Morphometric study for determining the anteroposterior position of the mental foramen in dentate human subjects.

BACKGROUND: The mental foramen (MnF) is the place where the mental nerve and mental artery exit the body of the mandible, being an important landmark for dentoalveolar surgery. MATERIALS AND METHODS: For the assessment of MnF topography, we performed a direct morphometric study and two morphometric imaging studies through cone-beam computed tomography (CBCT) scans and orthopantomography (OPG). The following locations of the MnF were investigated: anterior to the first premolar, at the first premolar level, between the two premolars, at the second premolar level, between the second premolar and the 6-year molar, and at the level of the mesial root of the 6-year molar. The data obtained were statistically analyzed by chi-squared test. RESULTS: Through direct morphometry on dentate dry human mandibles, no statistically significant differences were found for the number of MnF located between the two premolars, at the level of the second premolar and between the second premolar and the 6-year molar, depending on age and analyzed side. The number of MnF located between the second premolar and the first molar varies statistically significantly in relation to the subject's gender but does not vary statistically significantly depending on age and side. By means of imaging morphometry through OPG, we found that the number of MnF located at the first premolar level, between the two premolars, at the second premolar level and between the second premolar and the 6-year molar varies statistically significantly in relation to the age of the patients. Using imaging morphometry trough CBCT scans, we found that the number of MnF located between the two premolars, at the second premolar level and between the second premolar and the 6-year molar varies statistically significantly according to the age of the patients. Comparing the results obtained from the three studies, we found that only according to age the number of MnF located between premolars and at the level of the second premolar varies statistically significantly. CONCLUSIONS: Wide and accurate knowledge of both the MnF topography and the key anatomical landmarks used in locating it proves to be essential and clinically relevant in dentoalveolar and endodontic surgery, and for improving anesthesia techniques.

The Prevalence of HCV Infection and Risk Factors in a Hospital- Based Population Screening, a First Step to the Micro-Elimination of HCV Infection in Medical Institutions from Romania - Results of the HepC ALERT Study.

BACKGROUND AND AIMS: Elimination of hepatitis C worldwide is more feasible if micro-elimination screening strategies are adopted. We aimed to screen hepatitis C virus (HCV) in specific high-risk populations in certain sub-regions of Romania and link them to antiviral treatment. METHODS: A multicenter prospective study was conducted among the hospitalized or ambulatory adult patients from March 2019 to March 2020 in more than 20 medical institutions from 4 Romanian cities (Bucharest, Iasi, Timisoara, Cluj-Napoca). A rapid diagnostic test for HCV diagnosis was performed to all admitted patients and the positive ones were sent to gastroenterology departments for confirming the active infection, staging and treatment prescription. RESULTS: In total, 25,141 subjects signed the informed consent and were consequently enrolled into the study. The prevalence of anti-HCV antibodies was 1.39% (95%CI: 1.25-1.54) and increased with the number of risk factors presented by one subject. There was a positive association between the presence of anti-HCV antibodies and female gender (p<0.001), rural area of residence (p<0.001), advanced age (p<0.001), as well as a negative association with the education level (p<0.001). CONCLUSIONS: In a hospital-based screening micro-elimination program in Romania, HCV prevalence was lower than previously reported. This is a first step towards a cost-effective screening in a well-defined group of persons at risk and provides sufficient capacity to deliver access to HCV treatment and linkage to care in Romania.

Pre and post-liver transplant outcome of cirrhotic patients with acute on chronic liver failure.

Acute on chronic liver failure (ACLF) is a dynamic syndrome, but frequently associated with a high 1 month mortality rate. This is the first study applying the new European Association for the Study of the Liver- chronic liver failure consortium criteria to explore mortality on the waiting list (WL) and early after liver transplantation (LT) in a cohort of Romanian cirrhotic patients that improved or recovered after an episode of ACLF.To assess frequency and waitlist mortality for different grades of ACLF.An observational study was conducted; 257 patients with liver cirrhosis included on the WL between 2015 and 2017 were analyzed. The cumulative incidence of waitlist mortality or removal was calculated for combination of competing events using multivariable competing risks regression.ACLF-1 occurred in 12.07%, ACLF-2 in 7.39% and ACLF-3 in 8.56% of patients. Median Model for End Stage Liver Diseases (MELD) score at the moment of ACLF was 29. The main event while on the WL was death, followed by ACLF; patients with ACLF-3 had a significantly greater subhazard ratio for mortality of 2.25 (1.55-3.26) compared to patients with ACLF-1 or 2. LT proved to be associated with a significantly lower risk of death on the WL at 6 months after inclusion. One and 12 months post-transplant survival of patients with or without ACLF was similar (P = .77).Occurrence of an ACLF episode while on the WL is associated with a significantly high mortality rate, as well as MELD score at inclusion on the WL, renal and liver failure, presence of hepatic encephalopathy. Overall patient short and long term survival after LT is similar to non-ACLF patients in good selected cases.

