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.

A Potential Indicator for Assessing Patient Blood Management Standard Implementation.

(1) Background: Patient blood management (PBM) program as a multidisciplinary practice and a standard of care for the anemic surgical patient has an increasingly important role in reducing transfusions and optimizing both clinical outcomes and costs. Documented success of PBM implementation is not sufficient for implementation of recommendations and correct use at hospital level. The primary objective of our study was to define a composite patient blood management process safety index-Safety Index in PBM (SIPBM)-that measures the impact of screening and treating anemic patients on the efficiency and effectiveness of the patient care process undergoing elective surgery. (2) Methods: We conducted a retrospective comparative study in a tertiary hospital by collecting data and analyzing the Safety Index in PBM (SIPBM) in patients undergoing major elective surgical procedures. (3) Results: The percentage of patients from the total of 354 patients (178 in 2019 and 176 in 2022) included in the study who benefited from preoperative iron treatment increased in 2022 compared to 2019 from 27.40% to 36.71%. The median value of the SIPBM was 1.00 in both periods analyzed, although there is a significant difference between the two periods (p < 0.005), in favor of 2022. (4) Conclusions: Measuring the effectiveness of PBM implementation and providing ongoing feedback through the Safety Index in PBM (SIPBM) increases the degree to which opportunities to improve the PBM process are identified. The study represents a first step for future actions and baselines to develop tools to measure the safety and impact of the patient blood management process in the surgical field.

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.

The Effect of Platelet-Rich Plasma Injection on Short Term Vocal Outcomes Following Phonosurgery-A Pilot Study.

Background and Objectives: The efficiency and optimal voice rest period following phonosurgery remains debatable. Platelet-rich plasma (PRP) is a safe and cheap alternative to many bioactive agents being studied on animal models, and is already in use in many medical areas. We investigate the short-term effects of PRP and voice rest on voice outcomes following phonosurgery as an alternative to voice rest alone. Materials and Methods: A prospective single-blinded pilot study was conducted. Sixteen patients with a diagnosis of vocal fold cyst and polyps were included, forming equal groups (PRP and voice rest vs. voice rest alone). Voice analysis was carried out on the preoperative day, day three, and week three following surgery. The measured parameters were fundamental frequency (F0), noise-signal ratio (NSR), harmonic poverty (HP), attack alteration (AL), pitch instability (PI), and amplitude instability (AI).VHI(Voice Handicap Index)-30 questionnaires were carried out before surgery and three weeks following surgery to assess the impact of subjective voice change on quality of life. PRP was obtained using commercial kits with separator gel. Results: An average 3.68-fold increase in platelets was obtained with PRP. No side effects were noted after injection. All voice parameters improved on day three and week three following surgery. Statistical significance was noted only in the fundamental frequency of male patients (p = 0.048) in favor of the PRP-voice rest group. In addition, the VHI- 30 questionnaire results between preoperative and postoperative assessments showed statistically significant differences in total VHI score (p = 0.02) as well as the physical (p = 0.05) and emotional (p = 0.02) scale in favor of the PRP-voice rest group. Conclusions: PRP presents short term safety in patients who undergo phonosurgery, although long-term outcomes are unknown. PRP and voice rest are superior to voice rest alone when considering subjective assessment of the voice. When analyzing acoustic parameters, PRP and voice rest are not superior to voice rest alone.

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.

Evaluation of prognostic factors for 5 year-survival after surgery for colorectal cancer.

