Gastroprotection in patients on antiplatelet and/or anticoagulant therapy: a position paper of National Association of Hospital Cardiologists (ANMCO) and the Italian Association of Hospital Gastroenterologists and Endoscopists (AIGO).

Aspirin and P2Y12 receptor antagonists are widely used across the spectrum of cardiovascular and cerebrovascular diseases. Gastrointestinal complications, including ulcer and bleeding, are relatively common during antiplatelet treatment and, therefore, concomitant proton pump inhibitor (PPI) treatment is often prescribed. However, potential increased risk of cardiovascular events has been suggested for PPIs, and, in recent years, it has been discussed whether these drugs may reduce the cardiovascular protection by aspirin and, even more so, clopidogrel. Indeed, pharmacodynamic and pharmacokinetic studies suggested an interaction through hepatic CYP2C19 between PPIs and clopidogrel, which could translate into clinical inefficacy, leading to higher rates of cardiovascular events. The FDA and the EMA sent a warning in 2010 discouraging the concomitant use of clopidogrel with omeprazole or esomeprazole. In addition, whether the use of PPIs may affect the clinical efficacy of the new P2Y12 receptor antagonists, ticagrelor and prasugrel, remains less known. According to current guidelines, PPIs in combination with antiplatelet treatment are recommended in patients with risk factors for gastrointestinal bleeding, including advanced age, concurrent use of anticoagulants, steroids or non-steroidal anti-inflammatory drugs, and Helicobacter pylori infection. Like vitamin K antagonists (VKAs), DOACs can determine gastrointestinal bleeding. Results from both randomized clinical trials and observational studies suggest that high-dose dabigatran (150 mg bid), rivaroxaban and high-dose edoxaban (60 mg daily) are associated with a higher risk of GI bleeding as compared with apixaban and warfarin. In patients taking oral anticoagulant with GI risk factor, PPI could be recommended, even if usefulness of PPIs in these patients deserves further data. Helicobacter pylori should always be searched, and treated, in patients with history of peptic ulcer disease (with or without complication). Given the large number of patients treated with antithrombotic drugs and PPIs, even a minor reduction of platelet inhibition or anticoagulant effect potentially carries a considerable clinical impact. The present joint statement by ANMCO and AIGO summarizes the current knowledge regarding the widespread use of platelet inhibitors, anticoagulants, and PPIs in combination. Moreover, it outlines evidence supporting or opposing drug interactions between these drugs and discusses consequent clinical implications.

[ANMCO/AIGO Intersocietary consensus document: Gastroprotection in patients receiving antiplatelet and/or anticoagulant drugs]. / Documento di consenso intersocietario ANMCO/AIGO: Gastroprotezione nei pazienti in terapia antiaggregante e/o anticoagulante.

Aspirin and P2Y12 receptor antagonists are widely used across the spectrum of cardiovascular and cerebrovascular diseases. Gastrointestinal complications, including ulcer and bleeding, are relatively common during antiplatelet treatment and, therefore, concomitant proton pump inhibitor (PPI) treatment is often prescribed. However, potential increased risk of cardiovascular events has been suggested for PPIs, and, in recent years, it has been discussed whether these drugs may reduce the cardiovascular protection by aspirin and, even more so, clopidogrel. Indeed, pharmacodynamic and pharmacokinetic studies suggested an interaction through CYP2C19 between PPIs and clopidogrel, which could translate into clinical inefficacy, leading to higher rates of cardiovascular events. The Food and Drug Administration and the European Medicines Agency sent a warning in 2010 discouraging the concomitant use of clopidogrel with omeprazole or esomeprazole. In addition, whether the use of PPIs may affect the clinical efficacy of the new P2Y12 receptor antagonists, ticagrelor and prasugrel, remains less known. According to current guidelines, PPIs in combination with antiplatelet treatment are recommended in patients with risk factors for gastrointestinal bleeding, including advanced age, concurrent use of anticoagulants, steroids or non-steroidal anti-inflammatory drugs, and Helicobacter pylori infection. Like traditional anticoagulants, novel oral anticoagulants may cause gastrointestinal bleeding. Results from both randomized clinical trials and observational studies suggest that high-dose dabigatran (150 mg bid), rivaroxaban and high-dose edoxaban (60 mg daily) are associated with a higher risk of gastrointestinal bleeding as compared with warfarin. However, the usefulness of PPIs in patients receiving these anticoagulants deserves to be further demonstrated. Given the large number of patients treated with antithrombotic drugs and PPIs, even a minor reduction of platelet inhibition or anticoagulant effect potentially carries a considerable clinical impact. The present joint statement by ANMCO and AIGO summarizes the current knowledge regarding the widespread use of platelet inhibitors, anticoagulants, and PPIs in combination. Moreover, it outlines evidence supporting or opposing drug interactions between these drugs and discusses consequent clinical implications.

