Intraarrest transport, extracorporeal cardiopulmonary resuscitation, and early invasive management in refractory out-of-hospital cardiac arrest: an individual patient data pooled analysis of two randomised trialsResearch in context

Summary: Background: Refractory out-of-hospital cardiac arrest (OHCA) treated with standard advanced cardiac life support (ACLS) has poor outcomes. Transport to hospital followed by in-hospital extracorporeal cardiopulmonary resuscitation (ECPR) initiation may improve outcomes. We performed a pooled individual patient data analysis of two randomised controlled trials evaluating ECPR based approach in OHCA. Methods: The individual patient data from two published randomised controlled trials (RCTs) were pooled: ARREST (enrolled Aug 2019–June 2020; NCT03880565) and PRAGUE-OHCA (enrolled March 1, 2013–Oct 25, 2020; NCT01511666). Both trials enrolled patients with refractory OHCA and compared: intra-arrest transport with in-hospital ECPR initiation (invasive approach) versus continued standard ACLS. The primary outcome was 180-day survival with favourable neurological outcome (defined as Cerebral Performance Category 1–2). Secondary outcomes included: cumulative survival at 180 days, 30-day favourable neurological survival, and 30-day cardiac recovery. Risk of bias in each trial was assessed by two independent reviewers using the Cochrane risk-of-bias tool. Heterogeneity was assessed via Forest plots. Findings: The two RCTs included 286 patients. Of those randomised to the invasive (n = 147) and standard (n = 139) groups, respectively: the median age was 57 (IQR 47–65) and 58 years (IQR 48–66), and the median duration of resuscitation was 58 (IQR 43–69) and 49 (IQR 33–71) minutes (p = 0.17). In a modified intention to treat analysis, 45 (32.4%) in the invasive and 29 (19.7%) patients in the standard arm survived to 180 days with a favourable neurological outcome [absolute difference (AD), 95% CI: 12.7%, 2.6–22.7%, p = 0.015]. Forty-seven (33.8%) and 33 (22.4%) patients survived to 180 days [HR 0.59 (0.43–0.81); log rank test p = 0.0009]. At 30 days, 44 (31.7%) and 24 (16.3%) patients had favourable neurological outcome (AD 15.4%, 5.6–25.1%, p = 0.003), 60 (43.2%), and 46 (31.3%) patients had cardiac recovery (AD: 11.9%, 0.7–23%, p = 0.05), in the invasive and standard arms, respectively. The effect was larger in patients presenting with shockable rhythms (AD 18.8%, 7.6–29.4; p = 0.01; HR 2.26 [1.23–4.15]; p = 0.009) and prolonged CPR (>45 min; HR 3.99 (1.54–10.35); p = 0.005). Interpretation: In patients with refractory OHCA, the invasive approach significantly improved 30- and 180-day neurologically favourable survival. Funding: None

Neudesin in obesity and type 2 diabetes mellitus: the effect of acute fasting and weight reducing interventions

Helena Kratochvilova,1–3 Zdenka Lacinova,1–3 Jana Klouckova,1–3 Petra Kavalkova,2,3 Anna Cinkajzlova,1–3 Pavel Trachta,4 Jarmila Krizova,4 Marek Benes,5 Karin Dolezalova,6 Martin Fried,6 Zuzana Vlasakova,7 Terezie Pelikanova,7 Julius Spicak,5 Milos Mraz,2,3,7 Martin Haluzik1–3,7 1Centre for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic; 2Department of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University, Prague, Czech Republic; 3Department of Medical Biochemistry and Laboratory Diagnostics, General University Hospital, Prague, Czech Republic; 4Third Department of Medicine, Department of Endocrinology and Metabolism, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic; 5Hepatogastroenterology Department, Institute for Clinical and Experimental Medicine, Prague, Czech Republic; 6Department of Surgery, OB Clinic, Prague, Czech Republic; 7Diabetes Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic Context: Neudesin has recently been identified as a novel regulator of energy expenditure in experimental animals; however, its role in humans remains unexplored.Objective: The aim of this study was to assess the effects of obesity and type 2 diabetes mellitus (T2DM) along with selected weight reducing interventions on serum neudesin levels and adipose tissue mRNA expression.Patients and methods: Fifteen obese subjects with T2DM undergoing endoscopic duodenal-jejunal bypass liner (DJBL) implantation, 17 obese subjects (11 with T2DM, 6 without T2DM) scheduled for gastric plication (GP), 15 subjects with functional hypoglycemia subjected to 72-hour acute fasting (AF), and 12 healthy controls were included in the study.Results: Baseline neudesin levels were comparable between all groups. DJBL increased neudesin at 6 and 10 months after the procedure (1.77±0.86 vs 2.28±1.27 vs 2.13±1.02 ng/mL, P=0.001 for baseline vs 6 vs 10 months) along with reduction in body weight and improvement of HbA1c without any effect on neudesin mRNA expression in subcutaneous adipose tissue. Conversely, GP did not affect neudesin levels despite marked reduction in body weight and improvement of HbA1c. In contrast, AF decreased neudesin levels during the entire period (1.74±0.54 vs 1.46±0.48 ng/mL, P=0.001 for baseline vs 72 hours) with no impact of subsequent re-alimentation on neudesin concentrations.Conclusion: Neudesin levels are differentially regulated during AF and chronic weight reduction induced by DJBL or GP. Further studies are needed to assess its possible significance in energy homeostasis regulation in humans. Keywords: neudesin, obesity, type 2 diabetes mellitus, bariatric surgery, acute fasting, weight reduction, energy homeostasi

Increased lipid and lipoprotein concentrations in anorexia nervosa:A systematic review and meta-analysis

Objective: Alterations in blood lipid concentrations in anorexia nervosa (AN) have been reported; however, the extent, mechanism, and normalization with weight restoration remain unknown. We conducted a systematic review and a meta-analysis to evaluate changes in lipid concentrations in acutely-ill AN patients compared with healthy controls (HC) and to examine the effect of partial weight restoration. Method: A systematic literature review and meta-analysis (PROSPERO: CRD42017078014) were conducted for original peer-reviewed articles. Results: Forty-eight studies were eligible for review; 33 for meta-analyses calculating mean differences (MD). Total cholesterol (MD = 22.7 mg/dL, 95% CI = 12.5, 33.0), high-density lipoprotein (HDL; MD = 3.4 mg/dL, CI = 0.3, 7.0), low-density lipoprotein (LDL; MD = 12.2 mg/dL, CI = 4.4, 20.1), triglycerides (TG; MD = 8.1 mg/dL, CI = 1.7, 14.5), and apolipoprotein B (Apo B; MD = 11.8 mg/dL, CI = 2.3, 21.2) were significantly higher in acutely-ill AN than HC. Partially weight-restored AN patients had higher total cholesterol (MD = 14.8 mg/dL, CI = 2.1, 27.5) and LDL (MD = 16.1 mg/dL, CI = 2.3, 30.0). Pre- versus post-weight restoration differences in lipid concentrations did not differ significantly. Discussion: We report aggregate evidence for elevated lipid concentrations in acutely-ill AN patients compared with HC, some of which persist after partial weight restoration. This could signal an underlying adaptation or dysregulation not fully reversed by weight restoration. Although concentrations differed between AN and HC, most lipid concentrations remained within the reference range and meta-analyses were limited by the number of available studies