The Rate of Burnout Syndrome in A Tertiary Gastroenterology University Center in Romania.

BACKGROUND AND AIMS: The burnout syndrome (BOS) is commonly seen in healthcare professionals, particularly in physicians who are exposed to a high level of stress at work and has a negative impact on the medical activity. Physicians with BOS manifest a negative attitude, a reduction in compassion at work, and suboptimal patient care experiences. These all can lead to absenteeism, poor performance and more frequent medical errors. We aimed to assess the level of BOS in a tertiary gastroenterology university center in Romania. METHODS: This observational study involved 40 physicians from a tertiary gastroenterology university center. An online questionnaire assessed the presence of BOS using the Maslach Burnout Inventory. RESULTS: A total of 40 physicians responded to the questionnaire. The prevalence of overall BOS of 87.5%. In terms of high burnout, 15 doctors (37.5%) had emotional exhaustion, 10 doctors (25%) had depersonalization, and 30 doctors (80%) scored low for personal achievement. Men presented more frequently emotional exhaustion and women lower personal achievement scores, but there was no significant statistical difference. No significant relationship was found between marital status or the number of children and BOS. We identified multiple risk factors associated to BOS, the most important one being strict internal regulations. CONCLUSIONS: Physicians presented an increased risk for BOS. The high rate of BOS among physicians found in our study requires careful attention. Further studies aiming to identify other factors that contribute to BOS and to identify measures to combat this syndrome are necessary.

Enhancing Calprotectin's Predictive Power as a Biomarker of Endoscopic Activity in Ulcerative Colitis: A Machine Learning Use Case.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by periods of exacerbation and remission, making disease monitoring and management challenging. Endoscopy, the gold standard for assessing disease activity and severity, involves invasive procedures and is associated with patient discomfort and risks. Using machine learning (ML) to combine fecal calprotectin with other clinical or biological tests can significantly enhance the non-invasive prediction of endoscopic disease activity (EDA) in UC. Aim: To prove that by fusing fecal calprotectin with other clinical data into an ML model, the performance of the non-invasive prediction of EDA can be significantly improved. Methods: We conducted a prospective, observational, single-center study encompassing 103 patients diagnosed with UC. We employed multilayer perceptron models as the core ML algorithm for predicting EDA. For the constructed models, we utilized the varImp function from the caret library in R to assess the significance of each variable in predicting the outcome. Results: Calprotectin as a sole predictor obtained an accuracy of 70% and an area under the curve (AUC) of 0.68. Combining calprotectin with the list of selected predictors that were fed to the MLP models improved accuracy and the AUC. The accuracy of the algorithm on the test set was 85%. Similarly, the AUC increased to 0.93. This is the first study to propose the use of calprotectin as a predictor in an ML model to estimate UC endoscopic disease activity. Conclusion: The deployment of this ML model can furnish doctors and patients with valuable evaluation of endoscopic disease activity which can be highly beneficial for individuals with UC who need long-term treatment.

Safety, Efficacy and Persistence of Advanced Therapies in Inflammatory Bowel Disease: Results from ORIGINS. A Retrospective Observational Study.

BACKGROUND AND AIMS: Real-world assessments of efficacy and safety of advanced therapies used for inflammatory bowel disease (IBD) patients are limited. We aimed to report safety, efficacy and treatment persistence of new molecules (infliximab, adalimumab, vedolizumab, tofacitinib, ustekinumab) in a retrospective multicentric national Romanian analysis. METHODS: We conducted a nationwide, retrospective observational multicentric study. Data were collected retrospectively from electronic and paper files. Patients who started on one of the five investigated molecules during December 2019-December 2021 were included. The main outcome measures were clinical remission, endoscopic healing, persistence on treatment and safety data. RESULTS: A total of 678 adult patients from 24 Romanian IBD centers with a diagnosis of ulcerative colitis or Crohn's disease were included. Participants had previously failure to one (268, 39.5%), two (108, 15%) or more treatment lines and only 38% (259) were biologic naïve. In the 24 months study period, most patients were started on vedolizumab (192, 28%), followed by adalimumab, infliximab, ustekinumab and tofacitinib. In biologic-naïve patients, most physicians (72%) preferred anti-TNF treatment as first line biologic (93 patients started on infliximab, 92 on adalimumab), followed by vedolizumab, ustekinumab and tofacitinib. During follow-up, 71% (470, p=0.05) of patients achieved clinical remission and 36% (134, p=0.03) achieved mucosal healing. The 6 months milestone for persistence was reached in 78% (530) of cases. Almost half of patients (47%, 316 patients) persisted on their current treatment for over 12 months. Overall, an adverse reaction was reported for 67 (10.4%) patients, with no lethal events. CONCLUSIONS: Population of biologic-experienced IBD patients in Romania is increasing and is becoming more difficult to achieve long-term disease control. Discontinuation rates for advanced therapies are high.

