Post-mortem microbiology in sudden death: sampling protocols proposed in different clinical settings.

BACKGROUND: Autopsies, including minimally invasive autopsies, are a powerful tool for determination of the cause of death. When a patient dies from an infection, microbiology is crucial to identify the causative organism. Post-mortem microbiology (PMM) aims to detect unexpected infections causing sudden deaths; confirm clinically suspected but unproven infection; evaluate the efficacy of antimicrobial therapy; identify emergent pathogens; and recognize medical errors. Additionally, the analysis of the thanatomicrobiome may help to estimate the post-mortem interval. AIMS: The aim was to provide advice in the collection of PMM samples and to propose sampling guidelines for microbiologists advising autopsy pathologists facing different sudden death scenarios. SOURCES: A multidisciplinary team with experts in various fields of microbiology and autopsies on behalf of the ESGFOR (ESCMID - European Society of Clinical Microbiology and Infectious Diseases - study group of forensic and post-mortem microbiology and in collaboration with the European Society of Pathology) developed this narrative review based on a literature search using MedLine and Scopus electronic databases supplemented with their own expertise. CONTENT: These guidelines address measures to prevent sample contamination in autopsy microbiology; general PMM sampling technique; protocols for PMM sampling in different scenarios and using minimally invasive autopsy; and potential use of the evolving post-mortem microbiome to estimate the post-mortem interval. IMPLICATIONS: Adequate sampling is paramount to identify the causative organism. Meaningful interpretation of PMM results requires careful evaluation in the context of clinical history, macroscopic and histological findings. Networking and closer collaboration among microbiologists and autopsy pathologists is vital to maximize the yield of PMM.

Local colorectal cancer recurrence: pelvic MRI evaluation.

Surveillance of colorectal cancer is currently based on dosage of tumoral markers, colonoscopy and multidetector row computed tomography. However, pelvic magnetic resonance imaging (MRI) and PET-CT are two second-line useful imaging modalities to assess colorectal cancer local recurrence (LR). The anatomical information derived from MRI combined to the functional information provided by diffusion-weighted imaging currently remain of value. Pelvic MRI is accurate not only for detection of pelvic colorectal recurrence but also for the prediction of absence of tumoral invasion in pelvic structures, and it may thus provide a preoperative road map of the recurrence to allow for appropriate surgical planning. As always, correlation of imaging and clinical findings in the multidisciplinary forum is paramount. MRI can also be used to follow-up LR treated with radiofrequency ablation. The aim of this review is to discuss clinical practice and application of MRI in the assessment or pelvic recurrence from colorectal cancer.

Guidelines for autopsy investigation of sudden cardiac death.

Although sudden cardiac death is one of the most important mode of death in Western Countries, pathologists and public health physicians have not given this problem the attention it deserves. New methods of preventing potentially fatal arrhythmias have been developed and the accurate diagnosis of the causes of sudden cardiac death is now of particular importance. Pathologists are responsible for determining the precise cause of sudden death but there is considerable variation in the way in which they approach this increasingly complex task. The Association for European Cardiovascular Pathology developed these Guidelines, which represent the minimum standard that is required in the routine autopsy practice for the adequate assessment of sudden cardiac death, including not only a protocol for heart examination and histological sampling, but also for toxicology and molecular investigation. Our recommendations apply to University Medical Centres, Regional and District Hospitals and all types of Forensic Medicine Institutes. If a uniform method of investigation is adopted throughout the European Union, this will lead to improvements in standards of practice, allow meaningful comparisons between different communities and regions and, most importantly, permit future trends in the patterns of disease causing sudden death to be monitored.

