Diverticular disease and risk of dementia: a Danish population-based cohort study.

BACKGROUND AND AIM: Patients with diverticular disease (DD) have ongoing chronic inflammation associated with changes in the gut microbiome, which might contribute to the development of dementia. METHODS: Using Danish medical and administrative registries from 1980 to 2013, we conducted a nationwide population-based cohort study including all DD patients and a matched (5:1) general population comparison cohort without DD. A nested case-control analysis was then conducted using a risk set sampling, matching four DD controls without dementia to each DD patient with dementia. Clinical severity was categorized as uncomplicated DD (outpatient), conservatively treated DD (inpatient), and surgically treated DD. RESULTS: 149 527 DD patients and 747 635 general population comparators were identified. The 30-year cumulative incidence of dementia among DD patients and general population comparators were 12.4 (95% confidence interval [CI] 12.1-12.7) and 13.73% (95% CI 13.6-13.9), respectively. This corresponded to a 30-year hazard ratio (HR) of 1.10 (95% CI 1.1-1.1). The highest HRs were found in the conservatively treated DD group (1.15 95% CI 1.1-1.2) and the group with young onset of DD (1.52 95% CI 1.2-2.0). In the nested case-control analysis, we identified 8875 dementia cases and 35 491 matched controls. The adjusted odds ratio (OR) for conservatively treated DD was increased (1.08, 95% CI; 1.0-1.2) compared to the reference of uncomplicated DD. CONCLUSIONS: We observed a slight increased risk of dementia in patients with young onset DD and conservatively treated DD. Findings suggest an association between disease duration, perhaps reflecting the duration of gut inflammation, and the risk of developing dementia.

Does the microbiome play a role in the pathogenesis of colonic diverticular disease? A systematic review.

BACKGROUND AND AIMS: The role of the microbiota in diverticulosis and diverticular disease is underexplored. This systematic review aimed to assess all literature pertaining to the microbiota and metabolome associations in asymptomatic diverticulosis, symptomatic uncomplicated diverticular disease (SUDD), and diverticulitis pathophysiology. METHODS: Seven databases were searched for relevant studies published up to September 28, 2022. Data were screened in Covidence and extracted to Excel. Critical appraisal was undertaken using the Newcastle Ottawa Scale for case/control studies. RESULTS: Of the 413 papers screened by title and abstract, 48 full-text papers were reviewed in detail with 12 studies meeting the inclusion criteria. Overall, alpha and beta diversity were unchanged in diverticulosis; however, significant changes in alpha diversity were evident in diverticulitis. A similar Bacteroidetes to Firmicutes ratio compared with controls was reported across studies. The genus-level comparisons showed no relationship with diverticular disease. Butyrate-producing microbial species were decreased in abundance, suggesting a possible contribution to the pathogenesis of diverticular disease. Comamonas species was significantly increased in asymptomatic diverticulosis patients who later developed diverticulitis. Metabolome analysis reported significant differences in diverticulosis and SUDD, with upregulated uracil being the most consistent outcome in both. No significant differences were reported in the mycobiome. CONCLUSION: Overall, there is no convincing evidence of microbial dysbiosis in colonic diverticula to suggest that the microbiota contributes to the pathogenesis of asymptomatic diverticulosis, SUDD, or diverticular disease. Future research investigating microbiota involvement in colonic diverticula should consider an investigation of mucosa-associated microbial changes within the colonic diverticulum itself.

Gut Microbiota Association with Diverticular Disease Pathogenesis and Progression: A Systematic Review.

