N-Pep-12 supplementation after ischemic stroke positively impacts frequency domain QEEG.

BACKGROUND: N-Pep-12 is a dietary supplement with neuroprotective and pro-cognitive effects, as shown in experimental models and clinical studies on patients after ischemic stroke. We tested the hypothesis that N-Pep-12 influences quantitative electroencephalography (QEEG) parameters in patients with subacute to chronic supratentorial ischemic lesions. METHODS: We performed secondary data analysis on an exploratory clinical trial (ISRCTN10702895), assessing the efficacy and safety of 90 days of once-daily treatment with 90 mg N-Pep-12 on neurocognitive function and neurorecovery outcome in patients with post-stroke cognitive impairment against a control group. All participants performed two 32-channel QEEG in resting and active states at baseline (30-120 days after stroke) and 90 days later. Power spectral density on the alpha, beta, theta, delta frequency bands, delta/alpha power ratio (DAR), and (delta+theta)/(alpha+beta) ratio (DTABR) were computed and compared across study groups using means comparison and descriptive methods. Secondarily, associations between QEEG parameters and available neuropsychological tests were explored. RESULTS: Our analysis showed a statistically significant main effect of EEG segments (p<0.001) in alpha, beta, delta, theta, DA, and DTAB power spectral density. An interaction effect between EEG segments and time was noticed in the alpha power. There was a significant difference in theta spectral power between patients with N-Pep-12 supplementation versus placebo at 0.05 alpha level (p=0.023), independent of time points. CONCLUSION: A 90-day, 90 mg daily administration of N-Pep-12 had significant impact on some QEEG indicators in patients after supratentorial ischemic stroke, confirming possible enhancement of post-stroke neurorecovery. Further research is needed to consolidate our findings.

Cytokine TGF-ß1, TNF-α, IFN-γ and IL-6 Gene Polymorphisms and Localization of Premalignant Gastric Lesions in Immunohistochemically H. pylori-negative Patients.

Background: Cytokines and their gene variants are proven to play a role in pathogenic gastritis and carcinogenesis. The study assesses associations of the cytokine gene polymorphisms with extension of atrophic gastritis/intestinal metaplasia (AGIM) in patients without Helicobacter pylori infection on immunohistochemistry study. Methods: 224 adult consecutive patients undergoing an upper digestive endoscopy were included and grouped according to localization of AGIM: 37 patients with antrum-limited AGIM, 21 corpus-limited AGIM, 15 extended-AGIM (antrum and corpus) and 151 patients had no AGIM. Medical records of the patients were checked and a structured direct interview was applied in order to collect clinical data, including digestive symptoms. In all cases, IFN-γ +874T>A, TGF-ß1 +869T>C, TNF-α-308G>A and -238G>A, and IL-6 -174C>G polymorphisms were genotyped. Results: The mean age was significantly higher in the AGIM group, while the comorbidies were similar among patients with different localization of lesions or in patients without AGIM. There were no significant differences in digestive symptoms, nor in the consumption of non-steroidal anti-inflammatory drugs or proton pump inhibitor with the different extensions of AGIM. There was a significant association between oral anticoagulant consumption and localization of AGIM (P = 0.042), frequency being higher among patients with corpus-limited AGIM than those with no AGIM (P = 0.007, adjusted P = 0.041). TGF-ß1 +869T>C was less frequent among patients with corpus-limited AGIM (n=7, 33.3%) and extended AGIM (n=5, 33.3%) than in antrum-limited AGIM (n=25, 67.6%). There were no other significant differences regarding variant and wild genotype frequencies of IFN-γ +874T>A (86.5%, 81.0%, 86.7%, p=0.814), TNF-α-308G>A (35.1%, 28.6%, 53.3%, p=0.48) and IL-6 -174C>G (70.3%. 61.9%, 73.3% p=0.656) among patients with antrum-limited, corpus-limited or extended AGIM. TGF-ß1 +869T>C was associated with a decreased risk for corpus-affected AGIM (adjusted odds ratio: 0.42, 95% confidence interval: 0.19-0.93, P = 0.032). The dominant inheritance models no revealed significant association for IFN-γ +874T>A, TNF-α-308G>A and IL-6 -174C>G gene polymorphism and the risk of localization of AGIM. Conclusion: TGF-ß1 +869T>C gene polymorphism is associated with a decreased risk for corporeal localization of premalignant lesions, while IFN-γ +874T>A, TNF-α-308G>A and IL-6 -174C>G are not associated with the risk for AGIM in immunohistochemically H. pylori negative patients.

