From Gut to Brain: Uncovering Potential Serum Biomarkers Connecting Inflammatory Bowel Diseases to Neurodegenerative Diseases.

Inflammatory bowel diseases (IBDs) are characterized by chronic gastrointestinal inflammation due to abnormal immune responses to gut microflora. The gut-brain axis is disrupted in IBDs, leading to neurobiological imbalances and affective symptoms. Systemic inflammation in IBDs affects the brain's inflammatory response system, hormonal axis, and blood-brain barrier integrity, influencing the gut microbiota. This review aims to explore the association between dysregulations in the gut-brain axis, serum biomarkers, and the development of cognitive disorders. Studies suggest a potential association between IBDs and the development of neurodegeneration. The mechanisms include systemic inflammation, nutritional deficiency, GBA dysfunction, and the effect of genetics and comorbidities. The objective is to identify potential correlations and propose future research directions to understand the impact of altered microbiomes and intestinal barrier functions on neurodegeneration. Serum levels of vitamins, inflammatory and neuronal damage biomarkers, and neuronal growth factors have been investigated for their potential to predict the development of neurodegenerative diseases, but current results are inconclusive and require more studies.

Comprehensive analysis of adverse events associated with transmural use of LAMS in patients with liver cirrhosis: International multicenter study.

Background and study aims Endoscopic ultrasound (EUS)-guided transmural (TM) deployment of lumen-apposing metal stents (LAMS) is considered relatively safe in non-cirrhotic patients and is cautiously offered to cirrhotic patients. Patients and methods This was a retrospective, multicenter, international matched case-control study to study the safety of EUS-guided TM deployment of LAMS in cirrhotic patients. Results Forty-three cirrhotic patients with model for end-stage liver disease score 12.5 ± 5, with 23 having ascites and 16 with varices underwent EUS-guided TM LAMS deployment, including 19 for pancreatic fluid collection (PFC) drainage, 13 gallbladder drainage, six for endoscopic ultrasound-directed transgastric endoscopic retrograde cholangiopancreatography (ERCP), three for EDGI, one for endoscopic ultrasound-directed transenteric ERCP, and one postsurgical collection drainage. Technical failure occurred in one LAMS for PFC drainage. Clinical failure was encountered in another PFC. Nine adverse events (AEs) occurred. The most common AE was LAMS migration (3), followed by non-bleeding mucosal erosion (2), delayed bleeding (2), sepsis (1), and anesthesia-related complication (pulseless electrical activity) (1). Most AEs were graded as mild (6), followed by severe (2), and moderate (1); the majority were managed conservatively. On univariable comparison, risk of AE was higher when using a 20 × 10 mm LAMS and the absence of through-the-LAMS plastic stent(s). Conditional logistic regression of matched case-control patients did not show any association between potential predicting factors and occurrence of AEs. Conclusions Our study demonstrated that mainly in patients with Child-Pugh scores A and B cirrhosis and despite the presence of mild-to-moderate ascites in over half of cases, the majority of AEs were mild and could be managed conservatively. Further studies are warranted to verify the safety of LAMS in cirrhotic patients.

Endoscopic ultrasound-guided tissue acquisition for the diagnosis of focal liver lesion.

In patients with liver tumors, the histopathology examination can assist in diagnosis, staging, prognosis, and therapeutic management strategy. Endoscopic ultrasound (EUS)-guided tissue acquisition using fine needle aspiration (FNA) or more newly fine needle biopsy (FNB) is a well-developed technique in order to evaluate and differentiate the liver masses. The goal of the EUS-FNA or EUS-FNB is to provide an accurate sample for a histopathology examination. Therefore, malignant tumors such as hepatocarcinoma, cholangiocarcinoma and liver metastasis or benign tumors such as liver adenoma, focal hyperplastic nodular tumors and cystic lesions can be accurately diagnosed using EUS-guided tissue acquisition. EUS-FNB using 19 or 22 Ga needle provide longer samples and a higher diagnostic accuracy in patients with liver masses when compared with EUS-FNA. Few data are available on the diagnostic accuracy of EUS-FNB when compared with percutaneously, ultrasound, computer tomography or transjugulary-guided liver biopsies. This review will discuss the EUS-guided tissue acquisition options in patients with liver tumors and its efficacy and safety in providing accurate samples. The results of the last studies comparing EUS-guided liver biopsy with other conventional techniques are presented. The EUS-guided tissue acquisition using FNB can be a suitable technique in suspected liver lesions in order to provide an accurate histopathology diagnosis, especially for those who require endoscopy.

