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Background: Fecal microbiota transplantation (FMT) is a highly effective treatment for recurrent Clostridioides difficile infection (CDI). However, 10-20% of patients still fail to recover following FMT. There is a need to understand why these failures occur and if there are modifiable factors that can be addressed by clinicians performing FMT., Aims: We sought to identify factors related to the FMT procedure itself which could impact FMT outcomes. We also aimed to identify patient demographics which might be associated with FMT outcomes and whether any factors were associated with early FMT failure compared to late CDI recurrence., Methods: We performed a retrospective multicenter cohort analysis of FMT procedures between October 2005 and November 2020. We collected data on patient demographics, details of the FMT procedure, and procedure outcomes. Using univariate and multivariate regression, we evaluated whether these factors were associated with long-term FMT success, early FMT failure (less than 60 days following procedure), or late CDI recurrence (more than 60 days following procedure)., Results: Long-term success of FMT was strongly correlated with any delivery of stool to the terminal ileum (Odds Ratio [OR] 4.83, 95% confidence interval [CI] 1.359-17.167) and underlying neurologic disease (OR 8.012, 95% CI 1.041-61.684). Lower bowel prep quality was significantly associated with both early FMT failure (p = 0.034) and late CDI recurrence (p = 0.050)., Conclusions: Delivery of stool to the terminal ileum is significantly associated with long-term success following FMT. This is a relatively safe practice which could easily be incorporated into the standard of care for colonoscopic FMT., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: The study objective was to compare gut microbiome diversity and composition in SARS-CoV-2 PCR-positive patients whose symptoms ranged from asymptomatic to severe versus PCR-negative exposed controls., Design: Using a cross-sectional design, we performed shotgun next-generation sequencing on stool samples to evaluate gut microbiome composition and diversity in both patients with SARS-CoV-2 PCR-confirmed infections, which had presented to Ventura Clinical Trials for care from March 2020 through October 2021 and SARS-CoV-2 PCR-negative exposed controls. Patients were classified as being asymptomatic or having mild, moderate or severe symptoms based on National Institute of Health criteria. Exposed controls were individuals with prolonged or repeated close contact with patients with SARS-CoV-2 infection or their samples, for example, household members of patients or frontline healthcare workers. Microbiome diversity and composition were compared between patients and exposed controls at all taxonomic levels., Results: Compared with controls (n=20), severely symptomatic SARS-CoV-2-infected patients (n=28) had significantly less bacterial diversity (Shannon Index, p=0.0499; Simpson Index, p=0.0581), and positive patients overall had lower relative abundances of Bifidobacterium (p<0.0001), Faecalibacterium (p=0.0077) and Roseburium (p=0.0327), while having increased Bacteroides (p=0.0075). Interestingly, there was an inverse association between disease severity and abundance of the same bacteria., Conclusion: We hypothesise that low bacterial diversity and depletion of Bifidobacterium genera either before or after infection led to reduced proimmune function, thereby allowing SARS-CoV-2 infection to become symptomatic. This particular dysbiosis pattern may be a susceptibility marker for symptomatic severity from SARS-CoV-2 infection and may be amenable to preinfection, intrainfection or postinfection intervention., Trial Registration Number: NCT04031469 (PCR-) and 04359836 (PCR+)., Competing Interests: Competing interests: SH declares that she has pecuniary interest in Topelia Pty Ltd in Australia, and Topelia Pty Ltd in USA where development of COVID-19 preventative/treatment options is being pursued. She has also filed patents relevant to Coronavirus treatments. She is the founder and owner of Microbiome research foundation, Progenabiome and Ventura Clinical Trials. TJB declares that he has pecuniary interest in Topelia Pty Ltd in Australia, and Topelia Therapeutics Inc. in USA developing COVID-19 preventative/treatment medications. He has also filed patents relevant to COVID-19 treatments. SD declares she has corporate affiliation to McKesson Specialty Health/Ontada and North End Advisory, LLC. SD is unaware of SARS-CoV-2 and microbiome projects and not directly involved in COVID-19 relevant projects at McKesson, but they may exist. AJP and BDB have corporate affiliations to Progenabiome. EMMQ serves as a consultant to Precisionbiotics, Novazymes, Salix, Biocodex and Axon Pharma and has received research support from 4D Pharma., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

In this session diverse critical issues in diverticular disease were considered, including "In or outpatient management of uncomplicated diverticulitis?", "Segmental colitis associated with diverticulosis: what is it?"and "Diverticular inflammation is a risk factor for colorectal cancer?". The conclusions drawn are outlined in the statements but in summary, outpatient management is safe in selected patients, as long as correct diagnosis and stage are assured, and this can allow a cost effective treatment. Non-antibiotic management is also safe but should be confined as an outpatient treatment in carefully selected patients.  Segmental colitis associated with diverticulosis (SCAD) is a defined pathological entity (only diagnosed on biopsy) characterized by an inflammatory bowel disease-like pathology, occurring principally in the sigmoid colon, with rectal and right colon sparing.  The pathogenesis is unclear but may include a genetic predisposition, microbiome alteration and ischaemia. Treatment can last months, and depends on severity, options include antibiotics, 5 ASA and probiotics for mild cases. Severe disease needs systemic steroids or even anti TNFα treatment.  Whether diverticular inflammation is a risk factor for colorectal cancer was debated and the conclusion that within the first eighteen months of diagnosis of diverticular disease associations with cancer are found, likely due to similar symptoms and misclassification of disease. After that time, diverticular disease does not increase the risk of colorectal cancer. Therefore, this is recommended to exclude cancer with imaging and colonoscopy after healing of the first episode of diverticulitis.

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.

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.

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.

Acute uncomplicated diverticulitis (AUD) is generally felt to be caused by obstruction and inflammation of a colonic diverticulum and occurs in about 4-5% of patients with diverticulosis. The cornerstone of AUD treatment has conventionally been antibiotic therapy, but with a paradigm shift in the underlying pathogenesis of the disease from bacterial infection to more of an inflammatory process, as well as concerns about antibiotic overuse, this dogma has recently been questioned. We will review emerging data that supports more selective antibiotic use in this population, as well as newer guidelines that advocate this position as well. While there are no discrete algorithms to guide us, we will attempt to suggest clinical scenarios where antibiotics may reasonably be withheld.

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.

Goals: The aim of this study was to compare upper gastrointestinal (UGI) versus lower gastrointestinal (LGI) delivery routes of fecal microbiota transplantation (FMT) for refractory or recurrent/relapsing Clostridium difficile infection (CDI)., Background: FMT has been proven to be a safe and highly effective therapeutic option for CDI. Delivery, however, could be via the UGI or LGI routes, and it is unclear as to which route provides better clinical outcome., Study: A systematic search for studies that reported the use of FMT for CDI treatment was conducted. Individual patient data that included demographic (age and sex) and clinical (route of FMT delivery, CDI outcome after FMT, and follow-up time) information were obtained. Kaplan-Meier cumulative hazard curves and Cox proportional hazard models were used to assess clinical failure after FMT by the route of delivery., Results: Data from 305 patients treated with FMT (208 via LGI route and 97 via UGI route) for CDI were analyzed. At 30 and 90 days, the risk of clinical failure was 5.6% and 17.9% in the UGI group compared with 4.9% and 8.5% in the LGI delivery route group, respectively. A time-varying analysis suggested a 3-fold increase in hazard of clinical failure for UGI delivery (hazard ratio, 3.43; 95% confidence interval, 1.32-8.93) in the period after 30 days., Conclusions: FMT delivered via the LGI seems to be the most effective route for the prevention of recurrence/relapse of CDI. A randomized controlled trial is necessary to confirm whether FMT delivered via the LGI is indeed superior to that delivered via the UGI route.

Goal: Our aim was to investigate fecal microbiota transplantation (FMT) efficacy in patients with severe and/or complicated Clostridium difficile infection (CDI)., Background: FMT is successful for recurrent CDI, although its benefit in severe or complicated CDI has not specifically been evaluated., Study Methods: A multicenter long-term follow-up study was performed in patients who received FMT for severe and/or complicated CDI (diagnosed using standard criteria). Pre-FMT and post-FMT questionnaires were completed. Study outcomes included cure rates and time to resolution of symptoms., Results: A total of 17 patients (82% inpatients, 18% outpatients) were included (76.4% women; mean age, 66.4 y; mean follow-up, 11.4 mo). Patients had severe and complicated (76.4%) or either severe or complicated (23.6%) CDI. Sixteen patients (94.1%) had diarrhea, which resolved in 12 (75%; mean time to resolution, 5.7 d) and improved in 4 (25%) after FMT. Eleven patients (64.7%) had abdominal pain, which resolved in 8 (72.7%; mean time to resolution, 9.6 d) and improved in 3 (27.3%) after FMT. Two of 17 patients experienced early CDI recurrence (≤90 d) after FMT (primary cure rate, 88.2%); and in 1 patient, a second FMT resulted in cure (secondary cure rate, 94.1%). Late CDI recurrence (≥90 d) was seen in 1 of 17 patients (5.9%) in association with antibiotics and was successfully treated with a repeat FMT. No adverse effects directly related to FMT occurred., Conclusions: FMT was successful and safe in this cohort of patients with severe or complicated CDI. Primary and secondary cure rates were 88.2% and 94.1%, respectively.

Objectives: Clostridium difficile infection (CDI) in the elderly has a higher prevalence, greater morbidity and mortality, and lower response to conventional treatment than the general population. Fecal microbiota transplant (FMT) is highly effective therapy for CDI but has not been studied specifically in the elderly. This study aims to determine the long-term efficacy and safety of FMT for recurrent (RCDI), severe (SCDI), and complicated (CCDI) CDI in elderly patients., Methods: A multicenter, long-term follow-up study was performed with demographic, pre-FMT, and post-FMT data collected from elderly patients with RCDI, SCDI, and CCDI, through a 47-item questionnaire. Outcome measures included primary and secondary cure rates, early (<12 wk) and late (≥12 wk) recurrence rates, and adverse events (AEs), including post-FMT diagnoses., Results: Of 168 eligible patients, 146 patients met the inclusion criteria. Of these, 68.5% were women. The mean (range) age was 78.6 (65 to 97) years and the follow-up period was 12.3 (1 to 48) months. FMT was performed for RCDI in 89 (61%), SCDI in 45 (30.8%), and CCDI in 12 (8.2%) patients. The primary and secondary cure rates were 82.9% and 95.9%, respectively. Early and late recurrences occurred in 25 and 6 patients, respectively. AEs included CDI-negative diarrhea in 7 (4.8%) and constipation in 4 (2.7%) patients. Serious AEs, recorded in 6 patients, were hospital admissions for CDI-related diarrhea, one of which culminated in death. New diagnoses post-FMT included microscopic colitis (2), Sjogren syndrome (1), follicular lymphoma (1), contact dermatitis and idiopathic Bence-Jones proteinuria (1), and laryngeal carcinoma (1)-all, however, were associated with predisposing factors., Conclusions: FMT is a safe and effective treatment option for RCDI, SCDI, and CCDI in elderly patients.

Purpose of Review: Diverticular disease is the most commonly reported finding at the time of colonoscopy and one of the most common gastrointestinal indications for hospitalization. Much of our previous understanding of diverticular disease has recently been challenged., Recent Findings: There is emerging evidence that the long-accepted hypothesis of diverticulosis as a consequence of fiber deficiency may be more complex than commonly thought, with recent evidence suggesting that high-fiber diet and frequent bowel movements are associated with a greater and not lower prevalence of diverticular disease. There is also emerging support for the concept of low-grade inflammation in symptomatic uncomplicated diverticular disease (SUDD), and the role of anti-inflammatory treatment with mesalamine is being actively investigated. Additionally, elective 'prophylactic' surgery after diverticulitis, previously considered after a second confirmed diverticulitis episode, is being increasingly deferred., Summary: The pathogenesis of diverticular disease is likely multifactorial and complex. More studies are needed to evaluate the role of fiber in the pathogenesis and treatment of diverticular disease. The search for an effective medical therapy for SUDD and to prevent recurrent diverticulitis is being actively investigated. The efficacy of mesalamine does not appear to be strong data supported.