A Glimpse at the Size of the Fetal Liver-Is It Connected with the Evolution of Gestational Diabetes?

Gestational diabetes mellitus (GDM) is defined as an impairment of glucose tolerance, manifested by hyperglycemia, which occurs at any stage of pregnancy. GDM is more common in the third trimester of pregnancy and usually disappears after birth. It was hypothesized that the glycemic status of the mother can modulate liver development and growth early during the pregnancy. The simplest modality to monitor the evolution of GDM employs noninvasive techniques. In this category, routinely obstetrical ultrasound (OUS) examinations (simple or 2D/3D) can be employed for specific fetal measurements, such as fetal liver length (FLL) or volume (FLV). FLL and FLV may emerge as possible predictors of GDM as they positively relate to the maternal glycated hemoglobin (HbA1c) levels and to the results of the oral glucose tolerance test. The aim of this review is to offer insight into the relationship between GDM and fetal nutritional status. Risk factors for GDM and the short- and long-term outcomes of GDM pregnancies are also discussed, as well as the significance of different dietary patterns. Moreover, the review aims to fill one gap in the literature, investigating whether fetal liver growth can be used as a predictor of GDM evolution. To conclude, although studies pointed out a connection between fetal indices and GDM as useful tools in the early detection of GDM (before 23 weeks of gestation), additional research is needed to properly manage GDM and offspring health.

Therapeutic Compliance of Patients with Arterial Hypertension in Primary Care.

Background and Objectives: Arterial hypertension remains an important cause of cardiovascular morbidity and mortality, despite all the progress made in the methods of diagnosis, monitoring of target organs' damage and treatment. The main cause of the increased prevalence of uncontrolled blood pressure values is the low compliance to antihypertensive treatment. The objective of our study was to assess the compliance to the treatment of patients diagnosed with arterial hypertension and monitored in a primary care office. Materials and Methods: The cross-sectional, retrospective study included 129 patients, 65.89% (85) women, previously diagnosed with arterial hypertension. Data from the medical files were analyzed, as well as the patients' answers to a survey of 18 questions regarding arterial hypertension, comorbidities, complications, treatment and awareness of the condition. Results: The study included 129 patients, with a mean age of 66 ± 8 years. The majority of patients were overweight, 55.81% (72 patients), and 10.85% (14 patients) had grade I obesity. Most of the patients, 55.81% (72 patients) were diagnosed with grade III hypertension, while 37.98% (49 patients) were diagnosed with grade II hypertension and 6.2% (8 patients) with grade I hypertension. One third of the surveyed patients answered that they follow the recommendations of a low-sodium diet, 21.7% are adherent to treatment, but 56% think that the total cost of the medication is an impediment for their compliance to treatment. The majority, 82.17% (106 patients), of respondents had an affirmative answer to the questions: 'Do you think it would be easier to take one pill instead of 2, 3 or 4 pills?' Conclusion: The increased compliance to the antihypertensive treatment and control of blood pressure values are associated with the degree of awareness of arterial hypertension and the consequences if left untreated, emphasizing the role of the general practitioner in counseling for secondary prevention.

The relationship between MMP9 and ADRA2A gene polymorphisms and mothers-newborns' nutritional status: an exploratory path model (STROBE compliant article).

BACKGROUND: The aim of this study was to evaluate the direct effects of matrix metalloproteinase (MMP9 rs17577, MMP9 rs17576) and alfa 2 adrenergic receptor (ADRA2A rs553668) gene polymorphisms investigated in mothers and their newborns on maternal weight gain (MWG) during pregnancy and the newborn's birth weight (BW), taking into account the presence of other related factors. METHODS: We performed a cross-sectional study in 197 mother-newborn pairs in an Obstetrics Gynecology Clinic, in order to evaluate the demographic and anthropometric parameters, and gene polymorphism. RESULTS: BW was positively correlated with maternal age (p = 0.021) and the educational level (p = 0.002), and negatively correlated with smoking status in pregnant women (p < 0.001). The MMP9 rs17577 variant genotypes in mothers led to a lower BW (p = 0.049). The mothers with a variant genotype of ADRA2A rs553668 gene polymorphism had newborns with a higher BW (p = 0.030). MWG and gestational age (GesAge) influenced BW (p < 0.05). We noticed that newborns' variant genotype of MMP9 rs17577 was related to a significant increase in BW (p = 0.010), while the newborns who carried the variant genotype of MMP9 rs17576 expressed a negative correlation, decreasing the BW (p = 0.032). CONCLUSION: Our study emphasizes the role of MMP9 rs17577, MMP9 rs17576, and ADRA2A rs553668 SNPs in BW determinism.

