#Glucolipotoxicity initiates pancreatic #β-cell death through TNFR5/CD40-mediated STAT1 and NF-κB activation

http://www.nature.com/cddis/journal/v7/n8/full/cddis2016203a.html

Importantly, our data also show that the physiological ligand for TNFR5, CD40L, elicits NF-κB activity in β-cells, whereas selective knockdown of TNFR5 ameliorates glucolipotoxic induction of STAT1 expression and NF-κB activity. This data indicate for the first time that TNFR5 signalling has a major role in triggering glucolipotoxic islet cell death

#β-Blockers and #Mortality After Acute Myocardial #Infarction in Patients Without Heart Failure or Ventricular Dysfunction

http://www.onlinejacc.org/content/69/22/2710

Background For acute myocardial infarction (AMI) without heart failure (HF), it is unclear if β-blockers are associated with reduced mortality.

Objectives The goal of this study was to determine the association between β-blocker use and mortality in patients with AMI without HF or left ventricular systolic dysfunction (LVSD). Conclusions Among survivors of hospitalization with AMI who did not have HF or LVSD as recorded in the hospital, the use of β-blockers was not associated with a lower risk of death at any time point up to 1 year. (β-Blocker Use and Mortality in Hospital Survivors of Acute Myocardial Infarction Without Heart Failure; NCT02786654)

#Lixisenatide as add-on treatment among patients with different #β-cell function levels as assessed by HOMA-β index
http://onlinelibrary.wiley.com/doi/10.1002/dmrr.2897/full

The effect of lixisenatide—a prandial once-daily glucagon-like peptide-1 receptor agonist—on glycaemic control in patients with inadequately controlled type 2 diabetes mellitus (T2DM), stratified by baseline β-cell function, was assessed. The matched “low” and “high” HOMA-β index cohorts (N = 546 patients) had comparable baseline parameters. Mean change from baseline in glycated haemoglobin (HbA1c) was −0.85% and −0.94% for low and high HOMA-β cohorts, respectively (P = .2607). Reductions from baseline in fasting plasma glucose (FPG; −0.77 vs −1.04 mmol/L; P = .1496) and postprandial plasma glucose (PPG; −5.82 vs −5.61 mmol/L; P = .7511) were similar in the low versus high HOMA-β index cohorts. Reduction in body weight was significantly greater in the low versus high HOMA-β index cohort (–2.06 vs –1.13 kg, respectively; P = .0006).

In patients with T2DM, lixisenatide was associated with reduction in HbA1c and improvements in both FPG and PPG, regardless of β-cell function, indicating that lixisenatide is effective in reducing hyperglycaemia, even in patients with more advanced stages of T2DM and poor residual β-cell function.

Effectiveness of #β-Lactam Monotherapy vs Macrolide Combination Therapy for Children Hospitalized With #Pneumonia
https://jamanetwork.com/journals/jamapediatrics/fullarticle/2659321

β-Lactam monotherapy and β-lactam plus macrolide combination therapy are both common empirical treatment strategies for children hospitalized with pneumonia, but few studies have evaluated the effectiveness of these 2 treatment

..1019 (71.9%) received β-lactam monotherapy and 399 (28.1%) received β-lactam plus macrolide combination therapy. In the unmatched cohort, there was no statistically significant difference in length of hospital stay between children receiving β-lactam monotherapy and combination therapy (median, 55 vs 59 hours; adjusted hazard ratio, 0.87; 95% CI, 0.74-1.01). The propensity-matched cohort (n = 560, 39.5%) showed similar results. There were also no significant differences between treatment groups for the secondary outcomes.

Conclusions and Relevance Empirical macrolide combination therapy conferred no benefit over β-lactam monotherapy for children hospitalized with community-acquired pneumonia. The results of this study elicit questions about the routine empirical use of macrolide combination therapy in this population

!!
#β-Blocker Use in Pregnancy and the Risk for Congenital #Malformations: An International Cohort Study

http://annals.org/aim/article-abstract/2707333/blocker-use-pregnancy-risk-congenital-malformations-international-cohort-study

Of 3577 women with hypertensive pregnancies in the Nordic cohort and 14 900 in the U.S. cohort, 682 (19.1%) and 1668 (11.2%), respectively, were exposed to β-blockers in the first trimester. The pooled adjusted relative risk (RR) and risk difference per 1000 persons exposed (RD1000) associated with β-blockers were 1.07 (95% CI, 0.89 to 1.30) and 3.0 (CI, −6.6 to 12.6), respectively, for any major malformation; 1.12 (CI, 0.83 to 1.51) and 2.1 (CI, −4.3 to 8.4) for any cardiac malformation; and 1.97 (CI, 0.74 to 5.25) and 1.0 (CI, −0.9 to 3.0) for cleft lip or palate. For CNS malformations, the adjusted RR was 1.37 (CI, 0.58 to 3.25) and the RD1000 was 1.0 (CI, −2.0 to 4.0) (based on U.S. cohort data only).

Limitation:
Analysis was restricted to live births, exposure was based on dispensed medication, and cleft lip or palate and CNS malformations had few outcomes.

Conclusion:
The results suggest that maternal use of β-blockers in the first trimester is not associated with a large increase in the risk for overall malformations or cardiac malformations, independent of measured confounders.

!!
#β-Blocker Therapy and Risk of Chronic Obstructive #Pulmonary Disease – A Danish Nationwide Study of 1·3 Million Individuals

https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(19)30004-5/fulltext

Highlights
•
Users of β-blockers had an overall 19·7% lower risk of COPD hospitalization compared to users of any other antihypertensive drug during follow-up.
•
Users of β-blockers had an overall 44% lower risk of death from COPD compared to users of any other antihypertensive drug.
•
Results from this study advocates changes in the present hesitation of treatment with β-blockers in patients at risk of or with concomitant COPD.

Do #β-Blockers Cause #Depression? Systematic Review and Meta-Analysis of Psychiatric Adverse Events During β-Blocker Therapy
https://2medical.news/2021/03/18/do-%CE%B2-blockers-cause-depression-systematic-review-and-meta-analysis-of-psychiatric-adverse-events-during-%CE%B2-blocker-therapy/

β-Blockers are important drugs in the treatment of cardiovascular diseases. They are suspected of inducing various psychiatric adverse events (PAEs), particularly depression, affecting cardiovascular morbidity and mortality. We performed a systematic search for double-blind, randomized controlled trials investigating β-blockers to analyze the risk of PAEs or withdrawal of therapy due to PAEs. We extracted the frequencies of PAEs and rates of withdrawals and reviewed them …