Death by biscuit--exhumation, post-mortem CT, and revision of the cause of death one year after interment

We describe a case of exhumation, performed to investigate the circumstances and cause of death, one year after burial. Post mortem computed tomography (PMCT) revealed a mass in the pharynx. Imaging directed the subsequent forensic autopsy to careful retrieval of a foreign body. Histological analysis revealed a non-cellular composition. The detection of foreign material in the pharynx and its composition indicated accidental, rather than natural death, secondary to choking on food. This unusual case illustrates how post mortem imaging can significantly contribute to forensic investigation and stresses the importance of interdisciplinary collaboration between forensic pathologists and radiologists.

[Knowledge, attitude and reservations of medical students about organ transplantation: results of a survey during the first year of study]

AIM: Establish a list of first year medical students' attitudes, doubts, and knowledge in the fields of organ transplantation and donation. METHOD: Anonymized questionnaire handed out to students during class lectures. RESULTS: 183 questionnaires were distributed and 117 returned (participation: 64%). The average age of the students was 21.6 +/- 2.7 years (range 18 to 38 years); the sample included 71 women (60.7%) and 48 men (39.3%). Only 2 students (2%) were not interested in the subject of organ donation. The students knew very little of the legal aspects of organ donation and 1/4 of them thought there was even a Federal law regarding organ transplantation. When asked if they knew whether a law existed in the Canton of Berne, 44% replied yes, but only 24 (20%) knew that this is contradictory. There was no gender difference in the answers to these question. From 57 students (48%) 246 individual comments on doubts and concerns were analyzed. In this respect, the students mainly questioned whether the donor was truly dead when donation took place (n = 48), if illegal transplantation could be eliminated (n = 44) and if transplantation was truly necessary (n = 43). Some also mentioned religious/ethical doubts (n = 42). In regard to organ donation by a living individual, 27 students were concerned about the health of this donor. 20 students had doubts regarding the pressure possibly applied by family members and friends and as many voiced doubts in regard to premature diagnosis of brain death of potential donors. Only 2 students were concerned about the post-mortem presentation. 45 students (48%) indicated discomfort with the donation of certain organs. They ranked the kidney as the first organ to donate, followed by the pancreas, heart, cornea, intestine, lung and liver. CONCLUSION: The interest in organ donation and transplantation is already strong in fist year medical students in the pre-clinical stage. However, differences from lay public are not readably detectable at this stage of medical training. Adequate information could influence future physicians in their mediatory role.

Mortality of HIV-1-infected patients in the first year of antiretroviral therapy: comparison between low-income and high-income countries

BACKGROUND: Highly active antiretroviral therapy (HAART) is being scaled up in developing countries. We compared baseline characteristics and outcomes during the first year of HAART between HIV-1-infected patients in low-income and high-income settings. METHODS: 18 HAART programmes in Africa, Asia, and South America (low-income settings) and 12 HIV cohort studies from Europe and North America (high-income settings) provided data for 4810 and 22,217, respectively, treatment-naive adult patients starting HAART. All patients from high-income settings and 2725 (57%) patients from low-income settings were actively followed-up and included in survival analyses. FINDINGS: Compared with high-income countries, patients starting HAART in low-income settings had lower CD4 cell counts (median 108 cells per muL vs 234 cells per muL), were more likely to be female (51%vs 25%), and more likely to start treatment with a non-nucleoside reverse transcriptase inhibitor (NNRTI) (70%vs 23%). At 6 months, the median number of CD4 cells gained (106 cells per muL vs 103 cells per muL) and the percentage of patients reaching HIV-1 RNA levels lower than 500 copies/mL (76%vs 77%) were similar. Mortality was higher in low-income settings (124 deaths during 2236 person-years of follow-up) than in high-income settings (414 deaths during 20,532 person-years). The adjusted hazard ratio (HR) of mortality comparing low-income with high-income settings fell from 4.3 (95% CI 1.6-11.8) during the first month to 1.5 (0.7-3.0) during months 7-12. The provision of treatment free of charge in low-income settings was associated with lower mortality (adjusted HR 0.23; 95% CI 0.08-0.61). INTERPRETATION: Patients starting HAART in resource-poor settings have increased mortality rates in the first months on therapy, compared with those in developed countries. Timely diagnosis and assessment of treatment eligibility, coupled with free provision of HAART, might reduce this excess mortality.