Potential Clinical Predictors of Suspected Early and Late Onset Sepsis (EOS and LOS) in Preterm Newborns: a Single Tertiary Center Retrospective Study.

BACKGROUND: Neonatal sepsis represents one of the common diseases in the neonatal intensive care unit. Here we aim to evaluate the differences between a group of preterm newborns with sepsis and a control group in relation to clinical and laboratory variables. In addition, our goal is to establish potential predictors of early-onset sepsis (EOS) and late-onset sepsis (LOS). METHODS: The study included 113 preterm newborns with sepsis (EOS-63.72%/LOS-36.28%). Laboratory deter-minations included full blood count, CRP, biochemical determinations, blood culture. RESULTS: The most important univariate neonatal predictors were gestational age (p < 0.001), surfactant adminis-tration (p < 0.001), mechanical ventilation (p < 0.001), heart failure (p < 0.001), a history of hypocalcemia (p = 0.037), Apgar score at 1 minute lower than 7 (p = 0.001), birth weight < 1,500 g (p = 0.005), number of hospi-talization days (p = 0.048), and number of weight recovery days < 10 (p < 0.05). The WBC and CRP parameters remained significant univariate predictors of sepsis on day 7 (p = 0.002; OR = 2.01 per 10,000 mm3 increase of WBC, 95% CI: (1.30; 3.09) and p = 0.001; OR = 4.27, 95% CI: (1.85; 9.88), respectively). Logistic regression anal-ysis showed maternal urinary tract infection (OR = 3.05), heart failure (OR = 5.28), the number of hospitalization days (OR = 1.09) and CRP (OR = 3.26) were significant independent risk factors for neonatal sepsis in preterms. The univariate predictors of EOS were gestational age (p = 0.002), birth weight (p = 0.014), 1-minute Apgar score (p = 0.012), maternal urinary tract infection (p = 0.008), surfactant administration (p < 0.001), heart failure (p < 0.001), and CRP level (p < 0.001). Surfactant administration (OR = 6.73) and CRP level (OR = 3.51) represent predictors of EOS in preterms according to the multivariate model. The univariate predictors of LOS were gesta-tional age (p = 0.001), birth weight (p = 0.048), 1-minute Apgar score (p = 0.001), surfactant administration (p < 0.001), hypocalcemia (p = 0.03), heart failure (p = 0.003), CRP level (p < 0.001), mechanical ventilation (p < 0.001), and the number of hospitalization days (p < 0.001). In the multivariate model, the number of hospitali-zation days (OR = 1.11) and heart failure (OR = 5.98) are independent predictors for LOS in preterms. CONCLUSIONS: The study confirms the presence of maternal urinary tract infection, hospitalization days, heart fail-ure, and CRP level as predictors of neonatal sepsis in preterms with differences between EOS and LOS.

Predicting functional outcome of ischemic stroke patients in Romania based on plasma CRP, sTNFR-1, D-Dimers, NGAL and NSE measured using a biochip array.

In cerebral ischemia, evaluation of multiple biomarkers involved in various pathological pathways is a useful tool in assessing the outcome of the patients even from the early stages of the disease. In this study we investigated the utility of a panel of 5 peripheral biomarkers of inflammatory status, neuronal destruction and secondary fibrinolysis in the acute phase of ischemia, and evaluated the impact of these biomarkers on functional outcome after ischemic stroke. The 5 biomarkers (plasma CRP, D-Dimers, sTNFR-1, NGAL and NSE) were measured using a biochip array technology. Eighty nine patients in Romania were divided into 2 subgroups using the modified Rankin Scale evaluated at 3 months after ischemic stroke; the possible impact of analyzed biomarkers on unfavorable functional outcome was tested by binomial logistic regression. The subgroup with unfavorable outcome had higher concentrations of CRP, NGAL, sTNFR-1 and D-dimers, but CRP and NGAL values were not statistically different between the two subgroups. The univariate logistic regression analysis of plasma biomarkers revealed that CRP, D-Dimers, NGAL, sTNFR-1 were significant predictors of unfavorable clinical outcome. In the case of D-Dimers and sTNFR-1 we noticed an increased discrimination ability (versus baseline clinical model) to classify poor functional outcome with a tendency toward statistical signification. During the acute phase of the ischemic stroke, plasma concentrations of CRP, D-Dimers and sTNFR-1 were elevated in unfavorable outcome patients. D-Dimers and sTNFR-1 were independent predictors of poor outcome at 3 months after ischemic stroke. The biochip array technology offers the possibility to simultaneously measure several parameters involved in multiple pathophysiological pathways, in a small sample volume.

