Background: The goal of the study was to evaluate a potential role for tumor necrosis factor alpha (TNF-α) genetic variability as biomarker in sepsis. In particular, we aimed to determine if single nucleotide polymorphisms (SNPs) ofTNF-αgene are associated with sepsis in terms of risk, severity and outcome.Methods: We performed a prospective study on 163 adult critically ill septic patients (septic shock 65, sepsis 98, further divided in 40 survivors and 123 deceased) and 232 healthy controls. Genotyping ofTNF-αSNPs (-308G/A, -238G/A, -376G/A and +489G/A) was performed for all patients and controls and plasma cytokine levels were measured during the first 24 h after sepsis onset.Results: TNF-α +489G/A A-allele carriage was associated with significantly lower risk of developing sepsis and sepsis shock (AA+AG vs GG: OR = 0.53;p = 0.004; 95% CI = 0.34–0.82 and OR = 0.39;p = 0.003; 95% CI = 0.21–0.74, respectively) but not with sepsis-related outcomes. There was no significant association between any of the otherTNF-αpromoter SNPs, or their haplotype frequencies and sepsis or septic shock risk. Circulating TNF-α levels were higher in septic shock; they were not correlated with SNP genotype distribution; GG homozygosity for each polymorphism was correlated with higher TNF-α levels in septic shock.Conclusions: TNF-α +489G/A SNP A-allele carriage may confer protection against sepsis and septic shock development but apparently does not influence sepsis-related mortality. PromoterTNF-αSNPs did not affect transcription and were not associated with distinct sepsis, septic shock risk or outcomes.

Background and Aims. Diabetic neuropathy is a frequent complication of type 2 diabetes mellitus (T2DM). Genetic susceptibility and oxidative stress may play a role in the appearance of T2DM and diabetic neuropathy. We investigated the relation between polymorphism in genes related to oxidative stress such asGSTM1,GSTT1, andGSTP1and the presence of T2DM and diabetic neuropathy (DN).Methods. Samples were collected from 84 patients with T2DM (42 patients with DN and 42 patients without DN) and 98 healthy controls and genotyped by using polymerase chain reaction and restriction fragment length polymorphism method.Results.GSTP1Ile105Val polymorphism was associated with the risk of developing T2DM (p=0.05) but not with the risk of developing DN in diabetic cases.GSTM1andGSTT1gene polymorphisms were associated with neither the risk of developing T2DM nor the risk of DN occurrence in diabetic patients. No association was observed between the patients with T2DM and DSPN (diabetic sensorimotor peripheral neuropathy) and T2DM without DSPN regarding investigated polymorphism.Conclusion. Our data suggest thatGSTP1gene polymorphisms may contribute to the development of T2DM in Romanian population.GSTM1,GSTT1, andGSTP1gene polymorphisms are not associated with susceptibility of developing diabetic neuropathy in T2DM patients.

Autologous cell therapy uses patients’ own cells to deliver precise and ideal treatment through a personalized medicine approach. Isolation of patients’ cells from residual tissue extracted during surgery involves specific planning and lab steps. In the present manuscript, a path from isolation to in vitro research with human mesenchymal stem cells (MSCs) obtained from residual bone tissues is described as performed by a medical unit in collaboration with a research center. Ethical issues have been addressed by formulating appropriate harvesting protocols according to European regulations. Samples were collected from 19 patients; 10 of them were viable and after processing resulted in MSCs. MSCs were further differentiated in osteoblasts to investigate the biocompatibility of several 3D scaffolds produced by electrospinning and 3D printing technologies; traditional orthopedic titanium and nanostructured titanium substrates were also tested. 3D printed scaffolds proved superior compared to other substrates, enabling significantly improved response in osteoblast cells, indicating that their biomimetic structure and properties make them suitable for synthetic tissue engineering. The present research is a proof of concept that describes the process of primary stem cells isolation for in vitro research and opens avenues for the development of personalized cell platforms in the case of patients with orthopedic trauma. The demonstration model has promising perspectives in personalized medicine practices.

