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COMORBIDITY OF TYPE 1 DIABETES MELLITUS WITH OTHER CHRONIC PATHOLOGY IN CHILDREN.

Georgian Med News 2021 Mar(312):78-82

1V. Karazin Kharkiv National University, School of Medicine; 2SI "Institute of Health of Children and Adolescents of the National Academy of Medical Sciences of Ukraine", Kharkiv, Ukraine.

In this study was to investigate the сoexistence of diabetes mellitus type 1 with other chronic pathology in children and adolescents and their impact on the course of diabetes mellitus type 1 (DM1). The 88 children from 3 to 17 years who had DM1 were observed. The study was conducted by survey with the aim of finding risk factors and associated comorbidties with a questionnaire-based, objective-subjective study. Read More

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CLINICAL, PHARMACOTHERAPEUTIC AND BIORHYTHMOLOGICAL PECULIARITIES OF DEPRESSIVE DISORDERS, COMORBID WITH CARDIOVASCULAR PATHOLOGY.

Georgian Med News 2021 Mar(312):57-61

2Communal Еnterprise «Regional Institution for Providing Psychiatric Care of Poltava Regional Council», Ukraine.

The spread of depressive disorders is extra high nowadays. Depressive disorders are widespread mental disorders in the structure of mental pathology, both causes of psychiatrists' visit, and causes of medical aid. The presence of depressive syndrome in patients with cardiovascular system leads to deterioration patient's condition and adaptive abilities and aggravates somatic abnormality. Read More

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Are they too perfect to eat healthy? Association between eating disorder symptoms and perfectionism in adolescent rhythmic gymnasts.

Eat Behav 2021 May 1;41:101514. Epub 2021 May 1.

School of Physical Education & Sport Science, National & Kapodistrian University of Athens, Greece.

Objective: Eating disorders are associated with perfectionism in adults, but evidence is lacking in adolescent competitive athletes. This study examined eating disorder symptoms and perfectionism in a sample of 13-15 years old, adolescent rhythmic gymnasts.

Methods: Eighty-nine female rhythmic gymnasts (41 international and 48 recreational level gymnasts), completed the Eating Attitudes Tests 26 (EAT-26), the Sport Perfectionism Questionnaire (SPQ), the Social Desirability Scale (SDS) and provided information on their training. Read More

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Unclassified serrated lesion of the colon observed by magnifying endoscopy.

Gastrointest Endosc 2021 May 5. Epub 2021 May 5.

Division of Gastroenterology, Department of Internal Medicine.

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Sar1b mutant mice recapitulate gastrointestinal abnormalities associated with chylomicron retention disease.

J Lipid Res 2021 May 5:100085. Epub 2021 May 5.

Research Center, CHU Ste-Justine; Departments of Pharmacology & Physiology,; Nutrition. Electronic address:

Chylomicron retention disease (CRD) is an autosomal recessive disorder associated with biallelic Sar1b mutations leading to defects in intracellular chylomicron (CM) trafficking and secretion. To date, a direct cause-effect relationship between CRD and Sar1b mutation has not been established, but genetically modified animal models provide an opportunity to elucidate unrecognized aspects of these mutations. To examine the physiological role and molecular mechanisms of Sar1b function, we generated mice expressing either a targeted deletion or mutation of human Sar1b using the CRISPR/Cas9 system. Read More

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Non-thermal plasma-induced DMPO-OH yields hydrogen peroxide.

Arch Biochem Biophys 2021 May 5:108901. Epub 2021 May 5.

Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Showa-Ku, Nagoya, 466-8550, Japan; Center for Low-temperature Plasma Sciences, Nagoya University, Chikusa-ku, Nagoya, 464-8603, Japan. Electronic address:

Recent developments in electronics have enabled the medical applications of non-thermal plasma (NTP), which elicits reactive oxygen species (ROS) and reactive nitrogen species (RNS), such as hydroxyl radical (OH), hydrogen peroxide (HO), singlet oxygen (O), superoxide (O), ozone, and nitric oxide at near-physiological temperatures. In preclinical studies or human clinical trials, NTP promotes blood coagulation, eradication of bacterial, viral and biofilm-related infections, wound healing, and cancer cell death. To elucidate the solution-phase biological effects of NTP in the presence of biocompatible reducing agents, we employed electron paramagnetic resonance (EPR) spectroscopy to quantify OH using a spin-trapping probe, 5,5-dimethyl-1-pyrroline-N-oxide (DMPO); O using a fluorescent probe; and O and HO using luminescent probes in the presence of thiols or tempol. Read More

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ACE-2 down-regulation may act as a transient molecular disease causing RAAS dysregulation and tissue damage in the microcirculatory environment among COVID-19 patients.

Am J Pathol 2021 May 5. Epub 2021 May 5.

Department of Pathology, Faculty of Medicine, Fluminense Federal University, Niteroi, Rio de Janeiro, Brazil.

SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the etiological agent of COVID-19 (coronavirus disease 2019) and the cause of the current pandemic, produces multiform manifestations throughout the body, causing indiscriminate damage to multiple organ systems, particularly the lungs, heart, brain, kidney, and vasculature. The aim of this review is to provide a new look at the data already available for COVID-19, exploring it as a transient molecular disease that causes negative regulation of ACE-2 (angiotensin-converting enzyme 2) and, consequently, deregulates the renin-angiotensin-aldosterone system (RAAS), promoting important changes in the microcirculatory environment. In addition, the authors seek to demonstrate how these microcirculatory changes may be responsible for the wide variety of injury mechanisms observed in different organs in this disease. Read More

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Biallelic mutations in RNF220 cause laminopathies featuring leukodystrophy, ataxia and deafness.

Brain 2021 May 8. Epub 2021 May 8.

Genetics and Rare Diseases Research Division, Bambino Gesù Children's Hospital, IRCCS, 00146 Rome, Italy.

Leukodystrophies are a heterogeneous group of rare inherited disorders that involve preferentially the white matter of the central nervous system (CNS). These conditions are characterized by a primary glial cell and myelin sheath pathology of variable etiology, which causes secondary axonal degeneration, generally emerging with disease progression. Whole exome sequencing performed in 5 large consanguineous nuclear families allowed to identify homozygosity for two recurrent missense variants affecting highly conserved residues of RNF220 as the causative event underlying a novel form of leukodystrophy with ataxia and sensorineural deafness. Read More

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Serum angiopoietin-2 levels in dogs with splenic haemangiosarcoma, haemangioma, and splenitis.

Acta Vet Hung 2021 May 5. Epub 2021 May 5.

2Companion Animal Cancer Research Unit, Department of Pathology, Faculty of Veterinary Science, Chulalongkorn University, Bangkok 10330, Thailand.

Haemangioma (HA) and haemangiosarcoma (HSA) are among the most common splenic neoplasms in dogs. The survival time in splenic HSA is short, probably due to the lack of proper biological markers allowing early detection. We investigated the serum angiopoietin-2 (Ang-2) concentrations in 9 healthy dogs and 40 dogs with abnormal splenic masses. Read More

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Impact of the first surge of the COVID-19 pandemic on a tertiary referral centre for kidney cancer.

BJU Int 2021 May 8. Epub 2021 May 8.

Specialist Centre for Kidney Cancer, Royal Free London NHS Foundation Trust, UK.

Objectives: To analyse the impact of the COVID-19 pandemic on a centralised specialist kidney cancer care pathway.

Materials & Methods: Retrospective analysis of patient and pathway characteristics including prioritisation strategies at the Specialist Centre for Kidney Cancer (SCKC) located at the Royal Free London NHS Foundation Trust (RFH) before and during the surge of COVID-19.

