The widespread use of antibiotics has resulted in the emergence of drug-resistant populations of microorganisms. Clearly, one can see the need to develop new, more effective, antimicrobial agents that go beyond the explored ‘chemical space’. In this regard, their unique modes of action (e.g., reactive oxygen species (ROS) generation, redox activation, ligand exchange, depletion of substrates involved in vital cellular processes) render metal complexes as promising drug candidates. Several Ru(II/III) complexes have been included in, or are currently undergoing, clinical trials as anticancer agents. Based on the in-depth knowledge of their chemical properties and biological behavior, the interest in developing new ruthenium compounds as antibiotic, antifungal, antiparasitic, or antiviral drugs has risen. This review will discuss the advantages and disadvantages of Ru(II/III) frameworks as antimicrobial agents. Some aspects regarding the relationship between their chemical structure and mechanism of action, cellular localization, and/or metabolism of the ruthenium complexes in bacterial and eukaryotic cells are discussed as well. Regarding the antiviral activity, in light of current events related to the Covid-19 pandemic, the Ru(II/III) compounds used against SARS-CoV-2 (e.g., BOLD-100) are also reviewed herein.

Background: Numerous tools, including nutritional and inflammatory markers, have been evaluated as the predictors of poor outcomes in COVID-19 patients. This study aims to verify the predictive role of the prognostic nutritional index (PNI), CONUT Score, and inflammatory markers (monocyte to lymphocyte ratio (MLR), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), systemic inflammatory index (SII), Systemic Inflammation Response Index (SIRI), and Aggregate Index of Systemic Inflammation (AISI)) in cases of deep vein thrombosis (DVT) and acute pulmonary embolism (APE) risk, as well as mortality, in COVID-19 patients. Methods: The present study was designed as an observational, analytical, retrospective cohort study, and included 899 patients over the age of 18 who had a COVID-19 infection, confirmed through real time-polymerase chain reaction (RT-PCR), and were admitted to the County Emergency Clinical Hospital and Modular Intensive Care Unit of UMFST “George Emil Palade” of Targu Mures, Romania between January 2020 and March 20212. Results: Non-Surviving patients were associated with a higher incidence of chronic kidney disease (p = 0.01), cardiovascular disease (atrial fibrillation (AF) p = 0.01; myocardial infarction (MI) p = 0.02; peripheral arterial disease (PAD) p = 0.0003), malignancy (p = 0.0001), tobacco (p = 0.0001), obesity (p = 0.01), dyslipidemia (p = 0.004), and malnutrition (p < 0.0001). Multivariate analysis showed that both nutritional and inflammatory markers had a high baseline value and were all independent predictors of adverse outcomes for all enrolled patients (for all p < 0.0001). The presence of PAD, malignancy, and tobacco, were also independent predictors of all outcomes. Conclusions: According to our findings, higher MLR, NLR, PLR, SII, SIRI, AISI, CONUT Score, and lower PNI values at admission strongly predict DVT risk, APE risk, and mortality in COVID-19 patients. Moreover, PAD, malignancy, and tobacco, all predicted all outcomes, while CKD predicts APE risk and mortality, but not the DVT risk.

We report the synthesis and characterization of three new complexes of the natural flavonoid 5-hydroxyflavone (primuletin) and Al (III), Ga (III), In (III), respectively. The physico-chemical properties and structural features of these three novel compounds have been investigated by elemental and thermogravimetric analysis, molar conductance and several spectroscopic techniques, including FT-IR, UV-Vis and mass spectra. Based on the experimental data, the general chemical formula of the complexes iswhere M is the cation and n = 2 for Al (III), n = 0 for Ga (III), n = 1, for In (III); each one of the three 5-hydoxyflavone molecules acts as a monoanionic bidentate chelate ligand in the complexes. DFT calculations further sustain the proposed structures of the complexes. Cytotoxicity was studied using MTS assay on cervical, breast, colon and ovary adenocarcinoma cell lines.The central metal ions exert cytotoxic effects in a disparate manner: Al (III) enhances, while Ga (III) and In (III) decrease the cytotoxicity of the ligand.As a means to investigate the mechanism underlying the cytotoxic effects of the complexes, interactions with calf thymus DNA, human serum albumin and transferrin were also carried out.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Background: Chronic kidney disease (CKD) is a global public health problem with a high mortality rate and a rapid progression to end-stage kidney disease (ESKD). Recently, the role of inflammation and the correlation between inflammatory markers and CKD progression have been studied. This study aimed to analyze the predictive value of the neutrophil–lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) in assessing the outcome of ESKD patients. Methods: A retrospective study which included all patients admitted in the Department of Nephrology of the County Emergency Clinical Hospital, Târgu-Mureș, Romania, between January 2016 and December 2019, diagnosed with ESKD. Results: Mortality at 30 days was clearly higher in the case of the patients in the high-NLR groups (40.12% vs. 1.97%; p < 0.0001), high-MLR (32.35% vs. 4.81%; p < 0.0001, and respectively high-PLR (25.54% vs. 7.94%; p < 0.0001). There was also a significant increase in the number of hospital days and the average number of dialysis sessions in patients with high-NLR (p < 0.0001), high-MLR (p < 0.0001), and high-PLR (p < 0.0001). The multivariate analysis showed that a high baseline value for NLR (p < 0.0001), MLR (p < 0.0001), and PLR (p < 0.0001) was an independent predictor of 30-day mortality for all recruited patients. Conclusions: Our findings established that NLR, MLR, and PLR determined at hospital admission had a strong predictive capacity of all-cause 30-day mortality in ESKD patients who required RRT for at least 6 months. Elevated values of the ratios were also associated with longer hospital stays and more dialysis sessions per patient.

