Efficacy of abatacept treatment in a patient with enteropathy carrying a variant of unsignificance in CTLA4 gene: A case report.

BACKGROUND: Cytotoxic T Lymphocyte Antigen-4 (CTLA4) deficiency is a genetic defect that causes a common variable immunodeficiency (CVID) clinical phenotype. Several studies have reported an association between CTLA mutations or variants and various autoimmune diseases. Targeted therapy models, which have become increasingly popular in recent years, have been successful in treating CTLA4 deficiency. In this article, we discuss the clinical outcomes of abatacept treatment in a patient with CTLA4 and lipopolysaccharide-responsive beige-like anchor (LRBA) variants that was previously diagnosed with CVID. CASE SUMMARY: A 25-year-old female patient, who was visibly cachectic, visited our clinic over the course of five years, complaining of diarrhea. The patient was diagnosed with ulcerative colitis in the centers she had visited previously, and various treatments were administered; however, clinical improvement could not be achieved. Severe hypokalemia was detected during an examination. Her serum immunoglobulin levels, CD19+ B-cell percentage, and CD4/CD8 ratio were low. An endoscopic examination revealed erosive gastritis, nodular duodenitis, and pancolitis. Histopathological findings supported the presence of immune mediated enteropathy. When the patient was examined carefully, she was diagnosed with CVID, and intravenous immunoglobulin treatment was initiated. Peroral and rectal therapeutic drugs including steroid therapy episodes were administered to treat the immune mediated enteropathy. Strict follow-ups and treatment were performed due to the hypokalemia. After conducting genetic analyses, the CTLA4 and LRBA variants were identified and abatacept treatment was initiated. With targeted therapy, the patient's clinical and laboratory findings rapidly regressed, and there was an increase in weight. CONCLUSION: The heterozygous CTLA4 variant identified in the patient has been previously shown to be associated with various autoimmune diseases. The successful clinical outcome of abatacept treatment in this patient supports the idea that this variant plays a role in the immunopathogenesis of the disease. In the presence of severe disease, abatacept therapy should be considered until further testing can be conducted.

Relationship between Helicobacter pylori infection and white matter lesions in patients with migraine.

BACKGROUND/AIM: White matter lesions (WML) are more frequently observed in migraine patients than in the average population. Associations between Helicobacter pylori (H. pylori) infection and different extraintestinal pathologies have been identified. Here, we aimed to investigate the association between H. pylori infection and WML in patients diagnosed with episodic migraine. MATERIALS AND METHODS: A retrospective study was conducted with 526 subjects with a diagnosis of episodic migraine. Hyperintensity of WML had been previously evaluated in these patients with brain magnetic resonance imaging (MRI) examinations. Previous endoscopic gastric biopsy histopathological examination of the same patients and reports on H. pylori findings were recorded. The demographic characteristics of the patients, such as age, gender and chronic systemic diseases such as hypertension and diabetes mellitus (DM) were recorded. Statistical evaluation was made. RESULTS: Evaluation was made among 526 migraine patients who met the inclusion criteria, comprising 397 (75.5%) females and 129 (24.5%) males with a mean age of 45.57 ± 13.46 years (range, 18-69 years). WML was detected on brain MRI in 178 (33.8%) patients who were also positive for H. pylori (p <  0.05). Subjects who are H. pylori-positive with migraine, WML were observed at a 2.5-fold higher incidence on brain MRI (odds ratio: 2.562, 95% CI 1.784-3.680). WML was found to be more significant in patients with hypertension and migraine than those without (p <  0.001). Older age was also found to be associated with WML (OR = 1.07, 95% CI: 0.01-0.04, p <  0.001). The age (p <  0.001), H. pylori (p <  0.001), hypertension (p <  0.001), and hypertension + DM (p <  0.05), had significant associations in predicting WML according to the multivariate logistic regression analysis. The presence of hypertension had a higher odds ratio value than the other variables. CONCLUSION: It was concluded that H. pylori infection, as a chronic infection, can be considered a risk factor in developing WML in subjects with migraine.

Can the treatment duration be shortened in bismuth-containing therapies for Helicobacter pylori eradication?

