COVID-19 and Gastrointestinal Disease: Implications for the Gastroenterologist.

BACKGROUND: COVID-19 was initially considered a respiratory disease but the SARS-CoV-2 virus can lead to serious systemic consequences affecting major organs including the digestive system. SUMMARY: This review brings new clinically important information for the gastroenterologist. This includes: the mechanisms of tissue damage seen with the SARS-CoV-2 virus; the consequences of immunosuppression in patients with inflammatory bowel disease (IBD) and chronic liver disease with the additional risks of decompensation in patients with cirrhosis; the impact of COVID-19 on gastrointestinal emergencies, on gastrointestinal endoscopy, diagnosis and treatments. These highlight the need to understand the clinical pharmacology, toxicology and therapeutic implications of drugs commonly used by gastroenterologists and their links with COVID-19. Key Messages: Any part of the digestive system may be affected by the SARS-CoV-2 virus, and those with pre-existing disease are at greatest risk of adverse outcomes. The risk for drug-drug interactions is considerable in patients seriously ill with COVID-19 who often require mechanical ventilation and life support. Some repurposed drugs used against SARS-CoV-2 can cause or aggravate some of the COVID-19-related gastrointestinal symptoms and can also induce liver injury. Ongoing clinical studies will hopefully identify effective drugs with a more favourable risk-benefit ratio than many initially tried treatments.

Mechanisms of Damage to the Gastrointestinal Tract From Nonsteroidal Anti-Inflammatory Drugs.

Nonsteroidal anti-inflammatory drugs (NSAIDs) can damage the gastrointestinal tract, causing widespread morbidity and mortality. Although mechanisms of damage involve the activities of prostaglandin-endoperoxide synthase 1 (PTGS1 or cyclooxygenase [COX] 1) and PTGS1 (COX2), other factors are involved. We review the mechanisms of gastrointestinal damage induction by NSAIDs via COX-mediated and COX-independent processes. NSAIDs interact with phospholipids and uncouple mitochondrial oxidative phosphorylation, which initiates biochemical changes that impair function of the gastrointestinal barrier. The resulting increase in intestinal permeability leads to low-grade inflammation. NSAID inhibition of COX enzymes, along with luminal aggressors, results in erosions and ulcers, with potential complications of bleeding, protein loss, stricture formation, and perforation. We propose a model for NSAID-induced damage to the gastrointestinal tract that includes these complex, interacting, and inter-dependent factors. This model highlights the obstacles for the development of safer NSAIDs.

Revisiting Montreal: New Insights into Symptoms and Their Causes, and Implications for the Future of GERD.

The Montreal definition of gastroesophageal reflux disease (GERD) provided a rationale for acid suppression medication without investigation, thus enhancing the management of the substantial symptom burden in these patients. Increased proton-pump inhibitor use has also highlighted their limitations, with one third of "typical" symptoms known to be refractory. Most refractory symptoms are ascribed to reflux hypersensitivity (RH) and functional heartburn (FH). RH may be caused by impaired esophageal mucosal barrier function and sensitization of peripheral esophageal receptors. Central sensitization may also contribute to the perception of non-pathologic reflux in RH, and the perception of physiological stimuli in FH. Importantly, mechanisms underlying GERD, RH, and FH are (in theory) not mutually exclusive, further complicating patient management. Methods used to distinguish GERD from RH and FH are impractical for use in epidemiological studies and pragmatic care and may have limited diagnostic accuracy. This is impeding accurate prevalence estimates and risk factor determination and the identification of new therapies. Direct assessment of mucosal barrier function by measuring impedance is a promising candidate for improved diagnosis. Ultimately though the concept of GERD as a composite, symptom-based entity needs re-evaluation, so that new understandings of upper GI symptoms can direct more precise management.

Interplay between colonic inflammation and tachykininergic pathways in the onset of colonic dysmotility in a mouse model of diet-induced obesity.