The COVID-19 pandemic poses global healthcare challenges due to its unpredictable clinical course. The aim of this study is to identify inflammatory biomarkers and other routine laboratory parameters associated with in-hospital mortality in critical COVID-19 patients. We performed a retrospective observational study on 117 critical COVID-19 patients. Following descriptive statistical analysis of the survivor and non-survivor groups, optimal cut-off levels for the statistically significant parameters were determined using the ROC method, and the corresponding Kaplan-Meier survival curves were calculated. The inflammatory parameters that present statistically significant differences between survivors and non-survivors are IL-6 (p = 0.0004, cut-off = 27.68 pg/mL), CRP (p = 0.027, cut-off = 68.15 mg/L) and IL-6/Ly ratio (p = 0.0003, cut-off = 50.39). Additionally, other statistically significant markers are creatinine (p = 0.031, cut-off = 0.83 mg/dL), urea (p = 0.0002, cut-off = 55.85 mg/dL), AST (p = 0.0209, cut-off = 44.15 U/L), INR (p = 0.0055, cut-off = 1.075), WBC (p = 0.0223, cut-off = 11.68 × 10⁹/L) and pH (p = 0.0055, cut-off = 7.455). A survival analysis demonstrated significantly higher in-hospital mortality rates of patients with values of IL-6, IL-6/Ly, AST, INR, and pH exceeding previously mentioned thresholds. In our study, IL-6 and IL-6/Ly have a predictive value for the mortality of critically-ill patients diagnosed with COVID-19. The integration of these parameters with AST, INR and pH could contribute to a prognostic score for the risk stratification of critical patients, reducing healthcare costs and facilitating clinical decision-making.

Cardiovascular disease is most frequently caused by the development and progression of atherosclerosis. When coronary arteries are afflicted, and the stenoses caused by atherosclerotic plaques are severe enough, the metabolic supply-and-offer balance is disturbed, leading to myocardial ischemia. If atherosclerotic plaques become unstable and local thrombosis develops, a myocardial infarction occurs. Sometimes, myocardial ischemia and infarction may result in significant and irreversible heart failure. To prevent severe complications, such as acute coronary syndromes and ischemia-related heart failure, extensive efforts have been made for developing biomarkers that would help identify patients at increased risk for cardiovascular events. In this two-part study, we attempted to provide a review of existing knowledge of blood biomarkers that may be used in this setting. The first part of this work was dedicated to conventional biomarkers, which are already used in clinical practice. In the second part, here presented, we discuss emerging biomarkers which have not yet become mainstream.

The global escalation of severe infections due to carbapenemase-producing Enterobacterales (CPE) isolates has prompted increased usage of parenteral colistin. Considering the reported difficulties in assessing their susceptibility to colistin, the purpose of the study was to perform a comparative evaluation of six phenotypic assays—the colistin broth disc elution (CBDE), Vitek 2 Compact (bioMérieux SA, Marcy l’Etoile, France), the Micronaut MIC-Strip Colistin (Merlin Diagnostika GMBH, Bornheim-Hensel, Germany), the gradient diffusion strip Etest (bioMérieux SA, Marcy l’Etoile, France), ChromID Colistin R Agar (COLR) (bioMérieux SA, Marcy l’Etoile, France), and the Rapid Polymyxin NP Test (ELITechGroup, Signes, France)—versus the reference method of broth microdilution (BMD). All false resistance results were further assessed using population analysis profiling (PAP). Ninety-two nonrepetitive clinical CPE strains collected from two hospitals were evaluated. The BMD confirmed 36 (39.13%) isolates susceptible to colistin. According to the BMD, the Micronaut MIC-Strip Colistin, the CBDE, and the COLR medium exhibited category agreement (CA) of 100%. In comparison with the BMD, the highest very major discrepancy (VMD) was noted for Etest (n = 15), and the only false resistance results were recorded for the Rapid Polymyxin NP Test (n = 3). Only the PAP method and the Rapid Polymyxin NP Test were able to detect heteroresistant isolates (n = 2). Thus, there is an urgent need to further optimize the diagnosis strategies for colistin resistance.