Discharge protocol in acute pancreatitis: an international survey and cohort analysis.

There are several overlapping clinical practice guidelines in acute pancreatitis (AP), however, none of them contains suggestions on patient discharge. The Hungarian Pancreatic Study Group (HPSG) has recently developed a laboratory data and symptom-based discharge protocol which needs to be validated. (1) A survey was conducted involving all members of the International Association of Pancreatology (IAP) to understand the characteristics of international discharge protocols. (2) We investigated the safety and effectiveness of the HPSG-discharge protocol. According to our international survey, 87.5% (49/56) of the centres had no discharge protocol. Patients discharged based on protocols have a significantly shorter median length of hospitalization (LOH) (7 (5;10) days vs. 8 (5;12) days) p < 0.001), and a lower rate of readmission due to recurrent AP episodes (p = 0.005). There was no difference in median discharge CRP level among the international cohorts (p = 0.586). HPSG-protocol resulted in the shortest LOH (6 (5;9) days) and highest median CRP (35.40 (13.78; 68.40) mg/l). Safety was confirmed by the low rate of readmittance (n = 35; 5%). Discharge protocol is necessary in AP. The discharge protocol used in this study is the first clinically proven protocol. Developing and testifying further protocols are needed to better standardize patients' care.

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.

Cognitive Dysfunction and Affective Mood Disorder Screening in Patients With Chronic Inflammatory Bowel Disease: Protocol for a Prospective Case-Control Study.

BACKGROUND: Mild cognitive impairment (MCI) and Alzheimer's disease (AD) might be more frequent in patients with inflammatory bowel disease (IBD), but the relationship between these 2 entities is yet to be entirely established. Certain blood biomarkers (eg, serum amyloid A [SAA] and serum homocysteine [Hcy], which increase in IBD and MCI; brain-derived neurotrophic factor [BDNF], which decreases in MCI and AD but is not clearly modified in IBD; and S100 calcium-binding protein B [S100B], which increases in the blood-brain barrier and neuronal lesions) might predict the stage of MCI or dementia or progression to a further state. The gut-brain axis (GBA) might be the key to the development of MCI in patients with IBD, along with systemic inflammation and the possible and unknown adverse effects of disease-modifying medication. OBJECTIVE: The aim of this study is to investigate whether GBA interactions play a role in MCI development in patients with IBD. METHODS: A case-control study will be conducted on at least 100 patients diagnosed with IBD, matched with 100 healthy individual controls. The matching will include sex, age, and education. Patients will be fully examined, and a full interview and a neurological and cognitive examination will be performed. The primary clinical outcomes will be cognitive test scores (Montreal Cognitive Assessment, Trail Making Test, Digit Symbol Substitution Test, forward and backward digit span testing). Depression, stress, and anxiety screening will also be performed. Blood samples from all participants will be collected, and aliquots will be immediately stored in a biobank. Primary laboratory outcomes will include serum levels of presumed cognitive dysfunction blood biomarkers SAA, Hcy, S100B, and BDNF. Follow-up will be performed at 12, 24, 36, and 48 months. RESULTS: Data collection started in December 2021 and is ongoing. So far, 53 patients with IBD have been recruited and 50 HC matched. Data collection should end in January 2030. Intermediary analysis will be performed in April 2024. We expect patients with IBD to have lower scores on cognitive testing and a positive correlation between disease length and cognitive impairment level. In addition, the levels of stress, anxiety, and depression should be higher in the IBD group. The serum levels of the 4 biomarkers could correlate or anticorrelate with cognitive scores and serve as predictive factors for MCI or dementia development. A higher level of education, a younger age, the absence of malabsorption, and good disease control might serve as protectors against MCI. CONCLUSIONS: GBA interactions, along with systemic inflammation and the adverse effects of medication, might be a cause of MCI and AD development in patients with IBD. Serum biomarkers could prove cheap and useful predictors of MCI development. TRIAL REGISTRATION: ClinicalTrials.gov NCT05760729; https://clinicaltrials.gov/study/NCT05760729. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/50546.

