An assessment of the correlation between robust CT-derived ventilation and pulmonary function test in a cohort with no respiratory symptoms

OBJECTIVE: To evaluate CT-ventilation imaging (CTVI) within a well-characterized, healthy cohort with no respiratory symptoms and examine the correlation between CTVI and concurrent pulmonary function test (PFT). METHODS: CT scans and PFTs from 77 Caucasian participants in the NORM dataset (clinicaltrials.gov NCT00848406) were analyzed. CTVI was generated using the robust Integrated Jacobian Formulation (IJF) method. IJF estimated total lung capacity (TLC) was computed from CTVI. Bias-adjusted Pearson’s correlation between PFT and IJF-based TLC was computed. RESULTS: IJF- and PFT-measured TLC showed a good correlation for both males and females [males: 0.657, 95% CI (0.438–0.797); females: 0.667, 95% CI (0.416–0.817)]. When adjusting for age, height, smoking, and abnormal CT scan, correlation moderated [males: 0.432, 95% CI (0.129–0.655); females: 0.540, 95% CI (0.207–0.753)]. Visual inspection of CTVI revealed participants who had functional defects, despite the fact that all participant had normal high-resolution CT scan. CONCLUSION: In this study, we demonstrate that IJF computed CTVI has good correlation with concurrent PFT in a well-validated patient cohort with no respiratory symptoms. ADVANCES IN KNOWLEDGE: IJF-computed CTVI’s overall numerical robustness and consistency with PFT support its potential as a method for providing spatiotemporal assessment of high and low function areas on volumetric non-contrast CT scan

Factors influencing the total procedure time of CT-guided percutaneous core-needle biopsies of lung nodules: a retrospective analysis

PURPOSEThis study aims to investigate the factors that influence total procedure time when performing computed tomography (CT)-guided percutaneous core-needle lung biopsies.METHODSThis is a cross-sectional study of 673 patients, who underwent a CT-guided percutaneous coreneedle biopsy at a tertiary care center from March 2014 to August 2016. Data on patient, nodule, and procedural factors and outcomes were collected retrospectively. Univariate linear regression and a multivariate stepwise linear regression were utilized for analysis.RESULTSFactors most strongly associated with prolonged procedure duration include 20-gauge needle use when compared with 18-gauge needle use (estimated difference in time=1.19), collecting additional core biopsies (estimated difference in time=1.10), decubitus nodule side up (DNSU; estimated difference in time=1.42), and supine positioning (estimated difference in time=1.16) relative to decubitus nodule side down positioning, and increased nodule distance from the skin surface (estimated difference in time=1.03). Increased nodule length (estimated difference in time=0.93) was associated with reductions in procedure duration. Prolonged procedure time was associated with an increased rate of pneumothorax (odds ratio (OR)=1.02; P < .0001) and decreased rate of pulmonary hemorrhage (OR=0.97; P < .0001).CONCLUSIONThe use of 20-gauge biopsy needle, collecting additional core biopsies, DNSU and supine positioning, smaller nodule size, and increasing nodule distance from the skin surface were associated with increased procedure time for CT-guided core needle biopsies of lung nodules. Prolonged procedure time is associated with a higher rate of pneumothorax and a lower rate of pulmonary hemorrhage

SARS-COV-ATE risk assessment model for arterial thromboembolism in COVID-19

Patients with SARS-CoV-2 infection are at an increased risk of cardiovascular and thrombotic complications conferring an extremely poor prognosis. COVID-19 infection is known to be an independent risk factor for acute ischemic stroke and myocardial infarction (MI). We developed a risk assessment model (RAM) to stratify hospitalized COVID-19 patients for arterial thromboembolism (ATE). This multicenter, retrospective study included adult COVID-19 patients admitted between 3/1/2020 and 9/5/2021. Among 3531 patients from the training cohort, 15.5% developed acute in-hospital ATE, including stroke, MI, and other ATE, compared to 13.4% in the validation cohort. The 16-item final score was named SARS-COV-ATE (Sex: male = 1, Age [40-59 = 2, \u3e 60 = 4], Race: non-African American = 1, Smoking = 1 and Systolic blood pressure elevation = 1, Creatinine elevation = 1; Over the range: leukocytes/lactate dehydrogenase/interleukin-6, B-type natriuretic peptide = 1, Vascular disease (cardiovascular/cerebrovascular = 1), Aspartate aminotransferase = 1, Troponin-I [\u3e 0.04 ng/mL = 1, troponin-I \u3e 0.09 ng/mL = 3], Electrolytes derangement [magnesium/potassium = 1]). RAM had a good discrimination (training AUC 0.777, 0.756-0.797; validation AUC 0.766, 0.741-0.790). The validation cohort was stratified as low-risk (score 0-8), intermediate-risk (score 9-13), and high-risk groups (score ≥ 14), with the incidence of ATE 2.4%, 12.8%, and 33.8%, respectively. Our novel prediction model based on 16 standardized, commonly available parameters showed good performance in identifying COVID-19 patients at risk for ATE on admission

