Adult Autopsy Research Articles

EXPLORING THE ROLE OF NGS IN GENETIC PROFILING FOR UNDERSTANDING NON-VIOLENT SUDDEN CARDIAC DEATH IN ASTANA

Sudden cardiac death is an unexpected and often unpredictable event that can have serious consequences for the health and lives of individuals not only in middle age but also in young individuals. Mutations, particularly in genes associated with cardiovascular disease, may play a main role in the development of such events, but their exact role and impact require detailed study and prevention of the development of new mutations by using the Next-generation sequencing (NGS). To evaluate the diagnostic importance of next-generation sequencing (NGS) by using our developed cardiogenetic panel in molecular autopsy in sudden non-violent deaths. A prospective study was conducted from 2018 to 2023 focusing of young individuals aged 18 to 45 years resigning in Astana who died of non-violent CVD. The data were analyzed from RSCE "Forensic Expertise Centre of the Ministry of Justice of the Republic of Kazakhstan" "Research Institute of Forensic Expertise" in Astana, blood samples were obtained from SCD victims for further DNA extraction. We implemented a next-generation sequencing (NGS) using the customized panel to target enrichment of coding sequences of 96 candidate genes in molecular autopsies of young adults who died of SCD. All identified genetic variants were classified according to ACMG guidelines in cases with non-diagnostic and diagnostic cardiac abnormalities (ischemic heart disease postmortem). Targeted sequencing and stepwise filtering of annotated variants identified 251 unique variants in 86 genes out of 96 in the entire group of cases studied. In patients with SCD with ischemic changes in the heart postmortem, the most frequent mutations were identified in the TTN, MYBPC3, LAMA2, MYH6 and GAA genes. Pathogenic variants in the genes of ion channels KCNQ1, KCNJ2, SCN5A, RYR2 were detected in individuals with non-diagnostic structural anomalies of the heart. Genetic screening of individuals who died of SCD identified variants with likely pathogenic functional effects with high frequency in 63% and 35% of SCD cases with non-diagnostic and diagnostic cardiac abnormalities, respectively, showing the high diagnostic value of genetic screening using a panel of genes for targeted NGS. Data from our prospective study have shown that genetic testing using NGS in young Astana victims with SCD results in a significant number of mutations, consequently, may allow genetic counselling of relatives to prevent SCD due to coronary heart disease and arrhythmias and may support differential diagnosis postmortem. Supported by Committee of Science of the of Science and Higher Education of Republic of Kazakhstan (AP1486990) and Nazarbayev University CRP(211123CRP1608).

Autopsy findings from patients diagnosed with COVID-19 demonstrate unique morphological patterns in bone marrow and lymph node

AimsThe identification of haemophagocytosis in bone marrow (BM) is recurrently identified in patients with severe COVID-19. These initial COVID-19 autopsy studies have afforded valuable insight into the pathophysiology of this...

Prevalence of metabolic dysfunction-associated steatotic liver disease and steatohepatitis in Türkiye: A forensic autopsy study

Background and aimsMetabolic dysfunction-associated steatotic liver disease (MASLD) is a growing global epidemic in Türkiye and worldwide. The aim of this study was to evaluate the prevalence and predictors of MASLD and steatohepatitis among adults who died of unnatural causes including sudden death and non-burn trauma. MethodWe conducted a prospective review of all consecutive adult forensic autopsies for natural (sudden unexpected) and non-natural (Suicidal, homicidal and accidental) suspicious deaths carried out at the Istanbul Council of Forensic Medicine from February to May 2022. Four wedge biopsies were extracted from sagittal sectioned liver specimens. A liver pathologist with 20 years of experience examined each case for steatosis, ballooning, inflammation, and fibrosis. ResultsAmong 1797 autopsies, 62 met inclusion criteria. Overall, 43.3 % (n = 26) of autopsies showed evidence of steatotic liver disease, with a distribution of steatosis severity as: Grade I (28.3 %), Grade II (6.6 %), and Grade III (8.3 %). All these cases met at least one cardiometabolic criteria and diagnosed with MASLD. Ballooning was observed in 20.0 % of cases (5 cases grades 1 and 7 cases grade 2), and Inflammation was present in 51.7 % (9 cases with grade 0–1, 12 with 1–2, 7 with 2–3, and 3 with 5–6). Notably, 46.1 % (n = 12) of MASLD cases and 20.0 % (n = 12) of all cases were diagnosed with steatohepatitis, with three cases exhibiting delicate perisinusoidal fibrosis and one case showing portal fibrosis. ConclusionThe histopathological findings from this autopsy study confirmed the markedly high prevalence of MASLD and steatohepatitis within the general adult population, highlighting the concerning burden of steatotic liver disease in Türkiye.