EUS-guided fine needle biopsy for hepatocarcinoma of the right liver lobe as a rescue diagnostic technique after a negative percutaneousguided liver biopsy.

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Zenker's peroral endoscopic myotomy for management of large Zenker's diverticulum.

BACKGROUND: Zenker's diverticulum peroral endoscopic myotomy (zPOEM) is a minimally invasive treatment strategy for Zenker's diverticulum, with excellent results for management of small-to-moderate Zenker's diverticulum. We evaluated its use in the management of large Zenker's diverticulum. METHODS: This was a retrospective multicenter cohort study across 11 international centers including adult patients with large Zenker's diverticulum ≥ 40 mm treated by zPOEM between March 2017 and March 2022. The primary outcome was clinical success (dysphagia score ≤ 1 without need for further intervention). Secondary outcomes included technical success (complete myotomy as intended), adverse events (AEs), and rate of recurrence. RESULTS: 83 patients (male 62.7 %, mean age 72.6 [SD 11.5] years) underwent zPOEM for treatment of large Zenker's diverticulum (median size 50 mm, interquartile range [IQR] 41-55 mm, range 40-80 mm). The zPOEM procedure was technically successful in 82 patients (98.8 %), with a mean procedure time of 48.7 (SD 23.2) minutes. Clinical success was achieved in 71 patients (85.5 %). Median (IQR) symptom scores improved significantly from baseline for dysphagia (2 2 3 vs. 0 [0-2]; P < 0.001), regurgitation (3 2 3 4 vs. 0 [0-0]; P < 0.001), and respiratory symptoms (2 [0-3] vs. 0 [0-0]; P < 0.001). Among patients achieving clinical success, only one recurrence (1.4 %) was recorded during a median follow-up of 12.2 months (IQR 3-28). Post-procedure AEs, all mild to moderate, occurred in four patients (4.8 %). CONCLUSION: This study demonstrated safe and effective use of zPOEM in the management of large Zenker's diverticulum.

The impact of the COVID-19 pandemic on the mental health of patients diagnosed with inflammatory bowel diseases.

Understanding the profound impact of a viral pandemic on the mental health of patients with autoimmune diseases undergoing biological treatment is crucial for future insights. This cross-sectional case-control study aimed to assess the mental health implications of the COVID-19 pandemic on individuals with inflammatory bowel disease (IBD) in Romania, spanning from November 2022 to March 2023. A specialized self-report questionnaire in the Romanian language was developed to measure the multifaceted effects of COVID-19 on the mental well-being of these patients. The findings revealed a significant decline in the mental health of patients with IBD during the pandemic compared to the control group. Patients with IBD exhibited elevated levels of anxiety and concern regarding the virus. Intriguingly, despite the challenges, the vaccination rate was notably higher among patients with IBD, indicating a proactive approach to safeguarding their health. The study also shed light on various coping mechanisms employed by patients with IBD to navigate the pandemic-related restrictions. Engaging in activities such as social media and computer games emerged as effective strategies for managing heightened stress and limitations. In conclusion, the emergence of a novel viral pathogen represents a significant distress factor for patients with autoimmune diseases. Recognizing and comprehending these consequences enhances our understanding of the intricate interplay between physical and mental health and equips authorities with valuable insights to better manage future epidemics or viral outbreaks. This study underscores the importance of tailored support systems and strategies for patients with autoimmune diseases during global health crises.

