No abstract

Worldwide, various autopsy studies have shown a decrease in the diagnostic error rate over the last years. The cause of this positive development is mainly due to the improvement of modern medicine. However, intensive care unit patients are thought to have a higher risk for diagnostic errors, which is documented in several studies in the adult population. In contrast, there is only limited information about diagnostic errors in pediatrics, particularly in pediatric and neonatal intensive care units. The aims of this study were to analyze the spectrum of childhood death, determine the prevalence and distribution of autopsy-confirmed diagnostic errors, and describe patient characteristics that might have influenced the discordance between antemortem and postmortem findings. We analyzed 143 autopsy reports from 2004 to 2013 and correlated these with clinical reports. The overall autopsy rate during this interval was 20.3%. The leading causes of death were congenital malformations (28%), diseases closely associated with perinatal disorders (25%), disorders of the cardiovascular system (18%), and infections (15%). Additional findings were obtained in 23% of the autopsies. Major diagnostic errors were found in 6%, the lowest reported value in a developed country as yet. Most cases (75%) showed complete concordance between clinical diagnoses and postmortem findings, in line with improvements in diagnostic and therapeutic processes over the last decades. In conclusion, autopsy of neonates, infants, and children represents an important tool for monitoring the quality of pediatric and neonatal medical care.

Background: The proton-activated G protein-coupled receptor GPR4 is expressed in many tissues including white adipose tissue. GPR4 is activated by extracellular protons in the physiological pH range (i.e. pH 7.7 - 6.8) and is coupled to the production of cAMP. Methods: We examined mice lacking GPR4 and examined glucose tolerance and insulin sensitivity in young and aged mice as well as in mice fed with a high fat diet. Expression profiles of pro- and anti-inflammatory cytokines in white adipose tissue, liver and skeletal muscle was assessed. Results: Here we show that mice lacking GPR4 have an improved intraperitoneal glucose tolerance test and increased insulin sensitivity. Insulin levels were comparable but leptin levels were increased in GPR4 KO mice. Gpr4^-/- showed altered expression of PPARα, IL-6, IL-10, TNFα, and TGF-1β in skeletal muscle, white adipose tissue, and liver. High fat diet abolished the differences in glucose tolerance and insulin sensitivity between Gpr4^+/+ and Gpr4^-/- mice. In contrast, in aged mice (12 months old), the positive effect of GPR4 deficiency on glucose tolerance and insulin sensitivity was maintained. Liver and adipose tissue showed no major differences in the mRNA expression of pro- and anti-inflammatory factors between aged mice of both genotypes. Conclusion: Thus, GPR4 deficiency improves glucose tolerance and insulin sensitivity. The effect may involve an altered balance between pro- and anti-inflammatory factors in insulin target tissues.