BACKGROUND/AIMS: The duration of Helicobacter pylori (H. pylori) eradication therapy as a range (e.g., 10-14 days) is an ignored problem. There is no any particular treatment duration described in current guidelines, and the conditions for when to use 10-day therapy vs. 14-day therapy have not been elucidated. The aim of this study is to determine an effective and reliable H. pylori treatment duration in clinical practice. There were four different treatment modalities administered to groups, and success rates were compared. MATERIALS AND METHODS: Patients were eligible to participate in the study if they had a biopsy-proven H. pylori infection. Each patient was randomly assigned to one of the four treatment groups according to a predetermined sequence: 14-day or 10-day bismuth-containing quadruple therapy (BQT) groups and 14-day or 10-day moxifloxacin-bismuth-combined treatment (MBCT) groups. RESULTS: A total of 216 patients (54 per group) were enrolled. Two-hundred six patients (95.3%) completed therapy. There was no significant difference in the eradication rates between those patients who received 10- and 14-days BQT regimens (p=0.67). The 14-BQT protocol had the highest eradication rate, the MBCT regimes had the highest compliance, and the 10-MBCT protocol had the poorest results for H. pylori eradication. The posttreatment questionnaire on adverse effects identified nausea/vomiting as the most common side effect (35.7%). CONCLUSION: Overall, the results of our study suggest that shortening the BQT protocol duration to 10 days does not weaken the H. pylori eradication rate. Moreover, quinolone-containing therapies with the lowest eradication rate among the groups should not be offered as a salvage treatment in case of the BQT failure.

Can a 1-day clear liquid diet with a split -dose polyethylene glycol overcome conventional practice patterns during the preparation for screening colonoscopy?

BACKGROUND/AIMS: A successful screening colonoscopy is closely linked to the quality of a bowel preparation. In this study, we aimed to determine the impact of a 1-day clear liquid diet (CLD) compared to a 3-day combined diet (CMD) accompanied by a split-dose regimen of polyethylene glycol and electrolyte lavage solution (PEG-ELS) for screening colonoscopy. MATERIALS AND METHODS: This was a prospective, randomized, endoscopist-blinded study. Patients referred for screening colonoscopy were randomized to four groups as a 1-day CLD+PEG-ELS vs. a 1-day CLD+sulfate free (SF)-PEG-ELS and a 3-day CMD+PEG-ELS vs. a 3-day CMD+SF-PEG-ELS. An assessment of the quality of colon cleaning, tolerability to the preparation, and symptoms related to the preparation were recorded. RESULTS: A total of 506 patients were enrolled in this study. The quality of bowel preparation was significantly inferior in the CMD+PEG-ELS group than CLD+PEG-ELS (p=0.004) and CMD+SF-PEG-ELS groups (p=0.007). There were no statistical differences among the groups in terms of the polyp detection rate. With respect to an easy rating of diet following and the consumption of laxative, there were no significant differences among the four groups. Gastric fullness and nausea/vomiting were pointed out much more, especially in the SF-PEG-ELS users (p=0.008 and p=0.004, respectively). CONCLUSION: A 1-day CLD was not inferior to a 3-day CMD for colonoscopy preparation in terms of bowel cleaning, the polyp detection rate, and patient tolerance.

When abdominal pain knocks the door: an unusual presentation of chronic lymphocytic leukemia.

A 67-year-old man presented non-specific abdominal pain. Polypoid mass at appendiceal orifice in the cecum was found on endoscopic investigation without appendicitis sign. Histopathology elucidated underlying mucosal infiltration that was chronic lymphocytic leukemia. This is an isolated and unusual gastrointestinal involvement of hematologic disorder in an older patient.

Effect of Propranolol Treatment on the Incidence of Hepatocellular Carcinoma in Patients Waiting for Liver Transplant With Cirrhosis: A Retrospective, Surveillance Study in a Tertiary Center.

