Relationship between N-terminal pro-brain natriuretic peptide concentration and heart-type fatty acid-binding protein in postmortem urine.

The clinical use of N-terminal pro-brain natriuretic peptide (NT-proBNP) and blood concentrations of heart-type fatty acid-binding protein (HFABP) is well-established in diagnosing heart conditions. However, their applicability in forensics is controversial due to postmortem changes. NT-proBNP and HFABP are excreted in the urine due to their small molecular weights and may be found in postmortem urine samples; however, their correlation has not been evaluated. In this study, we compared the concentrations of urinary NT-proBNP and HFABP in 386 forensic autopsy cases. The urinary NT-proBNP levels were significantly higher in acute myocardial infarction (AMI), congestive heart failure (CHF), sepsis, and hyperthermia cases, with the highest levels in CHF cases. Similarly, HFABP concentration was significantly higher in CHF, sepsis, and hyperthermia cases, with the highest level observed in hyperthermia cases. However, the difference in urinary HFABP levels between the AMI and control cases was not significant. Our analysis revealed a correlation between postmortem urine NT-proBNP and HFABP levels, and the NT-proBNP/HFABP ratio was high in patients with CHF and sepsis cases and low in those with hyperthermia. The difference between the ratios was possibly due to the combined release of ventricular myocardial cells in response to ventricular wall stress and myocardial injury for NT-proBNP, as well as myocardial and skeletal muscle injuries for HFABP. This study, for the first time, demonstrates the utility of postmortem measurements of urinary NT-proBNP and HFABP levels, offering valuable insights for improving the accuracy of postmortem diagnosis in forensic medicine.

Postmortem pericardial fluid sLOX-1 levels and LOX-1 immunostaining in forensic specimens: Relation to cause of death.

Lectin-like oxidized LDL receptor-1 (LOX-1) is the endothelial receptor for oxidized LDL. This receptor's extracellular domain is released into the blood as soluble LOX-1 (sLOX-1) and has been linked to ischemic heart disease (IHD), cerebrovascular diseases (CVDs), obesity, and diabetes. We recently reported that sLOX-1 fluid levels in postmortem pericardial fluid were comparable to clinical values in live patients and that significant increases in sLOX-1 were observed in patients with IHD. However, postmortem serum and urine sLOX-1 levels were higher than serum levels in living patients. Here, we conducted LOX-1 immunostaining in forensic specimens (aorta and heart) and evaluated pericardial fluid sLOX-1 in 221 medicolegal autopsy cases (67 IHD, 11 CVD, 17 inflammatory diseases, and 126 control cases) with a postmortem interval < 72 h to assess the diagnostic efficiency of postmortem pericardial fluid sLOX-1. Furthermore, we evaluated the relationships between pericardial fluid sLOX-1 and body mass index (BMI), blood HbA1c, serum C-reactive protein (CRP), high-density lipoprotein cholesterol (HDL-C), and low-density-lipoprotein cholesterol (LDL-C). LOX-1 immunostaining positivity was found in the aortic intima. Pericardial fluid sLOX-1 levels were considerably higher in patients with IHD and CVD. However, there were no significant differences in patients with inflammatory diseases and controls. No associations between pericardial fluid sLOX-1 and BMI, HbA1c, CRP, HDL-C, or LDL-C were found. These results indicate sLOX-1 utility in the postmortem diagnosis of IHD and CVD.

Effectiveness of Rapid Antigen Testing in Forensic Cases of Severe Acute Respiratory Syndrome Coronavirus 2 Infection, Including Delta Variant.

ABSTRACT: The polymerase chain reaction is indispensable for diagnosing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in forensic cases. However, studies regarding the effectiveness of rapid antigen testing (RAT) in forensic cases remain limited. Therefore, we investigated the efficacy of RAT compared with reverse-transcription quantitative polymerase chain reaction (RT-qPCR) for confirming SARS-CoV-2 infection (including the delta variant). Before the external examination or autopsy, we collected samples from the nasopharyngeal mucosa, which were then assessed via RAT (QuickNavi COVID-19 Ag kit, QuickNavi-Flu+COVID-19 Ag kit) and RT-qPCR. Reverse-transcription quantitative polymerase chain reaction results were positive in 73 of 1255 cases, and 21 cases were identified as those of delta variants. Low RT-qPCR threshold cycle value cases and delta variant infections were more likely to result in coronavirus disease-related deaths. The sensitivity of the QuickNavi COVID-19 Ag kit was 76.32%, and that of the QuickNavi-Flu+COVID-19 Ag kit was 77.14%. The specificity of both RATs was 100%. In QuickNavi COVID-19 Ag kit cases, delta variant cases showed lower sensitivity than non-delta variant cases, even for a similar viral load. Thus, RAT in forensic cases is sufficiently useful as a screening test for SARS-CoV-2 infection. However, RAT carries a risk of false negatives, especially for delta variant cases.