BACKGROUND: The murine model of high fat diet (HFD)-induced obesity is characterized by an increment of intestinal permeability, secondary to an impairment of mucosal epithelial barrier and enteric inflammation, followed by morphofunctional rearrangement of the enteric nervous system. The present study investigated the involvement of abdominal macrophages in the mechanisms underlying the development of enteric dysmotility associated with obesity. METHODS: Wild type C57BL/6J mice were fed with HFD (60% kcal from fat) or normocaloric diet (NCD, 18% kcal from fat) for 8 weeks. Groups of mice fed with NCD or HFD were treated with clodronate encapsulated into liposomes to deplete abdominal macrophages. Tachykininergic contractions, elicited by electrical stimulation or exogenous substance P (SP), were recorded in vitro from longitudinal muscle colonic preparations. Substance P distribution was examined by confocal immunohistochemistry. The density of macrophages in the colonic wall was examined by immunohistochemical analysis. Malondialdehyde (MDA, colorimetric assay) and IL-1ß (ELISA assay) levels were also evaluated. RESULTS: MDA and IL-1ß levels were increased in colonic tissues from HFD-treated animals. In colonic preparations, electrically evoked tachykininergic contractions were enhanced in HFD mice. Immunohistochemistry displayed an increase in substance P immunoreactivity in myenteric ganglia, as well as in the muscular layers of colonic cryosections from obese mice. Macrophage depletion in HFD mice was associated with a significant reduction of colonic inflammation. In addition, the decrease in macrophage density attenuated the morphofunctional alterations of tachykininergic pathways observed in obese mice. CONCLUSION: Obesity elicited by HFD determines a condition of colonic inflammation, followed by a marked rearrangement of motor excitatory tachykininergic enteric nerves. Macrophage depletion counteracted the morphofunctional changes of colonic neuromuscular compartment, suggesting a critical role for these immune cells in the onset of enteric dysmotility associated with obesity.

The potential role of potassium-competitive acid blockers in the treatment of gastroesophageal reflux disease.

PURPOSE OF REVIEW: Gastroesophageal reflux disease (GERD) is primarily a motor disorder, but its pathogenesis is multifactorial. Although gastric acid secretion is usually normal in GERD patients, treatment with proton pump inhibitors (PPIs) has become the standard of care, despite increasing awareness of their shortcomings. In this article, a new class of antisecretory drugs (namely potassium-competitive acid blockers, P-CABs), developed to overcome these limitations, is discussed. RECENT FINDINGS: P-CABs block the K exchange channel of the proton pump, resulting in rapid, competitive, reversible inhibition of acid secretion. These drugs offer a more rapid elevation of intragastric pH than PPIs, while maintaining similar antisecretory effect, the duration of which is dependent on half-life and can be prolonged with extended release formulations. Thus, P-CABs offer advances in the treatment of GERD including rapid heartburn relief, faster and more reliable healing of severe grades of erosive esophagitis, as a consequence of better control of nighttime acid secretion than PPIs. SUMMARY: P-CABs overcome many of the drawbacks of PPIs. The unique antisecretory effects of vonoprazan might be especially useful in the long-term treatment of patients with Barrett's esophagus.

Gastric cancer prevention targeted on risk assessment: Gastritis OLGA staging.

Gastric cancer (GC) ranks among the most lethal epithelial malignancies, and its striking mortality rate prompts a global prevention strategy. Helicobacter pylori (H. pylori) gastritis is the main GC promoter, and the 2014 Global Kyoto conference recognized H. pylori gastritis as a (treatable) infectious disease. It is therefore plausible that any large-scale intervention for H. pylori eradication would result in cleansing the world of the fifth cause of cancer-related death. Atrophic gastritis is the cancerization field in which GCs (both intestinal and diffuse histotypes) mainly develop. Discontinuing the inflammatory cascade triggered by H. pylori is tantamount to preventing GC. For patients (still infected or eradicated) who have already developed gastric atrophy, the severity/topography of the atrophic changes correlates with their cancer risk. Gastritis OLGA (Operative Link for Gastritis Assessment) staging consistently ranks the atrophy-associated cancer risk, providing a solid clinical/biological rationale for establishing patient-specific surveillance programs. By combining primary and secondary prevention strategies, gastric cancer is a preventable disease.

Antiemetic Drug Use in Children: What the Clinician Needs to Know.

