Autopsy Studies Research Articles

The Missing Link in Antiamyloid Therapy.

Alzheimer's disease (AD) impacts millions of elderly adults worldwide causing cognitive decline and severe deterioration of activities of daily life. The popular causal hypotheses for several decades include beta-amyloid (Aβ) deposition and tau hyperphosphorylation. AD research and more than 34% of clinical trials in AD are based on these two hypotheses. A phase-III clinical trial of lecanemab in early AD and mild cognitive impaired (MCI) patients reported a delay in cognitive decline of 27% over an 18-month treatment schedule. This multicenter trial found high specificity of lecanemab toward toxic protofibrils and subsequent clearance of beta-amyloid. There were, however, adverse events, which included cerebral edema and intracerebral hemorrhages in 23.1% of patients compared to 9.3% for those who received a placebo. Suboptimal clinical outcomes, brain volume loss, and adverse events in lecanemab treatment prompted a search for an alternative etiopathogenic explanation. Our research and others have focused on the oxidative stress (OS) hypothesis in AD. Autopsy studies have found significant depletion of the master antioxidant glutathione (GSH) in the hippocampal region, and is believed to be an early event in AD progression. Hippocampal GSH depletion is positively correlated with memory impairment. We have confirmed non-invasively with magnetic resonance spectroscopy (MRS) the depletion of GSH in patients with MCI and AD. We therefore propose a combinational therapy involving oral supplementation of gamma-glutamylcysteine (GGC), an early precursor of glutathione, to replenish brain GSH in addition to lecanemab, potentially to maximize desirable outcomes from combined therapeutic approach.

Predation of sea turtles (Chelonia mydas) by southern sea lions (Otaria byronia) and its relationship with overfishing in northern Chile

The disruption of a new food chain in the South American sea lion (SSL, Otaria byronia), with predation on green sea turtles (GST, Chelonia mydas) is reported for Northern Chile, probably from “nutritional stress” as result of anchovy (Engraulis ringens) overfishing, its fundamental food, with implications that cross multinational barriers in the South Pacific due to the shared nature of the resource. From 2011 an increase in carcasses of GST turtles with damages attributable to attacks by larger predators was observed on beaches of Arica (18°28´S), for which a necropsy study for signs attributable to predation, was carried out between November 2013 and May 2019. Jointly, direct observations of SSL attacks were made between Arica (18°28´S) and Iquique (20°13´S), that document predation of GST by SSL. 195 strandings including 179 Chelonia mydas, 15 Lepidochelys olivacea y 1 Eretmochelys imbricatea were recorded. 96.01% were strandings, 2.23% concentrated in drift, 1.12% as ghost fishing and 0.56% by fishermen from a gillnet. The necropsies of 14 carcasses in stage 1 and 2, showed damage attributable to interaction (alive or dead) with predators and/or scavengers. Most part of the observed injuries (tears of breakage and detachment of skin, muscles, internal structures such as the trachea, esophagus, stomach and part of the intestines, heart and liver) were attributable to SSL attacks and agree with the direct observations. Attacks by sharks or killer whales, and death by immersion or health problems could not be confirmed. The effect of this new feeding strategy of the SSL casts a shadow of uncertainty about the success of the green sea turtle population recovery program of northern Chile started in 2012. The results also suggest the need for evaluation of anchovy management programs and standards and the incorporation of an ecosystem approach to management plans, including the trophic needs of top depredators of the system.

Inflammation of adenohypophysis is commonly associated with headache in surgically managed Rathke's cleft cysts.

Rathke's cleft cysts (RCC) are present in up to 20% of autopsy studies but only a minority necessitate surgical treatment. Inflammation of RCC is thought to be significant in three processes: the development of classical symptoms, a predisposition to rupture or apoplexy, and increasing the rate of RCC recurrence. We aim to characterize clinical presentation, histological and radiological findings in patients with surgically managed RCC. We conducted a retrospective case series of 31 RCC, which had undergone surgical management between April 2016 and April 2024. Histopathology and radiology were independently reviewed by neuropathologist and neuroradiologist, and case notes were reviewed for clinical and biochemical data. Median age was 43 years (IQR 32-63); 77% were female. 23/31 demonstrated inflammation of RCC cyst epithelium (n = 13), cyst wall (n = 20) or anterior pituitary (adenohypophysitis) (n = 12). 8 cases were not inflamed. Preoperative features included pituitary dysfunction (70%), headache (65%), visual disturbance (26%) and polyuria/polydipsia (7%). Six patients presented with features of apoplexy. Headache was more prevalent (92%) in patients with adenohypophysitis vs. those without (47%), p = 0.020, and present in all 11 cases where inflammation in the adenohypophysis was chronic. Pituitary dysfunction was not associated with inflammation overall (76% vs. 70% p = ns), nor specifically within the adenohypophysis (75 vs. 63% p = 0.69). Histological inflammation was associated with radiological loss of posterior bright spot (70% vs. 14% p = 0.024). Headache but not pituitary dysfunction was associated with adenohypophyseal inflammation. A trend of increasing headache prevalence was seen with increasing degree of inflammatory infiltrate within RCC.