Results: On March 18, 2020 all elective surgery was halted at RFH to redeploy resources and staff for the COVID-19 surge. Read More

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Post-mortem persistence of SARS-CoV-2: a preliminary study.

Forensic Sci Med Pathol 2021 May 8. Epub 2021 May 8.

Section of Legal Medicine, Department of Interdisciplinary Medicine, Bari Policlinico Hospital, University of Bari, 70124, Bari, Italy.

Since the beginning of March 2020, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been the cause of millions of deaths worldwide. The need to better define the pathogenesis of coronavirus disease 19 (Covid-19) as well as to provide the correct statistical records concerning deaths related to this virus, inevitably involves the role of forensic pathology and routine autopsy practice. Currently, some data on macroscopic and microscopic features in autopsies performed in suspected Covid-19 cases are reported in the literature. Read More

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Prediction of treatment response from the microenvironment of tumor immunity in cervical cancer patients treated with chemoradiotherapy.

Med Mol Morphol 2021 May 8. Epub 2021 May 8.

Department of Radiology, Sapporo Medical University School of Medicine, S1 W16, Chuo-ku, Sapporo, Hokkaido, 060-8543, Japan.

To supplement clinical decision-making in the management of cervical cancer, various prognostic factors, including tumor immune microenvironments, were examined in patients with cervical cancer treated with definitive chemoradiotherapy. We retrospectively analyzed the expression of CD8, FoxP3, HLA-1, PD-L1, and XRCC4 in 100 cases of cervical cancer. The observed tumor immune microenvironments were also classified into three types: inflamed, excluded, and cold type. Read More

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Prognostic relevance and putative histogenetic role of cytokeratin 7 and MUC5AC expression in Crohn's disease-associated small bowel carcinoma.

Virchows Arch 2021 May 8. Epub 2021 May 8.

Unit of Anatomic Pathology, Department of Molecular Medicine, University of Pavia and Fondazione IRCCS San Matteo Hospital, Via Carlo Forlanini 16 -, 27100, Pavia, Italy.

Most Crohn's disease-associated small bowel carcinomas (CrD-SBCs) are diagnosed in advanced stage and have poor prognosis. To improve diagnosis and therapy, a better knowledge of tumour precancerous lesions, histotypes and prognostic factors is needed. We investigated histologically and immunohistochemically 52 CrD-SBCs and 51 small bowel carcinomas unrelated to inflammatory disease, together with their tumour-associated mucosa, looking for Crohn-selective changes. Read More

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Prognostic value and characterization of NTRK1 variation by fluorescence in situ hybridization in esophageal squamous cell carcinoma.

J Cancer Res Clin Oncol 2021 May 8. Epub 2021 May 8.

Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, 200032, People's Republic of China.

Purpose: Rearrangement of the neurotrophic tyrosine kinase receptor (NTRK) 1 gene is a target of tropomyosin receptor kinase A (TRKA) inhibitors, and its targeted drug (larotrectinib) has been approved by the US Food and Drug Administration. We investigated the existence and prognostic importance of NTRK1 variation in esophageal squamous cell carcinoma (ESCC).

Methods: Fluorescence in situ hybridization of a NTRK1 rearrangement was conducted on 523 ESCC samples through tissue microarrays. Read More

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High spectral and spatial resolution MRI of prostate cancer: a pilot study.

Magn Reson Med 2021 May 8. Epub 2021 May 8.

Department of Radiology, University of Chicago, Chicago, Illinois, USA.

Purpose: High spectral and spatial resolution (HiSS) MRI is a spectroscopic imaging method focusing on water and fat resonances that has good diagnostic utility in breast imaging. The purpose of this work was to assess the feasibility and potential utility of HiSS MRI for the diagnosis of prostate cancer.

Methods: HiSS MRI was acquired at 3 T from six patients who underwent prostatectomy, yielding a train of 127 phase-coherent gradient echo (GRE) images. Read More

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SSX C-Terminus is a Useful Diagnostic Biomarker for Spermatocytic Tumour.