Vomiting is not only unpleasant for both children and families, but can lead to frequent hospital admission. The persistent vomiting hampers oral intake and increases the risk of dehydration, so the proper use of antiemetic drugs can be useful. The pharmacological treatment of vomiting in children remains a challenge for the pediatrician because several antiemetics are prescribed as "off-label," outside their authorized drug label. Domperidone and ondansetron are the most commonly known antiemetic drugs. A single oral dose of ondansetron has been shown to reduce the risk of recurrent vomiting, the need for intravenous fluids, and hospital admissions in children with acute gastroenteritis. There is enough evidence to support ondansetron administration in children, so the clinical use can be defined as "off-label/on evidence." This review aims to provide an overview of therapeutic use, safety, and main pharmacological properties of antiemetic drugs in children. A comprehensive search of published literature using the PubMed MEDLINE database was carried out to identify all articles published in English from 1998 to February 2018. At present time, the "off-label/on-evidence" use of some antiemetics could improve the success rate of oral rehydration therapy in pediatric emergency settings and to change the management of vomiting with the prevention of the complications.

Drug-Induced Small Bowel Injury: a Challenging and Often Forgotten Clinical Condition.

PURPOSE OF REVIEW: Most drugs are given by the oral route. Oral intake allows direct contact between the drug and the entire GI tract mucosa, exposing it to potential topical damage until absorption. Medication-induced GI symptoms and lesions are therefore commonly encountered in clinical practice. This review will examine the most common drugs or classes of drugs affecting small bowel function and/or structure. RECENT FINDINGS: Since non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely used medicines, NSAID enteropathy is highly prevalent and brings about considerable morbidity. Antimicrobials and proton-pump inhibitors profoundly modify intestinal microbiota, affecting gut sensory and motor functions, while other drugs (like iron and gold derivatives) impair intestinal permeability. Olmesartan (and likely ACE inhibitors) induce villous atrophy and consequent malabsorption. Mycophenolate mofetil, cancer chemotherapeutic agents, and immune checkpoint inhibitors cause intestinal inflammation, abdominal pain, and diarrhea. Potassium chloride supplements may induce small bowel ulceration, stenosis, and perforation while the cotraceptive pill and anticoagulants are associated with intestinal ischemia and spontaneous intramural hematoma, respectively. In clinical practice, a deep knowledge of clinical pharmacology and toxicology and a high degree of suspicion of drug-related adverse events are mandatory. Only then, the practicing physician will be able to diagnose medication-induced small bowel lesions correctly and will implement the best strategies to treat them.

Rifaximin Reduces the Number and Severity of Intestinal Lesions Associated With Use of Nonsteroidal Anti-Inflammatory Drugs in Humans.

The intestinal microbiota might contribute to enteropathy associated with use of nonsteroidal anti-inflammatory drugs (NSAIDs), but there have been few human studies of this association. We performed a placebo-controlled study to determine whether a delayed-release antibiotic formulation (rifaximin-extended intestinal release [EIR]) prevents the development of intestinal lesions in subjects taking daily NSAIDs. Sixty healthy volunteers (median age, 26 y; 42% female) were given the NSAID diclofenac (75 mg twice daily) plus omeprazole (20 mg once daily), and either rifaximin-EIR (400 mg) or placebo, twice daily for 14 days. Subjects were assessed by videocapsule endoscopy at baseline and after 2 weeks of treatment. The primary end point was the proportion of subjects developing at least 1 small-bowel mucosal break at week 2. Secondary end points were the change in the mean number of mucosal lesions and the number of subjects with large erosions and/or ulcers after 14 days of exposure. We detected mucosal breaks in 20% of subjects given rifaximin and in 43% of subjects given placebo (P = .05 in the post hoc sensitivity analysis). None of the subjects in the rifaximin group developed large lesions, compared with 9 subjects in the placebo group (P < .001). Our findings indicate that intestinal bacteria contribute to the development of NSAID-associated enteropathy in human beings. Clinical trial no: EudraCT 2013-000730-36.

Searching for a definition for pharmacologically refractory constipation: A systematic review.

