Follow-up evaluation and management of anemia in inflammatory bowel disease: A study by the Italian Group for Inflammatory Bowel Diseases (IG-IBD).

BACKGROUND: The RIDART I study found a 13.6% prevalence of anemia in Italian patients with inflammatory bowel disease (IBD); most cases were due to iron-deficiency anemia (IDA). AIMS: To evaluate changes in hemoglobin concentration during a 24-week follow-up of anemic patients with IBD. METHODS: Follow-up laboratory and clinical data were obtained from RIDART I study patients with anemia. Factors affecting hemoglobin concentration, the impact of anemia on fatigue and quality of life (QoL), and its relationship with treatment, disease activity and disease complications were investigated. RESULTS: Hemoglobin was 108 g/L at baseline, increased to 121 g/L at follow-up week 12 (p < 0.001) and then stabilized until week 24, but most patients remained anemic, with IDA, throughout the study. Hemoglobin improvement was greater in patients receiving either oral or parenteral iron supplementation. Following hemoglobin normalization, anemia relapse rate during follow-up was 30%. Oral iron did not cause disease reactivation. Lower follow-up hemoglobin was associated with a higher probability of having active disease, clinical complications, increased fatigue and reduced QoL. CONCLUSIONS: In anemic patients with IBD, anemia represents a long-lasting problem, in most cases persisting for up to 24 weeks, with high relapse rate and a negative impact on fatigue and QoL.

Relief from behind: enemas, the back door enforcement to help treating chronic constipation in adults.

INTRODUCTION: Chronic constipation is a frequent symptom encountered in the daily clinical practice. The treatment of this condition mainly relies on the use of laxatives. However, patients' satisfaction with this approach is limited, and alternative measures are often added to the treatment. Among these, particularly frequent worldwide is the use of enemas, even though literature data on its scientific validity are scarce. AREAS COVERED: In this article, by an extensive online search of Medline (through PubMed), Scopus, Cochrane CENTRAL, EMBASE, and the Science Citation Index, the available literature data on the use of enemas in adult patients with chronic constipation, also in the perspective of available guidelines on treatment of this pathological condition, were analyzed. EXPERT OPINION: Although the use of enemas remains a frequently employed method and it is considered as useful by many physicians as an adjunctive support for the treatment of chronic constipation in adults, this practice is not substantiated by rigorous scientific data, and some studies are available only for specific instances (fecal impaction, transanal irrigation). Thus, waiting for more robust scientific data, enemas treatment should be carried out on an individual patient's basis, according to the experience of the caring physicians.

Diverticular Inflammation and Complication Assessment classification, CODA score and fecal calprotectin in clinical assessment of patients with diverticular disease: A decision curve analysis.

BACKGROUND AND AIMS: The Diverticular Inflammation and Complication Assessment (DICA) classification and the Combined Overview on Diverticular Assessment (CODA) were found to be effective in predicting the outcomes of Diverticular Disease (DD). We ascertain whether fecal calprotectin (FC) can further aid in improving risk stratification. METHODS: A three-year international, multicentre, prospective cohort study was conducted involving 43 Gastroenterology and Endoscopy centres. Survival methods for censored observations were used to estimate the risk of acute diverticulitis (AD) in newly diagnosed DD patients according to basal FC, DICA, and CODA. The net benefit of management strategies based on DICA, CODA and FC in addition to CODA was assessed with decision curve analysis, which incorporates the harms and benefits of using a prognostic model for clinical decisions. RESULTS: At the first diagnosis of diverticulosis/DD, 871 participants underwent FC measurement. FC was associated with the risk of AD at 3 years (HR per each base 10 logarithm increase: 3.29; 95% confidence interval, 2.13-5.10) and showed moderate discrimination (c-statistic: 0.685; 0.614-0.756). DICA and CODA were more accurate predictors of AD than FC. However, FC showed high discrimination capacity to predict AD at 3 months, which was not maintained at longer follow-up times. The decision curve analysis comparing the combination of FC and CODA with CODA alone did not clearly indicate a larger net benefit of one strategy over the other. CONCLUSIONS: FC measurement could be used as a complementary tool to assess the immediate risk of AD. In all other cases, treatment strategies based on the CODA score alone should be recommended.

Prevalence, Pathogenesis and Management of Anemia in Inflammatory Bowel Disease: An IG-IBD Multicenter, Prospective, and Observational Study.

