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Background: Histologic activity has emerged as an aspirational therapeutic goal in ulcerative colitis management. It is not yet a formal treatment target in ulcerative colitis. However, it could be used as an adjunct to mucosal healing to represent a deeper level of healing. We investigated mucosal and histologic remission rates and potential predictors of these outcomes in a cohort of UC patients. Methods: We conducted a retrospective analysis of data collected from UC patients enrolled in an ongoing prospective cohort study. Mucosal healing was defined as Mayo endoscopic score = 0. Results: A total of 131 patients with ulcerative colitis were enrolled in our study and were prospectively followed for a median length of 2 years (range 0–5 years), totaling 266 study visits. Mucosal healing was recorded for 27 patients at 70 (26%) different study visits. For patients with mucosal healing, histologic remission was achieved in 18/27 (66%) patients. On univariate analysis, sustained clinical remission, SIBDQ scores ≥ 5.5, CRP ≤ 5 mg/dL and absence of corticotherapy were associated with mucosal healing and SIBDQ scores ≥ 5.5 and CRP ≤ 5 mg/dL with histologic healing, respectively. After logistic regression analysis, none of the investigated factors were associated with mucosal and histologic healing. The number of CD8+ intraepithelial lymphocytes (IELs) was significantly greater than the number of CD4+ IELs in periods of disease activity, as well as during mucosal healing (p < 0.01 in both cases). Conclusions: Mucosal healing and histologic remission rates are low in real-life settings. The results of univariate analysis indicate that a good quality of life (SIBDQ score) and normal inflammatory markers (CRP) are associated with mucosal and histologic healing. However, frequently used patient- and disease-related factors, including mucosal healing, are not reliable predictors for histologic remission. Greater CD8+ lymphocyte involvement and higher CD8+/CD4+ distribution can have a meaningful impact on understanding the pathogenesis and natural history of ulcerative colitis, as well as future treatment options for lymphocyte-targeting medications.

Background. Biliopancreatic tumors (BPT) are among the most aggressive solid malignancies, and their incidence is rising. Good patient outcome relies heavily on a multidisciplinary approach to therapy, including timely access to endoscopy, surgery and chemo/radiotherapy. We aimed to evaluate current practices as reflected in the management and outcome of patients diagnosed with BPT in the setting of a low-resource medical system in order to identify areas suitable for improvement. Material and methods. We conducted a prospective observational study of patients with pancreatic cancers and extrahepatic cholangiocarcinomas evaluated in 4 referral centers in Romania. We collected data on the pathology of the tumors, staging at diagnosis, ECOG status, surgical interventions, chemo/radiotherapy and endoscopic drainage where applicable. A telephonic follow-up visit at 3 months after the enrollment visit collected additional data regarding evolution, subsequent treatment, performance status and disease-related events and outcomes. Results and conclusions. One hundred seventy-two patients were included in the study during a one-year period at the four participating centers. 72.1% were diagnosed with pancreatic cancer while 27.9% had extrahepatic cholangiocarcinoma. We identified several unmet needs in the current practices of treatment for these malignancies: a lack of pathological confirmation in 25.6% of the cases, a very low percentage of resectable lesions (only 18% of the patients operated with curative intent), and suboptimal choice of drainage in patients who required palliative drainage at their first endoscopic intervention. Significant effort is required to ensure standard-of-care treatment for patient with BPT in low-resource medical systems, including comprehensive auditing and protocol surveillance.

Background Fibrogenesis and inflammation contribute to the progression of cirrhosis. However, it is unknown if these processes also contribute to the development of cirrhotic cardiomyopathy (CCM). Novel magnetic resonance imaging with quantification of the extracellular volume (ECV) provides an estimate of the fibrotic remodelling in the liver and heart. Aim To investigate the relationship between liver and cardiac ECV in cirrhosis and their association with collagen turnover and inflammation. Methods A prospective study of 52 patients with cirrhosis and 14 healthy controls. All patients underwent contrast-enhanced MRI with T1-mapping and quantification of myocardial and liver ECV, biochemical assessments of collagen turnover (PRO-C3, PRO-C5, PRO-C6, collagen type IV degradation fragment, collagen type V degradation fragment, LG1M) and inflammation (TNF alpha, IL-1 beta, IL-6, IL-8, IL-18, SDF1 alpha, sCD163, sMR, soluble macrophage mannose receptor). Results Myocardial and liver ECV were increased in patients compared with healthy controls (myocardial ECV 31.2 +/- 5.5% vs 27.4 +/- 2.9%,P = 0.037; liver ECV 44.1 +/- 9.6% vs 33.7 +/- 6.7%,P