Guías para la práctica de la autopsia en casos de muerte súbita cardíaca / Guidelines for autopsy investigation of sudden cardiac death

A pesar de que la muerte súbita cardíaca es una delas formas más importantes de muerte en los paísesoccidentales, este problema no ha recibido la atenciónque merece por parte de los patólogos y de los médicosde los sistemas públicos de salud. Se han desarrolladonuevos métodos de prevención de arritmias potencialmentemortales, y el diagnóstico de certeza de las causasde muerte súbita cardíaca es en este momento departicular importancia. Los patólogos son responsablesde determinar la causa exacta de la muerte súbita peroexisten diferencias considerables en el modo en el quese aborda esta cada vez más compleja tarea. LaAsociación Europea de Patología Cardiovascular desarrollóunas guías que representan el estándar mínimonecesario en la práctica habitual de la autopsia para lavaloración de la muerte súbita cardíaca, incluyendo nosólo un protocolo para el examen del corazón y el muestreohistopatológico, sino también para la investigacióntoxicológica y molecular. Nuestras recomendaciones sonaplicables a centros médicos universitarios, a hospitalesregionales y locales y a todo tipo de Institutos deMedicina Forense. La adopción a lo largo de la UniónEuropea de un método uniforme de investigaciónsupondrá la mejora de la práctica habitual, permitirárealizar comparaciones significativas entre distintascomunidades y regiones y, lo que es más importanteaún, favorecerá que se monitoricen los patrones de lasenfermedades que causan una muerte súbita(AU)

Although sudden cardiac death is one of the mostimportant mode of death in Western Countries,pathologists and public health physicians have not giventhis problem the attention it deserves. New methods ofpreventing potentially fatal arrhythmias have beendeveloped, and the accurate diagnosis of the causes ofsudden cardiac death is now of particular importance.Pathologists are responsible for determining the precisecause of sudden death but there is considerable variationin the way in which they approach this increasinglycomplex task. The Association for EuropeanCardiovascular Pathology developed guidelines, whichrepresent the minimum standard that is required in theroutine autopsy practice for the adequate assessment ofsudden cardiac death, including not only a protocol forheart examination and histological sampling, but also fortoxicology and molecular investigation. Ourrecommendations apply to university medical centres,regional and district hospitals and all types of forensicmedicine institutes. If a uniform method of investigation isadopted throughout the European Union, this will lead toimprovements in standards of practice, allow meaningfulcomparisons between different communities and regionsand, most importantly, permit future trends in thepatterns of disease causing sudden death to bemonitored(AU)

Preliminary ex vivo 3D microscopy of coronary arteries using a standard 1.5 T MRI scanner and a superconducting RF coil.

This paper presents the feasibility of three-dimensional (3D) magnetic resonance (MR) histology of atheromatous coronary lesions in the entire human heart ex vivo using a standard 1.5 T scanner and a 12 mm high-temperature superconducting (HTS) surface coil. The HTS coil was a five-turn transmission-line resonator operated at 77 K, affording a signal-to-noise ratio (SNR) gain of about ninefold as compared to a similar, room-temperature copper coil. Local microscopy at the surface of an explanted, entire heart was achieved by a 3D spoiled gradient echo sequence and assessed by comparison with conventional histology. One hundred and twenty four adjacent cross sections of the coronary artery, with voxels of 59 x 59 x 100 microm3 and an SNR of about 20, were obtained in 25 min. Consecutive data sets were combined to reconstruct extended views along the artery. Compared to histology, MR microscopy allowed precise nondestructive 3D depiction of the architecture of the atheromatous plaques. This is the first report of microscopic details (less than 10(-3) mm3 voxels) of diseased arteries obtained in an entire human heart preserving the arterial integrity and the spatial geometry of atheroma. This noninvasive microscopy approach using a HTS surface coil might be applied in vivo to study the architecture and components of superficial human structures, using routine MR scanners.

[Arrhythmogenic right ventricular dysplasia]. / Nouveautés dans la dysplasie ventriculaire droite arythmogène.

Congestive cardiac failure could be as important as cardiac arrhythmias in the natural history of arrhythmogenic right ventricular dysplasia. This can be related to the progressive replacement of myocardium by fat and fibrosis of the right ventricle. The left ventricle may also be involved by the same disease process. Moreover, inflammation can be superimposed on ARVD, resulting in a wide spectrum of clinical presentation which can mimick idiopathic dilated cardiomyopathy. Right ventricular cardiac failure has been controlled by anterior dynamic cardiomyoplasty.

