Using 8-Hydroxy-2'-Deoxiguanosine (8-OHdG) as a Reliable Biomarker for Assessing Periodontal Disease Associated with Diabetes.

In recent years, research has shown that oxidative stress plays a significant role in chronic inflammatory conditions. The alteration of the oxidant/antioxidant balance leads to the appearance of free radicals, important molecules involved in both diabetes mellitus and periodontal disease. Diabetes is considered to be one of the major risk factors of periodontal disease and the inflammation characterizing this condition is associated with oxidative stress, implicitly resulting in oxidative damage to DNA. 8-Hydroxydeoxyguanosine (8-OHdG) is the most common stable product of oxidative DNA damage caused by reactive oxygen species, and its levels have been reported to increase in body fluids and tissues during inflammatory conditions. 8-OHdG emerges as a pivotal biomarker for assessing oxidative DNA damage, demonstrating its relevance across diverse health conditions, including neurodegenerative disorders, cancers, inflammatory conditions, and periodontal disease. Continued research in this field is crucial for developing more precise treatments and understanding the detailed link between oxidative stress and the progression of periodontitis. The use of the 8-OHdG biomarker in assessing and managing chronic periodontitis is an area of increased interest in dental research, with the potential to provide crucial information for diagnosis and treatment.

Short Review on the Biological Activity of Cyclodextrin-Drug Inclusion Complexes Applicable in Veterinary Therapy.

Cyclodextrins (CDs) are a family of carrier molecules used to improve the pharmacokinetic parameters of therapeutic molecules. These cyclic oligosaccharides have medical and pharmaceutical applications by being able to form inclusion complexes with molecules that are poorly soluble in water. The benefits of these complexes are directed towards improving the chemical and biological properties-i.e., solubility, bioavailability, stability, non-toxicity and shelf life of drug molecules. Since the 1960s, the first inclusion complexes used in therapeutics were those with α-, ß- and γ-CD, which proved their usefulness, but had certain degrees of particularly renal toxicity. Currently, to correct these deficiencies, ß-CD derivatives are most frequently used, such as sulfobutylether-ß-CD, hydroxypropyl-ß-CD, etc. Therefore, it is of interest to bring to the attention of those interested the diversity of current and potential future clinical applications of inclusion complexes in veterinary medicine and to present the contribution of these inclusion complexes in improving drug efficacy. The most important biological activities of ß-CD complexed molecules in the veterinary field are summarized in this short review.

Medical Staff Training - Quality Initiative to Reduce Errors in the Pre-Preanalytical Phase.

BACKGROUND: Numerous studies indicate that most error sources in hemostasis laboratories occur during the pre preanalytical phase through biological product sampling. OBJECTIVES: The purpose of this study was documentation, monitoring, and reduction of preanalytical errors through operator training. METHODS: For a period of 4 months in the "St. SpiridonË® Hospital from Iasi, 978 specimens were identified with non-conformities, due to the following causes: insufficiently-collected, hemolyzed- and coagulated samples. Data collection was conducted in two stages: before and after training of medical staff in clinical departments, upon improving the coagulation specimen sampling practices. RESULTS: The study pointed out that subsequent to training, a reduction of the coagulated samples has been registered as follows: in medical departments from 33.33% to 16.78%, in surgery from 27.20% to 17.02%, ICU (intensive care units) from 10.63% to 8.74%, and slightly in EU (emergency) from 10.63% to 8.74%. Moreover, we noticed that the incidence of hemolyzed samples increased in clinical sections, as follows: EU from 4.50% to 14.89%, medical departments from 3.42% to 9.21%, surgery from 1.44% to 6.38%, and 4.50% to 14.89% for ICU. The insufficiently sampled volume persisted during the study in almost all sections: surgery from 1.80% to 4.96%, medical from 2.52% to 4.96%, EU from 1.80% to 3.78% with a slight decrease in ICU from 1.26% to 1.18%. CONCLUSIONS: Nurses traditionally represent the core of quality medical services. Peer education is effective and implementation and compliance of sample collection procedure rules ultimately providing patient safety.

Evaluation of cardiovascular risk factors in patients with familial hypercholesterolemia from the North-Eastern area of Romania.