Myasthenia Gravis Misunderstood - Identifying the historical misinterpretations, miscommunication, and misconceptions

Myasthenia Gravis (MG) is a serious disease and can present clinically with very severe symptoms in many patients; however, the fluctuating severity of MG results in the disease being commonly misdiagnosed as other conditions, including conversion disorder. The earliest recorded literature on MG provides evidence of the variability of signs and symptoms, including many patients who appeared to have mild symptoms initially but died suddenly and unexpectedly from MG. Often, these patients were initially believed to be suffering from hysteria. This review analyzes some of the most prominent MG literature still cited today. It found that many communication errors have led to today’s misunderstandings and have continued to cause difficulties in diagnosis and difficulty in understanding the MG patients’ lived experiences. These errors include the intended meaning for ‘gravis’ being misinterpreted as ‘severe’ instead of the intended meaning of ‘a painful weight in the limbs’, the false belief that ‘gravis’ is Latin for ‘grave’ and how the miscommunication of the early 1900’s MG autopsy studies added to this confusion, where MG continued to be referred to as a ‘grave’ condition. The continued omission of the sensory symptoms associated with MG from the literature has also been miscommunicated for decades, however such symptoms are now becoming recognized as a result of increasing patient led research. Myasthenia Gravis should continue to be regarded as a serious disease, due to the devastating effect on quality of life for many people, and the unpredictability of the myasthenic crisis potentially occurring in all people living with MG, including those who are undiagnosed. The dismissing of mild symptoms results in many MG patients remaining undiagnosed. The possibility that individuals in this group go on to become victims of Sudden Adult Unexplained Death (SUD) is yet to be investigated, and there is a need for research in this area. Miscommunication also includes omitting ‘old knowledge,’ not listening to the patient’s lived experience, and failing to integrate relevant interdisciplinary knowledge. Good examples of these are The Mary Walker Effect, and combining patient lived experience with ocular anatomy and physiology knowledge to develop new MG-specific ocular motility clinical tests. A new test is presented for evaluating MG eye signs utilizing knowledge of the ‘Safety Factor,’ and is referred to as The SLOWLY Test (Significant Level Of Weakness, Loci in Y Axis). Awareness of the historical misinterpretations, miscommunications, and misconceptions is crucial to preventing delay in diagnosis in MG patients, developing new clinical tests, rehabilitation interventions, and helping doctors and others understand the lived experience of MG patients

Frequency and consequences of immune checkpoint inhibitor-associated inflammatory changes in different organs: an autopsy study over 13-years.

While immune checkpoint inhibitors (ICIs) have revolutionized modern oncology, they are also associated with immune-related adverse events (irAEs). Previous histopathological descriptions of organ-related inflammatory changes do not consider systemic effects of ICIs, because of an absence of comprehensive autopsy studies. We performed a retrospective study on 42 whole-body autopsies of patients treated with ICIs from January 2011 to March 2024 to determine frequency, organ distribution and morphology of ICIs-associated inflammatory changes as well as their clinical relevance. Twenty-three of 42 patients (54.8%) presented irAEs with inflammatory changes in at least one organ. Most frequent irAEs were ICIs-related hypophysitis (N=12, 28.6%), myocarditis (N=8, 19.0%), pneumonitis (N=5, 11.9%), hepatitis (N=6, 14.3%), and adrenalitis (N=5, 11.9%). ICIs-related inflammation was mainly characterized by lympho-histiocytic and macrophage-rich tissue infiltrates, whereas a granulomatous "sarcoid-like" reaction was observed in one patient. Cause of death was attributable to ICIs-therapy in 7 patients (16.7%), with ICIs-associated myocarditis as the most common cause of death (N=5, 71.4%). Clinically, irAEs were unsuspected in 5 of 7 ICIs-related deaths (71.4%). Among irAEs, myocarditis has been clinically undiagnosed in 5 out of 8 cases (62.5%). Encephalitis was identified only at autopsy in all cases (N=2). Hypophysitis was clinically unsuspected in 8 of 12 cases (66.7%). Patients who died from irAEs developed more frequently a complete tumor regression than patients who died from other causes (P=0.018). Of note, ICIs-related myocarditis and pneumonitis were both associated with a systemic occurrence irAEs. Our study demonstrates that some irAEs, especially myocarditis, hypophysitis, and encephalitis are clinically underdiagnosed. Autopsy remains a valuable tool to monitor diagnostic accuracy and therapeutic side effects in patients who died under ICIs-therapy.