Drug-induced arterial hypertension - a frequently ignored cause of secondary hypertension: a review.

The prevalence of hypertension is likely to grow during the future years, mainly due to aging of the population and increasing prevalence of obesity, as an important risk factor for hypertension. One of the main causes of secondary hypertension, frequently ignored, is represented by certain categories of drugs, that can induce hypertension, increase the blood pressure values in previously controlled hypertension, decrease the effects of antihypertensive medication or induce a hypertensive emergency. These drugs may be over-the-counter medications, illicit drugs or prescription drugs used for the treatment of acute or chronic conditions. The most frequently incriminated drugs are steroids, nonsteroidal anti-inflammatory drugs, sympathomimetic agents, central nervous system stimulants (alcohol, amphetamine), dietary supplements (ginseng, natural liquorice etc), other therapeutic agents (sibutramine, antiemetic agents, oral physostigmine, L-dopa, leflunomide, growth hormone, thyroid hormone, recombinant human erythropoietin), antidepressants, immunosuppressants, antiangiogenic drugs, anaesthetics, heavy metals and toxins. Adding other drugs to antihypertensive treatment should be carefully evaluated by physicians, in order to avoid iatrogenic blood pressure elevations.

Developing a needs assessment questionnaire for women of reproductive age following breast cancer treatment: a cross-sectional pilot study in a Romanian sample.

PURPOSE: Studies addressing the needs of cancer patients highlight the necessity to identify what types of informational and support needs are specific to women of reproductive age after primary treatment for breast cancer. We developed a questionnaire for evaluating informational and treatment decision, psychological and socio-familial needs in young breast cancer patients following treatment. METHODS: 101 patients of reproductive age, treated for breast cancer at the Oncology Institute "Prof. Dr. Ion Chiricuta", Cluj-Napoca, between 2006 and 2013 were included. They all had completed surgery, chemo-radiotherapy, and were receiving hormone therapy. The questionnaire named Breast Cancer following Treatment Needs Assessment Scale (BCTNAS) consisted of 21 6-point Likert items. The validation procedures used were: construct validity performed by exploratory factor analysis (EFA), reliability and internal consistency analysis using ordinal Cronbach's alpha (α) and ordinal Omega (ω) correlation coefficients. RESULTS: According to EFA, the questionnaire evidenced four factors: needs concerning medical information and treatment decisions (PA1), needs for psycho-spiritual support (PA2), needs for socio-familial support (PA3), needs concerning medical support/assistance (PA4). The items of BCTNAS reported factor loadings (λi) greater than 0.40 for PA1 factor, λi ≥0.31 for PA2, λi ≥0.53 for PA3 and λi ≥0.33 for PA4, respectively. Reliability analysis demonstrated that BCTNAS is reliable: ordinal Cronbach's alpha of 0.81 (95% IC: 0.75-0.86) and ordinal omega of 0.85 (95% IC: 0.68-0.82) for the total scale score, with very good internal consistency. CONCLUSIONS: The BCTNAS questionnaire provides a potential instrument to identify and assess the needs of breast cancer patients in the post-treatment period, having a positive impact on the quality of patient care.

Assessing immunological surgical stress markers in patients undergoing digestive surgery for pancreatic, hepatic and gastric tumors.

