Expression of Selected Genes and Circulating microRNAs in Patients with Celiac Disease.

Background and Objectives: Celiac disease (CD) is an immune-mediated enteropathy with characteristic intestinal alterations. CD occurs as a chronic inflammation secondary to gluten sensitivity in genetically susceptible individuals. Until now, the exact cause of the disease has not been established, which is why new studies have appeared that address the involvement of various genes and microRNAs (miRNAs) in the pathogenesis. The aim of the study is to describe the expression of selected genes (Wnt family member 3, WNT3; Wnt family member 11, WNT11; tumor necrosis factor alpha, TNFα; mitogen-activated protein kinase 1, MAPK1; AKT serine/threonine kinase 3, AKT3; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha, PIK3CA; and cyclin D1, CCND1) and miRNAs (miR-192-5p, miR-194-5p, miR-449a and miR-638) in adult patients with CD. Materials and Methods: In total, 15 patients with CD at diagnosis (newly diagnosed), 33 patients on a gluten-free diet (GFD) for at least 1 year and 10 controls (control) were prospectively included. Blood samples were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). Results: The results show that TNFα, MAPK1 and CCND1 were significantly overexpressed (p = 0.0249, p = 0.0019 and p = 0.0275, respectively) when comparing the newly diagnosed group to the controls. The other genes studied in CD patients were mostly with high values compared to controls, without reaching statistical significance. Among the miRNAs, the closest to a statistically significant value was miR-194-5p when the newly diagnosed group versus control (p = 0.0510) and GFD group versus control (p = 0.0671) were compared. The DIANA and miRNet databases identified significant functional activity for miR-449a and miR-192-5p and an interconnection of miR-194-5p and miR-449a with CCND1. Conclusions: In conclusion, genes and circulating miRNAs require further studies as they could represent important biomarkers in clinical practice.

Adipokines and Arterial Stiffness in Obesity.

Adipokines are active molecules with pleiotropic effects produced by adipose tissue and involved in obesity-related metabolic and cardiovascular diseases. Arterial stiffness, which is a consequence of arteriosclerosis, has been shown to be an independent predictor of cardiovascular morbidity and mortality. The pathogenesis of arterial stiffness is complex but incompletely understood. Adipokines dysregulation may induce, by various mechanisms, vascular inflammation, endothelial dysfunction, and vascular remodeling, leading to increased arterial stiffness. This article summarizes literature data regarding adipokine-related pathogenetic mechanisms involved in the development of arterial stiffness, particularly in obesity, as well as the results of clinical and epidemiological studies which investigated the relationship between adipokines and arterial stiffness.

The Effects of Flavonoids in Cardiovascular Diseases.

Flavonoids are metabolites of plants and fungus. Flavonoid research has been paid special attention to in recent times after the observation of their beneficial effects on the cardiovascular system. These favorable effects are exerted by flavonoids mainly due to their antioxidant properties, which result from the ability to decrease the oxidation of low-density lipoproteins, thus improving the lipid profiles. The other positive effect exerted on the cardiovascular system is the ability of flavonoids to produce vasodilation and regulate the apoptotic processes in the endothelium. Researchers suggested that these effects, including their anti-inflammatory function, are consequences of flavonoids' potent antioxidant properties, but recent studies have shown multiple signaling pathways linked to them, thus suggesting that there are more mechanisms involved in the beneficial effect of the flavonoids on the human body. This review aims to present the latest data on the classification of these substances, their main mechanisms of action in the human body, and the beneficial effects on the physiological and pathological status of the cardiovascular system.

Risk factors of subclinical atherosclerosis in obesity and overweight.

OBJECTIVE: To examine the relationship of carotid intima-media thickness with weight-gain, overweight and obesity.. METHODS: The experimental, analytical study was conducted at the CF University Hospital, Cluj-Napoca, Romania, from 2012 to 2014, and comprised randomly selected in patients from the Medical Ward. The patients were divided into normal-weight subjects in Group I and overweight and obese subjects in Group II Intimate-media thickness was measured by carotid Doppler ultrasound. Data was analysed using SPSS 13. RESULTS: Of the 111 subjects, Group I had 27(%) and Group II had 84(%) subjects. Mean carotid intimamedia thickness was significantly greater (p<0.001) in Group II compared to Group I, especially in those with metabolic syndrome (p<0.001) and higher high-sensitivity C reactive protein (p<0.05). With the exception of Group II where there was a direct correlation (p<0.05) between triglycerides and intimamedia thickness, and an inverse correlation (p<0.05) between high-density lipoprotein and intimamedia thickness, no significant correlations were recorded (p>0.05). CONCLUSIONS: Intima-media thickness was found to be increased in asymptomatic overweight and obese subjects, significantly higher in those with associated metabolic syndrome and high levels of highsensitivity C-reactive protein, as an indication of the presence of early, subclinical atherosclerosis.

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.

Identifying predictive factors for mortality in patients with TBI at a neurosurgery department.

