Dysbiosis in Multiple Sclerosis: Can Immunoglobulin Y Supplements Help?

The role of gut microbiota in autoimmune disorders like multiple sclerosis is gaining attention. Multiple sclerosis is characterized by inflammation, demyelination, and neurodegeneration in the central nervous system. Alterations in gut microbiota have been linked to multiple sclerosis development, with decreased beneficial bacteria and increased harmful species. The gut-brain axis is a complex interface influencing bidirectional interactions between the gut and the brain. Dysbiosis, an imbalance in gut microbiota, has been associated with autoimmune diseases. The influence of gut microbiota in multiple sclerosis is reversible, making it a potential therapeutic target. Probiotics, prebiotics, and fecal microbiota transplantation have shown promise in multiple sclerosis treatment, with positive effects on inflammation and immune regulation. Immunoglobulin Y (IgY) supplements derived from chicken egg yolk have potential as nutraceuticals or dietary supplements. IgY technology has been effective against various infections, and studies have highlighted its role in modulating gut microbiota and immune responses. Clinical trials using IgY supplements in multiple sclerosis are limited but have shown positive outcomes, including reduced symptoms, and altered immune responses. Future research directions involve understanding the mechanisms of IgY's interaction with gut microbiota, optimal dosage determination, and long-term safety assessments. Combining IgY therapy with other interventions and investigating correlations between microbiota changes and clinical outcomes are potential avenues for advancing multiple sclerosis treatment with IgY supplements.

Association among VKORC1 rs9923231, CYP4F2 rs2108622, GGCX rs11676382 polymorphisms and acute ischemic stroke.

Acute ischemic stroke is a major cause of morbidity and mortality worldwide, and genetic factors play a role in the risk of stroke. Single nucleotide polymorphisms (SNPs) in the VKORC1, CYP4F2, and GGCX genes have been linked to clinical outcomes, such as bleeding and cardiovascular diseases. This study aimed to investigate the association between specific polymorphisms in these genes and the risk of developing the first episode of acute ischemic stroke in patients without a known embolic source. This retrospective, cross-sectional, observational, analytical, case-control study included adult patients diagnosed with acute ischemic stroke. The SNPs in VKORC1 rs9923231, CYP4F2 rs2108622, GGCX rs11676382 genes were genotyped and analyzed together with the demographic and clinical factors of the 2 groups of patients. The presence of SNPs in VKORC1 or CYP4F2 genes significantly increased the risk of ischemic stroke in the context of smoking, arterial hypertension, and carotid plaque burden. The multivariate logistic model revealed that smoking (odds ratio [OR] = 3.920; P < .001), the presence of carotid plaques (OR = 2.661; P < .001) and low-density lipoprotein cholesterol values >77 mg/dL (OR = 2.574; P < .001) were independently associated with stroke. Polymorphisms in the VKORC1 and CYP4F2 genes may increase the risk of ischemic stroke in patients without a determined embolic source. Smoking, the presence of carotid plaques, and high low-density lipoprotein cholesterol levels were reconfirmed as important factors associated with ischemic stroke.

The impact of oral anticoagulants on the characteristics of subdural hematomas and other brain lesions in patients with traumatic brain injury.

Background and aim: The aim of the study was to determine the impact of prior anticoagulant treatment on the characteristics of intracranial hematomas. Methods: We included in this retrospective study 135 patients who were diagnosed with subdural hematoma in the context of traumatic brain injury. We recorded the demographic and clinical data, the paraclinical examinations and the characteristics of subdural hematoma evidenced by preoperative computed tomography (CT). We also reported the other brain injuries, entailed by primary and secondary lesions, as described by CT. Results: The anticoagulation therapy was recorded in 35 patients, at the moment of diagnosis. Acute subdural hematoma was recorded in 89 (65.9%) patients, 21 (60%) of these had anticoagulation therapy on admission. There were 46 (34.1%) patients with chronic subdural hematoma, 14 (40%) of these were on anticoagulant therapy. The midline shift was significantly moved in patients with anticoagulation therapy. The thickness of the subdural hematoma was significantly higher in patients with anticoagulation. We did not find any significant association of the other brain lesions (cranial fracture, extradural hematoma, intraparenchymal hematoma, nor intracranial hypertension, brain herniation, brain swelling), and the presence of anticoagulation therapy. Conclusion: The study showed that anticoagulants significantly influence some neuroimaging aspects of the SDH in head trauma.

