Review article: do stimulant laxatives damage the gut? A critical analysis of current knowledge.

Stimulant laxatives are well established as first- or second-line treatments for constipation and although they have a reliable therapeutic effect, alleged safety concerns still exist, particularly with long-term use. The potential harmful effects on the gastrointestinal system (including carcinogenicity) of the long-term use of diphenylmethane [bisacodyl, sodium picosulfate (SPS)] and senna stimulant laxatives were assessed in a comprehensive review of the publications identified in literature searches performed in PubMed and Embase up to and including June 2023. We identified and reviewed 43 publications of interest. While stimulant laxatives at supratherapeutic doses have been shown to cause structural alterations to surface absorptive cells in animals and humans, these effects are reversible and not considered clinically relevant. No formal long-term studies have demonstrated morphological changes in enteric neural elements or intestinal smooth muscle with bisacodyl or SPS in humans. Furthermore, there is no convincing evidence that stimulant laxatives are associated with the development of colon cancer, and in fact, chronic constipation itself has been reported to potentially increase the risk of colon cancer, therefore, the use of stimulant laxatives might reduce this risk. Many studies suggesting a possible harmful effect from laxatives were limited by their failure to consider confounding factors such as concomitant neurological disease, metabolic disorders, and age. These findings highlight the lack of evidence for the harmful effects of laxatives on the colon, and thus, the benefits of treatment with stimulant laxatives, even in the long-term, should be reconsidered for the management of patients with constipation.

Do stimulant laxatives damage the gut? Stimulant laxatives are widely used treatments for constipation that work by causing the muscles in the gut to contract and so move stool more effectively. Examples of these treatments include senna, bisacodyl and sodium picosulfate. Treatments such as these are typically available without a doctor's prescription and have a long history of helping people relieve their constipation. However, some concerns have been expressed about the safety of these treatments, particularly when they are used for a long time. We did a critical review of published studies of the safety of stimulant laxatives to try to find out whether there is any strong evidence for harm being caused by these treatments. We found 43 papers with information on the gut safety of stimulant laxatives. These studies looked at whether the treatments are associated with changes to gut structure or function and at whether there might be a link between these treatments and bowel cancer. Unfortunately, many of the studies were of poor quality. For instance, they did not look for things, in addition to the laxatives, that could have affected the results, such as the age of the patients, other medications they were taking or whether they had other health conditions that might have affected the bowel. Also, the populations in which the studies were done differed a lot, so they were hard to compare with one another. However, we did not find any strong evidence suggesting that stimulant laxatives damage the gut or cause cancer. We therefore concluded that the harms associated with stimulant laxatives are likely to have been overstated, and that patients should not be denied the benefits of stimulant laxatives for constipation, especially as they have been on the market for a very long time with no serious problems emerging.

Predictive Score for Advanced Colorectal Neoplasia Based on Cardiovascular and Colorectal Cancer Risk Factors.

Background and Aims: Cardiovascular disease and colorectal cancer (CRC) are significant health problems and share some risk factors. The aim of our study was to develop and validate a predictive score for advanced colorectal neoplasia (CRN) based on risk factors for cardiovascular disease and CRC. Materials and Methods: A cross-sectional study comprising a derivation cohort and an external validation cohort of 1049 and 308 patients, respectively. A prediction score for advanced CRN (CRNAS: Colorectal Neoplasia Advanced Score) was developed from a logistic regression model, comprising sex, age, first-degree family history for CRC, systolic and diastolic blood pressure, total cholesterol, HDL cholesterol, body mass index, diabetes, smoking, and antihypertensive treatment. Other cardiovascular risk scores (Framingham-Wilson, REGICOR, SCORE, and FRESCO) were also used to predict the risk of advanced CRN. The discriminatory capacity of each score was evaluated using the area under the curve (AUC). Results: CRN were found in 379 subjects from the derivation cohort (36%), including 228 patients (22%) with an advanced CRN. Male sex, age, diabetes, and smoking were identified as independent risk factors for advanced CRN. The newly created score (CRNAS) showed an AUC of 0.68 (95% CI: 0.64-0.73) for advanced CRN, which was better than cardiovascular risk scores (p < 0.001). In the validation cohort, the AUC of CRNAS for advanced CRN was 0.67 (95% CI: 0.57-0.76). Conclusions: The newly validated CRNAS has a better discriminatory capacity to predict advanced CRN than cardiovascular scores. It may be useful for selecting candidates for screening colonoscopy, especially in those with cardiovascular risk factors.