Traumatic brain injury (TBI) can have severe consequences in most cases. Many therapeutic and neurosurgical strategies have been improved to optimize patient outcomes. However, despite adequate surgery and intensive care, death can still occur during hospitalization. TBI often results in protracted hospital stays in neurosurgery departments, indicating the severity of brain injury. Several factors related to TBI are predictive of longer hospital stays and in-hospital mortality rates. This study aimed to identify predictive factors for intrahospital days of death due to TBI. This was a longitudinal, retrospective, analytical, observational study that included 70 TBI-related deaths admitted to the Neurosurgery Clinic in Cluj-Napoca for a period of four years (January 2017 to December 2021) using a cohort model. We identified some clinical data related to intrahospital death after TBI. The severity of TBI was classified as mild (n=9), moderate(n=13), and severe (n=48) and was associated with significantly fewer hospital days (p=0.009). Patients with associated trauma, such as vertebro-medullary or thoracic trauma, were more likely to die after a few days of hospitalization (p=0.007). Surgery applied in TBI was associated with a higher median number of days until death compared to conservative treatment. A low GCS was an independent predictive factor for early intrahospital mortality in patients with TBI. In conclusion, clinical factors such as the severity of injury, low GCS, and polytrauma are predictive of early intrahospital mortality. Surgery was associated with prolonged hospitalization.

Arterial stiffness in aortic stenosis - complex clinical and prognostic implications.

Arterial stiffness and degenerative aortic stenosis (AoS) are frequently associated leading to a combined valvular and vascular load imposed on the left ventricle (LV). Vascular load consists of a pulsatile load represented by arterial stiffness and a steady load corresponding to vascular resistance. Increased vascular load in AoS has been associated with LV dysfunction and poor prognosis in pre-intervention state, as well as after aortic valve replacement (AVR), suggesting that the evaluation of arterial load in AoS may have clinical benefits. Nevertheless, studies that investigated arterial stiffness in AoS either before or after AVR used various methods of measurement and their results are conflicting. The aim of the present review was to summarize the main pathophysiological mechanisms which may explain the complex valvulo-arterial interplay in AoS and their consequences on LV structure and function on the patients' outcome. Future larger studies are needed to clarify the complex hemodynamic modifications produced by increased vascular load in AoS and its changes after AVR. Prospective evaluation is needed to confirm the prognostic value of arterial stiffness in patients with AoS. Simple, non-invasive, reliable methods which must be validated in AoS still remain to be established before implementing arterial stiffness measurement in patients with AoS in clinical practice.

Predictive factors of 30-day mortality in patients with traumatic subdural hematoma.

In the present study, we aimed to assess and analyze the predictive factors of 30-day mortality in patients with acute subdural hematoma (ASDH) who underwent surgical intervention after traumatic brain injury (TBI). We conducted a retrospective study, which included a cohort of 135 consecutive patients diagnosed with ASDH who required surgical evacuation. We assessed the demographic and clinical data, the imaging data of the hematoma described by preoperative computed tomography (CT) and the type of neurosurgical intervention for hematoma evacuation via either craniectomy or craniotomy. The patients were followed up for 30 days after head trauma and the occurrence of death was noted. Death was recorded in 63 (46.6%) patients at 30 days after TBI. There was a significant number of deceased patients who underwent craniectomy (71.4%). The Glasgow Coma Scale (GCS) was statistically significantly lower in patients who died (P<0.001), with a cut-off value of ≤12, under which the probability of death increased [AUC 0.830 (95% CI, 0.756-0.889); Se 90.48% (95% CI, 80.4-96.4); Sp 66.7% (95% CI, 54.6-77.3); P<0.001]. The midline shift was statistically significantly higher in deceased patients (P=0.005), with a cut-off value of >7 mm, over which the probability of death increased [AUC 0.637 (95% CI, 0.550-0.718); Se 38.1% (95% CI, 26.1-51.2); Sp 86.1% (95% CI, 75.9-93.1); P=0.003]. There were significantly more deceased patients with intracranial hypertension, brain herniation, brain swelling, intraparenchymal hematoma and cranial fracture. In multivariate analysis only a Glasgow score ≤12 and a midline shift >7 mm were independently linked to mortality. Brain herniation and intraparenchymal hematoma were associated with a higher probability of dying, but the statistical threshold was slightly exceeded. The type of neurosurgery performed for patients with ASDH was not an independent predictive factor for 30-day mortality. However, craniectomy was associated with a higher mortality in patients with ASDH.

Uric Acid and Arterial Stiffness.

Hyperuricemia is usually associated with hypertension, diabetes mellitus, metabolic syndrome and chronic kidney disease. Accumulating data from epidemiological studies indicate an association of increased uric acid (UA) with cardiovascular diseases. Possible pathogenic mechanisms include enhancement of oxidative stress and systemic inflammation caused by hyperuricemia. Arterial stiffness may be one of the possible pathways between hyperuricemia and cardiovascular disease, but a clear relationship between increased UA and vascular alterations has not been confirmed. The review summarizes the epidemiological studies investigating the relationship between UA and arterial stiffness and highlights the results of interventional studies evaluating arterial stiffness parameters in patients treated with UA-lowering drugs.

Cardiac Changes in Overweight and Obese Patients.