Objectives: Patients who are immunocompromised (IC) are at increased risk of Clostridium difficile infection (CDI), which has increased to epidemic proportions over the past decade. Fecal microbiota transplantation (FMT) appears effective for the treatment of CDI, although there is concern that IC patients may be at increased risk of having adverse events (AEs) related to FMT. This study describes the multicenter experience of FMT in IC patients., Methods: A multicenter retrospective series was performed on the use of FMT in IC patients with CDI that was recurrent, refractory, or severe. We aimed to describe rates of CDI cure after FMT as well as AEs experienced by IC patients after FMT. A 32-item questionnaire soliciting demographic and pre- and post-FMT data was completed for 99 patients at 16 centers, of whom 80 were eligible for inclusion. Outcomes included (i) rates of CDI cure after FMT, (ii) serious adverse events (SAEs) such as death or hospitalization within 12 weeks of FMT, (iii) infection within 12 weeks of FMT, and (iv) AEs (related and unrelated) to FMT., Results: Cases included adult (75) and pediatric (5) patients treated with FMT for recurrent (55%), refractory (11%), and severe and/or overlap of recurrent/refractory and severe CDI (34%). In all, 79% were outpatients at the time of FMT. The mean follow-up period between FMT and data collection was 11 months (range 3-46 months). Reasons for IC included: HIV/AIDS (3), solid organ transplant (19), oncologic condition (7), immunosuppressive therapy for inflammatory bowel disease (IBD; 36), and other medical conditions/medications (15). The CDI cure rate after a single FMT was 78%, with 62 patients suffering no recurrence at least 12 weeks post FMT. Twelve patients underwent repeat FMT, of whom eight had no further CDI. Thus, the overall cure rate was 89%. Twelve (15%) had any SAE within 12 weeks post FMT, of which 10 were hospitalizations. Two deaths occurred within 12 weeks of FMT, one of which was the result of aspiration during sedation for FMT administered via colonoscopy; the other was unrelated to FMT. None suffered infections definitely related to FMT, but two patients developed unrelated infections and five had self-limited diarrheal illness in which no causal organism was identified. One patient had a superficial mucosal tear caused by the colonoscopy performed for the FMT, and three patients reported mild, self-limited abdominal discomfort post FMT. Five (14% of IBD patients) experienced disease flare post FMT. Three ulcerative colitis (UC) patients underwent colectomy related to course of UC >100 days after FMT., Conclusions: This series demonstrates the effective use of FMT for CDI in IC patients with few SAEs or related AEs. Importantly, there were no related infectious complications in these high-risk patients.

Background/aims: We evaluated the efficacy of mesalamine (Asacol) in reducing gastrointestinal symptoms after an acute attack of diverticulitis., Methods: This was a 1-year double-blind, randomized, placebo-controlled study in which patients with computed tomography scan confirmed acute diverticulitis received placebo, mesalamine, or mesalamine+Bifidobacterium infantis 35624 (Align) for 12 weeks and followed for 9 additional months. Efficacy was assessed using a global symptom score (GSS) of 10 symptoms (abdominal pain, abdominal tenderness, nausea/vomiting, bloating, constipation, diarrhea, mucus, urgency, painful straining, and dysuria). Patients were required to have a GSS≥12 at baseline, including an abdominal pain score >2., Results: One hundred seventeen patients (placebo, 41; mesalamine, 40; mesalamine+probiotic, 36) were randomized and treated. GSS decreased in all groups during treatment without a statistically significant difference between mesalamine and placebo, however; scores were consistently lower for mesalamine at all time points. The rate of complete response (GSS=0) was significantly higher with mesalamine than placebo at weeks 6 and 52 (P<0.05), and was particularly high for rectosigmoid symptoms at weeks 6, 12, 26, and 52. Recurrence of diverticulitis was low and comparable across groups. Probiotic in combination with mesalamine did not provide additional efficacy., Conclusions: In the first US randomized placebo-controlled trial of anti-inflammatory treatment after a documented case of diverticulitis, mesalamine demonstrated a consistent trend in reducing symptoms. Addition of probiotic did not increase mesalamine efficacy. This study supports further investigation into the use of anti-inflammatory agents, such as mesalamine, in the long-term management of diverticulitis. ClinicalTrials.gov NCT00554099.