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.

Interferences between Clot in the Erythrocyte Sediment and Hemostasis Exploration.

BACKGROUND: The selection and rejection of non-conforming coagulation specimens is essential in safeguarding quality management in hemostasis laboratories that provide routine testing for bleeding and thrombotic disorders. In order to increase quality, it is important to reduce pre-analytical errors that generally account for 60 - 70% of total laboratory failure. The accidental presence of clots in vitro, in the pre-analytical phase of the coagulation, is a reason for coagulation specimen rejection, given that the reliability of test results can be adversely compromised. This study aimed to ascertain the effect of clots identified in the post-analytical phase within the blood sample sediments upon standard laboratory tests such as PT (prothrombin time) and APTT (activated partial thromboplastin time). METHODS: From a total of 24,670 coagulation specimens gathered and prospectively collected and analyzed at the Haematology Laboratory of the Ë®Sf. SpiridonË® Emergency County Hospital Iasi, Romania, during four months, 671 were identified with clot. Of the coagulated samples, 153 (22.80%) were considered for this study, including those specimens pinpointed with sediment clot through a post-analytical new reverification procedure. RESULTS: The comparative study of the PT and APTT results obtained based on the samples identified with sediment clots in relation to the actual results recorded after the repetition of the sampling, pointed out 43.93% false results for PT1 test, with a significant difference between the variances of the values at the two evaluated moments (t = 2.961, p = 0.0037). The pattern was congruent in the case of the APTT test as well, exhibiting 69.04% false results, for which the variances of values at the two evaluated moments displayed significant differences (t = 2.208, p = 0.0306). In both of the cases significantly lower mean values were noted in the second determination of PT (PT1: 33.1 ± 39.6 vs. PT2: 25.8 ± 30.5) and APTT (APTT1: 42.8 ± 42.7 vs. APTT2: 38.1 ± 26.1. Results are important as they highlight the actual interference between the clot in the erythrocyte sediment and the evaluation of the patient's hemostasis. CONCLUSIONS: Our results confirm that the presence of clots in the erythrocyte sediment, with no identification prior to centrifugation, significantly affect the PT and APTT analysis, their accurate results being critical for the proper diagnosis and monitoring of anticoagulant therapy.

Chronometric vs. Structural Hypercoagulability.

Prolonged tourniquet stasis induced by venepuncture can lead to the release of the plasma of cell lysis products, as well as tissue factor (TF), impairing the quality of coagulation test results. The accidental presence of TF in vitro can trigger the coagulation mechanism, generating a false decrease in prothrombin time (PT). Background and Objectives: Identification of short PT tests below the normal reference value that could suggest a situation of hypercoagulability. The study aimed to compare the results of the shortened PT tests at their first determination with the eventual correction following duplication of the analysis from the same sample. Materials and methods: Identification of the shortened PT tests has been carried out for a period of 4 months, upon 544 coagulation samples referred to the Hematology department of Sf. Spiridon County Clinical Emergency Hospital from Iasi, Romania. Results: Out of the 544 samples of which the results indicated a state of hypercoagulability, by repeating the determination from the same sample, for 200 (36.76%) PT tests (p = 0.001) the value was corrected, falling within the normal reference range. For 344 (63.24%) tests, the results suggested a situation of hypercoagulability. Conclusions: In order to guarantee the highest quality of the laboratory services, a proper interpretation and report of the patients' results must be congruent and harmoniously associated to the actual clinical condition of the patient. Duplication of the PT determination from the same sample would exclude situations of false hypercoagulability and would provide significant improvement for the patient's safety.

Blood Clot Identification Procedures in Clinical Laboratory Sampling.

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.

Ulcerated Hemangioma - Surveillance Only.

Infantile hemangiomas are reported in 10-12% of children less than 1 year of age, with ulceration in about 5-13% of cases. Little is known about the mechanism of this disease and explanations are still being looked for. We present a 4-month-old female infant with haemangioma on the left buttock; the hemangioma was noticed at 2 weeks of age, progressively enlarging and ulcerated.

Diabetic dermopathy ("shin spots") and diabetic bullae ("bullosis diabeticorum") at the same patient.