AIM: The aim of this study was to assess and analyze the prognostic factors for survival in patients undergoing curative surgery for colorectal cancer and to identify new prognostic factors. METHODS: The prospective study included 301 patients diagnosed with colorectal cancer, stages I-III, undergoing curative surgery. Demographic data, clinical and anamnestic data, laboratory exams, paraclinical examinations, morphological and pathological examination were recorded. The Petersen index was calculated. Tumor necrosis, desmoplasia and mucinous component were assessed. Local inflammatory response was calculated using Klintrup criteria. Patients were followed for five years after surgery. RESULTS: There were 197 patients (66.4%) who survived and 104 patients (34.6%) who died during the 5-year follow- up period. Multivariate analysis showed that death was mostly associated with patients over 60 years of age (p=0.05). Tumor location within the colon was associated with a better survival than tumor location within the rectum (HR - 0.57; p=0.02). Patients with T>2 had a poor prognosis compared to those with T=<2 (HR - 2.23; p=0.02). Patients with Klintrup score >1 had a better prognosis (HR - 0.20; p <0.001). Patients with venous invasion showed significantly worse prognosis (HR - 2.26; p=0.003). Patients with desmoplasia score 3 had lower death rates than those with score 1 (HR - 0.42; p=0.01). CONCLUSION: Survival was superior in patients with cancer of the colon. The following parameters had a strong independent prognostic factor for survival: age, stage T>2, venous invasion, mucinous component and desmoplasia. KEY WORDS: Colorectal cancer, Prognostic factors, Survival.

High-frequency ultrasonography of psoriatic skin: A non-invasive technique in the evaluation of the entire skin of patients with psoriasis: A pilot study.

Psoriasis is a chronic, systemic, inflammatory disorder which accelerates the life process of skin cells, based on a genetically induced deviant immune response. High-frequency ultrasonography (HF-USG) is a painless, non-invasive imaging technique that can be performed and repeated whenever the need arises. We evaluated lesional and non-lesional skin of psoriatic patients with the use of HF-USG, focusing on the immune-induced inflammation and skin thickness. Previous studies suggested that HF-USG, being a non-invasive technique, is useful as an aid to clinical evaluation of the severity of psoriatic plaques. Our goal was to determine whether the skin of psoriatic patients is influenced by the background or habits of the patients. The study included a total of 27 patients affected by psoriasis vulgaris. The thickness of the epidermis and dermis and the skin echogenicity were documented for the active plaques, as well as for the non-affected skin of all the patients included in the study, using a high-frequency ultrasonographic system. The patient's local background, sex, family history of psoriasis, smoking habits and sun exposure were analyzed. HF-USG of the psoriatic plaques exposes a three-band structure that is easily distinguished from the surrounding unaffected skin, due to a hypoechoic band in the upper dermis. Although not specific for psoriasis, it is a strong marker of inflammation. The obtained results confirm that, indeed, skin thickness is greater in lesional skin compared to non-lesional skin, by a mean of 1,180 µm (±340 µm). We consider that skin HF-USG should be used as a quantitative method in the clinical evaluation of the patients with psoriasis and may help as an objective means of assessing inflammation in lesional skin.

Systemic and Local Factors' Influence on the Topological Differences in Deep Vein Thrombosis.

Background and Objectives: Deep vein thrombosis (DVT) is a common cause of intra-hospital morbidity and mortality, and its most severe complication is pulmonary thromboembolism. The risk factors that influence the apparition of DVT are generally derived from Virchow's triad. Since the most severe complications of DVT occur in proximal rather than distal deep vein thrombosis, the aim of this study was to identify the factors influencing the apparition of proximal DVT. Materials and Methods: This was a transversal, cohort study. The study included 167 consecutive patients with lower limb DVT over a two-year period. The following data were recorded or determined: general data, conditions that are known to influence DVT, medical history and coagulation or thrombophilia-related genetic variations. Results: In the univariate analysis, male gender, neoplasia, previous DVT and mutated factor V Leiden were all associated with proximal DVT, while bed rest was associated with distal DVT. In the multivariate analysis, male gender, previous DVT and factor V Leiden mutation were independently correlated with proximal DVT, while bed rest was independently associated with distal deep vein thrombosis. Conclusion: Our observations point out that the factors indicating a systemic involvement of coagulation were correlated with proximal DVT, while local factors were associated with distal DVT.

Resistin-Can it be a new early marker for prognosis in patients who survive after a cardiac arrest? A pilot study.