Background: Peripheral arterial disease (PAD) changes the arterial structure and function, and is the most common manifestation of the atherosclerotic process, except for the coronary and cerebral arterial systems. Inflammation is well known to have a role in the progression of atherosclerosis and, by extension, in PAD. Among the recently studied markers in the literature, we list the neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR). This study aims to analyze the preoperative role of NLR and PLR in the medium-term outcome of patients surgically revascularized for femoropopliteal disease. Methods: A retrospective study included patients admitted to the Vascular Surgery Clinic of the County Emergency Clinical Hospital of Târgu-Mureș, Romania, between January 2017 and December 2019, diagnosed with femoropopliteal disease and having presented an indication for surgical revascularization. The patients included in the study were classified according to the 12 months primary patency in two groups: “patency” and “nonpatency”. Results: Depending on the Rutherford classification (RC), there was a higher incidence of stages II and III in the patency group and a higher incidence of stage V in the nonpatency group. Depending on the optimal cut-off value according to ROC for the 12 months primary patency, obtained from Youden’s index (3.95 for NLR (82.6% sensitivity and 89.9% specificity), and 142.13 for PLR (79.1% sensitivity and 82.6% specificity)), in all high-NLR and high-PLR groups, there was a higher incidence of all adverse outcomes. Moreover, a multivariate analysis showed that a high baseline value for NLR and PLR was an independent predictor of all outcomes for all recruited patients. Furthermore, for all hospitalized patients, RC 5 was an independent predictor of poor prognosis. Conclusions: Our findings establish that a high value of preoperative NLR and PLR determined at hospital admission is strongly predictive of primary patency failure (12 months after revascularization). Additionally, elevated ratio values are an independent predictor for a higher amputation rate and death for all patients enrolled in the study, except for mortality in RC 2, and both amputation and mortality in RC 5.

Background: An arteriovenous fistula (AVF) is the first-line vascular access pathway for patients diagnosed with end-stage renal disease (ESRD). In planning vascular access, it is necessary to check the diameters of the venous and arterial components for satisfactory long-term results. Furthermore, the mechanism underlying the maturation failure and short-term patency in cases of AVFs is not fully known. This study aims to verify the predictive role of inflammatory biomarkers (the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), systemic inflammatory index (SII), and C-reactive protein (CRP)), Ca-P product, the prognostic nutritional index (PNI), and the diameters of the venous and arterial components in the failure of AVF maturation. Methods: The present study was designed as an observational, analytical, and retrospective cohort study with a longitudinal follow-up, and included all patients with a diagnosis of ESRD that were admitted to the Vascular Surgery Clinic of the Targu Mures Emergency County Hospital, Romania, between January 2019 and December 2021. Results: The maturation of AVF at 6 weeks was clearly lower in cases of patients in the high-NLR (31.88% vs. 91.36%; p < 0.0001), high-PLR (46.94% vs. 85.55%; p < 0.0001), high-SII (44.28% vs. 88.89%; p < 0.0001), high-CRP (46.30% vs. 88.73%; p < 0.0001), high-Ca-P product (40.43% vs. 88.46%; p < 0.0001), and low-PNI (34.78% vs. 91.14%; p < 0.0001) groups, as well as in patients with a lower radial artery (RA) diameter (40% vs. 94.87%; p = 0.0009), cephalic vein (CV) diameter (44.82% vs. 97.14%; p = 0.0001) for a radio-cephalic AVF (RC-AVF), and brachial artery (BA) diameter (30.43% vs. 89.47%; p < 0.0001) in addition to CV diameter (40% vs. 94.59%; p < 0.0001) for a brachio-cephalic AVF (BC-AVF), respectively. There was also a significant increase in early thrombosis and short-time mortality in the same patients. A multivariate analysis showed that a baseline value for the NLR, PLR, SII, CRP, Ca-P product, and PNI was an independent predictor of adverse outcomes for all of the recruited patients. Furthermore, for all patients, a high baseline value for vessel diameter was a protective factor against any negative events during the study period, except for RA diameter in mortality (p = 0.16). Conclusion: Our findings concluded that higher NLR, PLR, SII, CRP, Ca-P product, and PNI values determined preoperatively were strongly predictive of AVF maturation failure, early thrombosis, and short-time mortality. Moreover, a lower baseline value for vessel diameter was strongly predictive of AVF maturation failure and early thrombosis.

