Role of antibiotics for treatment of inflammatory bowel disease

Inflammatory bowel disease is thought to be caused by an aberrant immune response to gut bacteria in a genetically susceptible host. The gut microbiota plays an important role in the pathogenesis and complications of the two main inflammatory bowel diseases: Crohn's disease(CD) and ulcerative colitis. Alterations in gut microbiota, and specifically reduced intestinal microbial diversity, have been found to be associated with chronic gut inflammation in these disorders. Specific bacterial pathogens, such as virulent Escherichia coli strains, Bacteroides spp, and Mycobacterium avium subspecies paratuberculosis, have been linked to the pathogenesis of inflammatory bowel disease. Antibiotics may influence the course of these diseases by decreasing concentrations of bacteria in the gut lumen and altering the composition of intestinal microbiota. Different antibiotics, including ciprofloxacin, metronidazole, the combination of both, rifaximin, and anti-tuberculous regimens have been evaluated in clinical trials for the treatment of inflammatory bowel disease. For the treatment of active luminal CD, antibiotics may have a modest effect in decreasing disease activity and achieving remission, and are more effective in patients with disease involving the colon. Rifamixin, a non absorbable rifamycin has shown promising results. Treatment of suppurative complications of CD such as abscesses and fistulas, includes drainage and antibiotic therapy, most often ciprofloxacin, metronidazole, or a combination of both. Antibiotics might also play a role in maintenance of remission and prevention of post operative recurrence of CD. Data is more sparse for ulcerative colitis, and mostly consists of small trials evaluating ciprofloxacin, metronidazole and rifaximin. Most trials did not show a benefit for the treatment of active ulcerative colitis with antibiotics, though 2 meta-analyses concluded that antibiotic therapy is associated with a modest improvement in clinical symptoms. Antibiotics show a clinical benefit when used for the treatment of pouchitis. The downsides of antibiotic treatment, especially with recurrent or prolonged courses such as used in inflammatory bowel disease, are significant side effects that often cause intolerance to treatment, Clostridium dificile infection, and increasing antibiotic resistance. More studies are needed to define the exact role of antibiotics in inflammatory bowel diseases.     

Infertility in men with inflammatory bowel disease

Inflammatory bowel disease(IBD) predominantly affects young adults. Fertility-related issues are therefore im-portant in the m-anagem-ent of patients with IBD. However, relatively m-odest attention has been paid to reproductive issues faced by m-en with IBD. To investigate the effects of IBD and its treatm-ent on m-ale fertility, we reviewed the current literature using a system-atic search for published studies. A PubM ed search were perform-ed using the m-ain search term-s "IBD AND m-ale infertility", "Crohn's disease AND m-ale infertility", "ulcerative colitis AND m-ale infertility". References in review articles were used if relevant. We noted that active inflammation, poor nutrition, alcohol use, sm-oking, m-edications, and surgery m-ay cause infertility in m-en with IBD. In surgery such as proctocolectom-y with ileal pouch-anal anastom-osis, rectal incision seem-s to be associated with sexual dysfunction. Of the m-edications used for IBD, sulfasalazine reversibly reduces m-ale fertility. No other m-edications appear to affect m-ale fertility significantly, although sm-all studies suggested som-e adverse effects. There are lim-ited data on the effects of drugs for IBD on m-ale fertility and pregnancy outcom-es; however, patients should be inform-ed of the possible effects of paternal drug exposure. This review provides inform-ation on fertility-related issues in m-en with IBD and discusses treatm-ent options.     

