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Background: Diverticular disease (DD) represents a common gastrointestinal condition that poses a heavy burden on healthcare systems worldwide. A high degree of uncertainty surrounds the therapeutic approaches for the control of symptoms in patients with symptomatic uncomplicated diverticular disease (SUDD) and primary and secondary prevention of diverticulitis and its consequences. Objectives: To review the current knowledge and discuss the unmet needs regarding the management of SUDD and the prevention of acute diverticulitis. Eligibility criteria: Randomized trials, observational studies, and systematic reviews on lifestyle/dietary interventions and medical treatment (rifaximin, mesalazine, and probiotics) of SUDD or prevention of acute diverticulitis. Sources of evidence: The literature search was performed from inception to April 2023, without language restriction, following the modified Preferred Reporting Items for Systematic review and Meta-Analyses (PRISMA) reporting guidelines. References of the papers selected were checked to identify additional papers of potential interest. The final list of references was evaluated by a panel of experts, who were asked to check for any lack of relevant studies. Charting methods: Information on patient population, study design, intervention, control group, duration of the observation, and outcomes assessed was collected by two authors independently. Results: The review shows a high degree of uncertainty about therapeutic interventions, both dietary/lifestyle and pharmacological, in patients with SUDD, because of the scarcity and weakness of existing evidence. Available studies are generally of low quality, heterogeneous, and outdated, precluding the possibility to draw robust conclusions. Similarly, acute diverticulitis prevention has been seldom investigated, and there is a substantial lack of evidence supporting the role of dietary/lifestyle or pharmacological approaches to reduce the risk of diverticulitis. Conclusion: The lack of robust evidence regarding therapeutic options for gastrointestinal symptoms in SUDD patients and for primary and secondary prevention of acute diverticulitis remains an important unmet need in the management of DD. [ABSTRACT FROM AUTHOR]

Background: The aim of the study was to compare the prognostic value of histological and endoscopic activity in patients with ulcerative colitis (UC). Methods: Patients in clinical remission for 1 year under treatment with mesalazine underwent a planned colonoscopy with biopsies. Histological activity was scored using the histological activity index (HAI). Endoscopic activity was scored using the Mayo endoscopic subscore (MES). The clinical course was evaluated measuring relapses needing steroids during a follow up of 3 years. Results: A total of 52 patients were enrolled into the study and followed up for 3 years. At baseline 29 patients (55.77%) had no endoscopic lesions, and 17 patients (32.69%) showed no histological alteration. At 3 years of follow up, overall, 26 patients (50%) were still in steroid-free remission. Using univariate logistic regression analysis, both histological (HAI ⩾ 1) and endoscopic activity (MES ⩾ 1) were significantly associated with outcome, showing, respectively, a relapse risk (odds ratio [OR]) 16.4 times higher than histological remission (HAI 0) (96% confidence interval [CI]: 3.2–84.3) and 6.3 times higher with respect to endoscopic remission (MES 0) (96% CI: 1.9–21.3). After multivariate logistic regression analysis, histological activity was the only factor significantly associated with outcome (OR 10.2; 95% CI: 1.7–59.4). Conclusions: Histological activity has the most powerful prognostic value in predicting the need for steroids in patients with UC in stable clinical remission on mesalazine. It could be considered as a target of therapy in UC. [ABSTRACT FROM AUTHOR]

The Multimatrix® (MMX®) preparation MMX® is a recently obtained drug formulation developed to facilitate release of high concentrations of active drugs into the colon, with a homogeneous distribution along all colonic segments, particularly the most distal ones; the distal colonic tracts, indeed, are the most difficult to reach in significant amounts when a drug is given orally. The MMX® formulation is characterized by a lipophilic matrix dispersed in a hydrophilic structure. Indeed, in the last few years, MMX® technology has been widely used in the development of various drugs for the treatment of inflammatory and infectious gastrointestinal diseases localized in the colon. In particular, MMX® mesalamine, budesonide and parnaparin formulations have been investigated in patients with ulcerative colitis, and the first two have reached worldwide registration for the treatment of this disease. Moreover, MMX®-rifamycin is being positively tested in the treatment of colonic bacterial infections, including traveler’s diarrhea. MMX® technology is, thus, proving to be a very effective formulation for the treatment of various colonic diseases.This effectiveness has been related not only to specific colonic delivery, but also to its ability to act in a once-daily dosage, thus favouring patients’ adherence to prescribed schedules of treatment. The effective delivery of the active molecule to the site of need in the colon is also associated with very low systemic absorption and very low rates of adverse events (AEs). In this paper, we have reviewed all clinical trials performed with an MMX®-bound drug and all possible real-life reports, in order to give an overall evaluation of MMX®. [ABSTRACT FROM AUTHOR]

