people with chronic pain and may impact use of other chronic pain treatments.

mutation analysis in circulating tumor cells of patients with hormone receptor positive metastatic breast cancer.

In metastatic breast cancer (MBC), blood is a source of circulating tumor cells (CTCs). CTCs may serve as a ''real-time liquid biopsy" as they represent metastatic tumor genetics better than primary tumor. is one of the most important oncogenes in treatment-unresponsive breast cancers.

The role of prescription opioid and cannabis supply policies on opioid overdose deaths.

Mandatory prescription drug monitoring programs and cannabis legalization have been hypothesized to reduce overdose deaths. We examined associations between prescription monitoring programs with access mandates ("must-query PDMPs"), legalization of medical and recreational cannabis supply, and opioid overdose deaths in United States counties in 2013-2020. Using data on overdose deaths from the National Vital Statistics System, we fit Bayesian spatiotemporal models to estimate risk differences and 95% credible intervals (CrI) in county-level opioid overdose deaths associated with enactment of these state policies.

Immunometabolism in atherosclerosis: a new understanding of an old disease.

Atherosclerosis, a chronic inflammatory condition, remains a leading cause of death globally, necessitating innovative approaches to target pro-atherogenic pathways. Recent advancements in the field of immunometabolism have highlighted the crucial interplay between metabolic pathways and immune cell function in atherogenic milieus. Macrophages and T cells undergo dynamic metabolic reprogramming to meet the demands of activation and differentiation, influencing plaque progression.

Fluorinated perhexiline derivative attenuates vascular proliferation in pulmonary arterial hypertension smooth muscle cells.

Increased proliferation and reduced apoptosis of pulmonary artery smooth muscle cells (PASMCs) is recognised as a universal hallmark of pulmonary arterial hypertension (PAH), in part related to the association with reduced pyruvate dehydrogenase (PDH) activity, resulting in decreased oxidative phosphorylation of glucose and increased aerobic glycolysis (Warburg effect). Perhexiline is a well-recognised carnitine palmitoyltransferase-1 (CPT1) inhibitor used in cardiac diseases, which reciprocally increases PDH activity, but is associated with variable pharmacokinetics related to polymorphic variation of the cytochrome P450-2D6 (CYP2D6) enzyme, resulting in the risk of neuro and hepatotoxicity in 'slow metabolisers' unless blood levels are monitored and dose adjusted. We have previously reported that a novel perhexiline fluorinated derivative (FPER-1) has the same therapeutic profile as perhexiline but is not metabolised by CYP2D6, resulting in more predictable pharmacokinetics than the parent drug.

Canonical and non-canonical roles of complement in atherosclerosis.

Cardiovascular diseases are the leading cause of death globally, and atherosclerosis is the major contributor to the development and progression of cardiovascular diseases. Immune responses have a central role in the pathogenesis of atherosclerosis, with the complement system being an acknowledged contributor. Chronic activation of liver-derived and serum-circulating canonical complement sustains endothelial inflammation and innate immune cell activation, and deposition of complement activation fragments on inflamed endothelial cells is a hallmark of atherosclerotic plaques.

Thioredoxin is a metabolic rheostat controlling regulatory B cells.

Metabolic programming is important for B cell fate, but the bioenergetic requirement for regulatory B (B) cell differentiation and function is unknown. Here we show that B cell differentiation, unlike non-B cells, relies on mitochondrial electron transport and homeostatic levels of reactive oxygen species (ROS). Single-cell RNA sequencing analysis revealed that TXN, encoding the metabolic redox protein thioredoxin (Trx), is highly expressed by B cells, unlike Trx inhibitor TXNIP which was downregulated.