Combined Treatment with Polynucleotides and Hyaluronic Acid Improves Tissue Repair in Experimental Colitis.

Inflammatory bowel diseases (IBDs) are chronic conditions that can benefit from the combined treatment of adenosine receptor agonists and hyaluronic acid (HA), which, binding the CD44, has pro-survival effects. Therefore, this study investigated the effects of a mixture of polynucleotides and HA in an experimental model of dinitrobenzenesulfonic acid (DNBS)-induced colitis. A group of 40 rats received a single intra-colonic instillation of DNBS, and after 6 h, animals were randomized to receive daily: (i) saline solution; (ii) polynucleotides (Poly; 8 mg/kg); (iii) polynucleotides (8 mg/kg) plus hyaluronic acid (HA; 15 mg/kg); and (iv) hyaluronic acid (HA; 15 mg/kg). Rats in the control group (n = 10) received saline solution only. Seven days after induction, animals receiving Poly plus HA showed reduced clinical signs, weight loss and colon shortening, ameliorated macroscopic and histological damage, and apoptosis. Moreover, the combined treatment reduced the positivity in the colonic infiltrate of CD3 positive T cells, CD20 positive B cells and CD44. Furthermore, Poly plus HA reduced colonic myeloperoxidase activity and malondialdehyde, indicating a dampening of the inflammatory infiltrate and oxidation products. Our research demonstrated that a combined treatment of polynucleotides with hyaluronic acid had a protective effect in a model of ulcerative colitis, suggesting that this association deserves further attention for the treatment of IBDs.

Pharmacologic treatment of GERD: Where we are now, and where are we going?

The introduction of acid inhibition in clinical practice has revolutionized the management of acid-related diseases, leading to the virtual abolition of elective surgery for ulcer disease and relegating antireflux surgery to patients with gastroesophageal reflux disease (GERD) not adequately managed by medical therapy. Proton pump inhibitors (PPIs) are the antisecretory drugs of choice for the treatment of reflux disease. However, these drugs still leave some unmet clinical needs in GERD. PPI-refractoriness is common, and persistent symptoms are observed in up to 40-55% of daily PPI users. Potassium-competitive acid blockers (P-CABs) clearly overcome many of the drawbacks and limitations of PPIs, achieving rapid, potent, and prolonged acid suppression, offering the opportunity to address many of the unmet needs. In recent years, it has been increasingly recognized that impaired mucosal integrity is involved in the pathogenesis of GERD. As a consequence, esophageal mucosal protection has emerged as a new, promising therapeutic avenue. When P-CABS are used as add-on medications to standard treatment, a growing body of evidence suggests a significant additional benefit, especially in the relief of symptoms not responding to PPI therapy. On the contrary, reflux inhibitors are considered a promise unfulfilled, and prokinetic agents should only be used on a case-by-case basis.

Gastrointestinal pharmacology: practical tips for the esophagologist.

Gastroesophageal reflux disease (GERD) is primarily a motor disorder, and its pathogenesis is multifactorial. As a consequence, treatment should be able to address the underlying pathophysiology. Proton pump inhibitors (PPIs) are the mainstay of medical therapy for GERD, but these drugs only provide the control of symptoms and lesions without curing the disease. However, continuous acid suppression with PPIs is recommended for patients with Barrett's esophagus because of their potential chemopreventive effects. In addition to the antisecretory activity, these compounds display several pharmacological properties, often overlooked in clinical practice. PPIs can indeed affect gastric motility, exert a mucosal protective effect, and an antioxidant, anti-inflammatory, and antineoplastic activity, also protecting cancer cells from developing chemo- or radiotherapeutic resistance. Even in the third millennium, current pharmacologic approaches to address GERD are limited. Reflux inhibitors represent a promise unfulfilled, effective and safe prokinetics are lacking, and antidepressants, despite being effective in selected patients, give rise to adverse events in a large proportion of them. While waiting for new drug classes (like potassium-competitive acid blockers), reassessing old drugs (namely alginate-containing formulations), and paving the new avenue of esophageal mucosal protection are, at the present time, the only reliable alternatives to acid suppression.

