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JACC. Case Reports Jul 2024The incidence of coronary artery aneurysm is between 1.4% and 4.9% based on autopsy or angiographic series. Mycotic coronary arteries aneurysms are very rare and...
The incidence of coronary artery aneurysm is between 1.4% and 4.9% based on autopsy or angiographic series. Mycotic coronary arteries aneurysms are very rare and represent less than 3% of all coronary aneurysms. We report the case of a patient who presented with multiple coronary mycotic aneurysms.
PubMed: 38912320
DOI: 10.1016/j.jaccas.2024.102385 -
Clinica Chimica Acta; International... Jun 2024The number of xylazine-involved overdose deaths tremendously increased from 2019 onwards in the US. This is due to the "tranq-dope" trend consisting in mixing opioids...
BACKGROUND AND AIMS
The number of xylazine-involved overdose deaths tremendously increased from 2019 onwards in the US. This is due to the "tranq-dope" trend consisting in mixing opioids with the sedative to reduce drug manufacturing costs and enhance their effects. In this study, we report the first fatality involving xylazine-adulterated heroin in the EU.
MATERIALS AND METHODS
The subject was a 33-year-old Caucasian male with a documented history of drug abuse who was found dead in a public area with puncture marks at the elbow. Peripheral blood and urine were collected at the autopsy and analyzed by liquid chromatography-high-resolution tandem mass spectrometry (LC-HRMS/MS) after protein precipitation.
RESULTS
6-Monoacetylmorphine, total/free morphine, and codeine blood concentrations of 20.3, 236/105, and 38.3 ng/mL, respectively, indicated recent heroin consumption. Methadone blood concentration was below 10 ng/mL. Alprazolam, nordiazepam, and flurazepam blood concentrations were 23.9, 61.4, and 55.0 ng/mL, respectively. Benzoylecgonine blood concentration was below 5 ng/mL. Xylazine blood and urine concentrations were 105 and 72.6 ng/mL, respectively.
CONCLUSION
The combination of central nervous system depressants, i.e., opioids, benzodiazepines, and xylazine, was the principal cause of death by cardiorespiratory failure. The case was promptly reported to the UE Early Warning System on drugs.
PubMed: 38909977
DOI: 10.1016/j.cca.2024.119826 -
PloS One 2024To evaluate the diagnostic accuracy of the aortic dissection detection risk score (ADD-RS) used alone or in combination with D-dimer for detecting acute aortic syndrome... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To evaluate the diagnostic accuracy of the aortic dissection detection risk score (ADD-RS) used alone or in combination with D-dimer for detecting acute aortic syndrome (AAS) in patients presenting with symptoms suggestive of AAS.
METHODS
We searched MEDLINE, EMBASE, and the Cochrane Library from inception to February 2024. Additionally, the reference lists of included studies and other systematic reviews were thoroughly searched. All diagnostic accuracy studies that assessed the use of ADD-RS alone or with D-Dimer for diagnosing AAS compared with a reference standard test (e.g. computer tomographic angiography (CTA), ECG-gated CTA, echocardiography, magnetic resonance angiography, operation, or autopsy) were included. Two reviewers independently selected and extracted data. Risk of bias was appraised using QUADAS-2 tool. Data were synthesised using hierarchical meta-analysis models.
RESULTS
We selected 13 studies from the 2017 citations identified, including six studies evaluating combinations of ADD-RS alongside D-dimer>500ng/L. Summary sensitivities and specificities (95% credible interval) were: ADD-RS>0 94.6% (90%, 97.5%) and 34.7% (20.7%, 51.2%), ADD-RS>1 43.4% (31.2%, 57.1%) and 89.3% (80.4%, 94.8%); ADD RS>0 or D-Dimer>500ng/L 99.8% (98.7%, 100%) and 21.8% (12.1%, 32.6%); ADD RS>1 or D-Dimer>500ng/L 98.3% (94.9%, 99.5%) and 51.4% (38.7%, 64.1%); ADD RS>1 or ADD RS = 1 with D-dimer>500ng/L 93.1% (87.1%, 96.3%) and 67.1% (54.4%, 77.7%).