BACKGROUND AND AIM: Surgery and other non-pharmacological treatments such as sacral nerve stimulation are used for the treatment of difficult-to-treat chronic constipation. Novel pharmacological therapeutic agents are also being introduced. To evaluate the efficacy of these treatments, it is imperative to have a consistent definition of pharmacologically refractory constipation. A systematic review of studies on refractory, difficult-to-treat or surgically treated constipation was carried out to determine the criteria that various authors used to define this group of patients. METHODS: A systematic review was performed for literature published from June 2005 to June 2015 using PubMed, Cochrane, and Scopus databases, as well as manual searches. Studies on patients with refractory or intractable constipation were extracted. Criteria used for defining refractory constipation, as well as pharmacological agents tried including dosage, frequency, and duration, were reviewed. RESULTS: Sixty-one studies were included in this review. Forty-eight involved surgical treatment of constipation, while 13 examined non-surgical therapies for refractory constipation. There is no generally accepted definition of refractory constipation. Authors consider constipation to be refractory when response to management is suboptimal, but there is no consensus on the choice of drug, order of usage, and dosage or treatment duration. Prior medical therapy was not mentioned at all in five studies. CONCLUSIONS: There is need for a detailed definition of pharmacologically refractory constipation before submitting patients to invasive treatments and to evaluate new pharmacological agents.

Colonic motor dysfunctions in a mouse model of high-fat diet-induced obesity: an involvement of A2B adenosine receptors.

Adenosine A2B receptors (A2BR) regulate several enteric functions. However, their implication in the pathophysiology of intestinal dysmotility associated with high-fat diet (HFD)-induced obesity has not been elucidated. We investigated the expression of A2BR in mouse colon and their role in the mechanisms underlying the development of enteric dysmotility associated with obesity. Wild-type C57BL/6J mice were fed with HFD (60% kcal from fat) or normocaloric diet (NCD; 18% kcal from fat) for 8 weeks. Colonic A2BR localization was examined by immunofluorescence. The role of A2BR in the control of colonic motility was examined in functional experiments on longitudinal muscle preparations (LMPs). In NCD mice, A2BR were predominantly located in myenteric neurons; in HFD animals, their expression increased throughout the neuromuscular layer. Functionally, the A2BR antagonist MRS1754 enhanced electrically induced NK1-mediated tachykininergic contractions in LMPs from HFD mice, while it was less effective in tissues from NCD mice. The A2B receptor agonist BAY 60-6583 decreased colonic tachykininergic contractions in LMPs, with higher efficacy in preparations from obese mice. Both A2BR ligands did not affect contractions elicited by exogenous substance P. Obesity is related with a condition of colonic inflammation, leading to an increase of A2BR expression. A2BR, modulating the activity of excitatory tachykininergic nerves, participate to the enteric dysmotility associated with obesity.

Effective and safe proton pump inhibitor therapy in acid-related diseases - A position paper addressing benefits and potential harms of acid suppression.

BACKGROUND: The introduction of proton pump inhibitors (PPIs) into clinical practice has revolutionized the management of acid-related diseases. Studies in primary care and emergency settings suggest that PPIs are frequently prescribed for inappropriate indications or for indications where their use offers little benefit. Inappropriate PPI use is a matter of great concern, especially in the elderly, who are often affected by multiple comorbidities and are taking multiple medications, and are thus at an increased risk of long-term PPI-related adverse outcomes as well as drug-to-drug interactions. Herein, we aim to review the current literature on PPI use and develop a position paper addressing the benefits and potential harms of acid suppression with the purpose of providing evidence-based guidelines on the appropriate use of these medications. METHODS: The topics, identified by a Scientific Committee, were assigned to experts selected by three Italian Scientific Societies, who independently performed a systematic search of the relevant literature using Medline/PubMed, Embase, and the Cochrane databases. Search outputs were distilled, paying more attention to systematic reviews and meta-analyses (where available) representing the best evidence. The draft prepared on each topic was circulated amongst all the members of the Scientific Committee. Each expert then provided her/his input to the writing, suggesting changes and the inclusion of new material and/or additional relevant references. The global recommendations were then thoroughly discussed in a specific meeting, refined with regard to both content and wording, and approved to obtain a summary of current evidence. RESULTS: Twenty-five years after their introduction into clinical practice, PPIs remain the mainstay of the treatment of acid-related diseases, where their use in gastroesophageal reflux disease, eosinophilic esophagitis, Helicobacter pylori infection, peptic ulcer disease and bleeding as well as, and Zollinger-Ellison syndrome is appropriate. Prevention of gastroduodenal mucosal lesions (and symptoms) in patients taking non-steroidal anti-inflammatory drugs (NSAIDs) or antiplatelet therapies and carrying gastrointestinal risk factors also represents an appropriate indication. On the contrary, steroid use does not need any gastroprotection, unless combined with NSAID therapy. In dyspeptic patients with persisting symptoms, despite successful H. pylori eradication, short-term PPI treatment could be attempted. Finally, addition of PPIs to pancreatic enzyme replacement therapy in patients with refractory steatorrhea may be worthwhile. CONCLUSIONS: Overall, PPIs are irreplaceable drugs in the management of acid-related diseases. However, PPI treatment, as any kind of drug therapy, is not without risk of adverse effects. The overall benefits of therapy and improvement in quality of life significantly outweigh potential harms in most patients, but those without clear clinical indication are only exposed to the risks of PPI prescription. Adhering with evidence-based guidelines represents the only rational approach to effective and safe PPI therapy. Please see related Commentary: doi: 10.1186/s12916-016-0724-1 .