Efficacy and Safety of Oral Beclomethasone Dipropionate in Ulcerative Colitis: A Systematic Review and Meta-Analysis.

BACKGROUND AND AIM: We performed a systematic review and meta-analysis of all the available evidence comparing efficacy and safety of oral prolonged released beclomethasone dipropionate (BDP) to active oral controls in patients with mild-to-moderate ulcerative colitis (UC). A subgroup-analysis compared the effectiveness of BDP and 5-ASA. METHODS: Literature research was performed in different databases, as well as manual search to identify abstracts from international meetings with data not included in extensive publications. Experts in the field and companies involved in BDP development and manufacture were contacted to identify unpublished studies used for registration purposes. Dichotomous data were pooled to obtain odds ratio meta-analysis. RESULTS: Five randomized controlled trials that compared oral BDP 5mg/day vs. all oral active controls in treating UC were identified as eligible. Efficacy and safety have been addressed after 4-week treatment period. One study evaluated efficacy and safety of BDP vs. prednisone and 4 of BDP vs. 5-ASA. Treatment with oral BDP 5 mg/day induces a significant better clinical response compared to oral 5-ASA (OR 1.86, 95% CI = 1.23-2.82, P = 0.003). The effect is detectable even when the comparison to prednisone is added (OR 1.41, 95% CI = 1.03-1.93, P = 0.03). Data on remission indicate that the potential clinical efficacy of BDP may be better than 5-ASA (OR 1.55, 95% CI = 1.00-2.40, P = 0.05). This difference is lost when the comparison with prednisone is added (OR 1.30, 95% CI = 0.76-2.23, P = 0.34). The safety analysis showed no differences between BDP and 5-ASA (OR 0.55, 95% CI = 0.24-1.27, P = 0.16). The lack of difference is maintained even when the study with prednisone is added (OR 0.67, 95% CI = 0.44-1.01, P = 0.06). However, the trend of difference is clear and indicates a more favourable safety profile of BDP compared to 5-ASA and PD. CONCLUSIONS: Oral prolonged release BDP showed a superior efficacy vs. oral 5-ASA in inducing clinical improvement of mild-to-moderate UC with a similar safety profile.

Quality of bowel cleansing in hospitalized patients undergoing colonoscopy: A multicentre prospective regional study.

BACKGROUND: Quality of bowel cleansing in hospitalized patients undergoing colonoscopy is often unsatisfactory. No study has investigated the inpatient or outpatient setting as cause of inadequate cleansing. AIMS: To assess degree of bowel cleansing in inpatients and outpatients and to identify possible predictors of poor bowel preparation in the two populations. METHODS: Prospective multicentre study on consecutive colonoscopies in 25 regional endoscopy units. Univariate and multivariate analysis with odds ratio estimation were performed. RESULTS: Data from 3276 colonoscopies were analyzed (2178 outpatients, 1098 inpatients). Incomplete colonoscopy due to inadequate cleansing was recorded in 369 patients (11.2%). There was no significant difference in bowel cleansing rates between in- and outpatients in both colonic segments. In the overall population, independent predictors of inadequate cleansing both at the level of right and left colon were: male gender (odds ratio, 1.20 [1.02-1.43] and 1.27 [1.05-1.53]), diabetes mellitus (odds ratio, 2.35 [1.68-3.29] and 2.12 [1.47-3.05]), chronic constipation (odds ratio, 1.60 [1.30-1.97] and 1.55 [1.23-1.94]), incomplete purge intake (odds ratio, 2.36 [1.90-2.94] and 2.11 [1.68-2.65]) and a runway time >12h (odds ratio, 3.36 [2.40-4.72] and 2.53 [1.74-3.67]). CONCLUSIONS: We found no difference in the rate of inadequate bowel preparation between hospitalized patients and outpatients.