The Potential Use of Artificial Intelligence in Irritable Bowel Syndrome Management.

Irritable bowel syndrome (IBS) has a global prevalence of around 4.1% and is associated with a low quality of life and increased healthcare costs. Current guidelines recommend that IBS is diagnosed using the symptom-based Rome IV criteria. Despite this, when patients seek medical attention, they are usually over-investigated. This issue might be resolved by novel technologies in medicine, such as the use of Artificial Intelligence (AI). In this context, this paper aims to review AI applications in IBS. AI in colonoscopy proved to be useful in organic lesion detection and diagnosis and in objectively assessing the quality of the procedure. Only a recently published study talked about the potential of AI-colonoscopy in IBS. AI was also used to study biofilm characteristics in the large bowel and establish a potential relationship with IBS. Moreover, an AI algorithm was developed in order to correlate specific bowel sounds with IBS. In addition to that, AI-based smartphone applications have been developed to facilitate the monitoring of IBS symptoms. From a therapeutic standpoint, an AI system was created to recommend specific diets based on an individual's microbiota. In conclusion, future IBS diagnosis and treatment may benefit from AI.

Laboratory Data and IBDQ-Effective Predictors for the Non-Invasive Machine-Learning-Based Prediction of Endoscopic Activity in Ulcerative Colitis.

A suitable, non-invasive biomarker for assessing endoscopic disease activity (EDA) in ulcerative colitis (UC) has yet to be identified. Our study aimed to develop a cost-effective and non-invasive machine learning (ML) method that utilizes the cost-free Inflammatory Bowel Disease Questionnaire (IBDQ) score and low-cost biological predictors to estimate EDA. Four random forest (RF) and four multilayer perceptron (MLP) classifiers were proposed. The results show that the inclusion of IBDQ in the list of predictors that were fed to the models improved accuracy and the AUC for both the RF and the MLP algorithms. Moreover, the RF technique performed noticeably better than the MLP method on unseen data (the independent patient cohort). This is the first study to propose the use of IBDQ as a predictor in an ML model to estimate UC EDA. The deployment of this ML model can furnish doctors and patients with valuable insights into EDA, a highly beneficial resource for individuals with UC who need long-term treatment.

Romanian Guidelines for the Diagnosis and Treatment of GERD-induced Respiratory Manifestations.

BACKGROUND AND AIMS: Gastroesophageal reflux disease (GERD) is a common condition present in daily practice with a wide range of clinical phenotypes. In this line, respiratory conditions may be associated with GERD. The Romanian Societies of Gastroenterology and Neurogastroenterology, in association with the Romanian Society of Pneumology, aimed to create a guideline regarding the epidemiology, diagnosis and treatment of respiratory conditions associated with GERD. METHODS: Delphi methodology was used and eleven common working groups of experts were created. The experts reviewed the literature according to GRADE criteria and formulated 34 statements and recommendations. Consensus (>80% agreement) was reached for some of the statements after all participants voted. RESULTS: All the statements and the literature review are presented in the paper, together with their correspondent grade of evidence and the voting results. Based on >80% voting agreement, a number of 22 recommendations were postulated regarding the diagnosis and treatment of GERD-induced respiratory symptoms. The experts considered that GERD may cause bronchial asthma and chronic cough in an important number of patients through micro-aspiration and vagal-mediated tracheobronchial reflex. GERD should be suspected in patients with asthma with suboptimal controlled or after exclusion of other causes, also in nocturnal refractory cough which needs gastroenterological investigations to confirm the diagnosis. Therapeutic test with double dose proton pump inhibitors (PPI) for 3 months is also useful. GERD induced respiratory conditions are difficult to treat; however,proton pump inhibitors and laparoscopic Nissen fundoplication are endorsed for therapy. CONCLUSIONS: This guideline could be useful for the multidisciplinary management of GERD with respiratory symptoms in current practice.