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Peptidylglycine α-amidating monooxygenase (PAM) is a processing enzyme involved in maturation of regulatory peptides. One product of PAM activity is adrenomedullin (bio-ADM), which regulates vascular tone and endothelial integrity. In this study, we examined PAM activity and bio-ADM concentrations in patients with various degrees of hepatic cirrhosis including the role of the liver in net release of the two markers. We enrolled 48 patients with cirrhosis and 16 control subjects: The patients were evenly distributed according to the Child-Turcotte classification. PAM activity was progressively increased in cirrhotic patients but without a net release across the liver, leg, or kidney. In contrast, bio-ADM concentrations were not only associated to severity of disease but also found to be directly released by the liver. Given the major expression of PAM in the heart, we propose that increased PAM activity in plasma from patients with cirrhosis may reflect cardiac involvement, e.g. cirrhotic cardiomyopathy.

Background Training in advanced endoscopic techniques such as endoscopic retrograde cholangiopancreatography (ERCP) should be driven by key performance measures and standardized competence assessment in order to provide safe and high-quality interventions. We aimed to determine whether the involvement of trainees influences the outcome of the procedure and the incidence of ERCP-related adverse events. Methods This was an international, multicenter, prospective, observational study conducted at six high- and low-volume centers across Europe between October 2016 and October 2018, and included independent operators and their trainees. Standard report forms documenting indication, trainee involvement, technical outcome, and complications over a 30-day follow-up of consecutive ERCP procedures were included in the analysis. Technical success of the procedure and procedure-related adverse events were compared between procedures in the trainee group and the control group using bivariable and multivariable analysis. Results 21 trainees and 16 control endoscopists performed 1843 ERCPs during the study period. Trainee involvement in ERCP procedures did not decrease technical success (92.4 % vs. 93.7 %; P = 0.30) or increase the risk of adverse events (14.7 % vs. 14.6 %; P > 0.99). Conversely, there were significantly more moderate or severe adverse events in the control group compared with the trainee group (6.2 % vs. 3.4 %, P = 0.01). On multivariable analysis, only increased bilirubin levels, time to cannulation, and procedure difficulty level increased the risk of any procedure-related adverse event. Conclusion Trainee involvement in ERCP interventions within a proper teaching setting is safe and does not compromise the success of the procedure.

Background . Endoscopic retrograde cholangiopancreatography has evolved significantly in recent years. The increase in complexity and range of applications has not been adequately reflected in an improvement of training methods for ERCP, with many endoscopists failing to meet required performance standards during their training period and limited available data on their performance immediately after completing training. We aimed to analyze the performance of an independent operator from a developing country after the completion of formal training with regard to procedure and patient-related outcomes. Methods . We conducted an observational study of ERCPs performed by a young endoscopist from a referral center. Data about the procedure, cannulation technique (including use of precut), trainee involvement and procedure-related outcomes was retrieved and analyzed from a prospectively maintained database on quality in ERCP (the QUASIE initiative). Results . Data from 679 consecutive ERCPs conducted or supervised by one endoscopist with < 200 independent procedures prior to the study period were included in the final analysis. Cannulation rates significantly improved over time, from 90% to 96% (p = 0.016). Use of precut techniques changed significantly over time, with an initial increase followed by a subsequent decrease as overall cannulation rates improved. Trainee involvement was significantly associated with prolonged cannulation times (p = 0.003) and use of precut (p = 0.001), but did not impact on technical success or patient safety. Conclusions . Independent practice of ERCP after the training period is characterized by ongoing changes in technique, especially with regard to cannulation and use of precut, showing significant improvements in performance over time.