CONCLUSIONS
Combinations of ADD-RS and D-dimer can be used to select patients with suspected AAS for imaging with a range of trade-offs between sensitivity (93.1% to 99.8%) and specificity (21.8% to 67.1%).
Topics: Humans; Fibrin Fibrinogen Degradation Products; Aortic Dissection; Syndrome; Sensitivity and Specificity; Acute Disease; Computed Tomography Angiography; Acute Aortic Syndrome
PubMed: 38905181
DOI: 10.1371/journal.pone.0304401 -
BMJ Open Jun 2024Childhood pneumonia is a leading cause of morbidity and mortality among children aged 2-59 months, particularly in low-income and middle-income countries (LMICs), where... (Observational Study)
Observational Study
Understanding the outcome and management of children aged 2-59 months with chest indrawing pneumonia: a study protocol for an observational study in Ethiopia, India, Nigeria, Pakistan, Uganda and Zambia.
INTRODUCTION
Childhood pneumonia is a leading cause of morbidity and mortality among children aged 2-59 months, particularly in low-income and middle-income countries (LMICs), where healthcare providers face significant challenges in diagnosing and treating childhood pneumonia. Many LMICs have taken steps to address this issue by revising their national policies and aligning them with WHO's revised guidelines for pneumonia management. These revised guidelines aim to facilitate the outpatient management of children aged 2-59 months chest indrawing pneumonia. Despite these efforts, there is limited empirical evidence regarding the management and outcomes of these children in primary-level healthcare settings. This study aims to assess the survival status of children aged 2-59 months with chest indrawing pneumonia presenting at primary healthcare facilities.
METHODS AND ANALYSIS
A prospective, observational cohort study will be conducted in Ethiopia, Nigeria, Uganda, Zambia, India and Pakistan on children aged 2-59 months presenting at selected primary-level healthcare facilities with chest indrawing pneumonia. Eligible participants will be enrolled and managed by facility healthcare providers who are trained in Integrated Management of Childhood Illness and will be followed up on day 15 to record the treatment-related information and vital status, including conducting verbal autopsies in case of child death. The sample size for each site will be 310. The analysis will involve exploring site-specific trends before conducting a pooled analysis of de-identified data from all sites. The first data collection started at the Ethiopian site in September 2022, followed by other sites. The data collection will continue until June 2025.
ETHICS AND DISSEMINATION
The study protocol, enrolment forms and consent forms will undergo ethical review by the Institutional Review Boards of the University of Gondar, Gondar, Ethiopia; the INCLEN Trust International Independent Ethics Committee, New Delhi, India; Ethical Review Committee of the University of Ibadan, Ethical Review Committees of Lagos State and Ethical Review Committee of University College London, UK; Institutional Review Board, International Research Force, Islamabad, Pakistan; Institutional Review Board, People's Primary Healthcare Initiative-Sindh, Karachi and National Bioethics Committee, Islamabad, Pakistan; Makerere University School of Biomedical Sciences Research Ethical Committee, Kampala, Uganda; University of Zambia Biomedical Research Ethics committee, Lusaka, Zambia and Ethical Review Committee of WHO, Geneva, Switzerland. Ethical procedures include WHO and local review board evaluations, parental consent in the local/national language, permits enrolment, follow-up, and, if required, clinical video recording for children with chest indrawing pneumonia, ensuring their eligibility. Adherence to local regulations encompasses precollection ethical approvals, risk management strategies and secure, de-identified data storage. Findings will be disseminated through seminars, publications and meetings, engaging diverse stakeholders to foster collaborations.
TRIAL REGISTRATION NUMBER
ISRCTN12687253.