Causes of death and determinants of outcome in critically ill patients

INTRODUCTION: Whereas most studies focus on laboratory and clinical research, little is known about the causes of death and risk factors for death in critically ill patients. METHODS: Three thousand seven hundred patients admitted to an adult intensive care unit (ICU) were prospectively evaluated. Study endpoints were to evaluate causes of death and risk factors for death in the ICU, in the hospital after discharge from ICU, and within one year after ICU admission. Causes of death in the ICU were defined according to standard ICU practice, whereas deaths in the hospital and at one year were defined and grouped according to the ICD-10 (International Statistical Classification of Diseases and Related Health Problems) score. Stepwise logistic regression analyses were separately calculated to identify independent risk factors for death during the given time periods. RESULTS: Acute, refractory multiple organ dysfunction syndrome was the most frequent cause of death in the ICU (47%), and central nervous system failure (relative risk [RR] 16.07, 95% confidence interval [CI] 8.3 to 31.4, p < 0.001) and cardiovascular failure (RR 11.83, 95% CI 5.2 to 27.1, p < 0.001) were the two most important risk factors for death in the ICU. Malignant tumour disease and exacerbation of chronic cardiovascular disease were the most frequent causes of death in the hospital (31.3% and 19.4%, respectively) and at one year (33.2% and 16.1%, respectively). CONCLUSION: In this primarily surgical critically ill patient population, acute or chronic multiple organ dysfunction syndrome prevailed over single-organ failure or unexpected cardiac arrest as a cause of death in the ICU. Malignant tumour disease and chronic cardiovascular disease were the most important causes of death after ICU discharge.

Stroke events, and case fatalities in Switzerland based on hospital statistics and cause of death statistics

OBJECTIVE: In Switzerland there is a shortage of population-based information on stroke incidence and case fatalities (CF). The aim of this study was to estimate stroke event rates and both in- and out-of-hospital CF rates. METHODS: Data on stroke diagnoses, coded according to I60-I64 (ICD 10), were taken from the Federal Hospital Discharge Statistics database (HOST) and the Cause of Death database (CoD) for the year 2004. The number of total stroke events and of age- and gender-specific and agestandardised event rates were estimated; overall CF, in-hospital and out-of-hospital, were determined. RESULTS: Among the overall number of 13 996 hospital discharges from stroke (HOST) the number was lower in women (n = 6736) than in men (n = 7260). A total of 3568 deaths (2137 women and 1431 men) due to stroke were recorded in the CoD database. The number of estimated stroke events was 15 733, and higher in women (n = 7933) than in men (n = 7800). Men presented significantly higher age-specific stroke event rates and a higher age-standardised event rate (178.7/100 000 versus 119.7/100 000). Overall CF rates were significantly higher for women (26.9%) than for men (18.4%). The same was true of out-of-hospital CF but not of in-hospital CF rates. CONCLUSION: The data on estimated stroke events obtained indicate that stroke discharge rate underestimates the stroke event rate. Out-of-hospital deaths from stroke accounted for the largest proportion of total stroke deaths. Sex differences in both number of total stroke events and deaths could be explained by the higher proportion of women than men aged 55+ in the Swiss population.

Short- and long-term mortality and causes of death in HIV/tuberculosis patients in Europe

Mortality of HIV/tuberculosis (TB) patients in Eastern Europe is high. Little is known about their causes of death. This study aimed to assess and compare mortality rates and cause of death in HIV/TB patients across Eastern Europe and Western Europe and Argentina (WEA) in an international cohort study. Mortality rates and causes of death were analysed by time from TB diagnosis (<3 months, 3-12 months or >12 months) in 1078 consecutive HIV/TB patients. Factors associated with TB-related death were examined in multivariate Poisson regression analysis. 347 patients died during 2625 person-years of follow-up. Mortality in Eastern Europe was three- to ninefold higher than in WEA. TB was the main cause of death in Eastern Europe in 80%, 66% and 61% of patients who died <3 months, 3-12 months or >12 months after TB diagnosis, compared to 50%, 0% and 15% in the same time periods in WEA (p<0.0001). In multivariate analysis, follow-up in WEA (incidence rate ratio (IRR) 0.12, 95% CI 0.04-0.35), standard TB-treatment (IRR 0.45, 95% CI 0.20-0.99) and antiretroviral therapy (IRR 0.32, 95% CI 0.14-0.77) were associated with reduced risk of TB-related death. Persistently higher mortality rates were observed in HIV/TB patients in Eastern Europe, and TB was the dominant cause of death at any time during follow-up. This has important implications for HIV/TB programmes aiming to optimise the management of HIV/TB patients and limit TB-associated mortality in this region.