Personality Disorders and Suicide. A Systematic Review of Psychological Autopsy Studies.

This systematic review explores the relationship between personality disorders (PDs) and lethal suicide behavior. Following PRISMA guidelines, the study examines psychological autopsy studies with suicide deaths and identified PDs. Inclusion criteria encompass studies using the psychological autopsy method, reporting PD diagnosis and suicide deaths, in English language and with no temporal restrictions. The search strategy, conducted in PubMed and Embase until December 2nd, 2023, utilized specific terms related to suicide, PD, and psychological autopsy. Quality assessment using the Newcastle Ottawa-Scale for case-control studies was employed. 56 psychological autopsy studies were included in the systematic review, revealing a prevalence of PDs among suicide deaths, and emphasizing their role as significant suicide risk factors. The review underscores the impact of comorbid PDs and Axis I disorders on suicide risk, particularly if additional stressors are present. Gender differences in PD prevalence are noted, with impulsivity and alcohol abuse identified as universal risk factors. Despite extensive global data collection, limitations include potential methodological variations and biases inherent in psychological autopsy studies. This study, registered in PROSPERO (CRD42022322359), contributes essential insights into the prevalence, characteristics, and risk factors of PDs among suicide deaths.

Rapunzel Syndrome: Clinical, Diagnostic and Forensic Aspects in Related Deaths-A Review of the Literature.

Background: Rapunzel syndrome is a rare and severe form of trichobezoar, characterized by the presence of hair masses in the stomach that often extend into the bowel, resembling the legendary "Rapunzel's" long hair. Methods: This review examines the clinical, diagnostic, forensic, and post-mortem aspects associated with Rapunzel syndrome, with a focus on cases resulting in mortality or those at high risk of death due to complications. In particular, the review systematically analyzes the existing literature on fatal cases of Rapunzel syndrome, emphasizing insights into risk factors, clinical manifestations, diagnostic methods, autopsy findings, and preventive measures to provide a focused understanding of these critical aspects. Results: The syndrome predominantly affects young females with a history of trichotillomania (hair-pulling) and trichophagia (hair-eating), often associated with underlying psychiatric conditions. Clinically, Rapunzel syndrome presents with non-specific gastrointestinal symptoms, including abdominal pain, vomiting, and malnutrition, which may complicate timely diagnosis. Diagnosis typically involves imaging techniques such as ultrasound, CT scans, and endoscopy, but cases often go unrecognized until complications like intestinal obstruction, perforation, or even fatal outcomes occur. Forensically, Rapunzel syndrome presents unique challenges, as misdiagnosis or delayed intervention can lead to fatalities that may raise questions in medico-legal investigations. Post-mortem investigations, particularly autopsies, have proven instrumental in elucidating rare complications and advancing understanding of the syndrome's long-term effects. Conclusions: Increased awareness, timely diagnosis, and comprehensive evaluation, including autopsy studies, are essential to improve patient outcomes and reduce the potential for life-threatening complications in this rare yet serious condition.