Histopathology 2021 May 7. Epub 2021 May 7.

Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.

Aims: Spermatocytic tumour (ST) is a rare testicular germ cell neoplasm that can be challenging to diagnose and for which there are few confirmatory biomarkers. Like normal spermatogonia, STs are known to express SSX proteins. Recently, a novel SSX antibody directed against the C-terminus (SSX_CT) of SSX1, SSX2 and SSX4, has emerged as a reliable biomarker for these SSX proteins and synovial sarcoma. Read More

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Postmortem pathological changes in extrapulmonary organs in SARS-CoV-2 rt-PCR-positive cases: a single-center experience.

Ir J Med Sci 2021 May 7. Epub 2021 May 7.

Council of Forensic Medicine, Istanbul, Turkey.

Background: Although the lung is seen as the main target organ affected by SARS-CoV-2, other organs are also damaged.

Aim: We aimed to determine the extrapulmonary findings of autopsies performed on cases with positive results with postmortem polymerase chain reaction test.

Methods: Pathological changes in extrapulmonary organs were examined with light microscopy. Read More

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Ubiquitin-mediated DNA damage response is synthetic lethal with G-quadruplex stabilizer CX-5461.

Sci Rep 2021 May 7;11(1):9812. Epub 2021 May 7.

Department of Molecular Oncology, BC Cancer Agency, 675 West 10th Avenue, Vancouver, BC, V5Z 1L3, Canada.

CX-5461 is a G-quadruplex (G4) ligand currently in trials with initial indications of clinical activity in cancers with defects in homologous recombination repair. To identify more genetic defects that could sensitize tumors to CX-5461, we tested synthetic lethality for 480 DNA repair and genome maintenance genes to CX-5461, pyridostatin (PDS), a structurally unrelated G4-specific stabilizer, and BMH-21, which binds GC-rich DNA but not G4 structures. We identified multiple members of HRD, Fanconi Anemia pathways, and POLQ, a polymerase with a helicase domain important for G4 structure resolution. Read More

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Loss of function mutations in GEMIN5 cause a neurodevelopmental disorder.

Nat Commun 2021 May 7;12(1):2558. Epub 2021 May 7.

Department of Pediatric Neurophysiology AP-HP, Necker Enfants Malades Hospital, Paris University, Paris, France.

GEMIN5, an RNA-binding protein is essential for assembly of the survival motor neuron (SMN) protein complex and facilitates the formation of small nuclear ribonucleoproteins (snRNPs), the building blocks of spliceosomes. Here, we have identified 30 affected individuals from 22 unrelated families presenting with developmental delay, hypotonia, and cerebellar ataxia harboring biallelic variants in the GEMIN5 gene. Mutations in GEMIN5 perturb the subcellular distribution, stability, and expression of GEMIN5 protein and its interacting partners in patient iPSC-derived neurons, suggesting a potential loss-of-function mechanism. Read More

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The AIM2 and NLRP3 inflammasomes trigger IL-1-mediated antitumor effects during radiation.

Sci Immunol 2021 May;6(59)

Department of Pathology, UT Southwestern Medical Center, Dallas, TX, USA.

The inflammasome promotes inflammation-associated diseases, including cancer, and contributes to the radiation-induced tissue damage. However, the role of inflammasome in radiation-induced antitumor effects is unclear. We observed that tumors transplanted in mice were resistant to radiation treatment compared with tumors in wild-type (WT) mice. Read More

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Immune cell composition and functional marker dynamics from multiplexed immunohistochemistry to predict response to neoadjuvant chemotherapy in the WSG-ADAPT-TN trial.

J Immunother Cancer 2021 May;9(5)

West German Study Group, Moenchengladbach, Germany.