Plasma-Rich Fibrin-Regenerative Material in Tympanic Membrane Surgery.

Background and Objectives: Platelet-rich fibrin (PRF) membrane plays an important role in cell proliferation and aids in healing. This study aimed to assess the safety and efficacy of the addition of PRF to the graft in tympanoplasty. Materials and Methods: A retrospective study was conducted involving 47 patients with chronic dry eardrum perforation, who were candidates for different types of tympanoplasty (type I-IV). The study took place in the ENT department, County Emergency Clinical Hospital of Cluj-Napoca. In group 1 (27 patients) tympanoplasty was performed with a cartilage graft, while in group 2 (20 patients) a cartilage graft was used with the addition of a PRF membrane. The PRF clot was extracted and transformed into a thin membrane. Postoperative evaluation included otoendoscopy and otomicroscopy at 1, 3, 6, and 12 months after surgery, as well as pure-tone audiometry at 12 months. Results: Postoperative follow-up at 1, 3, 6, and 12 months showed a higher rate of graft survival in the PRF group than in the non-PRF group. At the 12-month mark, a successful outcome was observed in 95.0% of patients in the PRF group, while the success rate in group 1 was 70.4% (p < 0.05). The postoperative hearing threshold value was statistically significantly lower in the group with PRF, compared to the non-PRF group, being 18.4 ± 10.4 dB and 27.6 ± 16.2 dB (p < 0.001), respectively. Although the postoperative air-bone gap value did not differ significantly between groups, there was a greater improvement in the PRF group (p < 0.7). The PRF was well tolerated, and the incisions healed perfectly. Conclusions: The PRF membrane increases the rate of autograft survival and is therefore an effective material for patients with chronic perforations of the tympanic membrane.

Biological Risk Factors Influencing Vascular Cognitive Impairments: A Review of the Evidence.

Vascular cognitive impairment encompasses several types of deficits, ranging from mild cognitive impairment to dementia. Cognitive reserve refers to the brain's ability to balance damage and improve performance through certain types of brain networks. The purpose of this review was to assess the relationship between reserve in vascular impairment, specifically looking at whether cognitive impairment is influenced by cognitive reserve, identifying significant vascular risk factors and their pathological pathways. To achieve this purpose, a review covering these issues was conducted within the Embase, Cochrane, and PubMed database. A total of 657 scientific articles were found, and 33 papers were considered for the final analysis. We concluded that there is no consensus on the protective effects of brain reserve on cognitive impairment. Stroke and diabetes can be considered significant risk factors for vascular cognitive impairment, while hypertension is not as damaging as blood pressure variability, which structurally alters the brain through a variety of mechanisms.

Predictors of Short-Term Mortality in Patients with Ischemic Stroke.

Background and Objectives: The purpose of this study is to investigate the predictive factors for intrahospital mortality in ischemic stroke patients. We will examine the association between a range of clinical and demographic factors and intrahospital mortality, including age, sex, comorbidities, laboratory values, and medication use. Materials and Methods: This retrospective, longitudinal, analytic, observational cohort study included 243 patients over 18 years old with a new ischemic stroke diagnosis who were hospitalized in Cluj-Napoca Emergency County Hospital. Data collected included the patient demographics, baseline characteristics at hospital admission, medication use, carotid artery Doppler ultrasound, as well as cardiology exam, and intrahospital death. Results: Multivariate logistic regression was used to determine which variables were independently associated with intrahospital death. An NIHSS score > 9 (OR-17.4; p < 0.001) and a lesion volume > 22.3 mL (OR-5.8; p = 0.003) were found to be associated with the highest risk of death. In contrast antiplatelet treatment (OR-0.349; p = 0.04) was associated with lower mortality rates. Conclusions: Our study identified a high NIHSS score and large lesion volume as independent risk factors for intrahospital mortality in ischemic stroke patients. Antiplatelet therapy was associated with lower mortality rates. Further studies are needed to explore the potential mechanisms underlying these associations and to develop targeted interventions to improve patient outcomes.