Increased Survival in Contemporary Parkinson’s Disease: A 47-Year Autopsy Study

Introduction: Parkinson’s disease (PD) is the second most common neurodegenerative disorder. The main clinical features are bradykinesia, rigidity, and resting tremor. Other neurodegenerative disorders such as progressive supranuclear palsy and multiple system atrophy share some of these clinical manifestations. All those disorders are collectively known as parkinsonism or Parkinson syndrome (PS). Definite diagnosis of PD requires brain autopsy. There is no known cure for PD. Since its discovery in the 1960s, levodopa (LD) has remained the best and most widely used medication in PD. The impact of that is important to understanding the neuroepidemiology of PD. The incidence of PD rises with advancing age. In the last six decades, life expectancy in the general population has increased resulting in a larger pool of at-risk persons. Onset age of PD is the most reliable indicator of PD survival as older onset cases have shorter survival. We report on survival in autopsy-confirmed PD cases with onset age <70 years treated with LD and compare that with similar onset-age cases of PD before the discovery of LD. Material and Methods: The Saskatchewan Movement Disorders Program (SMDP) has operated uninterrupted since 1968. Long follow-up and autopsy studies are a special interest of the SMDP. All PS cases followed by the SMPD during 47 years (1968–2015) that came to autopsy were considered. Those with autopsy-confirmed PD and onset <70 years were included and were compared with pre-LD cases of similar age of onset. Results: Overall, 392 PS cases were seen in our clinic between 1968 and 2015 and had brain pathology studies. A total of 314 (80%) of those had PD. Overall, 128 (41%) of the PD cases had onset <70 years and were included in this study. Their median survival was 18 years. Conclusion: Prior to widespread use of LD, nearly all PD cases had onset <70 years and mean survival was 9.4 years. Longer survival in our study is attributed primarily to modern treatment. Increased survival has resulted in a larger number of older, chronically treated, higher comorbidity, and complicated PD patients. These changes present new challenges. It requires a larger and increasingly diverse workforce for patient care and research.

What is the spectrum of kidney pathology associated with COVID-19?

Kidney involvement occurs in almost one third of patients hospitalised with coronavirus disease 2019 (COVID-19) and is associated with increased disease severity. This review aims to outline the spectrum of kidney pathology involved in COVID-19. Literature was reviewed systematically on the databases Medline OVID and Scopus in search of case reports, case series, cohort studies and autopsy studies of patients with COVID-19 who underwent kidney biopsies. Studies were published between August 2020 and November 2021. Fourteen studies consisting of 159 patients were included in this review. Acute tubular necrosis is the most common pathology followed by collapsing glomerulopathy, occurring in 40.1% and 28.9% of patients respectively. Of the 46 patients with collapsing glomerulopathy, 44 were of African descent with high-risk apolipoprotein L1 genotypes. Less common glomerular diseases include membranous nephropathy, secondary focal segmental glomerulosclerosis, minimal change disease and primary focal segmental glomerulosclerosis occurring in 5%, 4.4%, 3.1% and 2.5% of patients respectively. Glomerulonephritis occurred in a minority of patients. Direct viral infection has not been found as a definitive aetiology. Acute kidney injury occurs frequently in hospitalised COVID-19 patients and is associated with increased morbidity and mortality. The mechanisms underpinning acute kidney injury are multifactorial. Acute tubular necrosis is the most common. Collapsing glomerulopathy is the most common glomerular injury and is strongly linked to apolipoprotein L1 genotypes. Improved understanding of COVID-19-related kidney pathologies can guide treatment to improve patient outcomes and reduce progression of chronic kidney disease. The longitudinal impact of COVID-19-related kidney disease requires further research.

Religiosity, Spirituality, Meaning-Making, and Suicidality in Psychiatric Patients and Suicide Attempters: A Systematic Review and Meta-Analysis.

After participating in this CME activity, the psychiatrist should be better able to:• Explain current understanding of how religiosity, spirituality, and meaning-making (R/S/M) affect patients with psychiatric diagnoses. R/S/M generally protect against suicidality and suicide. Thus far, reviews on the topic have largely been descriptive, and there are no meta-analyses focused on psychiatric patients. This study systematically evaluates all empirical evidence on R/S/M's potential influences on suicidality for psychiatric patients and recent suicide attempters. A systematic PROSPERO preregistered search following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol was performed in MEDLINE and PsycInfo. Quantitative studies until 31 December 2022 on R/S/M and suicidality in psychiatric populations and recent suicide attempters were selected; psychological autopsy studies were excluded. The search identified 4,374 studies for screening. This resulted in 108 eligible studies for the systematic review and 75 studies for the meta-analysis, including 231 effect sizes (ES) and 17,561 subjects. Research focused mainly on the emotional, moral, and ritual aspects of R/S/M. Most research was cross-sectional; repeated R/S/M assessments were rarely reported. A combined significant and negative ES (Fisher Z = -0.13, p = .006, equivalent to Cohen's d = -0.26) was found for all good- and fair-quality studies. Overall, R/S/M was associated with lowering suicidality. Maladaptive-distressing dimensions of R/S/M correlated with higher rates of suicidality (e.g., religious struggles). The explanatory value was limited by the predominantly cross-sectional nature of ESs. PROSPERO registration 2023 CRD42023398692; there was no funding involved.

