Pyroptosis-Related Genes as Diagnostic Markers in Chronic Obstructive Pulmonary Disease and Its Correlation with Immune Infiltration.

Background: Chronic obstructive pulmonary disease (COPD) stands as a predominant cause of global morbidity and mortality. This study aims to elucidate the relationship between pyroptosis-related genes (PRGs) and COPD diagnosis in the context of immune infiltration, ultimately proposing a PRG-based diagnostic model for predicting COPD outcomes. Methods: Clinical data and PRGs of COPD patients were sourced from the GEO database. The "ConsensusClusterPlus" package was employed to generate molecular subtypes derived from PRGs that were identified through differential expression analysis and LASSO Cox analysis. A diagnostic signature including eight genes (CASP4, CASP5, ELANE, GPX4, NLRP1, GSDME, NOD1and IL18) was also constructed. Immune cell infiltration calculated by the ESTIMATE score, Stroma scores and Immune scores were also compared on the basis of pyroptosis-related molecular subtypes and the risk signature. We finally used qRT - PCR to detect the expression levels of eight genes in COPD patient and normal. Results: The diagnostic model, anchored on eight PRGs, underwent validation with an independent experimental cohort. The area under the receiver operating characteristic (ROC) curves (AUC) for the diagnostic model showcased values of 0.809, 0.765, and 0.956 for the GSE76925, GSE8545, and GSE5058 datasets, respectively. Distinct expression patterns and clinical attributes of PRGs were observed between the comparative groups, with functional analysis underscoring a disparity in immune-related functions between them. Conclusion: In this study, we developed a potential as diagnostic biomarkers for COPD and have a significant role in modulating the immune response. Such insights pave the way for novel diagnostic and therapeutic strategies for COPD.

The Long COVID Symptoms and Severity Score: Development, Validation, and Application.

OBJECTIVES: The primary focus of this research is the proposition of a methodological framework for the clinical application of the long COVID symptoms and severity score (LC-SSS). This tool is not just a self-reported assessment instrument developed and validated but serves as a standardized, quantifiable means to monitor the diverse and persistent symptoms frequently observed in individuals with long COVID. METHODS: A 3-stage process was used to develop, validate, and establish scoring standards for the LC-SSS. Validation measures included correlations with other patient-reported measures, confirmatory factor analysis, Cronbach's α for internal consistency, and test-retest reliability. Scoring standards were determined using K-means clustering, with comparative assessments made against hierarchical clustering and the Gaussian Mixture Model. RESULTS: The LC-SSS showed correlations with EuroQol 5-Dimension 5-Level (rs = -0.55), EuroQol visual analog scale (rs = -0.368), Patient Health Questionnaire-9 (rs = 0.538), Beck Anxiety Inventory (rs = 0.689), and Insomnia Severity Index (rs = 0.516), confirming its construct validity. Structural validity was good with a comparative fit index of 0.969, with Cronbach's α of 0.93 indicating excellent internal consistency. Test-retest reliability was also satisfactory (intraclass correlation coefficient 0.732). K-means clustering identified 3 distinct severity categories in individuals living with long COVID, providing a basis for personalized treatment strategies. CONCLUSIONS: The LC-SSS provides a robust and valid tool for assessing long COVID. The severity categories established via K-means clustering demonstrate significant variation in symptom severity, informing personalized treatment and improving care quality for patients with long COVID.

Elevated branched-chain amino acid promotes atherosclerosis progression by enhancing mitochondrial-to-nuclear H2O2-disulfide HMGB1 in macrophages.