Differential diagnosis in inflammatory bowel disease colitis:State of the art and future perspectives

Distinction between Crohn's disease of the colonrectum and ulcerative colitis or inflammatory bowel disease(IBD) type unclassified can be of pivotal importance for a tailored clinical management,as each entity often involves specific therapeutic strategies and prognosis.Nonetheless,no gold standard is available and the uncertainty of diagnosis may frequently lead to misclassification or repeated examinations.Hence,we have performed a literature search to address the problem of differential diagnosis in IBD colitis,revised current and emerging diagnostic tools and refined disease classification strategies.Nowadays,the differential diagnosis is an untangled issue,and the proper diagnosis cannot be reached in up to 10% of patients presenting with IBD colitis.This topic is receiving emerging attention,as medical therapies,surgical approaches and leading prognostic outcomes require more and more disease-specific strategies in IBD patients.The optimization of standard diagnostic approaches based on clinical features,biomarkers,radiology,endoscopy and histopathology appears to provide only marginal benefits.Conversely,emerging diagnostic techniques in the field of gastrointestinal endoscopy,molecular pathology,genetics,epigenetics,metabolomics and proteomics have already shown promising results.Novel advanced endoscopic imaging techniques and biomarkers can shed new light for the differential diagnosis of IBD,better reflecting diverse disease behaviors based on specific pathogenic pathways.     

Elderly patients and inflammatory bowel disease

The incidence and prevalence of inflammatory bowel disease(IBD) is increasing globally. Coupled with an ageing population, the number of older patients with IBD is set to increase. The clinical features and therapeutic options in young and elderly patients are comparable but there are some significant differences. The wide differential diagnosis of IBD in elderly patients may result in a delay in diagnosis. The relative dearth of data specific to elderly IBD patients often resulting from their exclusion from pivotal clinical trials and the lack of consensus guidelines have made clinical decisions somewhat challenging. In addition, age specific concerns such as co-morbidity; locomotor and cognitive function, poly-pharmacy and its consequences need to be taken into account. In applying modern treatment paradigms to the elderly, the clinician must consider the potential for more pronounced adverse effects in this vulnerable group and set appropriate boundaries maximising benefit and minimising harm. Meanwhile, clinicians need to make personalised decisions but as evidence based as possible in the holistic, considered and optimal management of IBD in elderly patients. In this review we will cover the clinical features and therapeutic options of IBD in the elderly; as well as addressing common questions and challenges posed by its management.     

Thiopurines and inflammatory bowel disease: Current evidence and a historical perspective

The use of thiopurines in inflammatory bowel disease(IBD) has been examined in numerous prospective, controlled trials, with a majority demonstrating a clinical benefit. We conducted this review to describe the historical and current evidence in the use of thiopurines in IBD. A systematic search was performed on MEDLINE between 1965 and 2016 to identify studies on thiopurines in IBD. The most robust evidence for thiopurines in IBD includes induction of remission in combination with anti-tumor necrosis factor(antiTNF) agents, and maintenance of remission and postoperative maintenance in Crohn's disease. Less evidence exists for thiopurine monotherapy in induction of remission, maintenance of ulcerative colitis, chemoprevention of colorectal cancer, and in preventing immunogenicity to anti-TNF. Evidence was often limited by trial design. Overall, thiopurines have demonstrated efficacy in a broad range of presentations of IBD. With more efficacious novel therapeutic agents, the positioning of thiopurines in the management of IBD will change and future studies will analyze the benefit of thiopurines alone and in conjunction with these new medications.     

Cytomegalovirus in inflammatory bowel disease: A systematic review

AIM: To identify definitions of cytomegalovirus(CMV) infection and intestinal disease, in inflammatory bowel disease(IBD), to determine the prevalence associated with these definitions.METHODS: We conducted a systematic review and interrogated Pub Med, EMBASE and Cochrane for literature on prevalence and diagnostics of CMV infection and intestinal disease in IBD patients. As medical headings we used "cytomegalovirus" OR "CMV" OR "cytomegalo virus" AND "inflammatory bowel disease" OR "IBD" OR "ulcerative colitis" OR "colitis ulcerosa" OR "Crohn's disease". Both Me SH-terms and free searches were performed. We included all types of English-language(clinical) trials concerning diagnostics and prevalence of CMV in IBD.RESULTS: The search strategy identified 924 citations, and 52 articles were eligible for inclusion. We identified 21 different definitions for CMV infection, 8 definitions for CMV intestinal disease and 3 definitions for CMV reactivation. Prevalence numbers depend on used definition, studied population and region. The highest prevalence for CMV infection was found when using positive serum PCR as a definition, whereas for CMV intestinal disease this applies to the use of tissue PCR 10 copies/mg tissue. Most patients with CMV infection and intestinal disease had steroid refractory disease and came from East Asia.CONCLUSION: We detected multiple different definitions used for CMV infection and intestinal disease in IBD patients, which has an effect on prevalence numbers and eventually on outcome in different trials.     

