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The aim of this prospective cohort study was: to identify the association between different biomarkers [proprotein convertase subtilisin/kexin 9-PCSK9, lipoprotein(a)-Lp(a) and high-sensitivity C-reactive protein-hsCRP] and the cardiovascular events; to evaluate the relationship between the 3 biomarkers mentioned above and the renal outcomes that contributed to end-stage renal disease (ESRD).We studied 110 patients with chronic kidney disease (CKD) stages 2 to 4. The identification of the new cardiovascular events and the renal outcomes were performed by clinical and paraclinical explorations.350 patients were examined and 110 (31.4%) were included in this study. The mean age was 55.6 ± 10.9 years, with a higher number of men compared to women. The CKD patients with de novo cardiovascular events and new renal outcome during the study, had significantly increased values of total cholesterol (TC), low density cholesterol lipoprotein (LDL-C) at 6 and 12 months and higher levels of Lp(a), PCSK9, hsCRP and low ankle-brachial index (ABI) and ejection fraction (EF) values compared to patients without cardiovascular and renal events. In CKD patients, PCSK9 220 ng/mL was a predictor of cardiovascular events, while the EF 50% was a predictor for renal outcomes. For CKD patients with PCSK9 220 ng/mL and hsCRP 3 mg/L levels, the time-interval for the new cardiovascular and renal events occurrence were significantly decreased compared to patients displaying low values of these biomarkers.The results of this study show that PCSK9 220 ng/mL was predictor for cardiovascular events, while EF 50% was predictor for CKD progression to ESRD. PCSK9 220 ng/mL and hsCRP 3 mg/L were associated with the occurrence of renal and cardiovascular events earlier.

The aim of this retrospective study was: to analyze the epidemiological patterns of the kidney disease based on clinical and histological features in a single-center in the N-E region of Romania, between 2011 and 2019 and to compare the biopsy results with the others periods, as well as the results from other countries. We studied 442 renal biopsies. The indications for renal biopsy were represented by the clinical features: nephrotic syndrome, nephritic syndrome, asymptomatic urinary abnormalities, acute kidney injury, and chronic kidney disease of unknown etiology. During the past 8 years, the annual incidence of renal biopsies was constant, albeit this incidence remained lower than in other countries. Nephrotic syndrome was the most common indication for renal biopsy (47.6%). Primary glomerulonephritis (GN) was the most common diagnosis in each of the three periods, followed by secondary GN. Vascular nephropathy and TIN were constant as a proportion from the overall biopsies in each of the three periods. The membranoproliferative GN (24.4%) and membranous nephropathy (MN) (21.9%) were the most prevalent primary GN, while lupus nephritis (LN) was the most common secondary glomerular disease in young female patients (7.5%). Compared to 1994–2004 period, we observed a significant decrease of incidence of focal segmental glomerulosclerosis (FSGS) and mesangial proliferative GN, and a significant increases in the frequency of MN. The results of this study show that the GN distribution model was constant in N-E Romania and became similar to that observed in many countries with high socio-economic status.

Background: Protein-energy loss and inflammation are the main risk factors in the occurrence of complications in hemodialysis patients. The Prognostic Inflammatory and Nutritional Index (PINI) is a simple, inexpensive test to identify the early onset of inflammation and malnutrition in hemodialysis patients, critically ill subjects and those with malignancies. Methods: A systemic review of English literature was conducted on the topic published between 1985 and 2022. A focused and sensitive search strategy was applied to the PUBMED database to identify relevant scientific articles in English. Once articles were identified, a detailed quality and bias assessment was performed. Two independent researchers analyzed the detailed data extraction. Results: PINI proved to be a sensitive, powerful, low-cost and simple test. PINI has been useful in assessing evolution and prognostics in clinical care, with values above one being associated with a high risk of mortality and morbidity. It is useful in cases with surgical and postoperative complications, long hospitalization, as well as increased associated expenses. Conclusions: This is the first review of the literature on the above-mentioned topic (PINI) and is a valuable candidate for validating prognosis in patients with different pathologies.