Transition of gastroenterological patients from paediatric to adult care: A position statement by the Italian Societies of Gastroenterology.

In 2013, four Italian Gastroenterological Societies (the Italian Society of Paediatric Gastroenterology, Hepatology and Nutrition, the Italian Society of Hospital Gastroenterologists and Endoscopists, the Italian Society of Endoscopy, and the Italian Society of Gastroenterology) formed a joint panel of experts with the aim of preparing an official statement on transition medicine in Gastroenterology. The transition of adolescents from paediatric to adult care is a crucial moment in managing chronic diseases such as celiac disease, inflammatory bowel disease, liver disease and liver transplantation. Improved medical treatment and availability of new drugs and surgical techniques have improved the prognosis of many paediatric disorders, prolonging survival, thus making the transition to adulthood possible and necessary. An inappropriate transition or the incomplete transmission of data from the paediatrician to the adult Gastroenterologist can dramatically decrease compliance to treatment and prognosis of a young patient, particularly in the case of severe disorders. For these reasons, the Italian gastroenterological societies decided to develop an official shared transition protocol. The resulting document discusses the factors influencing the transition process and highlights the main points to accomplish to optimize compliance and prognosis of gastroenterological patients during the difficult transition from childhood to adolescence and adulthood.

Incidence and distribution of coeliac disease in Campania (Italy): 2011-2013.

BACKGROUND: There exists a wide variation in the reported incidence of coeliac disease in recent decades. We aimed to evaluate the incidence rate of coeliac diagnoses performed in an Italian region, Campania, between 2011 and 2013 and its variation therein. METHODS: All coeliac diagnoses made from 2011 to 2013 and registered within the Campania coeliac disease register (CeliacDB) were identified. Incidence rates were analysed by sex, age and province of residence, with a Poisson model fitted to determine incidence rate ratios. RESULTS: We found 2049 coeliac disease diagnoses registered in the CeliacDB between 2011 and 2013; 1441 of these patients were female (70.4%) and 1059 were aged less than 19 years (51.7%). The overall incidence of coeliac disease in Campania was 11.8 per 100,000 person-years (95% CI 11.3-12.3) during the study period, with marked variation by age [27.4 per 100,000 person-years (95% CI 25.8-29.1) in children under 19 years of age and 7.3 per 100,000 (95% CI 6.8-7.8) in adults] and sex [16.1 per 100,000 person-years in females (95% CI 15.3-16.9) and 7.2 per 100,000 person-years in males (95% CI 6.6-7.8)]. Coeliac disease incidence was roughly similar in Naples, Salerno, Caserta and Avellino, but about half in Benevento. More than 80% of our study population was diagnosed by the combination of positive antitransglutaminase IgA and Marsh 3. More than half of the patients were symptomatic at the time of coeliac disease diagnosis (39.7% had a classical presentation and 21.1% a non-classical one according to the Oslo definition). CONCLUSIONS: Coeliac disease incidence was roughly similar among Campania provinces, except in Benevento where it was about half, probably due to less awareness of coeliac disease in this area. The incidence of coeliac disease in Campania appears to be lower than that reported by most of the previous literature, suggesting the necessity of new coeliac awareness programmes.

Electrochemiluminescence immunoassay method underestimates cortisol suppression in ulcerative colitis patients treated with oral prednisone.