Direct and imaging morphometry for the localization of the mandibular foramen (MF) in dentate and edentulous human subjects.

BACKGROUND: The mandibular foramen (MF) is the anatomic landmark where the interior alveolar nerve enters the mandibular ramus, and the area of choice where anesthesia of this nerve is performed. The position of the MF can vary, and accurately establishing its location and topographic variations is of great importance for the successful anesthesia of the inferior alveolar nerve. MATERIALS AND METHODS: We carried out two morphometric ex vivo studies concerning the topography of the MF, on dry human mandibles coming from dentate and completely edentulous human subjects of known age and gender and an in vivo morphometric study, through cone-beam computed tomography (CBCT) scans, concerning the topography of the MF in human subjects having Kennedy Class I mandibular edentulism. The morphological characteristics we investigated were: the distance between the MF and the anterior margin of the mandibular ramus (MF-AM distance), the distance between the MF and the posterior margin of the mandibular ramus (MF-PM distance), the distance between the MF and the inferior margin of the mandibular ramus (MF-IM distance), the distance between the MF and the temporal crest of the mandibular ramus (MF-TC distance), the distance between the MF and the superior margin of the mandibular ramus (MF-SM distance), and the vertical and transverse diameters of the MF. The results were statistically processed in Stata/MP13 software package using Student's t-test and two-way analysis of variance (ANOVA). RESULTS: Through direct morphometry on dentate dry human mandibles, the MF-AM and the MF-SM distances showed statistically significant differences for age, gender and for interactions, while the MF-PM and MF-IM distances showed statistically significant differences for age and for interactions. In the case of the MF-TC distance, the only significant difference observed was for the gender. No statistical significance was found for side, age, gender, and interactions in the cases of MF vertical and transverse diameters. Through direct morphometry on completely edentulous dry human mandibles, the MF-PM and MF-SM distances showed statistically significant differences for age, gender and for interactions, while the MF-AM, MF-IM, and MF-TC distances, as well as the MF vertical and transverse diameters showed statistically significant differences for age and for model (interactions). The results showed that MF is 2 mm closer to the anterior margin of the mandibular ramus after having lost teeth. Through imaging morphometry, the MF-PM distance and the vertical diameter of MF showed statistically significant differences for age, gender and for interactions, while the MF-AM, MF-IM, MF-SM and MF-TC distances, as well as the transverse diameter of MF showed statistically significant differences for age and for interactions. Comparing the results obtained by the three studies, we found no statistically significant differences in relation to the gender of the subjects. The MF-IM and MF-TC distances and the transverse diameter of MF showed statistically significant differences for age, study and for interactions, while the MF-AM, MF-PM and MF-SM distances, as well as MF vertical diameter showed statistically significant differences only for age and for interactions. Morphological symmetry was demonstrated through our three studies, no statistically significant differences being determined in relation to side. CONCLUSIONS: The results of this research should increase the level of awareness among dentists with respect to MF topography changes with loss of teeth and help dental practitioners in refining the inferior alveolar nerve block techniques.

Identification of Lynch syndrome risk variants in the Romanian population.

Two familial forms of colorectal cancer (CRC), Lynch syndrome (LS) and familial adenomatous polyposis (FAP), are caused by rare mutations in DNA mismatch repair genes (MLH1, MSH2, MSH6, PMS2) and the genes APC and MUTYH, respectively. No information is available on the presence of high-risk CRC mutations in the Romanian population. We performed whole-genome sequencing of 61 Romanian CRC cases with a family history of cancer and/or early onset of disease, focusing the analysis on candidate variants in the LS and FAP genes. The frequencies of all candidate variants were assessed in a cohort of 688 CRC cases and 4567 controls. Immunohistochemical (IHC) staining for MLH1, MSH2, MSH6, and PMS2 was performed on tumour tissue. We identified 11 candidate variants in 11 cases; six variants in MLH1, one in MSH6, one in PMS2, and three in APC. Combining information on the predicted impact of the variants on the proteins, IHC results and previous reports, we found three novel pathogenic variants (MLH1:p.Lys84ThrfsTer4, MLH1:p.Ala586CysfsTer7, PMS2:p.Arg211ThrfsTer38), and two novel variants that are unlikely to be pathogenic. Also, we confirmed three previously published pathogenic LS variants and suggest to reclassify a previously reported variant of uncertain significance to pathogenic (MLH1:c.1559-1G>C).

Profile of common prostate cancer risk variants in an unscreened Romanian population.