INTRODUCTION: Growing evidence supports the role of the intestinal microbiome in the development of different intestinal and extraintestinal diseases. Diverticular disease (DD) is one of the most common disorders in western countries. In the last years, different articles have suggested a possible role of the intestinal microbiome in DD pathogenesis and in the development of acute diverticulitis (AD). This systematic review aimed to clarify the current knowledge on the role of the intestinal microbiome in colonic diverticulitis in different stages according to the 2009 PRISMA guidelines. MATERIALS AND METHODS: Two independent reviewers searched the literature in a systematic manner through online databases, including Medline, Scopus, Embase, Cochrane Oral Health Group Specialized Register, ProQuest Dissertations and Theses Database, and Google Scholar. Patients with any stage of disease were included. The Newcastle-Ottawa scale for case-control and cohort studies was used for the quality assessment of the selected articles. RESULTS: Overall, nine studies were included in the review. Only one article was focused on patients with AD, while all other articles only considered patients with DD without acute inflammation signs. Enterobacteriaceae seems to be the microbiota most associated with the disease, followed by Bifidobacteria. CONCLUSIONS: All the included studies showed great heterogeneity in population characteristics and sampling methods. Therefore, given the high prevalence of colonic diverticulitis in the general population, further studies are needed to clarify the role of the intestinal microbiome, paving the way to new target therapies with important social implications.

Pathophysiology of Diverticular Disease: From Diverticula Formation to Symptom Generation.

Diverticular disease is a common clinical problem, particularly in industrialized countries. In most cases, colonic diverticula remain asymptomatic throughout life and sometimes are found incidentally during colonic imaging in colorectal cancer screening programs in otherwise healthy subjects. Nonetheless, roughly 25% of patients bearing colonic diverticula develop clinical manifestations. Abdominal symptoms associated with diverticula in the absence of inflammation or complications are termed symptomatic uncomplicated diverticular disease (SUDD). The pathophysiology of diverticular disease as well as the mechanisms involved in the shift from an asymptomatic condition to a symptomatic one is still poorly understood. It is accepted that both genetic factors and environment, as well as intestinal microenvironment alterations, have a role in diverticula development and in the different phenotypic expressions of diverticular disease. In the present review, we will summarize the up-to-date knowledge on the pathophysiology of diverticula and their different clinical setting, including diverticulosis and SUDD.

Treatment strategies for reducing early and late recurrence of colonic diverticular bleeding based on stigmata of recent hemorrhage: a large multicenter study.

BACKGROUND AND AIMS: Treatment strategies for colonic diverticular bleeding (CDB) based on stigmata of recent hemorrhage (SRH) remain unstandardized, and no large studies have evaluated their effectiveness. We sought to identify the best strategy among combinations of SRH identification and endoscopic treatment strategies. METHODS: We retrospectively analyzed 5823 CDB patients who underwent colonoscopy at 49 hospitals throughout Japan (CODE-BLUE J-Study). Three strategies were compared: find SRH (definitive CDB) and treat endoscopically, find SRH (definitive CDB) and treat conservatively, and without finding SRH (presumptive CDB) treat conservatively. In conducting pairwise comparisons of outcomes in these groups, we used propensity score-matching analysis to balance baseline characteristics between the groups being compared. RESULTS: Both early and late recurrent bleeding rates were significantly lower in patients with definitive CDB treated endoscopically than in those with presumptive CDB treated conservatively (<30 days, 19.6% vs 26.0% [P < .001]; <365 days, 33.7% vs 41.6% [P < .001], respectively). In patients with definitive CDB, the early recurrent bleeding rate was significantly lower in those treated endoscopically than in those treated conservatively (17.4% vs 26.7% [P = .038] for a single test of hypothesis; however, correction for multiple testing of data removed this significance). The late recurrent bleeding rate was also lower, but not significantly, in those treated endoscopically (32.0% vs 36.1%, P = .426). Definitive CDB treated endoscopically showed significantly lower early and late recurrent bleeding rates than when treated conservatively in cases of SRH with active bleeding, nonactive bleeding, and in the right-sided colon but not left-sided colon. CONCLUSIONS: Treating definitive CDB endoscopically was most effective in reducing recurrent bleeding over the short and long term, compared with not treating definitive CDB or presumptive CDB. Physicians should endeavor to find and treat SRH for suspected CDB.

Updates in the understanding and management of diverticular disease.