Steroids have been a mainstay of ulcerative colitis (UC) therapy for many years, based on a thoroughly established efficacy profile for the induction of remission. However, in light of the considerable side effects and negative perceptions they carry, it is important to ensure such treatments are used as effectively as possible. For severe UC, the need for steroids is rarely questioned, and rightly so; it is for moderate UC that the role of steroids should be considered. Both patients and clinicians place a high importance on rapid, effective resolution of symptoms, yet at the same time wish to avoid unnecessary side effects. Through consideration of the available evidence, it becomes clear that both steroids and high-dose 5-aminosalicylic acid (5-ASA) are supported by robust trials demonstrating their efficacy. Indeed, both therapies have been shown to give rise to resolution of symptoms after 2 weeks in many patients. However, a paucity of head-to-head comparisons makes conclusive interpretation challenging. This paper therefore presents a practical approach, which builds on the available evidence and is developed from informed discussions with patients. This approach involves initiating therapy with high-dose 5-ASA, followed by a review of symptom improvements after 2–3 weeks. Steroids can then be introduced, when needed, with minimal delay. In this way, symptoms can be resolved rapidly, yet many patients may avoid unpleasant side effects. [ABSTRACT FROM PUBLISHER]

Colonic diverticular disease is common in Western countries and its prevalence increases with age. The large majority of patients (80–85%) will remain entirely asymptomatic throughout their life. In symptomatic cases, most patients will have diverticulosis without inflammation while the remainder will have diverticulitis with or without complications. About 1–2% will require hospitalization and 0.5% will require surgery. Factors predicting the development of symptoms remain to be identified. However, it is generally recognized that diverticular disease is probably related to complex interactions between colon structure, intestinal motility, diet, and genetic features. Epidemiologic studies have demonstrated an association between diverticulosis and diets that are low in fiber and high in refined carbohydrates. Although the causes of symptom development are still unclear, it is thought that previous episodes of intestinal inflammation may play a role. Changes in intestinal microflora could be one of the putative mechanisms responsible for low-grade inflammation. In patients with uncomplicated diverticulosis, a diet abundant in fruit and vegetables is recommended. The current therapeutic approaches in preventing recurrence of symptoms are based on nonabsorbable antibiotics, mesalazine, and/or probiotics. Cyclic rifaximin administration seems to be an adequate approach to relieving symptoms and preventing acute diverticulitis in patients with symptomatic diverticulosis. [ABSTRACT FROM PUBLISHER]

Mesalazine [5-aminosalicylic acid (5-ASA)] has been used for over 30 years in the treatment of inflammatory bowel disease (IBD). It is a highly effective, safe, and well-tolerated drug for treatment of mild to moderate ulcerative colitis, which represents most patients with this disease. Recent studies of patient adherence to 5-ASA therapies in ulcerative colitis have highlighted the need for regimens that enable long-term compliance to significantly reduce the risk of troublesome and debilitating flares in the short term, and possibly colon cancer in the long term. Indeed, much of the recent innovation in clinical use of 5-ASA in colitis has come from studies of novel delivery mechanisms and simplified oral dosing schedules. These studies have provided much needed clarity on essential matters such as starting dose, dose escalation, and efficacy in terms of the ideal clinical endpoint - mucosal healing. Various manufacturers are re-evaluating their products to determine the safety and efficacy of such dosing regimens. Although once widely employed in the treatment of Crohn’s disease (CD), the accumulated body of evidence now suggests that there is a much more limited role for 5-ASA in this particular form of inflammatory bowel disease. Recent 5-ASA randomized-controlled trials, comparative studies, and outcomes research have led to refined treatment strategies and awareness for practitioners to better inform, engage and facilitate patients in optimal use of 5-ASA in inflammatory bowel disease. [ABSTRACT FROM PUBLISHER]

