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Orphanet Journal of Rare Diseases Jun 2023CSF1R mutations cause autosomal-dominant CSF1R-related leukoencephalopathy with axonal spheroids and pigmented glia (CSF1R-ALSP) and autosomal-recessive brain... (Review)
Review
CSF1R mutations cause autosomal-dominant CSF1R-related leukoencephalopathy with axonal spheroids and pigmented glia (CSF1R-ALSP) and autosomal-recessive brain abnormalities, neurodegeneration, and dysosteosclerosis (BANDDOS). The former is increasingly recognized, and disease-modifying therapy was introduced; however, literature is scarce on the latter. This review analyzes BANDDOS and discusses similarities and differences with CSF1R-ALSP.We systematically retrieved and analyzed the clinical, genetic, radiological, and pathological data on the previously reported and our cases with BANDDOS. We identified 19 patients with BANDDOS (literature search according to the PRISMA 2020 guidelines: n = 16, our material: n = 3). We found 11 CSF1R mutations, including splicing (n = 3), missense (n = 3), nonsense (n = 2), and intronic (n = 2) variants and one inframe deletion. All mutations disrupted the tyrosine kinase domain or resulted in nonsense-mediated mRNA decay. The material is heterogenous, and the presented information refers to the number of patients with sufficient data on specific symptoms, results, or performed procedures. The first symptoms occurred in the perinatal period (n = 5), infancy (n = 2), childhood (n = 5), and adulthood (n = 1). Dysmorphic features were present in 7/17 cases. Neurological symptoms included speech disturbances (n = 13/15), cognitive decline (n = 12/14), spasticity/rigidity (n = 12/15), hyperactive tendon reflex (n = 11/14), pathological reflexes (n = 8/11), seizures (n = 9/16), dysphagia (n = 9/12), developmental delay (n = 7/14), infantile hypotonia (n = 3/11), and optic nerve atrophy (n = 2/7). Skeletal deformities were observed in 13/17 cases and fell within the dysosteosclerosis - Pyle disease spectrum. Brain abnormalities included white matter changes (n = 19/19), calcifications (n = 15/18), agenesis of corpus callosum (n = 12/16), ventriculomegaly (n = 13/19), Dandy-Walker complex (n = 7/19), and cortical abnormalities (n = 4/10). Three patients died in infancy, two in childhood, and one case at unspecified age. A single brain autopsy evidenced multiple brain anomalies, absence of corpus callosum, absence of microglia, severe white matter atrophy with axonal spheroids, gliosis, and numerous dystrophic calcifications.In conclusion, BANDDOS presents in the perinatal period or infancy and has a devastating course with congenital brain abnormalities, developmental delay, neurological deficits, osteopetrosis, and dysmorphic features. There is a significant overlap in the clinical, radiological, and neuropathological aspects between BANDDOS and CSF1R-ALSP. As both disorders are on the same continuum, there is a window of opportunity to apply available therapy in CSF1R-ALSP to BANDDOS.
Topics: Humans; Neuroglia; Leukoencephalopathies; Brain; Mutation; Nervous System Malformations; Atrophy
PubMed: 37349768
DOI: 10.1186/s13023-023-02772-9 -
BMC Public Health Nov 2022Verbal autopsy (VA) has emerged as an increasingly popular technique to assign cause of death in parts of the world where the majority of deaths occur without proper...
BACKGROUND
Verbal autopsy (VA) has emerged as an increasingly popular technique to assign cause of death in parts of the world where the majority of deaths occur without proper medical certification. The purpose of this study was to examine the key characteristics of studies that have attempted to validate VA cause of death against an established cause of death.
METHODS
A systematic review was conducted by searching the MEDLINE, EMBASE, Cochrane-library, and Scopus electronic databases. Included studies contained 1) a VA component, 2) a validation component, and 3) original analysis or re-analysis. Characteristics of VA studies were extracted. A total of 527 studies were assessed, and 481 studies screened to give 66 studies selected for data extraction.