The autonomic nerves around the vein of Marshall: apostmortem study with clinical implications.

This study aims to analyze the vein of Marshall (VOM) in human autopsy hearts and its correlation with clinical data to elucidate the morphological substrates of atrial fibrillation (AF) and other cardiac diseases. Twenty-three adult autopsy hearts were studied, assessing autonomic nerves by immunohistochemistry with tyrosine hydroxylase (sympathetic nerves), choline acetyltransferase (parasympathetic nerves), growth-associated protein 43 (neural growth), and S100 (general neural marker) antibodies. Interstitial fibrosis was assessed by Masson trichrome staining. Measurements were conducted via morphometric software. The results were correlated with clinical data. Sympathetic innervation was abundant in all VOM-adjacent regions. Subjects with a history of AF, cardiovascular cause of death, and histologically verified myocardial infarction had increased sympathetic innervation and neural growth around the VOM at the mitral isthmus. Interstitial fibrosis increased with age and heart weight was associated with AF and cardiovascular cause of death. This study increases our understanding of the cardiac autonomic innervation in the VOM area in various diseases, offering implications for the development of new therapeutic approaches targeting the autonomic nervous system.

POSTMORTEM HEART DISSECTION FOR SUDDEN DEATH EXAMINATION

The article describes the postmortem heart examination technique during a forensic autopsy of adults. The heart examination technique is based on the recommendations of scientific societies of pathologists, publications on autopsy techniques used in recent decades. The achievements of morphologists of the second half of the 20th century are also taken into account. The postmortem heart examination technique provides an examination of the coronary vessels, as well as myocardium and heart valves. The possibilities for examination of the elements of the conductive system are also represented. The following method ensures preservation of topographic relationships of morphological structures within the heart and possibility of its re-examination. The postmortem heart examination includes the following stages: examination of the coronary arteries, the making of three transverse incisions from the apex to the middle of the ventricles, “blood flow” incisions taking into account the localization of the main nodes of the conducting system, as well as the peculiarities of the examination of the heart valves. Peer Review History: Received: 12 October 2023; Revised: 21 November; Accepted: 27 December, Available online: 15 January 2024 Academic Editor: Dr. Nuray Arı, Ankara University, Turkiye, ari@ankara.edu.tr Received file: Reviewer's Comments: Average Peer review marks at initial stage: 6.0/10 Average Peer review marks at publication stage: 7.0/10 Reviewers: Prof. Hassan A.H. Al-Shamahy, Sana'a University, Yemen, shmahe@yemen.net.ye Dr. Rima Benatoui,Laboratory of Applied Neuroendocrinology, Department of Biology, Faculty of Science, Badji Mokhtar University Annaba, Algeria. benattouiryma@gmail.com Dr. Bilge Ahsen KARA, Ankara Gazi Mustafa Kemal Hospital, Turkey, ahsndkyc@gmail.com

Autopsy Pathology of Heart and Coronary Vessels in Sudden Death: A Cross-sectional Study from Southern India