As the essential amino acids, branched-chain amino acid (BCAA) from diets is indispensable for health. BCAA supplementation is often recommended for patients with consumptive diseases or healthy people who exercise regularly. Latest studies and ours reported that elevated BCAA level was positively correlated with metabolic syndrome, diabetes, thrombosis and heart failure. However, the adverse effect of BCAA in atherosclerosis (AS) and its underlying mechanism remain unknown. Here, we found elevated plasma BCAA level was an independent risk factor for CHD patients by a human cohort study. By employing the HCD-fed ApoE-/- mice of AS model, ingestion of BCAA significantly increased plaque volume, instability and inflammation in AS. Elevated BCAA due to high dietary BCAA intake or BCAA catabolic defects promoted AS progression. Furthermore, BCAA catabolic defects were found in the monocytes of patients with CHD and abdominal macrophages in AS mice. Improvement of BCAA catabolism in macrophages alleviated AS burden in mice. The protein screening assay revealed HMGB1 as a potential molecular target of BCAA in activating proinflammatory macrophages. Excessive BCAA induced the formation and secretion of disulfide HMGB1 as well as subsequent inflammatory cascade of macrophages in a mitochondrial-nuclear H2O2 dependent manner. Scavenging nuclear H2O2 by overexpression of nucleus-targeting catalase (nCAT) effectively inhibited BCAA-induced inflammation in macrophages. All of the results above illustrate that elevated BCAA promotes AS progression by inducing redox-regulated HMGB1 translocation and further proinflammatory macrophage activation. Our findings provide novel insights into the role of animo acids as the daily dietary nutrients in AS development, and also suggest that restricting excessive dietary BCAA consuming and promoting BCAA catabolism may serve as promising strategies to alleviate and prevent AS and its subsequent CHD.

Coronary Angiography Within 48 Hours Before Cardiac Surgery Increases the Risk of Postoperative Acute Kidney Injury.

BACKGROUND: Cardiac surgery and coronary examination, such as invasive coronary angiography (CAG), are both possibly associated with acute kidney injury (AKI). Preoperative CAG examination and cardiac surgery within a short interval may increase the incidence of AKI. METHODS: We retrospectively reviewed 1112 patients who underwent CAG examination within 30 days prior to the cardiac operation in this study. Postoperative AKI was defined, according to Kidney Disease Improving Global Outcomes Definition and Staging (KDIGO) criteria. RESULTS: The total incidence of AKI was 40.8% and cystatin C level was 1.260 (1.028, 1.672) mg/L. For patients who received CAG, age, body mass index, cardiopulmonary time, and the time interval between preoperative CAG examination and cardiac operation within 48h was shown to be independent predictors of postoperative AKI. The incidence of AKI in patients undergoing preoperative CAG within 48h was 11.2% higher than in those more than 48h (P < 0.001). Patients undergoing valve surgery with or without coronary artery bypass grafting (CABG) exhibited a higher AKI risk than those only accepting CABG. The in-hospital stay of patients who developed AKI was 2 days longer than those without AKI. However, undergoing CAG within 48h prior to cardiac operation did not prolong ICU length of stay or hospital length of stay, nor did it increase the risk of death or renal failure after an operation. CONCLUSION: Undergoing CAG within 48 hours before cardiac surgery increases the risk of postoperative AKI.

Early outcomes of Sun's procedure in elderly patients with acute aortic dissection: a single-center retrospective study.

OBJECTIVE: The effect of patient age on the outcome of Sun's procedure for acute type A aortic dissection (ATAAD) remains controversial. We retrospectively investigated the early outcomes of Sun's procedure in elderly patients with ATAAD in our single center. METHODS: This study involved 106 patients who underwent Sun's procedure. The patients were divided into the elderly group (≥70 years, n = 17) and younger group (<70 years). Baseline, intraoperative, and postoperative data were compared between the groups. RESULTS: The mean age in the elderly and younger groups was 75.7 and 50.7 years, respectively. The type of aortic root operations were not significantly different between the groups. Concomitant surgeries were more frequently performed in the elderly group, but without statistical significance. All intraoperative cardiopulmonary bypass variables as well as the in-hospital and 30-day mortality rates were similar between the groups. The incidences of most postoperative complications were also similar except for a higher incidence of sepsis in the elderly group. CONCLUSIONS: Emergency performance of Sun's procedure for patients with ATAAD characterized by dissection and/or entry tear in the aortic arch should not be denied on the basis of advanced age alone. Comparable early in-hospital outcomes can be achieved in elderly patients.

Clinical efficacy and safety of neuroendoscopic surgery for severe thalamic hemorrhage with ventricle encroachment.