RESULTS
Sixty-six studies were included from multiple countries. Ten studies used an existing database. Sixteen studies used the World Health Organization VA questionnaire and 5 studies used the Population Health Metrics Research Consortium VA questionnaire. Physician certification was used in 36 studies and computer coded methods were used in 14 studies. Thirty-seven studies used high level comparator data with detailed laboratory investigations.
CONCLUSION
Most studies found VA to be an effective cause of death assignment method and compared VA cause of death to a high-quality established cause of death. Nonetheless, there were inconsistencies in the methodologies of the validation studies, and many used poor quality comparison cause of death data. Future VA validation studies should adhere to consistent methodological criteria so that policymakers can easily interpret the findings to select the most appropriate VA method.
PROSPERO REGISTRATION
CRD42020186886.
Topics: Humans; Autopsy; Research Design; Benchmarking; Certification; Databases, Factual
PubMed: 36447199
DOI: 10.1186/s12889-022-14628-1 -
Frontiers in Neuroscience 2023We critically review research findings on the unique changes in brain structure and cognitive function characteristic of Down syndrome (DS) and summarize the...
OBJECTIVES
We critically review research findings on the unique changes in brain structure and cognitive function characteristic of Down syndrome (DS) and summarize the similarities and differences with other neurodevelopmental disorders such as Williams syndrome, 22q11.2 deletion syndrome, and fragile X syndrome.
METHODS
We conducted a meta-analysis and systematic literature review of 84 studies identified by searching PubMed, Google Scholar, and Web of Science from 1977 to October 2022. This review focuses on the following issues: (1) specific neuroanatomic and histopathological features of DS as revealed by autopsy and modern neuroimaging modalities, (2) language and memory deficits in DS, (3) the relationships between these neuroanatomical and neuropsychological features, and (4) neuroanatomic and neuropsychological differences between DS and related neurodevelopmental syndromes.
RESULTS
Numerous post-mortem and morphometric neuroimaging investigations of individuals with DS have reported complex changes in regional brain volumes, most notably in the hippocampal formation, temporal lobe, frontal lobe, parietal lobe, and cerebellum. Moreover, neuropsychological assessments have revealed deficits in language development, emotional regulation, and memory that reflect these structural changes and are more severe than expected from general cognitive dysfunction. Individuals with DS also show relative preservation of multiple cognitive, linguistic, and social domains compared to normally developed controls and individuals with other neurodevelopmental disorders. However, all these neurodevelopment disorders exhibit substantial heterogeneity among individuals.
CONCLUSION
People with Down syndrome demonstrate unique neurodevelopmental abnormalities but cannot be regarded as a homogenous group. A comprehensive evaluation of individual intellectual skills is essential for all individuals with neurodevelopment disorders to develop personalized care programs.
PubMed: 37600012
DOI: 10.3389/fnins.2023.1225228 -
Forensic Science, Medicine, and... Jun 2021Although many clinical reports have been published, little is known about the pathological post-mortem findings from people who have died of the novel coronavirus...
Although many clinical reports have been published, little is known about the pathological post-mortem findings from people who have died of the novel coronavirus disease. The need for postmortem information is urgent to improve patient management of mild and severe illness, and treatment strategies. The present systematic review was carried out according to the Preferred Reporting Items for Systematic Review (PRISMA) standards. A systematic literature search and a critical review of the collected studies were conducted. An electronic search of PubMed, Science Direct Scopus, Google Scholar, and Excerpta Medica Database (EMBASE) from database inception to June 2020 was performed. We found 28 scientific papers; the total amount of cases is 341. The major histological feature in the lung is diffuse alveolar damage with hyaline membrane formation, alongside microthrombi in small pulmonary vessels. It appears that there is a high incidence of deep vein thrombosis and pulmonary embolism among COVID-19 decedents, suggesting endothelial involvement, but more studies are needed. A uniform COVID-19 post-mortem diagnostic protocol has not yet been developed. In a time in which international collaboration is essential, standardized diagnostic criteria are fundamental requirements.