BACKGROUND: Anemia is a common extraintestinal manifestation of inflammatory bowel disease (IBD), with a 6% to 74% prevalence and a negative impact on patient survival and quality of life, although the prevalence is apparently declining due to improved disease treatment. We aimed to investigate the prevalence, pathogenesis, and clinical correlates of anemia in Italian patients with IBD. METHODS: A multicenter, prospective, observational study, involving 28 Italian gastroenterology centers, was conducted to investigate the epidemiology and consequences of IBD-associated anemia. Clinical and laboratory data of anemic patients were obtained at study enrolment. RESULTS: Anemia was diagnosed in 737 of 5416 adult IBD outpatients (prevalence 13.6%); females were more commonly affected than males (odds ratio, 1.5; 95% confidence interval [CI], 1.2-1.7) and had more severe anemia. In the majority of cases, anemia was due to iron deficiency (62.5% of cases; 95% CI, 58.3%-66.6%), either isolated or in association with inflammation and/or vitamin deficiencies; anemia of inflammation accounted for only 8.3% of cases. More severe anemia was associated with increasing fatigue and worse quality of life. Only 68.9% of anemic patients with iron deficiency (95% CI, 63.4%-73.8%) and 34.6% of those with vitamin deficiencies (95% CI, 26.2%-44.2%) were properly treated with supplementation therapy. CONCLUSIONS: In Italy, the prevalence of IBD-associated anemia is lower than previously reported. Anemia of IBD is most commonly due to iron deficiency and contributes to fatigue and poor quality of life, but remains untreated in a large proportion of patients with iron and/or vitamin deficiencies. This study is registered at clinicaltrials.gov as NCT02872376.

The prevalence of inflammatory bowel disease­associated anemia is 13.6%. The prevalence is higher among females younger than 50. Anemia is usually due to iron deficiency and adversely affects fatigue and quality of life. Many patients with iron or vitamin deficiency (31% and 65%, respectively) remain untreated.

Gastroparesis: New insights into an old disease.

Gastroparesis (Gp) is a chronic disease characterized by a delayed gastric emptying in the absence of mechanical obstruction. Although this condition has been reported in the literature since the mid-1900s, only recently has there been renewed clinical and scientific interest in this disease, which has a potentially great impact on the quality of life. The aim of this review is to explore the pathophysiological, diagnostic and therapeutical aspects of Gp according to the most recent evidence. A comprehensive online search for Gp was carried out using MEDLINE and EMBASE. Gp is the result of neuromuscular abnormalities of the gastric motor function. There is evidence that patients with idiopathic and diabetic Gp may display a reduction in nitrergic inhibitory neurons and in interstitial cells of Cajal and/or telocytes. As regards diagnostic approach, 99-Technetium scintigraphy is currently considered to be the gold standard for Gp. Its limits are a lack of standardization and a mild risk of radiation exposure. The C13 breath testing is a valid and safe alternative method. 13C acid octanoic and the 13C Spirulina platensis recently approved by the Food and Drug Administration are the most commonly used diagnostic kits. The wireless motility capsule is a promising technique, but its use is limited by costs and scarce availability in many countries. Finally, therapeutic strategies are related to the clinical severity of Gp. In mild and moderate Gp, dietary modification and prokinetic agents are generally sufficient. Metoclopramide is the only drug approved by the Food and Drug Administration for Gp. However, other older and new prokinetics and antiemetics can be considered. As a second-line therapy, tricyclic antidepressants and cannabinoids have been proposed. In severe cases the normal nutritional approach can be compromised and artificial nutrition may be needed. In drug-unresponsive Gp patients some alternative strategies (endoscopic, electric stimulation or surgery) are available.

Definition and evaluation of mucosal healing in clinical practice.

Since the introduction of biological therapy, endoscopic and histological remission, i.e. mucosal healing, has become an important therapeutic goal in Crohn's Disease and Ulcerative Colitis. Mucosal healing is associated with lower rates of hospitalization and surgery, although its role in preventing progression and changing the natural history of the disease has not been clearly demonstrated. A precise definition of mucosal healing has not yet been established, although the concept used in clinical trials is the "complete absence of all inflammatory and ulcerative lesions in all segments of gut" at endoscopy. This definition does not include mucosal improvement and does not distinguish among grades of mucosal healing. In both Crohn's Disease and Ulcerative Colitis trials, several qualitative and quantitative numeric endoscopic indices have been proposed to measure and distinguish endoscopic changes. In addition, the microscopic features associated with inflammatory bowel diseases are considerably modified by the course of the disease and the treatments adopted. However, it is not yet clear whether microscopic healing should be a primary endpoint in clinical trials. In this paper we discuss endoscopic and histological findings and the limitations of the endoscopic and histological indices as a basis for a standardised diagnosis of mucosal healing.

Miocamycin-containing triple therapy for H. pylori infection.