PURPOSE: Cytokines like IL-6, IL-10 and other factors like CRP are involved in the postoperative inflammatory-stress response. The association between IL-6, IL-10, CRP, albumin and early postoperative complications and deaths was analyzed on a cohort of cancer patient. METHODS: The plasma levels of IL-6, IL-10 and serum levels of c-reactive protein (CRP) and albumin were measured in 85 patients undergoing surgical resection of pancreatic, hepatic and gastric tumors. The measurement of the studied biochemical parameters was made at three time points: before the operation, and on the 1st and 3rd day after the operation. RESULTS: Of the 85 patients, 28 suffered early postoperative complications (14 gastric cancer patients; 11 pancreatic cancer patients; 3 liver cancer patients) and 9 patients died in the early postoperative period (5 gastric cancer patients; 4 pancreatic cancer patients; 0 liver cancer patients). Patients with elevated levels of serum CRP on the 3rd postoperative day had a significant increased risk of death. Also, patients with higher levels of IL-10 on the 3rd postoperative day demonstrated a significantly increased risk of early postoperative complications. CONCLUSION: This study demonstrates that plasma IL-10 concentration is positively associated with postoperative complications.

Colorectal Cancer Carcinogenesis: a Multivariate Genetic Model in a Cohort of Romanian Population.

BACKGROUND: The molecular mechanism of carcinogenesis of sporadic colorectal cancer (CRC) involves genes with roles in folate metabolism, genes involved in metabolization of carcinogenic compounds from diet and tobacco smoke, and genes related to the DNA repair process. The aim of the study was to examine whether the MTHFRC677T, MTHFR- A1298C, TS-2rpt/3rpt, TS-1494del6bp, NAT2*5C-C481T, NAT2*5A-T341C, NAT2*6B-G590A, NAT2*7B-G857A, NAT2*18-A845C, GSTM1-null, XRCC1-Arg399Gln, XRCC3-Thr241Met, XPD-Lys751Gln genetic variations are associated with CRC prognosis, in the presence of environmental and demographic factors. METHODS: We genotyped 150 patients diagnosed with sporadic CRC using PCR-RFLP and sequencing methods. The performance of the final model was quantified using Nagelkerke's coefficient, the Hosmer-Lemeshow test, C statistics, and Somers' (D) index, capable of describing the model's goodness-of-fit and discrimination. RESULTS: Multiple logistic regression analysis established a significant independent association of NAT2*18-A845C, MTHFR-C677T, XRCC3-Thr241Met, NAT2*7B-G857A, XPD-Lys751Gln, XRCC1-Arg399Gln and NAT2*6BG590A with an increased prevalence of sporadic CRC, regardless of the presence/absence of colonic tumors. After an adjustment for other polymorphisms and environmental risk factors, the risk to develop sporadic CRC was 2.25 (p = 0.011) and 2.31 (p = 0.01) in association with the NAT2*18-A845C and MTHFR-C677T genetic variants, respectively. The risk increased to 3.22 (p = 0.0005) and 3.69 (p = 0.0009) in association with the XRCC3Thr241Met and NAT2*7B-G857A polymorphisms. Also, patients carrying the XPD-Lys751Gln, XRCC1Arg399Gln, and NAT2*6B-G590A polymorphisms had a 4.16 (p < 0.0001), 5.16 (p < 0.0001), and 5.46-fold (p < 0.0001) increased risk for sporadic CRC, under the dominant genetic comparison model. In addition, we found an interaction between gender and alcohol, the effect of alcohol consumption on the risk of developing sporadic CRC being different in female and male patients. CONCLUSIONS: Our study confirmed the predictive role of some polymorphisms associated with DNA methylation and procarcinogen transformation into carcinogenic compounds in sporadic CRC risk and, also, the influence of environmental risk factors such as diet, smoking, and alcohol consumption on this association.

N-acetyl transferase 2/environmental factors and their association as a modulating risk factor for sporadic colon and rectal cancer.

