Cause of death and the autopsy rate in an elderly population.

Autopsy rates are declining, while major discrepancies between autopsies and clinical diagnoses remain. Still, little is known about the impact of suspected underlying diseases, for example, a diagnosis of cancer, on the autopsy rate. The aim of this study was to investigate the relation between the clinical cause of death, a history of cancer, and the medical autopsy rate using data from the Netherlands Cohort Study on Diet and Cancer (NLCS), a large prospective cohort study with a long follow-up. The NLCS is a prospective study initiated in 1986 and includes 120,852 persons (58,279 males and 62,573 females), 55-69 years of age at the time of enrollment. The NLCS was linked with the Dutch Nationwide Pathology Databank (PALGA), the Dutch Population Register (GBA), the Netherlands Cancer Registry, and the causes of death registry (Statistics Netherlands). If applicable, the 95% confidence intervals were calculated. During the follow-up of the NLCS, 59,760 deaths were recorded by linkage with the GBA from 1991 until 2009. Of these, a medical autopsy was performed on 3736 deceased according to linkage with PALGA, resulting in an overall autopsy rate of 6.3%. Major variations in the autopsy rate were observed according to the cause of death. The autopsy rate increased according to the number of contributing causes of death. Lastly, a diagnosis of cancer affected the autopsy rate. The clinical cause of death and a history of cancer both influenced the medical autopsy rate in a large national cohort. The insight this study provides may help clinicians and pathologists counteracting the further downfall of the medical autopsy.

Efficacy of postmortem CT and tissue sampling in establishing the cause of death in clinical practice: a prospective observational study.

AIMS: The aim of this study is to evaluate whether agreement with autopsy-determined cause of death (COD) increases by use of postmortem CT (PMCT) or PMCT in combination with postmortem sampling (PMS), when compared with clinical assessment only. METHODS: This prospective observational study included deceased patients from the intensive care unit and internal medicine wards between October 2013 and August 2017. The primary outcome was percentage agreement on COD between the reference standard (autopsy) and the alternative postmortem examinations (clinical assessment vs PMCT or PMCT+PMS). In addition, the COD of patient groups with and without conventional autopsy were compared with respect to involved organ systems and pathologies. RESULTS: Of 730 eligible cases, 144 could be included for analysis: 63 underwent PCMT without autopsy and 81 underwent both PMCT and autopsy. Agreement with autopsy-determined COD was significantly higher for both PMCT with PMS (42/57, 74%), and PMCT alone (53/81, 65%) than for clinical assessment (40/81, 51%; p=0.007 and p=0.03, respectively). The difference in agreement between PMCT with PMS and PMCT alone was not significant (p=0.13). The group with autopsy had a significantly higher prevalence of circulatory system involvement and perfusion disorders, and a lower prevalence of pulmonary system involvement. CONCLUSION: PMCT and PMS confer additional diagnostic value in establishing the COD. Shortcomings in detecting vascular occlusions and perfusion disorders and susceptibility to pulmonary postmortem changes could in future be improved by additional techniques. Both PMCT and PMS are feasible in clinical practice and an alternative when autopsy cannot be performed.

Cutaneous metastases of internal malignancies: a single-institution experience.

AIMS: Cutaneous metastases of internal malignancies occur in 1-10% of cancer patients. The diagnosis can sometimes be challenging, especially in cases with an unknown primary cancer. MATERIALS AND METHODS: A retrospective case review was performed including all cases of skin metastases from primary internal malignancies diagnosed at the Department of Pathology at the Maastricht University Medical Centre+ from 2007 to 2021. The clinicopathological data were collected and immunohistochemical and molecular diagnostic tests were performed to confirm the primary origin of the metastases. RESULTS: We identified 152 cases (71 female; 31 male patients) of cutaneous metastases of internal malignancies. 28 patients (20 women and 8 men) were diagnosed with multiple cutaneous metastases. Among the female patients, the most common primary tumour was breast cancer (50% of the cases), followed by lung (13.6%), gynaecological (7.3%), and gastrointestinal origin (7.3%). Among the male patients, the most common primary sites were gastrointestinal and lung origin (altogether, 50% of the cases). In 19 patients, the cutaneous metastasis was the first presentation of a clinically silent internal malignancy (18.6%), of which most (78.9%) represented metastatic lung carcinomas. Finally, metastasizing patterns were different across tumour types and gender. CONCLUSION: Breast, lung, gastrointestinal, and gynaecologic cancers are the most common primary tumours demonstrating skin metastases. Infrequently, cutaneous metastases can be the first clinically visual manifestation of an underlying not yet diagnosed internal malignancy; therefore, occasional broad immunohistochemical profiling, molecular clonal analysis, and a continuous high level of awareness are necessary for a precise diagnosis of cutaneous metastases of internal malignancies.

