Tight control for Crohn's disease with adalimumab-based treatment is cost-effective: an economic assessment of the CALM trial.

OBJECTIVE: To evaluate the cost-effectiveness of an inflammatory biomarker and clinical symptom directed tight control strategy (TC) compared with symptom-based clinical management (CM) in patients with Crohn's disease (CD) naïve to immunosuppressants and biologics using a UK public payer perspective. DESIGN: A regression model estimated weekly CD Activity Index (CDAI)-based transition matrices (remission: CDAI <150, moderate: CDAI ≥150 to <300, severe: CDAI ≥300 to <450, very severe: CDAI ≥450) based on the Effect of Tight Control Management on Crohn's Disease (CALM) trial. A regression predicted hospitalisations. Health utilities and costs were applied to health states. Work productivity was monetised and included in sensitivity analyses. Remission rate, CD-related hospitalisations, adalimumab injections, other direct medical costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER) were calculated. RESULTS: Over 48 weeks, TC was associated with a higher clinical remission (CDAI <150) rate (58.2% vs 46.8%), fewer CD-related hospitalisations (0.124 vs 0.297 events per patient) and more injections of adalimumab (40 mg sc) (mean 31.0 vs 24.7) than CM. TC was associated with 0.032 higher QALYs and £593 higher total medical costs. The ICER was £18 656 per QALY. The ICER was cost-effective in 57.9% of simulations. TC became dominant, meaning less costly but more effective, when work productivity was included. CONCLUSION: A TC strategy as used in the CALM trial is cost-effective compared with CM. Incorporating costs related to work productivity increases the economic value of TC. Cross-national inferences from this analysis should be made with caution given differences in healthcare systems. TRIAL REGISTRATION NUMBER: NCT01235689; Results.

Predictive Value of Mean Platelet Volume in Variceal Bleeding due to Cirrhotic Portal Hypertension.

AIM: To investigate whether mean platelet volume (MPV) is a predictor of variceal bleeding in patients with cirrhotic portal hypertension. MATERIALS AND METHODS: This prospective cohort was performed in the internal medicine department of our tertiary care center. Cirrhotic patients were allocated into two groups: Group I consisted of 31 cases without a history of variceal bleeding, whereas group II was made up of 31 patients with a history of variceal bleeding. Data derived from medical history, physical examination, ultrasonography, gastrointestinal system endoscopy, complete blood count, hepatic, and renal function tests were recorded and compared between two groups. On physical examination, encephalopathy and ascites were evaluated and graded with respect to Child-Pugh-Turcotte classification. RESULTS: There was no significant difference between the two groups in terms of age, duration of the disease, and gender of the patient. The only remarkable difference was that hemoglobin (p = 0.02) and hematocrit (p = 0.02) values were lower in group II. Neither the etiology of bleeding was different between groups nor did MPV seem to have a noteworthy impact on bleeding. Interestingly, risk of variceal bleeding increased in parallel to the higher grade of varices. CONCLUSION: Our results imply that there is a correlation between the grade of varices and esophageal vari-ceal bleeding in cirrhotic patients. However, association between MPV and variceal bleeding could not be demonstrated. Utilization of noninvasive tests as predictors in these patients necessitates further controlled trials on larger series.How to cite this article: Erdogan MA, Benli AR, Acmali SB, Koroglu M, Atayan Y, Danalioglu A, Kayhan B. Predictive Value of Mean Platelet Volume in Variceal Bleeding due to Cirrhotic Portal Hypertension. Euroasian J Hepato-Gastroenterol 2017;7(1):6-10.

Effect of tight control management on Crohn's disease (CALM): a multicentre, randomised, controlled phase 3 trial.