Four novel monocationic Ru(II) polypyridyl complexes have been synthesized with the general formula [Ru(DIP)2flv]X, where DIP is 4,7-diphenyl-1,10-phenanthroline, flv stands for the flavonoid ligand (5-hydroxyflavone in [Ru(DIP) 2 (5-OHF)](PF 6), genistein in [Ru(DIP)2(gen)](PF6), chrysin in [Ru(DIP)2(chr)](OTf), and morin in [Ru(DIP)2(mor)](OTf)) and X is the counterion, PF6, and OTf ̄ (triflate, CF3SO3̄), respectively. Following the chemical characterisation of the complexes by 1 H and 13 C-NMR, mass spectrometry and elemental analysis, their cytotoxicity was tested against several cancer cell lines. The most promising complex, [Ru(DIP) 2 (gen)](PF 6), was further investigated for its biological activity. Metabolic studies revealed that this complex severely impaired mitochondrial respiration and glycolysis processes, contrary to its precursor, Ru(DIP)2Cl2, which showed a prominent effect only on the mitochondrial respiration. In addition, its preferential accumulation in MDA-MB-435S cells (a human melanoma cell line previously described as mammary gland/breast; derived from metastatic site: pleural effusion), that are used for the study of metastasis, explained the better activity in this cell line compared to MCF-7 (human, ductal carcinoma).

Acute Limb Ischemia (ALI) of the lower limb is defined as a sudden drop in arterial limb perfusion, which is a medical emergency requiring prompt intervention with high amputation and mortality rates in the absence of revascularization. This observational, analytical, and retrospective cohort study with longitudinal follow-up aimed to confirm the relevance of the preoperative inflammatory biomarkers neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in predicting the 30-day poor prognosis of patients with Rutherford classification (RC) grades II and III ALI. The ROC analysis found a strong association of an NLR > 4.33 with all studied outcomes, while a PLR > 143.34 was associated with all studied outcomes, except the composite endpoint in all RC stages. Depending on the optimal cut-off value, the ROC analysis found a higher incidence of all adverse outcomes in all high NLR (>4.33) and high PLR (>143.34) groups. A multivariate analysis showed that a high baseline value for NLR and PLR was an independent predictor of amputation (OR:11.09; 95% CI: 5.48–22.42; p < 0.0001; and OR:8.97; 95% CI: 4.44–18.16; p < 0.0001), mortality (OR:22.24; 95% CI: 9.61–51.47; p < 0.0001; and OR:8.32; 95% CI: 3.90–17.73; p < 0.0001), and composite endpoint (OR:21.93; 95% CI: 7.91–60.79; p < 0.0001; and OR:9.98; 95% CI: 3.89–25.55; p < 0.0001), respectively. Furthermore, for all hospitalized patients, the RC grade III (OR:7.33; 95% CI: 3.73–14.26; p < 0.0001) was an independent predictor of amputation (OR:7.33; 95% CI: 3.73–14.26; p < 0.0001), mortality (OR:8.40; 95% CI: 4.08–17.31; p < 0.0001), and composite endpoint (OR: 10.70; 95% CI: 4.48–25.56; p < 0.0001), respectively. The NLR and PLR are excellent predictors of risks associated with ALI for primary and secondary prevention. Our study showed that increased pre-operative values for NLR and PLR are indicators of a poor outcome in patients with RC grades II and III ALI.