Studying the clinical, radiological, histological, microbiological, and immunological evolution during the different COVID-19 disease stages using minimal invasive autopsy.
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ABSTRACT:
SUBMITTER: D'Onofrio V
PROVIDER: S-EPMC8789771 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundMinimally invasive autopsy (MIA) is a validated and safe method to establish the cause of death (COD), mainly in low-resource settings. However, the additional clinical value of MIA in Coronavirus disease (COVID-19) patients in a high-resource setting is unknown. The objective was to assess if and how MIA changed clinical COD and contributing diagnoses in deceased COVID-19 patients.Methods and findingsA prospective observational cohort from April to May 2020 in a 981-bed teaching hospital in the epicenter of the COVID-19 pandemic in Belgium was established. Patients who died with either PCR-confirmed or radiologically confirmed COVID-19 infection were consecutively included. MIA consisted of whole-body CT and CT-guided Tru-Cut® biopsies. Diagnostic modalities were clinical chart review, radiology, microbiology, and histopathology which were assessed by two independent experts per modality. MIA COD and contributing diagnoses were established during a multi-disciplinary meeting. Clinical COD (CCOD) and contributing diagnosis were abstracted from the discharge letter. The main outcomes were alterations in CCOD and contributing diagnoses after MIA, and the contribution of each diagnostic modality. We included 18 patients, of which 7 after intensive care unit hospitalization. MIA led to an alteration in 15/18 (83%) patients. The CCOD was altered in 5/18 (28%) patients. MIA found a new COD (1/5), a more specific COD (1/5), a less certain COD (1/5), or a contributing diagnosis to be the COD (2/5). Contributing diagnoses were altered in 14/18 (78%) patients: 9 new diagnoses, 5 diagnoses dismissed, 3 made more specific, and 2 made less certain. Overall, histopathology contributed in 14/15 (93%) patients with alterations, radiology and microbiology each in 6/15 (40%), and clinical review in 3/15 (20%). Histopathology was deemed the most important modality in 10 patients, radiology in two patients, and microbiology in one patient.ConclusionMIA, especially histological examination, can add valuable new clinical information regarding the cause of death in COVID-19 patients, even in a high-resource setting with wide access to premortem diagnostic modalities. MIA may provide important clinical insights and should be applied in the current ongoing pandemic.Trial registrationClinicaltrials.gov identifier: NCT04366882.
| S-EPMC7657516 | biostudies-literature
Project description:Clinical, immunological and microbiological characteristics of recurrent invasive pneumococcal disease (IPD) in children were evaluated, differentiating relapse from reinfection, in order to identify specific risk factors for both conditions.All patients <18 years-old with recurrent IPD admitted to a tertiary-care pediatric center from January 2004 to December 2011 were evaluated. An episode of IPD was defined as the presence of clinical findings of infection together with isolation and/or pneumococcal DNA detection by Real-Time PCR in any sterile body fluid. Recurrent IPD was defined as 2 or more episodes in the same individual at least 1 month apart. Among recurrent IPD, we differentiated relapse (same pneumococcal isolate) from reinfection.593 patients were diagnosed with IPD and 10 patients died. Among survivors, 23 episodes of recurrent IPD were identified in 10 patients (1.7%). Meningitis was the most frequent form of recurrent IPD (10 episodes/4 children) followed by recurrent empyema (8 episodes/4 children). Three patients with recurrent empyema caused by the same pneumococcal clone ST306 were considered relapses and showed high bacterial load in their first episode. In contrast, all other episodes of recurrent IPD were considered reinfections. Overall, the rate of relapse of IPD was 0.5% and the rate of reinfection 1.2%. Five out of 7 patients with reinfection had an underlying risk factor: cerebrospinal fluid leak (n = 3), chemotherapy treatment (n = 1) and a homozygous mutation in MyD88 gene (n = 1). No predisposing risk factors were found in the remainder.recurrent IPD in children is a rare condition associated with an identifiable risk factor in case of reinfection in almost 80% of cases. In contrast, recurrent IPD with pleuropneumonia is usually a relapse of infection.
| S-EPMC4349703 | biostudies-other
Project description:This data article describes biomechanical and histological information of abdominal aortas harvested in autopsy. Eight abdominal aorta aneurysms (AAA) and 30 normal diameter abdominal aortas were collected and submitted to an inflation test up to their rupture. This inflation procedure was part of the research entitled "Experimental study of rupture pressure and elasticity of abdominal aortic aneurysms found at autopsy", submitted to Annals of Vascular Surgery. The rupture borders and control samples (harvested from places other than the rupture site) were submitted to uniaxial destructive tensile test and to histological analysis. The following variables were evaluated in the biomechanical test: failure stress, failure tension and failure strain. The histological processing of the samples enabled a quantitative analysis of the percentage of coverage of collagen fibers and elastic fibers in the samples. The present data could be reutilized because they are experimental evidence that cadaveric abdominal aortas, even when previously stressed by inflation, conserve significant resistance against tearing comparable to no previously stressed aortas described in the literature. Considering real whole cadaveric AAAs are especially scarce, this information would be a useful reference source for further in-depth research in the aortic biomechanics field.
| S-EPMC8027288 | biostudies-literature
Project description:Between April and June 2020, i.e., during the first wave of pandemic coronavirus disease 2019 (COVID-19), 55 patients underwent long-term treatment in the intensive care unit at the University Hospital of Regensburg. Most of them were transferred from smaller hospitals, often due to the need for an extracorporeal membrane oxygenation system. Autopsy was performed in 8/17 COVID-19-proven patients after long-term treatment (mean: 33.6 days). Autopsy revealed that the typical pathological changes occurring during the early stages of the disease (e.g., thrombosis, endothelitis, capillaritis) are less prevalent at this stage, while severe diffuse alveolar damage and especially coinfection with different fungal species were the most conspicuous finding. In addition, signs of macrophage activation syndrome was detected in 7 of 8 patients. Thus, fungal infections were a leading cause of death in our cohort of severely ill patients and may alter clinical management of patients, particularly in long-term periods of treatment.
| S-EPMC7816067 | biostudies-literature
Project description:The cumulative risk score (CRS) is a mathematical salivary diagnostic model to define an individual's risk of having periodontitis. In order to further validate this salivary biomarker, we investigated how periodontal bacteria, lipopolysaccharide (LPS), and systemic and local host immune responses relate to CRS. Subgingival plaque, saliva, and serum samples collected from 445 individuals were used in the analyses. Plaque levels of 28 microbial species, especially those of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Porphyromonas endodontalis, Prevotella intermedia, and Tannerella forsythia, and serum and salivary levels of IgA and IgG against these five species were determined. Additionally, LPS activity was measured. High CRS associated strongly with all IgA/IgG antibody and LPS levels in saliva, whereas in serum the associations were not that obvious. In the final logistic regression model, the best predictors of high CRS were saliva IgA burden against the five species (OR 7.04, 95% CI 2.25-22.0), IgG burden (3.79, 1.78-8.08), LPS (2.19, 1.38-3.47), and the sum of 17 subgingival Gram-negative species (6.19, 2.10-18.3). CRS is strongly associated with microbial biomarker species of periodontitis and salivary humoral immune responses against them.