The role of multiple sclerosis therapies on the dynamic of human gut microbiota.

Gut microbiota, the total microorganisms in our gastrointestinal tract, might have an implication in multiple sclerosis (MS), a demyelinating neurological disease. Our study included 50 MS patients and 21 healthy controls (HC). Twenty patients received a disease modifying therapy (DMT), interferon beta1a or teriflunomide, 19 DMT combined with homeopathy and 11 patients accepted only homeopathy. We collected in total 142 gut samples, two for each individual: at the study enrolment and eight weeks after treatment. We compared MS patients' microbiome with HC, we analysed its evolution in time and the effect of interferon beta1a, teriflunomide and homeopathy. There was no difference in alpha diversity, only two beta diversity results related to homeopathy. Compared to HC, untreated MS patients had a decrease of Actinobacteria, Bifidobacterium, Faecalibacterium prauznitzii and increased Prevotella stercorea, while treated patients presented lowered Ruminococcus and Clostridium. Compared to the initial sample, treated MS patients had a decrease of Lachnospiraceae and Ruminococcus and an increased Enterococcus faecalis. Eubacterium oxidoreducens was reduced after homeopathic treatment. The study revealed that MS patients may present dysbiosis. Treatment with interferon beta1a, teriflunomide or homeopathy implied several taxonomic changes. DMTs and homeopathy might influence the gut microbiota.

The Management of Obstructive Sleep Apnea Patients during the COVID-19 Pandemic as a Public Health Problem-Interactions with Sleep Efficacy and Mental Health.

With the onset of the COVID-19 outbreak, it was stipulated that patients with obstructive sleep apnea (OSA) may have a greater risk of morbidity and mortality and may even experience changes in their mental health. The aim of the current study is to evaluate how patients managed their disease (sleep apnea) during the COVID-19 pandemic, to determine if continuous positive airway pressure (CPAP) usage changed after the beginning of the pandemic, to compare the stress level with the baseline, and to observe if any modifications are related to their individual characteristics. The present studies highlight the level of anxiety, which was high among patients with OSA during the COVID-19 pandemic (p < 0.05), with its influence on weight control (62.5% of patients with high levels of stress gained weight) and sleep schedule (82.6% reported a change in sleep schedule). Patients with severe OSA and high levels of stress increased their CPAP usage (354.5 min/night vs. 399.5 min/night during the pandemic, p < 0.05). To conclude, in OSA patients, the presence of the pandemic led to a greater level of anxiety, changes in sleep schedule and weight gain because of job loss, isolation, and emotional changes, influencing mental health. A possible solution, telemedicine, could become a cornerstone in the management of these patients.

Paraoxonase 1 and atrial fibrillation: Is there a relationship?

Atrial fibrillation (AF) is associated with oxidative stress and inflammation. Paraoxonase-1 (PON1), circulates in blood bound to high-density lipoproteins and reduces systemic oxidative stress. The aim of this study was to evaluate PON1 serum concentration and PON1 arylesterase activity (AREase) in patients with AF. We studied a group of 67 patients with symptomatic paroxysmal or persistent AF admitted for cardioversion and a control group of 59 patients without AF. Clinical parameters, lipid profile, PON1 concentration and AREase were evaluated. A significant difference in serum PON1 concentration and in AREase was found among the two groups. In a multivariate linear regression model, the presence of AF was associated with low PON1 concentration (P = .022). The body mass index was also independently associated with PON1 values (P < .001). Only the high-density lipoproteins-cholesterol level was independently associated with AREase (P = .002). PON1 serum concentrations and AREase were diminished in patients with AF, and the presence of AF was independently associated with low PON1 values.