Fat Embolism After Autologous Facial Fat Grafting.

BACKGROUND: Autologous facial fat grafting has gained popularity in recent years and is considered to be safe. This paper presents the case of a patient who died due to massive cerebral microfat embolism after facial fat grafting. OBJECTIVES: The aim of this study was to raise awareness and provide more evidence on the prevention and treatment of this potentially lethal complication of facial fat grafting. METHODS: A detailed report was made of the case. Two online databases were searched for similar cases of facial fat embolism resulting in neurologic and/or visual symptoms. Thereafter a literature search was conducted to verify the etiology, current treatment options, and preventive measures. RESULTS: Forty-nine cases with similar events were found in the literature. The most common injected area was the glabella (36.1%), and an average of 16.7 mL fat was injected. The main complications were visual impairment, with 88.5% of cases resulting in permanent monocular blindness, and neurologic symptoms, some of which never fully recovered. Including the present patient, 7 cases were fatal. Fat embolism can occur in the veins and arteries of the face. Two possible pathways for fat embolism exist: the macroscopic, mechanical pathway with immediate signs, and the microscopic, biochemical pathway with delayed symptoms. Mechanical embolectomy and corticosteroids are suggested treatment options but evidence for their efficacy is lacking. Several different preventive measures are described. CONCLUSIONS: Although facial fat grafting is considered a safe procedure, one should be aware of the risk of fat embolism. Underreporting of this adverse event is likely. With no effective treatment and often detrimental outcomes, preventive measures are of utmost importance to improve patient safety.

Clinical diagnoses vs. autopsy findings in early deceased septic patients in the intensive care: a retrospective cohort study.

Early death in sepsis occurs frequently; however, specific causes are largely unknown. An autopsy can contribute to ascertain causes of death. The objective of the study was to determine discrepancies in clinical diagnosis and postmortem findings in septic intensive care unit (ICU) patients deceased within 48 h after ICU admission. All septic ICU patients who deceased within 48 h after ICU admission were identified and included. Four intensivists determined the clinical cause of death by medical record review. An autopsy was performed within 24 h of death. Clinical diagnosis and postmortem findings were compared and classified as autopsy-identified missed clinical diagnoses and autopsy-refuted diagnoses. Class I and II missed major diagnoses using the Goldman criteria were scored. Between 2012 and 2017, 1107 septic patients were admitted to ICU. Of these, 344 patients (31%) died, of which 97 patients (28%) deceased within 48 h. In 32 (33%) early deceased patients, an autopsy was agreed. There were 26 autopsy-identified missed clinical diagnoses found, mostly myocardial infarction (n = 4) and pneumonia (n = 4). In four patients (13%), a class I discrepancy was found. In fourteen patients (42%), a class II discrepancy was found. In conclusion, an autopsy is an important diagnostic tool that can identify definite causes of death. These diagnoses deviate from diagnoses established during admission in early deceased sepsis patients.

Introduction of postmortem CT increases the postmortem examination rate without negatively impacting the rate of traditional autopsy in daily practice: an implementation study.