Video capsule endoscopy in inflammatory bowel disease

Video capsule endoscopy(VCE) has evolved to become an important tool for the non-invasive examination of the small bowel, which hitherto had been relatively inaccessible to direct visualisation. VCE has beenshown to play a role in monitoring the activity of small bowel Crohn's disease and can be used to assess the response to anti-inflammatory treatment in Crohn's disease. For those patients with Crohn's disease who have undergone an intestinal resection, VCE has been assessed as a tool to detect post-operative recurrence. VCE may also aid in the reclassification of patients with a diagnosis of Inflammatory Bowel Disease Unclassified to Crohn's disease. The evolution of colon capsule endoscopy(CCE) has expanded the application of this technology further. The use of CCE to assess the activity of ulcerative colitis has been described. This advance in capsule technology has also fuelled interest in its potential role as a minimally invasive tool to assess the whole of GI tract opening the possibility of its use for the panenteric assessment of Crohn's disease. VCE is a safe procedure. However, the risk of a retained capsule is higher in patients with suspected or confirmed Crohn's disease compared with patients having VCE examination for other indications. A retained video capsule is rare after successful passage of a patency capsule which may be utilised to pre-screen patients undergoing VCE. This paper describes the use of VCE in the assessment of inflammatory bowel disease.     

Disease monitoring in inflammatory bowel disease

The optimal method for monitoring quiescent disease in patients with Crohn's disease(CD) and ulcerative colitis is yet to be determined. Endoscopic evaluation with ileocolonoscopy is the gold standard but is invasive,costly,and time-consuming. There are many commercially available biomarkers that may be used in clinical practice to evaluate disease status in patients with inflammatory bowel disease(IBD),but the most widely adopted biomarkers are C-reactive protein(CRP) and fecal calprotectin(FC). This review summarizes the evidence for utilizing CRP and FC for monitoring IBD during clinical remission and after surgical resection. Endoscopic correlation with CRP and FC is evaluated in each disease state. Advantages and drawbacks of each biomarker are discussed with special consideration of isolated ileal CD. Fecal immunochemical testing,traditionally used for colorectal cancer screening,is mentioned as a potential new alternative assay in the evaluation of IBD. Based on a mixture of information gleaned from biomarkers,clinical status,and endoscopic evaluation,the best treatment decisions can be made for the patient with IBD.     

Inter- and intraobserver agreement in computed tomography enterography in inflammatory bowel disease

AIM To evaluate intra- and interobserver agreement in imaging features in inflammatory bowel disease and comparison with fecal calprotectin(FC) levels.METHODS Our institutional computed tomography enterography(CTE) database was retrospectively queried to identify patients who underwent CTE from January 2014 to June 2015. Patient inclusion criteria were confirmed inflammatory bowel disease(IBD) and FC collected 4 mo after CTE without any change in clinical treatment or surgical treatment during this interval. The exclusion criterion was poor image quality. Two blinded abdominal radiologists, with 12 and 3 years of experience analyzed the CTE regarding localization(small bowel, colonic, both, or no disease detected);type of IBD(inflammatory, stenosing, fistulizing, 1 pattern, or normal); and signs of active disease(present or absent). In 42 of 44 patients evaluated, routine CTE reports were made by one of the readers who reevaluated the CTEs ≥ 6 mo later, to determine the intraobserver agreement. FC was considered a sign of disease activity when it was higher than 250 μg/g.RESULTS Forty-four patients with IBD(38 with Crohn's disease and 6 with ulcerative colitis) were included. There was a moderate interobserver agreement regarding localization of IBD(k = 0.540), type of disease(k = 0.410) and the presence of active signs in CTE(k = 0.419). There was almost perfect intraobserver agreement regarding localization, type and signs of active disease in IBD. The k values were 0.902, 0.937 and 0.830, respectively. After a consensus between both radiologists regarding inflammatory activity in CTE, we found that 24(85.7%) of 28 patients who were classified with active disease had elevated FC, and six(37.5%) of 16 patients without inflammatory activity in CTE had elevated FC(P = 0.003). The correlation between elevated FC and the presence of active disease in CTE was significant(k = 0.495, P = 0.001).CONCLUSION We found almost perfect intraobserver and moderate interobserver agreement in the signs of active disease in CTE with concurrence of high FC levels.     