Admission Emergency Department Point-of-care Biomarkers for Prediction of Early Mortality in Spontaneous Intracerebral Hemorrhage.

BACKGROUND/AIM: Spontaneous intracerebral hemorrhage (sICH) has a significant morbidity and mortality, despite representing a non-dominant hemorrhagic stroke. The aim of the study was to assess the impact of the emergency department (ED) point-of-care (POC) biomarkers on early mortality in sICH patients. PATIENTS AND METHODS: Demographic data, medical history and admission clinical parameters from adult patients with imaging-based sICH diagnosis were collected retrospectively, upon their ED presentation over a period of 18 months. ED-based POC analyzers were used for blood biomarkers [complete blood count, C reactive protein (CRP), glycemia, hepatic and renal function, D-dimer and cardiac troponin I]. Derived inflammatory indexes were calculated. Mortality endpoints were collected (on day 7 and at discharge). RESULTS: Of the 219 included patients, mortality rates reached 30.14% on day 7 and 46.12% at discharge. In the univariate analysis, day 7 mortality was significantly associated with history of diabetes, atrial fibrillation, ongoing anticoagulant treatment, the need of endotracheal intubation and ED cardiopulmonary resuscitation, and the presence of intraventricular hemorrhage and mass effect on the initial CT scan. White blood cells and granulocytes (but not the neutrophil-to-lymphocytes ratio, nor the CRP) were significantly higher in the deceased groups, alongside serum glucose. Derived inflammatory indexes were not significantly correlated with mortality endpoints. Cut-off values of 9.6×109/l for granulocytes and 132 mg/dl for glucose were identified as day 7 mortality predictors. CONCLUSION: sICH is a potentially severe condition causing high early mortality. Emergency department point-of-care biomarkers could represent a readily available and simple to use prognostic tool.

Treatment of psoriasis - unburdened by fear during SARS-CoV2 menace.

In a matter of mere months, humanity was unexpectedly struck by the appearance of SARS-CoV-2, shifting our perception as medical practitioners regarding our day-to-day activity. One especially disconcerting change was patient addressability to medical facilities, as well as access to proper healthcare in various fields. As these changes occurred rapidly, dermatologists too had to adapt by means of teledermatology, giving us back the ability to reach, treat, and comfort our patients. Among the individuals requiring special dermatological attention are those suffering from psoriasis, especially considering that the biological therapies employed in treating this debilitating disease become questionable in the circumstance of the current pandemic. As more evidence surfaces concerning the pathophysiology of SARS-CoV-2, we become closer to understanding which therapies may interfere with its clearance, and which are actually safe to use. This review aims to answer the question, are biological therapies warranted in the treatment of psoriasis during the COVID-19 outbreak, or should they be discontinued?

A Prospective Study of CPAP Therapy in Relation to Cardiovascular Outcome in a Cohort of Romanian Obstructive Sleep Apnea Patients.

BACKGROUND: Despite efforts at treatment, obstructive sleep apnea (OSA) remains a major health problem, especially with increasing evidence showing an association with cardiovascular morbidity and mortality. The treatment of choice for OSA patients is Continuous Positive Airway Pressure (CPAP), which has been proven in randomized controlled trials to be an effective therapy for this condition. The impact of CPAP on the cardiovascular pathology associated with OSA remains, however, unclear. Although the effect of CPAP has been previously studied in relation to cardiovascular outcome, follow-up of the treatment impact on cardiovascular risk factors at one year of therapy is lacking in a Romanian population. Thus, we aimed to evaluate the one-year effect of CPAP therapy on lipid profile, inflammatory state, blood pressure and cardiac function, assessed by echocardiography, on a cohort of Romanian OSA patients. METHODS: We enrolled 163 participants and recorded their baseline demographic and clinical characteristics with a follow-up after 12 months. Inflammatory and cardiovascular risk factors were assessed at baseline and follow up. RESULTS: Our results show that CPAP therapy leads to attenuation of cardiovascular risk factors including echocardiographic parameters, while having no effect on inflammatory markers. CONCLUSION: Treatment of OSA with CPAP proved to have beneficial effects on some of the cardiovascular risk factors while others remained unchanged, raising new questions for research into the treatment and management of OSA patients.