Preliminary findings of the TB-HEART Study: prevalence of cardiac pathology among newly diagnosed patients with tuberculosis with and without HIV in Zambia

Abstract Background Cardiovascular diseases (CVD) burden is rapidly increasing in sub-Saharan Africa (SSA) where tuberculosis and HIV prevalence remain high.(1-3) Recent data suggest pulmonary tuberculosis (PTB) is associated with increased CVD morbidity.(4) However, the mechanisms of cardiac injury remain poorly understood. Purpose The TB-HEART study is a cross-sectional and natural history study consecutively recruiting participants with newly-diagnosed PTB, living with and without HIV in Zambia. The primary outcome is the burden of cardiac pathology in PTB patients with and without HIV. Methods Participants with bacteriologically-proven PTB, consecutively recruited from an outpatient settings in Zambia, undergo detailed clinical and functional assessments including point-of-care and standard two-dimensional (2D) echocardiography. Participants are reviewed at completion of TB treatment when all assessments are repeated. The target sample size is 250 participants with PTB, with and without HIV, matched 2: 1 to participants without PTB, stratified by HIV. Results Since 1 November 2023, we have recruited 73 participants with a mean age of 35.3±10.9 years of whom 51/73 (69.9%) are male and 19/73 (23.5%) are living with HIV. Baseline characteristics including cardiovascular risk factors, TB symptoms, anthropometry and clinical and functional observations at presentation, stratified by HIV status, are summarised in Table 1. We detected significant cardiac pathology (defined as left ventricular ejection fraction (LVEF) &amp;lt;51% and/or pericardial effusion &amp;gt;2cm in depth) in 8/65 (12.3%) participants for whom 2D-echocardiography had been completed. Median LVEF was 61.2% (IQR 57.7-67.8). LVEF was normal in 59/65 (91%); mildly abnormal in 5/65 (7.7%); and moderately abnormal in 1/65 (1.5%) participants, respectively. Pericardial effusion &amp;gt;0.5cm was detected in 16/65 (24.6% ) participants and maximum effusion depth was &amp;gt;2cm in 2/16 (3.1%), 1-2cm in 12/16 (75%) and &amp;lt;1cm in 2/16 (12.5%). 2D-echocardiography findings, stratified by HIV-status, are described in Table 2 alongside two echocardiography stills of typical pericardial effusion findings in one participant. Conclusions Our preliminary results demonstrate a higher than expected prevalence of cardiac pathology among participants with PTB with and without HIV, which ranges from 1-7% in autopsy studies and case series.(5-7) The most common cardiac pathology was pericardial effusion. Further analyses will include cardiac biomarkers; repeat clinical and echocardiographic assessments at TB treatment completion; and comparator data, to determine associations between prevalent cardiac pathology and PTB controlling for HIV and TB status, respectively. This may have important implications for clinical practice to prevent complications such as constrictive pericarditis; and policy design to better integrate TB and HIV patient services with preventative care to reduce future CVD risk.Table 1 - Baseline characteristicsFigure 1 and Table 2

Histological assessment of the shared vascular wall in anomalous aortic origin of coronary arteries with an interarterial course

Abstract Background In anomalous aortic origin of a coronary artery (AAOCA) an intramural segment is present if the proximal AAOCA courses through the aortic wall. This is defined as a shared tunica media of the aorta and AAOCA in the ‘intramural septum’. This definition is based on autopsy studies of selected AAOCA patients who suffered sudden cardiac death and is difficult to apprehend on imaging modalities. Therefore, the aim was to identify the histological features and variants of the interarterial vascular wall in living adult patients, and correlate this to CT-angiography (CTA). Methods This prospective multicenter study included consecutive adult AAOCA patients who underwent surgical unroofing between 2021 to 2024. The excised interatrial vascular wall tissue was embedded, sectioned, and immunohistochemically stained for physiological components, e.g. smooth muscle cells and connective tissue, and pathological components such as fibrosis. Microscopic examination and quantification was performed by two independent observers and findings were correlated with CTA. Results Fifteen patients (mean age 42.9±14.0 years, 60% female) and 1 postmortem specimen were included. Fourteen (93%) had a right-AAOCA and 1 (7%) a left-AAOCA, with a mean intramural length of 8.4±4.1mm. Histopathologically, disorganized elastic lamellae with fragmentation, presence of fibrosis and loss of nuclei were observed. No vasa vasorum or nervi vasorum were identified. Post-sectioning virtual 3D reconstructions enhanced the spatial insight in correlation of histological sections with CTA. Conclusion This first study of the intramural septum in adults with AAOCA reveals the histological structure of the shared vascular wall between the aorta and AAOCA. Marked vascular wall abnormalities such as lack of vasa and nervi vasorum, fragmentation of elastic lamellae and fibrotic changes were observed. These findings support a propensity to local vascular wall pathology in patients with AAOCA. 3D reconstruction supported the translation of histological data to clinical imaging techniques.Central Figure