Background: The association of early changes in the immune infiltrate during neoadjuvant chemotherapy (NACT) with pathological complete response (pCR) in triple-negative breast cancer (TNBC) remains unexplored.

Methods: Multiplexed immunohistochemistry was performed in matched tumor biopsies obtained at baseline and after 3 weeks of NACT from 66 patients from the West German Study Group Adjuvant Dynamic Marker-Adjusted Personalized Therapy Trial Optimizing Risk Assessment and Therapy Response Prediction in Early Breast Cancer - Triple Negative Breast Cancer (WSG-ADAPT-TN) trial. Association between CD4, CD8, CD73, T cells, PD1-positive CD4 and CD8 cells, and PDL1 levels in stroma and/or tumor at baseline, week 3 and 3-week change with pCR was evaluated with univariable logistic regression. Read More

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Lost clips after targeted lymph node biopsy in breast cancer patients: Follow-up of the CLIP-study.

Eur J Surg Oncol 2021 Apr 30. Epub 2021 Apr 30.

Department of Obstetrics and Gynecology, University of Rostock, Rostock, Germany.

Introduction: Clipping and selective removal of axillary lymph nodes in breast cancer patients presenting with initially node-positive disease and achieving a nodal downstaging after primary systemic therapy is a less invasive method for axillary staging. An imaging guided localization and successful extirpation of these clipped lymph nodes is not possible in all patients. To date no follow-up data regarding patients with lost clips are available. Read More

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Contralateral Masking in the Measurement of Auditory Brainstem Responses with Air-Conducted Tone Burst Stimuli in Individuals with Unilateral Hearing Loss.

J Am Acad Audiol 2021 May 7. Epub 2021 May 7.

Department of Audiology and Speech Pathology, Bauru School of Dentistry, University of São Paulo, Bauru, São Paulo, Brazil.

Background:  Contralateral noise masking is an important aspect of auditory brainstem response (ABR) measurements.

Purpose:  The primary aim of this study is to determine how contralateral white noise (WN) masking influences the amplitude and the latency of V wave generated during ABR measurements, using tone burst (TB), in adult ears with normal hearing (NH). The secondary aim of this study is to ascertain the need of contralateral masking in ABR measurements with the TB stimuli using a 3A insertion earphone, and to propose the applicability of WN masking in unilateral sensorineural hearing loss (USNHL). Read More

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Use of An Animal Model of Disease for Toxicology Enables Identification of a Juvenile No Observed Adverse Effect Level for Cyclocreatine in Creatine Transporter Deficiency.

Regul Toxicol Pharmacol 2021 May 4:104939. Epub 2021 May 4.

Lumos Pharma, 4200 Marathon Blvd Suite 200, Austin, TX, 78756, USA.

In standard general toxicology studies in two species to support clinical development, cyclocreatine, a creatine analog for the treatment of creatine transporter deficiency, caused deaths, convulsions, and/or multi-organ pathology. The potential translatability of these findings to patients was evaluated by comparing toxicity of cyclocreatine in wild-type mice to creatine transporter-deficient mice, a model of the human disease. A biodistribution study indicated greater accumulation of cyclocreatine in the brains of wild-type mice, consistent with its ability to be transported by the creatine transporter. Read More

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Theranostic AGuIX nanoparticles as radiosensitizer: A phase I, dose-escalation study in patients with multiple brain metastases (NANO-RAD trial).

Radiother Oncol 2021 May 4. Epub 2021 May 4.

Radiotherapy Department, Grenoble Alps University Hospital, Grenoble, France.

Background And Purpose: Brain metastasis impacts greatly on patients' quality of life and survival. The phase I NANO-RAD trial assessed the safety and maximum tolerated dose of systemic administration of a novel gadolinium-based nanoparticle, AGuIX, in combination with whole brain radiotherapy in patients with multiple brain metastases not suitable for stereotactic radiotherapy.