PURPOSE OF REVIEW: Diverticulosis leads to significant morbidity and mortality and is increasing in prevalence worldwide. In this paper, we review the clinical features, diagnosis, and management of diverticular disorders, followed by a discussion of recent updates and changes in the clinical approach to diverticular disease. RECENT FINDINGS: Recent literature suggests that antibiotics are likely not necessary for low-risk patients with acute uncomplicated diverticulitis, and not all patients with recurrent diverticulitis require colectomy. Dietary restrictions do not prevent recurrent diverticulitis. Visceral hypersensitivity is increasingly being recognized as a cause of persistent abdominal pain after acute diverticulitis and should be considered along with chronic smoldering diverticulitis, segmental colitis associated with diverticula, and symptomatic uncomplicated diverticular disease. SUMMARY: Clinicians should be aware that traditionally held assumptions regarding the prevention and management of diverticular disorders have recently been called into question and should adjust their clinical practice accordingly.

Diverticular Disease: A Review on Pathophysiology and Recent Evidence.

Diverticular disease is common condition globally, especially in Western countries. Diverticulitis, Symptomatic uncomplicated Diverticular disease and Segmental Colitis associated with diverticula constitute diverticular disease. Although most patients with diverticula are asymptomatic, around 25% of patients will experience symptoms whilst 5% of patients have an episode of acute diverticulitis. The prevalence increases with age with more than one theory being put forward to explain its pathogenesis. Faecolith entrapment in diverticula results in colonic mucosal damage and oedema, bacterial proliferation and toxin accumulation leading to perforation. This mechanism may explain diverticulitis in elderly patients with multiple, larger diverticula. Ischaemic damage could be the cause of acute diverticulitis in younger patients with sparse diverticula where more frequent and forceful muscular contractions in response to colonic stimuli occlude the vasculature leading to ischaemia and microperforation. Chronic colonic active inflammation in the presence of diverticular disease is termed Segmental colitis associated with diverticulosis. Its pathophysiology is still indeterminate but together with its clinical picture, may mimic Inflammatory Bowel Disease. Treatment includes a high fibre diet together with antibiotics and/or salicylates with surgery in severe cases. Indications for elective surgery in diverticular disease have changed over the past decades as this may not suggest a reduction in morbidity and mortality. Prophylaxis with probiotics, laxatives, anti-spasmotics, anticholinergic drugs and salicylates are at the centre of recent studies. Studies are also challenging previously believed facts regarding dietary fibre, nuts and seeds whilst emphasizing the effect of healthy lifestyle and smoking on the increasing incidence of DD.

Effectiveness of risk scoring systems in predicting endoscopic treatment in colonic diverticular bleeding.

BACKGROUND AND AIMS: The identification of stigmata of recent hemorrhage (SRH) in colonic diverticular bleeding (CDB) enables an endoscopic treatment and can improve the clinical outcome. However, SRH identification rate remains low. This study aims to investigate whether NOBLADS and Strate scoring systems are useful for predicting SRH identification rate of CDB pre-procedurally via colonoscopy. METHODS: In this single-center retrospective observational study, 302 patients who experienced their first episode of CDB from April 2008 to March 2018 were included. Patients were classified into SRH-positive and SRH-negative groups. The primary outcome was SRH identification rate. The secondary outcomes were active bleeding in SRH and early rebleeding rates. The usefulness of the NOBLADS and Strate scores as predicted values of SRH identification was evaluated using the area under the receiver operating characteristic curve. RESULTS: There were 126 and 176 patients in the SRH-positive and SRH-negative groups, respectively. The area under the receiver operating characteristic curve for SRH identification using the NOBLADS score was 0.74 (95% confidence interval, 0.69-0.80) and that using the Strate score was 0.74 (95% confidence interval, 0.68-0.79). Active bleeding and early rebleeding rates increased according to each score. By setting the cut-off of the NOBLADS score to four points, treatment was possible in 70.2% (66/94) patients. Addition of extravasation at computed tomography to a NOBLADS score of ≧ 4 points allowed treatment of all patients (24/24). CONCLUSIONS: Severity scoring in acute lower gastrointestinal bleeding was effective for predicting SRH identification in CDB. We suggest that combination of these scorings and CT findings could offer a new therapeutic strategy.