To summarize and analyze the clinical efficacy and safety of neuroendoscopic surgery (NES) in the treatment of patients for severe thalamic hemorrhage with ventricle encroachment (THVE). Eighty-three patients with severe THVE were treated in the Neurosurgery Department of Anqing Hospital Affiliated to Anhui Medical University from July 2019 to August 2021. Our study was approved by the ethics committee. The patients were randomly divided into NES group and extraventricular drainage (EVD) group. The hospital stay, Glasgow coma scale (GCS) scores on the 1st and 14th days postoperatively, the incidence of intracranial infections, and the clearance of postoperative hematomas were compared and analyzed between the two groups. The patients had follow-up evaluations 6 months postoperatively. The prognosis was evaluated based on the activity of daily living (ADL) score. A head CT or MRI was obtained to determine whether there was hydrocephalus, cerebral infarction, or other related complications. Eighty-three patients were randomly divided into 41 cases of NES group and 42 cases of EVD group. The length of postoperative hospital stay was 17.42 ± 1.53 days, the GCS scores were 6.56 ± 0.21, and 10.83 ± 0.36 on days 1 and 14, respectively; intracranial infections occurred in 3 patients (7.31%) and the hematoma clearance rate was 83.6 ± 5.18% in the NES group, all of which were significantly better than the EVD group (P < 0.05). After 6 months of follow-up, 28 patients (68.29%) had a good prognosis, 5 patients (12.19%) died, and 4 patients (9.75%) had hydrocephalus in the NES group. In the EVD group, the prognosis was good in 15 patients (35.71%), 12 patients (28.57%) died, and 17 patients (40.47%) had hydrocephalus. The prognosis, mortality rate, and incidence of hydrocephalus in the NES group were significantly better than the EVD group (P < 0.05). Compared to traditional EVD, NES for severe THVE had a higher hematoma clearance rate, and fewer intracranial infections and patients with hydrocephalus, which together improve the clinical prognosis and is thus recommended for clinical use.

Palmitic acid-induced defects in cell cycle progression and cytokinesis in Neuro-2a cells.

Obesity is associated with elevated levels of free fatty acids (FFAs). Excessive saturated fatty acids (SFAs) exhibit significant deleterious cytotoxic effects in many types of cells. However, the effects of palmitic acid (PA), the most common circulating SFA, on cell cycle progression in neuronal cells have not been well-examined. The aim of this study was to examine whether PA affects the proliferation and cell cycle progression in mouse neuroblastoma Neuro-2a (N2a) cells. Our studies found that 200 µM PA significantly decreased DNA synthesis and mitotic index in N2a cells as early as 4 h following treatment. 24 h treatment with 200 µM PA significantly decreased the percentage of diploid (2 N) cells while dramatically increasing the percentage of tetraploid (4 N) cells as compared to the BSA control. Moreover, our studies found that 24 h treatment with 200 µM PA increased the percentage of binucleate cells as compared to the BSA control. Our studies also found that unsaturated fatty acids (UFAs), including linoleic acid, oleic acid, α-linolenic acid, and docosahexaenoic acid, were able to abolish PA-induced decrease of 2 N cells, increase of 4 N cells, and accumulation of binucleate cells. Taken together, these results suggest that PA may affect multiple aspects of the cell cycle progression in N2a cells, including decreased DNA synthesis, G2/M arrest, and cytokinetic failure, which could be abolished by UFAs.Abbreviations: 4-PBA, 4-Phenylbutyric Acid; ALA, α-linolenic acid; BrdU, 5-bromo-2'-deoxyuridine; DAPI, 4',6-diamidino-2-phenylindole; ER, endoplasmic reticulum; FFA, free fatty acids; FITC, fluorescein isothiocyanate; LA, linoleic acid; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; N2a, Neuro-2a; NAC, N-acetyl cysteine; OA, oleic acid; PA, palmitic acid; pHH3, Phosphorylation of histone H3; PI, propidium iodide; SFA, saturated fatty acids; PUFA, polyunsaturated fatty acids; TUNEL, terminal deoxynucleotidyl transferase dUTP nick end labeling; UFA, unsaturated fatty acids.

Liver volume based prediction model for patients with hepatitis B virus-related acute-on-chronic liver failure.

BACKGROUND: Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a life-threatening disease with high short-term mortality. Early and accurate prognosis is significant for clinical decisions, in which liver volume (LV) imparts important information. However, LV has not been considered in current prognostic models for HBV-ACLF. METHODS: Three hundred and twenty-three patients were recruited to the deriving cohort, while 163 were enrolled to validation cohort. The primary end-point was death within 28 days since admission. Estimated liver volume (ELV) was calculated by the formula based on healthy population. Logistic regression was used to develop a prediction model. Accuracy of models were evaluated by receiver operating characteristic (ROC) curves. RESULTS: The ratio of LV to ELV (LV/ELV%) was significantly lower in non-survivors, and LV/ELV% ≤82% indicated poor prognosis. LV/ELV%, Age, prothrombin time (PT), the grade of hepatic encephalopathy (HE), ln-transformed total bilirubin (lnTBil), and log-transformed HBV DNA (Log10 HBV DNA) were identified as independent predictors to develop an LV-based model, LEAP-HBV. The mean area under the ROC (AUC) of LEAP-HBV was 0.906 (95% CI, 0.904-0.908), higher than other non-LV-based models. CONCLUSION: Liver volume was an independent predictor, and LEAP-HBV, a prediction model based on LV, was developed for the short-term mortality in HBV-ACLF. This study was registered on ClinicalTrails (NCT03977857).