We present a diabetic patient with associated two diabetic dermatoses: diabetic dermopathy ("shin spots") and diabetic bullae. A 34-year-old man, with long history of diabetes mellitus, hypertension, and moderate obesity presented to Dermatology Unit for diagnosis of his skin lesions. On clinical examination multiple, light brown, irregular patches, with atrophic scars and crusts over large bullae were observed on the anterior aspect of both legs.

Early Detection of Inflammation and Malnutrition and Prediction of Acute Events in Hemodialysis Patients through PINI (Prognostic Inflammatory and Nutritional Index).

Protein-energy wasting and inflammation are major risk factors for complications in hemodialysis patients. As these risk factors are triggered by a pro-inflammatory state, oxidative stress and hemodynamic dysfunction, which overlap in hemodialyzed subjects, we aimed to assess the efficacy of a cost-effective and straightforward screening tool, the Prognostic Inflammatory and Nutritional Index (PINI), in regularly screening maintenance hemodialysis (MHD) patients, to detect early signs of inflammation and malnutrition. A 12-month follow-up was carried out on a cohort of 102 adult patients undergoing maintenance dialysis, during which the Prognostic Inflammatory and Nutritional Index (PINI) was calculated using the formula alpha1-Acid Glycoprotein (AGP) × C-reactive protein (CRP)/albumin (ALB) × transthyretin (TTR). A PINI score < 1 was considered normal. The patients were stratified based on their PINI score: 66 patients (64.70%) had a normal score, below 1, while 36 patients (35.30%) had a PINI score ≥ 1. Despite the absence of clinical evidence of inflammation at enrollment, the latter group exhibited higher levels of CRP. During the follow-up period, all patients with a PINI score ≥ 1 experienced at least one acute event, compared to only 6% of patients with a normal PINI score, which presented COVID-19 infection as an acute event. The evaluation of the PINI can effectively identify the silent malnutrition-inflammation syndrome and predict the risk of acute events. This straightforward test appears to be a rapid tool that is independent of the examiner's experience and subjectivity, thereby potentially reducing hospitalization costs.

Environmental and Metabolic Risk Factors Linked to Gallbladder Dysplasia.

Gallbladder disorders encompass a spectrum from congenital anomalies to inflammatory and neoplastic conditions, frequently requiring surgical intervention. Epithelial abnormalities like adenoma and metaplasia have the potential to progress to carcinoma, emphasizing the importance of histopathological assessment for early detection of malignancy. Gallbladder cancer (GBC) may be incidentally discovered during cholecystectomy for presumed benign conditions, underscoring the need for a thorough examination. However, the lack of clarity regarding the molecular mechanisms of GBC has impeded diagnostic and therapeutic advancements. Timely detection is crucial due to GBC's aggressive nature and poor prognosis. Chronic inflammation plays a central role in carcinogenesis, causing DNA damage and oncogenic alterations due to persistent insults. Inflammatory cytokines and microRNAs are among the various mediators contributing to this process. Gallbladder calcifications, particularly stippled ones, may signal malignancy and warrant preemptive removal. Molecular pathways involving mutations in oncogenes and tumor suppressor genes drive GBC pathogenesis, with proposed sequences such as gallstone-induced inflammation leading to carcinoma formation. Understanding these mechanisms, alongside evaluating mucin characteristics and gene mutations, can deepen comprehension of GBC's pathophysiology. This, in turn, facilitates the identification of high-risk individuals and the development of improved treatment strategies, ultimately enhancing patient outcomes. Thus, in this review, our aim has been to underscore the primary mechanisms underlying the development of gallbladder dysplasia and neoplasia.

The synthesis and the biological evaluation of new thiazolidin-4-one derivatives containing a xanthine moiety.