Extrapancreatic necrosis volume: A new tool in acute pancreatitis severity assessment?

BACKGROUND: Many scores have been suggested to assess the severity of acute pancreatitis upon onset. The extrapancreatic necrosis volume is a novel, promising score that appears to be superior to other scores investigated so far. AIM: To evaluate the discriminatory power of extrapancreatic necrosis volume to identify severe cases of acute pancreatitis. METHODS: A total of 123 patients diagnosed with acute pancreatitis at Institute of Gastroenterology and Hepatology, St Spiridon Hospital between January 1, 2017 and December 31, 2019 were analyzed retrospectively. Pancreatitis was classified according to the revised Atlanta classification (rAC) as mild, moderate, or severe. Severity was also evaluated by computed tomography and classified according to the computed tomography severity index (CTSI) and the modified CTSI (mCTSI). The results were compared with the extrapancreatic volume necrosis to establish the sensitivity and specificity of each method. RESULTS: The CTSI and mCTSI imaging scores and the extrapancreatic necrosis volume were highly correlated with the severity of pancreatitis estimated by the rAC (r = 0.926, P < 0.001 and r = 0.950, P < 0.001; r = 0.784, P < 0.001, respectively). The correlation of C-reactive protein with severity was positive but not as strong, and was not significant (r = 0.133, P = 0.154). The best predictor for the assessment of severe pancreatitis was the extrapancreatic necrosis volume [area under the curve (AUC) = 0.993; 95% confidence interval (CI): 0.981-1.005], with a 99.5% sensitivity and 99.0% specificity at a cutoff value of 167 mL, followed by the mCTSI 2007 score (AUC = 0.972; 95%CI: 0.946-0.999), with a 98.0% sensitivity and 96.5% specificity, and the CTSI 1990 score (AUC = 0.969; 95%CI: 0.941-0.998), with a 97.0% sensitivity and 95.0% specificity. CONCLUSION: Radiological severity scores correlate strongly and positively with disease activity. Extrapancreatic necrosis volume shows the best diagnostic accuracy for severe cases.

Role of PNPLA3 in the Assessment and Monitoring of Hepatic Steatosis and Fibrosis in Patients with Chronic Hepatitis C Infection Who Achieved a Sustained Virologic Response.

Background and Objectives: Hepatic diseases are an important public health problem. All patients with chronic hepatitis C virus (HCV) infection receive treatment, regardless of hepatic fibrosis severity. However, evaluation of hepatic fibrosis and steatosis is still useful in assessing evolution, prognosis and monitoring of hepatic disease, especially after treatment with direct-acting antivirals (DAAs). The aim of this study was to assess the link between patatin-like phospholipase domain-containing 3 (PNPLA3) polymorphism and the degree of hepatic steatosis and fibrosis in patients with chronic HCV infection, as well as changes in steatosis and fibrosis three monthsafter obtaining a sustained viral response (SVR). Materials and Methods:Ourstudy included 100 patients with chronic hepatitis C (CHC) infection and compensated cirrhosis who received DAA treatment and who were evaluated using Fibromax prior to and 3 months after SVR. The influence of PNPLA3 (CC, CG, GG) genotype among these patients on the degree of post-treatment regression of steatosis and fibrosis was assessed. Results: Regression was noticed in the degree of both hepatic steatosis and hepatic fibrosis post-DAA treatment (three months after SVR). Analysis of the correlation between PNPLA3 genotype and fibrosis indicated that the average level of fibrosis (F) before DAA treatment was higher in patients with the GG genotype than in patients with the CC or CG genotype. Three months after SVR, the average level of fibrosis decreased; however, it remained significantly increased in GG subjects compared to that in CC or CG patients. The degree of hepatic steatosis before treatment was not significantly different among patients with different PNPLA3 genotypes, and no significant correlations were observed three months after SVR. Conclusions: The genetic variants of PNPLA3 influence the evolution of hepatic fibrosis. The GG subtype plays an important role in the degree of hepatic fibrosis both before and after treatment (three months after SVR)and could be a prognostic marker for assessment of post-SVR evolution.

Anemia in Crohn's Disease-The Unseen Face of Inflammatory Bowel Disease.

