Between-centre differences in care for in-hospital cardiac arrest:a prospective cohort study

Abstract Background Survival after in-hospital cardiac arrest is poor, but current literature shows substantial heterogeneity in reported survival rates. This study aims to evaluate care for patients suffering in-hospital cardiac arrest (IHCA) in the Netherlands by assessing between-hospital heterogeneity in outcomes and to explain this heterogeneity stemming from differences in case-mix or differences in quality of care. Methods A prospective multicentre study was conducted comprising 14 centres. All IHCA patients were included. The adjusted variation in structure and process indicators of quality of care and outcomes (in-hospital mortality and cerebral performance category [CPC] scale) was assessed with mixed effects regression with centre as random intercept. Variation was quantified using the median odds ratio (MOR), representing the expected odds ratio for poor outcome between two randomly picked centres. Results After excluding centres with less than 10 inclusions (2 centres), 701 patients were included of whom, 218 (32%) survived to hospital discharge. The unadjusted and case-mix adjusted MOR for mortality was 1.19 and 1.05, respectively. The unadjusted and adjusted MOR for CPC score was 1.24 and 1.19, respectively. In hospitals where personnel received cardiopulmonary resuscitation (CPR) training twice per year, 183 (64.7%) versus 290 (71.4%) patients died or were in a vegetative state, and 59 (20.8%) versus 68 (16.7%) patients showed full recovery (p < 0.001). Conclusion In the Netherlands, survival after IHCA is relatively high and between-centre differences in outcomes are small. The existing differences in survival are mainly attributable to differences in case-mix. Variation in neurological outcome is less attributable to case-mix

Adaptations in mitochondrial function parallel, but fail to rescue, the transition to severe hyperglycemia and hyperinsulinemia: a study in Zucker diabetic fatty rats.

Cross-sectional human studies have associated mitochondrial dysfunction to type 2 diabetes. We chose Zucker diabetic fatty (ZDF) rats as a model of progressive insulin resistance to examine whether intrinsic mitochondrial defects are required for development of type 2 diabetes. Muscle mitochondrial function was examined in 6-, 12-, and 19-week-old ZDF (fa/fa) and fa/+ control rats (n = 8-10 per group) using respirometry with pyruvate, glutamate, and palmitoyl-CoA as substrates. Six-week-old normoglycemic-hyperinsulinemic fa/fa rats had reduced mitochondrial fat oxidative capacity. Adenosine diphosphate (ADP)-driven state 3 and carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP)-stimulated state uncoupled (state u) respiration on palmitoyl-CoA were lower compared to controls (62.3 ± 9.5 vs. 119.1 ± 13.8 and 87.8 ± 13.3 vs. 141.9 ± 14.3 nmol O2/mg/min.). Pyruvate oxidation in 6-week-old fa/fa rats was similar to controls. Remarkably, reduced fat oxidative capacity in 6-week-old fa/fa rats was compensated for by an adaptive increase in intrinsic mitochondrial function at week 12, which could not be maintained toward week 19 (140.9 ± 11.2 and 57.7 ± 9.8 nmol O2/mg/min, weeks 12 and 19, respectively), whereas hyperglycemia had developed (13.5 ± 0.6 and 16.1 ± 0.3 mmol/l, weeks 12 and 19, respectively). This mitochondrial adaptation failed to rescue the progressive development of insulin resistance in fa/fa rats. The transition of prediabetes state toward advanced hyperglycemia and hyperinsulinemia was accompanied by a blunted increase in uncoupling protein-3 (UCP3). Thus, in ZDF rats insulin resistance develops progressively in the absence of mitochondrial dysfunction. In fact, improved mitochondrial capacity in hyperinsulinemic hyperglycemic rats does not rescue the progression toward advanced stages of insulin resistance

Needle-free pharmacological sedation techniques in paediatric patients for imaging procedures:a systematic review and meta-analysis

Background: Sedation techniques and drugs are increasingly used in children undergoing imaging procedures. In this systematic review and meta-analysis, we present an overview of literature concerning sedation of children aged 0–8 yr for magnetic resonance imaging (MRI) procedures using needle-free pharmacological techniques. Methods: Embase, MEDLINE, Web of Science, and Cochrane databases were systematically searched for studies on the use of needle-free pharmacological sedation techniques for MRI procedures in children aged 0–8 yr. Studies using i.v. or i.m. medication or advanced airway devices were excluded. We performed a meta-analysis on sedation success rate. Secondary outcomes were onset time, duration, recovery, and adverse events. Results: Sixty-seven studies were included, with 22 380 participants. The pooled success rate for oral chloral hydrate was 94% (95% confidence interval [CI]: 0.91–0.96); for oral chloral hydrate and intranasal dexmedetomidine 95% (95% CI: 0.92–0.97); for rectal, oral, or intranasal midazolam 36% (95% CI: 0.14–0.65); for oral pentobarbital 99% (95% CI: 0.90–1.00); for rectal thiopental 92% (95% CI: 0.85–0.96); for oral melatonin 75% (95% CI: 0.54–0.89); for intranasal dexmedetomidine 62% (95% CI: 0.38–0.82); for intranasal dexmedetomidine and midazolam 94% (95% CI: 0.78–0.99); and for inhaled sevoflurane 98% (95% CI: 0.97–0.99). Conclusions: We found a large variation in medication, dosage, and route of administration for needle-free sedation. Success rates for sedation techniques varied between 36% and 98%.</p

Prolonged Fasting Identifies Skeletal Muscle Mitochondrial Dysfunction as Consequence Rather Than Cause of Human Insulin Resistance