Starting from theophylline (1,3-dimethylxanthine) new thiazolidin-4-one derivatives 7a1₋7, 7b1₋7 have been synthesized as potential antidiabetic drugs. The structure of the new derivatives was confirmed using spectral methods (FT-IR, ¹H-NMR, ¹³C-NMR). The in vitro antioxidant potential of the synthesized compounds was evaluated according to the ferric reducing power, the total antioxidant activity and the DPPH and ABTS radical scavenging assays. Reactive oxygen species (ROS) and free radicals are considered to be implicated in a variety of pathological events, such as diabetes mellitus and its micro- and macrovascular complications. The results of chemical modulation of the thiazolidin-4-one intermediaries 6a, 6b through condensation with several aromatic aldehydes is the improvement of the antioxidant effect. All benzylidenethiazolidin-4-one derivatives 7a1₋7, 7b1₋7 are more active than their parent thiazolidin-4-ones. The most active compounds are the ones obtained by reaction of condensation with 4-hydroxybenzaldehyde (compounds 7a5, 7a6), 4-dimethylaminobenzaldehyde (compounds 7a6, 7b6) and 2-nitrobenzaldehyde (compounds 7a7, 7b7).

The Role and Involvement of Stem Cells in Periodontology.

Periodontitis is a widespread inflammatory condition, characterized by a progressive deterioration of the supporting structures of the teeth. Due to the complexity of periodontal tissue and the surrounding inflammatory microenvironment, the repair of lesions at this level represents a continuous challenge. The regeneration of periodontal tissues is considered a promising strategy. Stem cells have remarkable properties, such as immunomodulatory potential, proliferation, migration, and multilineage differentiation. Thus, they can be used to repair tissue damage and reduce inflammation, potentially leading to periodontal regeneration. Among the stem cells used for periodontal regeneration, we studied dental mesenchymal stem cells (DMSCs), non-dental stem cells, and induced pluripotent stem cells (IPSCs). Although these cells have well documented important physiological characteristics, their use in contemporary practice to repair the affected periodontium is still a challenge.

The Effectiveness of Laser Applications and Photodynamic Therapy on Relevant Periodontal Pathogens (Aggregatibacter actinomycetemcomitans) Associated with Immunomodulating Anti-rheumatic Drugs.

Considering the current context of the increasing resistance of bacterial species to antibiotics and other antimicrobial agents, a major objective is to develop other antimicrobial approaches, which would be able to inactivate pathogens with considerable effectiveness. Two such methods are photodynamic disinfection therapy and laser irradiation. In view of the immunocompromised status of some patients under immunosuppressive therapy and potential drug interactions that can be established between systemic antimicrobial agents, the research of local, minimally invasive methods of inactivating periodontal pathogens in the context of these systemic therapies with modifying drugs of the immune response is justified. This in vitro study evaluated the antimicrobial action of a diode laser, wavelength 940 nm, and photodisinfection therapy at 670 nm (photosensitizer, 3,7 dimethyl phenothiazine chloride) on a type strain of Aggregatibacter actinomycetemcomitans, a known periodontal pathogen, in the presence and absence of active substances used in autoimmune disease therapy (Etanercept, Infliximab, Metothrexate). The association of a conventional antirheumatic drug with anti-TNF-α therapy determined a significantly greater inhibition of the strain of A. actinomycetemcomitans compared to monotherapy, in vitro. Photodisinfection caused a significant reduction in bacterial burden after a 30 s exposure in vitro, regardless of the pharmaceutical associations of biological and conventional disease-modifying antirheumatic drugs (DMARDs). Irradiation with a diode laser for 30 s at a power of 5 W caused a greater reduction compared to irradiation with 1 W. The application of laser and photodisinfection induced a significant reduction in Aggregatibacter actinomycetemcomitans in vitro and could be considered important adjunctive measures for the eradication of this oral pathogen in the context of immunomodulating therapy.

Various Surgical Interventions in Treating Odontogenic Keratocyst: A Radiological Case Report.

The odontogenic keratocyst (OKC) is among the most aggressive odontogenic cysts because of its high recurrent rate. This study's objective was to describe a 7-year radiological and clinical follow-up of an OKC with two recurrences and a combination of surgical treatments. The cyst contents were drained at the biopsy to allow decompression, and then marsupialization (Partsch I) was carried out with good results. In the following two years, the endodontic and radiological evaluation of the neighboring teeth indicated endodontic avoidance. The remaining OKC enucleation (Partsch II) with chemical curettage and suture was performed two years after the first presentation, and the multifocal recurrences developed were also treated by enucleation and chemical curettage. At the last radiological follow-up, no recurrence was evident. Based on our experience, we concluded that patients diagnosed with a OKC should be radiologically evaluated at least once a year for at least 7 years, the endodontic diagnosis and treatment of neighboring teeth should be performed as early as possible, and the combination of surgical treatment and the long follow-up period is challenging.