Fulminant invasive pulmonary aspergillosis in immunocompetent patients--a two-case report.

Two cases of invasive aspergillosis (IA) in immunocompetent patients with a fulminant fatal outcome are reported. Both patients were elderly and had a history of chronic lung disease treated with prolonged inhaled corticosteroids and a short course of systemic corticosteroids. They presented with dyspnea and fever, their respiratory function deteriorated rapidly, and they died 7 days after admission. Aspergillus fumigatus was cultured from respiratory samples. IA was confirmed in one case by necropsy that showed diffuse bilateral necrotizing pneumonitis and myocarditis. In the other case, IA diagnosis was established by thoracic CT scan plus detection of Aspergillus antigen in two blood samples. These two cases demonstrate that short-term corticosteroid therapy in immunocompetent patients with underlying chronic lung conditions is a risk factor for IA, and that its evolution can be fulminant.

Myocarditis associated with Hashimoto's disease: a case report.

We report on a sudden cardiac death case involving a 40-year-old man with no known medical history. Forensic autopsy showed lymphocytic myocarditis associated with lymphocytic thyroiditis. In both the heart and the thyroid gland, the inflammatory foci often had a nodular pattern with a germinal centre. Virological and toxicological analyses were negative. Postmortem biochemistry showed a slight increase in TSH in combination with normal T3 and T4 blood levels suggesting hypothyroidism. High titres of antiperoxidase and antithyroglobulin antibodies with normal levels of TSH receptor antibodies, in addition to biological hypothyroidism and lymphocytic inflammation were consistent with the diagnosis of Hashimoto's thyroiditis. Immunohistochemical studies excluded a lymphoma and showed no evidence of viral myocarditis. In contrast to Grave's disease, Hashimoto's thyroiditis has never been reported in association with myocarditis as a cause of sudden death. We conclude that the cardiac immunological and histological pattern, similar to that found in the thyroid gland suggests an autoimmune myocarditis.

Survival, haemodynamics and cardiac remodelling follow up in mice after myocardial infarction.

1. In the present study, the time-course, over a 1 year period, of postischaemic dilated cardiomyopathy and/or development of congestive heart failure was investigated in mice in terms of survival and cardiac functional and structural characteristics. 2. C57BL/6 mice with myocardial infarction (MI mice; coronary ligation n = 78) or sham-operated animals (n = 45) were used and echocardiographic, haemodynamic and histomorphometric parameters were assessed at 3, 6 and 12 months post-MI. 3. At 12 months, the survival rate was 70% in MI mice. Left ventricular dysfunction was evidenced by a strong decrease in ejection fraction (EF; -48 and -53% at 6 and 12 months, respectively; both P < 0.05) and an increase in left ventricular end-diastolic pressure (+100% at both 6 and 12 months; both P < 0.05). There was no major worsening in cardiac function between 6 and 12 months, suggesting strong compensatory mechanisms. Cardiac remodelling was observed, characterized by strong left ventricular hypertrophy (+38 and +62% at 6 and 12 months, respectively; both P < 0.05) and dilatation (+53% at 6 months; P < 0.05), but collagen was not significantly increased. Significant correlations were found between EF (echocardiography) and dP/dtmax, between end-diastolic volume (echocardiography) and left ventricular internal perimeter (histomorphometry) and between left ventricular mass (echocardiography) and weight. 4. In conclusion, despite a high survival rate, the MI mouse model displays most of the hallmarks of postischaemic dilated cardiomyopathy and/or congestive heart failure, thus affording the necessary background for the subsequent evaluation of gene manipulation and/or drug effects. In addition, two-dimensional echocardiography appears to be a suitable tool for the long-term follow up of cardiac function and remodelling in this model.

Age and gender effects on cardiomyocyte apoptosis in the normal human heart.