BACKGROUND: Current recommendations on training in endoscopic retrograde cholangiopancreatography are predicated on a performance-centred approach designed to ensure that trainees achieve appropriate skills. We aimed to analyse how competence in endoscopic retrograde cholangiopancreatography is defined in the literature and what proportion of trainees actually reach this threshold. METHODS: We conducted a systematic MEDLINE search for studies reporting on endoscopic retrograde cholangiopancreatography training programmes in a clinical setting. The main outcome measure was threshold for achieving competence in endoscopic retrograde cholangiopancreatography; the secondary outcome measure was assessment of trainee performance. Quality was assessed using the Cochrane Risk of Bias tool and the Methodological Index for Non-Randomized Studies criteria. RESULTS: Of 522 initially identified articles, 20 were included in the analysis; most studies showed a high risk of bias. Cannulation rate of the desired duct was the main marker of competence in all studies; however, only 8/20 studies reported on the performance of individual trainees, who achieved their respective standard of competence in only 25.6% of reported cases. CONCLUSIONS: Current literature identifies cannulation rate of a native papilla to be the most appropriate measure of endoscopic retrograde cholangiopancreatography competence; however, most trainees do not reach predefined competence thresholds. Furthermore, due to the limitations of available studies, the most appropriate competence measure remains subject for debate.

Background and aims. Patients with COVID-19 frequently present abnormal elevated liver function tests of unknown clinical significance. We aimed to investigate the characteristics and factors influencing outcome in patients with confirmed SARS-CoV-2 infection and liver injury on admission. Methods. This is a retrospective observational study of patients hospitalized in two COVID units in Romania. Relevant data on clinical and laboratory parameters and medication administered during the admission were analyzed to identify predictors of a negative outcome. Patients with confirmed COVID-19 and liver function tests (LFTs) above the upper limit of normal were included in the analysis. Results. From 1,207 patients, we identified 134 patients (11%) with abnormal LFTs during hospitalization. The majority of patients had mildly elevated levels and a predominantly cholestatic pattern of liver injury. Patients who received lopinavir/ritonavir were more likely to have increased ALAT levels (p Conclusions. Mild liver injury is relatively common in COVID-19 and possibly influenced by medication. Patients with chronic liver disease are at high risk for negative outcome, but the severity of the infection is the only predictor of death.

Aims The unprecedented situation caused by the COVID-19 pandemic has profoundly affected endoscopic practice inregard to access, volume, and workflow. We aimed to assess the potential changes in the technical outcomes of ERCPprocedures carried out in patients with confirmed SARS-CoV-2 infection. Methods We conducted an international, multicenter, retrospective, matched case-control study of ERCP procedures carriedout in patients with confirmed COVID-19. The main outcome was technical success of the procedure as assessed by theendoscopist, and the secondary outcome was the development of procedure-related adverse events. Each case wasmatched in a 1:4 ratio with controls extracted from each center's database in order to identify relevant changes in outcomemeasures compared to the pre-pandemic era. Results Eighteen procedures performed in 16 COVID-19 patients (14 men, 65 years (9-82)) between the 15th of Marchand the 1st of July 2020 and 67 matched controls were included in the final analysis. Technical success was achieved in14/18 procedures in COVID-19 cases, which was significantly lower as compared to the control group (14/18 vs. 64/67, p=0.034), with an endoscopic reintervention required in 9/18 cases. However, the rate of procedure-related adverse eventswas low in both groups (1/18 vs. 10/67, p=0.44). On multivariable analysis COVID-19 status remained the only risk factorfor technical failure of the procedure (OR of 19.9 (95 %CI 1.4-269)).