OBJECTIVE-Type 2 diabetes and insulin resistance have been associated with mitochondrial dysfunction, but it is debated whether this is a primary factor in the pathogenesis of the disease. To test the concept that mitochondrial dysfunction is secondary to the development of insulin resistance, we employed the unique model of prolonged fasting in humans. Prolonged fasting is a physiologic condition in which muscular insulin resistance develops in the presence of increased free fatty acid (FFA) levels, increased fat oxidation and low glucose and insulin levels. It is therefore anticipated that skeletal muscle mitochondrial function is maintained to accommodate increased fat oxidation unless factors secondary to insulin resistance exert negative effects on mitochondrial function. RESEARCH DESIGN AND METHODS-While in a respiration chamber, twelve healthy males were subjected to a 60 h fast and a 60 h normal fed condition in a randomized crossover design. Afterward, insulin sensitivity was assessed using a hyperinsulinemic-euglycemic clamp, and mitochondrial function was quantified ex vivo in permeabilized muscle fibers using high-resolution respirometry. RESULTS-Indeed, FFA levels were increased approximately ninefold after 60 h of fasting in healthy male subjects, leading to elevated intramuscular lipid levels and decreased muscular insulin sensitivity. Despite an increase in whole-body fat oxidation, we observed an overall reduction in both coupled state 3 respiration and maximally uncoupled respiration in permeabilized skeletal muscle fibers, which could not be explained by changes in mitochondrial density. CONCLUSIONS-These findings confirm that the insulin-resistant State has secondary negative effects on mitochondrial function. Given the low insulin and glucose levels after prolonged fasting, hyperglycemia and insulin action per se can be excluded as underlying mechanisms, pointing toward elevated plasma FFA and/or intramuscular fat accumulation as possible causes for the observed reduction in mitochondrial capacity. Diabetes 59: 2117-2125, 201

Conservative Treatment in Diverticulitis Patients with Pericolic Extraluminal Air and the Role of Antibiotic Treatment

Background: Recently published studies advocate a conservative approach with observation and antibiotic treatment in diverticulitis patients with pericolic air on computed tomography (CT). The primary aim of this study was to assess the clinical course of initially conservatively treated diverticulitis patients with isolated pericolic air and to identify risk factors for conservative treatment failure. The secondary aim was to assess the outcome of non-antibiotic treatment. Methods: Patient data from a retrospective cohort study on risk factors for complicated diverticulitis were combined with data from the DIABOLO trial, a randomised controlled trial comparing non-antibiotic with antibiotic treatment in patients with uncomplicated diverticulitis. The present study identified all patients with Hinchey 1A diverticulitis with isolated pericolic air on CT. Pericolic air was defined as air located < 5 cm from the affected segment of colon. The primary outcome was failure of conservative management which was defined as need for percutaneous abscess drainage or emergency surgery within 30 days after presentation. A multivariable logistic regression of clinical, radiological and laboratorial parameters with respect to treatment failure was performed. Results: A total of 109 patients were included in the study. Fifty-two (48%) patients were treated with antibiotics. Nine (8%) patients failed conservative management, seven (13%) in the antibiotic treatment group and two (4%) in the non-antibiotic group (p = 0.083). Only (increased) CRP level at presentation was an independent predictor for treatment failure. Conclusions: Conservative treatment in diverticulitis patients with isolated pericolic air is a suitable treatment strategy. Moreover, non-antibiotic treatment might be reasonable in selected patients

Lower Intrinsic ADP-Stimulated Mitochondrial Respiration Underlies In Vivo Mitochondrial Dysfunction in Muscle of Male Type 2 Diabetic Patients

OBJECTIVE—A lower in vivo mitochondrial function has been reported in both type 2 diabetic patients and first-degree relatives of type 2 diabetic patients. The nature of this reduction is unknown. Here, we tested the hypothesis that a lower intrinsic mitochondrial respiratory capacity may underlie lower in vivo mitochondrial function observed in diabetic patients

The benefits of statins in people without established cardiovascular disease but with cardiovascular risk factors: meta-analysis of randomised controlled trials

Objectives To investigate whether statins reduce all cause mortality and major coronary and cerebrovascular events in people without established cardiovascular disease but with cardiovascular risk factors, and whether these effects are similar in men and women, in young and older (>65 years) people, and in people with diabetes mellitus

Differential Runx3, Eomes, and T-bet expression subdivides MS-associated CD4⁺ T cells with brain-homing capacity

Multiple sclerosis (MS) is a common and devastating chronic inflammatory disease of the CNS. CD4 + T cells are assumed to be the first to cross the blood–central nervous system (CNS) barrier and trigger local inflammation. Here, we explored how pathogenicity-associated effector programs define CD4 + T cell subsets with brain-homing ability in MS. Runx3- and Eomes-, but not T-bet-expressing CD4 + memory cells were diminished in the blood of MS patients. This decline reversed following natalizumab treatment and was supported by a Runx3 +Eomes +T-bet − enrichment in cerebrospinal fluid samples of treatment-naïve MS patients. This transcription factor profile was associated with high granzyme K (GZMK) and CCR5 levels and was most prominent in Th17.1 cells (CCR6 +CXCR3 +CCR4 −/dim). Previously published CD28 − CD4 T cells were characterized by a Runx3 +Eomes −T-bet + phenotype that coincided with intermediate CCR5 and a higher granzyme B (GZMB) and perforin expression, indicating the presence of two separate subsets. Under steady-state conditions, granzyme K high Th17.1 cells spontaneously passed the blood–brain barrier in vitro. This was only found for other subsets including CD28 − cells when using inflamed barriers. Altogether, CD4 + T cells contain small fractions with separate pathogenic features, of which Th17.1 seems to breach the blood–brain barrier as a possible early event in MS.</p