Clinicopathological correlates of out-of-hospital cardiac arrests.

Background: Sudden cardiac arrest with or without sudden cardiac death (SCD) represents a heterogeneous spectrum of underlying etiology but is often a catastrophic event. Despite improvements in pre-hospital response and post-resuscitation care, outcomes remain grim. Thus, we aim to evaluate the predictors of survival in out-of-hospital cardiac arrests (OHCAs) and describe autopsy findings of those with the uncertain cause of death (COD). Methods: This is a subgroup analysis of the Singapore cohort from the Pan Asian Resuscitation Outcome Study which studied 933 OHCAs admitted to two Singapore tertiary hospitals from April 2010 to May 2012. Results: Of the patients analysed, 30.2% (n = 282) had an initial return of spontaneous circulation (ROSC) at the emergency department, 18.0% (n = 168) had sustained ROSC with subsequent admission and 3.4% (n = 32) had survival to discharge. On multivariate analysis, an initial shockable rhythm, a witnessed event, prehospital defibrillation, and shorter time to hospital predicted ROSC as well as survival to discharge. A total of 163 (17.5%) autopsies were performed of which a cardiac etiology of SCD was noted in 92.1% (n = 151). Ischemic heart disease accounted for 54.3% (n = 89) of the autopsy cohort, with acute myocardial infarction (26.9%, n = 44) and myocarditis (3.7%, n = 6) rounding out the top three causes of demise. Conclusion: OHCA remains a clinical presentation that portends a poor prognosis. Of those with uncertain COD, cardiac etiology appears to predominate from autopsy study. Identification of prognostic factors will play an important role in improving individual-level and systemic-level variables to further optimize outcomes.

Pattern of coroner's autopsies at Health Sciences Authority, Singapore: a retrospective study (2009-2010).

Within a two-year period between 2009 and 2010, the Forensic Medicine Division of the Health Sciences Authority conducted a total of 3560 autopsies on cases reported to the coroner. This retrospective study reviews the type and distribution of these cases, and serves as a pilot study for future analysis of the various subgroups. Nearly half of these deaths (48.93%) are a result of natural disease processes, of which a cardiac cause by far predominates (64.64%), followed by diseases of the respiratory (16.92%) and central nervous (5.28%) systems. Of the deaths by unnatural means (51.07%), a substantial number of these deaths are consequent to fall from height, i.e. off a building (35.86%), with a smaller proportion of death arising from traffic and industrial accidents (17.60%), asphyxia (14.25%) and short distance falls (11.00%). Fall from height is the leading mode of suicide in this densely populated urban city where 85% of the population reside in high-rise apartments.

Negative regulatory responses to metabolically triggered inflammation impair renal epithelial immunity in diabetes mellitus.

Diabetes mellitus is characterized by chronic inflammation and increased risk of infections, particularly of tissues exposed to the external environment. However, the causal molecular mechanisms that affect immune cells and their functions in diabetes are unclear. Here we show, by transcript and protein analyses, signatures of glucose-induced tissue damage, chronic inflammation, oxidative stress, and dysregulated expression of multiple inflammation- and immunity-related molecules in diabetic kidneys compared with non-diabetic controls. Abnormal signaling involving cytokines, G-protein coupled receptors, protein kinase C isoforms, mitogen-activated protein kinases, nuclear factor-κB (NFκB), and Toll-like receptors (TLR) were evident. These were accompanied by overexpression of negative regulators of NFκB, TLR, and other proinflammatory pathways, e.g., A20, SOCS1, IRAK-M, IκBα, Triad3A, Tollip, SIGIRR, and ST2L. Anti-inflammatory and immunomodulatory molecules, e.g., IL-10, IL-4, and TSLP that favor TH2 responses were strongly induced. These molecular indicators of immune dysfunction led us to detect the cryptic presence of bacteria and human cytomegalovirus in more than one third of kidneys of diabetic subjects but none in non-diabetic kidneys. Similar signaling abnormalities could be induced in primary human renal tubular epithelial (but not mesangial) cell cultures exposed to high glucose, proinflammatory cytokines and methylglyoxal, and were reversed by combined pharmacological treatment with an antioxidant and a PKC inhibitor. Our results suggest that diabetes impairs epithelial immunity as a consequence of chronic and inappropriate activation of counter-regulatory immune responses, which are otherwise physiological protective mechanisms against inflammation. The immune abnormalities and cryptic renal infections described here may contribute to progression of diabetic nephropathy.

When is a peri-procedural death iatrogenic in nature?

In almost any instance of suspected iatrogenic fatality, the attending forensic pathologist faces the challenging and often daunting task in ascertaining the cause of death, determining if an iatrogenic injury had indeed occurred and if so, its contribution to the causation of death. The Forensic Medicine Division of the Health Sciences Authority in Singapore embarked on a 6 year study of such deaths to identify pertinent factors that may facilitate the assessment of iatrogenic injuries and their contribution to mortality. A total of 106 iatrogenic deaths, arising from 613 coroner's peri-procedural autopsies conducted during the period of 2005-2010 were reviewed with particular reference to the following parameters: (1) clinico-pathological correlation; (2) the length of survival; (3) the number of interventional procedures. A comprehensive analysis of these cases indicated that they could be classified into the following 3 categories, in relation to the role of clinico-pathological correlation in the ascertainment of the causes of death: (A) advantageous but not essential; (B) essential; (C) critical. A large proportion of the cases (76.5%) were assigned categories B and C. Only the minority of cases (23.6%) were assigned category A. Also, as the number of days of survival between injury and death, and the number of interventional procedures after injury increases, the greater the need for detailed clinical documentation to ascertain the cause of death.