AIM: The aim of our study was to evaluate the potential role of resistin in estimating the 30 days prognosis in patients with hypoxic-ischemic organ injury who survived after a cardiac arrest (CA). MATERIALS AND METHODS: The study included 40 patients resuscitated after a non-traumatic out-of-hospital CA admitted in Emergency Department (ED). All patients were followed for 30 days after CA or until death. Clinical data on admission were recorded. Blood samples were collected on admission in ED (0-time interval), and at 6, 12, 24, 48- and 72-hours following resuscitation. Serum concentrations of resistin, S100B and neuron specific enolase (NSE) were measured. Several predictive scores for the mortality at 30 days were created with logistic regressions. RESULTS: At each time interval, median serum levels of resistin and S100 B were significantly higher in non-survivors compared to survivors. For NSE, plasma levels were significantly lower in survivors as compared to non-survivors at 48 and 72 hours, respectively. Accurate predictive scores for 30-days mortality were the ones which included the values of resistin and S100B measured at 12 hours after admittance [AUC 0.938 (0.813-0.989), sensitivity 85.71% (67.3%- 96%), specificity 91.67% (61.5%'99.8%), p<0.001], which included the values of all three markers measured at 12 hours after admittance [AUC 0.955 (0.839-0.995), sensitivity 82.14% (63.1%'93.9%), specificity 100.00% (73.5%'100.0%), p<0.001] and the that included the values of resistin and S-100B at 6 hours together with serum lactate on admission [AUC = 0.994 (0.901-1.0), sensitivity 96.4% (81.7%'99.9%), specificity 100.00% (73.5%'100.0%), p<0.001]. CONCLUSION: In our study, serum levels of resistin or a combination of resistin with S-100B or resistin with S-100B and lactate, were highly predictive for 30 days mortality in resuscitated patients after CA. Further studies on large number of patients are needed to confirm our data.

Chemotherapy-related infectious complications in patients with Hematologic malignancies.

BACKGROUND: The objective of the present study was to determine the association between chemotherapy and infectious complications in patients diagnosed with Hematologic malignancies (HMs). MATERIALS AND METHODS: The study included 463 patients diagnosed with HMs multiple myeloma (MM), Hodgkin's lymphoma (HL), non-HL (NHL), acute myeloid leukemia (AML), acute lymphocytic leukemia, chronic lymphocytic leukemia, and chronic myeloid leukemia, between January 2014 and June 2015. The patients were followed for 1 year after inclusion, to record the infectious complications. The collected data included age, sex, type of chemotherapy regimen, and several blood tests at admission. All patients received prophylactic treatment with antibiotics and antifungal agents. For each infection, we recorded the microbiological diagnosis and the day of occurrence since HMs diagnosis. RESULTS: In patients with MM, we found that the treatment with growth factors (hazard ratio [HR] 2.2; confidence interval [CI] 95%: 1-4.6; P = 0.03) was associated with a higher chance of infectious complications. In patients with non-Hodgkin lymhoma (LNH), the following drugs were associated with a higher infectious incidence: cytarabine (HR: 2.3; CI 95%: 1-5; P = 0.03), methotrexate (HR: 2.1; CI 95%: 1.8-4; P = 0.01), dexamethasone (HR: 1.7; CI 95%: 0.9-3; P = 0.06), growth factors (HR: 1.7; CI 95%: 0.9-3.2; P = 0.001), and etoposide (HR: 2.5; CI 95%: 1.5-4.2; P = 0.002). Cytarabine (induction) (HR: 2; CI 95%: 1.1-3.7; P = 0.01), cytarabine (consolidation) (HR: 2.1; CI 95%: 1.3-3.5; P = 0.01), and growth factors (HR: 2.1; CI 95%: 1.3-3.5; P = 0.002) were often on the therapeutic plan of patients with AML, which developed infections. CONCLUSION: Regarding the chemotherapy regimen, the highest incidences of infectious complications were observed for growth factors and cytarabine.

Evaluation of the pancreatic tumors by transabdominal Shear Wave Elastography: preliminary results of a pilot study.