The Role of the Prognostic Inflammatory and Nutritional Index (PINI) in the Evolution of Patients with Chronic Kidney Disease and Other Pathologies.

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.

Mitochondrial Dysfunction, Oxidative Stress, and Therapeutic Strategies in Diabetes, Obesity, and Cardiovascular Disease.

Mitochondria are subcellular organelles involved in essential cellular functions, including cytosolic calcium regulation, cell apoptosis, and reactive oxygen species production. They are the site of important biochemical pathways, including the tricarboxylic acid cycle, parts of the ureagenesis cycle, or haem synthesis. Mitochondria are responsible for the majority of cellular ATP production through OXPHOS. Mitochondrial dysfunction has been associated with metabolic pathologies such as diabetes, obesity, hypertension, neurodegenerative diseases, cellular aging, and cancer. In this article, we describe the pathophysiological changes in, and mitochondrial role of, metabolic disorders (diabetes, obesity, and cardiovascular disease) and their correlation with oxidative stress. We highlight the genetic changes identified at the mtDNA level. Additionally, we selected several representative biomarkers involved in oxidative stress and summarize the progress of therapeutic strategies.

Atherosclerosis in Patients with Congenital Hemophilia: A Focus on Peripheral Artery Disease.

Advances in the treatment of hemophilia have increased the life expectancy of this population and we are currently facing diseases associated with aging, including cardiovascular ones. Coronary atherosclerosis, with acute myocardial infarction as the most severe form of manifestation, has been recognized as part of the comorbidities of hemophiliacs. However, little is known about peripheral artery disease. Available data show that hemophiliacs have cardiovascular risk factors and atherosclerosis similar to the general population. Impaired thrombus formation and phenotype of atheroma plaque rather than the burden of atherosclerosis explains their lower cardiovascular mortality. Since the effect of traditional cardiovascular risk factors overpowers that of decreased coagulability and promotes the onset and progression of atherosclerotic lesions, screening for traditional cardiovascular risk factors and peripheral artery disease should be integrated into standard hemophilia care. There is evidence that invasive treatments and long-term antithrombotic therapy are generally safe, provided that coagulation factor levels are taken into account and replacement therapy is given when necessary.

Mycobacterium tuberculosis and Pulmonary Rehabilitation: From Novel Pharmacotherapeutic Approaches to Management of Post-Tuberculosis Sequelae.

Tuberculosis (TB) is still a worldwide public health burden, as more than 1.3 million deaths are expected to be reported in 2021. Even though almost 20 million patients have completed specific anti-TB treatment and survived in 2020, little information is known regarding their pulmonary sequelae, quality of life, and their need to follow rehabilitation services as researchers shifted towards proper diagnosis and treatment rather than analyzing post-disease development. Understanding the underlying immunologic and pathogenic mechanisms during mycobacterial infection, which have been incompletely elucidated until now, and the development of novel anti-TB agents could lead to the proper application of rehabilitation care, as TB sequelae result from interaction between the host and Mycobacterium tuberculosis. This review addresses the importance of host immune responses in TB and novel potential anti-TB drugs' mechanisms, as well as the assessment of risk factors for post-TB disease and usefulness of guidance and optimization of pulmonary rehabilitation. The use of rehabilitation programs for patients who successfully completed anti-tuberculotic treatment represents a potent multifaceted measure in preventing the increase of mortality rates, as researchers conclude that a patient with a TB diagnosis, even when properly completing pharmacotherapy, is threatened by a potential life loss of 4 years, in comparison to healthy individuals. Dissemination of pulmonary rehabilitation services and constant actualization of protocols could strengthen management of post-TB disease among under-resourced individuals.

Evaluation of cardiovascular events and progression to end-stage renal disease in patients with dyslipidemia and chronic kidney disease from the North-Eastern area of Romania.

PURPOSE: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.