AIM: The aim of this implementation study was to assess the effect of postmortem CT (PMCT) and postmortem sampling (PMS) on (traditional) autopsy and postmortem examination rates. Additionally, the feasibility of PMCT and PMS in daily practice was assessed. METHODS: For a period of 23 months, PMCT and PMS were used as additional modalities to the autopsy at the Department of Internal Medicine. The next of kin provided consent for 123 postmortem examinations. Autopsy rates were derived from the Dutch Pathology Registry, and postmortem examination rates were calculated for the period before, during and after the study period, and the exclusion rate, table time, time interval to informing the referring clinicians with results and the time interval to the Multidisciplinary Mortality Review Board (MMRB) meeting were objectified to assess the feasibility. RESULTS: The postmortem examination rate increased (from 18.8% to 32.5%, p<0.001) without a decline in the autopsy rate. The autopsy rate did not change substantially after implementation (0.2% decrease). The exclusion rate was 2%, the table time was 23 min, and a median time interval of 4.1 hours between PMCT and discussing its results with the referring clinicians was observed. Additionally, more than 80% of the MMRB meetings were held within 8 weeks after the death of the patient. CONCLUSIONS: Our study shows that the implementation of a multidisciplinary postmortem examination is feasible in daily practice and does not adversely affect the autopsy rate, while increasing the postmortem examination rate.

Clinical Relevance of Unexpected Findings of Post-Mortem Computed Tomography in Hospitalized Patients: An Observational Study.

Background and objective: The current literature describing the use of minimally invasive autopsy in clinical care is mainly focused on the cause of death. However, the identification of unexpected findings is equally important for the evaluation and improvement of daily clinical care. The purpose of this study was to analyze unexpected post-mortem computed tomography (PMCT) findings of hospitalized patients and assess their clinical relevance. Materials and methods: This observational study included patients admitted to the internal medicine ward. Consent for PMCT and autopsy was requested from the next of kin. Decedents were included when consent for at least PMCT was obtained. Consent for autopsy was not obtained for all decedents. All findings reported by PMCT were coded with an International Classification of Diseases (ICD) code. Unexpected findings were identified and subsequently categorized for their clinical relevance by the Goldman classification. Goldman class I and III were considered clinically relevant. Additionally, correlation with autopsy results and ante-mortem imaging was performed. Results: In total, 120 decedents were included and evaluated for unexpected findings on PMCT. Of them, 57 decedents also underwent an autopsy. A total of 1020 findings were identified; 111 correlated with the cause of death (10.9%), 508 were previously reported (49.8%), 99 were interpreted as post-mortem changes (9.7%), and 302 were classified as unexpected findings (29.6%). After correlation with autopsy (in 57 decedents), 24 clinically relevant unexpected findings remained. These findings were reported in 18 of 57 decedents (32%). Interestingly, 25% of all unexpected findings were not reported by autopsy. Conclusion: Many unexpected findings are reported by PMCT in hospitalized patients, a substantial portion of which is clinically relevant. Additionally, PMCT is able to identify pathology and injuries not reported by conventional autopsy. A combination of PMCT and autopsy can thus be considered a more comprehensive and complete post-mortem examination.

Sudden death during physical restraint by the Dutch police.

BACKGROUND: and goal: The Police is sometimes confronted with the death of a subject during physical restraint. In most of these cases a clear Cause of Death (COD) cannot be determined by the Pathologist. The goal of this research is to find and clarify a pattern and pinpoint a clearer COD. METHOD: The research group is compiled of 38 closed police case files from the NPIID (National Police Internal Investigation Department) between 2005 and 2016. The control group is compiled of cases involving excitation and restraint, without leading to death. 148 cases were included from the NPIID between 2005 and 2016 and the Violence Registration Database of the Dutch National Police between 2014 and 2015. Case files of both the research and the control group were systematically analyzed and compared. RESULTS AND CONCLUSION: The observed patter shows that subjects dying during Physical Restraint are mostly males between 30 and 40 years old with a BMI above 30 kg/m2. Both BMI and age are remarkably lower in the control group. Subjects were encountered in a state of excitation mostly attributed to (multiple) drugs (cocaine, MDMA or cannabis). The physical restraint portrayed a pattern of escalation with restraint being mostly face-down, hands cuffed to the back, receiving thoracic pressure, resulting in a high total amount of force used. In the research group 44.7% (17/38) of subjects were encountered (partially) unclothed versus 4.1% (6/148) in the control group. Cause of death in these cases seems to be multifactorial and is comprised of both personal factors and factors during and after the struggle. The different factors are comingled and augment each other. The end effect is that the subjects end up in a fatal spiral.

Massive gas embolisms in diving fatalities visualized by radiology and neuropathology.