EASY-APP: An artificial intelligence model and application for early and easy prediction of severity in acute pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is a potentially severe or even fatal inflammation of the pancreas. Early identification of patients at high risk for developing a severe course of the disease is crucial for preventing organ failure and death. Most of the former predictive scores require many parameters or at least 24 h to predict the severity; therefore, the early therapeutic window is often missed. METHODS: The early achievable severity index (EASY) is a multicentre, multinational, prospective and observational study (ISRCTN10525246). The predictions were made using machine learning models. We used the scikit-learn, xgboost and catboost Python packages for modelling. We evaluated our models using fourfold cross-validation, and the receiver operating characteristic (ROC) curve, the area under the ROC curve (AUC), and accuracy metrics were calculated on the union of the test sets of the cross-validation. The most critical factors and their contribution to the prediction were identified using a modern tool of explainable artificial intelligence called SHapley Additive exPlanations (SHAP). RESULTS: The prediction model was based on an international cohort of 1184 patients and a validation cohort of 3543 patients. The best performing model was an XGBoost classifier with an average AUC score of 0.81 ± 0.033 and an accuracy of 89.1%, and the model improved with experience. The six most influential features were the respiratory rate, body temperature, abdominal muscular reflex, gender, age and glucose level. Using the XGBoost machine learning algorithm for prediction, the SHAP values for the explanation and the bootstrapping method to estimate confidence, we developed a free and easy-to-use web application in the Streamlit Python-based framework (http://easy-app.org/). CONCLUSIONS: The EASY prediction score is a practical tool for identifying patients at high risk for severe AP within hours of hospital admission. The web application is available for clinicians and contributes to the improvement of the model.

Expression of Selected Genes and Circulating microRNAs in Patients with Celiac Disease.

Background and Objectives: Celiac disease (CD) is an immune-mediated enteropathy with characteristic intestinal alterations. CD occurs as a chronic inflammation secondary to gluten sensitivity in genetically susceptible individuals. Until now, the exact cause of the disease has not been established, which is why new studies have appeared that address the involvement of various genes and microRNAs (miRNAs) in the pathogenesis. The aim of the study is to describe the expression of selected genes (Wnt family member 3, WNT3; Wnt family member 11, WNT11; tumor necrosis factor alpha, TNFα; mitogen-activated protein kinase 1, MAPK1; AKT serine/threonine kinase 3, AKT3; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha, PIK3CA; and cyclin D1, CCND1) and miRNAs (miR-192-5p, miR-194-5p, miR-449a and miR-638) in adult patients with CD. Materials and Methods: In total, 15 patients with CD at diagnosis (newly diagnosed), 33 patients on a gluten-free diet (GFD) for at least 1 year and 10 controls (control) were prospectively included. Blood samples were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). Results: The results show that TNFα, MAPK1 and CCND1 were significantly overexpressed (p = 0.0249, p = 0.0019 and p = 0.0275, respectively) when comparing the newly diagnosed group to the controls. The other genes studied in CD patients were mostly with high values compared to controls, without reaching statistical significance. Among the miRNAs, the closest to a statistically significant value was miR-194-5p when the newly diagnosed group versus control (p = 0.0510) and GFD group versus control (p = 0.0671) were compared. The DIANA and miRNet databases identified significant functional activity for miR-449a and miR-192-5p and an interconnection of miR-194-5p and miR-449a with CCND1. Conclusions: In conclusion, genes and circulating miRNAs require further studies as they could represent important biomarkers in clinical practice.

Zenker's peroral endoscopic myotomy, or flexible or rigid septotomy for Zenker's diverticulum: a multicenter retrospective comparison.