Aging hemophiliacs face cardiovascular disease. Lots of evidence has been gathered that hemophiliacs have a more unfavorable cardiovascular profile than the general population does, especially due to the increased prevalence of hypertension (HTN). Among the existing scattered evidence, our study provides the most comprehensive and systematized analysis of the determinants of HTN in hemophiliacs. We discussed the contribution to the HTN substrate of hemophilia-specific factors, such as type, severity and the presence of inhibitors. The complex mechanism of kidney dysfunction in relation to hematuria and viral infections was meticulously addressed. Furthermore, we highlighted the new pathogenic concepts of endothelial dysfunction and the association between HTN and hemophilic arthropathy. The clustering of cardiovascular risk factors is common in hemophiliacs, and it enhances the negative vascular effect of HTN and aggravates HTN. It usually leads to an increased risk for coronary and cerebrovascular events. Our work provides reliable evidence to guide and improve the management of HTN in hemophiliacs.

Venous thromboembolism (VTE) is a major healthcare problem due to its high incidence, significant mortality rate from pulmonary embolism, high recurrence rate and morbidity from long-term complications. After a first episode of VTE all patients must receive anticoagulant treatment for 3 months. Further anticoagulation is recommended in patients without transient risk factors for VTE or patients with active cancer, if they are not at a high risk for bleeding. The VTE-BLEED risk score was created with the purpose of enabling a better stratification of the bleeding risk during stable anticoagulation after a first VTE. Currently, it is the most validated risk score in VTE settings (selected and non-selected cohorts). It has a good prediction power for major bleeding events in patients receiving any of the currently available classes of oral anticoagulants, and it can identify patients at risk of intracranial and fatal bleeding events. The aim of our review was to highlight the strengths of the VTE-BLEED risk score, to acknowledge its weak points and to properly position its use in current medical practice.

Background Familial hypercholesterolemia(FH) is one of the most frequent and important monogenic cholesterol pathologies. Traditional and non-traditional cardiovascular risk factors increase the prevalence of atherosclerotic cardiovascular disease(ASCVD) in this population. The aims of the study were: (a) to identify FH patients in the North-Eastern part of Romania and to analyze demographic, clinical and paraclinical data (b) to evaluate the risk of new cardiovascular events at follow-up in FH patients stratified by lipid-lowering agents. Methods This first prospective study in the North-Eastern part of Romania was carried out between October 2017 and October 2019; out of 980 patients with dyslipidemia evaluated with the Dutch Lipid Network(DLCN) and Simon Broome(SM) scores, 61 patients with DLCN score above 3 and possible/probable FH(SM score) were included. Results Nine hundred-eighty patients were examined and 61 (6.2%) were received the clinical diagnosis of FH. The mean age was 48.5±12.5 years, with more female patients than male patients (63.9% versus 36%). Hypertension was the main cardiovascular risk factor for both genders, followed by physical inactivity and obesity for the female group and active smoking for the male group. The measured DLCN score recorded: “possible” FH identified in 39.4%, “probable” FH in 45.9% and “definite” FH in 14.7%. The effective lipid-lowering drugs used were statin alone and statin in association with fenofibrate, which improved both the lipid profile values and the subclinical atherosclerosis markers (ankle-brachial index, carotid intima-media thickness and high-sensitivity C-reactive protein). New ASCVDs that emerged during the study were most commonly represented by coronary heart disease and stroke. At the same time, the new cardiovascular events were delayed in patients receiving the lipid-lowering drugs, without significant differences between them. Conclusions In patients with suspected FH, the lipid-lowering agents during the follow-up period delayed the new cardiovascular events, yet failed to reach the goals proposed by the guidelines.