BACKGROUND: Obesity and overweight are two pathologies that are more and more frequent in the XXIst century diagnosis and are causing high morbidity and mortality rates in the general population, especially through cardiovascular complications. AIMS: Identification and early diagnosis of cardiac changes in overweight and obese patients. MATERIAL AND METHOD: We carried out a sectional, analytical and observational study on 111 subjects: 27 normal weight subjects and 84 overweight and obese patients, which were submitted to a clinical exam, biochemical exams and 2D ultrasound. RESULTS: The presence of diastolic dysfunction is twice more frequent in overweight patients in comparison to normal weight ones (30% vs 15%) and 5 times more frequent in obese patients than normal weight ones (75% vs 15%). The size increase of the interventricular septum is correlated with the body mass index, there being statistically significant differences between normal weight vs overweight vs obese patients, as well as between overweight and obese ones. Within the whole group and within the groups, both the left ventricle mass (g) as well as the left ventricle mass to body surface ratio (g/m²) are statistically significantly higher in patients with present diastolic dysfunction (E/A < 1). This indicates a relation between the presence of diastolic dysfunction, increased left ventricle mass and body mass index (p < 0.05). CONCLUSIONS: Overweight and obese patients, unlike normal weight ones, present early cardiac changes, such as: a decrease of left ventricle ejection fraction, diastolic dysfunction, thickening of the interventricular septum, increase of the left ventricle mass both per se as well as in ratio to body surface.

Two different types of diabetes mellitus in pancreatic cancer population. Comparative study between new onset and long standing diabetes mellitus on 76 patients with pancreatic cancer.

BACKGROUND: There are some studies which have reported a higher diagnosis probability for PC if the DM occurred within the past 2-3 years. Information on the clinical profile of pancreatic cancer (PC) associated with diabetes mellitus (DM) is limited. The aim of the study was to compare clinic-morphological features in patients with new onset DM and PC and long lasting DM and PC, in order to detect new factors or markers which can help in early diagnosis of PC. METHODS: This study included 76 patients with pancreatic cancer admitted between 2000-2009 in the 4th Medical Clinic Cluj-Napoca; in group A 56 patients with PC and new onset of DM (< 24 months duration) were included and in group B 20 patients with PC and long standing diabetes (> 60 months duration) were included. We compared the demographic, clinical, biochemical and morphological characteristics of new onset or long lasting DM and pancreatic cancer. RESULTS: New onset DM was more prevalent (74% vs. 26%, p < .05) than long lasting DM among patients with PC. The patients with long lasting DM had a greater frequency of urban environment (100% vs. 55.6% p = .02), a higher body mass index (BMI)(32.1 SD 8.4 vs. 29.9 SD 6.7 kg/m2, p = .05), higher fasting blood glucose levels (182 mg/dL vs. 134 mg/dL, p = .008) and urinary ketone bodies (60% vs. 10.7%, p = .002) compared with those with new-onset DM and PC. There was no statistical difference regarding gender, median age, blood group, location and staging of tumours, long and hard alcohol and cigarettes consumption, between group A and B. CONCLUSIONS: New onset DM was more significantly frequent than long lasting DM in patients with PC. New onset diabetes DM associated with PC is frequent, mild and non-decompensated. In patients with PC and long lasting DM, the metabolic status and diabetes are imbalanced.

Serum homocysteine levels, oxidative stress and cardiovascular risk in non-alcoholic steatohepatitis.

INTRODUCTION: Hyperhomocysteinemia is considered an independent risk factor for cardiovascular disease. Oxidative stress is one of the major pathogenic mechanisms in non-alcoholic fatty liver disease and atherosclerosis. AIM: Our study aimed to evaluate serum homocysteine levels and oxidative stress in patients with biopsy-proven non-alcoholic steatohepatitis and possible association with cardiovascular risk measured by carotid artery intima-media thickness (c-IMT). PATIENTS AND METHODS: 50 patients with non-alcoholic steatohepatitis and 30 healthy controls, age and gender matched, were recruited. Lipid profile, liver biochemical markers, serum homocysteine, vitamins B6 and B12, folic acid, glutathione (reduced and total), erythrocyte superoxide dismutase, whole blood glutathione peroxidase, malondialdehyde and carotid intima-media thickness were assayed. RESULTS: Patients had an altered lipid profile and liver biochemical markers; carotid intima-media thickness and serum homocysteine levels were significantly higher compared to controls, but there were no differences in folate, B12 and B6 vitamins levels. Patients had significantly lower levels of glutathione peroxidase activity, total and reduced glutathione and higher levels of malondialdehyde, but unchanged superoxide dismutase activity compared to control group. Also, serum homocysteine level showed significant positive correlation with waist circumference, body mass index, free cholesterol, triglycerides, LDL-cholesterol, amino transferases and negative correlation with reduced and total glutathione, superoxide dismutase and γ-GT. CONCLUSION: Non-alcoholic steatohepatitis is an independent cardiovascular risk factor, associated with elevated homocysteine levels, oxidative stress and c-IMT. c-IMT could be used as an indicator of early atherosclerotic changes initiated by dyslipidemia and oxidative stress, while higher level of homocysteine might be an effect of liver damage.