BACKGROUND: Treatment of Zenker's diverticulum has evolved from open surgery to endoscopic techniques, including flexible and rigid endoscopic septotomy, and more recently, peroral endoscopic myotomy (Z-POEM). This study compared the effectiveness of flexible and rigid endoscopic septotomy with that of Z-POEM. METHODS: Consecutive patients who underwent endoscopic septotomy (flexible/rigid) or Z-POEM for Zenker's diverticulum between 1/2016 and 9/2019 were included. Primary outcomes were clinical success (decrease in Dakkak and Bennett dysphagia score to ≤ 1), clinical failure, and clinical recurrence. Secondary outcomes included technical success and rate/severity of adverse events. RESULTS: 245 patients (110 females, mean age 72.63 years, standard deviation [SD] 12.37 years) from 12 centers were included. Z-POEM was the most common management modality (n = 119), followed by flexible (n = 86) and rigid (n = 40) endoscopic septotomy. Clinical success was 92.7 % for Z-POEM, 89.2 % for rigid septotomy, and 86.7 % for flexible septotomy (P = 0.26). Symptoms recurred in 24 patients (15 Z-POEM during a mean follow-up of 282.04 [SD 300.48] days, 6 flexible, 3 rigid [P = 0.47]). Adverse events occurred in 30.0 % rigid septotomy patients, 16.8 % Z-POEM patients, and 2.3 % flexible septotomy patients (P < 0.05). CONCLUSIONS: There was no difference in outcomes between the three treatment approaches for symptomatic Zenker's diverticulum. Rigid endoscopic septotomy was associated with the highest rate of complications, while flexible endoscopic septotomy appeared to be the safest. Recurrence following Z-POEM was similar to flexible and rigid endoscopic septotomy. Prospective studies with long-term follow-up are required.

Extrahepatic cholangiocarcinoma: Current status of endoscopic approach and additional therapies.

The prognosis of patients with advanced or unresectable extrahepatic cholangiocarcinoma is poor. More than 50% of patients with jaundice are inoperable at the time of first diagnosis. Endoscopic treatment in patients with obstructive jaundice ensures bile duct drainage in preoperative or palliative settings. Relief of symptoms (pain, pruritus, jaundice) and improvement in quality of life are the aims of palliative therapy. Stent implantation by endoscopic retrograde cholangiopancreatography is generally preferred for long-term palliation. There is a vast variety of plastic and metal stents, covered or uncovered. The stent choice depends on the expected length of survival, quality of life, costs and physician expertise. This review will provide the framework for the endoscopic minimally invasive therapy in extrahepatic cholangiocarcinoma. Moreover, additional therapies, such as brachytherapy, photodynamic therapy, radiofrequency ablation, chemotherapy, molecular-targeted therapy and/or immunotherapy by the endoscopic approach, are the nonsurgical methods associated with survival improvement rate and/or local symptom palliation.

Inflammation, Tumoral Markers and Interleukin-17, -10, and -6 Profiles in Pancreatic Adenocarcinoma and Chronic Pancreatitis.

BACKGROUND: Interleukin profiles can be used as biochemical markers regarding the early diagnosis of pancreatic cancer. AIMS: To assess CRP, CA 19-9, CEA levels, and interleukin-6, -10, and -17 profiles in pancreatic ductal adenocarcinoma, chronic pancreatitis was compared with a control group, and the correlation with pancreatic cancer survival. METHODS: A total of 87 patients were prospective divided in pancreatic cancer (n = 53), chronic pancreatitis (n = 22) ,and control group (n = 12). The diagnosis of PDAC was made histologically. The diagnosis of chronic pancreatitis was based on medical history, imaging methods, and endoscopic ultrasound. Systemic concentrations of interleukins were measured using ELISA kits. The patients were followed at 1, 3, and 6 months. RESULTS: CRP, CA 19-9, and CEA were higher in the pancreatic cancer group (p < 0.001). Interleukin-10 was significantly higher in the pancreatic cancer and chronic pancreatitis groups (p < 0.001). Interleukin-17 was statistically higher in the pancreatic cancer group (p < 0.0001). The cut-off of interleukin-17 of 0.273 had a sensitivity of 90.9 and a specificity of 80.9 with a curve under ROC of 0.80 in order to differentiate between pancreatic cancer and chronic pancreatitis. The serum levels of interleukins are not correlated with the stage of the disease. CRP, CA 19-9, CEA, and interleukin-6, -10, and -17 were lower in patients with survival more than 6 months. CONCLUSIONS: We detected high levels of interleukin-6, -10, and -17 in chronic pancreatitis and pancreatic cancer. Serum interleukin-17 levels can discriminate between pancreatic cancer and chronic pancreatitis. The prognostic role of interleukins needs to be established.