Diverticular disease of the colon (DDC) includes a spectrum of conditions from asymptomatic diverticulosis to symptomatic uncomplicated diverticulosis, segmental colitis associated with diverticulosis, and acute diverticulitis without or with complications that may have serious consequences. Clinical and scientific interest in DDC is increasing because of the rising incidence of all conditions within the DDC spectrum, a better, although still limited understanding of the pathogenic mechanisms involved; the increasing socioeconomic burden; and the new therapeutic options being tested. The goals of treatment in DDC are symptom and inflammation relief and preventing disease progression or recurrence. The basis for preventing disease progression remains a high-fiber diet and physical exercise, although evidence is poor. Other current strategies do not meet expectations or lack a solid mechanistic foundation; these strategies include modulation of gut microbiota or dysbiosis with rifaximin or probiotics, or using mesalazine for low-grade inflammation in uncomplicated symptomatic diverticulosis. Most acute diverticulitis is uncomplicated, and the trend is to avoid hospitalization and unnecessary antibiotic therapy, but patients with comorbidities, sepsis, or immunodeficiency should receive broad spectrum and appropriate antibiotics. Complicated acute diverticulitis may require interventional radiology or surgery, although the best surgical approach (open versus laparoscopic) remains a matter of discussion. Prevention of acute diverticulitis recurrence remains undefined, as do therapeutic strategies. Mesalazine with or without probiotics has failed to prevent diverticulitis recurrence, whereas new studies are needed to validate preliminary positive results with rifaximin. Surgery is another option, but the number of acute events cannot guide this indication. We need to identify risk factors and disease progression or recurrence mechanisms to implement appropriate preventive strategies. [ABSTRACT FROM AUTHOR]

Diverticulosis is a common anatomical condition, which appears to be age-dependent. Individuals who develop chronic gastrointestinal symptoms or complications are referred to as having diverticular disease. Although the diagnosis of this condition can be relatively straightforward, randomized controlled trials are scarce and management often follows tradition rather than principles of evidence-based medicine. This report deals with the topics discussed during a symposium held during the United European Gastroenterology Week (Barcelona, October 2017). During the meeting, the role of dysbiosis in the pathogenesis of diverticular disease and its treatment were thoroughly discussed, by examining the efficacy and mechanisms of action of the currently used drugs. Recent studies have shown the presence of dysbiosis in patients with diverticular disease and suggest an imbalance in favor of bacteria with pro-inflammatory and pathogenetic potential. These microbiota changes correlate with mucosal immune activation, mirrored by a marked increase of macrophages in colonic mucosa, both in the diverticular region and at distant sites. The low-grade inflammation, driven by bacteria-induced immune activation, could be involved in the pathophysiology of symptoms. As a consequence, pharmacological approaches targeting enteric bacteria (with poorly absorbed antibiotics, like rifaximin, or probiotics) or intestinal inflammation (with 5-ASA derivatives or rifaximin) have shown capability of controlling symptoms and also preventing complications, albeit more research is needed to establish the optimal regimen (daily dose and duration) of therapy. Well-designed randomized-controlled trials (RCTs), including homogeneous populations of patients, are therefore needed. The future of management of many GI diseases, including symptomatic uncomplicated diverticular disease, will rely on the so-called 'microbiota-directed therapies'. [ABSTRACT FROM AUTHOR]

The Multimatrix ® (MMX ® ) preparation MMX ® is a recently obtained drug formulation developed to facilitate release of high concentrations of active drugs into the colon, with a homogeneous distribution along all colonic segments, particularly the most distal ones; the distal colonic tracts, indeed, are the most difficult to reach in significant amounts when a drug is given orally. The MMX ® formulation is characterized by a lipophilic matrix dispersed in a hydrophilic structure. Indeed, in the last few years, MMX ® technology has been widely used in the development of various drugs for the treatment of inflammatory and infectious gastrointestinal diseases localized in the colon. In particular, MMX ® mesalamine, budesonide and parnaparin formulations have been investigated in patients with ulcerative colitis, and the first two have reached worldwide registration for the treatment of this disease. Moreover, MMX ® -rifamycin is being positively tested in the treatment of colonic bacterial infections, including traveler's diarrhea. MMX ® technology is, thus, proving to be a very effective formulation for the treatment of various colonic diseases. This effectiveness has been related not only to specific colonic delivery, but also to its ability to act in a once-daily dosage, thus favouring patients' adherence to prescribed schedules of treatment. The effective delivery of the active molecule to the site of need in the colon is also associated with very low systemic absorption and very low rates of adverse events (AEs). In this paper, we have reviewed all clinical trials performed with an MMX ® -bound drug and all possible real-life reports, in order to give an overall evaluation of MMX ® ., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest.