Fatal unexpected death due to familial hemophagocytic lymphohistiocytosis type 3.

Familial hemophagocytic lymphohistiocytosis is a rare autosomal recessive disorder of immune dysregulation associated with uncontrolled activation of cytotoxic T cells and macrophages. Herein, we report a case of a 14-month-old Chinese boy who presented with fever, abdominal distension and thrombopenia, and died within 3 days of admission to the hospital. Postmortem examination revealed pleuroperitoneal fluid, enlarged mesenteric lymph nodes and hepatosplenomegaly. Histopathological examination showed interstitial pneumonia, hepatonecrosis and hemophagocytosis. Immunohistochemical staining of the spleen, lymph node and liver specimens revealed numerous cytotoxic T cells (CD8+) and histiocytes (CD68+). EBER1-positive cells were observed in lymphocytes of the spleen, lymph node, liver and lungs by in situ hybridization. UNC13D mutation was identified, although the boy had no family history. The following medico-legal autopsy case is being reported for its rarity in the forensic setting. We addresses the need for genetic testing in addition to a thorough clinical history, appropriate laboratory tests, histological examination and immunohistochemical analysis for the rapid and accurate diagnosis of familial hemophagocytic lymphohistiocytosis.

Remodelling of myocardial intercalated disc protein connexin 43 causes increased susceptibility to malignant arrhythmias in ARVC/D patients.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a primary cardiomyopathy characterised by fibrofatty replacement and ventricular arrhythmias. The occurrence of malignant arrhythmias may be associated with fatty infiltration and intercalated disk remodelling, but the specific pathological remodelling pattern is not yet clear. METHODS: Twelve explanted hearts from patients diagnosed with ARVC/D according to the 2010 Task Force Criteria and pathology examination were divided into two groups with (SVT, n=6) or without (non-SVT, n=6) recurrent sustained ventricular tachycardia (SVT) before heart transplantation. Six ARVC autopsy hearts and six normal donor hearts were also collected. We evaluated the fibrofatty infiltration by Masson staining and the expression of intercalated disc proteins through immunohistochemistry staining combined with western blot using the ventricular tissue of ARVC as well as normal hearts. RESULTS: There was significant fatty replacement in the right ventricles of both the SVT and the non-SVT groups compared to normal hearts, but no significant differences were found in fibre, fatty and residual myocardium components between these two groups. Immunohistochemistry and western blot further showed disturbed distribution and significantly reduced expression of Connexin 43 (Cx43) in the SVT group (SVT vs. Normal P=0.010, SVT vs. non-SVT P=0.012). No significantly diminished expression was found in the non-SVT group. The cardiac histology of ARVC/D patients with sudden death verified by forensic pathology confirmed a similar phenomenon. CONCLUSION: Our pathology study on explanted and autopsied hearts indicates that the expression of Cx43 was significantly reduced and disturbed in distribution in ARVC/D myocardium with sustained ventricular tachycardia, but not in patients without malignant ventricular arrhythmias. This implies a correlation between Cx43 remodelling and malignant arrhythmias in ARVC/D patients.

Sudden Unexplained Nocturnal Death Syndrome in Central China (Hubei): A 16-Year Retrospective Study of Autopsy Cases.

A retrospective study was conducted at Tongji Forensic Medical Center in Hubei (TFMCH) from 1999 to 2014. Forty-nine cases of sudden unexplained nocturnal death syndrome (SUNDS) were collected. The SUNDS rate was 1.0% in the total number of cases, in which an incidence was fluctuating over the years. Interestingly, April and January, and 3:00 to 6:00 AM were the peak months and times of death. Among the decedents, farmers and migrant workers accounted for 67.3%. The syndrome predominantly attacked males in their 30s. One victim had sinus tachycardia. Thirteen victims (26.5%) were witnessed and had abnormal symptoms near death. Macroscopically, compared to sudden noncardiac deaths, the weights of brain, heart, and lungs had no statistical difference in SUNDS. Microscopically, the incidence of lung edema (45 cases, 91.8%) was significantly higher in SUNDS group than in the control group (27 cases, 55.1%). 82.9% of 35 SUNDS cases examined displayed minor histological anomalies of the cardiac conduction system (CCS), including mild or moderate fatty, fibrous or fibrofatty tissue replacement, insignificant stenosis of node artery, and punctate hemorrhage in the node area. These findings suggested that minor CCS abnormalities might be the substrates for some SUNDS deaths. Therefore, SUNDS victims might suffer ventricular fibrillation and acute cardiopulmonary failure before death. Further in-depth studies are needed to unveil the underlying mechanisms of SUNDS.

Commotio Cordis Caused by Violence in China: Epidemiological Characteristics Detected at the Tongji Forensic Medical Center.

Commotio cordis (CC) is a recognized rare cause of sudden death in which an apparently minor blow to the chest causes ventricular fibrillation and cardiac arrest. CC diagnosis is still a challenge for forensic pathologists. A retrospective study of 9794 autopsy cases was conducted at the Department of Forensic Medicine, Tongji Medical College (DFM-TMC, China) from 1955 to 2014. A total of 39 cases (0.4%) were determined to be caused by CC. A male preponderance (male to female of 37:2) was found in the victims, whose age ranged from 13 to 47 years, including more than 85% individuals in their 10s and 20s. Most victims (27 cases, 69.2%) came from village. The highest rate of victims was found for middle school and college students (15 cases, 38.5%), followed by prisoners (11 cases, 28.2%), farmers (9 cases, 23.1%), workers (3 cases, 7.7%), and office staff (1 case, 2.6%). Chest blows were produced by fists (28 cases, 71.8%), feet (6 cases, 15.4%), knee (2 case, 5.1%), head (1 case, 2.6%), or objects (2 cases, 5.1%). Witness statements indicated that most victims collapsed after being impacted in the precordium. The autopsy findings were unremarkable except bruises, contusions, or subcutaneous hemorrhage in the anterior chest (13 cases), bleeding of intercostal muscles (5 cases), and disperse focal petechiae of the epicardium (11 cases). All CC cases in this study were caused by violent attacks and related to criminal processes. Correct diagnosis of CC due to violence has important implications in the judicial system.

Single nucleotide polymorphisms of ERß and coronary atherosclerotic disease in Chinese Han women.

BACKGROUND: Growing evidence has shown that with the increase of age, the incidence of coronary atherosclerotic disease (CAD) in women increases to equal that of men. Several studies on the single nucleotide polymorphisms [SNPs] seem to provide evidence in support of the protective role estrogen receptor ß (ERß) has in reducing the risk of CAD. OBJECTIVE: To determine the association of ERß SNPs rs1256049 RsaI 1082 A > G and rs4986938 AluI 1730 G > A with coronary atherosclerotic disease in Chinese Han women. METHODS: We designed a nested case-control research, in which 120 case women and 30 control women were selected from the Forensic Medicine Department of Tongji Medical College, HUST. We isolated DNA from their lung paraffin blocks, and then screened for these two SNPs for each DNA sample. Post-statistical analysis of their genotypes and haplotypes was used to figure out the targeted association. RESULTS: We found no significant difference between the genotypes or haplotypes of the two SNPs and the risk of CAD. However, the rs4986938 heterozygote AG variant was correlated with a significantly lower risk for CAD than did homozygote GG variant in the group of less than 40 years old. Haplotype AA of the two SNPs was correlated with a higher risk for CAD in the same group. CONCLUSION: The rs4986938 AluI 1730 G > A seems to be quite involved in the genetic basis of the disease and needs more attention in future studies. Meanwhile, this very association made between CAD and the mentioned SNP seems to be affected quite a bit by age.