A Prospective Study of Sudden Cardiac Death among Children and Young Adults.

BACKGROUND: Sudden cardiac death among children and young adults is a devastating event. We performed a prospective, population-based, clinical and genetic study of sudden cardiac death among children and young adults. METHODS: We prospectively collected clinical, demographic, and autopsy information on all cases of sudden cardiac death among children and young adults 1 to 35 years of age in Australia and New Zealand from 2010 through 2012. In cases that had no cause identified after a comprehensive autopsy that included toxicologic and histologic studies (unexplained sudden cardiac death), at least 59 cardiac genes were analyzed for a clinically relevant cardiac gene mutation. RESULTS: A total of 490 cases of sudden cardiac death were identified. The annual incidence was 1.3 cases per 100,000 persons 1 to 35 years of age; 72% of the cases involved boys or young men. Persons 31 to 35 years of age had the highest incidence of sudden cardiac death (3.2 cases per 100,000 persons per year), and persons 16 to 20 years of age had the highest incidence of unexplained sudden cardiac death (0.8 cases per 100,000 persons per year). The most common explained causes of sudden cardiac death were coronary artery disease (24% of cases) and inherited cardiomyopathies (16% of cases). Unexplained sudden cardiac death (40% of cases) was the predominant finding among persons in all age groups, except for those 31 to 35 years of age, for whom coronary artery disease was the most common finding. Younger age and death at night were independently associated with unexplained sudden cardiac death as compared with explained sudden cardiac death. A clinically relevant cardiac gene mutation was identified in 31 of 113 cases (27%) of unexplained sudden cardiac death in which genetic testing was performed. During follow-up, a clinical diagnosis of an inherited cardiovascular disease was identified in 13% of the families in which an unexplained sudden cardiac death occurred. CONCLUSIONS: The addition of genetic testing to autopsy investigation substantially increased the identification of a possible cause of sudden cardiac death among children and young adults. (Funded by the National Health and Medical Research Council of Australia and others.).

Postmortem serum tryptase levels in anaphylactic and non-anaphylactic deaths.

BACKGROUND: The postmortem diagnosis of anaphylaxis remains difficult due to the lack of specific biomarkers. Mast cell tryptase (MCT) levels are used as a marker of mast cell degranulation in living patients and elevated levels have also been described in postmortem serum samples in anaphylaxis-associated deaths, although elevated levels may also be seen in non-anaphylaxis-associated deaths. OBJECTIVE: To investigate the effects of cause of death, site of blood sampling, degree of sample haemolysis and the presence of opiates on postmortem MCT levels. METHOD: We obtained sera from three collection sites from 189 non-suspicious coronial postmortems and aortic samples from 10 anaphylactic deaths to characterise postmortem MCT. RESULTS: MCT were elevated (>11.4 µg/L) in 57% of aortic samples, 58% of femoral samples and 30% of subclavian samples. In aortic samples, there were significantly higher levels of MCT in anaphylaxis-associated deaths compared with other causes of death. Aortic MCT levels >110 µg/L had a sensitivity of 80% and specificity of 92.1% for anaphylaxis-associated deaths. There was a significant correlation between MCT and degree of sample haemolysis but no correlation with the presence of opiates. CONCLUSIONS: Moderately elevated MCT levels are common in postmortem sera. Aortic values >110 µg/L may support a diagnosis of anaphylaxis-associated death, although the diagnosis should not be based on this test alone. There was significant variation between sample sites and reference ranges for individual sample sites should be established.

Community-acquired pneumonia due to pandemic A(H1N1)2009 influenzavirus and methicillin resistant Staphylococcus aureus co-infection.

BACKGROUND: Bacterial pneumonia is a well described complication of influenza. In recent years, community-onset methicillin-resistant Staphylococcus aureus (cMRSA) infection has emerged as a contributor to morbidity and mortality in patients with influenza. Since the emergence and rapid dissemination of pandemic A(H1N1)2009 influenzavirus in April 2009, initial descriptions of the clinical features of patients hospitalized with pneumonia have contained few details of patients with bacterial co-infection. METHODOLOGY/PRINCIPAL FINDINGS: Patients with community-acquired pneumonia (CAP) caused by co-infection with pandemic A(H1N1)2009 influenzavirus and cMRSA were prospectively identified at two tertiary hospitals in one Australian city during July to September 2009, the period of intense influenza activity in our region. Detailed characterization of the cMRSA isolates was performed. 252 patients with pandemic A(H1N1)2009 influenzavirus infection were admitted at the two sites during the period of study. Three cases of CAP due to pandemic A(H1N1)2009/cMRSA co-infection were identified. The clinical features of these patients were typical of those with S. aureus co-infection or sequential infection following influenza. The 3 patients received appropriate empiric therapy for influenza, but inappropriate empiric therapy for cMRSA infection; all 3 survived. In addition, 2 fatal cases of CAP caused by pandemic A(H1N1)2009/cMRSA co-infection were identified on post-mortem examination. The cMRSA infections were caused by three different cMRSA clones, only one of which contained genes for Panton-Valentine Leukocidin (PVL). CONCLUSIONS/SIGNIFICANCE: Clinicians managing patients with pandemic A(H1N1)2009 influenzavirus infection should be alert to the possibility of co-infection or sequential infection with virulent, antimicrobial-resistant bacterial pathogens such as cMRSA. PVL toxin is not necessary for the development of cMRSA pneumonia in the setting of pandemic A( H1N1) 2009 influenzavirus co-infection.

Gastric adenocarcinoma presenting as uterine metastasis--a case report.

BACKGROUND: Metastases to the uterus are rare, especially from extrapelvic malignancies. CASE: We report a 75-year-old woman who underwent hysterectomy for a FIGO Grade I endometrial carcinoma and was found to have evidence of a second malignant process involving the myometrium. The patient underwent a gastroscopy, which showed nonspecific superficial gastric and duodenal erosions. Random biopsies, however, confirmed a diagnosis of primary gastric adenocarcinoma. CT scan also showed pulmonary metastasis. The patient developed progressive disease despite two cycles of chemotherapy consistent of etoposide, doxorubicin and carboplatin. CONCLUSION: This case illustrates the presence of two spatially separated tumours found in the uterus. Malignant cells present deep in the lymphovascular spaces have morphological features different from the primary endometrial carcinoma. The microscopic appearances of these cells are similar to that of the gastric biopsy, supporting the diagnosis of metastatic gastric adenocarcinoma.