Health care index score and risk of death following tuberculosis diagnosis in HIV-positive patients

OBJECTIVES: To assess health care utilisation for patients co-infected with TB and HIV (TB-HIV), and to develop a weighted health care index (HCI) score based on commonly used interventions and compare it with patient outcome. METHODS: A total of 1061 HIV patients diagnosed with TB in four regions, Central/Northern, Southern and Eastern Europe and Argentina, between January 2004 and December 2006 were enrolled in the TB-HIV study. A weighted HCI score (range 0–5), based on independent prognostic factors identified in multivariable Cox models and the final score, included performance of TB drug susceptibility testing (DST), an initial TB regimen containing a rifamycin, isoniazid and pyrazinamide, and start of combination antiretroviral treatment (cART). RESULTS: The mean HCI score was highest in Central/Northern Europe (3.2, 95%CI 3.1–3.3) and lowest in Eastern Europe (1.6, 95%CI 1.5–1.7). The cumulative probability of death 1 year after TB diagnosis decreased from 39% (95%CI 31–48) among patients with an HCI score of 0, to 9% (95%CI 6–13) among those with a score of ≥4. In an adjusted Cox model, a 1-unit increase in the HCI score was associated with 27% reduced mortality (relative hazard 0.73, 95%CI 0.64–0.84). CONCLUSIONS: Our results suggest that DST, standard anti-tuberculosis treatment and early cART may improve outcome for TB-HIV patients. The proposed HCI score provides a tool for future research and monitoring of the management of TB-HIV patients. The highest HCI score may serve as a benchmark to assess TB-HIV management, encouraging continuous health care improvement.

Heart transplantation with donation after circulatory determination of death.

The constant shortage of available organs is a major obstacle and limiting factor in heart transplantation; the discrepancy between the number of donors and potential recipients leads to waiting-list mortality of 10-12% per year in Europe and the USA. If adopted for heart transplantation, donation after circulatory determination of death (DCDD) would be expected to improve the availability of organs substantially for both adults and children. With DCDD, however, hearts to be transplanted undergo a period of warm ischaemia before procurement, which is of particular concern because tissue damage occurs rapidly and might be sufficient to preclude transplantation. Nonetheless, the heart is able to withstand limited periods of warm ischaemia, which could provide a window of opportunity for DCDD. Development of clinical approaches specifically for DCDD is critical for the exploitation of these organs, because current practices for donor heart procurement, evaluation, and storage have been optimized for conventional donation after brain death, without consideration of warm ischaemia before organ procurement. Establishment of clinical protocols and ethical and legal frameworks for DCDD of other organs is underway. This Review provides a timely evaluation of the potential for DCDD in heart transplantation.

A clinical prediction model to identify patients at high risk of death in the emergency department.

PURPOSE Rapid assessment and intervention is important for the prognosis of acutely ill patients admitted to the emergency department (ED). The aim of this study was to prospectively develop and validate a model predicting the risk of in-hospital death based on all available information available at the time of ED admission and to compare its discriminative performance with a non-systematic risk estimate by the triaging first health-care provider. METHODS Prospective cohort analysis based on a multivariable logistic regression for the probability of death. RESULTS A total of 8,607 consecutive admissions of 7,680 patients admitted to the ED of a tertiary care hospital were analysed. Most frequent APACHE II diagnostic categories at the time of admission were neurological (2,052, 24 %), trauma (1,522, 18 %), infection categories [1,328, 15 %; including sepsis (357, 4.1 %), severe sepsis (249, 2.9 %), septic shock (27, 0.3 %)], cardiovascular (1,022, 12 %), gastrointestinal (848, 10 %) and respiratory (449, 5 %). The predictors of the final model were age, prolonged capillary refill time, blood pressure, mechanical ventilation, oxygen saturation index, Glasgow coma score and APACHE II diagnostic category. The model showed good discriminative ability, with an area under the receiver operating characteristic curve of 0.92 and good internal validity. The model performed significantly better than non-systematic triaging of the patient. CONCLUSIONS The use of the prediction model can facilitate the identification of ED patients with higher mortality risk. The model performs better than a non-systematic assessment and may facilitate more rapid identification and commencement of treatment of patients at risk of an unfavourable outcome.