BACKGROUND: Animal studies have suggested that apoptosis could play a significant role in the myocardial aging process. Although no information is available in humans, the paradigm that cardiomyocyte apoptosis is increased in the aged human heart has been widely propagated. Moreover, it is unknown whether gender differences may influence cardiomyocyte apoptosis. METHODS: Cardiomyocyte apoptosis was compared between subjects ranging in age from 21 to 93 years (22 men and 19 women), free of any cardiovascular disease, who died of either violent or natural causes. Strict inclusion and exclusion criteria were used to ensure that the selected hearts accurately represented normal aging. RESULTS: Apoptosis was detected using the TdT-mediated dUTP digoxigenin nick end labeling (TUNEL) technique (controls for TUNEL included negative staining for splicing factor SC-35 and for Ki-67 antigen). The percentage of cardiomyocyte death ranged from 0% to 0.0437%, with no correlation with the age of the subject (p =.85). However, the percentage of apoptosis was threefold higher in men than in women (0.0133% +/- 0.0030% vs 0.0042% +/- 0.0008%, respectively; p <.01). CONCLUSIONS: Our results in humans do not support the hypothesis that aging influences the percentage of cardiomyocyte apoptosis. However, gender appears to be an important determinant of the occurrence of apoptosis.

Combined angiotensin II AT1-receptor blockade and angiotensin I-converting enzyme inhibition on survival and cardiac remodeling in chronic heart failure in rats.

BACKGROUND: Angiotensin I-converting enzyme inhibition (ACEI) and angiotensin II AT(1)-receptor blockade are effective at improving survival and limiting cardiac remodeling in the rat model of postischemic heart failure. Whether their combination yields additive/synergistic effects is unknown. METHODS AND RESULTS: Rats underwent coronary artery ligation and 7 days later were treated orally for 9 months with placebo (controls), 5 mg/kg valsartan, 1 mg/kg enalapril (doses submaximally effective at reducing mortality in the experimental model used), or 5 mg/kg valsartan and 1 mg/kg enalapril combined. Compared with controls, valsartan, enalapril, and their combination decreased mortality by 40% (P =.006), 21% (P =.065), and 33% (P =.032), respectively, but there was no significant difference between the 3 treatments. At the doses used, valsartan, but neither enalapril nor the combination, slightly limited cardiac hypertrophy and fibrosis development and reduced left ventricular end-diastolic pressure as assessed in the surviving animals at 9 months. CONCLUSIONS: In experimental chronic heart failure in rats, valsartan reduces mortality similar to other AT(1)-receptor blockers and a combination of AT(1)-receptor blockade (valsartan) and ACEI (enalapril) at submaximal doses does not exert additive/synergistic beneficial effects on mortality.

[Sudden death and physical activity and sports]. / Mort subite et activité physique et sportive.

A growing number of people are involved in recreational physical activity. We examined the clinical and cardiac pathological patterns in 29 persons who died suddenly during a sport activity and were autopsied at the Institute of Forensic Medicine of Paris, 1990-1999. Twenty-seven males ranging in age from 13 to 57 years, mean 30.5, and two females, 8 and 60 years old, died suddenly during a sport activity. The sports included running, 11 cases; cycling, 4; soccer, 3; swimming, 2; basket-ball, 2; rugby, 1, gymnastic exercises, 2; tennis, 1; gockart, 1; skiing, 1; hand-ball, 1 case. The causes of deaths were as follows; coronary artery disease, 9 cases; congenital anatomic anomaly of a coronary artery, 1; hypertrophic cardiomyopathy, 5; right ventricular dysplasia, 3; myocarditis, 2; endomyocardial fibrosis, 1; bridging of the left anterior descending coronary artery, 2; stroke, 2; rupture of aortic aneurysm, 4. Despite severity of lesions, only 4 victims had a known cardiovascular disease. Efforts should be continued to improve sensitivity and specificity of diagnostic tools and screening strategies. Therefore, medico-legal autopsies should be systematically performed for a better knowledge of sport-related mortality.