Surgical Treatment of Primary Cardiac Paragangliomas: A Single-Center Experience.

BACKGROUND: Cardiac paragangliomas are rare neuroendocrine tumors that will cause significant morbidity if left undiagnosed. Because of the paucity of cohort data, their rapid diagnosis and appropriate management still pose unique challenges to cardiac surgeons. We aimed to investigate the clinical features and surgical management of primary cardiac paragangliomas in our single center. METHODS: From May 2014 to October 2020, patients diagnosed with primary cardiac paragangliomas retrospectively were reviewed. Demographic data, clinical presentation, preoperative imaging methods, surgical resection, perioperative management, histological analysis, and outcomes were recorded. Postoperative follow up also was reviewed. RESULTS: With multiple imaging methods, including echocardiography, computed tomography, positron-emission tomographic-computed tomography, and biochemical tests, there were five cases of primary cardiac paraganglioma verified by postoperative immunohistochemical staining, two of which were hormonally active. There were no metastatic cardiac paragangliomas, according to positron-emission tomographic-computed tomography, and all patients accepted surgical treatment. Preoperative adrenoceptor blockade was given to hormonally active patients, accordingly. Complete resection of the tumor was accomplished under cardiopulmonary bypass in each case. Tumor distribution included two masses on the roof of the left atrium, two masses in the right atrioventricular groove, and one between the ascending aorta and main pulmonary artery. Immunohistochemical staining for chromogranin, neuron-specific enolase, synaptophysin, and S-100 were positive, which were typical of cardiac paraganglioma. There were no operative deaths. All the patients had an uneventful recovery except one patient who underwent low cardiac output syndrome. During follow up (mean 4.2 years, range 0.6-7.0 years), all patients were well with New York Heart Association class I or II. Only one patient developed thyroid carcinoma three years after surgery but with no paraganglioma recurrence during periodic computed tomography, and this patient recovered well after thyroidectomy. CONCLUSION: Although cardiac paragangliomas are rare and may present surgical challenges for clinicians, surgical resection remains the choice of treatment with favorable outcomes through a multidisciplinary heart team. Moreover, lifelong surveillance still is recommended to detect possible recurrence or associated nonchromaffin tumors in time.

Role of CD36 in Palmitic Acid Lipotoxicity in Neuro-2a Neuroblastoma Cells.

Elevated level of palmitic acid (PA), a long-chain saturated fatty acid (SFA), is lipotoxic to many different types of cells including Neuro-2a (N2a) neuroblastoma cells. CD36 is a multifunctional membrane glycoprotein that acts as a fatty acid translocase (FAT) facilitating the transport of long-chain free fatty acids (FFAs) into cells, serves a fatty acid (FA) sensing function in areas including taste buds and the proximal gut, and acts as a scavenger receptor that binds to many ligands, including FAs, collagen, oxidized low-density lipoproteins, and anionic phospholipids. However, the involvement of CD36 in FA uptake and PA lipotoxicity in N2a cells remains unclear. In this study, we examined FA uptake in BSA- and PA-treated N2a cells and investigated the involvement of CD36 in FA uptake and PA lipotoxicity in N2a cells. Our data showed that PA treatment promoted FA uptake in N2a cells, and that treatment with sulfo-N-succinimidyl oleate (SSO), a CD36 inhibitor, significantly decreased FA uptake in BSA- and PA-treated N2a cells, and ameliorated PA-induced decrease of cell viability, decrease of diploid cells, and increase of tetraploid cells. We also found that CD36 knockdown significantly decreased FA uptake in both BSA- and PA-treated cells as compared to their corresponding wild-type controls, and dramatically attenuated PA-induced cell cycle defects in N2a cells. Our data suggest that CD36 may play a critical role in FA uptake and PA lipotoxicity in N2a cells. CD36 may therefore represent a regulatory target against pathologies caused by excess FAs.