Topics: Humans; Infant; Pneumonia; Child, Preschool; Prospective Studies; Uganda; Pakistan; India; Female; Observational Studies as Topic; Male; Zambia; Nigeria; Ethiopia
PubMed: 38904143
DOI: 10.1136/bmjopen-2024-084350 -
Respirology Case Reports Jun 2024Amyloidosis is a pathological deposition disease that causes a spectrum of organ dysfunction. Pulmonary involvement is generally associated with immunoglobulin light...
Amyloidosis is a pathological deposition disease that causes a spectrum of organ dysfunction. Pulmonary involvement is generally associated with immunoglobulin light chain type (AL) amyloid. Transthyretin (ATTR) amyloid build up in the lung is thought to be a senile disease observed usually as a finding at autopsy. We describe a case of pulmonary ATTR amyloidosis with concurrent mycobacterial tuberculosis infection.
PubMed: 38903946
DOI: 10.1002/rcr2.1418 -
Pathology, Research and Practice Jun 2024The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), presents diverse clinical manifestations and...
INTRODUCTION
The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), presents diverse clinical manifestations and multi-organ involvement. This study aimed to evaluate the extra-pulmonary histopathological patterns underpinning COVID-19-induced lesions in cardiac, hepatic, renal, brainstem, and splenic tissues.
MATERIALS AND METHODS
The research involved conventional forensic autopsies conducted between April 2020 and April 2021 on individuals with confirmed SARS-CoV-2 infection in Cluj-Napoca, Romania. Tissues were processed and stained for histological examination. Differences in patients with and without diffuse alveolar damage (DAD) were evaluated.
RESULTS
In our study of 79 COVID-19 autopsies conducted on unvaccinated patients besides lung involvement, the patients had histological changes in at least two out of five (brain, heart, liver, kidney, and spleen) organs. Notable findings include hepatitis observed in 46.8 % of cases, 21.5 % with lobular hepatitis, and 41.8 % with liver steatosis. Additionally, 69.6 % exhibited acute tubular necrosis, and 55.7 % had varying degrees of splenic lymphocyte depletion. Almost 41 % of cases had pericardial effusion, 36.7 % myocarditis, 24.1 % myocardial infarction, and 12.7 % of cases had encephalitis. Acute tubular necrosis (78.6 %) was the most frequent histopathological finding observed in patients with DAD. Myocarditis was described in 45.9 % of the patients without DAD.
DISCUSSION
The autopsy findings in our cohort of COVID-19 victims align with international scientific literature. Distinguishing viral-induced myocarditis, encephalitis, hepatitis, or systemic inflammatory syndrome remains challenging.
CONCLUSION
Post-mortem analysis identified lesions associated with SARS-CoV-2 in multiple organs, highlighting the systemic nature of the virus and emphasizing the need for continued research into organ-specific damage and long-term sequelae of COVID-19.
PubMed: 38901140
DOI: 10.1016/j.prp.2024.155373 -
Cell Reports. Medicine Jun 2024Small-cell lung cancer (SCLC) is the most fatal form of lung cancer. Intratumoral heterogeneity, marked by neuroendocrine (NE) and non-neuroendocrine (non-NE) cell...
Small-cell lung cancer (SCLC) is the most fatal form of lung cancer. Intratumoral heterogeneity, marked by neuroendocrine (NE) and non-neuroendocrine (non-NE) cell states, defines SCLC, but the cell-extrinsic drivers of SCLC plasticity are poorly understood. To map the landscape of SCLC tumor microenvironment (TME), we apply spatially resolved transcriptomics and quantitative mass spectrometry-based proteomics to metastatic SCLC tumors obtained via rapid autopsy. The phenotype and overall composition of non-malignant cells in the TME exhibit substantial variability, closely mirroring the tumor phenotype, suggesting TME-driven reprogramming of NE cell states. We identify cancer-associated fibroblasts (CAFs) as a crucial element of SCLC TME heterogeneity, contributing to immune exclusion, and predicting exceptionally poor prognosis. Our work provides a comprehensive map of SCLC tumor and TME ecosystems, emphasizing their pivotal role in SCLC's adaptable nature, opening possibilities for reprogramming the TME-tumor communications that shape SCLC tumor states.