| S-EPMC7460115 | biostudies-literature
Project description:ObjectivesPhysiological changes and shifts in the oral microbiota composition during pregnancy may affect the maternal immune system. Uncomplicated pregnancy is associated with a T-helper (Th) 2 predominant cytokine regulation (anti-inflammatory), while oral health deterioration during pregnancy is reflected by severe gingival inflammation, a primarily Th1 cytokine phenotype (pro-inflammatory), and oral microbiome alterations. This prospective observational study aimed to evaluate Th cytokine shifts and changes in the oral microbiota composition in saliva of women before and after birth.Material and methodsSaliva (n = 96) was collected before and 6 months after birth, and medical, oral health, and periodontal status were assessed. In a multiplex immunoassay, 10 cytokines were simultaneously analyzed and cumulative Th1 and Th2 cytokine levels and Th1/Th2 ratio were calculated for all groups. Putative periodontal pathogens (n = 6) were evaluated by quantitative real-time polymerase chain reaction.ResultsTh2 cytokine levels were significantly lower (p = 0.014) while pro-inflammatory cytokine levels were significantly higher (p < 0.01) during pregnancy than postpartum. Similar Th1 levels were found between the groups (p = 0.143). Th1 and Th2 cytokines positively correlated with periodontal parameters (p < 0.001) and levels of studied bacteria during pregnancy (p < 0.05).ConclusionsThis study identified a significantly increased Th1/Th2 cytokine ratio during pregnancy and a positive association with putative periodontal pathogens. This immunological and microbiological deregulation in the oral milieu during pregnancy is suggestive of a destructive inflammatory periodontal profile.Study registrationClinical Trials.gov (Record BAP-2015).Clinical relevanceUnderstanding altered oral immunological and microbiological regulation patterns during pregnancy may help improve the inflammatory periodontal profile in pregnant women.
| S-EPMC10756889 | biostudies-literature
Project description:Severe neurological symptoms are associated with Coronavirus disease 2019 (COVID-19). However, the morphologic features, pathological nature and their potential mechanisms in patient brains have not been revealed despite evidence of neurotropic infection. In this study, neuropathological damages and infiltrating inflammatory cells were quantitatively evaluated by immunohistochemical staining, ultrastructural examination under electron microscopy, and an image threshold method, in postmortem brains from nine critically ill COVID-19 patients and nine age-matched cadavers of healthy individuals. Differentially expressed proteins were identified by quantitative proteomic assays. Histopathological findings included neurophagocytosis, microglia nodules, satellite phenomena, extensive edema, focal hemorrhage, and infarction, as well as infiltrating mononuclear cells. Immunostaining of COVID-19 brains revealed extensive activation of both microglia and astrocytes, severe damage of the blood-brain barrier (BBB) and various degrees of perivascular infiltration by predominantly CD14+/CD16+/CD141+/CCR7+/CD11c+ monocytes and occasionally CD4+/CD8+ T lymphocytes. Quantitative proteomic assays combined with bioinformatics analysis identified upregulated proteins predominantly involved in immune responses, autophagy and cellular metabolism in COVID-19 patient brains compared with control brains. Proteins involved in brain development, neuroprotection, and extracellular matrix proteins of the basement membrane were downregulated, potentially caused by the activation of transforming growth factor β receptor and vascular endothelial growth factor signaling pathways. Thus, our results define histopathological and molecular profiles of COVID-19-associated monocytic encephalitis (CAME) and suggest potential therapeutic targets.
| S-EPMC9816522 | biostudies-literature
Project description:Development of minimally invasive cardiac surgery (MICS) served the purpose of performing surgery while avoiding the surgical stress triggered by a full median sternotomy. Minimizing surgical trauma is associated with improved cosmesis and enhanced recovery leading to reduced morbidity. However, it has to be primarily appreciated that the extracorporeal circulation (ECC) stands for the basis of nearly all MICS procedures. With some fundamental modification and advancement in perfusion techniques, the use of ECC has become the enabling technology for the development of MICS. Less invasive cardiopulmonary bypass (CPB) techniques are based on remote cannulation and optimization of perfusion techniques with assisted venous drainage and use of centrifugal pump, so as to facilitate the demanding surgical maneuvers, rather than minimizing the invasiveness of the CPB. This is reflected in the increased duration of CPB required for MICS procedures. Minimal invasive Extracorporeal Circulation (MiECC) represents a major breakthrough in perfusion. It integrates all contemporary technological advancements that facilitate best applying cardiovascular physiology to intraoperative perfusion. Consequently, MiECC use translates to improved end-organ protection and clinical outcome, as evidenced in multiple clinical trials and meta-analyses. MICS performed with MiECC provides the basis for developing a multidisciplinary intraoperative strategy towards a "more physiologic" cardiac surgery by combining small surgical trauma with minimum body's physiology derangement. Integration of MiECC can advance MICS from non-full sternotomy for selected patients to a "more physiologic" surgery, which represents the real face of modern cardiac surgery in the transcatheter era.