Topics: Alveolar Epithelial Cells; Autopsy; Brain; COVID-19; Fibrin; Fibroblasts; Humans; Kidney; Leukocytes, Mononuclear; Lung; Myositis; Respiratory Mucosa; Thrombosis
PubMed: 33026628
DOI: 10.1007/s12024-020-00310-8 -
International Journal of Environmental... Feb 2022A ligature mark is a common injury in cases of hanging or strangulation. Estimation of age and vitality of the ligature mark can be crucial for differentiating... (Review)
Review
BACKGROUND
A ligature mark is a common injury in cases of hanging or strangulation. Estimation of age and vitality of the ligature mark can be crucial for differentiating antemortem and postmortem wounds and to distinguish between simulated suicidal hanging or accidental strangulation to conceal a crime and not simulated events. The immunohistochemistry has been recommended by several Authors as a reliable tool to determine whether an injury was sustained during life or not. Unfortunately, no general agreement on the immunohistochemical markers to be used has been found among the scientific community. The aim of the study was to detect the type and function of the immunohistochemical markers useful in the assessment of the vitality and age of the ligature marks for routine diagnostics.
METHODS
Papers available on Pubmed, Scopus, and Web of Science were reviewed according to the PRISMA statement.
RESULTS
Only eight papers satisfied all the following inclusion criteria: full texts in English dealing with human ligature marks and immunohistochemistry published on impacted or indexed scientific journals.
CONCLUSIONS
The assessment of the vitality of a ligature mark is still a challenging topic in forensic science. Under ideal conditions and in compliance with autopsy protocols, the diagnosis of death by hanging or strangulation on fresh bodies can be better supported by autopsy findings other than a ligature mark. The validation of immunohistochemical markers on large series could be of help in doubtful cases and differential diagnoses.
Topics: Asphyxia; Autopsy; Humans; Skin; Suicide
PubMed: 35206225
DOI: 10.3390/ijerph19042035 -
Frontiers in Cardiovascular Medicine 2021Although thrombosis events have been reported in patients with coronavirus disease 2019 (COVID-19), the association between thrombosis and COVID-19-related critical...
BACKGROUND
Although thrombosis events have been reported in patients with coronavirus disease 2019 (COVID-19), the association between thrombosis and COVID-19-related critical status or risk of mortality in COVID-19 has been inconsistent.
OBJECTIVE
We conducted a meta-analysis of reports assessing the association between thrombosis and the prognosis of COVID-19.
METHODS
The EMBASE, Ovid-MEDLINE, and Web of Science databases were searched up to December 9, 2021, and additional studies were retrieved manual searching. Studies were included if they reported the risk of COVID-19-related critical status or COVID-19-related mortality in relation to thrombosis. The related data were extracted by two authors independently, and a random effects model was conducted to pool the odds ratios (ORs). In addition, stratified analyses were conducted to evaluate the association.
RESULTS
Among 6,686 initially identified studies, we included 25 studies published in 2020 and 2021, with a total of 332,915 patients according to predefined inclusion criteria. The associations between thrombosis and COVID-19-related mortality and COVID-19-related critical status were significant, with ORs of 2.61 (95% CI, 1.91-3.55, < 0.05) and 2.9 (95% CI, 1.6-5.24, < 0.05), respectively. The results were statistically significant and consistent in stratified analyses.
CONCLUSIONS
Thrombosis is associated with an increased risk of mortality and critical status induced by COVID-19. Further prospective studies with large sample sizes are required to establish whether these associations are causal by considering more confounders and to clarify their mechanisms.Observational studies cannot prove causality. However, autopsy studies show thrombosis events preceding COVID-19-related deaths. The results of this meta-analysis reported that thrombosis was associated with a 161% increased risk of mortality from COVID-19 and a 190% increased risk of COVID-19-related critical status. The type of thrombosis included in the original studies also seemed to be related to the results.