Impact of prior treatment on feasibility and outcomes of Zenker's peroral endoscopic myotomy (Z-POEM).

BACKGROUND: Zenker's peroral endoscopic myotomy (Z-POEM) is a novel procedure for the management of symptomatic Zenker's diverticulum. This study aims to report the technical feasibility and outcomes of Z-POEM in the management of Zenker's diverticulum after prior failed interventions. METHODS: Patients with persistent or recurrent symptoms after prior endoscopic and/or surgical intervention for Zenker's diverticulum were retrospectively included. The primary outcome was clinical success, defined as complete or near complete resolution of dysphagia (dysphagia score of 0 or 1) without the need for repeat endoscopic or surgical intervention during follow-up. RESULTS: Z-POEM was technically successful in 30/32 patients (93.8 %). Clinical success was achieved in 29/30 patients (96.7 %), and Z-POEM significantly reduced the median (interquartile range [IQR]) dysphagia score of patients from 2 (1 - 2) to 0 (0) (P < 0.001) over a median duration of follow up of 166 days (IQR 39 - 566). Four patients (12.5 %) had adverse events (two inadvertent mucosotomies and two leaks found on post-procedural esophagrams). CONCLUSION: Z-POEM is feasible, safe, and effective in the majority of patients with recurrent symptoms after prior surgical or endoscopic interventions.

Renal Cell Carcinoma With Extensive Tumor Thrombus Into the Inferior Vena Cava and Right Atrium in a 70-Year-Old Man.

The case of a male patient is reported, who presented with renal carcinoma and tumor thrombus in the inferior vena cava (IVC) extending from the right atrium (RA) to the bifurcation of IVC, common and external right iliac vein thrombosis, common and deep right femoral vein thrombosis, right popliteal vein thrombosis, with pulmonary and hepatic metastasis, treated with sorafenib. Renal cell carcinoma (RCC), the most common form of kidney cancer, occurs in 90% of cases and is nearly twice as common in men as in women. The diagnosis of RCC is accompanied by intravascular tumor thrombus in 10% of cases, and further extension of the tumor reaching RA is detected in approximately 1% of all patients. Therapy for advanced renal cell cancer has evolved considerably in the past decade, with new agents greeted like "buried treasure." Before 2005, the widely used systemic agents were cytokine interferon alfa and interleukin-2, which yielded modest efficacy and substantial toxicity. Tyrosine kinase inhibitors (TKIs) increase progression-free survival and/or overall survival as both first-line and second-line treatments for metastatic RCC. Sorafenib is an oral multikinase inhibitor with activity against Raf-1 serine/threonine kinase, B-Raf, vascular endothelial growth factor receptor-2 (VEGFR-2), platelet-derived growth factor receptor (PDGFR), FMS-like tyrosine kinase 3 (FLT-3), and c-KIT.

Flexible endoscopic treatment for Zenker's diverticulum - experience on 31 patients.

