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[A Psychological Autopsy Study Based on 626 German Police Records].

In Germany roughly 10.000 persons commit suicide per year. To develop prevention strategies data regarding risk factors and potential interventions.

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Acute stressors and clinical characteristics differentiate death by suicide, accident, or natural causes among illicit and prescription opiate users.

Opiate misuse has reached epidemic levels. Prevention efforts depend on distinguishing opiate users from abusers. The current study compared opioid users who died by natural cases, accidents, and suicide using psychological autopsy methods. Groups were compared on substance use characteristics, treatment history, experiences of negative life events, and circumstances at the time of death.

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Fulminant corticobasal degeneration: a distinct variant with predominant neuronal tau aggregates.

Corticobasal degeneration typically progresses gradually over 5-7 years from onset till death. Fulminant corticobasal degeneration cases with a rapidly progressive course were rarely reported (RP-CBD). This study aimed to investigate their neuropathological characteristics. Of the 124 autopsy-confirmed corticobasal degeneration cases collected from 14 centres, we identified 6 RP-CBD cases (4.8%) who died of advanced disease within 3 years of onset. These RP-CBD cases had different clinical phenotypes including rapid global cognitive decline (N = 2), corticobasal syndrome (N = 2) and Richardson's syndrome (N = 2). We also studied four corticobasal degeneration cases with an average disease duration of 3 years or less, who died of another unrelated illness (Intermediate-CBD). Finally, we selected 12 age-matched corticobasal degeneration cases out of a cohort of 110, who had a typical gradually progressive course and reached advanced clinical stage (End-stage-CBD). Quantitative analysis showed high overall tau burden (p = 0.2) and severe nigral cell loss (p = 0.47) in both the RP-CBD and End-stage-CBD groups consistent with advanced pathological changes, while the Intermediate-CBD group (mean disease duration = 3 years) had milder changes than End-stage-CBD (p < 0.05). These findings indicated that RP-CBD cases had already developed advanced pathological changes as those observed in End-stage-CBD cases (mean disease duration = 6.7 years), but within a significantly shorter duration (2.5 years; p < 0.001). Subgroup analysis was performed to investigate the cellular patterns of tau aggregates in the anterior frontal cortex and caudate by comparing neuronal-to-astrocytic plaque ratios between six RP-CBD cases, four Intermediate-CBD and 12 age-matched End-stage-CBD. Neuronal-to-astrocytic plaque ratios of Intermediate-CBD and End-stage-CBD, but not RP-CBD, positively correlated with disease duration in both the anterior frontal cortex and caudate (p = 0.02). In contrast to the predominance of astrocytic plaques we previously reported in preclinical asymptomatic corticobasal degeneration cases, neuronal tau aggregates predominated in RP-CBD exceeding those in Intermediate-CBD (anterior frontal cortex: p < 0.001, caudate: p = 0.001) and End-stage-CBD (anterior frontal cortex: p = 0.03, caudate: p = 0.01) as demonstrated by its higher neuronal-to-astrocytic plaque ratios in both anterior frontal cortex and caudate. We did not identify any difference in age at onset, any pathogenic tau mutation or concomitant pathologies that could have contributed to the rapid progression of these RP-CBD cases. Mild TDP-43 pathology was observed in three RP-CBD cases. All RP-CBD cases were men. The MAPT H2 haplotype, known to be protective, was identified in one RP-CBD case (17%) and 8 of the matched End-stage-CBD cases (67%). We conclude that RP-CBD is a distinct aggressive variant of corticobasal degeneration with characteristic neuropathological substrates resulting in a fulminant disease process as evident both clinically and pathologically. Biological factors such as genetic modifiers likely play a pivotal role in the RP-CBD variant and should be the subject of future research.

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Low Grade Islet but Marked Exocrine Pancreas Inflammation in an Adult with Autoimmune Pre-Diabetes.