PubMed: 35146009
DOI: 10.3389/fcvm.2021.819318 -
Forensic Science International Dec 2023Vertebrate scavengers frequently affect forensic casework by feeding on human remains or by scattering body parts and bones. Therefore, animal activity can influence... (Review)
Review
Vertebrate scavengers frequently affect forensic casework by feeding on human remains or by scattering body parts and bones. Therefore, animal activity can influence complete recovery of bodies, trauma analysis, and the estimation of the postmortem interval (PMI), potentially hampering identification of the deceased and elucidation of the perimortem circumstances. Experimental research is well suited to investigate scavengers and their impact on carcasses over time, generating knowledge on the forensic relevance of certain scavenger species or communities. However, there are currently no systematised standards to conduct these investigations with a forensic focus, impeding comparison and synthesis of the studies. In our work, we performed a systematic literature review and found 79 publications featuring terrestrial experiments on vertebrate scavenging and/or scattering within a forensic context. We extracted 21 variables describing the study environment, experimental design and the specimens. The results show that there is considerable inconsistency in the study designs and that some of the variables are insufficiently reported. We point out research questions and areas that require attention in future studies, stressing the importance of infrequently mentioned or applied variables. Furthermore, we recommend guidelines to include and report a list of variables in forensic scavenging and scattering experiments. These guidelines will help standardising future research in the field, facilitating inter-study consolidation of results and conclusions, and consequently, inform forensic casework.
Topics: Animals; Humans; Postmortem Changes; Feeding Behavior; Forensic Anthropology; Cadaver; Autopsy
PubMed: 37931469
DOI: 10.1016/j.forsciint.2023.111862 -
Journal of Clinical Medicine Mar 2023Although COVID-19 may cause various and multiorgan diseases, few research studies have examined the postmortem pathological findings of SARS-CoV-2-infected individuals... (Review)
Review
Although COVID-19 may cause various and multiorgan diseases, few research studies have examined the postmortem pathological findings of SARS-CoV-2-infected individuals who died. Active autopsy results may be crucial for understanding how COVID-19 infection operates and preventing severe effects. In contrast to younger persons, however, the patient's age, lifestyle, and concomitant comorbidities might alter the morpho-pathological aspects of the damaged lungs. Through a systematic analysis of the available literature until December 2022, we aimed to provide a thorough picture of the histopathological characteristics of the lungs in patients older than 70 years who died of COVID-19. A thorough search was conducted on three electronic databases (PubMed, Scopus, and Web of Science), including 18 studies and a total of 478 autopsies performed. It was observed that the average age of patients was 75.6 years, of which 65.4% were men. COPD was identified in an average of 16.7% of all patients. Autopsy findings indicated significantly heavier lungs, with an average weight of the right lung of 1103 g, while the left lung mass had an average weight of 848 g. Diffuse alveolar damage was a main finding in 67.2% of all autopsies, while pulmonary edema had a prevalence of between 50% and 70%. Thrombosis was also a significant finding, while some studies described focal and extensive pulmonary infarctions in 72.7% of elderly patients. Pneumonia and bronchopneumonia were observed, with a prevalence ranging from 47.6% to 89.5%. Other important findings described in less detail comprise hyaline membranes, the proliferation of pneumocytes and fibroblasts, extensive suppurative bronchopneumonic infiltrates, intra-alveolar edema, thickened alveolar septa, desquamation of pneumocytes, alveolar infiltrates, multinucleated giant cells, and intranuclear inclusion bodies. These findings should be corroborated with children's and adults' autopsies. Postmortem examination as a technique for studying the microscopic and macroscopic features of the lungs might lead to a better knowledge of COVID-19 pathogenesis, diagnosis, and treatment, hence enhancing elderly patient care.
PubMed: 36902856
DOI: 10.3390/jcm12052070 -
PloS One 2021Civil registration and vital statistics (CRVS) systems do not produce comprehensive data on maternal and child deaths in most low- and middle-income countries (LMICs),...
