[Cardiac sarcoidosis as an infrequent cause of sudden death in asymptomatic young patients]. / Sarcoidosis cardíaca como causa muy infrecuente de muerte súbita en pacientes jóvenes asintomáticos.

Cardiac involvement in sarcoidosis has been described in both symptomatic and asymptomatic patients. The aim of this report is to further the understanding of sarcoidosis and its clinical presentation. We report the autopsy and toxicology results of two cases of sudden death in young men. A 37-year-old male had generalized sarcoidosis, in mediastinal glands and intramyocardial sarcoid granulomas in the left ventricle, which had caused a 14mm thickening of the ventricular wall and a secondary dilated myocardiopathy causing sudden death. A 27-year-old male had extensive sarcoidosis of the lungs and mediastinum. Granulomas with a fibrotic background were found in the cardiac wall which could have originated an arrhythmogenic mechanism causing sudden death. Post-mortem study including careful examination of cardiac conduction pathways are vital to ascertain the cause of sudden death.

Carbamazepine Overdose after Psychiatric Conditions: A Case Study for Postmortem Analysis in Human Bone.

Carbamazepine is the main option used as a preventive medication to treat bipolar disorder when there is no response to lithium. Carbamazepine toxicity is defined as serum levels greater than 12 µg/mL, with severe toxicity occurring over 40 µg/mL, reduced to 30 µg/mL when combined with pharmacological treatment, i.e., benzodiazepines or antidepressants. For these reasons, it is necessary to find a validated tool to determine carbamazepine levels in an autopsy to rule out suicide or to know if the death was a consequence of an adverse drug reaction (ADR), especially when only bones can be accessed. We have validated a tool to detect and quantify drug concentration in bone. Our results showed a peak for carbamazepine at minute 12 and a mass fragment of 193 m/z. This case study is the first time in the literature that carbamazepine has been detected and quantified in bone. These results demonstrate that carbamazepine can be detected in bone tissue from forensic cases, but almost more importantly, that the method proposed is valid, reliable, and trustworthy.

Diagnostic Application of Postmortem Cardiac Troponin I Pericardial Fluid/Serum Ratio in Sudden Cardiac Death.

In approximately 5% of unexpected deaths, establishing a conclusive diagnosis exclusively on the basis of anatomo-pathological findings in a classic autopsy is difficult. Postmortem biomarkers have been actively investigated as complementary indicators to help to reach valid conclusions about the circumstances of death. Several studies propose either the pericardial fluid or peripheral veins as a location for troponin determination, but the optimum sampling site is still a matter of debate. Our objective was to evaluate the association between the ratio of troponin values in the pericardial fluid and serum (determined postmortem) and the diagnosis of acute myocardial infarction (AMI) in the context of sudden cardiac death. We included 175 forensic cases. Two groups were established: AMI deaths (48; 27.4%) and the control group (127; 72.6%). The cardiac Troponin I (cTnI) values in the pericardial fluid and the troponin ratio were found to be associated with the cause of death. Univariate regression analyses showed that both age and the cTnI ratio were significantly associated with the diagnosis of AMI death. In a multivariate analysis, adjusting for confounding factors, the age and cTnI ratio were independent predictors of death from myocardial infarction. We performed a receiver operating characteristic (ROC) curve for the cTnI ratio for AMI death and selected a cut-off point. Our biomarker was found to be a valuable and highly effective tool for use in the forensic field as a complementary method to facilitate diagnosis in nonconclusive autopsies.

Muerte súbita en embarazada por embolia trofoblástica vs. tiroiditis vs. canalopatía / Sudden death in pregnancy caused by trophoblastic embolism vs. thyroiditis vs. channelopathy

Mujer de 43 años, gestante de 37 semanas con controles periódicos normales que fallece súbitamente tras cuadro de náuseas y vómitos. Se realiza autopsia forense con estudio histopatológico de todos los órganos (maternos y fetales), toxicológico y genético. Los hallazgos fundamentales fueron: múltiples émbolos trofoblásticos en pulmón; extensa tiroiditis linfocitaria crónica e hipofisitis focal. El análisis genético demostró un polimorfismo en el gen SCN5A del canal del sodio. Se plantean 3 posibles causas de muerte: 1) embolismo trofoblástico; 2) arritmia por alteración electrolítica asociada a hipotiroidismo y potenciada por las náuseas y los vómitos, y 3) síndrome de QT largo por hipertiroidismo y polimorfismo en el gen SCN5A. Este caso es ilustrativo de que la determinación de la causa de la muerte durante el embarazo o puerperio puede ser muy compleja, por lo que la autopsia debe ser exhaustiva incluyendo el estudio histopatológico de los órganos endocrinos, análisis genético y análisis bioquímico