To find sequence variants affecting prostate cancer (PCA) susceptibility in an unscreened Romanian population we use a genome-wide association study (GWAS). The study population included 990 unrelated pathologically confirmed PCA cases and 1034 male controls. DNA was genotyped using Illumina SNP arrays, and 24.295.558 variants were imputed using the 1000 Genomes data set. An association test was performed between the imputed markers and PCA. A systematic literature review for variants associated with PCA risk identified 115 unique variants that were tested in the Romanian sample set. Thirty of the previously reported SNPs replicated (P-value < 0.05), with the strongest associations observed at: 8q24.21, 11q13.3, 6q25.3, 5p15.33, 22q13.2, 17q12 and 3q13.2. The replicated variants showing the most significant association in Romania are rs1016343 at 8q24.21 (P = 2.2 × 10-4 ), rs7929962 at 11q13.3 (P = 2.7 × 10-4 ) and rs9364554 at 6q25.2 (P = 4.7 × 10-4 ). None of the variants tested in the Romanian GWAS reached genome-wide significance (P-value <5 × 10-8 ) but 807 markers had P-values <1 × 10-4 . Here, we report the results of the first GWAS of PCA performed in a Romanian population. Our study provides evidence that a substantial fraction of previously validated PCA variants associate with risk in this unscreened Romanian population.

Replication study of 34 common SNPs associated with prostate cancer in the Romanian population.

Prostate cancer is the third-most common form of cancer in men in Romania. The Romanian unscreened population represents a good sample to study common genetic risk variants. However, a comprehensive analysis has not been conducted yet. Here, we report our replication efforts in a Romanian population of 979 cases and 1027 controls, for potential association of 34 literature-reported single nucleotide polymorphisms (SNPs) with prostate cancer. We also examined whether any SNP was differentially associated with tumour grade or stage at diagnosis, with disease aggressiveness, and with the levels of PSA (prostate specific antigen). In the allelic analysis, we replicated the previously reported risk for 19 loci on 4q24, 6q25.3, 7p15.2, 8q24.21, 10q11.23, 10q26.13, 11p15.5, 11q13.2, 11q13.3. Statistically significant associations were replicated for other six SNPs only with a particular disease phenotype: low-grade tumour and low PSA levels (rs1512268), high PSA levels (rs401681 and rs11649743), less aggressive cancers (rs1465618, rs721048, rs17021918). The strongest association of our tested SNP's with PSA in controls was for rs2735839, with 29% increase for each copy of the major allele G, consistent with previous results. Our results suggest that rs4962416, previously associated only with prostate cancer, is also associated with PSA levels, with 12% increase for each copy of the minor allele C. The study enabled the replication of the effect for the majority of previously reported genetic variants in a set of clinically relevant prostate cancers. This is the first replication study on these loci, known to associate with prostate cancer, in a Romanian population.

Hepatitis Delta Virus Infection in Romania: Prevalence and Risk Factors.

BACKGROUND: Hepatitis delta virus (HDV) infection is associated with accelerated progression of fibrosis, early occurrence of hepatic decompensation and an increased risk for hepatocellular carcinoma. Epidemiological data on hepatitis delta virus (HDV) in Romania are still lacking. AIM: To assess the prevalence, virological, clinical and epidemiological features of HDV infection in Romanian patients. METHODS: We conducted a multicenter study in 10 centers. Data on sociodemographic characteristics and potential risk factors were collected through a questionnaire. Virological markers of HBV and HDV infection, biochemical and clinical features of liver disease were evaluated. RESULTS: The study population comprised 2,761 HBsAg(+) patients with a mean age of 43.8+/-13.8 years, out of whom 5.2% were HBeAg(+) and 55.7% were males. Liver cirrhosis was detected in 17.9% of patients, while 80.4% had chronic hepatitis. The prevalence of IgG anti-HDV(+) patients was 23.1%, out of whom 16.4% were HDV RNA positive. The highest prevalence of HDV infection was encountered in patients aged 50-59 years (28.9%) and patients aged >/= 60 (24.8%) (p=0.0001). Seroprevalence of HDV was significantly higher in AgHBs(+) cirrhotics vs. noncirrhotics (43.4% vs 19.0%, p=0.0001). Risk factors for HDV infection were: occupational hazard, no HCV chronic infection, lack of anti-HBV vaccination, presence of blood transfusions, any previous surgery, frequent hospitalization or endoscopies, tattoos, body piercing, use of glass syringes, number of female sexual partners. CONCLUSIONS: HBsAg(+) population in Romania is characterized by a high prevalence of HBeAg(-) HBV infection as well as HDV co-infection. A cohort phenomenon for HDV prevalence is also observed similar to that of HCV/HBV monoinfections.

Single nucleotide polymorphisms in colorectal cancer: associations with tumor site and TNM stage.