Emerging role of novel biomarkers in the diagnosis of inflammatory bowel disease

There is currently no gold standard test for the diagnosis of inflammatory bowel disease(IBD). Physicians must rely on a number of diagnostic tools including clinical and endoscopic evaluation as well as histologic, serologic and radiologic assessment. The real difficulty for physicians in both primary and secondary care is differentiating between patients suffering from functional symptoms and those with true underlying IBD. Alongside this, there is always concern regarding the possibility of a missed, or delayed diagnosis of ulcerative colitis(UC) or Crohn's disease. Even once the diagnosis of IBD has been made, there is often uncertainty in distinguishing between cases of UC or Crohn's. As a consequence, in cases of incorrect diagnosis, optimal treatment and management may be adversely affected. Endoscopic evaluation can be uncomfortable and inconvenient for patients. It carries significant risks including perforation and in terms of monetary cost, is expensive. The use of biomarkers to help in the diagnosis and differentiation of IBD has been increasing over time. However, there is not yet one biomarker, which is sensitive of specific enough to be used alone in diagnosing IBD. Current serum testing includes C-reactive protein and erythrocyte sedimentation rate, which are cheap, reliable but non-specific and thus not ideal. Stool based testing such as faecal calprotectin is a much more specific tool and is currently in widespread clinical use. Noninvasive sampling is of the greatest clinical value and with the recent advances in metabolomics, genetics and proteomics, there are now more tools available to develop sensitive and specific biomarkers to diagnose and differentiate between IBD. Many of these new advances are only in early stages of development but show great promise for future clinical use.     

Pancreatic disorders in inflammatory bowel disease

An increased incidence of pancreatic disorders either acute pancreatitis or chronic pancreatitis has been rec-orded in patients with inflammatory bowel disease(IBD) compared to the general population.Although most of the pancreatitis in patients with IBD seem to be related to biliary lithiasis or drug induced,in some cases pancreatitis were defined as idiopathic,suggesting a direct pancreatic damage in IBD.Pancreatitis and IBD may have similar presentation therefore a pancreatic disease could not be recognized in patients with Crohn's disease and ulcerative colitis.This review will discuss the most common pancreatic diseases seen in patients with IBD.     

营养与炎症性肠病

营养和炎症性肠病的发病机制及治疗有密切的关系,深入研究两者的关系对临床有重要的意义。此文对饮食中的营养成分是否和发病有关、如何营养支持等问题作一简要概述。     

Endoscopic evaluation in diagnosis and management of inflammatory bowel disease

Endoscopy is a keystone in the management of patients with inflammatory bowel disease(IBD).It is the fundamental diagnostic tool for IBD,and can help discern between ulcerative colitis and Crohn's disease.Endoscopic assessment provides an objective end point in clinical trials,and identifies patients in clinical practice who may benefit from treatment escalation and may assist risk stratification in patients seeking to discontinue therapy.Recent advances in endoscopic assessment of patients with IBD include video capsule endoscopy,and chromoendoscopy.Technological advances enable improved visualization and focused biopsy sampling.Endoscopic resection and close surveillance of dysplastic lesions where feasible is recommended instead of prophylactic colectomy.     