Aims An outbreak of coronavirus disease 19 (COVID-19) has altered the dynamic of endoscopic practices. Many guidelines, questionnaires have been published addressing service resumption during the pandemic. Curious about the situation indifferent endoscopic units across the globe, the study was designed to evaluate different aspects of practice resumptionworldwide and their adherence to guidelines. Methods An online questionnaire was created and distributed by national/regional representatives and societies. Redcapplatform was used as the interface;afterwards, Microsoft Excel 2016 and Prism 5 were utilized for data analysis. Results From a total of 307 responses from 47 countries/regions was collected, 290 valid answers were analyzed. Almosthalf (47 %) were in post-peak period by August, 2020. Many units were not designated to be COVID-oriented facility. About15.5 % of centers remained unrecovered, mainly in North and South America;those were recovered, training was still withheld significantly. Nevertheless, opened centers kept safety measurements strictly. Patient load was decreased by 37 %,but waiting list was increased 0-25 %. Among many surveillance methods, body temperature, PCR and chest CT were themost common. 74.8 % increased post-procedural disinfection time and 68.2 % increase in per-case inspection were noted.PPE usage was implemented highly and shortage of these posed as one of the resumption barriers. Post-procedural patientsurveillance was not reinforced. Conclusions The study represented real-time global endoscopic service's adaptation to COVID-19 pandemic. Previouslypublished barriers upon practice resumption remained. Despite Delphi consensus' emphasis on post-procedural surveillance, application was not widely reinforced, raising concerns in disease control.

Background. Adequate sedation is a prerequisite for quality endoscopic examination of the digestive tract. We aimed to evaluate the current practices and safety profile of sedation for gastrointestinal endoscopy in Romania and its impact on the technical success of the procedure and procedure-related adverse events. Methods. We conducted a prospective, multicentric, observational study including all patients undergoing digestive endoscopic procedures under various degrees of sedation. We collected data regarding the endoscopic procedure, type and degree of sedation, drug regimens, personnel in charge of sedation, and relevant patient related information. The main study outcome was the rate of sedation-related adverse events; secondary study outcomes included procedure-related adverse events and the impact of sedation on procedure success. Results. 1,043 consecutive endoscopic procedures from eight Romanian endoscopy units were included in our study. Sedation regimens were highly variable between participating centers, with 566 (54%) of procedures being performed under sedation provided by an anaesthesiologist. Sedation-related adverse events occurred in 40 cases (3.8%), most of them were mild respiratory and cardiovascular events and all reversed spontaneously. On multivariate analysis, male gender, procedure type (endoscopic ultrasound and endoscopic retrograde cholangiopancreatography) and deep sedation were risk factors for complications. The endoscopy unit, ASA status, age and type of sedative did not influence the complication rate. Conclusion. In conclusion, sedation for endoscopic procedures is generally safe, despite a high variability in sedation practices between centers in Romania. Establishing a national guideline on sedation for gastrointestinal endoscopy will ensure consistent and safe practice for these procedures.

Background:The unprecedented situation caused by the coronavirus disease 2019 (COVID-19) pandemic has profoundly affected endoscopic practice in regard to access, volume, and workflow. We aimed to assess the potential changes in the technical outcomes of endoscopic retrograde cholangiopancreatography (ERCP) procedures carried out in patients with confirmed SARS-CoV-2 infection.Methods:We conducted an international, multicenter, retrospective, matched case-control study of ERCP procedures carried out in patients with confirmed COVID-19. The main outcome was technical success of the procedure as assessed by the endoscopist, and the secondary outcome was the development of procedure-related adverse events. Each case was matched in a 1:4 ratio with controls extracted from each center’s database in order to identify relevant changes in outcome measures compared with the pre-pandemic era.Results:Eighteen procedures performed in 16 COVID-19 patients [14 men, 65 years (9–82)] and 67 controls were included in the final analysis. Technical success was achieved in 14/18 COVID-19 cases, which was significantly lower as compared with the control group (14/18 versus 64/67, p = 0.034), with an endoscopic reintervention required in 9/18 cases. However, the rate of procedure-related adverse events was low in both groups (1/18 versus 10/67, p = 0.44). On multivariable analysis, COVID-19 status remained the only risk factor for technical failure of the procedure [odds ratio of 19.9 (95% confidence interval 1.4–269.0)].Conclusions:The COVID-19 pandemic has affected the volume and practice of ERCP, resulting in lower technical success rates without significantly impacting patient safety. Prioritizing cases and following recommendations on safety measures can ensure good outcome with minimal risk in dedicated centers.