Massive vascular gas embolism is a feared and often lethal symptom of decompression illness, resulting from diving accidents. The aim of this case report was to correlate post-mortem computed tomography scan (PMCT) findings with autopsy in cases of massive vascular gas embolism. Two cases of fatal diving accidents were retrospectively selected from a forensic radiological pathological database. The PMCT results were initially shared with the forensic pathologist prior to autopsy, enabling a more accurate overall assessment. Both cases were in retrospect thoroughly studied to compare the PMCT findings with the autopsy results. In general, intra- and extra-vascular gas collections are easily detected on PMCT in all body regions. We focused on abundant intravascular gas collections, mainly in the large brain vessels. General autopsy findings are described in both cases, and in one case we elaborate on specific intracerebral changes found at autopsy. Both cases were diagnosed as pulmonary barotrauma with subsequent vascular gas embolisms. We conclude that PMCT excels in the detection of macroscopic gas collections in the body, whereas microscopic gas collections identified at autopsy aid in the differentiation between decompression sickness and pulmonary barotrauma followed by vascular gas embolism. The presented cases highlight the advantages of using both PMCT and autopsy in the post-mortem evaluation of fatal diving accidents.

A quarter century of decline of autopsies in the Netherlands.

OBJECTIVE: Autopsy rates have been declining worldwide. The present study reports the outcome of a retrospective analysis of all non-forensic autopsies in the Netherlands over a course of 25 years, and compares these with the most recent Dutch study. METHOD: Retrospectively, 25 years of data on clinical autopsies from the Nationwide Network and Registry of Histo- and Cytopathology in the Netherlands (PALGA) was paired with the mortality registry (Statistics Netherlands). RESULTS: The crude prevalence of autopsies declined from 7.07% in 1991 to 2.73% in 2015. After adjusting for age at death, there was no difference in autopsy rate between males and females. An increasing age significantly decreased the autopsy rate. CONCLUSION: In the Netherlands, clinical autopsies have been declining over the last quarter century. Age at death, but not sex, was associated with the autopsy rate. These different results stress the importance of correct collection and analysis methods of data.

The needle in the haystack: Histology of post-mortem computed tomography guided biopsies versus autopsy derived tissue.

OBJECTIVE: The last decennia autopsies have been declining worldwide, whereas non-invasive methods have been proposed as an alternative for the conventional autopsy. Some of these methods add needle biopsies to imaging techniques to provide an alternative to histological examination of autopsy-derived tissue. The aim of this study was to investigate the representativeness of the histology of computed tomography (CT) -guided post-mortem needle biopsies in comparison to autopsy derived tissue from the same organ. METHOD: Consent of next of kin was obtained from relatives of deceased within the department of Internal Medicine to perform an autopsy, postmortem CT and CT-guided needle biopsies. The lungs and the liver were routinely sampled with CT-guided postmortem biopsies and during the autopsy. In some cases extra CT-guided biopsies of lesions reported on the CT were sampled. The biopsy and the autopsy reports were independently reported and retrospectively coded according to the Nationwide Network and Registry of Histo- and Cytopathology in the Netherlands (PALGA). Three pathologists with an interest in autopsy pathology and three physicians of the department of internal medicine separately and independently interpreted all histological results in relation to the cause of death as formulated in the autopsy report. Fleiss's Kappa was calculated and a consensus grade was defined. RESULTS: Fleiss's Kappa showed substantial agreement in both lungs and moderate agreement in the liver. Of the 60 included cases 44% of the CT-guided postmortem biopsies in the left lung and 30% in the right lung showed false negative findings, primarily concerning a bronchopneumonia. In contrast, 91% of the liver biopsies showed concordant results, however only 22% of all liver biopsies concerned a major diagnosis related to the cause of death. The positive predictive value of the biopsies of the left lung, right lung and the liver were respectively 86.6%, 88.8% and 100%. The negative predictive values of these biopsies were 32.4%, 50% and 92.7%. CONCLUSION: CT-guided postmortem biopsies of the lungs have a mediocre predictive value. Due to a low prevalence of relevant findings the overall usefulness of biopsies of the liver are limited. Conventional autopsy should still be preferred to biopsy-based postmortem examination. Postmortem biopsies are only an alternative if consent for an autopsy cannot be obtained. In the forensic setting, where no consent of the relatives is necessary, complete autopsy should always be the method of choice.

Can virtual autopsy with postmortem CT improve clinical diagnosis of cause of death? A retrospective observational cohort study in a Dutch tertiary referral centre.