BACKGROUND
Civil registration and vital statistics (CRVS) systems do not produce comprehensive data on maternal and child deaths in most low- and middle-income countries (LMICs), with most births and deaths which occur outside the formal health system going unreported. Community-based death reporting, investigation and review processes are being used in these settings to augment official registration of maternal and child deaths and to identify death-specific factors and associated barriers to maternal and childcare. This study aims to review how community-based maternal and child death reporting, investigation and review processes are carried out in LMICs.
METHODS
We conducted a scoping review of the literature published in English from January 2013 to November 2020, searching PubMed, EMBASE, PsycINFO, Joanna Briggs, The Cochrane Library, EBM reviews, Scopus, and Web of Science databases. We used descriptive analysis to outline the scope, design, and distribution of literature included in the study and to present the content extracted from each article. The scoping review is reported following the PRISMA reporting guideline for systematic reviews.
RESULTS
Of 3162 screened articles, 43 articles that described community-based maternal and child death review processes across ten countries in Africa and Asia were included. A variety of approaches were used to report and investigate deaths in the community, including identification of deaths by community health workers (CHWs) and other community informants, reproductive age mortality surveys, verbal autopsy, and social autopsy. Community notification of deaths by CHWs complements registration of maternal and child deaths missed by routinely collected sources of information, including the CRVS systems which mostly capture deaths occurring in health facilities. However, the accuracy and completeness of data reported by CHWs are sub-optimal.
CONCLUSIONS
Community-based death reporting complements formal registration of maternal and child deaths in LMICs. While research shows that community-based maternal and child death reporting was feasible, the accuracy and completeness of data reported by CHWs are sub-optimal but amenable to targeted support and supervision. Studies to further improve the process of engaging communities in the review, as well as collection and investigation of deaths in LMICs, could empower communities to respond more effectively and have a greater impact on reducing maternal and child mortality.
Topics: Africa; Asia; Autopsy; Child; Child Mortality; Community Health Workers; Developing Countries; Female; Humans; Maternal Mortality; Pregnancy; Research Report; Residence Characteristics
PubMed: 33725013
DOI: 10.1371/journal.pone.0248143 -
Surgical Neurology International 2021Patients with computed tomography (CT) findings consistent with subarachnoid hemorrhage without evidence of hemorrhage following autopsy or cerebrospinal fluid testing... (Review)
Review
BACKGROUND
Patients with computed tomography (CT) findings consistent with subarachnoid hemorrhage without evidence of hemorrhage following autopsy or cerebrospinal fluid testing are termed to have pseudosubarachnoid hemorrhage (pSAH).
METHODS
A systematic review of literature was conducted based on the preferred reporting items for systematic reviews and meta-analysis statement. Studies were evaluated for associated cause of pSAH, imaging modality used in assessment, method of confirmatory testing, and clinical outcome.
RESULTS
Fifty studies were included in qualitative analysis including 197 cases of pSAH. Systematic review revealed 23 studies including 110 patients with pSAH attributed to hypoxic-ischemic brain injury following cardiac arrest. Three studies were included in meta-analysis that quantitatively analyzed differences in CT densities in patients with pSAH and true subarachnoid hemorrhage (true SAH). A random effects model meta-analysis showed a statistically significant decrease in densities in the Sylvian fissure in patients with pSAH compared to true SAH and a statistically significant decrease in densities in adjacent parenchyma in patients with pSAH compared to true SAH. Systematic review further revealed 32 patients with pSAH associated with spontaneous intracranial hypotension, 11 patients with pSAH related to infectious etiologies, 15 patients with pSAH associated with subdural hemorrhage, 20 cases of pSAH related to hyperhemoglobinemia, 2 cases related to valproate toxicity, and individual cases related to hyponatremia, diabetic ketoacidosis, sudden infant death syndrome, cerebellar infarction, and dialysis disequilibrium syndrome.
CONCLUSION
This study is the first systematic review of causes, diagnostic modalities, and outcomes in patients who present with pSAH. A diagnosis of pSAH may be considered following assessment of CT densities following cardiac arrest.
PubMed: 33598345
DOI: 10.25259/SNI_905_2020