Background and Objectives: Anemia is the most frequent complication of inflammatory bowel diseases. Clinically, anemia can affect important quality-of-life (QoL) components, such as exercise capacity, cognitive function, and the ability to carry out social activities. The disease activity has a significant impact on QoL, mainly due to clinical manifestations, which are more severe during the periods of disease activity. Our aim was to estimate the impact of anemia on QoL in patients with Crohn's disease. Material and Methods. We made a prospective study on 134 patients with Crohn's disease (CD) in a Romanian tertiary center. The CD diagnosis was established by colonoscopy and histopathological examination. In particular cases, additional examinations were required (small bowel capsule endoscopy, computed tomography enterography, and magnetic resonance enterography). Anemia was defined according to the World Health Organization's definition, the activity of the disease was assessed by Crohn's disease activity index (CDAI) score, and the QoL was evaluated by Inflammatory Bowel Disease Questionnaire 32 (IBDQ 32). Results: 44.8% patient had anemia, statistically related to the activity of the disease and corticoids use. We found a strong association between QoL and disease activity on all four sub-scores: patients with more severe activity had a significantly lower IBDQ (260.38 ± 116.96 vs. 163.85 ± 87.20, p = 0.001) and the presence of anemia (127.03 vs. 148.38, p = 0.001). In multiple regression analyses, both disease activity and anemia had an impact on the QoL. Conclusions: Anemia has high prevalence in the CD in northeastern region of Romania. Anemia was more common in female patients, in patients undergoing corticosteroid treatment, and in those with active disease. Both anemia and disease activity had a strong negative and independent impact on QoL.

Romanian Guidelines for Nonpharmacological Therapy of IBS.

BACKGROUND AND AIMS: The nonpharmacological therapy in irritable bowel syndrome (IBS) is expanding rapidly. Practitioners and medical educators need to be aware of progress and changes in knowledge of this topic. The Romanian Society of Neurogastroenterology aimed to create guidelines based on best evidence on the use of nonpharmacological therapy in IBS. METHODS: A group of experts was constituted. This was divided in eleven subgroups dedicated to eleven categories of nonpharmacological therapy. The subgroups searched the literature and formulated statements and recommendations. These were submitted to vote in order to obtain consensus. RESULTS: The outcome of this activity is represented by the guidelines of the Romanian Society of Neurogastroenterology, presented in this paper. The recommendations are seen as complementary to the pharmacological therapy and are not intended to recommend avoiding pharmacological drugs. CONCLUSIONS: These guidelines were elaborated by a Delphi process and represent a useful tool for physicians managing patients with IBS.

Gut microbiota changes in inflammatory bowel diseases and ankylosing spondilytis.

BACKGROUND AND AIMS: Both inflammatory bowel diseases (IBD) and ankylosing spondylitis (AS) can be considered chronic immune disorders sharing common etiopathogenetic mechanisms. Changes in the composition of the intestinal microbiota, which can lead to an abnormal mucosal response, could be the missing link between these two diseases. Our study evaluate the composition of intestinal microbiota and to characterize gut dysbiosis in patients with IBD and AS. METHODS: We conducted a prospective case-control study that enrolled 124 patients [20 Crohn's disease (CD), 27 ulcerative colitis (UC), 28 AS, 17 IBD + AS and 32 controls). Intestinal microbiota analysis was performed by real-time polymerase chain reaction in stool samples. RESULTS: The total quantity of bacteria was decreased in all investigated groups compared to the control group. In studied groups, we noticed an increased percentage of Bacteroides and Escherichia coli (E.coli) and a decreased percentage of Clostridium coccoides, Clostridium leptum, and Faecalibacterium prausnitzii compared to the control group. The percentages of Bifidobacterium (p=0.010) as well as Lactobacillus group (p=0.023) were higher in the L3 form of CD patients. In the E2 form of UC, the quantity of Bacteroides was much higher compared to the E3 form (p=0.004). In AS patients, significant correlations were observed only for the Bifidobacterium species, significantly increased in the axial form compared to peripheral disease (p=0.035). Statistically significant correlations were demonstrated between the Crohn Disease Activity Index score and the total bacterial group (p=0.023, r=-0.507), respectively Bacteroides (p=0.021, r=-0.511) and between the Mayo score and Lactobacillus (p=0.001), respectively E. coli (p=0.001). In IBD + AS group, the Crohn Disease Activity Index score was inversely correlated with the total bacterial group (p=0.010) and directly correlated with Lactobacillus (p=0.047). CONCLUSIONS: Intestinal dysbiosis is associated with both IBD and AS. In the association of IBD with AS, dysbiosis is intermediate, but it is associated with the more severe articular disease. Bifidobacterium and Lactobacillus (commonly used as probiotics!) were found to be increased in the association between active IBD and active AS. Further studies are needed to understand how dysbiosis regulates the gut immune system and contributes to intestinal and articular inflammation.