OBJECTIVES: Hepatocellular carcinoma is the most frequent primary malignant tumor of the liver and the third most common cause of all cancer-related mortalities. There is a need to develop new strategies to prevent hepatocellular carcinoma, as the incidence of this cancer continues to increase despite all advancements. In this study, our aim was to determine the effects of propranolol treatment on the incidence of hepatocellular carcinoma in cirrhotic patients waiting for liver transplant. MATERIALS AND METHODS: We retrospectively reviewed the data of patients waiting for liver transplant with cirrhosis due to various causes registered at the Hepatocellular Carcinoma Surveillance Program between June 2011 and December 2017 in our center. These data were compared between patients using propranolol and those not using propranolol. RESULTS: Of the 231 patients, 135 (58.4%) were male and 96 (41.6%) were female. The mean age was 58.1 ± 14 years. We noted that 153 of total patients (66.2%) were using propranolol. Three patients (2%) were using 20 mg propranolol, 125 (81.7%) were using 40 mg propranolol, 10 (6.5%) were using 60 mg propranolol, and 15 (9.8%) were using 80 mg propranolol. Of total patients, 36 (15.6%) developed hepatocellular carcinoma, including in 12 patients (7.8%) using propranolol and 24 patients (30.8%) who did not use this agent (P < .001). Thus, the hepatocellular carcinoma frequency was 5.22 times lower in patients receiving propranolol than in those not receiving propranolol. CONCLUSIONS: Although causes of cirrhosis and initial stages were similar in both groups using and not using propranolol, incidence of hepatocellular carcinoma was significantly lower in the propranolol group than in the group without propranolol. This result showed that propranolol treatment has a protective effect for hepatocellular carcinoma in patients waiting for liver transplant with cirrhosis.

Successful Treatment With Direct-Acting Antiviral Agents of Hepatitis C in Patients With End-Stage Renal Disease and Kidney Transplant Recipients.

OBJECTIVES: The introduction of direct-acting antiviral agents has allowed significant chances for treatment for difficult-to-treat populations. This study aimed to investigate the efficacy, tolerability, and safety of these therapies in both patients with end-stage renal disease and kidney transplant recipients with chronic hepatitis C virus infection. MATERIALS AND METHODS: This study was a retrospective analysis with prospective follow-up of patients. The antiviral combination of ombitasvir 25 mg, paritaprevir 75 mg, ritonavir 50 mg, and dasabuvir 50 mg was prescribed to patients with end-stage renal disease or kidney transplant recipients with noncirrhotic or compensated cirrhotic liver disease. The other antiviral combination consisted of sofosbuvir 400 mg and ledipasvir 90 mg, which was recommended to patients with decompensated cirrhosis or those who could not tolerate the first combination regimen. Ribavirin was given to all patients with genotype 1a hepatitis C virus infection. All clinical and laboratory data were recorded at week 4, at end of the treatment, and at 12 weeks after completion of treatment. RESULTS: In terms of efficacy, sustained virologic response at 12 weeks was achieved in 94% of patients in the end-stage renal disease group and 92% of patients in the kidney transplant group. In terms of tolerability, antiviral treatment was well tolerated in both groups. Cardiac arrest and cerebrovascular accident were seen in the end-stage renal disease group; severe mucositis and glossitis were seen in the kidney transplant group. Hospitalization was needed in 2 patients for treatment of drug interactions with tacrolimus and sirolimus. Renal allograft function worsened in 2 patients, with 1 patient having biopsyproven antibody-mediated rejection. CONCLUSIONS: We observed great efficacy and safety in both kidney transplant recipients and patients with end-stage renal disease with these agents in treatment of chronic hepatitis C. However, clinicians should remain aware of drug interactions and adverse events in this fragile patient population.

Management of suspected common bile duct stone: diagnostic yield of current guidelines.

BACKGROUND: The American Society for Gastrointestinal Endoscopy (ASGE) has recently published a guideline for suspected CBDS with the intention of reducing unnecessary ERCP and thereby complications. The aim of this study was to assess the diagnostic efficacy of the ASGE guideline. METHODS: Data of patients who underwent ERCP with suspected CBDS were analyzed retrospectively. Patients were classified into high, intermediate and low risk groups based on predictors that have been suggested by the ASGE. Very strong predictors of the presence of ductal stones included: CBDS on transabdominal ultrasonography (US), clinical ascending cholangitis or total bilirubin (TBIL) >4 mg/dL). Strong predictors included dilated CBD >6 mm on US with gallbladder in situ and TBIL level of 1.8-4.0 mg/dL whereas moderate predictor included abnormal liver biochemical test other than bilirubin, age more than 55 years and clinical findings of biliary pancreatitis. RESULTS: Of 888 enrolled patients, 704 had CBDS demonstrated by ERCP and the remainder did not. All very strong and strong predictors were found to be significantly higher among patients who had CBDS. Detection of CBDS by ultrasonography and a dilated common biliary duct were observed to be independent risk factors associated with the existence of CBDS. The high risk group had a high (86.7%) positive predictive value (PPV), however, sensitivity and specificity were observed to be moderate (67.8% and 60.3% respectively). PPV was 67.9% in the intermediate risk group and the sensitivity and specificity were very low (31.9% and 42.3%). DISCUSSION: The probability of CBDS was observed to be high in the intermediate and high risk groups. However due to low sensitivity and specificity values, the ASGE guideline needs additional or different predictors.