BACKGROUND AND AIM: Colon tumor carcinogenesis and rectal tumor carcinogenesis have each been associated with different genetic features, but data are still controversial and are insufficient to support their distinct molecular biology. Recently, genome-wide association studies (GWAS) have also found heterogeneity in colorectal cancer (CRC) risks based on population ethnicity and tumor features. Several single nucleotide polymorphism (SNP) markers are described in the literature as having site and/or stage specificity, including rs10795668, rs3802842, rs6983267, and rs4939827. Replication of initial findings in different ethnic groups by independent studies is required to unravel the population-specific differences in risk. METHODS: We examined whether inherited risk variants at rs10795668, rs3802842, rs6983267, and rs4939827 exerted a differential effect on colon and rectal cancers in a Romanian hospital based series of 153 CRC cases and 182 non-affected control subjects prospectively recruited between 2007 and 2010. RESULTS: Rectal tumors were significantly associated with rs4939827 (OR = 4.85, P = 0.002) and rs6983267 (OR = 3.00, P = 0.036), suggesting that carriers of risk alleles at these loci had increased susceptibility to development of rectal cancer rather than colon cancer. Carrying the C allele at rs3802842 appeared to be associated with a lower risk for rectal tumors in our dataset. We found no association between genotypes and tumor aggressiveness as reflected by TNM staging. CONCLUSIONS: The associations between SNPs, and tumor site and staging remain to be further clarified. Our results should be considered cautiously, but may be taken into account in future, larger epidemiological studies.

The prevalence and risk factors of hepatitis C virus infection in adult population in Romania: a nationwide survey 2006 - 2008.

AIMS: This study was aimed at determining the seroprevalence of hepatitis C virus (HCV) infection in Romania and the possible risk factors and modality of HCV transmission. METHODS: A nationwide cross-sectional survey among the adult population was conducted between 2006-2008 in Romania through a population multicenter stratified random cluster sampling. Serum samples from 13,460 subjects were tested with a 3rd generation ELISA and a standardized questionnaire concerning the socio-demographic characteristics and potential risk factors was used. RESULTS: The prevalence rate of HCV infection in Romanian adult population was 3.23% with significant differences between the main geographical regions (Moldavia 4.25%, Wallachia & Dobrogea 3.35% and Transylvania & Banat 2.63%), as well as between different counties (maximum 7.19%, minimum 0.56%). Overall participation rate to the survey of the selected subjects was 74.69%. Risk factors for HCV infection were: blood/blood products transfusions (p=0.0001), previous surgery (elective and emergency, p=0.0001 and p=0.043, respectively), frequent hospitalizations (p=0.0001), injections at home (p=0.0001), accidents/trauma (p=0.0001), occupational hazard related to blood exposure (p=0.025), intravenous drug administration (p=0.002), a partner chronically infected with HCV/hepatitis B virus (HBV) (p=0.046), first sexual intercourse <18 years (p=0.019), familial exposure to HCV/HBV infection (p=0.001) or to chronic HBV/HCV liver disease (p=0.001), personal history of chronic HBV infection (p=0.001). HCV RNA positivity was detected in 91% of the anti HCV positive subjects. CONCLUSIONS: Overall HCV prevalence in Romania is 3.23%. Both nosocomial and non-nosocomial routes are implicated as risk factors for HCV infection.

Access to peginterferon plus ribavirin therapy for hepatitis C in Romania between 2002-2009.

BACKGROUND: An overall prevalence rate of HCV infection in Romanian adult population was recently estimated to be 3.23%. The proportion of treated patients with chronic hepatitis C in our country has never been assessed. AIMS: 1) to analyze the quality and quantity of antiviral therapy delivery; 2) to determine the proportion of patients being annually and ever treated with antiviral therapy in Romania and 3) to identify barriers against treatment of HCV infected-population in Romania. RESULTS: The number of annually treated patients remained relatively stable between 2002 and 2007 (1,813 patients treated with pegylated interferon and ribavirin in 2002 and 2,446 in 2007). There was a doubled increase in reimbursed treatment in 2008 and 2009 (4,503 and respectively 4,701 treated patients) due to a special campaign organized to increase awareness and prevention of HCV transmission. The median time to therapy approval varies from county to county; overall it is 10.23 months. A total number of 25,318 patients with chronic C hepatitis were treated between 2002-2009, corresponding to a cumulative proportion of 4.1% of the prevalent cases of HCV infection treated in Romania until 1st January 2010. The main limiting factor of access to antiviral therapy for hepatitis C in Romania remains the lack of funds. CONCLUSIONS: This is the first analysis of the nationwide practice for treatment of hepatitis C in Romania. Increased public health efforts are required to improve access to antiviral therapy for hepatitis C in Romania.