INTRODUCTION: In Northern Sardinia, one-week triple standard therapies containing a proton-pump inhibitor and two antibiotics for H. pylori infection have an average cure rate of 57% largely due to a high prevalence of antimicrobial resistance. The efficacy of miocamycin-containing treatment for 10 days was evaluated. MATERIALS AND METHODS: Patients referred to the endoscopy service for dyspeptic symptoms were enrolled. H. pylori infection was defined as a positive rapid urease test, presence of the bacteria on gastric biopsies, and a positive 13C-UBT. Treatment consisted of 10 days with omeprazole 20 mg, miocamycin water-soluble 900 mg, and tinidazole 500 mg all bid. Success was evaluated 40-50 days after the end of therapy and defined by a negative 13C-UBT. Compliance was considered good if at least 90% of the total number of the pills were taken. Fluorescent in situ hybridization (FISH) technique was applied on paraffin-embedded gastric tissue sections to test susceptibility to clarithromycin of the bacteria. RESULTS: 50 patients were enrolled (mean age; 52, 36% men). Miocamycin-containing therapy cured 86% (42/49; 95% CI = 72-94%) of infected patients by PP analysis. Susceptibility data (FISH) was available for 38 patients. Cure rates for the 28 with clarithromycin-susceptible infection was 96% vs 50% for those with resistant or mixed infection, (p = .003). Good compliance was recorded in 48 patients. None of the patients discontinued therapy. CONCLUSIONS: Miocamycin appears to be a valid alternative for clarithromycin for H. pylori eradication. Head-to-head studies will be needed to ascertain whether it is superior.

Small intestinal bacterial overgrowth and warfarin dose requirement variability.

The dose of warfarin needed to obtain a therapeutic anticoagulation level varies widely among patients and can undergo abrupt changes for unknown reasons. Drug interactions and genetic factors may partially explain these differences. Intestinal flora produces vitamin K2 (VK2) and patients with small intestinal bacterial overgrowth (SIBO) rarely present reduced INR values due to insufficient dietary vitamin K. The present study was undertaken to investigate whether SIBO occurrence may affect warfarin dose requirements in anticoagulated patients. Based on their mean weekly dose of warfarin while on stable anticoagulation, 3 groups of 10 patients each were defined: low dose (LD, or=70 mg/wk). Each patient underwent a lactulose breath test to diagnose SIBO. Plasma levels of warfarin and vitamin K-analogues were also assessed. Patients with an altered breath test were 50% in the VHD group, 10% in the HD group, and none in the LD group (P=0.01). Predisposing factors to SIBO were more frequent in the VHD group, while warfarin interfering variables were not. VHD patients were younger and had a higher plasma vitamin K1 (VK1) concentration (P>0.05). On the contrary, the plasma VK2 levels tended to be lower. This pilot study suggests that SIBO may increase a patient's warfarin dose requirement by increasing dietary VK1 absorption through the potentially damaged intestinal mucosa rather than increasing intestinal VK2 biosynthesis. Larger studies are needed to confirm these preliminary data and to evaluate the effects of SIBO decontamination on warfarin dosage.

Audit of constipation in a gastroenterology referral center.

This study was designed to assess the various subtypes of functional constipation in a referral gastrointestinal center of a Latino-American country. All patients referred for evaluation of constipation during a 10-year period were audited, and those with functional constipation according to Rome I criteria classified by physiologic tests of colonic transit, as well as tests of anorectal and pelvic floor function. More than 70% of patients with functional constipation had evidence of pelvic floor dysfunction, whereas those with slow transit and constipation-predominant irritable bowel syndrome subtypes were less frequently represented. Even in a setting different from those most frequently reported in the literature, pelvic floor dysfunction represents the most common cause of functional constipation. Simple, physiologic testing is needed and useful for the diagnosis. This fact has therapeutic implications, especially because many such patients may benefit from biofeedback.

Biofeedback is superior to laxatives for normal transit constipation due to pelvic floor dyssynergia.

BACKGROUND & AIMS: Uncontrolled trials suggest biofeedback is an effective treatment for pelvic floor dyssynergia (PFD), a type of constipation defined by paradoxical contraction, or inability to relax, pelvic floor muscles during defecation. The aim was to compare biofeedback to laxatives plus education. METHODS: Patients with chronic, severe PFD were first treated with 20 g/day fiber plus enemas or suppositories up to twice weekly. Nonresponders were randomized to either 5 weekly biofeedback sessions (n = 54) or polyethylene glycol 14.6-29.2 g/day plus 5 weekly counseling sessions in preventing constipation (n = 55). Satisfaction with treatment, symptoms of constipation, and pelvic floor physiology were assessed 6 and 12 months later. The biofeedback group was also assessed at 24 months. Laxative-treated patients were instructed to increase the dose of polyethylene glycol from 14.6 to 29.2 g/day after 6 months. RESULTS: At 6 months, major improvement was reported by 43 of 54 (80%) biofeedback patients vs 12 of 55 (22%) laxative-treated patients (P < .001). Biofeedback's benefits were sustained at 12 and 24 months. Biofeedback also produced greater reductions in straining, sensations of incomplete evacuation and anorectal blockage, use of enemas and suppositories, and abdominal pain (all P < .01). Stool frequency increased in both groups. All biofeedback-treated patients reporting major improvement were able to relax the pelvic floor and defecate a 50-mL balloon at 6 and 12 months. CONCLUSIONS: Five biofeedback sessions are more effective than continuous polyethylene glycol for treating PFD, and benefits last at least 2 years. Biofeedback should become the treatment of choice for this common and easily diagnosed type of constipation.