Endoscopic Management of the Difficult Bile Duct Stones: A Single Tertiary Center Experience.

Background. Most common bile duct (CBD) stones can be removed with standard techniques using endoscopic retrograde cholangiopancreatography (ERCP), but in some cases additional methods are needed. In this study we aimed to investigate the management of patients with difficult stones and the factors that affect the outcome of patients that have undergone periodic endobiliary stenting. Materials and Methods. Data of 1529 patients with naive papilla who had undergone ERCP with an indication of CBD stones was evaluated retrospectively. Stones that could not be removed with standard techniques were defined as "difficult stones." Cholangiograms of patients who had difficult stones were revised prospectively. Results. Two hundred and eight patients (13.6%) had difficult stones; 150 of these patients were followed up with periodic endobiliary stenting and successful biliary clearance was achieved in 85.3% of them. Both CBD (p < 0.001) and largest stone size (p < 0.001) were observed to be significantly reduced between the first and the last procedure. This difference was even more significant in successfully treated patients. Conclusions. Periodic endobiliary stenting can be used as an effective treatment for patients with difficult stones. Sizes of the CBD and of the largest stone are independent risk factors that affect the success rate.

The role of soluble tumor necrosis factor like weak inducer of apoptosis and interleukin-17A in the etiopathogenesis of celiac disease: A cross-sectional study.

Our aim in this study was to determine soluble tumor necrosis factor (TNF)-like weak inducer of apoptosis (sTWEAK) and interleukin-17A (IL-17A) levels in celiac disease, and their association with the gluten diet and autoantibodies. Eighty patients with celiac diagnosis and 80 healthy control individuals with similar age, gender and body mass index to the patient group were included in the study. Serum sTWEAK and IL-17A levels were measured by the serum enzyme-linked immunosorbent assay kit. The median IL-17A (117.5 pg/mL vs. 56.7 pg/mL; P = 0.001) level in celiac patients was higher than in the control group, while the median sTWEAK (543 pg/mL vs. 643 pg/mL; P = 0.016) level in patients was determined to be lower. In the patient group, patients who complied with the gluten diet had a lower level of median IL-17A (98.1 pg/mL vs. 197.5 pg/mL; P = 0.034) and a higher level of sTWEAK (606 pg/mL vs. 522.8 pg/mL; P = 0.031) than those who did not adhere. Furthermore, the IL-17A level was higher and the sTWEAK level was lower in celiac patients with positive antibody than those with negative antibody. A positive correlation was determined among anti-gliadin antibody IgA, anti-gliadin antibody IgG, anti-tissue transglutaminase IgG levels and the IL-17A level, and a negative correlation was determined with the sTWEAK level. In celiac disease, the sTWEAK and IL-17A levels differ between patients who cannot adapt to the gluten diet and who are autoantibody positive, and patients who adapt to the diet and are autoantibody negative. We believe that sTWEAK and IL-17A are associated with the inflammation in celiac pathogenesis.

Is Gastric Xanthelasma an Alarming Endoscopic Marker for Advanced Atrophic Gastritis and Intestinal Metaplasia?