Gastric metastasis of small cell lung carcinoma: A rare but noteworthy entity to consider.

Small cell lung carcinoma (SCLC) is an aggressive malignancy known for its propensity for early and extensive metastatic spread. Gastric metastasis, where cancer cells disseminate from the lung to the stomach, is a rare but increasingly recognized complication of SCLC. This review provides a comprehensive overview of gastric metastasis in SCLC, addressing its clinical significance, diagnostic challenges, management strategies, and prognosis. Additionally, it examines the broader metastatic patterns of SCLC and compares them with other malignancies known for gastric metastasis. Gastric metastasis in SCLC, though infrequent, is clinically significant and often indicates advanced disease with a poor prognosis. SCLC typically metastasizes to the liver, brain, bones, and adrenal glands, with the stomach being an unusual site. The incidence of gastric metastasis ranges from 1% to 5% in autopsy studies, although this may be underestimated due to diagnostic difficulties and asymptomatic early lesions. Diagnosing gastric metastasis presents several challenges, including the asymptomatic nature of many cases, limitations of conventional imaging techniques, and difficulties in distinguishing metastatic lesions from primary gastric cancer via endoscopy. Histopathological diagnosis requires careful examination to identify SCLC cells through their characteristic small cell morphology and neuroendocrine markers. Management of gastric metastasis in SCLC typically involves a multidisciplinary approach. Systemic therapy, primarily chemotherapy, remains the cornerstone of treatment, with palliative care addressing symptoms and complications. Surgical intervention is usually reserved for specific cases requiring symptomatic relief. The prognosis for patients with gastric metastasis from SCLC is generally poor, reflecting the advanced stage of the disease. Median survival is significantly reduced compared to patients without gastric metastasis. This review emphasizes the need for enhanced awareness and early detection to improve patient outcomes and highlights the importance of ongoing research into better diagnostic and therapeutic strategies.

Hypercholesterolemia and Alzheimer's Disease: Unraveling the Connection and Assessing the Efficacy of Lipid-Lowering Therapies.

This article examines the relationship between cholesterol levels and Alzheimer's disease (AD), beginning with the early observation that individuals who died from heart attacks often had brain amyloid deposition. Subsequent animal model research proved that high cholesterol could hasten amyloid accumulation. In contrast, cholesterol-lowering treatments appeared to counteract this effect. Human autopsy studies reinforced the cholesterol-AD connection, revealing that higher cholesterol levels during midlife significantly correlated with higher brain amyloid pathology. This effect was especially pronounced in individuals aged 40 to 55. Epidemiological data supported animal research and human tissue observations and suggested that managing cholesterol levels in midlife could reduce the risk of developing AD. We analyze the main observational studies and clinical trials on the efficacy of statins. While observational data often suggest a potential protective effect against AD, clinical trials have not consistently shown benefit. The failure of these trials to demonstrate a clear advantage is partially attributed to multiple factors, including the timing of statin therapy, the type of statin and the appropriate selection of patients for treatment. Many studies failed to target individuals who might benefit most from early intervention, such as high-risk patients like APOE4 carriers. The review addresses how cholesterol is implicated in AD through various biological pathways, the potential preventive role of cholesterol management as suggested by observational studies, and the difficulties encountered in clinical trials, particularly related to statin use. The paper highlights the need to explore alternate therapeutic targets and mechanisms that escape statin intervention.