Introduction: Cardiac diseases emerge as the primary culprits behind sudden and unexplained deaths. Morphological evaluation through autopsy is invaluable in establishing the prevalence of cardiac lesions and coronary atherosclerosis within the general population. It provides healthcare researchers with valuable insights to develop preventive measures and early detection strategies crucial for improving survival rates. Aim: To estimate the prevalence of cardiac lesions in postmortem specimens of the heart from autopsies of sudden and unexplained deaths. Materials and Methods: The present cross-sectional study was conducted in the Department of Pathology, Government Medical College (a public sector hospital), Cochin, Kerala, India, from January to December 2021 on 140 specimens of the heart. Medicolegal autopsies were performed in the Department of Forensic Medicine, with specimens forwarded to the Pathology Department for histopathological examination. Hearts dissected by the modified Virchow’s method were examined for gross pathology in the cardiac wall, chambers, valves, coronaries and aorta. Microscopy findings were documented and the grading of coronary atherosclerosis was done using the Modified American Heart Association (AHA) criteria. Proportions were analysed from the compiled data using a Chi-square test. Statistical analysis was done using Statistical Package for the Social Sciences (SPSS) software version 21.0 software. Results: In the study encompassing 140 adult autopsies, the mean age of the study population was 45.98 with a Standard Deviation (SD) of 15.82 years and the male to female ratio was 3.5:1. The prevalence of cardiac lesions was as follows: coronary artery atherosclerosis (80.70%), Ischaemic Heart Disease (IHD) (44.28%), cardiac hypertrophy and hypertension (10%), pericarditis (6.42%) and myocarditis (3.50%). The male- to-female ratio for coronary atherosclerosis was 4.4:1, with triple vessel disease observed in 42.90% of cases. Atherosclerosis severity grades included early non atheromatous lesions (19.3%), Pathological Intimal Thickening (PIT) (23.6%), and advanced atherosclerotic lesions (37.80%). Among cases associated with Coronavirus Disease 2019 (COVID-19)-related deaths (10.7%), changes noted included myocarditis, microhaemorrhages, oedema, capillary dilatation, fibrin deposition and inflammatory infiltrates. Conclusion: The present study revealed a high prevalence of coronary atherosclerosis affecting all three vessels, particularly among the younger population. This underscores the significance of screening for cardiovascular risk factors and implementing preventive measures from an early age.

Unravelling the Histomorphological Features of Kidney: An Autopsy-based Study

Introduction: Renal failure and End-stage Renal Disease (ESRD) are one of the leading causes of mortality. The presence of co-morbidities like Diabetes Mellitus (DM), Hypertension (HT), pregnancy, liver diseases, and various infections accelerates renal failure. Understanding the pathophysiology of Acute Renal Failure (ARF) is necessary to interpret and correlate the spectrum of morphologic changes associated with it. Aim: To study the aetiopathological causes of renal failure and evaluate the histopathological features associated with them. Materials and Methods: A cross-sectional autopsy-based study was performed in the Department of Pathology, Topiwala National Medical College, Mumbai, Maharashtra, India over three consecutive years. A total of 650 adult autopsies were studied. Clinical and laboratory details were obtained from hospital records. Gross and histopathological examinations were performed with a special focus on the kidneys. Special stains were performed wherever required to highlight any characteristic features. Results: It was found that males (n=460) were more affected than females (n=190). The age range was 13-90 years. The majority of autopsies were performed within 24 hours of hospital stay. Acute febrile illness was found to be the most common cause of ARF. Maximum number of cases were from medical units (n=520, 80%), followed by surgical (n=94, 14.5%) and gynaecological units (n=36, 5.5%). Features of Acute Kidney Injury (AKI) were seen in (n=374) 57.6% of cases, while Advanced Renal Disease (ARD) was noted in 10.9% of cases. Incidental findings at autopsy included two cases of renal cortical adenoma, one case each of renal cell carcinoma and medullary fibroma. Conclusion: Acute febrile illness does not just a reflect ion of co-existent pathologies but also directly contributes to mortality, possibly due to the risk of non renal complications like bleeding and sepsis. In the present study, the majority of cases were from medical units, in a young age group with a male predominance. Maximum cases had a short hospital stay. Several characteristic histopathological features in the kidney were identified in different clinical settings, aiding in pinpointing the cause of death. Autopsy findings of the kidney are indeed a treasure untouched and needs to be explored and warrants meticulous investigation.