Potential proton pump inhibitor-related adverse effects.

Proton pump inhibitors (PPIs) are one of the most common medications taken by patients worldwide. PPIs are used to treat acid-related disorders, including gastroesophageal reflux disease, peptic ulcer disease, Helicobacter pylori infection, and nonsteroidal anti-inflammatory drug/stress ulceration. For some of these diseases, long-term treatment is necessary. With such prolonged use, concern and investigation into potential adverse effects has increased. In addition, data are available regarding potential anticancer effects of PPIs, especially regarding solid tumors. The aim of this review is to assess the literature on PPIs with regard to common concerns, such as drug-drug interactions, the intestinal microbiome, dementia and central nervous system disease, and osteoporosis, as well as to highlight potential negative and positive impacts of the drug in cancer.

Colonic diverticular disease.

Diverticula are outpouchings of the intestinal wall and are common anatomical alterations detected in the human colon. Colonic diverticulosis (the presence of diverticula in the colon; referred to as diverticulosis) remains asymptomatic in most individuals but ~25% of individuals will develop symptomatic diverticulosis, termed colonic diverticular disease (also known as diverticular disease). Diverticular disease can range in severity from symptomatic uncomplicated diverticular disease (SUDD) to symptomatic disease with complications such as acute diverticulitis or diverticular haemorrhage. Since the early 2000s, a greater understanding of the pathophysiology of diverticulosis and diverticular disease, which encompasses genetic alterations, chronic low-grade inflammation and gut dysbiosis, has led to improvements in diagnosis and management. Diagnosis of diverticular disease relies on imaging approaches, such as ultrasonography, CT and MRI, as biomarkers alone are insufficient to establish a diagnosis despite their role in determining disease severity and progression as well as in differential diagnosis. Treatments for diverticular disease include dietary fibre, pharmacological treatments such as antibiotics (rifaximin), anti-inflammatory drugs (mesalazine) and probiotics, alone or in combination, and eventually surgery. Despite being effective in treating primary disease, their effectiveness in primary and secondary prevention of complications is still uncertain.

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.

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.

The "DICA" endoscopic classification for diverticular disease of the colon shows a significant interobserver agreement among community endoscopists.

BACKGROUND AND AIM: An endoscopic classification of Diverticular Disease (DD), called DICA (Diverticular Inflammation and Complication Assessment) is currently available. It scores severity of the disease as DICA 1, DICA 2 and DICA 3. Our aim was to assess the agreement levels for this classification among an endoscopist community setting. METHODS: A total of 66 endoscopists independently scored a set of DD endoscopic videos. The percentages of overall agreement on the DICA score and a free-marginal multirater kappa (κ) coefficient were reported as statistical measures of the inter-rater agreement. RESULTS: The overall agreement levels were: 70.2% for DICA 1, 70.5% for DICA 2, 81.3% for DICA 3. The free marginal κ was: 0.553 for DICA 1, 0.558 for DICA 2, 0.719 for DICA 3. The agreement levels among the expert group were: 78.8% for DICA 1, 80.2% for DICA 2, 88.5% for DICA 3. The free marginal κ among the expert group were: 0.682 for DICA 1, 0.712 for DICA 2, 0.828 for DICA 3. The agreement of expert raters on the single item of the DICA classification was superior to the agreement of the overall group. CONCLUSIONS: The overall inter-rater agreement for DICA score in this study ranges from moderate to good, with a significant improvement in the expert subgroup of raters. Diverticular Inflammation and Complication Assessment is a simple and reproducible endoscopic scoring system.

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.

The DICA Endoscopic Classification for Diverticular Disease of the Colon Shows a Significant Interobserver Agreement among Community Endoscopists: an International Study.