Clostridium difficile infection rates are Climbing in frequency and severity, and the spectrum of susceptible patients is expanding beyond the traditional scope of hospitalized patients receiving antibiotics. Fecal microbiota transplantation is becoming increasingly accepted as an effective and safe intervention in patients with recurrent disease, likely due to the restoration of a disrupted microbiome. Cure rates of > 90% are being consistently reported from multiple centers. Transplantation can be provided through a variety of methodologies, either to the lower proximal, lower distal, or upper gastrointestinal tract. This review summarizes reported results, factors in donor selection, appropriate patient criteria, and the various preparations and mechanisms of fecal microbiota transplant delivery available to clinicians and patients.

Helicobacter pylori infection is highly prevalent, affecting approximately half of the world's population. While the majority of infected individuals are asymptomatic, H. pylori infection is associated with certain diseases, including peptic ulcers (either duodenal or gastric), gastritis, and 2 malignancies-gastric cancer and gastric mucosa-associated lymphoid tissue lymphoma. Many of the epidemiologic associations between these diseases and H. pylori infection have been further validated by treatment studies, which show that effective eradication therapy correlates with a decreased risk of disease. A variety of testing strategies are used to detect H. pylori infection. Serologic techniques are widely available and inexpensive, but they are no longer preferred as they have low sensitivities and specificities, and they may show a positive result for a long period following effective therapy. The remaining testing methods are divided into 2 categories: invasive tests (which require endoscopy) and noninvasive tests. Noninvasive test methods such as the urea breath test and stool antigen test have gained popularity due to their high sensitivities and specificities. Further, both of these methods may be used to confirm the absence of infection following eradication therapy. Due to the increasing incidence of treatment failure (caused in part by antibiotic resistance), post-treatment testing is recommended to confirm H. pylori eradication.

Objectives: Clostridium difficile infection (CDI) has increased to epidemic proportions over the past 15 years, and recurrence rates of 30-65% with failure to respond to multiple courses of antimicrobials are common. The aim of this study was to report the efficacy of fecal microbiota transplantation (FMT) in patients with recurrent CDI in five geographically disparate medical centers across the United States., Methods: A multicenter long-term follow-up study was performed on the use of FMT for recurrent CDI. We were able to contact 77 of 94 eligible patients who had colonoscopic FMT for recurrent CDI ≥ 3 months before. Respondents completed a 36-item questionnaire via mail and/or phone that solicited pre-FMT, post-FMT, and donor data. Study outcomes included primary cure rate (resolution of symptoms without recurrence within 90 days of FMT) and secondary cure rate (resolution of symptoms after one further course of vancomycin with or without repeat FMT)., Results: Seventy-three percent of patients were women and the average age was 65 years. The long-term follow-up period ranged from 3 to 68 months between FMT and data collection (mean: 17 months). The majority of patients were living independently at the time of FMT; however, 40% were ill enough to be hospitalized, homebound, or living in a skilled nursing facility. Spouses and partners accounted for 60% of donors and 27% were either first-degree relatives or otherwise related to the patient. The average symptom duration before FMT was 11 months and patients had failed an average of five conventional antimicrobial regimens; nonetheless, 74% of patients had resolution of their diarrhea in ≤ 3 days. Diarrhea resolved in 82% and improved in 17% of patients within an average of 5 days after FMT. The primary cure rate was 91%. Seven patients either failed to respond or experienced early CDI recurrence (≤ 90 days) after FMT. Four of these patients were successfully treated with vancomycin with or without probiotics; two patients were treated unsuccessfully with vancomycin, but subsequent FMT was successful; one patient was not treated and died in hospice care of unclear cause. The secondary cure rate was 98%. All late recurrences of CDI occurred in the setting of antimicrobial therapy for treatment of infections unrelated to C. difficile. In all, 53% of patients stated they would have FMT as their preferred first treatment option if CDI were to recur. While no definite adverse effects of FMT were noted, two patients had improvement in a pre-existing medical condition and four patients developed diseases of potential interest after FMT., Conclusions: FMT is a rational, durable, safe, and acceptable treatment option for patients with recurrent CDI.