A statistical study of postmortem heart weight in Chinese adults

IntroductionObjective assessment of cardiac hypertrophy in forensic pathology practice is of great significance for forensic pathologists, for whom reference values for normal heart weights are needed. Developed regions such as Europe, the United States, and Japan recalculate the weight of human organs at regular intervals, but in China, there has been no systematic calculation of the weights of human organs since 2006. AimsTo statistically analyse the heart weight of Chinese adults postmortem and obtain a reference range. Materials and Methods4170 adult autopsy reports were collected from 12 forensic departments in 10 provinces in China. The causes of death were classified by sex, and heart weight and the heart weight/body height ratio reference values were further calculated according to different body mass index and body heights. Finally, the cutoff value of cardiac hypertrophy in Chinese adults was calculated. ResultsIn the group of non-cardiovascular disease causes of death, the cardiac weight of the electric death group was higher, while the heart weight of the prolonged bed-rest group was significantly reduced. After the electric death and prolonged bed-rest groups were excluded, heart weight, the heart weight/body height ratio, and cutoff values for cardiac hypertrophy were further classified and analysed according to body mass index. The mean reference values for heart weight in men and women with normal weight status were 325.82 ± 41.60 g and 286.39 ± 44.84 g, and the heart weight/body height ratios were 1.95 ± 0.23 in men and 1.82 ± 0.27, respectively. The cutoff values for cardiac hypertrophy were 387.35 g for men and 346.80 g for women. ConclusionThe heart weight reference values of both sexes in this study were significantly higher than those in 2006, which is considered related to the development of China's economy and the improvement of people's living standards. This study also suggests the need for a new round of statistical surveys and updated data on the weight of other organs.

Error codes at autopsy to study potential biases in diagnostic error.

Current autopsy practice guidelines do not provide a mechanism to identify potential causes of diagnostic error (DE). We used our autopsy data registry to ask if gender or race were related to the frequency of diagnostic error found at autopsy. Our autopsy reports include International Classification of Diseases (ICD) 9 or ICD 10 diagnostic codes for major diagnoses as well as codes that identify types of error. From 2012 to mid-2015 only 2 codes were used: UNDOC (major undocumented diagnoses) and UNCON (major unconfirmed diagnoses). Major diagnoses contributed to death or would have been treated if known. Since mid-2015, codes included specific diagnoses, i.e. undiagnosed or unconfirmed myocardial infarction, infection, pulmonary thromboembolism, malignancy, or other diagnosis as well as cause of death. Adult autopsy cases from 2012 to 2019 were assessed for DE associated with reported sex or race (nonwhite or white). 528 cases were evaluated between 2012 and 2015 and 699 between 2015 and 2019. Major DEs were identified at autopsy in 65.9 % of cases from 2012 to 2015 and in 72.1 % from 2015 to 2019. From 2012 to 2015, female autopsy cases showed a greater frequency in 4 parameters of DE, i.e., in the total number of cases with any error (p=0.0001), in the number of cases with UNDOC errors (p=0.0038) or UNCON errors (p=0.0006), and in the relative proportions of total numbers of errors (p=0.0001). From 2015 to 2019 undocumented malignancy was greater among males (p=0.0065); no other sex-related error was identified. In the same period some DE parameters were greater among nonwhite than among white subjects, including unconfirmed cause of death (p=0.035), and proportion of total error diagnoses (p=0.0003), UNCON diagnoses (p=0.0093), and UNDOC diagnoses (p=0.035). Coding for DE at autopsy can identify potential effects of biases on diagnostic error.

Severe Obesity Associated With Pituitary Corticotroph Hyperplasia and Neoplasia

ObjectiveTo investigate the incidence of corticotroph hyperplasia (CH) or lymphocyte infiltration in the pituitary of patients with obesity. MethodsThe pituitary and adrenal glands from 161 adult autopsies performed between 2010 and 2019 at our institution were reviewed. The clinical history, body mass index (BMI), and cause of death were recorded. Routine hematoxylin and eosin staining, reticulin staining, and immunohistochemical staining for adrenocorticotropic hormone, CD3, and CD20 were performed. The results were analyzed using the Fisher and chi-square statistics. Decedents were separated into 4 groups based on BMI (kg/m2): (1) lean (BMI, <25.0), (2) overweight (BMI, 25.0-29.9), (3) obesity class I (BMI, 30.0-34.9), and (4) obesity classes II to III (BMI, >34.9). ResultsCH/neoplasia was identified in 44 of 161 pituitary glands. Four (9.1%) of 53 lean patients had pituitary lesions, whereas 27.3% (12) of overweight, 22.7% (10) of obesity class I, and 40.9% (18) of obesity class II patients had hyperplasia (P < .0001). Small corticotroph tumors were identified in 15 patients; only 1 was a lean patient, and the tumor was associated with the Crooke hyaline change of nontumorous corticotrophs. The presence of CH and neoplasia was associated with adrenal cortical hyperplasia and lipid depletion. Microscopic foci of T and B lymphocytes were identified in the pituitaries of patients in each weight category; no independent association between BMI and lymphocyte inflammation was found. ConclusionOur data indicate an association between CH/neoplasia and obesity. It remains unclear whether obesity is the cause or effect of adrenocorticotropic hormone and cortisol excess.