BACKGROUND/AIM: The clinical significance of gastric xanthelasmas is unknown. We conducted a case-control study in order to evaluate whether gastric xanthelasma is an indicator of advanced atrophic gastritis and intestinal metaplasia. MATERIAL AND METHOD: The study was conducted among 1400 patients who underwent elective upper endoscopy. Patients with gastric xanthelasma and atrophy and/or intestinal metaplasia constituted the study group (n = 55). The control group involved patients with only atrophic gastritis and/or intestinal metaplasia (n = 50). Histopathologic findings of the groups including the distribution of atrophic gastritis and/or intestinal metaplasia, operative link on gastritis assessment score, operative link on gastritis intestinal metaplasia assessment (OLGIM) score, and presence of dysplasia and malignancy were compared. Subgroup analysis was performed in order to establish the relation between the characteristics (size, number, and localization) of xanthelasmas, atrophy, and intestinal metaplasia. RESULTS: Multifocal atrophic gastritis was significantly more common in patients with a gastric xanthelasma (41.8 vs. 26.0 %, p = 0.03). Patients with multiple xanthelasmas had a significantly higher rate of intestinal metaplasia (p = 0.02) and a higher OLGIM score (p = 0.02) compared to those with a single xanthelasma. Dysplasia was detected in 8 (14.5 %) patients with a xanthelasma and 4 (8.0 %) patients without a xanthelasma (p = 0.2). CONCLUSION: Gastric xanthelasma(s) is a warning endoscopic sign for the presence of multifocal atrophic gastritis and advanced intestinal metaplasia.

Double balloon enteroscopy: A 7-year experience at a tertiary care Centre.

BACKGROUND: Double Balloon Enteroscopy (DBE) provides the opportunity not only to investigate but also apply endoscopic therapeutic interventions for small intestinal disturbances. The aim of this study is to assess the indications, diagnosis, therapeutic interventions, complications and safety in clinical practise of DBE procedures that have been performed in our clinic. MATERIAL-METHODS: The data of patients who had undergone DBE procedure in our clinic between October 2007 and December 2014 were retrospectively investigated. All features including indications, findings, histopathological results, applied interventions and complications due to procedure were noted. RESULTS: A total of 297 patients, 160 (53,9%) male and 137 (46,1%) female were enrolled in the study. Total number of procedures for these 297 patients were 372 [256 (68,8%) oral and 116 (31,2%) anal]. Mean age of the patients was 46,9 (14-94) years. The most common indications were; obscure gastrointestinal (GI) bleeding (28,3%), iron deficiency anaemia (17,5% ) and abnormal findings in a prior imaging study (13,8%), respectively. The rate of new diagnosis with DBE was 11.8%, where the rate for confirmation of a possible diagnosis was 16.2%, rate of endoscopic treatment with definite diagnosis was 11%, rate for ruling out possible diagnosis or showing normal findings was 34.7% and rate for insufficient or unsuccessful procedures was 26.3%. Ulcers, inflammation and erosions (13%), polyposis syndromes (9.8%) and vascular pathologies (7.4%) were the most common endoscopic findings. CONCLUSION: Our study shows that DBE has high efficacy for diagnosis and ability to perform treatment of small intestinal disturbances with safety.

The Prevalence of Barrett Esophagus Diagnosed in the Second Endoscopy: A Retrospective, Observational Study at a Tertiary Center.

At present, we do not know the exact prevalence of Barrett esophagus (BE) developing later in patients without BE in their first endoscopic screening. The purpose of this study was to determine the prevalence of BE on the second endoscopic examination of patients who had no BE in their first endoscopic examination.The data of the patients older than 18 years who had undergone upper gastrointestinal system endoscopy more than once at the endoscopy unit of our clinic during the last 6 years were retrospectively analyzed.During the last 6 years, 44,936 patients had undergone at least one endoscopic examination. Among these patients, 2701 patients who had more than one endoscopic screening were included in the study. Of the patients, 1276 (47.3%) were females and 1425 (52.7%) were males, with an average age of 54.9 (18-94) years. BE was diagnosed in 18 (0.66%) of the patients who had no BE in the initial endoscopic examination. The patients with BE had reflux symptoms in their medical history and in both endoscopies, they revealed a higher prevalence of lower esophageal sphincter laxity, hiatal hernia, and reflux esophagitis when compared to patients without BE (P < 0.001).Our study showed that in patients receiving no diagnosis of BE on their first endoscopic examination performed for any reason, the prevalence of BE on their second endoscopy within 6 years was very low (0.66%).