Bio-feedback treatment of fecal incontinence: where are we, and where are we going?

Fecal incontinence is a disabling disease, often observed in young subjects, that may have devastating psycho-social consequences. In the last years, numerous evidences have been reported on the efficacy of bio-feedback techniques for the treatment of this disorder. Overall, the literature data claim a success rate in more than 70% of cases in the short term. However, recent controlled trials have not confirmed this optimistic view, thus emphasizing the role of standard care. Nonetheless, many authors believe that this should be the first therapeutic approach for fecal incontinence due to the efficacy, lack of side-effects, and scarce invasiveness. Well-designed randomized, controlled trial are eagerly awaited to solve this therapeutic dilemma.

One-year follow-up study on the effects of electrogalvanic stimulation in chronic idiopathic constipation with pelvic floor dyssynergia.

BACKGROUND: Constipation is a commonly reported symptom, and pelvic floor dyssynergia is frequently documented in constipated patients. The standard therapeutic approach for pelvic floor dyssynergia is biofeedback training, but long-term studies show that a significant percentage of patients remain symptomatic. Alternative or adjunctive therapeutic options are needed. AIMS: The purpose of this study was to evaluate the long-term effects of electrogalvanic stimulation in patients with pelvic floor dyssynergia and severe constipation, to see whether this treatment may be of some benefit. PATIENTS AND METHODS: Thirty consecutive constipated patients with clinical and instrumental evidence of pelvic floor dyssynergia entered the study and were treated with a standard high-frequency galvanic electrostimulation protocol. Clinical and instrumental (colon transit time, anorectal manometry, defecography, rectal balloon expulsion) assessment evaluations were performed basally and one year after the treatment. RESULTS: Overall, approximately 50 percent of patients showed significant improvement after electrogalvanic treatment, from both a clinical and an instrumental point of view, as shown by the objective measurements obtained through manometry, defecography, and the balloon expulsion test. The benefit was limited to normal transit constipation patients. CONCLUSIONS: Because of the relatively simple, painless and effective nature of electrogalvanic stimulation, we concluded that it may represent a useful adjunct to the therapeutic armamentarium for pelvic floor dyssynergia in normal transit constipation.

Long-term study on the effects of visual biofeedback and muscle training as a therapeutic modality in pelvic floor dyssynergia and slow-transit constipation.

PURPOSE: Biofeedback training has been shown as an effective therapeutic measure in patients with pelvic floor dyssynergia, at least in the short term. Long-term effects have received less attention. Moreover, its effects in patients with slow-transit constipation have been scarcely investigated. This study was designed to assess in an objective way the medium- and long-term effects of biofeedback and muscle training in patients with pelvic floor dyssynergia and slow-transit constipation. METHODS: Twenty-four patients (14 with pelvic floor dyssynergia and 10 with slow transit) meeting the Rome II criteria for constipation, and unresponsive to conventional treatments, entered the study. Clinical evaluation and anorectal manometry were performed basally and three months after a cycle of electromyographic biofeedback and muscle training; moreover, a clinical interview was obtained one year after biofeedback. Patients with slow-transit constipation also had colonic transit time reassessed at one year. RESULTS: Clinical variables (abdominal pain, straining, number of evacuations/week, use of laxatives) all significantly improved in both groups at three-month assessment; anorectal manometric variables remained unchanged, apart from a significant decrease of sensation threshold in the pelvic floor dyssynergia group and of the maximum rectal tolerable volume in the slow-transit constipation group. At one-year control, 50 percent of patients with pelvic floor dyssynergia still maintained a beneficial effect from biofeedback, whereas only 20 percent of those complaining of slow-transit constipation did so. Moreover, the latter displayed no improvement in colonic transit time. CONCLUSIONS: In our experience, patients with pelvic floor dyssynergia are likely to have continued benefit from biofeedback training in the time course, whereas its effects on slow-transit constipation seems to be maximal in the short-term course.