Investigating the association of traditional and non-traditional tobacco product use with subclinical and clinical cardiovascular disease: The Cross-Cohort Collaboration-Tobacco working group rationale, design, and methodology.

While the impact of combustible cigarette smoking on cardiovascular disease (CVD) is well-established, the longitudinal association of non-traditional tobacco products with subclinical and clinical CVD has not been fully explored due to: 1) limited data availability; and 2) the lack of well-phenotyped prospective cohorts. Therefore, there is the need for sufficiently powered well-phenotyped datasets to fully elucidate the CVD risks associated with non-cigarette tobacco products. The Cross-Cohort Collaboration (CCC)-Tobacco is a harmonized dataset of 23 prospective cohort studies predominantly in the US. A priori defined variables collected from each cohort included baseline characteristics, details of traditional and non-traditional tobacco product use, inflammatory markers, and outcomes including subclinical and clinical CVD. The definitions of the variables in each cohort were systematically evaluated by a team of two physician-scientists and a biostatistician. Herein, we describe the method of data acquisition and harmonization and the baseline sociodemographic and risk profile of participants in the combined CCC-Tobacco dataset. The total number of participants in the pooled cohort is 322782 (mean age: 59.7 ± 11.8 years) of which 76% are women. White individuals make up the majority (73.1%), although there is good representation of other race and ethnicity groups including African American (15.6%) and Hispanic/Latino individuals (6.4%). The prevalence of participants who never smoked, formerly smoked, and currently smoke combustible cigarettes is 50%, 36%, and 14%, respectively. The prevalence of current and former cigar, pipe, and smokeless tobacco is 7.3%, 6.4%, and 8.6%, respectively. E-cigarette use was measured only in follow-up visits of select studies, totaling 1704 former and current users. CCC-Tobacco is a large, pooled cohort dataset that is uniquely designed with increased power to expand knowledge regarding the association of traditional and non-traditional tobacco use with subclinical and clinical CVD, with extension to understudied groups including women and individuals from underrepresented racial-ethnic groups.

Transitioning to GLP-1 RAs and SGLT2 Inhibitors as the First Choice for Managing Cardiometabolic Risk in Type 2 Diabetes.

PURPOSE OF REVIEW: This forward-looking review summarizes existing evidence from cardiovascular outcome trials on cardiometabolic risk-reduction in type 2 diabetes (T2DM) management, with attention to updating and personalizing recommendations from recent diabetes practice guidelines issued by cardiology societies. RECENT FINDINGS: T2DM management has shifted towards cardiometabolic outcome improvement rather than purely glycemic control. According to large clinical trials, sodium-glucose cotransporter-2 inhibitors showed robust results in reducing heart failure (HF) hospitalization and chronic kidney disease (CKD) progression, while glucagon-like peptide-1 receptor agonists demonstrated the largest effects on HbA1c reduction, weight loss, and atherosclerotic cardiovascular disease outcomes prevention, including stroke. Considering the distinct features of these new cardiometabolic agents, initial selection of therapy should be targeted to each individual patient, with consideration of combination therapy for the highest risk patients. Moreover, future studies should investigate the addition of obesity-predominant risk, in conjunction with coronary artery disease, stroke, CKD, and HF, as a new influential indicator for choosing the optimal cardiometabolic agent.

Prognostic implications of prior contrast reaction in patients with emergency premedication before undergoing percutaneous coronary intervention.

BACKGROUND: Patients with iodinated contrast material (ICM) adverse reactions are at increased risk for breakthrough reactions. Previous studies suggest that the severity of a prior ICM adverse reaction corresponds to the severity of a repeat reaction. OBJECTIVE: We investigated whether the severity of prior ICM adverse reactions in patients receiving emergency premedication therapy prior to PCI predicts outcomes. METHODS: A retrospective observational study of percutaneous coronary intervention (PCI) encounters between January 1, 2005, and May 30, 2018, was conducted at Geisinger Medical Center. Patients with ICM adverse reactions premedicated with an emergency premedication regimen prior to PCI were included in the study. PCIs were stratified based on the severity of the index ICM adverse reactions; PCIs with a prior severe reaction were compared to PCIs with a prior mild-moderate reaction. RESULTS: We evaluated 604 PCI, of these, 144 (23.8%) had prior severe reactions and 460 (76.2%) had mild-to-moderate reactions. Nine patients had breakthrough reactions, of which seven were of the same or decreased severity in comparison to the index reactions. The overall breakthrough reactions occurred in 1 of 144 patients (0.7%) with an initial severe reaction and in 8 of 460 (1.7%) with an initial mild/moderate reaction (p = 0.69). Outcomes including length of hospital stay and 30-day mortality were similar for PCI with or without severe index ICM reactions. CONCLUSION: Frequency and severity of breakthrough reaction and clinical outcomes in patients treated with emergency premedication regimen prior to PCI were independent of the severity of index ICM reactions.

Anti-proliferative and anti-malarial activities of spiroisoxazoline analogues of artemisinin.

A series of spiroisoxazoline analogues of artemisinin was synthesized by employing 1,3-dipolar cycloaddition between various in situ generated nitrile oxides and artemisitene. All the synthesized compounds were tested for their anti-proliferative and anti-malarial activities. Among the compounds tested, compound 11a was found to be potent against the HCT-15 cancer cell line with IC50 = 4.04 µM when compared to 5-fluorouracil (IC50 = 35.53 µM). DNA cell cycle analysis shows that 11a was inhibiting cell proliferation at the G2/M phase. Compound 11b was found to be most active against Plasmodium falciparum with IC50 = 0.1 µM and also blocked host hemoglobin hydrolysis by the falcipain-3 receptor. It was demonstrated to have better dynamics of parasite killing efficiency than artemisinin. Molecular docking studies revealed that these compounds interacted with falcipain-3 receptor sites.

Palytoxin-induced acute respiratory failure.

Palytoxin is one of the most potent toxins known to mankind and poses a high risk to humans through ingestion, inhalation and dermal routes [1,2]. Although the exact mechanism of action is unknown it is postulated that palytoxin binds to the Na+/K + ATPase pump resulting in K+ efflux, Ca2+ influx and membrane depolarization leading to widespread secondary pharmacological actions [2]. Palytoxin is highly toxic and can affect multiple organs causing severe symptoms including death. Palytoxin poisoning is mainly developed after ingesting seafood. We are reporting a case of suspected inhalational palytoxin poisoning in a healthy healthcare provider from who developed severe respiratory distress within 12 hours of exposure to vapors. We have highlighted diagnostic clues and clinical features in the patients' history that may help intensivists to diagnose a case of ARDS secondary to palytoxin poisoning.