COVID-19 and Inflammatory Bowel Diseases: Risk Assessment, Shared Molecular Pathways, and Therapeutic Challenges.

BACKGROUND: The novel coronavirus SARS-CoV-2 causing COVID-19 disease is yielding a global outbreak with severe threats to public health. In this paper, we aimed at reviewing the current knowledge about COVID-19 infectious risk status in inflammatory bowel disease (IBD) patients requiring immunosuppressive medication. We also focused on several molecular insights that could explain why IBD patients appear not to have higher risks of infection and worse outcomes in COVID-19 than the general population in an attempt to provide scientific support for safer decisions in IBD patient care. METHODS: PubMed electronic database was interrogated for relevant articles involving data about common molecular pathways and shared treatment strategies between SARS-CoV-2, SARS-CoV-1, MERS-CoV, and inflammatory bowel diseases. Besides, Neural Covidex, an artificial intelligence tool, was used to answer queries about pathogenic coronaviruses and possible IBD interactions using the COVID-19 Open Research Dataset (CORD-19). Discussions. Few molecular and therapeutic interactions between IBD and pathogenic coronaviruses were explored. First, we showed how the activity of soluble angiotensin-converting enzyme 2, CD209L other receptors, and phosphorylated α subunit of eukaryotic translation initiation factor 2 might exert protective impact in IBD in case of coronavirus infection. Second, IBD medication was discussed in the context of possible beneficial effects on COVID-19 pathogeny, including "cytokine storm" prevention and treatment, immunomodulation, interferon signaling blocking, and viral endocytosis inhibition. CONCLUSIONS: Using the current understanding of SARS-CoV-2 as well as other pathogenic coronaviruses immunopathology, we showed why IBD patients should not be considered at an increased risk of infection or more severe outcomes. Whether our findings are entirely applicable to the pathogenesis, disease susceptibility, and treatment management of SARS-CoV-2 infection in IBD must be further explored.

Pancreatico-Pleural Fistula - from Diagnosis to Management. A Case Report.

Pancreatic pseudocysts are frequent complications of both acute and chronic pancreatitis. By contrast, pancreatico-pleural fistula is rare. Here we report a case of massive pleural effusion secondary to a fistula in the left hemi-diaphragm, between a pancreatic pseudocyst and the left pleura, in a patient with a right kidney tumor and bilateral massive pulmonary thromboembolism. This fistula developed after several episodes of un-investigated acute pancreatitis. The pleural effusion was treated by three thoracocenteses, without recurrence.

Bidirectional Relationship between Gastric Emptying and Plasma Glucose Control in Normoglycemic Individuals and Diabetic Patients.

Gastric emptying and glycemic control pathways are closely interrelated processes. Gastric chyme is transferred into the duodenum with velocities depending on its solid or liquid state, as well as on its caloric and nutritional composition. Once nutrients enter the intestine, the secretion of incretins (hormonal products of intestinal cells) is stimulated. Among incretins, glucagon-like peptide-1 (GLP-1) has multiple glycemic-regulatory effects that include delayed gastric emptying, thus triggering a feedback loop lowering postprandial serum glucose levels. Glycemic values also influence gastric emptying; hyperglycemia slows it down, and hypoglycemia accelerates it, both limiting glycemic fluctuations. Disordered gastric emptying in diabetes mellitus is understood today as a complex pathophysiological condition, with both irreversible and reversible components and high intra- and interindividual variability of time span and clinical features. While limited delays may be useful for reducing postprandial hyperglycemias, severely hindered gastric emptying may be associated with higher glycemic variability and worsened long-term glycemic control. Therapeutic approaches for both gastric emptying and glycemic control include dietary modifications of meal structure or content and drugs acting as GLP-1 receptor agonists. In the foreseeable future, we will probably witness a wider range of dietary interventions and more incretin-based medications used for restoring both gastric emptying and glycemic levels to nearly physiological levels.

Looking beyond gut inflammation in inflammatory bowel disease.