BACKGROUND AND AIMS: The aim of this study is to present the experience of our center over the last 8 years in a series of patients with Zenker's diverticulum (ZD), treated using an endoscopic, minimally invasive procedure. METHODS: We retrospectively included 31 patients with a previously established diagnosis of ZD based on endoscopic and oral contrast examinations. Patients' age, comorbidities, size of the diverticulum or previous endoscopic treatment were not considered exclusion criteria. A soft, flexible diverticuloscope to expose the septum and a dual knife for "cutting" the diverticular septum were used. We analyzed the short term efficacy based on symptomatic relief and occurrence of side effects, and long term efficiency at 6 and 12 months by clinical assessment, upper gastrointestinal endoscopy and oral contrast media passage. RESULTS: Patients had a mean age of 67 years (range 42-86); 55% of them were male. All patients reported symptom relief after the procedure. A decrease of more than 70% from the initial size of the diverticulum was noted. There were 3 cases (9.67%) of intraprocedural hemorrhage, endoscopically managed. No serious post-procedural complications and no mortality were reported. The mean procedural time was 21.87 minutes (range 15-25 minutes). Average hospitalization was 2.5 days. Five patients developed recurrence and needed a second session of endoscopic treatment for achieving complete myotomy. CONCLUSIONS: Endoscopic management for ZD was efficient and safe in our series of patients. A short hospitalization period was required.

Barrett's Esophagus - State of the Art.

Barrett's Esophagus (BE) is defined as a premalignant condition, where the esophageal squamous epithelium is replaced by intestinal epithelium. Specialized intestinal columnar metaplasia, typical for Barrett's esophagus, does not generate any symptoms. Most of the patients are initially seen for symptoms associated with the gastroesophageal reflux disease (GERD), such as heartburn, regurgitation and dysphagia. The histological progression from intestinal metaplasia to dysplasia and then to BE-associated adenocarcinoma forms the argument for screening and endoscopic monitoring. The examination of Barrett's esophagus is controversial. Certain groups suggest a screening of the patients who exhibit more risk factors for the development of esophageal adenocarcinoma (for instance, gastroesophageal reflux disease, age 50, male, high body mass index with abdominal fat distribution). The main reason behind the treatment of acid reflux is that it may lead to chronic esophageal inflammation, which in its turn may predispose to the development of cancer.

Real-world efficacy and safety of ombitasvir, paritaprevir/r+dasabuvir+ribavirin in genotype 1b patients with hepatitis C virus cirrhosis.

BACKGROUND: Direct antiviral agents (DAA) showed very good results in terms of efficacy and safety in clinical trials, but real-life data are still needed in order to confirm this profile. MATERIAL AND METHODS: In Romania, through a nationwide government-funded programme in 2015-2016, approx.5800 patients with virus C cirrhosis received fully reimbursed DAA therapy with OBV/PTV/r+DSV+RBV for 12 weeks. We analysed a national prospective cohort enrolling the first 2070 patients, all with genotype 1b. The only key inclusion criteria was advanced fibrosis (Metavir stage F4) confirmed by Fibromax testing (or liver biopsy/Fibroscan). Efficacy was assessed by the percentage of patients achieving SVR 12 weeks post-treatment (SVR12). RESULTS: Forty patients stopped the treatment because of hepatic decompensation (1.9%), 21 stopped because of other adverse events and one was lost to follow-up. This cohort was 51% females, mean age 60 years (25÷82), 67% pretreated, 70% associated NASH, 67% with severe necro-inflammation (severity score 3-Fibromax), 37% with comorbidities, 10.4% with Child Pugh A6, 0.5% B7. The median MELD score was 8.09 (6 ÷ 22). SVR by intention-to-treat was reported in 1999/2070(96.6%), 55/2070 failed to respond. Liver decompensation was statistically associated in multivariate analysis with platelets< 105 /mm3 (P = .03), increased total bilirubin (P < .001), prolonged INR (P = .02), and albumin<3.5 g/dL (P = .03). CONCLUSIONS: OBV/PTV/r+DSV+RBV proved to be highly efficient in our population of cirrhotics with a 96.6% SVR. Serious adverse events related to therapy were reported in 61/2070(2.9%), most of them liver decompensation (1.9%), related to hepatic dysfunction, and lower platelet count.