An updated guide in the management of psoriasis for every practitioner.

BACKGROUND: Psoriasis is one of the most common chronic cutaneous skin disorders, having genetic and immunological components. It is currently unknown what exactly triggers it, or how far reaching are the etiological factors, although great strides have been made in uncovering the pathophysiological cascade. Presently, there is a wide diversity of treatment methods for psoriasis, yet not all are applicable for each patient. Selection of both drug and dosage depends on both the knowledge and experience of the treating dermatologist and also on the specific characteristics of each patient. Therefore, the treating physicians should be made aware of the management possibilities, their advantages and their side effects. METHODS: We have performed a non-systematic literature review on the current treatment methods for psoriasis. We have included the studies, articles, and prescription information that provided the most relevant information regarding each therapeutic agent. Afterward, we divided the treatment methods according to delivery and illustrated the management protocols for adult, paediatric, and pregnant patients. DISCUSSION AND CONCLUSIONS: Current therapies are divided into topical drugs, phototherapy, systemic and biological agents. Topical therapies and phototherapy are generally the first and second line of management respectively, being typically effective in treating mild to moderate forms of psoriasis. On the other hand, the chronic moderate to severe forms usually benefit from systemic drugs, whereas biologic agents are reserved for severe or unremitting cases, especially those suffering from psoriatic arthritis. Also of importance is the understanding of the pathophysiological mechanisms in psoriasis and how the selected drugs interfere in the pathological cascade. Furthermore, physicians should be able to recommend the appropriate therapy not only for adults but also for paediatric and pregnant patients as well. In the following manuscript, we present an updated version of these management options, alongside their indications, posology and most common side effects, a guide that may be useful for every practitioner in this field.

Cardiovascular Risk Factors and Physical Activity for the Prevention of Cardiovascular Diseases in the Elderly.

Cardiovascular diseases create an important burden on the public health systems, especially in the elderly, mostly because this group of patients frequently suffer from multiple comorbidities. Accumulating cardiovascular risk factors during their lifetime has a detrimental effect on an older adult's health status. The modifiable and non-modifiable cardiovascular risk factors are very diverse, and are frequently in a close relationship with the metabolic comorbidities of the elderly, mainly obesity and Diabetes Mellitus. In this review, we aim to present the most important cardiovascular risk factors which link aging and cardiovascular diseases, starting from the pathophysiological links between these factors and the aging process. Next, we will further review the main interconnections between obesity and Diabetes Mellitus and cardiovascular diseases of the elderly. Lastly, we consider the most important aspects related to prevention through lifestyle changes and physical activity on the occurrence of cardiovascular diseases in the elderly.

Novel concepts in psoriasis: histopathology and markers related to modern treatment approaches.

Psoriasis is a chronic autoimmune disease affecting over 2% of the worldwide population. From an anatomopathological point of view, psoriasis is characterized by immune cells infiltration, epidermal hyperproliferation, and abnormal keratinocyte differentiation. Understanding the pathogenesis of psoriasis will allow clinicians to manage this complex disease. Under these conditions, the application of effective treatments requires a thorough knowledge of all the pathogenetic mechanisms that lead to psoriasis. Numerous immunopathological pathways play crucial roles in the development of new therapies, such as biological therapies, which have been a breakthrough in psoriasis's treatment. Pharmacogenetics is an essential factor in the patient's response to treatment. One important pathway targeted by modern treatments is the interleukin (IL)-23∕T-helper (Th)17 axis. Like IL-17 inhibitors, IL-23 blockers are a very effective therapy for this autoimmune disease. It is considered that micro-ribonucleic acids (microRNAs) are the starting point for any autoimmune disease. Studying certain microRNA (miR) involved in the inflammatory pathway in psoriasis can find direct targets to future treatments that can even be more specific than actual biological therapies. As such, miR-210 has proven to be up-regulated in psoriasis, also leading to the up-regulation of the Th1∕Th17 axis. On the other hand, miR-187 was found to be down-regulated, influencing the outcome of psoriasis by increasing the proliferation of IL-6 stimulated keratinocytes and consecutively generating epidermal thickening. In this review, we are aiming to do an up-to-date briefing of psoriasis histopathology and pharmacogenetic factors that are considered for the accurate evaluation of treatment response.

