The effect of anti-TNF therapy on thyroid function in patients with inflammatory bowel disease.

The aim of this study was to investigate for first time the thyroid function in patients with inflammatory bowel disease (IBD) and the potential effect of anti-TNF (tumor necrosis factor) therapy. We evaluated 41 patients with IBD (25M/16F, 36.5 ± 11.3 y, 27 with Crohn's disease and 14 with ulcerative colitis), without any known thyroid disorder. Eighteen patients (9M/9F, 33.6 ± 8.8 y) were on anti-TNF therapy, while 23 patients (16M/7F, 38.7 ± 12.5 y) were treated with Azathioprine and Mesalazine (Aza/Mes) for more than 1 year. Twelve patients from the second group were then treated with anti-TNF and studied 6 months later. We assessed thyroid function by measuring thyroid stimulating hormone (TSH), free thyroxine (FT4), triiodothyronine (T3), thyroid peroxidase autoantibodies (TPOAb) and thyroglobulin autoantibodies (TgAb) levels. One patient presented with overt and one with subclinical hyperthyroidism. Thyroid auto-antibodies were positive in 12.2%. Patients from the anti-TNF group had lower levels of FT4 (1.09 ± 0.15 vs. 1.38 ± 0.9 ng/dL, p = 0.042), while TSH and T3 were comparable. The percentage of patients with positive thyroid auto-antibodies was lower in the anti-TNF group (5.6% vs. 17.4%). In the subgroup of patients who changed to anti-TNF, we found statistically significant reduction in FT4 after 6 months (1.26 ± 0.24 vs. 1.08 ± 0.15 ng/dL, p = 0.044), without changes in TSH and T3 levels. There was no change regarding thyroid auto-antibodies. In conclusion, patients with IBD showed a quite high percentage of thyroid autoimmunity. After treatment with anti-TNF, FT4 levels were found to be reduced, while no changes in TSH, T3 levels and thyroid auto-antibodies were noted.

Characterization of the ascending colon fluids in ulcerative colitis.

PURPOSE: To characterize the fluid composition in ascending colon of fasted adults with ulcerative colitis in relapse and in remission with a view to predicting variations on dosage form performance in the lower inflamed gut. METHODS: Twelve patients participated in a two-phase, crossover study. Enrollment to the relapse phase (Phase A) and designation of the remission state for the second colonoscopy (Phase B) were based on Clinical Rachmilewicz Index values. Samples were analyzed for pH and buffer capacity immediately upon collection. After ultracentrifugation, osmolality, surface tension, soluble protein, soluble carbohydrates, and the levels of ten bile acids, seven short-chain fatty acids (SCFAs), three long-chain fatty acids, triglycerides, diglycerides, monoglycerides, phosphatidylcholine, and cholesterol were measured. RESULTS: Total SCFAs are significantly decreased in relapse, but pH remains unaffected. Regardless of remission/relapse status, pH and isobutyric acid levels are lower than in healthy adults. Buffer capacity, osmolality, and soluble protein are higher than in healthy adults. Treatment with prednisolone increases the volume of intracolonic contents. CONCLUSION: Variations in fluid composition of the ascending colon with activity and severity of ulcerative colitis may have an impact on the performance of orally administered products that are targeted to release the therapeutic agent in the colon.

Rectal versus intramuscular diclofenac in prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis: experience of a Greek tertiary referral center.

BACKGROUND: Independent patient-related and procedure-related factors increase the risk of pancreatitis after endoscopic retrograde cholangiopancreatography (post-ERCP pancreatitis [PEP]). Non-steroidal anti-inflammatory drugs (NSAIDs) have demonstrated efficacy in reducing the incidence of PEP. This study investigated the difference in the incidence of PEP between intramuscular and rectal prophylactic administration of diclofenac before ERCP. METHODS: We performed a retrospective analysis of data from 516 patients who underwent ERCP during the period 2014-2017. The route of diclofenac administration (rectal or intramuscular), patient-related and procedure-related risk factors, as well as serum amylase levels 18 h after the endoscopic procedure and immediate bleeding during ERCP were recorded and evaluated. RESULTS: The overall incidence of PEP was 4.5%, without significant differences between the rectal (5.2%) and intramuscular (3.9%) routes of administration. The factor that appeared to be of significance was pre-cut sphincterotomy, since patients who underwent that procedure showed a higher probability of PEP (P=0.05; odds ratio 2.67, 95% confidence interval). Intraprocedural bleeding was almost twice as frequent in the rectal compared to the intramuscular group. Pancreatic stent placement did not appear to be statistically significant in the prevention of PEP, either alone or in combination with diclofenac administration. CONCLUSIONS: The results of our study did not reveal any statistically significant difference between the rectal or intramuscular administration of diclofenac in the prevention of PEP, contradicting the results of the majority of studies and meta-analyses published so far. One of the known risk factors associated with increased risk of PEP was also confirmed.

Exploring the impact of Crohn's disease on the intragastric environment of fasted adults.

We explored the potential impact of Crohn's disease on the intragastric environment of fasted adults with a view to potential effects on intragastric performance of orally administered drugs in the fasted state. Data were collected from 15 healthy individuals and 15 patients with Crohn's disease. All subjects remained fasted for at least 12h prior to gastroscopy. Intragastric resting volume and pH were measured upon aspiration. Osmolality, surface tension, pepsin activity, and content of six bile acids were measured within 4 months upon sample collection. Unlike intragastric volumes, intragastric osmolality was significantly increased by Crohn's disease. However, mean osmolality value in patients was only slightly higher than in healthy individuals (293 vs. 257 mOsmol/kg, respectively), therefore, unlikely to affect intragastric drug product performance. Primarily due to the high variability of data in healthy individuals, the potential effects on intragastric pH and surface activity could not be evaluated on a statistical basis. However, based on average (mean and median) values, even if they are statistically significant, it seems unlikely to be of clinical significance. Inter-subject variability of pepsin activity, and total bile acids content was high in both the healthy and the patients' groups. Statistical investigation of the potential impact of Crohn's disease on these parameters requires prior designation of the minimum differences to be detected; such differences will determine the minimum sample size required of relevant investigations.

Acute ischemic colitis during scuba diving: report of a unique case.

The presentation of clinical symptoms due to decompression during diving, varies significantly, as mainly minor disturbances for the gastrointestinal tract in particular have been reported. The following case debates whether diving can cause severe symptoms from the gastrointestinal system. We describe a clinical case of ischemic colitis presented in a 27-year-old male, who manifested abdominal pain while in the process of scuba diving 20 meters undersea, followed by bloody diarrhoea as soon as he ascended to sea level. Taking into account his past medical history, the thorough, impeccable clinical and laboratory examinations and presence of no other factors predisposing to ischemia of the colon, we assume that a possible relationship between diving conditions and the pathogenesis of ischemic colitis may exist. This unusual case might represent a hematologic manifestation of decompression sickness, due to increased coagulability and/or transient air emboli, occurring during a routine scuba diving ascent to sea level.

Favorable Effect of Anti-TNF Therapy on Insulin Sensitivity in Nonobese, Nondiabetic Patients with Inflammatory Bowel Disease.

BACKGROUND: The aim of this study was to investigate the effect of anti-TNF therapy on glucose and lipid metabolism in nondiabetic, nonobese patients with inflammatory bowel disease (IBD). PATIENTS AND METHODS: We studied 44 patients with IBD, without a known history of diabetes. Three of the patients were diagnosed with overt diabetes and were excluded. Eighteen of the remaining patients (9 M/9 F, 33.6 ± 8.8 years) were on anti-TNF therapy for longer than 1 year, while 23 patients (16 M/7 F, 38.7 ± 12.5 years) were treated with aminosalicylates (AMSs). Twelve of the patients from the second group were then treated with anti-TNF and reassessed 6 months later. Fasting glucose, insulin, c-peptide, HbA1c, lipid, CRP, and fibrinogen levels were determined, and HOMA-IR index was calculated in all patients. RESULTS: Patients from the two therapy groups were matched for age and BMI and were not obese. We did not find any differences between patients from the two therapy groups regarding fasting glucose, c-peptide, HbA1c, total cholesterol, HDL, LDL, triglycerides, CRP, and HOMA-IR index. In patients who were treated for 6 months with anti-TNF, a statistically significant decrease in insulin (before 15.5 ± 5.9 versus after 9.9 ± 2.9 µIU/ml, p = 0.042) and c-peptide (before 2.4 ± 1 versus after 1.3 ± 0.4 ng/ml, p = 0.030) levels as well as the HOMA-IR index (before 4.2 ± 1.9 versus after 2.2 ± 0.9, p = 0.045) was observed, without any changes in weight, BMI, glucose, HbA1c, lipid, CRP, and fibrinogen levels. CONCLUSION: Anti-TNF therapy exerts a favorable effect on insulin sensitivity, while it has no effect on lipid levels in nondiabetic, nonobese patients with inflammatory bowel disease.

High-dose vs. Low-dose Proton Pump Inhibitors post-endoscopic hemostasis in patients with bleeding peptic ulcer. A meta-analysis and meta-regression analysis.

BACKGROUND/AIMS: Present meta-analysis aims to evaluate studies of low- versus high-dose proton pump Inhibitors (PPI) post-endoscopic hemostasis, including the newly published randomized controlled trials (RCTs) and to conclude whether low-dose PPI can generate the comparable results as high-dose PPI. MATERIALS AND METHODS: To identify suitable trials, the electronic databases PubMed, Medline, Cochrane Library, and the Embase were used. All RCTs concerning low- versus high-dose PPI administration post-endoscopic hemostasis published until December 2016 were identified. Primary outcomes were rebleeding rates, need for surgical intervention, and mortality. RESULTS: Studies included a total of 1.651 participants. There were significantly less cases of rebleeding in the low-dose PPI treatment arm (p=0.003). All but one study provided data concerning need for Surgical Intervention and Mortality. The respective effect sizes were [odds ratio (OR), 95% confidence intervals (CI): 1.35, 0.72-2.53] and [OR, 95% CI: 1.20, 0.70-2.05]. Both treatment arms were comparable considering the aforementioned outcomes (p=0.35 and p=0.51, respectively). Meta-regression analysis likewise unveiled comparable outcomes between studies using pantoprazole versus lansoprazole concerning all three outcomes [rebleeding (p=0.944), surgical intervention (p=0.884), and mortality (p=0.961)]. CONCLUSION: A low-dose PPI treatment is equally effective as a high-dose PPI treatment following endoscopic arresting of bleeding. However, we anticipate the completion of more high-quality RCTs that will embrace distinct ethnicities, standardized endoscopic diagnosis and management, double-blind strategies, and appraisal of results working specific standards over clear-cut follow-up periods.

Microproteinuria in patients with inflammatory bowel disease: is it associated with the disease activity or the treatment with 5-aminosalicylic acid?

AIM: To investigate whether microproteinuria in patients with inflammatory bowel disease (IBD) is associated with the disease activity or the treatment with 5-aminosalicylic acid (5-ASA). METHODS: We prospectively studied microproteinuria in 86 consecutive patients with IBD, 61 with ulcerative colitis (UC) and 25 with Crohn's disease (CD), before as well as 2 and 6 months after their inclusion in the study. Forty-six patients received 5-ASA for a period of 28.8 months (range 1-168 mo). Microalbuminuria (mALB) and urine levels of the renal tubular proteins beta2-microglobulin (beta2mGLB) and beta-N-acetyl-D-glucosamidase (beta-NAG) as well as the creatinine clearance were determined in a 12-h overnight urine collection. Tumor necrosis factor-alpha (TNF-alpha) serum levels were also measured. RESULTS: A total of 277 measurements (194 in UC patients and 83 in CD patients) were performed. The prevalence of abnormal microproteinuria in UC and CD patients was 12.9% and 6.0% for mALB, 22.7% and 27.7% for beta2mGLB, and 11.3% and 8.4% for beta-NAG, respectively. mALB was not associated with IBD activity. Beta2mGLB and beta-NAG urine levels were correlated to UC activity (UCAI: P<0.01; UCEI: P<0.005). mALB in UC patients and beta-NAG urine levels in CD patients were related to TNF-alpha serum levels. An association was noticed between microproteinuria and smoking habit. Treatment with 5-ASA was not correlated to the severity of microproteinuria or to the changes of creatinine clearance. CONCLUSION: Microproteinuria is mainly associated with UC and its activity but not affected by 5-ASA.

Role of endoscopic intervention in biliary complications of hepatic hydatid cyst disease.

OBJECTIVE: Biliary complications of hepatic hydatidosis are often difficult to detect and manage. The aim of this study was to present our experience on the effectiveness of endoscopic treatment modalities in cases of biliary complications of hepatic hydatid cysts. MATERIAL AND METHODS: Over the past 10 years, 15 patients diagnosed with hepatic hydatidosis and manifesting symptoms and signs indicative of biliary involvement were examined by means of endoscopic retrograde cholangiopancreatography (ERCP) in our Gastroenterology Endoscopic Unit; 7 patients had already been operated on for hepatic hydatid cysts; one of them had a concomitant hydatid cyst in the lung. Diagnosis of the disease was based on a combination of ultrasonography (US), computed tomography (CT) and specific immunologic and/or microbiologic studies. RESULTS: Biliary complications of hydatid cysts were detected by ERCP in 9 patients (60%). Eight (88.9%) patients displayed a communication between the hydatid cyst or its residual cavity and the biliary tree; 5 patients had daughter cysts or residual hydatid material within the biliary tree, 1 patient had a biliocutaneous fistula, 1 patient a postoperative biliary leakage and 1 patient had only an opacification of the hydatid cyst during ERCP. In one patient, ERCP showed stenoses of both of the main hepatic ducts due to their compression by the cyst. Jaundice (88.9%), fever (33.3%) and right upper quadrant abdominal pain (88.9%) were the most frequent manifestations. These complications were demonstrated by US and CT imaging in only 25% of the cases. Four patients underwent ERCP before surgery and 5 after surgery. Endoscopic management was successful in all patients, resulting in clearance of the biliary tree, closure of fistulas, stopping of biliary leakage and jaundice remission. No serious endoscopy-related complications were recorded, with the exception of a pulmonary hydatid cyst rupture during ERCP. CONCLUSIONS: This study suggests that endoscopic treatment modalities are helpful and safe methods in the treatment of biliary complications of hepatic hydatidosis before and after definitive surgical management of the hydatid cysts.