Derivation and validation of novel integrated inpatient mortality prediction score for COVID-19 (IMPACT) using clinical, laboratory, and AI-processed radiological parameter upon admission: a multicentre study.

Limited studies explore the use of AI for COVID-19 prognostication. This study investigates the relationship between AI-aided radiographic parameters, clinical and laboratory data, and mortality in hospitalized COVID-19 patients. We conducted a multicentre retrospective study. The derivation and validation cohort comprised of 512 and 137 confirmed COVID-19 patients, respectively. Variable selection for constructing an in-hospital mortality scoring model was performed using the least absolute shrinkage and selection operator, followed by logistic regression. The accuracy of the scoring model was assessed using the area under the receiver operating characteristic curve. The final model included eight variables: anosmia (OR: 0.280; 95%CI 0.095-0.826), dyspnoea (OR: 1.684; 95%CI 1.049-2.705), loss of consciousness (OR: 4.593; 95%CI 1.702-12.396), mean arterial pressure (OR: 0.928; 95%CI 0.900-0.957), peripheral oxygen saturation (OR: 0.981; 95%CI 0.967-0.996), neutrophil % (OR: 1.034; 95%CI 1.013-1.055), serum urea (OR: 1.018; 95%CI 1.010-1.026), affected lung area score (OR: 1.026; 95%CI 1.014-1.038). The Integrated Inpatient Mortality Prediction Score for COVID-19 (IMPACT) demonstrated a predictive value of 0.815 (95% CI 0.774-0.856) in the derivation cohort. Internal validation resulted in an AUROC of 0.770 (95% CI 0.661-0.879). Our study provides valuable evidence of the real-world application of AI in clinical settings. However, it is imperative to conduct prospective validation of our findings, preferably utilizing a control group and extending the application to broader populations.

Markers of Renal Complications in Beta Thalassemia Patients with Iron Overload Receiving Chelation Agent Therapy: A Systematic Review.

Objective: The emerging renal complications in beta-thalassemia patients have raised the global exchange of views. Despite better survival due to blood transfusion and iron chelation therapy, the previously unrecognized renal complication remain a burden of disease affecting this population -the primary concern on how iron overload and chelation therapy correlated with renal impairment is still controversial. Early detection and diagnosis is crucial in preventing further kidney damage. Therefore, a systematic review was performed to identify markers of kidney complications in beta thalassemia patients with iron overload receiving chelation therapy. Methods: Searches of PubMed, Scopus, Science Direct, and Web of Science were conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) to identify studies of literature reporting renal outcome in ß-TM patients with iron overload and receiving chelation therapy. The eligible 17 studies were obtained. Results: uNGAL/NGAL, uNAG/NAG, uKIM-1 are markers that can be used as predictor of renal tubular damage in early renal complications, while Cystatin C and uß2MG showed further damage at the glomerular level. Discussion and Conclusion: The renal complication in beta-thalassemia patients with iron overload receiving chelating agent therapy may progress to kidney disease. Early detection using accurate biological markers is a substantial issue that deserves further evaluation to determine prevention and management.

Chondroitin Sulfate N-acetylgalactosaminyltransferase-2 Impacts Foam Cell Formation and Atherosclerosis by Altering Macrophage Glycosaminoglycan Chain.

OBJECTIVE: Chondroitin sulfate proteoglycans are the primary constituents of the macrophage glycosaminoglycan and extracellular microenvironment. To examine their potential role in atherogenesis, we investigated the biological importance of one of the chondroitin sulfate glycosaminoglycan biosynthesis gene, ChGn-2 (chondroitin sulfate N-acetylgalactosaminyltransferase-2), in macrophage foam cell formation. Approach and Results: ChGn-2-deficient mice showed decreased and shortened glycosaminoglycans. ChGn-2-/-/LDLr-/- (low-density lipoprotein receptor) mice generated less atherosclerotic plaque after being fed with Western diet despite exhibiting a metabolic phenotype similar to that of the ChGn-2+/+/LDLr-/- littermates. We demonstrated that in macrophages, ChGn-2 expression was upregulated in the presence of oxLDL (oxidized LDL), and glycosaminoglycan was substantially increased. Foam cell formation was significantly altered by ChGn-2 in both mouse peritoneal macrophages and the RAW264.7 macrophage cell line. Mechanistically, ChGn-2 enhanced oxLDL binding on the cell surface, and as a consequence, CD36-an important macrophage membrane scavenger receptor-was differentially regulated. CONCLUSIONS: ChGn-2 alteration on macrophages conceivably influences LDL accumulation and subsequently accelerates plaque formation. These results collectively suggest that ChGn-2 is a novel therapeutic target amenable to clinical translation in the future. Graphic Abstract: A graphic abstract is available for this article.

Chondroitin sulfate N-acetylgalactosaminyltransferase-2 deletion alleviates lipoprotein retention in early atherosclerosis and attenuates aortic smooth muscle cell migration.

Glycosaminoglycans (GAGs) play an integral role in low-density lipoprotein (LDL) retention in the vascular intimal layer and have emerged as attractive therapeutic targets for atherosclerosis. GAG biosynthesis involves the cooperation of numerous enzymes. Chondroitin sulfate N-acetylgalactosaminyltransferase-2 (ChGn-2) is a vital Golgi transferase that participates in enzymatic elongation of GAGs. Here, we investigated the effects of ChGn-2 gene deletion on the development of atherosclerosis. Partial carotid artery ligation was performed on ChGn-2-/-/LDLr-/- and ChGn-2+/+/LDLr-/- mice to induce diffuse intimal thickening (DIT). Aortic smooth muscle cells (ASMCs) were isolated to investigate cellular LDL binding and migration. Histological analysis of human coronary artery sections revealed that ChGn-2 was expressed in early and advanced atherosclerotic lesions. Deletion of the ChGn-2 gene significantly reduced LDL retention in the DIT mouse model. Furthermore, LDL binding, visualized using rhodamine-labeled LDLs, was dramatically reduced. Interestingly, a functional assay of ASMCs prepared from ChGn-2-/- mice displayed abrogation of platelet-derived growth factor (PDGF)-mediated migration via reduced PDGF receptor phosphorylation. Taken together, these findings indicate that ChGn-2 is functionally involved in the progression of atherosclerosis both in its early and advanced stages. Therefore, ChGn-2 may serve as a plausible target to treat atherosclerotic-related diseases in the future.