The correlation between sleep bruxism, salivary cortisol, and psychological status in young, Caucasian healthy adults.

Objective: To analyze the association between sleep bruxism (SB), salivary cortisol, and psychological state in healthy adults.Methods: Sixty healthy students (with or without SB) were included in the study. The subjects completed a questionnaire that evaluated the presence of SB and analyzed the general and work-related psychological states and job-related frustration. Clinical examinations of TMJs and dental wear were performed. The salivary cortisol was determined using ELISA technique.Results: Subjects with SB had a general status characterized by anxiety or stress compared to subjects without SB. They also presented a work-induced depressive or anxious attitude compared to healthy individuals. The salivary cortisol levels were higher in subjects with SB and in females and were correlated with subjects' general anxiety, but not with a job-induced psychological state.Conclusion: SB is correlated with general and job-induced psychological changes. Salivary cortisol could be a non-invasive marker for the evaluation of SB severity.

Oral Anticoagulants Preference in Hospitalized Patients with Acute Deep Vein Thrombosis or Non-Valvular Atrial Fibrillation.

(1) Aim: The aim of this study was to assess the preferences of oral anticoagulants (OA) in patients diagnosed with deep vein thrombosis (DVT) of lower limbs or non-valvular atrial fibrillation (AF) requiring anticoagulation for medium/long term. (2) Materials and methods: the study included consecutive patients admitted with a diagnosis of either acute DVT of lower limbs (without signs of pulmonary embolism) or non-valvular AF who required oral anticoagulation, in a time frame of 18 months from January 2017 until June 2018. The following data were recorded: demographic variables, comorbidities (ischemic heart disease, arterial hypertension, heart failure, stroke, peripheral artery disease, diabetes mellitus, obesity), type and dose of OA (acenocoumarol, dabigatran, apixaban, rivaroxaban), complications due to the use of OA. (3) Results: AF patients were older and had considerably more cardiovascular comorbidities than DVT patients. Vitamin K antagonists (VKA) were more likely to be administered in patients with AF, as they had indication for indefinite anticoagulation. VKA were more frequently prescribed in patients with ischemic heart disease, heart failure, and diabetes compared with DVT patients. Moreover, complications related to OA use were more frequent in the VKA group. Almost half of patients with acute DVT (48.5%) were treated with direct OA (DOAC) rather than VKA, and only a quarter of AF patients (24.8%) were treated with DOACs.

Nigella Sativa's Anti-Inflammatory and Antioxidative Effects in Experimental Inflammation.

Nigella sativa (NS) has been used for centuries in various inflammatory conditions because of its anti-inflammatory and antioxidant activities. The study aimed to evaluate the anti-inflammatory, antinociceptive and antioxidant activity of Nigella sativa oil (NSO) in two models of acute (carrageenan-induced) and sub-acute inflammation (complete Freund's adjuvant induced) in rats. MATERIALS AND METHODS: NSO was administered orally 1, 2 and 4 mL/kg in the acute phase. For subacute phase, NSO was administered 4 mL/kg, 7 days before or after inflammation induction, or in association with diclofenac 5 mg/kg. RESULTS: The gas chromatography coupled with mass spectroscopy (GC-MS) analysis showed that NSO is an important source of bioactive compounds, especially p-cymene and thymoquinone. In the acute phase, 1.5 h after administration, NSO (2 and 4 mL/kg) determined an anti-inflammatory effect comparable with that of diclofenac. In the sub-acute administration, NSO had no anti-inflammatory effect. The analgesic effect of NSO was observed only in the sub-acute inflammation in the analgesy-meter test. NSO as treatment proved its antioxidant effect through the reduction of malondialdehyde (MDA) and oxidized glutathione (GSSG), and increases in hydrogen donor capacity (DH) compared to the control group, but the effect was not as intense as that of diclofenac. CONCLUSION: The present study has proven inconstant anti-inflammatory, analgesic and antioxidative properties of NSO.

