Cytokines and sudden infant death.

BACKGROUND: It has been hypothesised that inflammatory reactions could play an important role in the pathway(s) leading to sudden and unexpected death in infancy. On a molecular level, these reactions are regulated by various cytokines. METHODS: To characterise the role of IL-1ß, IL-6 and TNFα more precisely, the concentrations of these cytokines were determined quantitatively using specific ELISA techniques in serum and cerebrospinal fluid (CSF) in 119 cases of sudden infant death. The infants were grouped into four categories (SIDS, SIDS with infection, natural death due to infection and unnatural death). RESULTS: A good correlation was found between CSF and serum for IL-6 (Spearman correlation coefficients (SCC), 0.73) and also for TNFα (SCC, 0.57), although the CSF concentrations were lower than that from the serum. There were no significant differences between the categories of death for any of the serum or CSF cytokines. Compared with normal values, increased serum concentrations of IL-1ß, IL-6 and TNFα were found in 70%, 69% and 38% of the cases respectively, indicating possible agonal or post-mortem changes of cytokine concentrations. In three cases very high cytokine concentrations were found (mainly for IL-6). This may have contributed to the mechanism of death (cytokine storm) in two of the cases. CONCLUSIONS: In a small group of patients, very high cytokine concentrations are a possible explanation for the cause of death ("cytokine storm").

Estimation of the postmortem interval by analyzing potassium in the vitreous humor: could repetitive sampling enhance accuracy?

The relationship between the postmortem interval and the potassium concentration in the vitreous humor has been described by different authors. A limitation of most previous studies might be that all of the vitreous humor has been extracted in 1 sample from different subjects and that the sample was therefore inhomogeneous. In 32 traumatic deaths with known postmortem intervals, small quantities of vitreous humor have been sampled repetitively in 3-hour interval. The bodies were stored at 20°C. The average concentrations of potassium in relation to the postmortem interval were 6.11 to 14.46 mmol/L. An equation that allows accurate prediction of the postmortem interval was established: postmortem interval (h) = 2.749 × [K] - 11.978.

Molecular consequences of SARS-CoV-2 liver tropism.

Extrapulmonary manifestations of COVID-19 have gained attention due to their links to clinical outcomes and their potential long-term sequelae1. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) displays tropism towards several organs, including the heart and kidney. Whether it also directly affects the liver has been debated2,3. Here we provide clinical, histopathological, molecular and bioinformatic evidence for the hepatic tropism of SARS-CoV-2. We find that liver injury, indicated by a high frequency of abnormal liver function tests, is a common clinical feature of COVID-19 in two independent cohorts of patients with COVID-19 requiring hospitalization. Using autopsy samples obtained from a third patient cohort, we provide multiple levels of evidence for SARS-CoV-2 liver tropism, including viral RNA detection in 69% of autopsy liver specimens, and successful isolation of infectious SARS-CoV-2 from liver tissue postmortem. Furthermore, we identify transcription-, proteomic- and transcription factor-based activity profiles in hepatic autopsy samples, revealing similarities to the signatures associated with multiple other viral infections of the human liver. Together, we provide a comprehensive multimodal analysis of SARS-CoV-2 liver tropism, which increases our understanding of the molecular consequences of severe COVID-19 and could be useful for the identification of organ-specific pharmacological targets.

The German case-control scene investigation study on SIDS: epidemiological approach and main results.

The present study, which was part of the German SIDS Study (GeSID), enrolled sudden infant death syndrome (SIDS) cases and population controls and obtained objective scene data via specifically trained observers shortly after discovery of each dead infant. Infants who had died suddenly and unexpectedly at ages between 8 and 365 days were enrolled in five regions of Germany between November 1998 and October 2001. Shortly after discovery of each dead infant, a specially trained doctor of legal medicine visited the bereaved family at home. Data were obtained by measurements and observations. Dead infants underwent a standardised autopsy, additional information being obtained by standardised parent interviews. Investigation of the sleep environment and wake-up scene in matched controls followed the same protocol. A total of 52 SIDS cases and 154 controls were enrolled, 58% were boys, and median age of cases vs. controls was 126 vs. 129 days. Risk factors in the sleeping environment were pillow use (adjusted OR 4.3; 95%CI 1.6-11.6), heavy duvets (OR 4.4; 1.5-13.3), soft underlay (OR 3.0; 1.1-8.7), face covered by bedding (OR 15.8; 2.5-102.1) and entire body covered by bedding (OR 35.5; 5.5-228.3). Using a standardised protocol, including objective measurements of the sleep environment and a case-control design, this study was able to confirm many risk factors for SIDS.