Patients diagnosed with inflammatory bowel disease (IBD) often develop one or more extraintestinal manifestations (EIM). We performed a prospective study that included 517 patients with IBD (Crohn's disease - CD, ulcerative colitis - UC or undifferentiated colitis - CN) diagnosed between 1975 and 2016 in the Northeastern region of Romania. The patients were extracted from the national database (IBD Prospect). UC cases predominated compared to CD cases (n=368 vs. n=135). Only 10 patients were diagnosed with CN. In the study group, 51 cases with IBD and EIM were identified, having a prevalence of 9.9%. Musculoskeletal manifestations were the most common EIM. Peripheral involvement - arthritis (n=26, 68.42%) predominated, followed by axial damage - sacroiliitis/ankylosing spondylitis (SI∕AS) (n=12, 31.58%) (p=0.001). Patients with CD had a 3.48-fold greater risk of developing joint manifestations [p<0.001, odds ratio (OR)=3.478, 95% confidence interval (CI) 1.779-6.801]. In both CD and UC patients, arthritis cases were the most frequent observed (68.42% vs. 31.58%). Patients with CD had a 5-fold higher risk of developing arthritis (p<0.001, OR=5.009, 95% CI 2.21-11.34). Neither CD, nor UC patients, had a confirmed risk of developing SI∕AS (p=0.468, OR=1.565, 95% CI 0.463-5.293 for CD) (p=0.586, OR=0.714, 95% CI 0.211-2.413 for UC). Cases of arthritis and CD (n=16) mainly correlated with the colonic localization of inflammation (n=7, p=0.723) followed by ileo-colonic form of CD (n=7, p=0.321). Patients with arthritis and UC (n=10) initially correlated with pancolitis (n=5, p=0.072, OR=3.023, 95% CI 0.855-10.69) then with proctitis (n=3, p=0.392) and left-sided colitis (n=2, p=0.024, OR=0.196, 95% CI 0.041-0.938).

Atrial fibrillation and sympathovagal balance in patients with gastroesophageal reflux disease.

BACKGROUND/AIMS: Similar autonomic innervation of the esophagus and left atrium with sympathovagal imbalance seems to explain the association between non-valvular atrial fibrillation (AF) and gastroesophageal reflux disease (GERD). We aimed to assess this association via parameters of heart rate variability in time (SDNN) and frequency (low-frequency (LF)/high-frequency (HF) ratio) domains by 24-hour electrocardiographic (ECG) Holter monitoring. MATERIALS AND METHODS: One hundred thirty-five patients were prospectively included by a joint team consisting of a gastroenterologist and a cardiologist on the basis of the patients' complaints. A diagnosis of GERD was assessed by the gastroenterologist clinically. All patients also underwent upper gastrointestinal endoscopy. RESULTS: The patients were included in two groups: 61 patients with GERD (group I) and 74 patients without GERD (group II), with demographic data of 41% male, age 61.5±9 years, and body mass index (BMI) 28.8±4 kg/m2 versus 46% male, age 58±9 years, and BMI 29±4 kg/m2 (all p>0.05). In groups I and II the percentages of patients with AF were 33% and 39%, respectively (p=0.52). Patients with GERD had a relative risk of AF of 1.17 (95% confidence interval [CI] 0.78-1.75; p=0.34). Heart rate variability in terms of the time-domain parameter (SDNN) was statistically significantly lower in the GERD group (97.6±13.7 ms versus 139.9±44.6 ms; p=0.001). The mean value of the frequency-domain parameter (LF/HF ratio) was also lower in the GERD group (0.75±0.17 ms versus 0.76±0.24 ms), but without statistical significance (p=0.930). CONCLUSION: Sympathovagal balance seems to be disrupted in patients with GERD, with dominance of the parasympathetic system and an increased risk of arrhythmias, although AF was not significantly more frequent in these patients.

Efficacy and safety of paritaprevir/ritonavir, ombitasvir, and dasabuvir with ribavirin for the treatment of HCV genotype 1b compensated cirrhosis in patients aged 70 years or older.