Introduction There was no evidence concerning the prophylaxis with hydroxychloroquine, and only low‐grade evidence regarding the use of hydroxychloroquine as a treatment for COVID‐19 patients. We performed a survey among Romanian physicians in order to see how many of them would administer prophylactically hydroxychloroquine to themselves or to people close to them, and if they would participate to a randomized controlled trial. Methods Between March 30 and April 02, 2020, a 16‐item questionnaire was shared in a Romanian Facebook group of 2645 physicians dedicated to COVID‐19 information, asking to be completed by physicians who could be directly involved in the care of these patients. Results A total of 785 answers were collected. Nine physicians (1.1%) thought that there was clear evidence on prescribing hydroxychloroquine prophylaxis, 375 (48%) considered the evidence acceptable, 348 (44.3%) considered it weak, whereas 53 (6.8%) answered there was no evidence. 59 (7.5%) respondents were determined to take it (of which 31 = 4% already took), 192 (24.5%) were inclined to take, 271 (34.5%) were not decided yet. 175 (22.3%) of respondents declared they (would) give the treatment to their close ones, and this decision was associated with a higher age (P = 0.003), and the opinion that there was evidence (P

Summary Background Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. Findings Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial. Funding UK National Institute for Health Research Health Technology Assessment Programme.

Chronic pancreatitis entails a heavy burden on the healthcare system because of its often protracted evolution, requiring complex diagnostic and therapeutic procedures.This review focuses on novel imaging and endoscopic diagnostic and therapeutic interventions that have changed the management of patients with chronic pancreatitis. We have conducted an extensive search of original papers and guidelines, in order to provide a comprehensive and up to date review of available evidence in these areas of interest.The traditional challenges in managing chronic pancreatitis patients stemmed from the limitations of diagnostic modalities, which could not correctly identify patients in an early stage of the disease, as well as from the scarcity of therapeutic options available. Advances in imaging of CT-scan, MRI, and EUS have opened the way for early diagnosis and staging. This has allowed more aggressive and tailored therapeutic modalities, particularly in endoscopic therapy and minimally invasive surgical interventions. Although high-quality data from large RCTs is still scarce, evidence-based algorithms for diagnosis and therapy are now changing the way we address this chronic disease. In the near future, we can expect a tailored approach based on patient and disease-related predictive factors, relying on a vast armamentarium of endoscopic and surgical solutions.

ERCP training remains a sensitive issue, with current data showing that traditional training methods, based on a hands-on, master-disciple paradigm, fall short of producing competent trainees. We aimed to evaluate whether a novel approach to training might improve the learning curve for novice endoscopists training in ERCP. We conducted a multicenter randomized control trial, using a validated mechanical simulator(the Boskoski-Costamagna trainer). Trainees with no experience in ERCP were either asigned to a group undergoing standard cannulation training or a group undergoing “motion-training”, which implied performing familiar motor functions such as writing and drawing, using instruments previously unfamiliar to the trainee(e.g. duodenoscope and dedicated ERCP catheters), before undergoing standard cannulation training. All trainees were timed and graded on their performance in selective cannulation of 4 different papilla configurations, with the aid of a validated score (TEESAT). 30 trainees(13 E-motion group, 17 standard group) each performed 20 timed- cannulation attempts, for a total of 600 procedures. Successful cannulation of the bile duct was achieved in 582/600 attempts(97%), with no significant difference between the two study groups(96.2 vs. 97.6%, p=0.33). Trainees in the E-motion group had significantly lower median cannulation times compared to trainees in the standard group (35 vs 44 seconds, p=0.036). On subgroup analysis, this difference was only statistically significant in terms of the first 20 attempts(papilla type 1), with further timed cannulation attempts not differing significantly between the study groups. The overall performance assessment by the supervisor using the TEESAT score showed similar results between the two study groups (p=0.559) We concluded that “motion training” had a positive impact on cannulation time during the first stages of the training, thus having the potential to improve training in ERCP. Future studies need to establish its usefulness in supplementing current training programmes.