Biventricular false tendons

Biventricular false tendons

Neuronal nitric oxide synthase positive neurons in the human corpus callosum: a possible link with the callosal blood-oxygen-level dependent (BOLD) effect.

Brain functions have been investigated in the past decades via the blood-oxygen-level dependent (BOLD) effect using functional magnetic resonance imaging. One hypothesis explaining the BOLD effect involves the Nitric Oxide (NO) gaseous neurotransmitter, possibly released also by cells in the corpus callosum (CC). The eventual presence of NO releasing neurons and/or glial cells in the CC can be assessed by immunohistochemistry. Serial sections both from paraffin-embedded and frozen samples of CC obtained from adult human brains autopsy were studied with immunohistochemistry and immunofluorescence analysis, using an antibody against the neuronal isoform of Nitric Oxide Synthase (nNOS), the enzyme synthetizing the NO. The staining revealed the presence of many nNOS-immunopositive cells in the CC, shown to be neurons with immunofluorescence. Neuronal NOS-positive neurons presented different morphologies, were more numerous 4mm apart from the midline, and displayed a peak in the body of the CC. In some cases, they were located at the upper boundary of the CC, more densely packed in the proximity of the callosal arterioles. The significant presence of nNOS-immunopositive neurons within the commissure suggests their probable role in the CC neurovascular regulation in the adult brain and could explain the BOLD effect detected in human CC.

Normal organ weights and their correlations in a Tunisian population: Analysis of 696 adult autopsies

Normal organ weights and their correlations in a Tunisian population: Analysis of 696 adult autopsies

Elevated plasma levels of Krebs von den Lungen-6 and geographic appearance on high-resolution computed tomography are associated with diffuse alveolar damage in autopsy cases of acute respiratory distress syndrome: a retrospective study

BackgroundAlthough diffuse alveolar damage (DAD) is a histopathological hallmark of acute respiratory distress syndrome (ARDS), its detection without lung biopsy is challenging. In patients with ARDS, the specificity of the Berlin definition to diagnose DAD as a reference standard is not adequately high, making it difficult to adequately diagnose DAD. The purpose of this study was to investigate the relationship between DAD and clinical findings, including KL-6 and geographic appearance, in ARDS patients and to identify more specific diagnostic criteria for DAD.MethodsAmong all adult autopsy cases at a tertiary hospital in Japan between January 2006 and March 2021, patients with ARDS who met the Berlin definition criteria were included. The patients’ conditions were classified according to histopathological patterns as DAD or non-DAD, and clinical characteristics, laboratory data, and high-resolution computed tomography (HRCT) findings were compared between the two groups.ResultsDuring the study period, 27 met the Berlin definition (median age: 79 years, 19 men), of whom 18 (67%) had DAD and 9 (33%) did not. In the non-DAD group, histopathologic findings revealed organizing pneumonia in seven patients and pulmonary hemorrhage in two patients. On HRCT at onset, patients with DAD had more geographic appearance than those without DAD (89% vs. 44%). In patients with geographic appearance and elevated KL-6 (> 500 U/mL), the sensitivity and specificity for DAD diagnosis were 56% and 100%, respectively. All three patients with no geographic appearance and normal KL-6 did not have DAD.ConclusionsGeographic appearance on HRCT combined with KL-6 levels may predict the presence of DAD in patients with ARDS.

Digital histological morphometry of the human pineal gland in a postmortem study, with endocrine and neurological clinical implications.