Advanced age has been a major limitation of interferon-based treatment for chronic hepatitis C virus (HCV) infection because of its poor response and tolerability. Direct-acting antiviral (DAA) drug regimens are safe and highly effective, allowing administration of treatment also in elderly. This study aims to assess the efficacy and safety of paritaprevir/ritonavir, ombitasvir, and dasabuvir (PrOD) with ribavirin for the treatment of patients aged ≥70 years with HCV genotype 1b compensated cirrhosis.A total of 1008 patients with HCV genotype 1b compensated cirrhosis were prospectively treated with PrOD + ribavirin for 12 weeks, between December 2015 and July 2016. Sustained virologic response 12 weeks after the end of treatment (SVR12), adverse effects (AEs), comorbidities, discontinuation, and death rates were recorded. Efficacy and safety of therapy were assessed in patients aged ≥70 years and compared with data from patients <70 years.There were 117 patients aged ≥70 years, preponderantly females (58.9%), mean age 73.3 ±â€Š2.8 years (range 70-82), and 37 (31.6%) were treatment-experienced. Comorbidities were reported in 60.6% of patients ≥70 years and in 39.8% of those <70 years (P < .001). SVR12 rates based on intention-to-treat and per-protocol analyses were 97.4% and 100%, respectively, in patients ≥70 years, compared to 97.8% and 99.6%, respectively, in patients <70 years (P = ns and P = ns). Severe AEs were reported in 4 (3.4%) patients ≥70 years, compared to 23 (2.6%) in those <70 years (P = ns). One death was recorded in a patient aged 79 years (0.9%) and 6 deaths (0.8%) in those <70 years (P = ns).Treatment with PrOD + ribavirin in patients 70 years of age or older with HCV genotype 1b compensated cirrhosis proved as effective, safe, and well tolerated, as it did in younger patients.

Diagnosis of minimal hepatic encephalopathy in a tertiary care center from eastern Romania: validation of the psychometric hepatic encephalopathy score (PHES).

The psychometric hepatic encephalopathy score (PHES) is frequently used as a "gold standard" for the diagnosis of minimal hepatic encephalopathy (MHE). In Romania, there are currently no widely available tests for the detection of MHE. In this study we aimed to standardize the PHES in a healthy Romanian population and to estimate the prevalence of MHE in a group of Romanian patients with liver cirrhosis. A total of 260 healthy volunteers and 106 patients with liver cirrhosis were included in the study. The five neuropsychological tests comprising the PHES were administered to all enroled subjects. Blood samples for routine tests and serum ammonia were collected. In the healthy volunteer group age and education years were found to be predictors of all tests and gender only in two tests: digit symbol test and serial dotting test. The PHES of the healthy volunteer group was 0,43 ± 1,37 and the cut-off between normal and pathological values was set at -3 points. In the liver cirrhosis group the mean PHES was -2,44 ± 3,41, significantly lower than in the control group (p = 0,001). The estimated prevalence of MHE was 34,7 % (37 patients). In patients with cirrhosis there was a significant correlation between PHES and the severity of the liver disease according to Child-Pugh classification (r = 0,529, p = 0,001) and MELD score (r = -0,525, p = 0,001). According to our results, accurate Romanian PHES norms for the diagnosis of MHE have been developed. MHE was diagnosed in a significant proportion of Romanian patients with liver cirrhosis.

E-cadherin expression in primary colorectal cancer and metastatic lymph nodes.

Colorectal cancer (CRC) is one of the most prevalent malignancies and fourth cause of cancer death worldwide but the current TNM staging system together with clinicopathological characteristics are not sufficient to identify cases that have a poor prognosis. The aim of the current study was to compare E-cadherin expression in primary CRC and lymph node metastases with the one exhibited by normal colic mucosa and normal lymph nodes, and to evaluate its association with disease severity. The authors retrospectively analyzed 65 patients that underwent colectomy for CRC at the First Surgical Clinic, "Sf. Spiridon" Emergency Hospital from Iassy, Romania, over a 10 years period, from January 2004 to December 2013. In all cases, immunohistochemical staining against E-cadherin was performed on primary CRC and associated lymph nodes slices. Primary CRC presented a higher rate (64.62%) of abnormal E-cadherin expression (no staining, cytoplasmic or mixed staining) compared to normal colic mucosa (16.67%) (p<0.001). Both primary CRC and corresponding metastatic lymph nodes displayed a predominantly membranous expression (pure or mixed) of E-cadherin (67.69% and 89.23%, respectively). Well and moderately differentiated tumors displayed an increased E-cadherin expression (44 of 56 cases) compared to poorly differentiated tumors that lacked E-cadherin expression in six out of nine cases. In conclusion, E-cadherin expression abnormalities in CRC are rather qualitative than quantitative and E-cadherin is an important marker of tumor aggressiveness and spreading potential.