BACKGROUND AND AIMS: The Diverticular Inflammation and Complication Assessment (DICA) endoscopic classification of diverticulosis and diverticular disease (DD) is currently available. It scores severity of the disease as DICA 1, DICA 2 and DICA 3. Our aim was to assess the agreement on this classification in an international endoscopists community setting. METHODS: A total of 96 doctors (82.9% endoscopists) independently scored a set of DD endoscopic videos. The percentages of overall agreement on DICA score and a free-marginal multirater kappa (κ) coefficient were reported as statistical measures of interrater agreement. RESULTS: Overall agreement in using DICA was 91.8% with a free-marginal kappa of 88% (95% CI 80-95). The overall agreement levels were: DICA 1, 85.2%; DICA 2, 96.5%; DICA 3, 99.5%. The free marginal κ was: DICA 1 = 0.753, DICA 2 = 0.958, DICA 3 = 0.919. The agreement about the main endoscopic items was 83.4% (k 67%) for diverticular extension, 62.6% (k 65%) for number of diverticula for each district, 86.8% (k 82%) for presence of inflammation, and 98.5 (k 98%) for presence of complications. CONCLUSIONS: The overall interrater agreement in this study ranges from good to very good. DICA score is a simple and reproducible endoscopic scoring system for diverticulosis and DD.

Course of the Diverticular Disease: What is changing?

In this session several critical issues in diverticular disease were considered, including "It is Symptomatic Diverticular Disease or Irritable Bowel Syndrome?", "What do determine evolution to diverticulitis, bowel habits alteration or inflammation?", and "Prevention of acute diverticulitis: Is it at all possible?". The first talking compared symptoms and laboratory findings between Symptomatic Uncomplicated Diverticular Disease  (SUDD) and Irritable Bowel Syndrome (IBS). Although both disease share some symptoms, and although IBS can occur in patients having diverticulosis,  SUDD and IBS can be differentiate using a combination of symptoms and laboratory tools. The second talking debated what are the most important risk factors for the evolution towards acute diverticulitis. Current data seem to exclude a significant role of bowel habits alteration, while inflammation seems to have a stronger role, especially in causing acute diverticulitis recurrence. The third talking analyzed about the acute diverticulitis prevention. Primary prevention seem to be little better when using mesalazine, while no definite conclusion can be drawn about the use of fiber and rifaximin. About the secondary prevention, no drugs can be currently advised due to lacking of definite results. At the same time, surgery should be advised on case-by-case basis.

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.

Pathophysiology of NSAID-Associated Intestinal Lesions in the Rat: Luminal Bacteria and Mucosal Inflammation as Targets for Prevention.

Non-steroidal anti-inflammatory drugs (NSAIDs) can damage the small intestine, mainly through an involvement of enteric bacteria. This study examined the pathophysiology of NSAID-associated intestinal lesions in a rat model of diclofenac-enteropathy and evaluated the effect of rifaximin on small bowel damage. Enteropathy was induced in 40-week old male rats by intragastric diclofenac (4 mg/kg BID, 14 days). Rifaximin (delayed release formulation) was administered (50 mg/kg BID) 1 h before the NSAID. At the end of treatments, parameters dealing with ileal damage, inflammation, barrier integrity, microbiota composition, and TLR-NF-κB-inflammasome pathway were evaluated. In addition, the modulating effect of rifaximin on NLRP3 inflammasome was tested in an in vitro cell system. Diclofenac induced intestinal damage and inflammation, triggering an increase in tissue concentrations of tumor necrosis factor and interleukin-1ß, higher expression of TLR-2 and TLR-4, MyD88, NF-κB and activation of caspase-1. In addition, the NSAID decreased ileal occludin expression and provoked a shift of bacterial phyla toward an increase in Proteobacteria and Bacteroidetes abundance. All these changes were counterbalanced by rifaximin co-administration. This drug was also capable of increasing the proportion of Lactobacilli, a genus depleted by the NSAID. In LPS-primed THP-1 cells stimulated by nigericin (a model to study the NLRP3 inflammasome), rifaximin reduced IL-1ß production in a concentration-dependent fashion, this effect being associated with inhibition of the up-stream caspase-1 activation. In conclusion, diclofenac induced ileal mucosal lesions, driving inflammatory pathways and microbiota changes. In conclusion, rifaximin prevents diclofenac-induced enteropathy through both anti-bacterial and anti-inflammatory activities.

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 .

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.