Introduction: An outbreak of coronavirus disease 19 (COVID-19) has altered the dynamic of world’s healthcare system, including endoscopic practices. Curious about the situation in different endoscopic units across the globe, the study was designed to evaluate different aspects of practice resumption worldwide. Methods: An online questionnaire was created and distributed by national/regional representatives. Redcap® platform was used as the interface; afterwards, Microsoft Excel 2016 and Prism 5 were utilized for data analysis. Results: A total of 307 responses from 47 countries/regions was collected, from which 290 valid answers were inducted and further analyzed. Almost half (47%) were in post-peak period by August, 2020. Many units were not designated to be COVID-oriented facility. About 15.5% of centers remained unrecovered, mainly in North and South America; those were recovered, training was still withheld significantly. Nevertheless, opened centers kept safety measurement strictly. Though patient load was decreased by 37% in most centers, waiting list was increased 0-25%. Among many surveillance methods, body temperature, PCR and chest CT prevailed the be the most commonly used. 74.8% claimed to have increased post-procedural disinfection time and 68.2% also observed an increased in per-case inspection. PPE usage was implemented highly and shortage of these posed as one of the resumption barriers. Post-procedural patient surveillance was not reinforced. Conclusions: The study reflected closely the global revolution of the pandemic. Shortage in staff and PPE as well as difficulty in training resumption remained barriers worldwide. Incapacity of patient post-procedural surveillance raised concerns in disease control. Funding Statement: None to declare. Declaration of Interests: None to declare. Ethics Approval Statement: The study was approved by the Institutional Review Board of the National Liver Institute, Menoufia University, Egypt (NLI IRB 00003413) in June 2020, protocol number 00203/2020.

The impact of trainee involvement on the outcome of complex endoscopic procedures such as ERCP remains unclear. We aimed to evaluate the degree of trainee involvement in the real-life practice of ERCP procedures in a teaching setting.

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Background. We aimed to determine the relationship between endocan and cirrhotic cardiomyopathy. Materials and methods. Patients with liver cirrhosis and no heart disease were included in a prospective observational study with liver disease decompensation and death as primary outcomes. Results. 83 cirrhotic patients were included and 32 had cirrhotic cardiomyopathy. Endocan levels were significantly lower in patients with cirrhotic cardiomyopathy (5.6 vs. 7 ng/mL, p = 0.034). Endocan correlated with severity of cirrhosis, time to decompensation or death from liver disease (OR 4.5 95% CI 1.06-31.1). Conclusion. Endocan is a promising biomarker of severity of cirrhosis and may help in the diagnosis of cardiac dysfunction in this population.

Bile acids (BAs) are potent signaling molecules involved in the regulation of several metabolic and functional aspects of cardiovascular homeostasis. BA pool alteration in cirrhosis may contribute toward the development of hemodynamic and cardiac disturbances. We aimed to investigate the association between total BA levels and echocardiographic and biochemical markers of cardiac dysfunction in cirrhotic patients.Cirrhotic patients were enrolled prospectively in this hypothesis-generating study and evaluated for cardiac and hemodynamic dysfunction through clinical, echocardiographic, and biochemical means. Associations between total serum BA concentrations and markers of systolic or diastolic dysfunction and the presence of cirrhotic cardiomyopathy were tested through univariate and multivariate analyses.Fifty-eight patients with cirrhosis were assessed in this monocentric study. 49 (85%) patients had decompensated cirrhosis according to the Child class. The median total BA level was 45 µmol/l. There was no correlation between BA levels and the etiology of cirrhosis (P=0.2), current alcohol use (P=0.8), sex (P=0.1), smoking status (P=0.2), age, or BMI. Systolic and diastolic dysfunction were rare in the cohort. Total BA levels associated with several echocardiographic parameters of the hyperdynamic syndrome in univariate analysis but only with left atrial volume in multivariate analysis (P=0.007). BA concentrations did not differ according to the presence of echocardiographically diagnosed cirrhotic cardiomyopathy in the two models tested.Total serum BA levels are associated with enlarged left atrial volume and markers of the hyperdynamic circulation in patients with cirrhosis irrespective of the etiology or the severity of liver disease.