Cardiac metastasis from carcinoma gall bladder - a rare case detected on autopsy

Metastasis to the heart is uncommon compared to other organs, posing notable diagnostic challenges. Incidence in autopsy studies typically ranges between 0.7% and 3.5%. Lung, breast, and hematologic cancers are the main sources of such metastases, leading to varied clinical presentations and severe complications. Postmortem viscera from a 47 year old male with a suspected history of jaundice. Only limited information was available. Gross examination showed a solid mass in the gall bladder with areas of hemorrhage and necrosis, while no other abnormalities were observed in other viscera received. Brain examination showed congested blood vessels, while heart sections exhibited atypical cell deposits in the pericardium and myocardium. Coronary arteries displayed pathological thickening. Lung and liver sections also displayed similar metastatic atypical cell deposits, infiltrating tissue and causing necrosis. Gall bladder examination revealed irregular glandular formations lined with polygonal tumor cells positive for cytokeratin. The final diagnosis based on histomorphological features and immunohistochemistry confirmed gall bladder adenocarcinoma metastasising to the heart, liver and lungs.

Detection of H1N1 Influenza Virus in the Bile of a Severe Influenza Mouse Model.

Influenza virus infection may lead to fatal complications including multi-organ failure and sepsis. The influenza virus was detected in various extra-pulmonary organs in autopsy studies during the 2009 pandemic. However, limited research has been conducted on the presence of viral particle or viral components in the peripheral blood. We established a mouse model for severe H1N1 influenza. The bile and blood samples were collected over time and inoculated into embryonated chicken eggs. We detected live influenza virus in bile and blood samples in early infection. Immunofluorescence showed influenza viral components in the liver tissue. No live virus was isolated in the bile in mice intragastrically administered with influenza virus, indicating that the virus was spread from the blood stream. Targeted metabolomics analysis of bile acid and liver tissues showed that a secondary bile acid (3-dehydrocholic acid) was decreased after influenza H1N1 infection. Genes related with fatty acid metabolism and bile secretion pathways were down-regulated in liver after influenza virus infection. Our study indicated that influenza virus viremia is present in severe influenza, and that the liver is a target organ for influenza viral sepsis.

When is prostate cancer really cancer?

Prostate cancer (PC) is a major cause of cancer-related deaths worldwide, with far more diagnoses than deaths annually. Recent discussions have challenged whether Grade Group 1 (GG1) PC should be labeled "cancer" due to its indolent nature. To address this question, an international symposium convened stakeholders from various fields. We summarize key discussion points: autopsy studies reveal GG1 is so common in aging males as to be perhaps a normal aspect of aging. Pure GG1 has no capacity to metastasize. Modern diagnostic pathways focus on detecting higher-grade disease, explicitly omitting biopsy if GG 2 or higher is not suspected, so GG1 has effectively become an "incidentaloma." Recent spatial transcriptomics of prostate sections identifies a continuum of genomic changes-including alterations characteristic of malignancy in histologically normal regions, so the designation of cancer based entirely on conventional pathology findings increasingly seems arbitrary at least to an extent. Pathologists discussed heterogeneity and diagnostic challenges, suggesting "acinar neoplasm" as one possible alternative label. GG1 should not be considered "normal," and absolutely requires ongoing active surveillance; whether patients would adhere to surveillance absent a cancer diagnosis is unknown. Patient perspectives highlighted the adverse effects of overtreatment and the burden of a cancer diagnosis. The anticipated impact on screening and treatment varies across health-care systems, but many believe public health would on balance greatly improve if GG1-along with lesions in other organs with no capacity to cause symptoms or threaten life-were labeled something other than "cancer." Ultimately, our goal is to reduce PC mortality while minimizing harms associated with both overdiagnosis and overtreatment.

The Association Between Neuropathological Lesions and Body Mass Index Is Independent of Cognitive Abilities.

The association of moderate and severe dementia with low body mass index (BMI) is well described, but weight decline seems to also occur in individuals with preclinical neuropathologies. Considering that up to one-fifth of individuals with normal cognition meet the criteria for a dementia-related neuropathological diagnosis, autopsy studies are key to detecting preclinical neurodegenerative and cerebrovascular diseases that could be underlying weight changes. We investigated the association between dementia-related brain lesions and BMI and evaluated whether the cognitive function was a mediator of this association. In 1,170 participants, sociodemographic data, clinical history, and cognitive post-mortem evaluation were assessed with an informant. Neuropathological evaluation was performed in all cases. Linear regression models were used to investigate the association between neuropathological lesions (exposure variable) and BMI (outcome) adjusted for demographic, clinical, and cognitive variables in the whole sample, and in only those with normal cognition. Corrections for multiple comparisons were performed. In addition, a mediation analysis was performed to investigate the direct and indirect effects of cognitive abilities on the association between neuropathology and BMI. Individuals with lower BMI had a higher burden of neuropathological lesions and poorer cognitive abilities. Only neurofibrillary tangles (NFT) and neuropathological comorbidity were associated with low BMI, while other neurodegenerative and cerebrovascular lesions were not. NFT were indirectly associated with BMI through cognitive abilities, and also directly, even in participants with normal cognition. Neurofibrillary tangles were directly associated with low BMI even in individuals with preclinical Alzheimer's disease.