Network Meta-analysis on the Changes of Amyloid Precursor Protein Expression Following SARS-CoV-2 Infection.

SARS-CoV-2 infection begins with the attachment of its spike (S) protein to angiotensin-converting enzyme-2 (ACE2) followed by complex host immune responses with cardiovascular and neurological implications. Our meta-analyses used QIAGEN Ingenuity Pathway Analysis (IPA) and Knowledge Base (QKB) to investigate how the expression of amyloid precursor protein (APP) was modulated by attachment of SARS-CoV-2 S protein in the brain microvascular endothelial cells (BMVECs) and during COVID-19 in progress. Published 80 host response genes reported to be modulated in BMVECs following SARS-CoV-2 S protein binding were used to identify key canonical pathways and intermediate molecules mediating the regulation of APP production following the attachment of S protein to endothelial cells. This revealed that the attachment of SARS-CoV-2 S protein may inhibit APP expression in the BMVECs. Our results shed light on the molecular mechanisms by which SARS-CoV-2 infection may potentiate the incidence of stroke by inhibiting the production of APP in the BMVECs. We also analyzed molecules associated with COVID-19, which revealed six upstream regulators, TNF, IFNG, STAT1, IL1ß, IL6, and STAT3. The upstream regulators mediate the increased production of APP via intermediators, with eleven regulated by all six upstream regulators. These COVID-19 upstream regulators increased APP expression with a statistically significant Z-score of 3.705 (p value = 0.000211). These findings have revealed molecular mechanisms by which COVID-19 disease may lead to long-term neurological manifestations resulting from the elevated APP expression in line with immune response in the host. Altogether, our study revealed two distinct scenarios which may have differential impact on APP expression.

Palmitic Acid Lipotoxicity in Microglia Cells Is Ameliorated by Unsaturated Fatty Acids.

Obesity and metabolic syndrome are associated with cognitive decline and dementia. Palmitic acid (PA) is increased in the cerebrospinal fluid of obese patients with cognitive impairment. This study was therefore designed to examine fatty acid (FA) lipotoxicity in BV2 microglia cells. We found that PA induced time- and dose-dependent decrease in cell viability and increase in cell death without affecting the cell cycle profile and that PA lipotoxicity did not depend on cell surface free fatty acid receptors but rather on FA uptake. Treatment with sulfosuccinimidyl oleate (SSO), an irreversible inhibitor of fatty acid translocase CD36, significantly inhibited FA uptake in BSA- and PA-treated cells and blocked PA-induced decrease in cell viability. Inhibition of ER stress or treatment with N-acetylcysteine was not able to rescue PA lipotoxicity. Our study also showed that unsaturated fatty acids (UFAs), such as linoleic acid (LA), oleic acid (OA), α-linolenic acid (ALA), and docosahexaenoic acid (DHA), were not lipotoxic but instead protected microglia against PA-induced decrease in cell viability. Co-treatment of PA with LA, OA, and DHA significantly inhibited FA uptake in PA-treated cells. All UFAs tested induced the incorporation of FAs into and the amount of neutral lipids, while PA did not significantly affect the amount of neutral lipids compared with BSA control.

Molecular Mechanisms of Palmitic Acid Augmentation in COVID-19 Pathologies.

The coronavirus disease 2019 (COVID-19) pandemic has claimed over 2.7 million lives globally. Obesity has been associated with increased severity and mortality of COVID-19. However, the molecular mechanisms by which obesity exacerbates COVID-19 pathologies are not well-defined. The levels of free fatty acids (FFAs) are elevated in obese subjects. This study was therefore designed to examine how excess levels of different FFAs may affect the progression of COVID-19. Biological molecules associated with palmitic acid (PA) and COVID-19 were retrieved from QIAGEN Knowledge Base, and Ingenuity Pathway Analysis tools were used to analyze these datasets and explore the potential pathways affected by different FFAs. Our study found that one of the top 10 canonical pathways affected by PA was the coronavirus pathogenesis pathway, mediated by key inflammatory mediators, including PTGS2; cytokines, including IL1ß and IL6; chemokines, including CCL2 and CCL5; transcription factors, including NFκB; translation regulators, including EEF1A1; and apoptotic mediators, including BAX. In contrast, n-3 fatty acids may attenuate PA's activation of the coronavirus pathogenesis pathway by inhibiting the activity of such mediators as IL1ß, CCL2, PTGS2, and BAX. Furthermore, PA may modulate the expression of ACE2, the main cell surface receptor for the SARS-CoV-2 spike protein.