Neuropathology of patients with COVID-19 in Germany: a post-mortem case series.

BACKGROUND: Prominent clinical symptoms of COVID-19 include CNS manifestations. However, it is unclear whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, gains access to the CNS and whether it causes neuropathological changes. We investigated the brain tissue of patients who died from COVID-19 for glial responses, inflammatory changes, and the presence of SARS-CoV-2 in the CNS. METHODS: In this post-mortem case series, we investigated the neuropathological features in the brains of patients who died between March 13 and April 24, 2020, in Hamburg, Germany. Inclusion criteria comprised a positive test for SARS-CoV-2 by quantitative RT-PCR (qRT-PCR) and availability of adequate samples. We did a neuropathological workup including histological staining and immunohistochemical staining for activated astrocytes, activated microglia, and cytotoxic T lymphocytes in the olfactory bulb, basal ganglia, brainstem, and cerebellum. Additionally, we investigated the presence and localisation of SARS-CoV-2 by qRT-PCR and by immunohistochemistry in selected patients and brain regions. FINDINGS: 43 patients were included in our study. Patients died in hospitals, nursing homes, or at home, and were aged between 51 years and 94 years (median 76 years [IQR 70-86]). We detected fresh territorial ischaemic lesions in six (14%) patients. 37 (86%) patients had astrogliosis in all assessed regions. Activation of microglia and infiltration by cytotoxic T lymphocytes was most pronounced in the brainstem and cerebellum, and meningeal cytotoxic T lymphocyte infiltration was seen in 34 (79%) patients. SARS-CoV-2 could be detected in the brains of 21 (53%) of 40 examined patients, with SARS-CoV-2 viral proteins found in cranial nerves originating from the lower brainstem and in isolated cells of the brainstem. The presence of SARS-CoV-2 in the CNS was not associated with the severity of neuropathological changes. INTERPRETATION: In general, neuropathological changes in patients with COVID-19 seem to be mild, with pronounced neuroinflammatory changes in the brainstem being the most common finding. There was no evidence for CNS damage directly caused by SARS-CoV-2. The generalisability of these findings needs to be validated in future studies as the number of cases and availability of clinical data were low and no age-matched and sex-matched controls were included. FUNDING: German Research Foundation, Federal State of Hamburg, EU (eRARE), German Center for Infection Research (DZIF).

Current recommendations on infants' sleeping position are being followed-initial results of a population-based sentinel study on risk factors for SIDS, 1996-2006, in Hamburg, Germany.

Sudden infant death syndrome (SIDS) is a target for public health care in Germany. The aim of this study was to monitor data on risk-related behavior in the population of Hamburg, Germany, in order to respond to changes quickly and to estimate the effectiveness of prevention activities. Data have been gathered using the sentinel system with repeated surveys (1996, 1998, 2001, and 2006) in pediatric practices, thus allowing an estimate of the prevalence of risk factors in an urban population, both transversally and vertically. From 1996 to 2007, the SIDS rate in Hamburg fell from 0.9/1,000 live births to 0.1. The prevalence of infants sleeping prone declined from 8.1% in 1996 to 3.5% in 2006. In this small subgroup, up to 81.7% (2006) of the caretakers were well aware of the risk of sleeping prone. The prevalence of infants sleeping on their sides fell from 55.3% in 1998 to 10.6% in 2006. The sentinel setting is suitable for gathering risk-related data on SIDS. Despite the fact that, so far, no nationwide back-to-sleep campaign has been instituted in Germany, local campaigns have proved successful in reducing prone sleeping for infants. Moreover, the substantial reduction of side sleeping within a short time span going along with a reduced SIDS rate is an indicator of the effectiveness of prevention activities on a local basis.

Avulsion of the left internal mammary artery graft after minimally invasive coronary surgery: fatal complication or medical error? A case report.

Minimally invasive direct coronary artery bypass (MIDCAB) is performed through a left anterior mini-thoracotomy without the use of a cardiopulmonary bypass and offers greater potential for more rapid recovery, reduced pain and a decreased need for blood transfusion than conventional coronary artery bypass grafting. Few major complications of the MIDCAB procedure have been reported in the literature since the first intervention was performed in 1995, but the most serious one is avulsion of the left internal mammary artery (LIMA) graft near the site of anastomosis with the left anterior descending coronary artery. Forensic issues regarding the role of the surgeon in causing this life-threatening emergency condition have not been discussed. We report here the case of a 48-year-old man who died 18 days after a MIDCAB of massive thoracic bleeding due to the avulsion of the LIMA graft. We discuss the probable etiopathogenesis of this fatal complication from a forensic point of view.