AIM: To identify the mean values of Shear Wave Elastography (SWE) in pancreatic neoplasms. MATERIAL AND METHOD: This pilot case-control study was conducted in a tertiary care setting and data were collected in a prospective manner. Thirty-three subjects were included and divided into two groups: 18 healthy subjects and 15 patients with pancreatic neoplasm, from which 14 patients were diagnosed with adenocarcinoma and one with intraductal papillary mucinous neoplasia. Inclusion criteria for patients with pancreatic neoplasia were histopathological confirmation obtained by endoscopic ultrasonography (EUS) with fine needle aspiration or surgically and imaging confirmation by computed tomography with contrast enhancement. A number of minimum 5 shear wave velocity (SWV) measurements regarding each segment respectively at the tumoral level was obtained among a series of elastograms. RESULTS: The mean SWV of the pancreas in the control group was 1.21±0.27 m/s. Data regarding the pathological parenchyma indicated an increase of the SWV at the tumoral (cephalic) level corresponding to 1.54±0.32 m/s, with significant statistical difference between the control batch and tumoral group, p=0.02. CONCLUSIONS: Transabdominal SWE represents a surrogate but feasible method for differentiation cancer from the normal pancreatic tissue. In a clinical setting, data regarding the stiffness complementary to an ultrasound evaluation could guide high-risk patients for a close-up pancreatic monitoring.

Regression and Sentinel Lymph Node Status in Melanoma Progression.

BACKGROUND The purpose of this study was to assess the role of regression and other clinical and histological features for the prognosis and the progression of cutaneous melanoma. MATERIAL AND METHODS Between 2005 and 2016, 403 patients with melanoma were treated and followed at our Department of Dermatology. Of the 403 patients, 173 patients had cutaneous melanoma and underwent sentinel lymph node (SLN) biopsy and thus were included in this study. RESULTS Histological regression was found in 37 cases of melanoma (21.3%). It was significantly associated with marked and moderate tumor-infiltrating lymphocyte (TIL) and with negative SLN. Progression of the disease occurred in 42 patients (24.2%). On multivariate analysis, we found that a positive lymph node and a Breslow index higher than 2 mm were independent variables associated with disease free survival (DFS). These variables together with a mild TIL were significantly correlated with overall survival (OS). The presence of regression was not associated with DFS or OS. CONCLUSIONS We could not demonstrate an association between regression and the outcome of patients with cutaneous melanoma. Tumor thickness greater than 2 mm and a positive SLN were associated with recurrence. Survival was influenced by a Breslow thickness >2 mm, the presence of a mild TIL and a positive SLN status.

The impact of minimal invasive surgery on early complications and mortality after radical cystectomy for muscle-invasive urothelial bladder cancer.

PURPOSE: to evaluate the 30-day death rate and the factors associated with short-term complications after radical cystectomy for muscle-invasive urothelial bladder cancer. METHODS: The study included 123 patients (age 64.1±7.9 years; 111 (90.2%) males and 12 (9.8%) females) previously diagnosed with urothelial bladder cancer, admitted for radical cystectomy in a tertiary center. The following data were noted: age, gender, perioperative chemotherapy and radiotherapy, pre- and postoperative hemoglobin and creatinine levels, tumor stage, type of surgery, type of diversion and Clavien classification. Patients were followed for 30 days and several complications were noted: cardiovascular, gastrointestinal, local, or infectious complications, anemia. Death rate was also recorded. RESULTS: Open cystectomy was performed in 81 (65.9%) patients, and laparoscopic approach was used in 43 (34.1%) patients. An ileal neobladder was created for 11 (8.9%) patients and noncontinent diversion for 112 (91.1%). There were 2 (1.6%) deaths following surgery. The following complication rates were noted: 27 local (22%), 16 infectious (13%), 54 cases of postoperative anemia (43.9%). Postoperative anemia was independently associated with open cystectomy (OR, 5.7; p=0.001), ileal neobladder (Odds ratio/OR, 14.6, p=0.002) and male gender (OR, 0.15, p=0.01). The Clavien classification did not differ between open and laparoscopic cystectomy (p=0.3), even though the complication grade was higher in the former. CONCLUSIONS: The 30-day death rate after radical cystectomy for muscle-invasive urothelial bladder cancer was low. Open cystectomy was associated with more severe short-term complications as compared with the laparoscopic approach. Postoperative anemia was associated with the type of surgery, diversion type and male gender.