Materials And Methods: Patients with measurable brain metastases received escalating doses of AGuIX nanoparticles (15, 30, 50, 75, or 100 mg/kg intravenously) on the day of initiation of WBRT (30 Gy in 10 fractions) in 5 cohorts of 3 patients each. Read More

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Overexpression of oncogenic H-Ras in hTERT-immortalized and SV40-transformed human cells targets replicative and specialized DNA polymerases for depletion.

PLoS One 2021 7;16(5):e0251188. Epub 2021 May 7.

Department of Pathology, The Jake Gittlen Laboratories for Cancer Research, Penn State University College of Medicine, Hershey, Pennsylvania, United States of America.

DNA polymerases play essential functions in replication fork progression and genome maintenance. DNA lesions and drug-induced replication stress result in up-regulation and re-localization of specialized DNA polymerases η and κ. Although oncogene activation significantly alters DNA replication dynamics, causing replication stress and genome instability, little is known about DNA polymerase expression and regulation in response to oncogene activation. Read More

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The effect of Candidatus Phytoplasma pruni infection on sweet cherry fruit.

Phytopathology 2021 May 7. Epub 2021 May 7.

Plant Pathology, 24106 N. Bunn Rd, Prosser, Washington, United States, 99350;

In sweet cherry (Prunus avium L.), infection by Candidatus Phytoplasma pruni results in small fruit with poor color and taste, rendering the fruit unmarketable. Yet, the disease pathology is poorly understood, particularly at the cultivar level. Read More

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3-O-trans-caffeoyloleanolic acid improves acute lung injury via antiinflammation and antioxidative stress involved PI3K/AKT pathway.

Chem Biol Drug Des 2021 May 7. Epub 2021 May 7.

Department of Respiratory and Critical Care Medicine, Jiangxi Chest (Third people) Hospital, Nanchang, Jiangxi, 330006, PR China.

3-O-trans-caffeoyloleanolic acid (COA) is a pentacyclic triterpenoid compound, with significant anti-inflammatory effects. In this study, we report the protective effects of COA on LPS-induced acute lung injury (ALI) and explored its mechanism of action. LPS was used to construct in vivo mouse ALI models to observe the effects of COA pretreatment on lung pathology, inflammation and oxidative stress. Read More

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Persistent effects of pair bonding in lung cancer cell growth in monogamous .

Elife 2021 May 7;10. Epub 2021 May 7.

Department of Drug Discovery and Biomedical Sciences, College of Pharmacy, University of South Carolina, Columbia, United States.

Epidemiological evidence suggests that social interactions and especially bonding between couples influence tumorigenesis, yet whether this is due to lifestyle changes, homogamy (likelihood of individuals to marry people of similar health), or directly associated with host-induced effects in tumors remains debatable. In the present study, we explored if tumorigenesis is associated with the bonding experience in monogamous rodents at which disruption of pair bonds is linked to anxiety and stress. Comparison of lung cancer cell spheroids that formed in the presence of sera from bonded and bond-disrupted deer mice showed that in monogamous and , but not in polygamous , the disruption of pair bonds altered the size and morphology of spheroids in a manner that is consistent with the acquisition of increased oncogenic potential. Read More

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A series of COVID-19 autopsies with clinical and pathologic comparisons to both seasonal and pandemic influenza.

J Pathol Clin Res 2021 May 7. Epub 2021 May 7.

Department of Pathology, University of Chicago Medical Center, Chicago, IL, USA.

Autopsies of patients who have died from COVID-19 have been crucial in delineating patterns of injury associated with SARS-CoV-2 infection. Despite their utility, comprehensive autopsy studies are somewhat lacking relative to the global burden of disease, and very few comprehensive studies contextualize the findings to other fatal viral infections. We developed a novel autopsy protocol in order to perform postmortem examinations on victims of COVID-19 and herein describe detailed clinical information, gross findings, and histologic features observed in the first 16 complete COVID-19 autopsies. Read More

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