Estimation of reference curves for the urinary steroid metabolome in the first year of life in healthy children: tracing the complexity of human postnatal steroidogenesis

CONTEXT Complex steroid disorders such as P450 oxidoreductase deficiency or apparent cortisone reductase deficiency may be recognized by steroid profiling using chromatographic mass spectrometric methods. These methods are highly specific and sensitive, and provide a complete spectrum of steroid metabolites in a single measurement of one sample which makes them superior to immunoassays. The steroid metabolome during the fetal-neonatal transition is characterized by a) the metabolites of the fetal-placental unit at birth, b) the fetal adrenal androgens until its involution 3-6 months postnatally, and c) the steroid metabolites produced by the developing endocrine organs. All these developmental events change the steroid metabolome in an age- and sex-dependent manner during the first year of life. OBJECTIVE The aim of this study was to provide normative values for the urinary steroid metabolome of healthy newborns at short time intervals in the first year of life. METHODS We conducted a prospective, longitudinal study to measure 67 urinary steroid metabolites in 21 male and 22 female term healthy newborn infants at 13 time-points from week 1 to week 49 of life. Urine samples were collected from newborn infants before discharge from hospital and from healthy infants at home. Steroid metabolites were measured by gas chromatography-mass spectrometry (GC-MS) and steroid concentrations corrected for urinary creatinine excretion were calculated. RESULTS 61 steroids showed age and 15 steroids sex specificity. Highest urinary steroid concentrations were found in both sexes for progesterone derivatives, in particular 20α-DH-5α-DH-progesterone, and for highly polar 6α-hydroxylated glucocorticoids. The steroids peaked at week 3 and decreased by ∼80% at week 25 in both sexes. The decline of progestins, androgens and estrogens was more pronounced than of glucocorticoids whereas the excretion of corticosterone and its metabolites and of mineralocorticoids remained constant during the first year of life. CONCLUSION The urinary steroid profile changes dramatically during the first year of life and correlates with the physiologic developmental changes during the fetal-neonatal transition. Thus detailed normative data during this time period permit the use of steroid profiling as a powerful diagnostic tool.

Low Risk of Death, but Substantial Program Attrition, in Pediatric HIV Treatment Cohorts in Sub-Saharan Africa

BACKGROUND: To date, an estimated 10% of children eligible for antiretroviral treatment (ART) receive it, and the frequency of retention in programs is unknown. We evaluated the 2-year risks of death and loss to follow-up (LTFU) of children after ART initiation in a multicenter study in sub-Saharan Africa. METHODS: Pooled analysis of routine individual data from 16 participating clinics produced overall Kaplan-Meier estimates of the probabilities of death or LTFU after ART initiation. Risk factors analysis used Weibull regression, accounting for between-cohort heterogeneity. RESULTS: The median age of 2405 children at ART initiation was 4.9 years (12%, younger than 12 months), 52% were male, 70% had severe immunodeficiency, and 59% started ART with a nonnucleoside reverse transcriptase inhibitor. The 2-year risk of death after ART initiation was 6.9% (95% confidence interval [CI]: 5.9 to 8.1), independently associated with baseline severe anemia (adjusted hazard ratio [aHR]: 4.10 [CI: 2.36 to 7.13]), immunodeficiency (adjusted aHR: 2.95 [CI: 1.49 to 5.82]), and severe clinical status (adjusted aHR: 3.64 [CI: 1.95 to 6.81]); the 2-year risk of LTFU was 10.3% (CI: 8.9 to 11.9), higher in children with severe clinical status. CONCLUSIONS: Once on treatment, the 2-year risk of death is low but the LTFU risk is substantial. ART is still mainly initiated at advanced disease stage in African children, reinforcing the need for early HIV diagnosis, early initiation of ART, and procedures to increase program retention.

Human Rhinovirus Types and Association with Respiratory Symptoms During the First Year of Life.

Human rhinoviruses (HRV) cause respiratory infections and are associated with asthma development. We assessed HRV prevalence, types and association with respiratory symptoms in the first year of life in 20 unselected infants. HRV was detected in 32% of 825 weekly nasal swabs. Seventy-four different types of all three species were identified. HRV presence and related respiratory symptoms are highly heterogeneous.

Inhibition of tissue transglutaminase sensitizes TRAIL-resistant lung cancer cells through upregulation of death receptor 5

Tissue transglutaminase (TG2) is implicated in cellular processes such as apoptosis and cell migration. Its acyl transferase activity cross-links certain proteins, among them transcription factors were described. We show here that the TG2 inhibitor KCC009 reversed resistance to tumor necrosis factor-related apoptosis-inducing factor (TRAIL) in lung cancer cells. Sensitization required upregulation of death receptor 5 (DR5) but not of death receptor 4. Upregulation of DR5 involved the first intron of the DR5 gene albeit it was independent from p53 and nuclear factor kappa B. In conclusion, inhibition of tissue transglutaminase provides an interesting strategy for sensitization to TRAIL-induced apoptosis in p53-deficient lung cancer cells.