Predictors of 1-year postoperative mortality in radical colon cancer surgery.

AIM: The aim of this study was to determine the impact of patient, tumor and surgery-related parameters on 1-year postoperative mortality in a cohort of patients operated in a single tertiary center. MATERIALS AND METHODS: The study included 605 patients diagnosed with colon cancer between January 2013 and December 2015 that underwent radical surgery in a tertiary center. Patient demographics, comorbidities, preoperative biological parameters alongside with tumor and surgery-related factors were prospectively recorded and then analyzed in relation 1-year postoperative mortality. RESULTS: One-year mortality rate in the study group was 10.9%. Independent risk factors in relation to 1-year mortality were advanced TNM stage (OR 3.10, 1.10 - 8.75 95% CI ), emergency surgery (OR 1.91, 1.11 - 3.74 95% CI ), location of the tumor in the ascending colon (OR 2.17, 1.32 - 3.57 95% CI ), multiorgan resections (OR 2.07, 1.15 - 3.74 95% CI), age over 63 years (OR 2.05, 1.16 - 3.62 95% CI) and the history of alcohol consumption (OR 2.058, 1.17 - 3.61 95% CI ). DISCUSSION: Postoperative complications are still being reported in colon cancer surgery, despite technological progress and constant research in the field. So far, factors that influence postoperative mortality have been mostly studied up to 30 days postoperatively. According to some recent papers, reporting 30-day mortality data can underestimate accurate communication of postoperative adverse events. Thus, 1-year mortality in colon cancer surgery could be a better indicator of the impact on surgery on postoperative period of this patients and factors that influence it should be well known. KEY WORDS: Surveillance, Colon cancer, 1-year mortality.

The prognostic role of microsatellite instability in colorectal cancer patients.

BACKGROUND: Data from the literature regarding the prognostic role of DNA mismatch repair system (MMR) in colorectal cancer are still controversial. AIM: The aim of the study was to identify the prognostic role of different phenotypic, clinical and pathological characteristics in microsatellite unstable vs. microsatellite stable colorectal cancer in terms of survival and disease free interval. METHODS: We conducted a retrospective study that included a total of 103 patients who underwent curative surgery for colorectal cancer. Immunohistochemistry testing revealed MLH1, MLH2, MLH6, PMS2 genes and mutations of the BRAF gene. We identified three groups of patients: patients with colorectal tumors with MSI produced by hypermethylation, (MLH1/BRAF+) group, patients with microsatellite instable tumours produced by genetic mutations MSI groupb(MLH1, MLH2, MLH6, PMS2) and patients with microsatellite stable tumours (MSS). RESULTS: The study shows that: MSI tumours (MLH1/BRAF+) group occur more frequently in women (p=0.05), on the right side of the colon (p=0.001). The 5-year survival rate was higher in patients with MSI tumours (MLH1/BRAF+) group than in those with microsatellite stable tumours, the differences were not statistically significant ; relapse rate was higher in patients with MSI tumors than in those with MSI tumours (MLH1/BRAF+) group (p=0.03) or with MSS tumors (p=0.004). CONCLUSIONS: The identification of microsatellite unstable colorectal tumours is an important molecular marker with role in recognition subgroups of patients with different phenotypic characteristics, survival and relapse rates. KEY WORDS: Colorectal cancer, Mismatch repair genes, Prognostic role.

Serum metabolomics can predict the outcome of first systematic transrectal prostate biopsy in patients with PSA <10 ng/ml.