Small bowel protection against NSAID-injury in rats: Effect of rifaximin, a poorly absorbed, GI targeted, antibiotic.

Nonsteroidal anti-inflammatory drugs, besides exerting detrimental effects on the upper digestive tract, can also damage the small and large intestine. Although the underlying mechanisms remain unclear, there is evidence that enteric bacteria play a pivotal role. The present study examined the enteroprotective effects of a delayed-release formulation of rifaximin-EIR (R-EIR, 50mg/kg BID, i.g.), a poorly absorbed antibiotic with a broad spectrum of antibacterial activity, in a rat model of enteropathy induced by indomethacin (IND, 1.5mg/kg BID for 14 days) administration. R-EIR was administered starting 7 days before or in concomitance with IND administration. At the end of treatments, blood samples were collected to evaluate hemoglobin (Hb) concentration (as an index of digestive bleeding). Small intestine was processed for: (1) histological assessment of intestinal damage (percentage length of lesions over the total length examined); (2) assay of tissue myeloperoxidase (MPO) and TNF levels, as markers of inflammation; (3) assay of tissue malondialdehyde (MDA) and protein carbonyl concentrations, as an index of lipid and protein peroxidation, respectively; (4) evaluation of the major bacterial phyla. IND significantly decreased Hb levels, this effect being significantly blunted by R-EIR. IND also induced the occurrence of lesions in the jejunum and ileum. In both intestinal regions, R-EIR significantly reduced the percentage of lesions, as compared with rats receiving IND alone. Either the markers of inflammation and tissue peroxidation were significantly increased in jejunum and ileum from IND-treated rats. However, in rats treated with R-EIR, these parameters were not significantly different from those observed in controls. R-EIR was also able to counterbalance the increase in Proteobacteria and Firmicutes abundance induced by INDO. To summarize, R-EIR treatment significantly prevents IND-induced intestinal damage, this enteroprotective effect being associated with a decrease in tissue inflammation, oxidative stress and digestive bleeding as well as reversal of NSAID-induced alterations in bacterial population.

Risk of gastrointestinal complications associated to NSAIDs, low-dose aspirin and their combinations: Results of a pharmacovigilance reporting system.

Gastrointestinal (GI) complications are one of the most limiting cause of use of NSAIDs. Beyond others well defined factors, history of peptic ulcer, older age, Helicobacter pylori infection and use of gastrotoxic drugs may affect their GI safety profile. In particular, the risk of GI complications associated to the use of antiplatelet drugs, especially low-dose acetylsalicylic acid (LDA) should deserve much attention. However, only few studies have focused on the effect of combination LDA/NSAIDs on the GI tract compared with the monotherapy and much less studies assessed this effect with multiple NSAIDs use. We aimed to characterize the GI safety profile of NSAIDs and LDA as monotherapy or their combinations in real-life conditions by analysing spontaneous adverse drug reactions (ADRs) reporting system in a Southern Italy. We used the case/non-case method in the Italian Pharmacovigilance Network (RNF). Cases were reports of GI events in the RNF between January 2007 and December 2011. Non-cases were all other reports during the same period. The association between NSAID and suspected GI ADRs was calculated using the reporting odds ratio (ROR) with 95% confidence intervals as a measure of disproportionality while adjusting for age, and concomitant use of antineoplastic agents or drugs for cardiovascular diseases. Sub-analysis were performed within the NSAID class. Among the 2816 adverse drug reactions recorded, we identified 374 (13.3%) cases of GI complications. Upper GI complications were the most frequently reported type of events. The highest associations were found for the combined use of NSAIDs and/or LDA, whilst the lowest associations were for their respective monotherapy. Looking at individual NSAIDs the highest association with GI events was observed for ketorolac exposure followed by nimesulide, diclofenac, aspirin, ketoprofen, and ibuprofen. This study highlights the primary role of the national spontaneous reporting system to bring out potential signals, such as the inappropriate drug use pattern, which however, have to be furtherly studied in-depth with ad hoc population-based studies.