Gastrointestinal complications frequently occur in patients admitted to the intensive care unit. Of these, ulceration and bleeding related to stress-related mucosal disease (SRMD) can lengthen hospitalization and increase mortality. The purpose of this review is to discuss the many risk factors and underlying illnesses that have a role in the pathophysiology of SRMD and evaluate the evidence pertaining to SRMD prophylaxis in the intensive care unit population. Suppressing acid production is fundamental to preventing stress-related mucosal ulceration and clinically important gastrointestinal bleeding. Traditional prophylactic options for SRMD in critically ill patients include antacids, sucralfate, histamine 2 -receptor antagonists (H 2 RAs), and proton pump inhibitors. Many clinicians prescribe intermittent infusions of H 2 RAs for stress ulcer prophylaxis, a practice that has not been approved for this indication and may not provide the necessary degree or duration of acid suppression required to prevent stress ulcer-related bleeding. New data suggest that proton pump inhibitors suppress acid production more completely in critically ill patients, but more studies are required to assess their clinical effectiveness and safety for this indication. The prophylactic regimen chosen to prevent stress ulcer bleeding should take into account the risk factors and underlying disease state of individual patients to provide the best therapy to those most likely to benefit.

While medical therapy, particularly with proton pump inhibitors, is effective for the large majority of patients with reflux disease, there remains a subset of patients who are dissatisfied, due to cost, side effects of medications, or persistent symptoms such as regurgitation. For this population, surgical fundoplication has been, and remains, an appropriate option. A new class of endoluminal interventions, attempting to create a mechanical antireflux barrier, has emerged recently. Three such devices are currently approved and available, and a number of others are in various stages of evaluation. This article will review the approved technologies, as well as selected promising emerging ones. with particular emphasis on the scientific evidence available to date supporting their efficacy.

The main treatment goals in amyloidosis are twofold: 1) to diagnose the underlying disease state accurately to guide effective primary therapy (if available) and 2) to ameliorate symptoms. The correct diagnosis is essential because disease-modifying therapies vary widely according to the underlying primary pathology. Primary treatment options remain limited. The best evidence is for high-dose chemotherapy, followed by autologous stem cell transplantation in patients with primary systemic amyloidosis. High-flux hemodialysis (HD) may prevent HD-related amyloidosis. Liver transplantation may be an option for patients with familial amyloidotic polyneuropathy. Several novel specific therapies are under investigation, including small molecule drugs and vaccines. Their efficacy and safety in humans remain to be demonstrated. In the absence of specific cures, symptom-directed therapy assumes a paramount role and can improve quality of life by mitigating diarrhea or pain, for example.

Diverticulosis, which is an acquired condition marked by mucosal herniation through defects in the colonic wall, has been termed both a "disease of the 20th century" and a "disease of Western civilization" due to its increasing prevalence in modern times and its striking geographical variability. Both of these epidemiological observations may provide interesting insights into the pathophysiology of diverticulosis. This chapter will review the known epidemiology of diverticulosis coli and its main complications: diverticulitis and diverticular haemorrhage. Where possible, attempts will be made to place these observational reports in the context of both the cause and clinical behaviour of this disorder.