AIM: To evaluate cortisolemia by using conventional electrochemiluminescence immunoassay (ECLIA) method compared to liquid chromatography-tandem mass spectrometry (LC-MS/MS) method in active ulcerative colitis (UC) patients treated with oral prednisone (PD). METHODS: Twenty patients (12 males) with acute relapse of UC started oral PD at a dose of 40 mg once a day, tapered of 10 mg every 2 wk. When a stable 2-wk daily dose of 30 mg was reached, blood samples for cortisol levels' measurement were drawn in the morning in fasting conditions to determine circulating cortisol by LC-MS/MS and ECLIA assay. RESULTS: Median interquartile range cortisolemia with ECLIA and LC-MS/MS method was 54.1 (185.8) nmol/L and 32.1 (124.0) nmol/L, respectively (P < 0.001). The within-patient median differences between the two methods was 23.2 (40.6) nmol/L, with higher cortisol levels for the ECLIA method. The estimated geometric mean ratio between methods was 1.85 (95%CI: 2.39-1.43) considering all data or 1.58 (95%CI: 2.30-1.09) considering only data above the limit of quantification (n = 12). The 95%CIs of the geometric mean ratio between methods confirm a statistically significant difference. CONCLUSION: Blood cortisol levels detected with ECLIA method seems to be higher than the ones measured by LC-MS/MS, indicating a possible overestimation of them in patients treated with PD. Therefore, the cortisol suppression in patients under treatment with oral PD should not be measured using ECLIA method.

A simplified clinical risk score predicts the need for early endoscopy in non-variceal upper gastrointestinal bleeding.

BACKGROUND: Pre-endoscopic triage of patients who require an early upper endoscopy can improve management of patients with non-variceal upper gastrointestinal bleeding. AIMS: To validate a new simplified clinical score (T-score) to assess the need of an early upper endoscopy in non variceal bleeding patients. Secondary outcomes were re-bleeding rate, 30-day bleeding-related mortality. METHODS: In this prospective, multicentre study patients with bleeding who underwent upper endoscopy were enrolled. The accuracy for high risk endoscopic stigmata of the T-score was compared with that of the Glasgow Blatchford risk score. RESULTS: Overall, 602 patients underwent early upper endoscopy, and 472 presented with non-variceal bleeding. High risk endoscopic stigmata were detected in 145 (30.7%) cases. T-score sensitivity and specificity for high risk endoscopic stigmata and bleeding-related mortality was 96% and 30%, and 80% and 71%, respectively. No statistically difference in predicting high risk endoscopic stigmata between T-score and Glasgow Blatchford risk score was observed (ROC curve: 0.72 vs. 0.69, p=0.11). The two scores were also similar in predicting re-bleeding (ROC curve: 0.64 vs. 0.63, p=0.4) and 30-day bleeding-related mortality (ROC curve: 0.78 vs. 0.76, p=0.3). CONCLUSIONS: The T-score appeared to predict high risk endoscopic stigmata, re-bleeding and mortality with similar accuracy to Glasgow Blatchford risk score. Such a score may be helpful for the prediction of high-risk patients who need a very early therapeutic endoscopy.

The effectiveness of current acute variceal bleed treatments in unselected cirrhotic patients: refining short-term prognosis and risk factors.

OBJECTIVES: The mortality from esophageal variceal hemorrhage in liver cirrhosis patients remains approximately 15-20%. Predictors of short-term outcomes, such as the hepatic venous pressure gradient, are often unavailable in the acute setting. Clinical variables seem to have a similar predictive performance, but some variables including active bleeding during endoscopy have not been reevaluated after the utilization of endoscopic banding as endoscopic procedure. In addition, patients with severe liver failure are often excluded from clinical trials. The aim of this study was to prospectively reevaluate the risk factors affecting a 5-day failure after acute variceal bleeding in unselected cirrhotic patients, managed with the current standard treatment using vasoactive drugs, band ligation, and antibiotics. METHODS: One hundred and eighty five patients with liver cirrhosis and variceal bleeding admitted from January 2010 to July 2011 were evaluated. RESULTS: Hepatocellular carcinoma was present in 28.1% of cases and portal vein thrombosis (PVT) was present in 17.3% of cases. Band ligation was feasible in 92.4% of cases. Five-day failure occurred in 16.8% of cases; 12 patients (6.5%) experienced failure to control bleeding or early rebleeding, and 66.7% of patients died within 5 days. The overall 5-day mortality rate was 14.6%. By multivariate analysis, we determined that Child-Pugh class C, a white blood cell count over 10 × 10(9)/l, and the presence of PVT were the only independent predictors of the 5-day failure. CONCLUSIONS: The prognosis of a consistent group of liver cirrhosis patients with variceal bleeding remains poor. The current treatment is highly effective in controlling variceal bleeding, but mortality is related mainly to the severity of liver failure.

Helicobacter pylori infection in bleeding peptic ulcer patients after non-steroidal antiinflammatory drug consumption.

AIM: To establish the prevalence of Helicobacter pylori (H. pylori) infection in patients with a bleeding peptic ulcer after consumption of non-steroidal antiinflammatory drugs (NSAIDs). METHODS: A very early upper endoscopy was performed to find the source of upper gastrointestinal bleeding and to take biopsy specimens for analysis of H. pylori infection by the rapid urease (CLO) test, histological examination, and bacterial culture. IgG anti-CagA were also sought. The gold standard for identifying H. pylori infection was positive culture of biopsy specimens or contemporary positivity of the CLO test and the presence of H. pylori on tissue sections. RESULTS: Eighty patients, 61 males (76.3%), mean age 61.2 ± 15.9 years, were consecutively enrolled. Forty-seven (58.8%) patients occasionally consumed NSAIDs, while 33 (41.3%) were on chronic treatment with low-dose aspirin (LD ASA). Forty-four (55.0%) patients were considered infected by H. pylori. The infection rate was not different between patients who occasionally or chronically consumed NSAIDs. The culture of biopsy specimens had a sensitivity of 86.4% and a specificity of 100%; corresponding figures for histological analysis were 65.9% and 77.8%, for the CLO test were 68.2% and 75%, for the combined use of histology and the CLO test were 56.8% and 100%, and for IgG anti-CagA were 90% and 98%. The highest accuracy (92.5%) was obtained with the culture of biopsy specimens. CONCLUSION: Patients with a bleeding peptic ulcer after NSAID/LD ASA consumption frequently have H. pylori infection. Biopsy specimen culture after an early upper gastrointestinal tract endoscopy seems the most efficient test to detect this infection.

Antiestrogenic and antigenotoxic activity of bee pollen from Cystus incanus and Salix alba as evaluated by the yeast estrogen screen and the micronucleus assay in human lymphocytes.

The estrogenic/antiestrogenic activity and the genotoxicity/antigenotoxicity of bee pollen from Salix alba L. and Cystus incanus L. and its derivative extracts in yeast and human cells was investigated. All samples showed a marked inhibitory effect on the activity of the natural estrogen 17 beta-estradiol (higher than 90% for extracts 2) and failed to cause estrogenic activity and chromosome damage. At least one preparation from each species showed a marked antigenotoxic effect against the action of the anticancer drugs mytomicin C, bleomycin, and vincristine. Bee pollens from C. incanus and S. alba were found to be neither genotoxic nor estrogenic as well as effective estrogen inhibitors, and able to reduce the chromosome damage induced by the three cancer drugs used, thus supporting their use as a safe food supplement and future chemoprotective/chemopreventive agents.

Surgical treatment of non-variceal upper gastrointestinal bleeding: our experience with 1482 patients.

We retrospectively evaluated the medical records of patients admitted to the U.O.C. of General and Emergency Surgery with Surgical and Polyspecialistic Observation of the Emergency Unit of A.O.R.N. A. Cardarelli of Naples for non-variceal upper gastrointestinal bleeding from 2003 to 2006. All data regarding patients submitted to surgery for non-variceal upper gastrointestinal bleeding were collected including the number of patients submitted to surgery after failure of the endoscopic procedure, the diseases most frequently requiring surgery, the endoscopic and surgical procedures most frequently used, and the reasons that prompted the surgical procedure. Of 1482 patients admitted for non-variceal upper gastrointestinal bleeding the lesions that most frequently required surgery were peptic ulcer disease complicated by bleeding in 31 patients (70.5%) and cancer in 13 (29.5%). The most frequent surgical procedure was subtotal gastrectomy (17 patients [38.6%]), followed by direct haemostasis of the ulcer (13 patients [29.5%]), total gastrectomy (11 patients [25%]), and ulcer excision (3 patients [6.9%]). Subtotal or total gastrectomy is the surgical procedure of choice in patients with non-variceal upper gastrointestinal bleeding after failure of endoscopic treatment. The indication for gastrectomy should be determined on the basis of the patient's haemodynamic condition.

In-hospital mortality in non-variceal upper gastrointestinal bleeding Forrest 1 patients.

OBJECTIVE: Non-variceal upper gastrointestinal bleeding (NVUGIB) is recognized world-wide as a common cause of emergency hospitalization, and it often represents a life-threatening event. The purpose of this prospective study was to assess in-hospital mortality in NVUGIB Forrest 1 patients admitted to the emergency unit owing to active bleeding. MATERIAL AND METHODS: We enrolled all patients consecutively admitted to the emergency unit for NVUGIB, acutely bleeding at endoscopy (spurting or oozing). Demographic characteristics, clinical and biochemical parameters, endoscopic findings and treatments were evaluated. RESULTS: Of a total of 142 patients (98 M (69%), mean age+/-SD=66+/-14 years), spurting (16 (11.3%)) and oozing (126 (88.7%)) were identified. All patients received endoscopic treatment within 6 h of admission and were managed according to the guidelines. Seventeen (12%) patients suffered rebleeding, 4 patients (2.8%) required surgery to stop the bleeding, and 8 (5.6%) died during hospitalization (4 within 5 days and the remainder within 24 days of admission) - 3 as a consequence of bleeding (2.1%) and 5 of non-surgical complications (3.5%). Cox regression analysis showed that the lesions in more than one segment of the esophagogastroduodenal tract (p=0.008, hazard ratio (95% CI)=7.623 (1.680-34.600)) and the number of blood units transfused during the first 48 h of hospitalization (p=0.038, 2.075 (1.041-4.135)) were predictive of in-hospital death. CONCLUSIONS: In Forrest 1 patients given rapid endoscopic treatment, in-hospital mortality seems to be related to the contemporaneous presence of bleeding and non-bleeding lesions in more than one segment of the esophagogastroduodenal tract and the number of blood units transfused during the first 48 h of hospitalization.

Prophylaxis with meropenem of septic complications in acute pancreatitis: a randomized, controlled trial versus imipenem.

OBJECTIVES: Prophylactic antibiotics are helpful in decreasing the incidence of septic complications in acute pancreatitis. The aim of this study was to compare the efficacy of meropenem, a new carbapenem antibiotic, with that of imipenem, which is the standard prophylactic treatment in patients with severe acute pancreatitis. METHODS: One hundred seventy-six patients with necrotizing pancreatitis were prospectively randomized to prophylactic treatment with 0.5 g meropenem t.i.d. intravenously or 0.5 g imipenem q.i.d. intravenously. The occurrence of infection of pancreatic necrosis, rate of extrapancreatic infections, systemic and local complications, need for surgery, mortality rate, and length of hospitalization were recorded for each group. When a septic complication of pancreatic necrosis was suspected, fine needle aspiration with cultures of the sample was performed. Surgery was performed in cases of verified infected necrosis. CONCLUSION: No difference was observed between patients treated with meropenem and those treated with imipenem in terms of incidence of pancreatic infection (11.4% versus 13.6%) and extrapancreatic infections (21.6% versus 23.9%) and clinical outcome. Meropenem is as effective as imipenem in preventing septic complications of patients with severe acute pancreatitis.