Enfermedad diverticular: nuevas perspectivas en el tratamiento dieto-terapéutico / Diverticular disease: new perspectives in diet-therapeutic treatment

La enfermedad diverticular corresponde a una condición habitual en el territorio occidental, siendo el hallazgo más frecuente en población de zonas urbanizadas. Respecto a su origen, se ha planteado la influencia de factores ambientales y genéticos, incluyendo en su etiología una inadecuada ingesta de fibra dietética, disbiosis de la microbiota intestinal y niveles alterados de vitamina D. A su vez, la enfermedad diverticular sintomática no complicada (EDNC) corresponde a un tipo de diverticulosis crónica cuyas características asemejan al síndrome de intestino irritable, lo que resalta la importancia en la comprensión de esta condición. Recientemente, se ha discutido la forma en que se aborda la enfermedad diverticular y en el siguiente escrito se expondrá evidencia sobre la patogénesis y su actual manejo.

Diverticular disease corresponds to a habitual condition in the western territory, being frequently found among the population of urban areas. Regarding its origin, the influence of environmental and genetic factors, including the etiology of dietary fiber intake, intestinal microbiota dysbiosis and altered levels of vitamin D have been recognized. Symptomatic uncomplicated diverticular disease corresponds to a type of chronic diverticulosis whose characteristics resemble irritable bowel syndrome, highlighting the importance of understanding this condition. Recently, the treatment of the disease has been discussed and the following review presents evidence on pathogenesis and its management.

Diverticular Disease in the Elderly.

PURPOSE OF REVIEW: While few diseases are limited solely to the elderly, diverticular disease is clearly more prevalent with increasing age and therefore the aim of this review is to focus on the clinical implications of diverticular disease in the elderly. RECENT FINDINGS: Diverticulitis in the elderly is best managed with an individualized treatment approach including considerations for selective antibiotic usage even in uncomplicated disease. Furthermore, due to the increased prevalence of ischemic colitis in the elderly and the similarities in presentation with diverticular hemorrhage, there needs to be a high index of suspicion and appropriate evaluation for ischemic colitis in patients with hematochezia, particularly if they have abdominal pain. The elderly are a vulnerable population where the index of suspicion for complications of diverticular disease should be high.

Diverticular disease management in primary care: How do estimates from community-dispensed antibiotics inform provision of care?

BACKGROUND: The literature regarding diverticular disease of the intestines (DDI) almost entirely concerns hospital-based care; DDI managed in primary care settings is rarely addressed. AIM: To estimate how often DDI is managed in primary care, using antibiotics dispensing data. DESIGN AND SETTING: Hospitalisation records of New Zealand residents aged 30+ years during 2007-2016 were individually linked to databases of community-dispensed oral antibiotics. METHOD: Patients with an index hospital admission 2007-2016 including a DDI diagnosis (ICD-10-AM = K57) were grouped by acute/non-acute hospitalisation. We compared use of guideline-recommended oral antibiotics for the period 2007-2016 for these people with ten individually-matched non-DDI residents, taking the case's index date. Multivariable negative binomial models were used to estimate rates of antibiotic use. RESULTS: From almost 3.5 million eligible residents, data were extracted for 51,059 index cases (20,880 acute, 30,179 non-acute) and 510,581 matched controls; mean follow-up = 8.9 years. Dispensing rates rose gradually over time among controls, from 47 per 100 person-years (/100py) prior to the index date, to 60/100py after 3 months. In comparison, dispensing was significantly higher for those with DDI: for those with acute DDI, rates were 84/100py prior to the index date, 325/100py near the index date, and 141/100py after 3 months, while for those with non-acute DDI 75/100py, 108/100py and 99/100py respectively. Following an acute DDI admission, community-dispensed antibiotics were dispensed at more than twice the rate of their non-DDI counterparts for years, and were elevated even before the index DDI hospitalisation. CONCLUSION: DDI patients experience high use of antibiotics. Evidence is needed that covers primary-care and informs self-management of recurrent, chronic or persistent DDI.

Current and Evolving Concepts on the Pathogenesis of Diverticular Disease.