The pineal gland is a small-sized, photo neuroendocrine organ in the midline of the brain that synthesises and secretes melatonin and serotonin. Chords and islands of pinealocytes constitute the secretory parenchyma, while glial tissue and calcifications represent degenerative changes. This study examined human postmortem pineal glands to microscopically assess morphological changes possibly associated with clinical data, by using digital techniques. A retrospective autopsy study has been performed on 72 paediatric and adult autopsy cases. The glands have been processed for histological analysis and immunohistochemical staining with synaptophysin (SYN), neuron-specific enolase (NSE), and neurofilament (NF). Slides were digitally scanned. Morphometric data were obtained using CaseViewer and ImageJ. The comorbidities used for correlation with morphometric data were obesity, type 2 diabetes, adrenal gland adenoma, goitre, chronic pancreatitis, arterial hypertension, and mixed dementia. Thirty-three females and 39 males were included in the study. Increased secretory parenchyma was found in patients with chronic pancreatitis, arterial hypertension, and adrenal gland adenoma. Reduced activity was found in patients with type 2 diabetes, obesity, advanced pineal calcification, mixed dementia, and old age. There were no changes associated with goitre, cachexia, or Willis's polygon atherosclerosis. No significant differences between gender were found. The activity of the pineal gland can be assessed by quantitative immunohistochemistry of neuroendocrine and structural pinealocyte markers and observation of glial tissue and calcifications. There is a need for further research to evaluate the clinical impact of these morphological changes on the neuroendocrine systems, with clinical implications in endocrinology, neurology, and even psychiatry. Digital techniques offer a more exact analysis of histological data.

Cardiac Metastasis From Solid Cancers: A 35-Year Single-Center Autopsy Study.

Cardiac metastases are more prevalent than primary cardiac tumors, and although rare, the incidence is anticipated to increase with the extended survival of oncology patients. To estimate the current incidence of cardiac metastasis from solid tumors in adult autopsies. Adult autopsy cases from 1984 through 2019 from patients diagnosed with any type of solid cancer were retrieved. The medical charts and pathologic autopsy data were reviewed in detail. A total of 1294 adult autopsies performed on patients diagnosed with any type of cancer within the past 35 years were reviewed. We found 124 secondary cardiac tumors. Eighty-five were due to cardiac involvement by solid tumors. Of these, 61 were true cardiac metastases of solid cancers. We focused on these 61 cases. The age range was 32 to 85 years. Forty-four patients were men and 17 were women. The lung was the most common primary site, with 21 cases (34.43%). The most frequent histologic type was carcinoma, with 54 cases (88.52%). The predominant layer of the heart involved was the pericardium, with 35 cases (57.38%). Twenty-one cases (34.43%) had pericardial effusion, with 4 being hemorrhagic. All cases had multiple extracardiac metastases, with 56 cases (91.8%) having distant metastases in 4 or more different organs. Cardiac metastasis is a rare occurrence, with an incidence of 4.71% (61 of 1294 cases) in our series. Lung cancer accounted for most of the cardiac metastases seen, and carcinomas were the most frequent histologic type. The pericardium was the most frequent location. Cardiac metastases occurred most frequently in cases of massive metastatic dissemination.

Postmortem survey of haemoglobin A1c, non-alcoholic steatohepatitis and liver fibrosis within a general population

AimsNon-alcoholic steatohepatitis (NASH), fatty liver disease and fibrosis are associated with diabetes mellitus and obesity. Previous autopsy series have reported prevalence of fatty liver disease to be 11%–24%. Recent studies,...

COVID-19 and the Brain: The Neuropathological Italian Experience on 33 Adult Autopsies.

Neurological symptoms are increasingly recognized in SARS-CoV-2 infected individuals. However, the neuropathogenesis remains unclear and it is not possible to define a specific damage pattern due to brain virus infection. In the present study, 33 cases of brain autopsies performed during the first (February–April 2020) and the second/third (November 2020–April 2021) pandemic waves are described. In all the cases, SARS-CoV-2 RNA was searched. Pathological findings are described and compared with those presently published.

Air Pollution, Ultrafine Particles, and Your Brain: Are Combustion Nanoparticle Emissions and Engineered Nanoparticles Causing Preventable Fatal Neurodegenerative Diseases and Common Neuropsychiatric Outcomes?