OBJECTIVES: The aim of this study was to evaluate the association between environmental factors and colon or rectal cancer after adjusting for N-acetyl transferase 2 (NAT2) phenotypes. METHODS: Ninety-six patients with sporadic colon cancer, 54 with sporadic rectal cancer and 162 control subjects were genotyped for NAT2-T341C, G590A, G857A, A845C, and C481T using sequencing and PCR-RFLP analysis. RESULTS: The risk for colon cancer was increased in carriers of the homozygous negative genotypes for NAT2*5C-T341C, NAT2*6B-G590A, NAT2*7B-G857A, NAT2*18-A845C, and NAT2*5A-C481T. The risk for rectal cancer was increased in carriers of the homozygous negative genotypes for NAT2*5C-T341C, NAT2*7B-G857A, and NAT2*5A-C481T. High fried red meat intake associated with NAT2-T341C, G590A, G857A, A845C, and C481T rapid acetylator allele determines a risk of 2.39 (P=.002), 2.39 (P=.002), 2.37 (P=.002), 2.28 (P=.004), and 2.51 (P=.001), respectively, for colon cancer, whereas in the case of rectal cancer, the risk increased to 7.55 (P<.001), 7.7 (P<.001), 7.83 (P<.001), 7.51 (P<.001), and 8.62 (P<.001), respectively. Alcohol consumption associated with the NAT2 -T341C, G590A, G857A, A845C, and C481T rapid acetylator allele induces a risk of 10.63 (P<.001), 12.04 (P<.001), 9.76 (P<.001), 10.25 (P<.001), and 9.54 (P<.001), respectively, for colon cancer, whereas the risk for rectal cancer is 9.72 (P<.001), 11.24 (P<.001), 13.07 (P<.001), 10.04 (P<.001), and 9.43 (P<.001), respectively. Smokers with NAT2-T341C, G590A, G857A, A845C, and C481T rapid acetylator allele have a risk of 4.87, 4.25, 4.18, 3.81, and 3.82, respectively, to develop colon cancer. CONCLUSIONS: Fried red meat, alcohol, and smoking increase the risk of sporadic CRC, especially of colon cancer, in the case of rapid acetylators for the NAT2 variants.

Influence of XPC, XPD, XPF, and XPG gene polymorphisms on the risk and the outcome of acute myeloid leukemia in a Romanian population.

XPC, XPD, XPF, and XPG genes are implicated in the nucleotide excision repair (NER) system. Gene polymorphisms in NER repair system may influence the individual's capacity to recognize and repair DNA lesions, thus increasing the cancer risk. We hypothesized that these gene polymorphisms might influence the probability of developing acute myeloid leukemia (AML). We investigated the XPC, XPD, XPF, and XPG gene polymorphisms in 108 AML cases and 163 healthy controls. Also cytogenetic analyses besides FLT3 and DNMT3A mutations status were investigated. We found that variant genotypes (heterozygous and homozygous) of XPD 2251A > C and 22541A > C and the heterozygous genotype of XPG 3507G > C were associated with the risk of developing AML (OR = 2.55; 95% CI = 1.53-4.25; p value <0.001; OR = 1.66, 95 % CI = 1.02-2.72; p value = 0.047, and OR = 2.36; 95 % CI = 1.32-4.21; p value = 0.004, respectively). No association was found between white blood cell counts, FLT3, DNMT3A mutations, cytogenetic risk group, and variant genotypes of none of the analyzed polymorphisms. Variant homozygous XPF 673C > T genotype was associated with higher dose of cytosine arabinoside treatment administrated to AML patients (p value = 0.04). No differences were found regarding survival time and variant genotype in the investigated gene polymorphisms with the exception of XPD 2251A > C. In conclusion, XPD 22541A > C, XPD 2251A > C, and XPG 3507G > C gene polymorphisms confer susceptibility to AML, while XPC 2920A > C, XPF-673C > T, XPF 11985A > G are not associated with AML.

Expression of Nestin and CD133 in serous ovarian carcinoma.

Pupose: Nestin and CD133 are regarded as putative markers of cancer stem cells (CSCs) and related to poor prognosis in various cancer sites. Since few studies have focused on their role in ovarian cancer, we aimed to investigate their predictive value and association with neoangiogenesis. METHODS: Immunohistochemical analysis for nestin and CD133 was performed on 85 serous ovarian carcinoma tumor samples using tissue microarray technique. Nestin immunoreactivity was detected in both tumor and endothelial cells, whilst CD133 was only identified in tumor cells. CD34 endothelial expression was used to assess intratumor microvessel density (MVD). RESULTS: Of the tissue samples 49.4% were nestin-positive and 24.7% were positive for CD133. In both univariate and multivariate analysis nestin or CD133 expressions in tumor cells were not significantly associated with clinicopathological parameters (age, serum CA125, peritoneal carcinomatosis, malignant ascites, tumor grade). However, in multivariate analysis nestin expression in tumor cells proved to be an independent prognostic factor, associated with poorer survival and time to progression (p=0.025 and p=0.05, respectively). This has not been achieved for CD133. Furthermore, a significant concordance between nestin endothelial expression (nestin-determined MVD) and CD34-determined MVD was achieved. CONCLUSION: In addition to the well-known clinicopathological characteristics, tumor expression of nestin might be a valuable prognostic factor for survival in patients with advanced ovarian cancer. With regard to its endothelial expression, nestin might be as reliable as CD34 for quantifying tumor angiogenesis. Further investigation is justified in order to better clarify the role of these biomarkers.