There is unexplained deficit in size and function of the exocrine pancreas in type 1 diabetes (T1D). We obtained pancreas from an individual with pre-T1D obtained at surgery and addressed the question, what is the relative inflammation in the exocrine and endocrine pancreas in pre-T1D in the absence of the potential confounding changes at autopsy or in brain dead organ donors. Pancreas was removed surgically from a 36 year woman for benign neuroendocrine tumors (NET). The patient had gestational diabetes at age 29 and has a 23 year old sister with T1D. Pre-operative fasting glucose of 109 mg/dl and HbA1C 5.8% revealed prediabetes with an anti-GAD 1,144 (5-250 U/ml) together with family history implying pre-T1D. There was patchy low grade immune infiltration in some, but not all, islets that met criteria for autoimmune insulitis. The exocrine pancreas showed more abundant inflammation with areas of chronic pancreatitis and acinar to ductal metaplasia, and with other areas of atrophy and fatty infiltration. In pre-T1D inflammation may be more prominent in the exocrine than the endocrine pancreas, calling into question the sequence of events and assumed islet centric basis of autoimmunity leading to T1D.

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An analysis of forensic autopsies performed in the Gwangju and Jeollanam-do areas of the Republic of Korea during the past decade.

Autopsy is regarded as the gold standard in death investigation. Moreover, the statistical data from autopsies provides basic statistics for various aspects of society. However, the autopsy rate is low in the Republic of Korea. For a stable forensic autopsy, the Police Agency, the National Forensic Service, and the Department of Forensic Medicine, Chonnam National University concluded an agreement regarding forensic autopsies in the Honam area (Gwangju and Jeollanam-do areas) in 2007. This study aimed to review forensic autopsies performed over the past 10 years according to the trilateral agreement in the Gwangju and Jeollanam-do areas. A total of 3,899 cases were categorized based on the specific region; the manner and cause of death were investigated, and autopsy rates were calculated. The analysis of the manner of death revealed that 2,125 cases (54.5%) were unnatural deaths, 1,347 cases (34.5%) were natural deaths, and 427 cases (11.0%) were from an unknown cause of death. The number of autopsies was relatively stable until 2013 but increased from 2014. Since then, there was a fluctuation in the annual autopsy rates in each region. A negative correlation was noted between the distances from the region requesting autopsies to the institution performing autopsies and the autopsy rates. The authors believe that this study could be used as foundational data to guide the development of a postmortem investigation system and a reference for improving social security and public health.

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Reverse Takotsubo Pattern in the Setting of Undiagnosed Pheochromocytoma and Pulmonary Embolism: A Rare Presentation.

BACKGROUND Takotsubo cardiomyopathy is a rare acute cardiac event with varied manifestations characterized by abrupt onset of transient regional dysfunction in a characteristic pattern. A reverse Takotsubo pattern is also well recognized but can also be seen in non-Takotsubo cardiomyopathies. CASE REPORT A 23-year-old woman with history of migraines and palpitations presented with nausea, vomiting, pleuritic chest pain, and dyspnea. On initial presentation her vitals were stable and her physical exam was unremarkable. Lab test results were significant for an elevated troponin and D-dimer. An initial CXR was unremarkable. The differential was concerning for pulmonary embolism. Prior to getting a CTA to establish diagnosis, she quickly decompensated. She was emergently intubated due to hypoxia and altered mental status. A repeat CXR showed acute pulmonary edema and repeat lab work showed increasing troponin and creatinine. EKG showed lateral ST depressions the lateral leads and ST elevations in aVL. ECHO showed akinesia of ½ to 2/3rd of proximal LV with a hyperdynamic functioning distal 1/3 LV and an estimated LVEF of 31%, a pattern consistent with reverse Takotsubo. She quickly developed multi-organ failure and, despite aggressive measures, underwent a PEA arrest and was unable to be successfully resuscitated. The autopsy showed hemorrhagic rupture of pheochromocytoma and bilateral thromboemboli of the main pulmonary arteries. CONCLUSIONS Reverse Takotsubo variant pattern can be seen in non-Takotsubo cardiomyopathies, and in our patient was noted in the presence of pheochromocytoma and pulmonary embolism. In this scenario, the presence of both would have significantly affected management, if she had not decompensated so quickly.