BACKGROUND AND AIMS: Diverticulosis of the colon is the most common anatomic alteration of the human colon, and it is characterized by the out-pouching of the colonic mucosa and submucosa through the muscular layer. Recurrent abdominal pain is experienced by about 20% of patients with diverticulosis, and inflammation of diverticula may lead to acute diverticulitis. In the past few years, several studies have investigated the factors predisposing or triggering diverticular disease (DD) occurrence. Moreover, new physiopathological knowledge has been acquired. The aim of this study was to review current knowledge regarding the pathogenesis of DD. METHODS: A search of PubMed and EMBASE database was performed to identify articles relevant to the pathogenesis of DD. RESULTS: Several papers have shown that genetic predisposition, environmental factors, and colonic dysmotility are implicated in the pathogenesis of DD. More recent studies have associated specific host immune responses, gut microbiota imbalance and therefore low-grade inflammation as contributors to symptom occurrence in DD and diverticulitis. CONCLUSIONS: Current and evolving evidence highlighted the role of genetic susceptibility, environment, colonic motility, visceral sensitivity, immune response, and microbiota in the pathogenesis of this disease. Further studies are required to identify potential targets for medical or surgical decision-making.

Role of Inflammation in the Pathogenesis of Diverticular Disease.

Diverticulosis of the colon is the most common condition in Western societies and it is the most common anatomic alteration of the human colon. Recurrent abdominal pain is experienced by about 20% of patients with diverticulosis, but the pathophysiologic mechanisms of its occurrence are not completely understood. In the last years, several fine papers have showed clearly the role of low-grade inflammation both in the occurrence of symptoms in people having diverticulosis, both in symptom persistence following acute diverticulitis, even if the evidence available is not so strong. We do not know yet what the trigger of this low-grade inflammation occurrence is. However, some preliminary evidence found colonic dysbiosis linked to low-grade inflammation and therefore to symptom occurrence in those patients. The aim of this paper is to summarize current evidences about the role of inflammation in symptom occurrence in symptomatic uncomplicated diverticular disease and in symptom persistence after an episode of acute diverticulitis.

International Consensus on Diverticulosis and Diverticular Disease. Statements from the 3rd International Symposium on Diverticular Disease.

The statements produced by the Chairmen and Speakers of the 3rd International Symposium on Diverticular Disease, held in Madrid on April 11th-13th 2019, are reported. Topics such as current and evolving concepts on the pathogenesis, the course of the disease, the news in diagnosing, hot topics in medical and surgical treatments, and finally, critical issues on the disease were reviewed by the Chairmen who proposed 39 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 124 physicians from 18 countries, and agreement with all statements was provided. Comments were added explaining some controversial areas.

Pathogenesis of Diverticulosis and Diverticular Disease.

In this session different problems regarding the pathogenesis of diverticular disease were considered, including "Genetics", "Neuromuscular function abnormalities", "Patterns of mucosa inflammation", and "Impact of lifestyle". The patients affected by diverticular disease have clear genetic pattern, that might predispose to the occurrence of the disease as well as to its complications. Neuromuscular abnormalities may be recognized already at the stage of diverticulosis, and inflammation may explain symptoms occurrence in symptomatic uncomplicated diverticular disease (SUDD) or symptoms persistence after an episode of acute diverticulitis. Finally, lifestyle might also have an impact on symptoms' occurrence. Specifically smoking, but also obesity seem to play an important role, while the role of low-fiber diet and constipation is now under debate.

Topical haemostatic powder as a novel endoscopic therapy for severe colonic diverticular bleeding.