RISK FACTORS OF ARTERIAL THROMBOEMBOLISM IN HOSPITALIZED COVID-19 PATIENTS: A MULTICENTER COHORT STUDY

Background: Endothelial cell dysfunction from infection by SARS-CoV-2 and inflammatory cytokines leading to hyperinflammatory and hypercoagulable state is thought to be the mechanism of arterial thromboembolism (ATE) in COVID-19 patients. COVID-19 infection is known to be an independent risk factor for acute stroke and myocardial infarction (MI). However, data on the risk factors of ATE in hospitalized COVID-19 patients is limited. Methods: This retrospective, multicenter cohort study included adult patients admitted to one quaternary care and three community hospitals with PCR-proven SARS-CoV-2 infection between 3/1/2020 and 12/31/2020. The composite outcome was in-hospital ATE events, including acute ischemic stroke, MI, and other ATE identified by ICD-10 codes. Student t-test was conducted for continuous variables and the Chi-square test for categorical variables. Multivariate logistic regression using forward selection was conducted. All statistical tests were 2-sided with an α level of 0.05. All data was analyzed using R version 4.0.4. Results: The cohort included 3531 patients with 371 (10.5%) patients who developed acute ATE. There were 398 ATE events: 270 patients had MI, 43 had stroke, 85 had other ATE, 12 had MI + stroke, 13 had MI + other ATE, and 2 had stroke + other ATE. The model suggested that initial systolic blood pressure (BP) \u3c90 mmHg and \u3e160 mmHg; elevated initial biomarkers including B-type natriuretic peptide (\u3e100 pg/mL), troponin-I (\u3e0.03 ng/mL), lactate dehydrogenase (\u3e192 U/L), creatine phosphokinase (male \u3e280 U/L and female \u3e155 U/L), C-reactive protein (\u3e0.5 mg/dL), leukocytes (\u3e11 K/uL), lactate (\u3e2.2 mmol/L), and aspartate aminotransferase (\u3e41 U/L); presenting hypoalbuminemia (\u3c3.5 g/dL) and hypomagnesemia (\u3c1.8 mg/dL); age \u3e60; male sex; and history of cerebrovascular accident (CVA), coronary artery disease (CAD), hyperthyroidism, and cigarette smoking were associated with an increased risk of ATE (all p\u3c0.05). Conclusion: Hypo or hypertension on admission, elevated inflammatory and cardiac markers, hypoalbuminemia, hypomagnesemia, smoking, and comorbidities including CAD and CVA are associated with ATE in hospitalized COVID-19 patients

Venous thromboembolism in COVID-19 patients and prediction model: a multicenter cohort study

BACKGROUND: Patients with COVID-19 infection are commonly reported to have an increased risk of venous thrombosis. The choice of anti-thrombotic agents and doses are currently being studied in randomized controlled trials and retrospective studies. There exists a need for individualized risk stratification of venous thromboembolism (VTE) to assist clinicians in decision-making on anticoagulation. We sought to identify the risk factors of VTE in COVID-19 patients, which could help physicians in the prevention, early identification, and management of VTE in hospitalized COVID-19 patients and improve clinical outcomes in these patients. METHOD: This is a multicenter, retrospective database of four main health systems in Southeast Michigan, United States. We compiled comprehensive data for adult COVID-19 patients who were admitted between 1st March 2020 and 31st December 2020. Four models, including the random forest, multiple logistic regression, multilinear regression, and decision trees, were built on the primary outcome of in-hospital acute deep vein thrombosis (DVT) and pulmonary embolism (PE) and tested for performance. The study also reported hospital length of stay (LOS) and intensive care unit (ICU) LOS in the VTE and the non-VTE patients. Four models were assessed using the area under the receiver operating characteristic curve and confusion matrix. RESULTS: The cohort included 3531 admissions, 3526 had discharge diagnoses, and 6.68% of patients developed acute VTE (N = 236). VTE group had a longer hospital and ICU LOS than the non-VTE group (hospital LOS 12.2 days vs. 8.8 days, p \u3c 0.001; ICU LOS 3.8 days vs. 1.9 days, p \u3c 0.001). 9.8% of patients in the VTE group required more advanced oxygen support, compared to 2.7% of patients in the non-VTE group (p \u3c 0.001). Among all four models, the random forest model had the best performance. The model suggested that blood pressure, electrolytes, renal function, hepatic enzymes, and inflammatory markers were predictors for in-hospital VTE in COVID-19 patients. CONCLUSIONS: Patients with COVID-19 have a high risk for VTE, and patients who developed VTE had a prolonged hospital and ICU stay. This random forest prediction model for VTE in COVID-19 patients identifies predictors which could aid physicians in making a clinical judgment on empirical dosages of anticoagulation