Meta-Analysis of Methamphetamine Modulation on Amyloid Precursor Protein through HMGB1 in Alzheimer's Disease.

The deposition of amyloid-beta (Aß) through the cleavage of amyloid-beta precursor protein (APP) is a biomarker of Alzheimer's disease (AD). This study used QIAGEN Ingenuity Pathway Analysis (IPA) to conduct meta-analysis on the molecular mechanisms by which methamphetamine (METH) impacts AD through modulating the expression of APP. All the molecules affected by METH and APP were collected from the QIAGEN Knowledge Base (QKB); 78 overlapping molecules were identified. Upon simulation of METH exposure using the "Molecule Activity Predictor" feature, eight molecules were found to be affected by METH and exhibited activation relationships on APP expression at a confidence of p = 0.000453 (Z-score = 3.51, two-tailed). Core Analysis of these eight molecules identified High Mobility Group Box protein 1 (HMGB1) signaling pathway among the top 5 canonical pathways with most overlap with the 8-molecule dataset. Simulated METH exposure increased APP expression through HMGB1 at a confidence of p < 0.00001 (Z-score = 7.64, two-tailed). HMGB1 is a pathogenic hallmark in AD progression. It not only increases the production of inflammatory mediators, but also mediates the disruption of the blood-brain barrier. Our analyses suggest the involvement of HMGB1 signaling pathway in METH-induced modulation of APP as a potential casual factor of AD.

Imaging pediatric acute head trauma using 100-kVp low dose CT with adaptive statistical iterative reconstruction (ASIR-V) in single rotation on a 16 cm wide-detector CT.

OBJECTIVE: To demonstrate the ability of achieving low dose and high-quality head CT images for children with acute head trauma using 100 kVp and adaptive statistical iterative reconstruction (ASIR-V) algorithm in single rotation on a 16 cm wide-detector system. MATERIALS AND METHODS: We retrospectively analyzed the CT dose index (CTDI) and image quality of 104 children aged 0-6 years with acute head trauma (1 hour -3 days) in two groups: Group 1(n = 50) on a 256-row CT with single rotation at a reduced-dose of 100 kVp/240 mA and reconstructed using ASIR-V at 70%level; Group 2(n = 54) on a 64-row CT with multiple rotations at a standard dose of 120 kVp/ 180mA and reconstructed using a conventional filtered back-projection (FBP). Both groups used the 0.5 s/r axial scan mode. CT dose index (CTDI) and quantitative image quality measurements were compared using the Student t test; qualitative image quality comparison was carried out using Mann-Whitney rank test and the inter-reviewer agreement was evaluated using Kappa test. RESULTS: The exposure time was 0.5 s for Group 1 and 3.27±0.29 s for Group 2. The CTDI in Group 1 was 9.74±0.86mGy, 36.38%lower than the 15.31mGy in Group 2 (p < 0.001). Group 1 and Group 2 had similar artifact index (2.06±1.06 vs. 2.37±1.18) in the cerebellar hemispheres, and similar contrast-to-noise ratio (2.32±0.83 vs. 1.69±0.68), (1.47±0.72 vs. 1.10±0.43) respectively for cerebellum and thalamus (p > 0.05). Image quality was acceptable for diagnosis, and motion artifacts were reduced in Group 1 (p < 0.001). CONCLUSION: Single rotation CT with 100 kVp and 70%ASIR-V on 16 cm wide-detector CT reduces radiation dose and motion artifacts for children with acute head trauma without compromising diagnostic quality as compared with standard dose protocol. Thus, it provides a novel imaging method in management of pediatric acute head trauma.