OBJECTIVE: To investigate whether virtual autopsy with postmortem CT (PMCT) improves clinical diagnosis of the immediate cause of death. DESIGN: Retrospective observational cohort study. INCLUSION CRITERIA: inhospital and out-of-hospital deaths over the age of 1 year in whom virtual autopsy with PMCT and conventional autopsy were performed. EXCLUSION CRITERIA: forensic cases, postmortal organ donors and cases with incomplete scanning procedures. Cadavers were examined by virtual autopsy with PMCT prior to conventional autopsy. The clinically determined cause of death was recorded before virtual autopsy and was then adjusted with the findings of virtual autopsy. Using conventional autopsy as reference standard, we investigated the increase in sensitivity for immediate cause of death, type of pathology and anatomical system involved before and after virtual autopsy. SETTING: Tertiary referral centre. PARTICIPANTS: 86 cadavers that underwent conventional and virtual autopsy between July 2012 and June 2016. INTERVENTION: PMCT consisted of brain, cervical spine and chest-abdomen-pelvis imaging. Conventional autopsy consisted of thoracoabdominal examination with/without brain autopsy. PRIMARY AND SECONDARY OUTCOME MEASURES: Increase in sensitivity for the immediate cause of death, type of pathology (infection, haemorrhage, perfusion disorder, other or not assigned) and anatomical system (pulmonary, cardiovascular, gastrointestinal, other or not assigned) involved, before and after virtual autopsy. RESULTS: Using PMCT, the sensitivity for immediate cause of death increased with 12% (95% CI 2% to 22%) from 53% (41% to 64%) to 64% (53% to 75%), with 18% (9% to 27%) from 65% (54% to 76%) to 83% (73% to 91%) for type of pathology and with 19% (9% to 30%) from 65% (54% to 76%) to 85% (75% to 92%) for anatomical system. CONCLUSION: While unenhanced PMCT is an insufficient substitute for conventional autopsy, it can improve diagnosis of cause of death over clinical diagnosis alone and should therefore be considered whenever autopsy is not performed.

Postmortem radiological case series of acetabular fractures after fatal aviation accidents.

The purpose of this study was to describe radiological fracture patterns of the acetabulum sustained after fatal small aircraft aviation accidents, aiming at facilitating a better understanding of trauma mechanisms in a forensic setting. Postmortem conventional radiographs or CT scans of 29 victims of 20 small aircraft aviation accidents were analyzed for skeletal acetabular trauma. Among the 29 fatalities (27 males and 2 females, median age 55 years (range: 21-76 years)), 20 victims had pelvic fractures (69%), of which 19 victims (66%) had one or more acetabular fractures. Bilateral acetabular fractures occurred in 11 victims. When considering left and right acetabula in each victim as separate entities, 38 of the 58 acetabula included in this case series exhibited one or more fractures. Both the anterior and posterior acetabular columns were fractured in 28 acetabula. Acetabular fractures were frequently encountered in this series of 29 victims of small fatal aircraft accidents. Fractures of the acetabulum occur from ventrally directed impact (i.e. to the knee) or laterally directed impact (i.e. to the greater trochanter of the femur). Radiological descriptions of the fracture patterns can therefore aid in the forensic analysis of the mechanism of trauma in aviation accidents. Postmortem multi-slice CT scan images are preferrable in the assessment of acetabular fractures.

Persistent Retinal Iron in Abusive Head Trauma.

Retinal hemosiderin deposition is a histologic indicator of sustained hemorrhage but cannot be used to precisely estimate the elapsed time since an episode of trauma. A 5-month-old male infant was admitted to hospital after acute deterioration. Examination revealed encephalopathy, subdural hematomas, and retinal hemorrhages consistent with abusive head trauma (AHT). At the age of 3, he was readmitted to hospital with spontaneous osteopenic fracture of the right femur. The patient deteriorated and died after unsuccessful resuscitation. Ophthalmopathological investigation showed atrophy of the retina and optic nerve and hemosiderin deposition in both eyes. Retinal hemosiderin deposition is currently generally assumed to disappear within 6-8 weeks after the occurrence of hemorrhage in AHT. This case report describes an infant with bilateral retinal hemosiderin depositions due to hemorrhages sustained from AHT occurring 32 months prior to death. Implications of this finding for the interpretation of retinal hemosiderin depositions in AHT are discussed.