Probiotics for the Treatment of Symptomatic Uncomplicated Diverticular Disease: Rationale and Current Evidence.

Changes in the colonic microbiota are critical to the pathogenesis of diverticular complications such as diverticulitis and peridiverticular abscesses. However, more subtle changes in microbiota composition may well be important to the more chronic manifestations of diverticulosis. Some studies have shown the presence of bacterial overgrowth in subgroups of patients with diverticular disease and recent studies, using molecular biology techniques, found an increase of proteobacteria and actinobacteria in patients with symptomatic uncomplicated diverticular disease (SUDD), compared with healthy controls. The use of probiotics to modulate intestinal microecology in SUDD appears therefore rational. Although several investigations evaluating the clinical efficacy of probiotics have been performed, no definitive results have yet been achieved, mainly due to the heterogeneity of the available studies. Most of the studies used probiotics in combination with poorly absorbed antimicrobials or anti-inflammatory drugs. In only 4 studies, there was a harm using probiotics alone, but only 1 was a placebo-controlled, double-blind trial. The analysis of the available evidence reveals a poor quality of the published studies, whose design was heterogeneous, with only 2 out of 11 trials being double-blind and randomized. Therefore, available data can only suggest a benefit of probiotics in SUDD, but do not allow any evidence-based definite conclusion. As a consequence, current guidelines state that there is insufficient evidence to recommend probiotics for symptom relief in patients with diverticular disease.

Management of Patients With Diverticulosis and Diverticular Disease: Consensus Statements From the 2nd International Symposium on Diverticular Disease.

The statements produced by the Chairmen of the 2nd International Symposium on Diverticular Disease, held in Rome on April 8th to 9th, 2016, are reported. Topics such as epidemiology, risk factors, diagnosis, medical and surgical treatment of diverticular disease in patients with uncomplicated and complicated diverticular disease were reviewed by the Chairmen who proposed 41 statements graded according to level of evidence and strength of recommendation. Each topic was explored focusing on the more relevant clinical questions. The vote was conducted on a 6-point scale and consensus was defined a priori as 67% agreement of the participants. The voting group consisted of 80 physicians from 6 countries, and agreement with all statements was provided. Comments were added explaining some controversial areas.

Prognostic Role of the Endoscopic Classification "DICA".

Diverticular inflammation and complication assessment (DICA) endoscopic classification has been recently developed for patients suffering from diverticulosis and diverticular disease. Its predictive value in those patients was recently retrospectively assessed. For each patient, the following parameters were recorded: age, severity of DICA, presence of abdominal pain, C-reactive protein, fecal calprotectin test (if available) at the time of diagnosis, months of follow-up, therapy taken during the follow-up to maintain remission (if any), occurrence/recurrence of diverticulitis, and need of surgery. A total of 1651 patients (793 male, 858 female, mean age 66.6±11.1 y) were enrolled: 939 (56.9%) classified as DICA 1, 501 (30.3%) as DICA 2, and 211 (12.8%) as DICA 3. The median follow-up was 24 (9 to 138) months. Acute diverticulitis (AD) occurred/recurred in 263 (15.9%) patients, and surgery was necessary in 57 (21.7%) cases. DICA was the only factor significantly associated with the occurrence/recurrence of diverticulitis and surgery either at univariate (χ=405.029; P<0.0001) or multivariate analysis (hazard ratio=4.319; 95% CI, 3.639-5.126; P<0.0001). Only in DICA 2 patients scheduled therapy was effective for prevention of AD occurrence/recurrence with a hazard ratio (95% CI) of 0.598 (0.391-0.914) (P=0.006, log-rank test). Mesalazine-based therapies reduced the risk of AD occurrence/recurrence and need of surgery with a hazard ratio (95% CI) of 0.2103 (0.122-0.364) and 0.459 (0.258-0.818), respectively. DICA classification seems to be a valid parameter to predict the risk of diverticulitis occurrence/recurrence in patients suffering from diverticular disease of the colon.