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Sudden unexpected death in epilepsy (SUDEP) in New Zealand; a retrospective review.

Sudden unexpected death in epilepsy (SUDEP) is well recognised and widely reported but remains poorly understood. SUDEP in young adults is 27 times more common than sudden death in control populations. The incidence of SUDEP in New Zealand is not known but up to 40 people with epilepsy may die from SUDEP every year. A review of coroner's reports of SUDEP was undertaken to learn more about SUDEP in New Zealand.

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Two autopsy cases of desmoplastic small round cell tumor.

Desmoplastic small round cell tumor (DSRCT) is a rare aggressive malignant tumor. It is a refractory tumor and the median overall survival is very short. We report two autopsy cases of DSRCT, both of which were already advanced and metastasized at the first medical examination. Both cases showed typical DSRCT findings in terms of localization of the lesions, histopathology and genetics, but the rate of disease progression was quite different. Survival after initial symptoms in Case 1 was only 12 months. On the other hand, survival after primary hospitalization in Case 2 was 42 months. The Case 2 patient initially received chemotherapy for advanced pancreatic carcinoma, because a nodule of the pancreatic tail was found on computed tomography (CT) scan. After chemotherapy, tumor regression was observed on CT scan. It is thus implied that adoption of the regimen for pancreatic carcinoma might have been one of reasons of the long survival in Case 2.

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Cognitive trajectory in mild cognitive impairment due to primary age-related tauopathy.

Primary age-related tauopathy is increasingly recognized as a separate neuropathological entity different from Alzheimer's disease. Both share the neuropathological features of tau aggregates and neuronal loss in the temporal lobe, but primary age-related tauopathy lacks the requisite amyloid plaques central to Alzheimer's disease. While both have similar clinical presentations, individuals with symptomatic primary age-related tauopathy are commonly of more advanced ages with milder cognitive dysfunction. Direct comparison of the neuropsychological trajectories of primary age-related tauopathy and Alzheimer's disease has not been thoroughly evaluated and thus, our objective was to determine how cognitive decline differs longitudinally between these two conditions after the onset of clinical symptoms. Data were obtained from the National Alzheimer's Coordinating Center on participants with mild cognitive impairment at baseline and either no neuritic plaques (i.e. primary age-related tauopathy) or moderate to frequent neuritic plaques (i.e. Alzheimer neuropathological change) at subsequent autopsy. For patients with Alzheimer's disease and primary age-related tauopathy, we compared rates of decline in the sum of boxes score from the CDR® Dementia Staging Instrument and in five cognitive domains (episodic memory, attention/working memory, executive function, language/semantic memory, and global composite) using z-scores for neuropsychological tests that were calculated based on scores for participants with normal cognition. The differences in rates of change were tested using linear mixed-effects models accounting for clinical centre clustering and repeated measures by individual. Models were adjusted for sex, age, education, baseline test score, Braak stage, apolipoprotein ε4 (APOE ε4) carrier status, family history of cognitive impairment, and history of stroke, hypertension, or diabetes. We identified 578 participants with a global CDR of 0.5 (i.e. mild cognitive impairment) at baseline, 126 with primary age-related tauopathy and 452 with Alzheimer's disease. Examining the difference in rates of change in CDR sum of boxes and in all domain scores, participants with Alzheimer's disease had a significantly steeper decline after becoming clinically symptomatic than those with primary age-related tauopathy. This remained true after adjusting for covariates. The results of this analysis corroborate previous studies showing that primary age-related tauopathy has slower cognitive decline than Alzheimer's disease across multiple neuropsychological domains, thus adding to the understanding of the neuropsychological burden in primary age-related tauopathy. The study provides further evidence to support the hypothesis that primary age-related tauopathy has distinct neuropathological and clinical features compared to Alzheimer's disease.

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Downregulation of HNRNPK in human cancer cells inhibits lung metastasis.

Lung cancer frequently occurs in the clinic, leading to poor prognosis and high mortality. Markers for early diagnosis of lung cancer are scarce, and further potential therapeutic targets are also urgently needed.

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