Dopamine induces lipid accumulation, NADPH oxidase-related oxidative stress, and a proinflammatory status of the plasma membrane in H9c2 cells.

Excess catecholamine levels are suggested to be cardiotoxic and to underlie stress-induced heart failure. The cardiotoxic effects of norepinephrine and epinephrine are well recognized. However, although cardiac and circulating dopamine levels are also increased in stress cardiomyopathy patients, knowledge regarding putative toxic effects of excess dopamine levels on cardiomyocytes is scarce. We now studied the effects of elevated dopamine levels in H9c2 cardiomyoblasts. H9c2 cells were cultured and treated with dopamine (200 µM) for 6, 24, and 48 h. Subsequently, the effects on lipid accumulation, cell viability, flippase activity, reactive oxygen species (ROS) production, subcellular NADPH oxidase (NOX) protein expression, and ATP/ADP and GTP/GDP levels were analyzed. Dopamine did not result in cytotoxic effects after 6 h. However, after 24 and 48 h dopamine treatment induced a significant increase in lipid accumulation, nitrotyrosine levels, indicative of ROS production, and cell death. In addition, dopamine significantly reduced flippase activity and ATP/GTP levels, coinciding with phosphatidylserine exposure on the outer plasma membrane. Furthermore, dopamine induced a transient increase in cytoplasmic and (peri)nucleus NOX1 and NOX4 expression after 24 h that subsided after 48 h. Moreover, while dopamine induced a similar transient increase in cytoplasmic NOX2 and p47phox expression, in the (peri)nucleus this increased expression persisted for 48 h where it colocalized with ROS. Exposure of H9c2 cells to elevated dopamine levels induced lipid accumulation, oxidative stress, and a proinflammatory status of the plasma membrane. This can, in part, explain the inflammatory response in patients with stress-induced heart failure.

Myocardial infarction induces atrial inflammation that can be prevented by C1-esterase inhibitor.

AIMS: Inflammation plays an important role in the pathogenesis of myocardial infarction (MI). Whether MI induces atrial inflammation is unknown however. Here, we analysed atrial inflammation in patients with MI and in rats with experimentally induced MI. The effect of the anti-inflammatory agent C1-esterase inhibitor (C1inh) on atrial inflammation in rats was also analysed. METHODS: In the hearts of patients who died at different time points after MI (total n=24, mean age=60), neutrophils (myeloperoxidase-positive cells), lymphocytes (CD45-positive cells) and macrophages (CD68-positive cells) were quantified in the myocardium of the left and right atria and the infarcted left and non-infarcted right ventricles and compared with control patients (n=5, mean age=59). For the left and right atria, inflammatory cells were also quantified in the atrial adipose tissue. MI was induced in 17 rats, of which 10 were subsequently treated with C1inh for 6 days. Forty-two days post-MI, lymphocytes, macrophages and the endothelial inflammation marker Nε-(carboxymethyl)lysine (CML) were analysed in the myocardium of both the atria and ventricles. RESULTS: In all investigated areas of the human hearts increased lymphocytes and macrophages were observed to a varying extent, especially between 6 h and 5 days following MI. Similarly, in rats MI resulted in an increase of inflammatory cells and CML in the atria. C1inh treatment decreased atrial inflammation. CONCLUSIONS: MI induces atrial inflammation in patients and in rats. C1inh treatment could counteract this MI-induced atrial inflammation in rats.

The radiodensity of cerebrospinal fluid and vitreous humor as indicator of the time since death.