Current Management of Patients With Diverticulosis and Diverticular Disease: A Survey From the 2nd International Symposium on Diverticular Disease.

BACKGROUND: Management of diverticular disease (DD) remains a point of debate. GOALS: To investigate the current opinion of participants of the 2nd International Symposium on Diverticular Disease, on real-life management of patients with DD of the colon. STUDY: Twelve questions were aimed at the diagnosis, treatment, and management options for diverticulosis and symptomatic DD. RESULTS: In total, 115 surveys from 8 European Countries were filled out. High fiber diet was widely prescribed in diverticulosis (59.1%). Probiotics (25%) were the most frequent prescribed drug, whereas 29.8% of participants did not prescribe any treatment in diverticulosis. Colonoscopy was frequently prescribed in symptomatic patients (69.3%), whereas 72.9% of participants did not prescribe any instrumental tool in their follow-up. Rifaximin, probiotics, and mesalazine were the most frequent prescribed drugs both in symptomatic patients (28.1, 14.9%, and 11.4%, respectively) and to prevent recurrence of the disease (42.5%, 12.4%, and 28.2%, respectively). With respect to laboratory exams, 57.9% of participants prescribed them during follow-up. The majority of participants (64.9%) managed suspected acute diverticulitis at home. Rifaximin, probiotics, and mesalazine were the most frequent prescribed drugs to prevent recurrence of the disease (32.2%, 13.2%, and 11.4%, respectively), whereas 25.4% of participants did not prescribe any drugs. Finally, no differences were found among gastroenterologists, surgeons, and general practitioners in managing this disease. CONCLUSIONS: This surveys shows that current management of DD is similar between different medical specialities, generally in line with current literature.

Mesalazine for the Treatment of Symptomatic Uncomplicated Diverticular Disease of the Colon and for Primary Prevention of Diverticulitis: A Systematic Review of Randomized Clinical Trials.

BACKGROUND: Symptomatic uncomplicated diverticular disease (SUDD) is a common gastrointestinal disease, because it affects about one fourth of the patient harboring colonic diverticula. GOAL: To assess the effectiveness of mesalazine in improving symptoms (namely abdominal pain) and in preventing diverticulitis occurrence in patients with SUDD. STUDY: Only randomized clinical trials (irrespective of language, blinding, or publication status) that compared mesalazine with placebo or any other therapy in SUDD were evaluated. The selected endpoints were symptom relief and diverticulitis occurrence at maximal follow-up. Absolute risk reduction (ARR, with 95% confidence interval) and the number needed to treat were used as measures of the therapeutic effect. RESULTS: Six randomized clinical trials enrolled 1021 patients: 526 patients were treated with mesalazine and 495 with placebo or other therapies. Symptom relief with mesalazine was always larger than that with placebo and other therapies. However, absolute risk reduction was significant only when mesalazine was compared with placebo, a high-fiber diet, and low-dose rifaximin. The incidence of diverticulitis with mesalazine was lower than that observed with placebo and other treatments, being significant only when compared with placebo. CONCLUSIONS: Mesalazine is effective in achieving symptom relief and primary prevention of diverticulitis in patients with SUDD.

Floating modular drug delivery systems with buoyancy independent of release mechanisms to sustain amoxicillin and clarithromycin intra-gastric concentrations.

Release modules of amoxicillin and clarithromycin combined in a single dosage form designed to float in the gastric content and to sustain the intra-gastric concentrations of these two antibiotics used for the eradication of Helicobacter pylori have been studied. The modules having a disc shape with curved bases were formulated as hydrophilic matrices. Two modules of clarithromycin were assembled by sticking the concave base of one module to the concave base of the other, creating an internal void chamber. The final dosage form was a floating assembly of three modules of clarithromycin and two of amoxicillin in which the drug release mechanism did not interfere with the floatation mechanism. The assembled system showed immediate in vitro floatation at pH 1.2, lasting 5 h. The in vitro antibiotics release profiles from individual modules and assembled systems exhibited linear release rate during buoyancy for at least 8 h. The predicted antibiotic concentrations in the stomach maintained for long time levels significantly higher than the respective minimum inhibitory concentrations (MIC). In addition, an in vivo absorption study performed on beagle dogs confirmed the slow release of clarithromycin and amoxicillin from the assembled system during the assembly's permanence in the stomach for at least 4 h.