BACKGROUND: Although most diverticular bleeding resolve spontaneously, up to 30% can bleed torrentially, necessitating angioembolization, endoscopic or surgical intervention. Non-contact endoscopic therapies, such as topical haemostatic powders, do not require precise targeting and are attractive because identification of specific culprit diverticulum is difficult. While their use in non-variceal upper gastrointestinal bleeding is well established, its role in lower gastrointestinal bleeding remains unclear. We used topical Hemospray in a novel setting of severe diverticular bleeding, evaluating its efficacy in achieving haemostasis, reducing re-bleeding and the need for re-intervention. METHODS: Consecutive patients from a tertiary colorectal unit who underwent colonoscopy and Hemospray for severe diverticular bleeding from November 2016 to October 2017 were included. Hemospray was endoscopically applied to colonic segments with major stigmata of recent haemorrhage. RESULTS: Ten patients had a median time to colonoscopy of 22 h (range: 8-54) from admission. Median of 3.5 units (range: 0-10) of packed cells were transfused pre-endoscopy. All achieved immediate haemostasis without further haemodynamic instability or re-bleeding. No endoscopic, radiological or surgical re-intervention was required. Patients were fit for discharge within a median of 3 days (range: 2-7) following Hemospray. There were no morbidities, mortalities or readmissions for diverticular bleeding after a median follow-up of 9.5 months (range: 3-16). CONCLUSION: This feasibility study shows that topical haemostatic powders can offer a safe and effective therapeutic endoscopic option in severe diverticular bleeding with high haemostatic rate. Prospective controlled trials are required to establish its efficacy compared to conventional therapy.

The Use of Probiotics in Different Phases of Diverticular Disease.

BACKGROUND & AIMS: Diverticular Disease (DD) is a common clinical condition with a dramatic increasing of the prevalence among industrialized countries. Based on the most used classification, DD may be divided into asymptomatic diverticulosis, symptomatic uncomplicated diverticular disease and complicated diverticular disease. Since recent studies pointed out the role of GUT microbiota imbalance in promoting diverticular formation and inflammation, we have designed a systematic review focusing on the possible role of probiotics in the management of this condition. METHODS: According to PRISMA, we identified studies on DD patients treated with probiotics, by searching on Pubmed, Embase, Cochrane and ResearchGate. RESULTS: 13 studies were included in this review based on our selection criteria: 3 double-blind randomized placebo-controlled, 6 open randomized, and 4 non-randomized open studies. CONCLUSION: This is the first systematic review providing an updated measure of evidence on the efficacy of probiotics in a different phase of DD. Even though the majority of studies are still preliminary, current data show a possible clinical application of certain probiotic strains in all stages of DD. Further investigation is then required to better understand when and how probiotics can be used in different phases of DD.

Diverticular Disease: The Old, the New, and the Ever-Changing View.

Our understanding of diverticular disease has evolved significantly during the last 25 years, and as such, a reexamination is in order. We performed a literature search for the years 1960-2017 of PubMed, Medline, and Google Scholar for updates regarding the epidemiology, risk factors, and therapies for traditional diverticulitis as well as the recently described subtypes of diverticular disease, segmental colitis associated with diverticulosis, and symptomatic uncomplicated diverticular disease. Although the prevalence of diverticulosis is still extremely common in the general population, the literature suggests that the incidence of diverticulitis is much less than previously believed and occurrences do not necessarily increase with age. In addition, the commonly held beliefs that low-fiber diets alone contribute to the development of diverticulosis and diverticulitis have not been verified; however, the combination of a low-fiber diet and a high red meat/high-fat diet is a risk factor for diverticulitis. Surgery continues to be the treatment for severe complications of diverticulitis, but new literature suggests that it has a poor utility in preventing a recurrence of diverticulitis in the long term; therefore, elective surgery after two episodes of diverticulitis is no longer the standard.

Diverticular Disease: An Update on Pathogenesis and Management.

Diverticular disease is one of the most common conditions in the Western world and one of the most common findings identified at colonoscopy. Recently, there has been a significant paradigm shift in our understanding of diverticular disease and its management. The pathogenesis of diverticular disease is thought to be multifactorial and include both environmental and genetic factors in addition to the historically accepted etiology of dietary fiber deficiency. Symptomatic uncomplicated diverticular disease (SUDD) is currently considered a type of chronic diverticulosis that is perhaps akin to irritable bowel syndrome. Mesalamine, rifaximin and probiotics may achieve symptomatic relief in some patients with SUDD, although their role(s) in preventing complications remain unclear. Antibiotic use for acute diverticulitis and elective prophylactic resection surgery are considered more individualized treatment modalities that take into account the clinical status, comorbidities and lifestyle of the patient. Our understanding of the pathogenesis of diverticular disease continues to evolve and is likely to be diverse and multifactorial. Paradigm shifts in several areas of the pathogenesis and management of diverticular disease are explored in this review.