PURPOSE: After death, a series of changes occur naturally in the human body in a fairly regular pattern. These postmortem changes are detectable on postmortem CT scans (PMCT) and may be useful in estimating the postmortem interval (PMI). The purpose of our study is to correlate the PMCT radiodensities of the cerebrospinal fluid (CSF) and vitreous humor (VH) to the PMI. METHODS: Three patient groups were included: group A consisted of 5 donated cadavers, group B, 100 in-hospital deceased patients, and group C, 12 out-of-hospital forensic cadavers. Group A were scanned every hour for a maximum of 36 h postmortem, and the tympanic temperature was measured prior to each scan. Groups B and C were scanned once after death (PMI range 0.2-63.8 h). Radiodensities of the VH and CSF were measured in Hounsfield units. Correlation between density and PMI was determined using linear regression and the influence of temperature was assessed by a multivariate regression model. Results from group A were validated in groups B and C. RESULTS: Group A showed increasing radiodensity of the CSF and VH over time (r (2) CSF, 0.65). PMI overruled the influence of temperature (r = 0.99 and p = 0.000). Groups B and C showed more diversity, with CSF and VH radiodensities below the mean regression line of Group A. The formula of this upper limit indicated the maximum PMI and was correct for >95 % of the cadavers. CONCLUSION: The results of group A showed a significant correlation between CSF radiodensity and PMI. The radiodensities in groups B and C were higher than in group A, therefore the maximum PMI can be estimated with the upper 95 % confidence interval of the correlation line of group A.

Ventricular myocarditis coincides with atrial myocarditis in patients.

INTRODUCTION: Atrial fibrillation (AF) is a common complication in myocarditis. Atrial inflammation has been suggested to play an important role in the pathophysiology of AF. However, little is known about the occurrence of atrial inflammation in myocarditis patients. Here, we analyzed inflammatory cell numbers in the atria of myocarditis patients without symptomatic AF. METHODS: Cardiac tissue was obtained postmortem from lymphocytic myocarditis patients (n=6), catecholamine-induced myocarditis patients (n=5), and control patients without pathological evidence of heart disease (n=5). Tissue sections of left and right ventricle and left and right atrium were stained for myeloperoxidase (neutrophilic granulocytes), CD45 (lymphocytes), and CD68 (macrophages). These cells were subsequently quantified in atrial and ventricular myocardium and atrial adipose tissue. RESULTS: In lymphocytic myocarditis patients, a significant increase was observed for lymphocytes in the left atrial adipose tissue. In catecholamine-induced myocarditis patients, significant increases were found in the atria for all three inflammatory cell types. Infiltrating inflammatory cell numbers in the atrial myocardium correlated positively with those in the ventricles, especially in catecholamine-induced myocarditis patients. CONCLUSIONS: To a varying extent, atrial myocarditis occurs concurrently with ventricular myocarditis in patients diagnosed with myocarditis of different etiology. This provides a substrate that potentially predisposes myocarditis patients to the development of AF and subsequent complications such as sudden cardiac death and heart failure.

ß-Amyloid Precursor Protein and Ubiquitin Immunohistochemistry Aid in the Evaluation of Infant Autopsy Eyes With Abusive Head Trauma.

PURPOSE: To investigate ß-amyloid precursor protein (ß-APP), ubiquitin, and glial fibrillary acid protein (GFAP) immunostaining as a diagnostic tool to aid in the discrimination between abusive head trauma and nonabusive head trauma in postmortem ocular histopathologic investigation. DESIGN: Retrospective cross-sectional study. METHODS: Seventy-four eyes of 37 infants were studied for hemorrhage and immunohistochemical expression of ß-APP, ubiquitin, and GFAP in the retina and optic nerve. Infants were assigned to abusive head trauma or control groups, according to published criteria. RESULTS: In the abusive head trauma group, positive ß-APP and ubiquitin immunostaining of the retina was significantly more likely to be found than in the control group, odds ratio (OR) 11.4, confidence interval (CI) 2.9-44.3; P < .001 and OR 8.8, CI 2.2-34.5; P = .002, respectively. Positive correlations were found between retinal expression of ß-APP and ubiquitin immunostaining and retinal hemorrhage. Vitreal hemorrhages, orbital fat hemorrhages, and macular folds could only be identified in abusive head trauma cases. Retinal hemorrhages were significantly more severe, occupied a larger proportion of the retina, and involved more retinal layers in abusive head trauma compared to controls (OR 2.7, CI 1.7-4.4; P < .001). CONCLUSIONS: This study shows correlations between positive retinal ß-APP and ubiquitin immunostaining as a sign of axonal injury in abusive head trauma. Axonal injury is a useful pathologic feature that can be demonstrated in postmortem ocular investigation of deceased children using immunohistochemical staining for ß-APP and ubiquitin with a high OR for abusive head trauma when compared to controls.