AIM: To assess the predictive value of metabolomic analysis for the presence of prostate cancer (PCa) at first systematic biopsy. PATIENTS & METHODS: Ninety serum samples from patients with suspicion for PCa were included. Targeted and nontargeted metabolomic analysis was performed. RESULTS: Six metabolites were combined into a predictive score. A cutoff value of 0.528 for the metabolomic score showed a good accuracy for the prediction of PCa at biopsy (Area under the curve (AUC): 0.779; p < 0.001). These results were validated in a subgroup of patients, showing similar accuracy (p = 0.1). For patients with prostate specific antigen (PSA) less than 10 ng/ml, the score showed a Se 80.95%, Sp 64.52% for the detection of PCa at biopsy. CONCLUSION: Metabolomic analysis can predict the outcome of the first systematic biopsy.

Cytokines Genotype-Phenotype Correlation in Nonalcoholic Steatohepatitis.

NASH consists in lipid accumulation in hepatocytes that trigger oxidative stress, secretion of proinflammatory cytokines leading to steatohepatitis (NASH). The study aimed to investigate the levels of proinflammatory (TNF-α and IL-6) along with anti-inflammatory cytokine IL-10 in patients with NASH and to correlate the cytokines' level with their polymorphism. Sixty-six patients with NASH and 30 healthy volunteers were included in the study. The plasmatic level of IL-6, IL-10, and TNF-α were determined by ELISA. IL-10 -1082 G/A, IL-6 -174 G/C, and TNF-α -308 G/A polymorphisms were determined using the PCR-RFLP technique. IL-6, TNF-α, and CRP levels were significantly higher in patients with NASH. There was a positive correlation between proinflammatory cytokines and a negative correlation between IL-10 and proinflammatory markers. The G allele and GG genotype of IL-6 -174 G/C polymorphism were more frequently noticed in NASH patients. Regarding IL-10 -1082 G/A polymorphism, the AA genotype was correlated with NASH and with a low plasmatic level of IL-10. The A allele in position 308 of the TNF-α gene was associated with high level of cytokine. In conclusion, there was an imbalance between pro- and anti-inflammatory cytokines in NASH patients. IL-10 -1082 G/A and TNF-α -308 G/A genotypes were correlated with the plasmatic levels of cytokines.

VKORC1-1639 G>A Polymorphism and the Risk of Non-Variceal Upper Gastrointestinal Bleeding.

BACKGROUND AND AIMS: The mutations in the gene that encodes vitamin K epoxide reductase (VKOR) enzyme are responsible for low levels of vitamin K. The purpose of this study was to evaluate whether the presence of the VKORC1 -1639 G> A polymorphism is a risk factor for non-variceal upper gastrointestinal bleeding (UGIB) in patients without concomitant therapy with vitamin K antagonists. METHODS: This case-control study comprised 163 consecutive patients diagnosed with UGIB and 178 controls, in whom the diagnosis of UGIB was excluded. The following data were recorded: age, gender, alcohol consumption, smoking, history of UGIB, nonsteroidal anti-inflammatory drugs (NSAIDs) or low-dose aspirin consumption. Genetic analysis included genotyping for the VKORC1 -1639 G>A polymorphism. RESULTS: History of UGIB (OR 3.463, CI95% 1.463-8.198, p=0.005), smoking (OR 2.498, CI95% 1.358-4.597, p=0.003), alcohol consumption (OR 3.283, CI95% 1.796-6.000, p<0.001), use of NSAIDs (OR 4.542, CI95% 2.502-8.247, p<0.001) or of low-dose aspirin (OR 2.390, CI95% 1.326-4.310), and the VKORC1 -1639 G> A AA genotype (OR 1.364, CI95% 0.998-1.863, p=0.05) were associated with an increased risk of UGIB. The risk of UGIB was analyzed in patients with genotype AA who used aspirin or NSAIDs. The genotype AA has not kept its status of independent risk factor (p=0.3). In subjects with NSAIDs/aspirin therapy and genotype AA there was a two times higher chance of UGIB compared to those under NSAIDs/aspirin therapy alone (OR 7.6 vs. 3.6, p<0.001). CONCLUSION: Patients with non-variceal UGIB caused by the use of NSAIDs or low-dose aspirin are more frequent carriers of the VKORC1 -1639 G>A AA genotype, as compared to those without UGIB.