Larvicidal activities of 2-Aryl-2,3-Dihydroquinazolin -4-ones against malaria vector Anopheles arabiensis, In Silico ADMET prediction and molecular target investigation

Malaria, affecting all continents, remains one of the life-threatening diseases introduced by parasites that are transmitted to humans through the bites of infected Anopheles mosquitoes. Although insecticides are currently used to reduce malaria transmission, their safety concern for living systems, as well as the environment, is a growing problem. Therefore, the discovery of novel, less toxic, and environmentally safe molecules to effectively combat the control of these vectors is in high demand. In order to identify new potential larvicidal agents, a series of 2-aryl-1,2-dihydroquinazolin-4-one derivatives were synthesized and evaluated for their larvicidal activity against Anopheles arabiensis. The in silico absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of the compounds were also investigated and most of the derivatives possessed a favorable ADMET profile. Computational modeling studies of the title compounds demonstrated a favorable binding interaction against the acetylcholinesterase enzyme molecular target. Thus, 2-aryl-1,2-dihydroquinazolin-4-ones were identified as a novel class of Anopheles arabiensis insecticides which can be used as lead molecules for the further development of more potent and safer larvicidal agents for treating malaria.Fil: Venugopala, K. N.. Durban University Of Technology; SudáfricaFil: Pushpalatha, R.. Reva University; IndiaFil: Tratat, C.. King Faisal University; Arabia SauditaFil: Gleiser, Raquel M.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Instituto Multidisciplinar de Biología Vegetal (P). Grupo Vinculado Centro de Relevamiento y Evaluación de Recursos Agrícolas y Naturales; ArgentinaFil: Bhandary, S.. Indian Institute Of Science Education And Research Bhopal; IndiaFil: Chopra, D.. Indian Institute Of Science Education And Research Bhopal; IndiaFil: Morsy, M.. King Faisal University; Arabia SauditaFil: Al-Dhubiab, B. E.. King Faisal University; Arabia SauditaFil: Attimarad, M. B.. King Faisal University; Arabia SauditaFil: Nair, A.. King Faisal University; Arabia SauditaFil: Sreeharsha, N.. King Faisal University; Arabia SauditaFil: Venugopala, R.. University Of Kwazulu-natal; SudáfricaFil: Deb, P. K.. Philadelphia University; JordaniaFil: Chandrashekharappa, S.. Institute For Stem Cell Biology And Regenerative Medicine; IndiaFil: Khalil, H.. King Faisal University; Arabia SauditaFil: Alwassil, O.. King Saud Bin Abdulaziz University For Health Sciences; Arabia SauditaFil: Abed, S. N.. Philadelphia University; JordaniaFil: Bataineh, Y. A.. Philadelphia University; JordaniaFil: Palenge, R.. Reva University; IndiaFil: Haroun, M.. King Faisal University; Arabia SauditaFil: Pottathil, S.. King Faisal University; Arabia SauditaFil: Girish, M. B.. Reva University; IndiaFil: Akrawi, S. H.. King Faisal University; Arabia SauditaFil: Mohanlall, V.. Durban University Of Technology; Sudáfric

Fermentation, Isolation, Structure, and antidiabetic activity of NFAT-133 produced by Streptomyces strain PM0324667

Type-2 diabetes is mediated by defects in either insulin secretion or insulin action. In an effort to identify extracts that may stimulate glucose uptake, similar to insulin, a high throughput-screening assay for measuring glucose uptake in skeletal muscle cells was established. During the screening studies to discover novel antidiabetic compounds from microbial resources a Streptomyces strain PM0324667 (MTCC 5543, the Strain accession number at Institute of Microbial Technology, Chandigarh, India), an isolate from arid soil was identified which expressed a secondary metabolite that induced glucose uptake in L6 skeletal muscle cells. By employing bioactivity guided fractionation techniques, a tri-substituted simple aromatic compound with anti-diabetic potential was isolated. It was characterized based on MS and 2D NMR spectral data and identified as NFAT-133 which is a known immunosuppressive agent that inhibits NFAT-dependent transcription in vitro. Our investigations revealed the antidiabetic potential of NFAT-133. The compound induced glucose uptake in differentiated L6 myotubes with an EC50 of 6.3 ± 1.8 μM without activating the peroxisome proliferator-activated receptor-γ. Further, NFAT-133 was also efficacious in vivo in diabetic animals and reduced systemic glucose levels. Thus it is a potential lead compound which can be considered for development as a therapeutic for the treatment of type-2 diabetes. We have reported herewith the isolation of the producer microbe, fermentation, purification, in vitro, and in vivo antidiabetic activity of the compound