Background and aims. Selective cannulation of the desired duct is a key element in ERCP procedures and an important step in the training of fellows. However, there is limited data about technical success and patient safety for ERCPs conducted in a training setting.We aimed to evaluate the impact of trainee involvement on the cannulation technique and procedure related outcomes at ERCP. Materials and methods. We conducted an observational study of all ERCP conducted in an endoscopy unit with an on-going training program. Patient related data and procedure-related data (method of cannulation, time to cannulation, degree of trainee involvement, technical success and procedure-related adverse events) were collected using a standard form. The method of cannulation, time to cannulation and procedure-related adverse events were compared between ERCPs with trainee involvement and those without. Results. 641 consecutive ERCPs were evaluated and 474 native papilla cases performed by 4 trainers and 3 trainees were included in the final analysis. Trainees were involved in 171 procedures (36.1%), achieving cannulation of the desired duct in 50.8% of the cases. Cannulation rates were similar in the trainee group compared to the control group (91.7% vs. 88.7%) and there was no increase in the rate of adverse events. However, cannulation time was significantly longer in the trainee group with a significant increase in the rate of precut use (32.1% vs. 23.4%, p < 0.001). Conclusions. Trainee involvement resulted in longer cannulation times and increased use of precut sphincterotomy, but, was not associated with an increased risk of procedure related adverse events.

We have read with interest the latest paper by Boskoski et al 1 on the virological status of reprocessed endoscopes used for critically ill patients during the COVID-19 pandemic. Proper reprocessing of endoscopes and accessories is essential to patient safety. Although existing data suggest that the risk of viral transmission via endoscopic equipment is extremely low (with virtually no reported cases of hepatitis B and C or HIV transmission following current disinfection guidelines2), the present COVID-19 pandemic has put a spotlight on quality control as a guarantor of patient and healthcare worker safety. Boskoski et al report no evidence of viral contamination of endoscopes in critically ill patients …

Cirrhotic cardiomyopathy and the hyperdynamic syndrome are clinically important complications of cirrhosis, but their exact pathogenesis is still partly unknown. Experimental models have proven the cardiotoxic effects of bile acids and recent studies of their varied receptor-mediated functions offer new insight into their involvement in cardiovascular dysfunction in cirrhosis. Bile acid receptors such as farnesoid X-activated receptor and TGR5 are currently under investigation as potential therapeutic targets in a variety of pathological conditions. These receptors have also recently been identified in cardiomyocytes, vascular endothelial cells and smooth muscle cells where they seem to play an important role in cellular metabolism. Chronic cholestasis leading to abnormal levels of circulating bile acids alters the normal signalling pathways and contributes to the development of profound cardiovascular disturbances. This review summarizes the evidence regarding the role of bile acids and their receptors in the generation of cardiovascular dysfunction in cirrhosis.

Background & Aims. Considering the ability of anti-TNF alpha drugs to lower the burden intestinal inflammation in patients with inflammatory bowel disease (IBD), and the similarity between IBD and ankylosing spondylitis (AS) regarding inflammatory intestinal involvement, we aimed to investigate the impact of anti-TNF alpha biologic therapy on subclinical intestinal inflammation in AS patients. Methods. Between January 2008 and December 2013, 38 AS patients and 23 controls were enrolled in the study and investigated with small bowel videocapsule endoscopy examination and ileocolonoscopy. Each tertile of the small bowel (proximal, mid and distal) was assessed by calculating the Lewis score based on the image stream. Results. The Lewis scores were significantly higher in the AS group compared to controls (580.9 ± 818 vs. 81 ± 121, pvs. 790 ± 1038, p = 0.015), its proximal and distal tertiles (238 ± 154 vs. 560 ± 543, p = 0.021, and 140 ± 189 vs. 300 ± 220, p = 0.027, respectively). The Lewis score was also lower in patients receiving Adalimumab/Infliximab compared to those on Etanercept for the entire bowel and its distal tertile (262 ± 165 vs. 380 ± 148, p = 0.069 and 62 ± 101 vs. 273 ± 236, p = 0.060, respectively). Conclusion. Anti-TNF alpha therapy in patients with AS reduces the subclinical intestinal inflammation, but the magnitude seems to depend upon the class anti-TNF alpha agent used (Clinical Trials. gov NCT00768950).

Coeliac disease incidence raised during the last 50 years and represents a concern by diagnostic problems and costs. The recent data regarding etiology, pathogeny, comparative diagnostic value of serology and small intestinal biopsy are summarised. New data about refractory celiac disease to gluten free diet and therapeutic perspectives are also presented (glutenases, larazotide acetate, genetic alteration of cereals, tissulary transglutaminase inhibitors etc).