Oral pathology in inflammatory bowel disease

The incidence of inflammatory bowel diseases(IBD)-Crohn's disease(CD) and ulcerative colitis(UC)- has been increasing on a global scale, and progressively, more gastroenterologists will be included in the diagnosis and treatment of IBD. Although IBD primarily affects the intestinal tract, extraintestinal manifestations of the disease are often apparent, including in the oral cavity, especially in CD. Specific oral manifestations in patients with CD are as follows: indurate mucosal tags, cobblestoning and mucogingivitis, deep linear ulcerations and lip swelling with vertical fissures. The most common non-specific manifestations, such as aphthous stomatitis and angular cheilitis, occur in both diseases, while pyostomatitis vegetans is more pronounced in patients with UC. Non-specific lesions in the oral cavity can also be the result of malnutrition and drugs. Malnutrition, followed by anemia and mineral and vitamin deficiency, affects the oral cavity and teeth. Furthermore, all of the drug classes that are applied to the treatment of inflammatory bowel diseases can lead to alterations in the oral cavity due to the direct toxic effects of the drugs on oral tissues, as well as indirect immunosuppressive effects with a risk of developing opportunistic infections or bone marrow suppression. There is a higher occurrence of malignant diseases in patients with IBD, which is related to the disease itself and to the IBD-related therapy with a possible oral pathology. Treatment of oral lesions includes treatment of the alterations in the oral cavity according to the etiology together with treatment of the primary intestinal disease, which requires adequate knowledge and a strong cooperation between gastroenterologists and specialists in oral medicine.     

Faecal calprotectin: Management in inflammatory bowel disease

Inflammatory bowel disease (IBD) is a chronic and relapsing disorder which leads to an inflammation of the gastrointestinal tract. A tailored therapy to achieve mucosal healing with the less adverse events has become a key issue in the management of IBD. In the past, the clinical remission was the most important factor to consider for adapting diagnostic procedures and therapeutic strategies. However, there is no a good correlation between symptoms and intestinal lesions, so currently the goals of treatment are to achieve not only the control of symptoms, but deep remission, which is related with a favourable prognosis. Thus, the determination of biological markers or biomarkers of intestinal inflammation play a crucial role. Many biomarkers have been extensively evaluated in IBD showing significant correlation with endoscopic lesions, risk of recurrence and response to treatment. One of the most important markers is faecal calprotectin (FC). Despite calprotectin limitations, this biomarker represents a reliable and noninvasive alternative to reduce the need for endoscopic procedures. FC has demonstrated its performance for regular monitoring of IBD patients, not only to the diagnosis for discriminating IBD from non-IBD diagnosis, but for assessing disease activity, relapse prediction and response to therapy. Although, FC provides better results than other biomarkers such as C-reactive protein and erythrocyte sedimentation rate, these surrogate markers of intestinal inflammation should not be used isolation but in combination with other clinical, endoscopic, radiological or/and histological parameters enabling a comprehensive assessment of IBD patients.     

Danish cohort of monozygotic inflammatory bowel disease twins: Clinical characteristics and inflammatory activity

AIM: To describe the establishment of a Danish inflammatory bowel diseases(IBD) twin cohort with focus on concordance of treatment and inflammatory markers.METHODS: We identified MZ twins, likely to be discordant or concordant for IBD, by merging information from the Danish Twin Register and the National Patient Register. The twins were asked to provide biological samples, questionnaires, and data access to patient files and public registries. Biological samples were collected via a mobile laboratory, which allowed for immediate centrifugation, fractionation, and storage of samples. The mean time from collection of samples to storage in the-80 ℃ mobile freezer was less than one hour. The diagnoses where validated using the Copenhagen diagnostic criteria.RESULTS: We identified 159 MZ IBD twin pairs, in a total of 62(39%) pairs both twins agreed to participate. Of the supposed 62 IBD pairs, the IBD diagnosis could be confirmed in 54 pairs. The cohort included 10 concordant pairs, whereof some were discordant for either treatment or surgery. The 10 concordant pairs, where both pairs suffered from IBD, included eight CD/CD pairs, one UC/UC pair and one UC/IBDU pair. The discordant pairs comprised 31 UC, 5 IBDU(IBD unclassified), and 8 CD discordant pairs. In the co-twins not affected by IBD, calprotectin was above 100 μg/g in 2 participants, and above 50 μg/g in a further 5 participants.CONCLUSION: The presented IBD twin cohorts are an excellent resource for bioinformatics studies with proper adjustment for disease-associated exposures including medication and inflammatory activity in the co-twins.     

