Examining Medicaid Waivers-An Opportunity to Promote Equity in Cancer Care.

This Viewpoint discusses the impact of Medicaid Section 1115 waivers on the equity of cancer care delivery in the US.

Longitudinal outcomes of final kissing balloon inflation in coronary bifurcation lesions treated with a single stent.

Background: Final kissing balloon inflation (FKBI) is a percutaneous coronary intervention (PCI) technique that is considered mandatory to improve outcomes in two-stent strategies, but its use in single-stent bifurcation PCI remains controversial. Methods: In this retrospective cohort study, we identified patients with coronary bifurcation lesions treated with one stent from January 2012 to March 2021 at a single academic medical center. Incidence rates per 1,000 patient-years (IR1000) were calculated for the outcomes of all-cause mortality, myocardial infarction (MI), stent thrombosis (ST), target lesion revascularization (TLR), coronary artery bypass graft (CABG), and cardiac readmission between patients who received FKBI and those who did not over a median follow up of 2.3 years. Studied outcomes were adjusted for all baseline clinical and procedural characteristics. Results: This study included 893 consecutive patients of which 256 received FKBI and 637 did not. The IR1000 for MI were 51.1 and 27.6 for patients who received FKBI and patients who did not, respectively (adjusted HR = 2.44, p = 0.001). The IR1000 for death were 31.2 and 52.3 for patients who received FKBI and patients who did not, respectively (adjusted HR = 0.68, p = 0.141). The incidence rates of ST, TLR, CABG, and cardiac readmissions were similar between patients who received FKBI and those who did not. Conclusions: These results suggest that performing FKBI in a one-stent technique was associated with higher rates of myocardial infarction, particularly in the first 6 months, and no difference in death, ST, TLR, CABG, and cardiac readmission rates.

Aberrant Ca2+ signaling by IP3Rs in adipocytes links inflammation to metabolic dysregulation in obesity.

Chronic metabolic inflammation is a key feature of obesity, insulin resistance, and diabetes. Here, we showed that altered regulation of the Ca2+ channel inositol trisphosphate receptor (IP3R) was an adipocyte-intrinsic event involved in the emergence and propagation of inflammatory signaling and the resulting insulin resistance. Inflammation induced by cytokine exposure in vitro or by obesity in vivo led to increases in the abundance and activity of IP3Rs and in the phosphorylation of the Ca2+-dependent kinase CaMKII in adipocytes in a manner dependent on the kinase JNK. In mice, adipocyte-specific loss of IP3R1/2 protected against adipose tissue inflammation and insulin resistance, despite the mice exhibiting substantial diet-induced weight gain. Thus, this work suggests that increased IP3R activity is a key link between obesity, inflammation, and insulin resistance. These data also suggest that approaches to target IP3R-mediated Ca2+ homeostasis in adipocytes may offer new therapeutic opportunities against metabolic diseases, especially because GWAS studies also implicate this locus in human obesity.

Membrane Trafficking Protein CDP138 Regulates Fat Browning and Insulin Sensitivity through Controlling Catecholamine Release.

CDP138 is a calcium- and lipid-binding protein that is involved in membrane trafficking. Here, we report that mice without CDP138 develop obesity under normal chow diet (NCD) or high-fat diet (HFD) conditions. CDP138-/- mice have lower energy expenditure, oxygen consumption, and body temperature than wild-type (WT) mice. CDP138 is exclusively expressed in adrenal medulla and is colocalized with tyrosine hydroxylase (TH), a marker of sympathetic nervous terminals, in the inguinal fat. Compared with WT controls, CDP138-/- mice had altered catecholamine levels in circulation, adrenal gland, and inguinal fat. Adrenergic signaling on cyclic AMP (cAMP) formation and hormone-sensitive lipase (HSL) phosphorylation induced by cold challenge but not by an exogenous ß3 adrenoceptor against CL316243 were decreased in adipose tissues of CDP138-/- mice. Cold-induced beige fat browning, fatty acid oxidation, thermogenesis, and related gene expression were reduced in CDP138-/- mice. CDP138-/- mice are also prone to HFD-induced insulin resistance, as assessed by Akt phosphorylation and glucose transport in skeletal muscles. Our data indicate that CDP138 is a regulator of stress response and plays a significant role in adipose tissue browning, energy balance, and insulin sensitivity through regulating catecholamine secretion from the sympathetic nervous terminals and adrenal gland.