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      Recent advances in understanding and managing diverticulitis

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          Abstract

          In the past few decades, the increasing socioeconomic burden of acute diverticulitis (AD) has become evident, and with the growth of the population age, this significant economic impact will likely continue to rise. Furthermore, recent evidence showed an increased rate of hospital admissions especially evident among women and younger individuals. The natural history and pathophysiology of this clinical condition is still to be fully defined, and efforts continue to be made in the identification of risk factors and the establishment of relative preventive strategies. The actual therapeutic strategies aimed to modulate gut microbiota, such as rifaximin or probiotics, or to reduce mucosal inflammation, such as mesalazine, present a relatively poor efficacy for both the prevention of the first AD episode (primary prevention) and its recurrence (secondary prevention). In the last few years, the main goal achieved has been in the management of AD in that uncomplicated AD can, to a larger extent, be managed in an outpatient setting with no or little supportive therapy, a strategy that will certainly impact on the health costs of this disease. The problem of AD recurrence remains a topic of debate.

          The aim of this review is to present updated evidence on AD epidemiology and relative open clinical questions and to analyze in detail predisposing and protective factors with an attempt to integrate their possible modes of action into the several pathogenic mechanisms that have been suggested to contribute to this multifactorial disease. A unifying hypothesis dealing with the colonic luminal and extra-luminal microenvironments separately is provided. Finally, evidence-based changes in therapeutic management will be summarized. Because of an ascertained multifactorial pathogenesis of uncomplicated and complicated AD, it is probable that a single ‘causa prima’ will not be identifiable, and a better stratification of patients could allow one to pursue tailored therapeutic algorithm strategies.

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          Most cited references118

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          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.
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            Long-term risk of acute diverticulitis among patients with incidental diverticulosis found during colonoscopy.

            Colonic diverticulosis is the most common finding during routine colonoscopy, and patients often question the significance of these lesions. Guidelines state that these patients have a 10% to 25% lifetime risk of developing acute diverticulitis. However, this value was determined based on limited data, collected before population-based colonoscopy, so the true number of cases of diverticulosis was not known. We measured the long-term risk of acute diverticulitis among patients with confirmed diverticulosis discovered incidentally on colonoscopy.
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              The management of complicated diverticulitis and the role of computed tomography.

              Acute diverticulitis is a disease with a wide clinical spectrum, ranging from a phlegmon (stage Ia), to localized abscesses (stages Ib and II), to free perforation with purulent (stage III) or feculent peritonitis (stage IV). While there is little debate about the best treatment for mild episodes and/or very severe episodes, uncertainty persists about the optimal management for intermediate stages (Ib and II). The aim of our study was therefore to define the role of computed tomography (CT) and to analyze its impact on the management of acute diverticulitis. We retrospectively analyzed 511 patients (296 males, 215 females) admitted for acute diverticulitis between January 1994 and December 2003. Excluded were patients with stoma reversal only, "diverticulitis" mimicked by cancer, or significantly deficient patient records. Patients were analyzed either as a whole or subgrouped according to age ( 40 yr). A modified Hinchey classification was used to stage the severity of acute diverticulitis. In 99 patients (19.4%), an abscess was found (74 pericolic, 25 pelvic, median diameter: 4.0 cm). CT-guided drainage was performed in 16 patients, one failure requiring a two-stage operation. Whereas conservative treatment failed in 6.8% in patients without abscess or perforation, 22.2% of patients with an abscess required an urgent resection (68.2%, one-stage, 31.8%, two-stage). Recurrence rates were 13% for mild cases, as compared to 41.2% in patients with a pelvic abscess (stage II) treated conservatively with/without CT-guided drainage. Of all surgical cases, resection/primary anastomosis was achieved in 73.6% with perioperative mortality of 1.1% and leak rate was 2.1%. CT evidence of a diverticular abscess has a prognostic impact as it correlates with a high risk of failure from nonoperative management regardless of the patient's age. After treatment of diverticulitis with CT evidence of an abscess, physicians should strongly consider elective surgery in order to prevent recurrent diverticulitis.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Funding AcquisitionRole: Writing – Original Draft Preparation
                Role: ConceptualizationRole: Writing – Original Draft Preparation
                Role: Investigation
                Role: Investigation
                Role: Writing – Review & Editing
                Journal
                F1000Res
                F1000Res
                F1000Research
                F1000Research
                F1000 Research Limited (London, UK )
                2046-1402
                29 June 2018
                2018
                : 7
                : F1000 Faculty Rev-971
                Affiliations
                [1 ]Department of Internal Medicine and Medical Specialties, University Sapienza of Rome, Viale del Policlinico 155, 00161 Rome, Italy
                [2 ]Medical-Surgical Department of Clinical Sciences and Translational Medicine, University Hospital S. Andrea, University Sapienza of Rome, Via di Grottarossa 1035-1039, 00189 Roma, Italy
                Author notes

                No competing interests were disclosed.

                Author information
                https://orcid.org/0000-0001-9249-1318
                Article
                10.12688/f1000research.14299.1
                6039950
                ee8d634c-70b0-46f4-a1c3-ce270e0f4c44
                Copyright: © 2018 Severi C et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 21 June 2018
                Funding
                Funded by: University Sapienza grant
                Award ID: 000324_17_RS_SEVERI_SAPIENZA_PROGETTI2016
                Carola Severi receives funding from the University Sapienza of Rome, 000324_17_RS_SEVERI_SAPIENZA_PROGETTI 2016. The funders had no role in decision to publish, or preparation of the manuscript.
                The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Review
                Articles

                diverticulitis,risk factors,prevention,therapy,diet,microbiota,colonic muscle,drugs

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