BACKGROUND: Biomarkers of intestinal inflammation, such as faecal calprotectin and C-reactive protein, have been recommended for monitoring patients with Crohn's disease, but whether their use in treatment decisions improves outcomes is unknown. We aimed to compare endoscopic and clinical outcomes in patients with moderate to severe Crohn's disease who were managed with a tight control algorithm, using clinical symptoms and biomarkers, versus patients managed with a clinical management algorithm. METHODS: CALM was an open-label, randomised, controlled phase 3 study, done in 22 countries at 74 hospitals and outpatient centres, which evaluated adult patients (aged 18-75 years) with active endoscopic Crohn's disease (Crohn's Disease Endoscopic Index of Severity [CDEIS] >6; sum of CDEIS subscores of >6 in one or more segments with ulcers), a Crohn's Disease Activity Index (CDAI) of 150-450 depending on dose of prednisone at baseline, and no previous use of immunomodulators or biologics. Patients were randomly assigned at a 1:1 ratio to tight control or clinical management groups, stratified by smoking status (yes or no), weight (<70 kg or ≥70 kg), and disease duration (≤2 years or >2 years) after 8 weeks of prednisone induction therapy, or earlier if they had active disease. In both groups, treatment was escalated in a stepwise manner, from no treatment, to adalimumab induction followed by adalimumab every other week, adalimumab every week, and lastly to both weekly adalimumab and daily azathioprine. This escalation was based on meeting treatment failure criteria, which differed between groups (tight control group before and after random assignment: faecal calprotectin ≥250 µg/g, C-reactive protein ≥5mg/L, CDAI ≥150, or prednisone use in the previous week; clinical management group before random assignment: CDAI decrease of <70 points compared with baseline or CDAI >200; clinical management group after random assignment: CDAI decrease of <100 points compared with baseline or CDAI ≥200, or prednisone use in the previous week). De-escalation was possible for patients receiving weekly adalimumab and azathioprine or weekly adalimumab alone if failure criteria were not met. The primary endpoint was mucosal healing (CDEIS <4) with absence of deep ulcers 48 weeks after randomisation. Primary and safety analyses were done in the intention-to-treat population. This trial has been completed, and is registered with ClinicalTrials.gov, number NCT01235689. FINDINGS: Between Feb 11, 2011, and Nov 3, 2016, 244 patients (mean disease duration: clinical management group, 0·9 years [SD 1·7]; tight control group, 1·0 year [2·3]) were randomly assigned to monitoring groups (n=122 per group). 29 (24%) patients in the clinical management group and 32 (26%) patients in the tight control group discontinued the study, mostly because of adverse events. A significantly higher proportion of patients in the tight control group achieved the primary endpoint at week 48 (56 [46%] of 122 patients) than in the clinical management group (37 [30%] of 122 patients), with a Cochran-Mantel-Haenszel test-adjusted risk difference of 16·1% (95% CI 3·9-28·3; p=0·010). 105 (86%) of 122 patients in the tight control group and 100 (82%) of 122 patients in the clinical management group reported treatment-emergent adverse events; no treatment-related deaths occurred. The most common adverse events were nausea (21 [17%] of 122 patients), nasopharyngitis (18 [15%]), and headache (18 [15%]) in the tight control group, and worsening Crohn's disease (35 [29%] of 122 patients), arthralgia (19 [16%]), and nasopharyngitis (18 [15%]) in the clinical management group. INTERPRETATION: CALM is the first study to show that timely escalation with an anti-tumour necrosis factor therapy on the basis of clinical symptoms combined with biomarkers in patients with early Crohn's disease results in better clinical and endoscopic outcomes than symptom-driven decisions alone. Future studies should assess the effects of such a strategy on long-term outcomes such as bowel damage, surgeries, hospital admissions, and disability. FUNDING: AbbVie.

Does CPAP treatment lead to gastroesophageal reflux in patients with moderate and severe OSA?

Obstructive sleep apnea (OSA) leads to upper respiratory tract obstruction, causing increased abdominal-gastric pressure and decreased lower esophageal sphincter (LES) pressure and thus gastroesophageal reflux (GER). Continuous positive airway pressure (CPAP) is known to be an effective method for OSA treatment, but its effect on GER is still controversial. There are a very few studies investigating CPAP and GER relationship and performed based on pre- and post-treatment objective parameters of GER in patients with OSA. The study investigated the effect of CPAP treatment in patients with moderate and severe OSA without GER complaints on pre- and post-treatment objective GER parameters. The study included 25 patients with respiratory disturbance indices >15 without reflux symptoms who had undergone polysomnography at sleep laboratory. Age, sex, body mass index (BMI), waist, and neck circumference of the patients were documented. DeMeester score, LES pressure, and polysomnography parameters were evaluated pre- and post-CPAP. The results were statistically evaluated, and p value <0.05 is considered significant. Out of 25 patients, 21 were male (84 %) and mean age was 49.2 ± 8.6 (range 31-66). At the pre-CPAP phase, mean sphincter pressure was 22.2 ± 1.2 (range 8-73), and mean DeMeester score was 18 ± 15.5 (range 0.2-57). At the post-CPAP, mean sphincter pressure was 22.9 ± 1.6 (range 9-95), and mean DeMeester score was 16.3 ± 14.8 (range 0.2-55). No significant difference (p > 0.05) was found comparing pre-CPAP and post-CPAP measurements. Objective criteria show that CPAP treatment does not cause reflux in patients with OSA. Unlike studies reported in the literature, this conclusion has been reached by pre- and post-CPAP assessments.

Gastric myoelectrical activity abnormalities of electrogastrography in patients with functional dyspepsia.

BACKGROUND/AIMS: Pathogenesis of functional dyspepsia (FD) is unclear and not well documented. Some gastric motility abnormalities have been reported to be important factors. Transcutaneous electrogastrography (EGG) is an experimental method that is used to assess FD. We aimed to compare FD patients with control subjects in terms of motility abnormalities according to the EGG results. MATERIALS AND METHODS: Thirty patients with FD and thirty control subjects were included. EGG was preprandially and postprandially performed. The recordings were analyzed and compared between the two groups. RESULTS: Mean ages of the cases and controls were 31.4±9.3 and 32.58±7.6 years, respectively. Female subjects constituted 80% of the FD group and 76.67% of the control group. In terms of the preprandial dominant frequency (DF), the FD group demonstrated lower incidence of normal subjects than the control group [13 (43.3%) and 22 (73.3%), respectively] and a higher incidence of bradygastria than the control group [17 (56.7%) and 8 (26.6%), respectively]. In the FD group, the rate of cases with normal postprandial DF was lower than that in the control group [10 (33.3%) and 23 (76.7%), respectively], whereas the rates of bradygastria [18 (60%) and 7 (23.3%), respectively] and tachygastria [2 (6.7%) and 0 (0%), respectively] were higher in the FD group (p<0.05). Preprandial and postprandial DF values were statistically significant in both groups. CONCLUSION: A high incidence of gastric motility and myoelectrical activity abnormalities was observed in patients with FD. EGG is an effective, reliable, and non-invasive method in differentiating the subgroups. After standardization of some parameters, EGG may be an essential and irreplaceable test to diagnose and follow-up FD patients with motor dysfunction.

Eltrombopag: How secure in triple therapy of HCV?

Triple therapy of hepatitis C usually leads to some hematological and dermatological side effects. Thrombocytopenia is one of the most common side effects that are encountered during triple therapy. Eltrombopag was approved for the treatment of patients with chronic hepatitis C and thrombocytopenia to allow the initiation and maintenance of interferon based therapies. During eltrombopag therapy, some side effects like headache, abdominal pain, and some complications such as portal vein thrombosis, deep vein thrombosis and arterial thrombosis were observed more frequently than placebo. We described here a patient who developing thrombosis secondary to eltrombopag in receiving triple therapy.

Acute pancreatitis following adult liver transplantation: A systematic review.

Although uncommon, acute pancreatitis is a well-recognized, but generally serious, complication following liver transplantation. In addition to being more prevalent in patients who underwent liver transplantation than in the general population, it has a more aggressive course and can be responsible for significant morbidity and mortality. The post-liver transplant population has altered anatomy, increased comorbidities, and requires a myriad of drugs. These characteristics make them different from the pre-transplant population. Despite their retrospective nature, prior studies have identified numerous etiological factors that are associated with an increased risk of acute pancreatitis following liver transplantation. These can be broadly classified into the following four categories: surgical and anatomical factors, infections, post-transplant management, and post-transplant complications. The aim of this systematic review is to assimilate the available information regarding acute pancreatitis following adult liver transplantation to describe the risk factors and natural history of the disease and to highlight possible areas for further investigation.

EUS-guided FNA of a portal vein thrombus in hepatocellular carcinoma.

Portal vein thrombosis is a relatively rare but well-known complication of cirrhosis that has a prevalence of between 1% and 5.7%. On the contrary, in case of hepatocellular carcinoma (HCC), it is a much more frequent complication. In this paper, we presented three cases that had liver cirrhosis, mass and portal vein thrombosis in liver. We were not able to diagnose the cases through imaging methods, laboratory results or histopathologically, however, they were diagnosed with endoscopic ultrasonography- fine needle aspiration EUS-FNA from portal vein thrombus.

Acromegaly can be associated with impairment of LES relaxation in the oesophagus.

INTRODUCTION: Although prolonged small intestine and colonic transit time has been demonstrated in acromegaly patients, the influence of acromegaly on oesophagus motility and the pathological mechanisms involved are still not clarified. We aimed to investigate manometric measurements to ascertain whether oesophagus motility is affected in active acromegaly patients. MATERIAL AND METHODS: The study was performed in an institutional referral centre at a tertiary care hospital. Twenty-three acromegaly patients (mean age 43.2 ± 13.2 years) and 25 sex- and age-matched healthy control subjects (mean age 48.6 ± 7.9 years) were recruited to a case-control study. Oesophageal manometry was performed using MMS (Medical Measurement Systems, Netherlands) Solar GI - Air Charged Intelligent Gastrointestinal Conventional Manometry. RESULTS: In manometric measurements the lower oesophageal sphincter pressure was 18 ± 7 mmHg in acromegaly patients and 15.6 ± 4.4 mm Hg in controls, and there was no significant difference (p = 0.17). The percentage of relaxation was 64.8% and 81.8%, respectively, and it was significantly lower in acromegaly patients than in controls (p < 0.001). Additionally, the duration of relaxation was found to be 4 ± 1.9 seconds and 5 ± 1.7 seconds in patients and controls, respectively (p = 0.049). CONCLUSIONS: Our study has demonstrated a significant reduction in the percentage and duration of lower oesophageal sphincter relaxation in oesophagus motility even in acromegaly patients without any gastrointestinal symptoms. Further clinical and pathophysiological studies are required to clarify the underlying mechanisms of gastrointestinal motility disorders in acromegaly.

Concurrent acute pancreatitis and pericardial effusion.

While pleural effusion and ascites secondary to acute pancreatitis are common, clinically relevant pericardial effusion and cardiac tamponade are observed rarely. In a study by Pezzilli et al., pleural effusion was noted in 7 of the 21 patients with acute pancreatitis whereas the authors detected pericardial effusion development in only three. The authors asserted that pleural effusion was associated with severe acute pancreatitis, while pericardial effusion and the severity of acute pancreatitis were not significantly related.

The importance of upper gastrointestinal endoscopy in morbidly obese patients.

BACKGROUND/AIMS: Obesity is an epidemic and its prevalence and number of patients underwent bariatric surgery continue to increase worldwide. This study aimed to evaluate endoscopic findings and co-morbidities, to investigate the prevalence of Helicobacter pylori (H. pylori) infection and the relationship between body mass index (BMI) and gastroesophageal sphincter incompetency in obese patients. MATERIALS AND METHODS: An upper gastrointestinal system endoscopy and mucosal sampling were performed in all patients hospitalized for bariatric surgery. Age, gender, BMI, co-morbidities and endoscopic findings were recorded. Gastroesophageal sphincter incompetency was classified according to Hill classification. The patients were divided into two groups: group I, endoscopically normal and group II, endoscopically abnormal. RESULTS: Total 127 patients were enrolled into prospective study. Of these, 93 (%73.2) were female and the mean age was 38.9±12.5 years (range: 16-68). Abnormal endoscopic findings and H. pylori were detected in 80.4% and 44.9% of patients, respectively. In group II, patients were older, BMI higher and H. pylori more prevalent (all statistically significant). Diabetes mellitus, hypertension and dyslipidemia were the most frequent common co-morbidities. Rate of multiple co-morbidities were more common in group II. Gastroesophageal sphincter incompetency in total group was observed in a rate of 46.5% and was weakly correlated with BMI. CONCLUSION: Four-fifths of obese patients have at least one endoscopic abnormal finding, three fourth at least one co-morbidity and half H. pylori positivity. Upper gastrointestinal system endoscopy should be performed routinely in all patients to predict and prevent complications following bariatric surgery.

Role of serum myeloperoxidase, CPK, CK-MB, and cTnI tests in early diagnosis of myocardial ischemia during ERCP.

BACKGROUND/AIMS: Some patients may experience retrosternal pain during ERCP, which may be a pioneer of a serious myocardial problem, and early diagnosis is very important for the prognosis and management. In the study, we aimed to investigate the role of serum cardiac biomarkers, such as myeloperoxidase (MPO), creatine phospokinase (CPK), creatine kinase- myocardial band (CK-MB), and cTnI, on early diagnosis of myocardial ischemia during endoscopic retrograde cholangio pancreaticograpy (ERCP) procedures. MATERIALS AND METHODS: In this prospective observational study, ERCP patients were separated into ischemic cardiac (n:48) and non-ischemic (n:76) groups. Serious cardiac, kidney, and liver disease patients were excluded from the study. Changes in electrocardigrapy (ECG), blood pressure, pulse rate, oxygen saturation, and serum MPO, CPK, CK-MB, and cTnI levels were investigated before and after the ERCP. Results were evaluated statistically (p<0.05). RESULTS: Mean age was 59.76±16.62 (55♀, 69♂). Only one patient had clinically unimportant retrosternal pain (0.8%). ST-elevation was detected in 10.4% (n:5), ST-depression in 12.5% (n:6), and negative-T in 31.3% (n:15) of ischemic patients during ERCP. Systolic and diastolic blood pressure and pulse rates in both groups and oxygen saturations in the ischemic group were reduced after ERCP. Significance was not detected with MPO and CPK tests. CK-MB levels showed an increase after the ERCP in the non-ischemic group (p<0.001). cTnI means were higher among the ischemics when pre- and post-ERCP periods (p:0.001) were compared. CONCLUSION: Clinically unimportant retrosternal pain, T negativity, and ST segment changes as well as reduced systolic, diastolic blood pressure, and heart rates can be seen during ERCP. MPO and CPK levels remain insignificant if myocardial injury does not develop. Increased CK-MB levels in non-ischemic patients and increased cTnI levels in ischemics may be seen.

Roles of serum and biliary CEA, CA19-9, VEGFR3, and TAC in differentiating between malignant and benign biliary obstructions.

BACKGROUND/AIMS: Despite the presence of many diagnostic methods, the differential diagnosis between benign and malignant biliary obstructions is still not easy. We aimed to evaluate the role of serum/biliary carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9), vascular endothelial growth factor receptor-3(VEGFR-3), and total antioxidant capacity (TAC) tests in this differential diagnosis. MATERIALS AND METHODS: Patients (n:225; 110♂, 115♀) with diagnosis of malignant (n:96) or benign (n:129) biliary obstruction were included in this cross-sectional study. Serum and biliary CEA, CA 19-9, VEGFR-3, and TAC tests were analyzed, statistics were obtained, and significance was defined as p<0.05. RESULTS: Mean age was 54.9±16.4 for the benign and 54.2±19.6 for the malignant group (p=0.89). Head of pancreas cancer (18.2%), cholangiocarcinoma (11.4%) and choledochal stone (48%) were the most common etiologies. The area under the curve (AUC)s by ROC analysis of serum/biliary CA 19-9, VEGFR-3, and TAC and serum CEA were 0.701/0.616, 0.622/0.663, 0.602/0.581, and 0713, respectively. Serum TAC had higher sensitivity (61.1%) and CEA had lower sensitivity (42.7%), whereas CEA had higher specificity (89.9%) and TAC had lower specificity (60.5%). In biliary tumor markers, CA 19-9 had higher sensitivity (74%) and VEGFR-3 had lower sensitivity (56.2%); however, VEGFR-3 had higher specificity (79.1%) and CA 19-9 had lower specificity (34.1%). Additionally, combination of serum CEA (p<0.001), CA 19-9 (p<0.001), VEGFR-3 (p<0.001), and biliary CA 19-9 (p=0.028) markers achieved 95% estimation probability, and the sensitivity, specificity, and accuracy were 88.5%, 45.7%, and 64%, respectively. CONCLUSION: Serum and biliary CEA, CA 19-9, VEGFR-3, and TAC tests would not be useful in the differentiation between malignant and benign biliary obstructions.

Endoscopic repair of duodenal perforation with over-the-scope clipping system and endoclips: a case report.

Herein, we present an endoscopic repair of iatrogenic duodenal perforation by over-the-scope clipping system (OTSC) and endoclips in an 84-year-old woman that occurred during linear endosonography (EUS) examination. One OTSC and 8 clips were used for repairing the perforation hole. After 3 days in the intensive care unit (ICU) by chest tube and without oral feeding, she was discharged from the hospital at 6. admission day, and she also had an acute coronary attack during 4. hospital day. OTSC and clipping devices are very useful for repair of iatrogenic perforations, especially in older patients who have comorbid diseases and who can not tolerate the surgery.

A randomized controlled trial of home monitoring versus hospitalization for mild non-alcoholic acute interstitial pancreatitis: a pilot study.

BACKGROUND/OBJECTIVES: Acute pancreatitis (AP) is a disease typically requiring in-hospital treatment. We conducted a trial to assess the feasibility of early discharge from the hospital for patients with mild non-alcoholic acute pancreatitis (NAAP). METHODS: Eighty-four patients with mild NAAP were randomized to home or hospital groups after a short hospital stay (≤24 h). AP was defined by the revised Atlanta criteria. Mild AP was defined as an Imrie score≤5 and a harmless acute pancreatitis score (HAPS)≤2 in the first 24-h of presentation. A nurse visited all patients in the home group on the 2nd, 3rd and 5th days. All patients presented for follow-up in clinic on the 7th, 14th, and 30th days. The primary outcome was the time to resolution of pain. Secondary outcomes evaluated included time to resumption of an oral diet, 30 day hospital readmission rate as well as the total costs associated with either approach to care. RESULTS: There was no difference between the groups with regards to demographics, prognostic severity scores, symptoms, and biliary findings. No patients developed organ failure, pancreatic necrosis, or died in either group. Time to the resolution of pain and resumption of solid food intake were similar. Three (3.6%) patients required readmission within 30 days, 1 from home and 2 from the hospital groups. The total cost was significantly less in home group ($139 ± 73 vs. $951 ± 715,p < 0.001). CONCLUSIONS: Mild NAAP can be safely treated at home with regular visits by a nurse under the supervision of a physician. Widespread adoption of this practice may result in large cost savings.

Esophagus motility in overt hypothyroidism.

PURPOSE: Gastrointestinal tract is one of the most affected systems in hypothyroidism. Despite decreased esophageal emptying, prolonged esophageal and gastric transit time have been indicated in previous reports, the mechanism of thyroid hormones activity and antibodies on the esophagus motility is not yet fully understood. This study was conducted to evaluate the esophagus motility by manometry in hypothyroid patients. METHODS: The study enrolled with 28 overt, newly diagnosed hypothyroid patients and 29 age- and sex-matched healthy controls. Twenty-one females and 7 males with overt hypothyroidism and 22 females and 7 males with healthy control subjects were recruited to study. Esophageal manometry was performed using MMS (Medical Measurement Systems bv. The Netherlands) Solar GI-Air-Charged Intelligent Gastrointestinal Conventional Manometry. RESULTS: The lower esophageal sphincter pressure (LESP) was 19.5 ± 6.5 mmHg in hypothyroid patients and 17.48 ± 4.65 mmHg in controls, and there was no significant difference (p = 0.18). Percentage of relaxation was 61.5 and 80.9 %, and it was significantly lower in hypothyroid patients than controls (p < 0.001). Additionally, duration of relaxation was found 3.85 ± 2.3 and 5.5 ± 2.28 s in patients and controls, respectively (p = 0.009). In patient group, LESP was positively correlated with fT3 (p = 0.033), and the duration of the contraction was negatively correlated with fT4 (p = 0.044). CONCLUSION: In this study, we observed that hypothyroid state can affect esophagus motility via shortened duration of relaxation and reduced percentage of relaxation even if in patients without any gastrointestinal symptoms. Further studies are needed to clarify the effect of thyroid hormones on esophagus motility.