Network Meta-Analysis on the Mechanisms Underlying Alcohol Augmentation of COVID-19 Pathologies.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is a worldwide crisis caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Many COVID-19 patients present with fever in the early phase, with some progressing to a hyperinflammatory phase. Ethanol (EtOH) exposure may lead to systemic inflammation. Network meta-analysis was conducted to examine possible relationships between EtOH consumption and COVID-19 pathologies. METHODS: Molecules affected by EtOH exposure were identified by analysis with QIAGEN Knowledge Base. Molecules affected by COVID-19 were identified from studies in MEDLINE, bioRxiv, and medRxiv reporting gene expression profiles in COVID-19 patients, QIAGEN Coronavirus Network Explorer, and analysis of the RNA-sequencing data of autopsied lungs of COVID-19 patients retrieved from the GEO database. Network meta-analysis was then conducted on these molecules using QIAGEN Ingenuity Pathway Analysis (IPA). RESULTS: Twenty-eight studies reporting significant gene expression changes in COVID-19 patients were identified. One RNA-sequencing dataset on autopsied lungs of COVID-19 patients was retrieved from GEO. Our network meta-analysis suggests that EtOH exposure may augment the effects of SARS-CoV-2 infection on hepatic fibrosis signaling pathway, cellular metabolism and homeostasis, inflammation, and neuroinflammation. EtOH may also enhance the activity of key mediators including cytokines, such as IL-1ß, IL-6, and TNF, and transcription factors, such as JUN and STAT, while inhibiting the activity of anti-inflammatory mediators including glucocorticoid receptor. Furthermore, IL-1ß, IL-6, TNF, JUN, and STAT were mapped to 10 pathways predicted to associate with SARS-CoV-2 proteins, including HMGB1, IL-1, and IL-6 signaling pathways. CONCLUSIONS: Our meta-analyses demonstrate that EtOH exposure may augment SARS-CoV-2-induced inflammation by altering the activity of key inflammatory mediators. Our findings suggest that it is important for clinicians to caution patients about the risk of alcohol consumption, which has increased during the COVID-19 pandemic. The findings also call for further investigation into how alcohol exposure affects viral infections.

A Pattern Categorization of CT Findings to Predict Outcome of COVID-19 Pneumonia.

Background: As global healthcare system is overwhelmed by novel coronavirus disease (COVID-19), early identification of risks of adverse outcomes becomes the key to optimize management and improve survival. This study aimed to provide a CT-based pattern categorization to predict outcome of COVID-19 pneumonia. Methods: One hundred and sixty-five patients with COVID-19 (91 men, 4-89 years) underwent chest CT were retrospectively enrolled. CT findings were categorized as Pattern 0 (negative), Pattern 1 (bronchopneumonia pattern), Pattern 2 (organizing pneumonia pattern), Pattern 3 (progressive organizing pneumonia pattern), and Pattern 4 (diffuse alveolar damage pattern). Clinical findings were compared across different categories. Time-dependent progression of CT patterns and correlations with clinical outcomes, i.e." discharge or adverse outcome (admission to ICU, requiring mechanical ventilation, or death), with pulmonary sequelae (complete absorption or residuals) on CT after discharge were analyzed. Results: Of 94 patients with outcome, 81 (86.2%) were discharged, 3 (3.2%) were admitted to ICU, 4 (4.3%) required mechanical ventilation, 6 (6.4%) died. 31 (38.3%) had complete absorption at median day 37 after symptom onset. Significant differences between pattern-categories were found in age, disease severity, comorbidity and laboratory results (all P < 0.05). Remarkable evolution was observed in Pattern 0-2 and Pattern 3-4 within 3 and 2 weeks after symptom-onset, respectively; most of patterns remained thereafter. After controlling for age, CT pattern significantly correlated with adverse outcomes [Pattern 4 vs. Pattern 0-3 [reference]; hazard-ratio [95% CI], 18.90 [1.91-186.60], P = 0.012]. CT pattern [Pattern 3-4 vs. Pattern 0-2 [reference]; 0.26 [0.08-0.88], P = 0.030] and C-reactive protein [>10 vs. ≤ 10 mg/L [reference]; 0.31 [0.13-0.72], P = 0.006] were risk factors associated with pulmonary residuals. Conclusion: CT pattern categorization allied with clinical characteristics within 2 weeks after symptom onset would facilitate early prognostic stratification in COVID-19 pneumonia.

Evaluation of dynamic lung changes during coronavirus disease 2019 (COVID-19) by quantitative computed tomography.