3D laparoscopic enucleation vs standard partial nephrectomy for cT1 renal masses: assessment of functional outcomes at 1-year follow-up.

AIM: To evaluate renal function after laparoscopic nephron-sparing surgery (NSS) and to establish the factors that might influence its dynamic one year after surgery. METHODS: The prospective study included 83 patients previously diagnosed with renal cell carcinoma who underwent laparoscopic NSS. Demographic, clinical, laboratory and surgery related data were recorded. Patients were followed up for one year after surgery. RESULTS: The majority of cases (63 (76.8%)) were included in stage T1a. Almost two thirds of patients underwent partial nephrectomy (PN) (54 (65.1%)). A slight decrease in GFR was observed 1 year after surgery (80.1±21.5 ml/min; 75.3±22.4 ml/min respectively) in all patients. Univariate analysis showed a significant decrease in GFR values one year after surgery for patients who underwent standard PN as compared with those from the enucleation group (p=0.003). Male patients showed a significant decrease in GFR one year after surgery, as compared with female patients (p<0.001), and elderly patients were more likely to show lower GFR. When considering the simultaneous influence of age, gender and type of surgery on the evolution of GFR, the threshold for statistical significance was slightly crossed (p=0.2). CONCLUSION: Partial nephrectomy as compared to enucleation, advanced age and male gender are associated with impaired renal function at one year after laparoscopic NSS. KEY WORDS: Enucleation, Laparoscopic partial nephrectomy, Renal cell carcinoma.

CYP4F2 and VKORC1 Polymorphisms Amplify the Risk of Carotid Plaque Formation.

INTRODUCTION: Atherosclerosis represents the process by which fibrous plaques are formed in the arterial wall, increasing its rigidity with a subsequent decrease in blood flow which can lead to several cardiovascular events. Seeing as vitamin K antagonists are involved in the pathogenesis of atherosclerosis, we decided to investigate whether polymorphisms in genes that influence vitamin K metabolism might have an impact in modulating the risk of plaque formation. PATIENTS AND METHODS: In the current study we included adult patients admitted in the Clinical Municipal Hospital of Cluj-Napoca without any carotid or femoral plaques clinically visible at the initial investigation, and a five year follow-up was subsequently performed. We recorded the following patient characteristics: age at inclusion, gender, area of living, smoking, presence of carotid and/or femoral plaques at five years, ischemic heart disease, arterial hypertension, atrial fibrillation, heart failure, diabetes mellitus, obesity, dyslipidemia, drug (oral anticoagulants, antihypertensives, hypolipidemic, anti-diabetic) use and status for the following gene polymorphisms: VKORC1 1639 G>A, CYP4F2 1347 G>T and GGCX 12970 C>G. RESULTS: We observed that the major predictor of both carotid and femoral plaque formation is represented by ischemic cardiac disease. VKORC1 and CYP4F2 polymorphisms did not predict plaque formation, except for VKORC1 homozygous mutants. Nonetheless, both VKORC1 and CYP4F2 interacted with ischemic cardiac disease, increasing the risk of developing a carotid plaque, while only CYP4F2, but not VKORC1, interacted with ischemic cardiac disease to increase the risk of femoral plaque formation. CONCLUSIONS: We documented that CYP4F2 and VKORC1 polymorphisms boost the proinflammatory plaque environment (observed indirectly through the presence of ischemic heart disease), increasing the risk of plaque development.