Purpose. Nontraditional cardiovascular risk factors as apolipoprotein A (ApoA), apolipoprotein B (ApoB), and the proprotein convertase subtilisin/kexin type 9 (PCSK9) increase the prevalence of cardiovascular mortality in chronic kidney disease (CKD) or in end-stage renal disease (ESRD) through quantitative alterations. This review is aimed at establishing the biomarker (ApoA, ApoB, and PCSK9) level variations in uremic patients, to identify the studies showing the association between these biomarkers and the development of cardiovascular events and to depict the therapeutic options to reduce cardiovascular risk in CKD and ESRD patients.Methods. We searched the electronic database of PubMed, Scopus, EBSCO, and Cochrane CENTRAL for studies evaluating apolipoproteins and PCSK9 in CKD and ESRD. Randomized controlled trials, observational studies (including case-control, prospective or retrospective cohort), and reviews/meta-analysis were included if reference was made to those keys and cardiovascular outcomes in CKD/ESRD.Results. 18 studies met inclusion criteria. Serum ApoA-I has been significantly associated with the development of new cardiovascular event and with cardiovascular mortality in ESRD patients. ApoA-IV level was independently associated with maximum carotid intima-media thickness (cIMT) and was a predictor for sudden cardiac death. The ApoB/ApoA-I ratio represents a strong predictor for coronary artery calcifications, cardiovascular mortality, and myocardial infarction in CKD/ESRD. Plasma levels of PCSK9 were not associated with cardiovascular events in CKD patients.Conclusions. Although the “dyslipidemic status” in CKD/ESRD is not clearly depicted, due to different research findings, ApoA-I, ApoA-IV, and ApoB/ApoA-I ratio could be predictors of cardiovascular risk. Serum PCSK9 levels were not associated with the cardiovascular events in patients with CKD/ESRD. Probably in the future, the treatment of dyslipidemia in CKD/ESRD will be aimed at discovering new effective therapies on the action of these biomarkers.

This study identifies the genetic background of familial hypercholesterolemia (FH) patients in Romania and evaluates the association between mutations and cardiovascular events. We performed a prospective observational study of 61 patients with a clinical diagnosis of FH selected based on Dutch Lipid Clinic Network (DLCN) and Simon Broome score between 2017 and 2020. Two techniques were used to identify mutations: multiplex ligation-dependent probe amplification (MLPA) and Sanger sequencing. The mutation rate was 37.7%, i.e., 23 patients with mutations were identified, of which 7 subjects had pathogenic mutations and 16 had polymorphisms. Moreover, 10 variants of the low-density lipoprotein receptor (LDLR) gene were identified in 22 patients, i.e., one variant of the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene in six patients, and one variant of the apolipoprotein B (APOB) gene in three patients. Of the LDLR gene variants, four were LDLR pathogenic mutations (c.81C &gt, G, c.502G &gt, A, c.1618G &gt, A mutations in exon 2, exon 4, exon 11, and exon 13–15 duplication). The PCSK9 and APOB gene variants were benign mutations. The pathogenic LDLR mutations were significant predictors of the new cardiovascular events, and the time interval for new cardiovascular events occurrence was significantly decreased, compared to FH patients without mutations. In total, 12 variants were identified, with four pathogenic variants identified in the LDLR gene, whereas 62.3% of the study population displayed no pathological mutations.

Background Monitoring of anticoagulation therapy is based on screening tests: prothrombin time (PT) and activated partial thromboplastin time (APTT). The accidental presence of a clot in the coagulation samples determines a false prolongation of PT by fibrinogen (FI) consumption and the false or delayed prolongation of APTT, depending on FI consumption or activation. The purpose of this study is to document from the present data re-garding procedures used to exclude the accidental presence of clot in the sample. Methods For a more efficient approach, we conducted a study based on research from the main databases that included original and peer-reviewed studies. Results We have reported studies in which pre-analytical procedures have been recommended and studies that have also presented post-analytical protocols. A correlation between the efficiency of the procedures in terms of additional laboratory costs has been performed, as well. Conclusions Focusing on patient safety, it remains a continuous challenge for each laboratory to be able to establish its own pre-analytical and post-analytical procedure for highlighting accidental clot presence, thus ensuring provision of results with maximum confidence to the clinicians.