OBJECTIVES: This study aims to trace the dynamic lung changes of coronavirus disease 2019 (COVID-19) using computed tomography (CT) images by a quantitative method. METHODS: In this retrospective study, 28 confirmed COVID-19 cases with 145 CT scans are collected. The lesions are detected automatically and the parameters including lesion volume (LeV/mL), lesion percentage to lung volume (LeV%), mean lesion density (MLeD/HU), low attenuation area lower than - 400HU (LAA-400%), and lesion weight (LM/mL*HU) are computed for quantification. The dynamic changes of lungs are traced from the day of initial symptoms to the day of discharge. The lesion distribution among the five lobes and the dynamic changes in each lobe are also analyzed. RESULTS: LeV%, MLeD, and LM reach peaks on days 9, 6 and 8, followed by a decrease trend in the next two weeks. LAA-400% (mostly the ground glass opacity) declines to the lowest on days 4-5, and then increases. The lesion is mostly seen in the bilateral lower lobes, followed by the left upper lobe, right upper lobe and right middle lobe (p < 0.05). The right middle lobe is the earliest one (on days 6-7), while the right lower lobe is the latest one (on days 9-10) that reaches to peak among the five lobes. CONCLUSIONS: Severity of COVID-19 increases from the day of initial symptoms, reaches to the peak around on day 8, and then decreases. Lesion is more commonly seen in the bilateral lower lobes.

Quantitative computed tomography analysis for stratifying the severity of Coronavirus Disease 2019.

To examine the feasibility of using a computer tool for stratifying the severity of Coronavirus Disease 2019 (COVID-19) based on computed tomography (CT) images. We retrospectively examined 44 confirmed COVID-19 cases. All cases were evaluated separately by radiologists (visually) and through an in-house computer software. The degree of lesions was visually scored by the radiologist, as follows, for each of the 5 lung lobes: 0, no lesion present; 1, <1/3 involvement; 2, >1/3 and < 2/3 involvement; and 3, >2/3 involvement. Lesion density was assessed based on the proportion of ground-glass opacity (GGO), consolidation and fibrosis of the lesions. The parameters obtained using the computer tool included lung volume (mL), lesion volume (mL), lesion percentage (%), and mean lesion density (HU) of the whole lung, right lung, left lung, and each lobe. The scores obtained by the radiologists and quantitative results generated by the computer software were tested for correlation. A Chi-square test was used to test the consistency of radiologist- and computer-derived lesion percentage in the right/left lung, upper/lower lobe, and each of the 5 lobes. The results showed a strong to moderate correlation between lesion percentage scores obtained by radiologists and the computer software (r ranged from 0.7679 to 0.8373, P < 0.05), and a moderate correlation between the proportion of GGO and mean lesion density (r = -0.5894, P < 0.05), and proportion of consolidation and mean lesion density (r = 0.6282, P < 0.05). Computer-aided quantification showed a statistical significant higher lesion percentage for lower lobes than that assessed by the radiologists (χ2 = 8.160, P = 0.004). Our experiments demonstrated that the computer tool could reliably and accurately assess the severity and distribution of pneumonia on CT scans.

Evolution of CT findings in patients with mild COVID-19 pneumonia.

OBJECTIVES: To delineate the evolution of CT findings in patients with mild COVID-19 pneumonia. METHODS: CT images and medical records of 88 patients with confirmed mild COVID-19 pneumonia, a baseline CT, and at least one follow-up CT were retrospectively reviewed. CT features including lobar distribution and presence of ground glass opacities (GGO), consolidation, and linear opacities were analyzed on per-patient basis during each of five time intervals spanning the 3 weeks after disease onset. Total severity scores were calculated. RESULTS: Of patients, 85.2% had travel history to Wuhan or known contact with infected individuals. The most common symptoms were fever (84.1%) and cough (56.8%). The baseline CT was obtained on average 5 days from symptom onset. Four patients (4.5%) had negative initial CT. Significant differences were found among the time intervals in the proportion of pulmonary lesions that are (1) pure GGO, (2) mixed attenuation, (3) mixed attenuation with linear opacities, (4) consolidation with linear opacities, and (5) pure consolidation. The majority of patients had involvement of ≥ 3 lobes. Bilateral involvement was more prevalent than unilateral involvement. The proportions of patients observed to have pure GGO or GGO and consolidation decreased over time while the proportion of patients with GGO and linear opacities increased. Total severity score showed an increasing trend in the first 2 weeks. CONCLUSIONS: While bilateral GGO are predominant features, CT findings changed during different time intervals in the 3 weeks after symptom onset in patients with COVID-19. KEY POINTS: • Four of 88 (4.5%) patients with COVID-19 had negative initial CT. • Majority of COVID-19 patients had abnormal CT findings in ≥ 3 lobes. • A proportion of patients with pure ground glass opacities decreased over the 3 weeks after symptom onset.