Background & Aims: Prognostic factors for poor evolution are critical in the setting of limited access to liver transplantation for patients with cirrhosis. We aimed to investigate the impact of hypoxaemia on the outcome in cirrhosis and the evolution of arterial oxygen tension during long-term follow-up in these patients. Methods: Consecutive cirrhotic patients were prospectively enroled and followed-up in our tertiary referral center. Clinical features, biological tests, arterial blood gases, NT-proBNP levels, pulse oximetry measurements, 12-lead ECG, and transthoracic contrast echocardiography were documented on enrolment. The main outcomes were death and decompensation due to liver disease. Results: 87 cirrhotic patients were included in the analysis and followed-up for a mean of 16 months. At enrolment, 27 (31%) patients were hypoxaemic, 19 had hepatopulmonary syndrome (HPS), but only 6 of those who were sampled at follow-up had persistent hypoxaemia. During the study period, 22 patients died of liver-related complications. Nine of them (41%) were hypoxaemic on enrolment but none had severe hypoxaemia. Hypoxaemia present at enrollment was not a risk factor for death (p=0.29) or decompensation of liver disease (p=0.7). A higher MELD score at baseline or increase during follow-up was a risk factor for death (p=0.02) and correlated with the presence of hypoxaemia. Normalization of the arterial oxygen levels was accompanied by a significant decrease in NT-proBNP (83 pg/ml vs 0 pg/mL, p=0.023). Conclusion: Mild and moderate hypoxaemia was frequent in our patients but was not associated with adverse outcome in cirrhosis. Repeated arterial blood gas sampling is advisable, especially in patients diagnosed with hepatopulmonary syndrome. Abbreviations: AaO2: alveolar-arterial oxygen gradient; IPVDs: intrapulmonary vascular dilations; HBV: hepatitis B virus; HCV: hepatitis C virus; HPS: hepatopulmonary syndrome; MELD: model for end-stage liver disease; NT-proBNP: aminoterminal pro-brain natriuretic peptide; PaCO2: arterial carbon dioxide tension; PaO2: arterial oxygen tension.

A 67-year-old Caucasian man presented to our department with a 10-day history of painless jaundice and generalised pruritus. He reported no alcohol or drug intake, no history of travelling abroad and no significant personal or family medical history. Physical examination was normal except for excoriations. Laboratory studies revealed cholestasis with markedly increased conjugated bilirubin (466.9 µmol/L) and an alkaline phosphatase (AP) level of 445 IU/mL. Transaminase, gamma-glutamyl transferase (GGT), serum albumin and prothrombin levels were within normal range. The extended viral hepatitis panel was negative as were the antimitochondrial and antinuclear antibodies. Abdominal ultrasound showed gallbladder stones and a 7 mm diameter common bile duct with no visible obstruction or intrahepatic biliary dilatations. The abdominal …

Background and aims: Pancreas divisum (PD) is the most common congenital variant of the pancreatic ductal system and a potential cause of acute recurrent pancreatitis (ARP). Endoscopic therapy is a...

IMPACT OF TRAINEE INVOLVEMENT ON TECHNICAL OUTCOME OF ERCP PROCEDURES AND PATIENT SAFETY: RESULTS OF A PROSPECTIVE MULTICENTER TRIAL

Ulcerative colitis (UC) is a chronic, relapsing inflammatory bowel disease that slightly increases the risk of colorectal cancer in patients with long-standing extended disease. Overexpression of p53 and p21 in colonic epithelia is usually detected in UC patients when no dysplasia is histologically seen and it is used by pathologists as a discriminator between regenerative changes and intraepithelial neoplasia, as well as a tissue biomarker useful to predict the risk of evolution toward malignancy. We present a one-year prospective observational study including a cohort of 45 patients with UC; p53 and p21 were evaluated in epithelial cells. p53 was positive in 74 samples revealed in 5% to 90% of epithelial cells, while 63 biopsies had strong positivity for p21 in 5% to 50% of epithelial cells. Architectural distortion was significantly correlated with p53 overexpression in epithelial cells. Thus, we consider that architectural distortion is a good substitute for p53 and p21 expression. We recommend use of p53 as the most valuable tissue biomarker in surveillance of UC patients, identifying the patients with higher risk for dysplasia. Association of p21 is also recommended for a better quantification of risk and for diminishing the false-negative results.