Non-invasive assessment of liver fibrosis in chronic viral hepatitis.

BACKGROUND: Hyaluronic acid (HA), ASAT to Platelet Ratio Index (APRI), ASAT/ALAT ratio, Fibrosis 4 score (FIB4) and FibroScan were studied as non-invasive markers of liver fibrosis (F) in chronic viral hepatitis B (CHB) and C (CHC), in an attempt to avoid the complications of liver puncture biopsy, considered the gold standard in the evaluation of F. The aim of our research was to study whether HA, APRI, ASAT/ALAT ratio, FIB4 and FibroScan are useful non-invasive markers in predicting severe F in Romanian patients. PATIENTS AND METHODS: This was a prospective multicenter transversal and observational study, which included 76 patients with CHB/CHC. The independent effect of studied markers was tested using multiple binary logistic regression. RESULTS: In patients with CHB and CHC, the APRI cut-off value for F4 was 0·70 ng/mL (Se = 77%, Sp = 78%), the FIB4 cut-off value was 2·01 (Se = 77%, Sp = 69%), and the FibroScan cut-off value was 13·15 (Se = 92%, Sp = 88%). For patients with CHB/CHC, there was a significant linear positive correlation between F and HA (r = 0·42, P = 0·001), FibroScan (r = 0·67, P < 0·001), APRI (r = 0·46, P < 0·001) and FIB4 (r = 0·51, P < 0·001). Considering age, sex and body mass index as possible confounding factors or covariates in multivariable logistic modelling, FibroScan was the unique test that able to significantly highlight the presence of F4 score in CHB/CHC patients (P = 0·009) while FIB4 test seems to have a tendency to statistical significance. CONCLUSION: FibroScan, APRI and FIB4 are useful non-invasive tests for the evaluation of F4 in patients with CHB and CHC.

The methylenetetrahydrofolate reductase (MTHFR) 677 C>T polymorphism increases the risk of developing chronic myeloid leukemia-a case-control study.

The methylenetetrahydrofolate reductase (MTHFR) 677 C>T and 1298 A>C polymorphisms are associated with variations in folate levels, a phenomenon linked to the development of various malignancies. The aim of this study was to investigate the influence of the 677 C>T and 1298 A>C polymorphisms in the MTHFR gene on the risk of developing chronic myeloid leukemia (CML). Our study included 151 patients with CML and 305 controls. The MTHFR 677 C>T and 1298 A>C polymorphisms were investigated by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) and allele-specific PCR techniques. The CT and TT genotypes of the MTHFR 677 C>T polymorphism were associated with an increased risk of developing CML (odds ratio (OR) = 1.556, 95% confidence interval (CI) = 1.017-2.381, p value = 0.041, and OR = 1.897, 95% CI = 1.046-3.44, p value = 0.035, respectively). No association was observed between the prognostic factors (blasts, basophils, additional chromosomal abnormalities, EUTOS score, Sokal and Hasford risk groups) and the MTHFR 677 C>T and 1298 A>C variant genotypes in CML patients. Our study shows that the MTHFR 677 C>T polymorphism is significantly associated with the risk of CML in Romanian patients.

New HLA associations identified in Romanian juvenile idiopathic arthritis patients.

BACKGROUND: Several associations between HLA polymorphisms and JIA subtypes have been reported in multiple populations, but with significant variations across different ethnic groups. The aim of our study was to search specific HLA-DRB1, -DQA1 and -DQB1 polymorphisms that are associated with JIA and different disease phenotypes in Romanian patients compared with other ethnic groups. METHODS: HLA genotyping was performed in 61 JIA patients and 30 ethnicity-matched controls using molecular biology methods, PCR-SSOP. RESULTS: A protective effect across the whole cohort was observed for HLA-DRB1*15 (OR = 0.179, 95% CI: 0.054 -0.58) and HLA-DQB1*06 (OR = 0.285, 95% CI: 0.11-0.72). Each ILAR subgroup had a characteristic pattern of HLA associations. Unlike other populations, we found a positive association of HLA-DQA1*03 with chronic uveitis (OR = 14.67, 95% CI: 1.5-143) and a negative association of HLA-DQA1*01 with early disease onset (OR = 0.175, 95% CI: 0.036- 0.862), suggesting that the HLA-DR/DQ profile can affect the clinical expression of the disease. CONCLUSIONS: The study reveals multiple HLA-DR/DQ associations with JIA, not only similar with those found in other populations, but also some distinctive associations. However, some of the previously established associations were not replicated in Romanian patients. These results might be due to the small size of our cohort or to true population differences.