A scoping review on adult patients with de novo glomerular diseases following COVID-19 infection or vaccine.

There are increasing reports of glomerular disease (GD) following COVID-19 infection and vaccination. Current evidence on the possible link between COVID-19 infection or vaccination and GD is conflicting. The present study undertakes a scoping review of research to describe the relationship between COVID-19 infection and vaccination with GD and the common management strategies and overall outcomes of the disease to identify knowledge gaps and guide further research. All original research studies published in English until 5th September 2022 were considered for inclusion in the review. Exclusion criteria were animal studies, autopsy studies, and data involving patients who were paediatric patients (< 16years), were transplant recipients, had a recurrence of glomerular disease, had concomitant cancer or non-COVID-19 infection which may cause glomerular disease, or did not receive a renal biopsy. The five electronic databases searched were MEDLINE, PubMed, Scopus, EMBASE, and Cochrane. Two separate search strings related to COVID-19, and glomerular disease were combined using the Boolean operator 'AND'. Filters were used to limit publications to original research studies published in English. Search results from each database were imported into Covidence software ( www.covidence.org ) and used for de-duplication, article screening, and data extraction. Descriptive analyses were used to summarise demographics, diagnoses, and treatment outcomes. After removing duplicates, 6853 titles and abstracts were screened. Of the 188 studies included, 106 studies described 341 patients with GD following COVID-19 infection and 82 described 146 patients with GD following a COVID-19 vaccination. IgA nephropathy was the most common GD pathology reported following COVID-19 vaccination with GD most common following mRNA vaccines. Collapsing focal segmental glomerulosclerosis was the most common GD following COVID-19 infection. Immunosuppressive treatment of GD was more common in the vaccine cohort than in the infection cohort. Despite the significant number of COVID-19 infections and vaccinations around the world, our understanding of GD associated with COVID-19 infection and vaccination remains poor, and more research is needed to understand the possible relationship better.

Study of histopathological and ultrastructural changes in the lungs of COVID-19 patients

BackgroundCOVID 19 infection is a multi-systemic disease with the lungs bearing the maximum brunt. Very few autopsy studies have been done on the deceased patients. The present study aimed to study the clinical spectrum and lab parameters of COVID-19 patients along with the morphological spectrum of the lung changes in these patients by histology, Immunohistochemistry and Electron microscopy. We also compared the Clinical severity and Lab parameters with the histopathological phase of the lung involvement. MethodsWe conducted a cross sectional observational study between Jun 2021 to Dec 2022 where in needle necropsy of lung tissue of COVID 19 confirmed fatal cases were studied by histopathology, immunohistochemistry (using CD3, CD4, CD8, CD19, CD20, CD68 and Pan CK markers) and Electron microscopy. Various hematological, histopathological and ultrastructural parameters were studied. The results were analyzed using SPSS 25.0 software. ResultsA total of 24 cases were studied. The mean age was 65.9 yrs, male: female ratio was 2:1. Five had moderately severe COVID while 19 had severe COVID infection. Diffuse alveolar damage (DAD) was seen in 83% of all the cases. On the basis of clinical severity and histopathological staging, broadly two histopathological groups were made (Proliferative and Organizing). Difference between TLC, N/L ratio and L/Platelet ratio in two histopathological groups was assessed using unpaired t test, however no significant difference was noted. We did not find any correlation between clinical severity and histopathological groups though severe cases of COVID-19 were found to have a shorter time between admission to the hospital and death. All the biopsies were subjected to electron microscopy and in two of the cases we could demonstrate corona virus particles. ConclusionOur study has shown that severe cases of COVID 19 are associated with a shorter time between admission to hospital and death. While the histopathology of the lung showed diffuse alveolar damage as the most common finding; the Transmission Electron Microscopy (TEM) played an important role in characterizing the ultrastructure of these cells and demonstrating corona virus particles.