Topics: Tumor Microenvironment; Humans; Small Cell Lung Carcinoma; Lung Neoplasms; Cancer-Associated Fibroblasts; Neuroendocrine Tumors; Neuroendocrine Cells; Female; Male; Prognosis
PubMed: 38897168
DOI: 10.1016/j.xcrm.2024.101610 -
Acta Neuropathologica Jun 2024TAR DNA-binding protein 43 (TDP-43) is an RNA binding protein found within ribonucleoprotein granules tethered to lysosomes via annexin A11. TDP-43 protein forms...
TAR DNA-binding protein 43 (TDP-43) is an RNA binding protein found within ribonucleoprotein granules tethered to lysosomes via annexin A11. TDP-43 protein forms inclusions in many neurodegenerative diseases including amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP) and limbic predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC). Annexin A11 is also known to form aggregates in ALS cases with pathogenic variants in ANXA11. Annexin A11 aggregation has not been described in sporadic ALS, FTLD-TDP or LATE-NC cases. To explore the relationship between TDP-43 and annexin A11, genetic analysis of 822 autopsy cases was performed to identify rare ANXA11 variants. In addition, an immunohistochemical study of 368 autopsy cases was performed to identify annexin A11 aggregates. Insoluble annexin A11 aggregates which colocalize with TDP-43 inclusions were present in all FTLD-TDP Type C cases. Annexin A11 inclusions were also seen in a small proportion (3-6%) of sporadic and genetic forms of FTLD-TDP types A and B, ALS, and LATE-NC. In addition, we confirm the comingling of annexin A11 and TDP-43 aggregates in an ALS case with the pathogenic ANXA11 p.G38R variant. Finally, we found abundant annexin A11 inclusions as the primary pathologic finding in a case of progressive supranuclear palsy-like frontotemporal dementia with prominent striatal vacuolization due to a novel variant, ANXA11 p.P75S. By immunoblot, FTLD-TDP with annexinopathy and ANXA11 variant cases show accumulation of insoluble ANXA11 including a truncated fragment. These results indicate that annexin A11 forms a diverse and heterogeneous range of aggregates in both sporadic and genetic forms of TDP-43 proteinopathies. In addition, the finding of a primary vacuolar annexinopathy due to ANXA11 p.P75S suggests that annexin A11 aggregation is sufficient to cause neurodegeneration.
Topics: Humans; Aged; Annexins; Female; Male; DNA-Binding Proteins; Frontotemporal Lobar Degeneration; Middle Aged; Aged, 80 and over; TDP-43 Proteinopathies; Neurodegenerative Diseases; Amyotrophic Lateral Sclerosis; Inclusion Bodies; Brain; Protein Aggregation, Pathological
PubMed: 38896345
DOI: 10.1007/s00401-024-02753-7 -
Diagnostics (Basel, Switzerland) May 2024Neck infections are often prone to being underestimated and can manifest insidiously. The spread of infection can lead to translocation into thoracic areas, causing... (Review)
Review
Neck infections are often prone to being underestimated and can manifest insidiously. The spread of infection can lead to translocation into thoracic areas, causing descending necrotizing mediastinitis (DNM). However, the application of the post-mortem approach in such cases is not well-described in the literature. A literature review was carried out according to the PRISMA methods. Nine papers were included in the final review, revealing different levels of involvement of neck layers that can be linked to different causes. Expertise with respect to the anatomy of the fasciae and spaces of the neck enables an understanding of the pathogenesis of DNM. However, a clear autoptic description was not provided in any of the articles. Therefore, we also employed a practical post-mortem approach to cases of death due to DNM. It is fundamental for pathologists to identify the exact head and neck structures involved. Providing dissectors with support from an otolaryngologist could be useful. This paper could help address such difficult cases.
PubMed: 38893677
DOI: 10.3390/diagnostics14111150