Changes in NT-proBNP in young children with congenital heart malformations.

OBJECTIVE: We measured serum NT-proBNP levels in 2 groups of young patients (0-36 months) with congestive heart failure (CHF) secondary to congenital heart malformations (CHM). METHODS: The first group included 23 patients prior to surgery for heart malformations. The second group included 12 patients with CHM within 24 hours post-operation. NT-proBNP levels were measured by an enzyme-linked immunosorbent immunoassay (ELISA) using the Chem Well 2910 (Awareness Technology Inc.) automated analyzer. RESULTS: NT-proBNP values were 4 times higher in patients with unoperated CHM compared to healthy controls (P < 0.001), and 12 times higher in patients with CHM 24 hours after surgery compared to controls (P = 0.0001). CONCLUSIONS: These results demonstrated significant changes in NT-proBNP concentrations before and after surgery to correct congenital heart malformations.

Importance of Prenatal Diagnosis of Ileal Atresia in Gestational Diabetes Cases.

BACKGROUND Maldevelopment of the fetal bowel can result in the rare condition of intestinal atresia, which results in congenital bowel obstruction. This report describes a case of prenatal diagnosis of fetal ileal atresia at 22 weeks' gestation. CASE REPORT Here, we present a 24-year old woman who was 22 weeks into her first pregnancy when she underwent routine fetal ultrasound. She was diagnosed with gestational diabetes mellitus. Her body mass index was normal and she had normal weight gain. The ultrasonographic examination performed revealed a hyperechoic bowel and a small dilatation of the bowel. The couple was counselled for possible intestinal atresia and its postnatal implications. At 33 weeks of gestation, polyhydramnios appeared, and the intestinal distension was much more pronounced, with hyperechoic debris in the intestinal lumen (succus-entericus). After birth, surgery was performed and we concluded the patient had type II atresia, which was surgically treated. CONCLUSIONS This report has highlighted the importance of antenatal ultrasound in detecting fetal abnormalities, and has shown that rare conditions such as intestinal atresia can be accurately diagnosed and successfully managed. Surgical correction, if implemented promptly after stabilizing the general condition, can have a relatively good prognosis. Coexisting fetal ileal atresia and gestational diabetes mellitus are rare occurrences, which can make each condition even more difficult to treat.

Vitamin D Status among 2-18-Year-Old Romanian Pediatric Patients: A Single-Center Study.

An adequate vitamin D level is essential for optimal bone mass formation during growth. The present study aimed to assess (i) the sex-specific, age-specific, and potential seasonal (spring, summer, winter) influences on the pediatric circulating levels of 25-hydroxyvitamin D (25(OH)D); (ii) determine the frequency of pediatric patients with vitamin D deficiency (VDD) or insufficiency (VDI); and (iii) quantify the association between age category, sex, and season types and susceptibility to VDD and VDI, respectively. Laboratory data were collected on serum 25(OH)D levels in children aged between 2 and 18 years (n = 1674) who underwent blood sampling following admission to a university pediatric hospital in Cluj-Napoca (Romania) between January and June 2023. VDD (<20 ng/mL) was observed in 27% of pediatric patients. Among toddlers and preschoolers (2-5 years), VDD was 11%, while it was 33% among school-aged children (6-11 years) and 39% among adolescents (12-18 years). We found a significant difference in the frequencies of vitamin D status between females and males (p = 0.006). Also, we found significant associations of vitamin D status with age categories (p < 0.0001) and seasonal variations (p = 0.03). After adjusting for season of blood collection, the multinomial logistic regression model showed that children aged 6-11 years old (adjusted OR = 7, 95% CI: (4.9, 9.4)), children aged 12-18 years old (adjusted OR = 14, 95% CI: (9.3, 19.6)), and females (adjusted OR = 1.43, 95% CI: (1.10, 1.86)) were significantly associated with higher odds of VDD. In conclusion, the study revealed a significant difference in the frequency of VDD and VDI among pediatric patients older than six years, with a significant difference according to sex and season, being more pronounced among girls and during the winter and spring seasons.