Promises and paradoxes of regulatory T cells in inflammatory bowel disease

Since their discovery two decades ago,CD4+CD25+Foxp3+ regulatory T cells(Tregs) have become the subject of intense investigation by immunologists. Unlike other T cells,which promote an immune response,Tregs actively inhibit inflammation when activated by their cognate antigen,thus raising hope that these cells could be engineered into a highly targeted,antigenspecific,immunosuppressant therapy. Although Tregs represent less than 10% of circulating CD4+T cells,they have been shown to play an essential role in preventing or limiting inflammation in a variety of animal models and human diseases. In particular,spontaneous intestinal inflammation has been shown to occur in the absence of Tregs,suggesting that there may be a Treg defect central to the pathogenesis of human inflammatory bowel disease(IBD). However,over the past decade,multiple groups have reported no qualitative or quantitative deficits in Tregs from the intestines and blood of IBD patients to explain why these cells fail to regulate inflammation in Crohn's disease and ulcerative colitis. In this review,we will discuss the history of Tregs,what is known about them in IBD,and what progress and obstacles have been seen with efforts to employ them for therapeutic benefit.     

Minimally invasive surgery for paediatric inflammatory bowel disease: Personal experience and literature review

The incidence of paediatric inflammatory bowel disease(PIBD) has dramatically increased in the last 20 years. Although first reported in mid 1970s',diagnostic laparoscopy has started to be routinely adopted in paediatric surgical practice since late 1990s'. Minimally invasive surgery was first limited to diagnostic purposes. After 2002 it was also applied to the radical treatment of PIBD,either Crohn's disease(CD) or Ulcerative colitis. During the last decade minimally invasive approaches to PIBD have gained popularity and have recently became the "gold standard" for the treatment of such invalidating and troublesome chronic diseases. The authors describe and track the historical evolution of minimally invasive surgery for PIBD and address all available opportunities,including most recent advancements such as robotic surgery,single port approaches and minimally invasive treatment of perianal fistulising CD. A systematic review of all series of PIBD treated with minimally invasive approaches published so far is provided in order to determine the incidence and type of patients' complications reported up to present days. The authors also describe their experience with minimally invasive surgery for PIBD and will report the results of 104 laparoscopic procedures performed in a series of 61 patients between January 2006 and December 2014.     

Immunogenicity and mechanisms impairing the response to vaccines in inflammatory bowel disease

Inflammatory bowel disease(IBD) is an immunological disorder that is usually treated with immunosuppressive therapy,potentially leading to increases in vulnerability to infections. Although many infections can be pre-vented by vaccination,vaccination coverage in these patients in clinical practice is insufficient. Therefore,the seroprotection condition should be verified,even for routine vaccines,such as hepatitis B or pneu-mococcus. Response to vaccines in IBD patients is thought to be impaired due to the immunological alterations generated by the disease and to the immunomodulatory treatments. The immunogenicity of hepatitis B,influenza,and pneumococcal vaccines is impaired in IBD patients,whereas the response to papillomavirus vaccine seems similar to that observed in the healthy population. On the other hand,data on the immunogenicity of tetanus vaccine in IBD patients are conflicting. Studies assessing the response to measles-mumps-rubella,varicella,and herpes zoster vaccines in IBD patients are scarce. The cellular and molecular mechanisms responsible for the impairment of the response to vaccination in IBD patients are poorly understood. Studies aiming to assess the response to vaccines in IBD patients and to identify the mechanisms involved in their immunogenicity are warranted. A better understanding of the immune response,specifically to vaccines,in patients with immune-mediated diseases(such as IBD),is crucial when developing vaccines that trigger more potent immunologic responses.