A 43-year-old, 37-week-pregnant woman with normal periodic controls dies suddenly after nausea and vomiting. A complete forensic autopsy is performed with histopathological study of all organs (maternal and foetal), and toxicological and genetic analysis. The main findings were: multiple trophoblastic embolism in the lung; extensive chronic lymphocytic thyroiditis; and focal hypophysitis. Genetic analysis demonstrated a polymorphism in the SCN5A gene of the sodium channel. There are three possible causes of death: 1) trophoblastic embolism; 2) arrhythmia due to electrolyte disturbance associated with hypothyroidism and enhanced by nausea and vomiting; 3) long QT syndrome due to hyperthyroidism and polymorphism in the SCN5A gene. This case illustrates that determination of cause of death during pregnancy or puerperium can be very complex, so the autopsy must be exhaustive including histopathological study of the endocrine organs, and genetic and biochemical analysis

Study of chemiluminescence measured by luminometry and its application in the estimation of postmortem interval of bone remains.

A substantial challenge faced by forensic medicine is determining the postmortem interval (PMI) of skeletonized remains. Currently, the luminol method is of limited forensic usefulness, since it uses qualitative and subjective methods to estimate PMI by the naked eye assessing the degree of chemiluminescence (CL) emitted by bone remains, a technique which is not sensitive enough to distinguish between historical or forensically significant time intervals. The aim of the present study was to use a direct and accurate measurement of the CL by luminol technique in relative light units (RLU) using a luminometer to establish this method as a possible complementary and low cost tool for the determination of the PMI for distinguishing between remains of medical-legal (<20 years) and historical (≥20 years) interest in 102 femur remains with a range of PMI between 15 and 64 years. The results suggest that, under favorable conditions, the luminol technique can detect haemoglobin in the bone in a PMI range of 0-65 years, finding significant differences in the CL intensity among samples with PMI < 20 years and PMI ≥ 20 years. In addition, the intensities of CL measured at 10 s, 15 s and 20 s after reaction with luminol show a statistically significant inverse relationship with PMI in the bone studied, following a decreasing logarithmic model. The conclusion is that this quantitative, objective and contrastable technique could be very useful for determining the PMI in bone remains, since it allows a good degree of precision and eliminates the subjectivity introduced by qualitative techniques.

Somatic MYH7, MYBPC3, TPM1, TNNT2 and TNNI3 mutations in sporadic hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a clinically heterogeneous genetic heart disease characterized by left ventricular hypertrophy in the absence of another disease that could explain the wall thickening. Elucidation of the genetic basis of HCM lead to the identification of several genes encoding sarcomeric proteins, such as MYH7, MYBPC3, TPM1, TNNT2, and TNNI3. Sarcomeric genes are mutated in approximately 40% of HCM patients and a possible explanation for the incomplete yield of mutation-positive HCM may be somatic mutations. METHODS AND RESULTS: We studied 104 unrelated patients with non-familial HCM. Patients underwent clinical evaluation and mutation screening of 5 genes implicated in HCM (MYH7, MYBPC3, TPM1, TNNT2, and TNNI3) in genomic DNA isolated from resected cardiac tissue; 41 of 104 were found to carry a mutation, but as several patients carried the same mutations, the total amount of different mutations was 37; 20 of these mutations have been previously described, and pathogenicity has been assessed. To determine the effect of the 17 new mutations an in silico assay was performed and it predicted that 4 variants were damaging mutations. All identified variants were also seen in the DNA isolated from the corresponding blood, which demonstrated the absence of somatic mutations. CONCLUSIONS: Somatic mutations in MYH7, MYBPC3, TPM1, TNNT2, and TNNI3 do not represent an important etiologic pathway in HCM.