Comprehensive Severe Acute Respiratory Syndrome Coronavirus 2 Detection Using Polymerase Chain Reaction and Rapid Antigen Testing in Postmortem Specimens.

ABSTRACT: Polymerase chain reaction (PCR) is indispensable for diagnosing coronavirus disease 2019 (COVID-19) in autopsy cases. In this study, we performed comprehensive reverse transcription quantitative PCR (RT-qPCR) and rapid antigen tests for COVID-19 on forensic postmortem specimens, regardless of the antemortem symptoms and causes of death. Immediately before forensic external examination and autopsy, a wiping solution was collected from the nasopharynx with a dry swab, and rapid antigen testing and RT-qPCR were performed. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was detected by RT-qPCR in 12 of the 487 cases; the infection rate was 2.46%. Of the RT-qPCR-positive cases, 7 were associated with COVID-19-related deaths. Cycle threshold values were not correlated with the cause of death or postmortem time. The sensitivity and specificity of the rapid antigen test were 91.67% and 100.00%, respectively. The RT-qPCR positivity rate of forensic cases was higher than the cumulative infection rate for the entire population. SARS-CoV-2 could be detected with the rapid antigen test and RT-qPCR within 216 hours of death. Because the rapid antigen test showed the same sensitivity and specificity as those observed in clinical practice, the test combined with RT-qPCR may be useful for diagnosing COVID-19 even in postmortem specimens.

Postmortem urine concentration of N-terminal pro-brain natriuretic peptide in relation to the cause of death.

The utility of biochemical marker analysis in forensic autopsy cases is still uncertain due to the postmortem changes which they undergo. Thus, research is required to elucidate alternative samples and biochemical markers which are less affected by postmortem changes. Levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) are known to be elevated in congestive heart failure (CHF), acute myocardial infarction (AMI), and sepsis patients. Although NT-proBNP is reportedly excreted into the urine, no study has previously evaluated the diagnostic efficacy of urinary concentrations in a forensic setting. The aim of this study was to evaluate the diagnostic efficacy of NT-proBNP concentration in urine obtained postmortem in a series of forensic autopsy cases. METHODS: Urinary NT-proBNP was measured in 36 AMI, 10 CHF, and 19 sepsis cases, and in 124 control cases (all with postmortem interval [PMI]<72h). RESULTS: Urinary NT-proBNP was significantly higher in AMI, CHF, and sepsis cases than in control cases. Cut-off values for diagnosing AMI, CHF, and sepsis-related fatalities were 98 (sensitivity, 55.6 %; specificity, 73.4 %), 1050 (sensitivity, 80.0 %; specificity, 94.4 %), and 363pg/mL (sensitivity, 84.2 %; specificity, 85.5 %), respectively. Furthermore, we subdivided the control cases according to the death process as either acute death (87 cases) or prolonged death cases (37 cases). Although urine NT-proBNP of CHF and sepsis cases were significantly higher compared with both cases, the concentration in the AMI cases were significantly high only when compared with the acute death cases. CONCLUSION: This study is the first to elucidate the diagnostic utility of NT-proBNP measurement in urine obtained postmortem in a series of causes of death. This study suggests the diagnostic efficacy for AMI, CHF, and sepsis-related fatality in cases in which the PMI was within 72h.

Utility of soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) in the postmortem diagnosis of ischemic heart disease.

PURPOSE: Ischemic heart disease (IHD) is a major cause of death in developed countries. Postmortem IHD diagnosis using biochemical markers is difficult because of the postmortem changes. In the present study, we investigated the utility of soluble lectin-like low-density lipoprotein receptor-1 (sLOX-1) in body fluids obtained from forensic autopsy cases. METHODS: We measured pericardial fluid, urine, and serum sLOX-1 levels; these samples were obtained from medicolegal autopsy cases (n = 149, postmortem interval <72 h), and the utility of these biomarkers postmortem acute IHD diagnosis was evaluated. RESULTS: The pericardial fluid and urine of patients with acute IHD had higher sLOX-1 levels (p < .05) compared to the controls. No significant differences were found between the sLOX-1 level and the degree of coronary atherosclerosis, body mass index, and postmortem interval. CONCLUSION: sLOX-1 levels in pericardial fluid and urine samples obtained postmortem are useful markers of acute IHD.