| S-EPMC8024827 | biostudies-literature
Project description:Feline chronic gingivostomatitis (FCGS) is an immune-mediated inflammatory condition affecting the oral mucosa that results in substantial pain and suffering. The goal of this study was to complete an in-depth immunohistochemistry analysis of affected FCGS mucosa, to perform and compare immune cell phenotypes in the blood of FCGS and healthy controls cats, and to determine a transcriptomic profile of the affected and normal oral mucosa of FCGS cats. We hypothesized that cats with FCGS would have circulating activated CD8+ T cells and that tissues would be infiltrated with activated B and T cells with a highly proinflammatory transcriptome. We found that oral mucosal tissues from cats with FCGS have high tissue infiltration of B cells and that T cells include both CD4+ and CD8+ lymphocytes. Cells positive for CD25 (IL2 receptor, indicative of lymphocyte activation) and FOXP3 (indicative of regulatory T cells) were scattered throughout the mucosa. Compared to healthy individuals, cats with FCGS had high circulating CD8+ effector memory cells with a concurrent decrease in central memory cells and evidence of circulating activated CD8+ T cells (CD25+, CD62L-). Gene expression in the affected tissues was enriched for genes associated with T-cell signaling, cell adhesion molecules, leukocyte migration, inflammatory signaling pathways, extracellular matrix-receptor interactions, cytokine-cytokine receptor interactions, and natural killer cell-mediated cytotoxicity, among others. These data are essential to understand disease pathogenesis, to inform mechanism of action studies for future and current therapies, and to help select prognostic biomarkers and potency assays for stem cell treatment of FCGS.
| S-EPMC7283503 | biostudies-literature
Project description:BACKGROUND:The objective was to analyze clinical, microbiological, and immunological periodontal parameters in patients in corrective orthodontic treatment. MATERIALS AND METHODS:Twenty-eight patients were selected. Plaque index (PI), bleeding on probing (BOP), width of keratinized gingiva, levels of 40 bacterial species, and of 3 cytokines (IL-1?, MMP-8, and TNF-?) in gingival crevicular fluid (GCF) were evaluated at T0, before orthodontic treatment; T1, 6?months; and T2, 12?months post-treatment. Non-parametric, Friedman, Wilcoxon, ANOVA, and Spearman correlation coefficient tests were used for statistical analyses, with the significance level of 5%. RESULTS:No significant difference was found for the width of keratinized gingiva, but PI presented a significant increase at T1 and T2 (p?<?0.05) when compared with T0. The percentage of sites with BOP increased significantly from T0 to T1 (p?<?0.05); however, at T2, the values decreased and did not differ anymore from T0 (p?>?0.05). In the microbiological analysis, red complex pathogens were in significantly greater proportions in T2 compared with T0 (p?<?0.05). There was no statistically significant difference in the cytokine levels between the periods but there was a positive correlation between BOP and IL-1? (r?=?0.49 p?=?.01) and TNF-? (r?=?0.39 and p?=?.05). CONCLUSION:In conclusion, corrective orthodontic treatment caused clinical periodontal alterations regarding biofilm accumulation and gingival bleeding, with alteration of periodontopathogens.
| S-EPMC7024686 | biostudies-literature