Exposure to particulate matter (PM) pollution damages the human brain. Fossil fuel burning for transportation energy accounts for a significant fraction of urban air and climate pollution. While current United States (US) standards limit PM ambient concentrations and emissions, they do not regulate explicitly ultrafine particles (UFP ≤ 100 nm in diameter). There is a growing body of evidence suggesting UFP may play a bigger role inflicting adverse health impacts than has been recognized, and in this perspective, we highlight effects on the brain, particularly of young individuals. UFP penetrate the body through nasal/olfactory, respiratory, gastrointestinal, placenta, and brain-blood barriers, translocating in the bloodstream and reaching the glymphatic and central nervous systems. We discuss one case study. The 21.8 million residents in the Metropolitan Mexico City (MMC) are regularly exposed to fine PM (PM2.5) above the US 12 μg/m3 annual average standards. Alzheimer's disease (AD), Parkinson's disease (PD), and TAR DNA-binding protein (TDP-43) pathologies and nanoparticles (NP ≤ 50 nm in diameter) in critical brain organelles have been documented in MMC children and young adult autopsies. MMC young residents have cognitive and olfaction deficits, altered gait and equilibrium, brainstem auditory evoked potentials, and sleep disorders. Higher risk of AD and vascular dementia associated with residency close to high traffic roadways have been documented. The US is not ready or prepared to adopt ambient air quality or emission standards for UFP and will continue to focus regulations only on the total mass of PM2.5 and PM10. Thus, this approach raises the question: are we dropping the ball? As research continues to answer the remaining questions about UFP sources, exposures, impacts, and controls, the precautionary principle should call us to accelerate and expand policy interventions to abate or eliminate UFP emissions and to mitigate UFP exposures. For residents of highly polluted cities, particularly in the developing world where there is likely older and dirtier vehicles, equipment, and fuels in use and less regulatory oversight, we should embark in a strong campaign to raise public awareness of the associations between high PM pollution, heavy traffic, UFP, NP, and neuropsychiatric outcomes, including dementia. Neurodegenerative diseases evolving from childhood in polluted, anthropogenic, and industrial environments ought to be preventable.

Pathology of pulmonary tuberculosis: has the tiger changed it's stripes?

:BackgroundIndia accounts for the highest number of TB cases globally (almost one-fifth of the global burden and almost two-thirds of the cases in South East Asia. Furthermore, the development of drug resistance of varying levels such as multi-drug resistant TB (MDR-TB), extensively-drug resistance TB (XDR-TB) and total-drug resistant TB (TDR-TB) has been on the increase, and now India also features in the 27 high-MDRTB-burden countries. Almost parallel to these developments, in the last few years, we have been encountering less common morphological forms of pulmonary TB (PTB) at autopsies. With these less common manifestations of the disease, we undertook this study to examine the changing trends in the morphological pattern of pulmonary TB over the recent years.MethodsIn this 3-year retrospective study, adult autopsy cases of PTB (that significantly contributed to the final cause of death) were studied in detail. HIV-positive cases were excluded from the study. The clinical details, gross appearances of the pulmonary lesions, microscopic pattern and Ziehl-Neelsen (ZN) staining were studied. Extrapulmonary involvement and causes of death were documented.ResultsPulmonary tuberculosis as a cause of death at autopsy was seen in 130 adult patients over 3 years. The age range was between 12 to 70 years. Anti-tuberculous therapy had been administered in 33 of them, but only one patient had taken complete therapy. Dyspnea was the commonest respiratory symptom seen in 51 cases (39.2%). Tuberculous bronchopneumonia was the commonest lesion (45.3%), miliary lesions (including localized miliary) accounted for 26% while fibrocavitary lesions (including the ones not involving apex) were seen in 13% cases. Other morphologies included nodular forms of TB (13%), localized miliary lesions (11.9%), and fibrocavitary lesions, not necessarily involving the apex (11.7% of all fibrocavitary cases), and predominant pleuritis with underlying lung involvement by TB in 1 case. Many cases of TB bronchopneumonia had a bronchocentric pattern of distribution (14.7%). On microscopy, caseating granulomas were seen in 93% cases, only caseation necrosis was seen in 4.6% cases, and necrotizing granulomas with abscess-like reaction in 11.5% cases. ZN staining was positive in 92 cases (70.7%). All the extrapulmonary lesions showed caseating granulomas histologically. The final cause of death was found to be primarily tuberculous in 106 cases (81.5%), whereas in 24 cases (19.5%) pulmonary TB was attributed to the secondary cause of death.ConclusionThe typical apical involvement of secondary TB was not seen in most of our cases. This could indicate a difference in the morphology and the pattern of lung involvement in recent years. The difference in gross morphology does not affect the pattern of involvement of the lung. In our study, we have observed both; a change in morphology, i.e., more cases of TB bronchopneumonia, and a change in the pattern of involvement like nodular forms, localized miliary forms, and fibrocavitary lesions not necessarily involving the apex. We postulate that this less common manifestation of pulmonary TB is closely related to the development of multi-drug and microbial resistance posing serious medical challenges.