Coronary artery disease mortality in patients treated for Hodgkin's disease.

The authors conducted a follow-up study of the association between mediastinal irradiation, chemotherapy, and mortality from coronary artery disease in 4665 patients treated for Hodgkin's disease. Study subjects were followed after the diagnosis of Hodgkin's disease until death or the closing date of the study. The average duration of follow-up was 7 years; 2415 patients died, and 124 cases of coronary artery disease were identified from death certificates, including 68 cases of acute myocardial infarction. The age-adjusted relative risks (RR) of death with any coronary artery disease after mediastinal irradiation and after chemotherapy were 1.87 (95% confidence interval [CI], 0.92 to 3.80) and 1.28 (CI, 0.77 to 2.15), respectively. A significantly increased risk of death in the subcategory myocardial infarction was observed after mediastinal irradiation (RR, 2.56; CI, 1.11 to 5.93) but not after chemotherapy (RR, 0.97; CI, 0.53 to 1.77). These results support the hypothesis that radiation therapy to the mediastinum increases the risk of coronary artery disease.     

Merkel Cell Polyomavirus DNA in Persons without Merkel Cell Carcinoma

Merkel cell polyomavirus (MCPyV) DNA was detected in 88% of Merkel cell carcinomas in contrast to 16% of other skin tumors. MCPyV was also found in anogenital and oral samples (31%) and eyebrow hairs (50%) of HIV-positive men and in forehead swabs (62%) of healthy controls. MCPyV thus appears to be widespread.     

Association between a hospitalization for heart failure and the initiation/discontinuation of guideline-recommended treatments: An analysis from the Swedish Heart Failure Registry

Aims

To investigate whether a heart failure (HF) hospitalization is associated with initiation/discontinuation of guideline-directed medical HF therapy (GDMT) and consequent outcomes.

Methods and results

Among patients in the Swedish HF registry with an ejection fraction <50% enrolled in 2009–2018, initiation/discontinuation of GDMT was investigated by assessing dispensations of GDMT in those with versus without a HF hospitalization. Of 14 737 patients, 6893 (47%) were enrolled when hospitalized for HF. Initiation of GDMT was more likely than discontinuation following a HF hospitalization compared to a control group of patients without a HF hospitalization (odds ratio range 2.1–4.0 vs. 1.4–1.6 for the individual medications), although the proportion of patients not on GDMT was still high (8.1–44.0%). Key patient characteristics triggering less use of GDMT (i.e. less initiation or more discontinuation) were older age and worse renal function. Following a HF hospitalization, initiation of renin–angiotensin system inhibitors/angiotensin receptor–neprilysin inhibitors or beta-blockers was associated with lower and their discontinuation with higher mortality risk, but no association with mortality was observed for initiation/discontinuation of mineralocorticoid receptor antagonists.

Conclusions

Following a HF hospitalization, initiation of GDMT was more likely than discontinuation, although still limited. Perceived or actual low tolerance were barriers to GDMT implementation. Early re-/initiation of GDMT was associated with better survival. Our findings represent a call for further implementing the current guideline recommendation for an early re-/initiation of GDMT following a HF hospitalization.     

Central insulin action regulates peripheral glucose and fat metabolism in mice

Insulin resistance is a hallmark of type 2 diabetes, and many insights into the functions of insulin have been gained through the study of mice lacking the IR. To gain a better understanding of the role of insulin action in the brain versus peripheral tissues, we created 2 mouse models with inducible IR inactivation, 1 in all tissues including brain (IRDeltawb), and 1 restricted to peripheral tissues (IRDeltaper). While downregulation of IR expression resulted in severe hyperinsulinemia in both models, hyperglycemia was more pronounced in IRDeltawb mice. Both strains displayed a dramatic upregulation of hepatic leptin receptor expression, while only IRDeltaper mice displayed increased hepatic Stat3 phosphorylation and Il6 expression. Despite a similar reduction in IR expression in white adipose tissue (WAT) mass in both models, IRDeltawb mice had a more pronounced reduction in WAT mass and severe hypoleptinemia. Leptin replacement restored hepatic Stat3 phosphorylation and normalized glucose metabolism in these mice, indicating that alterations in glucose metabolism occur largely as a consequence of lipoathrophy upon body-wide IR deletion. Moreover, chronic intracerebroventricular insulin treatment of control mice increased fat mass, fat cell size, and adipose tissue lipoprotein lipase expression, indicating that CNS insulin action promotes lipogenesis. These studies demonstrate that central insulin action plays an important role in regulating WAT mass and glucose metabolism via hepatic Stat3 activation.     

Resuscitation strategies from bupivacaine-induced cardiac arrest

Objectives: Local anesthetic (LA) intoxication with cardiovascular arrest is a potential fatal complication of regional anesthesia. Lipid resuscitation has been recommended for the treatment of LA‐induced cardiac arrest. Aim of the study was to compare four different rescue regimens using epinephrine and/or lipid emulsion and vasopressin to treat cardiac arrest caused by bupivacaine intoxication. Methods: Twenty‐eight piglets were randomized into four groups (4 × 7), anesthetized with sevoflurane, intubated, and ventilated. Bupivacaine was infused with a syringe driver via central venous catheter at a rate of 1 mg·kg^?1·min^?1 until circulatory arrest. Bupivacaine infusion and sevoflurane were then stopped, chest compression was started, and the pigs were ventilated with 100% oxygen. After 1 min, epinephrine 10 μg·kg^?1 (group 1), Intralipid^® 20% 4 ml·kg^?1 (group 2), epinephrine 10 μg·kg^?1 + Intralipid^® 4 ml·kg^?1 (group 3) or 2 IU vasopressin + Intralipid^® 4 ml·kg^?1 (group 4) were administered. Secondary epinephrine doses were given after 5 min if required. Results: Survival was 71%, 29%, 86%, and 57% in groups 1, 2, 3, and 4. Return of spontaneous circulation was regained only by initial administration of epinephrine alone or in combination with Intralipid^®. Piglets receiving the combination therapy survived without further epinephrine support. In contrast, in groups 2 and 4, return of spontaneous circulation was only achieved after secondary epinephrine rescue. Conclusions: In cardiac arrest caused by bupivacaine intoxication, first‐line rescue with epinephrine and epinephrine + Intralipid^® was more effective with regard to survival than Intralipid^® alone and vasopressin + Intralipid^® in this pig model.