Faecalibacterium prausnitzii is not decreased in symptomatic uncomplicated diverticular disease of the colon.

In this letter, assessment of the amount of fecal Faecalibacterium prausnitzii in symptomatic uncomplicated diverticular disease (SUDD) is described. Among 44 consecutive patients, comprising 15 SUDD patients, 13 patients with asymptomatic diverticulosis (AD), and 16 healthy controls (HC), the fecal amount of Faecalibacterium prausnitzii was not found to be significantly different between HC, AD and SUDD subjects (p=0.871). Moreover, its count in the HC microbiota (-4.57 ± 2.15) was lower compared with those in the AD (-4.11 ± 1.03) and SUDD subjects (-4.03 ± 1.299). This behavior seems to be different from that occurring in inflammatory bowel disease (IBD) and similar to that of other mucin-degrading species in a SUDD setting.

Comparison of Performances of Adalimumab Biosimilars SB5, ABP501, GP2017, and MSB11022 in Treating Patients with Inflammatory Bowel Diseases: A Real-Life, Multicenter, Observational Study.

BACKGROUND: Adalimumab (ADA) biosimilars have entered the therapeutic armamentarium of inflammatory bowel disease (IBD), allowing for the treatment of a greater number of patients for their reduced cost than the originator. However, comparative data on the efficacy and safety of the various ADA biosimilars remains scarce.We compare the efficacy and safety of ADA biosimilars SB5, ABP501, GP2017, and MSB11022 in treating IBD outpatients in a real-life Italian setting. METHODS: A retrospective analysis was performed on consecutive IBD outpatients with complete clinical, laboratory, and endoscopic data. Clinical activity was measured using the Mayo score in ulcerative colitis (UC) and the Harvey-Bradshaw Index in Crohn's disease (CD). The primary endpoints were the following: (1) induction of remission in patients new to biologics and patients new to ADA but previously exposed to other anti-tumor necrosis factor agents or other biologics; (2) maintenance of remission in patients switched from the ADA originator to an ADA biosimilar; and (3) safety of various biosimilars. RESULTS: A total of 533 patients were enrolled according to the inclusion criteria: 162 patients with UC and 371 patients with CD. Clinical remission was obtained in 79.6% of patients new to biologics and 59.2% of patients new to ADA but not to other biologics; clinical remission was maintained in 81.0% of patients switched from the originator, and adverse events were recorded in 6.7% of patients. There was no significant difference between the 4 ADA biosimilars for each predetermined endpoint. CONCLUSIONS: Adalimumab biosimilars are effective and safe in IBD treatment, both in new patients and in patients switched from the ADA originator. No difference in efficacy and safety was found between ADA biosimilars.

We treated 533 IBD patients with adalimumab (ADA) biosimilars SB5, APB501, GP2017, and MSB11022. No differences between these 4 ADA biosimilars were found for reaching remission in naive patients, maintaining remission for nonmedical switching, clinical response, steroid-free remission, surgery rate, mucosal healing, or safety.

Replacement of Adalimumab Originator to Adalimumab Biosimilar for a Non-Medical Reason in Patients with Inflammatory Bowel Disease: A Real-life Comparison of Adalimumab Biosimilars Currently Available in Italy.

BACKGROUND AND AIMS: Adalimumab (ADA) biosimilars have been included into the therapeutic armamentarium of inflammatory bowel disease (IBD); however, comparative data on the efficacy and safety of the different ADA biosimilars after replacing the ADA originator for a non-medical reason remains scarce. We aimed to compare in a real-life setting the efficacy and safety of four ADA biosimilars SB5, APB501, GP2017, and MSB11022 in IBD patients after replacing the originator for a non-medical reason. METHODS: A multicenter retrospective study was performed on consecutive IBD patients, analyzing clinical, laboratory, and endoscopic data. The primary endpoints of the study were maintenance of clinical remission and safety of the different biosimilars. RESULTS: 153 patients were enrolled, 26 with UC and 127 with CD. Clinical remission was maintained in 124 out of 153 (81%) patients after a median (IQR) follow-up of 12 (6-24) months, without any significant difference between the four ADA biosimilars. ADA biosimilars dosage was optimized in five patients (3.3%). Loss of remission was significantly higher in UC patients (10/26 patients, 38.5%) than in CD patients (19/127 patients, 14.9%, p<0.025). Adverse events occurred in 12 (7.9%) patients; the large majority were mild. CONCLUSIONS: No difference in efficacy and safety was found between ADA biosimilars when used to replace the ADA originator for a non-medical reason. However, in UC patients the replacement of ADA originator for this reason should be carefully assessed.

Clinical nutrition in internal medicine: An Italian survey by the scientific societies FADOI and SINPE.

OBJECTIVES: Patients hospitalized in internal medicine are frequently malnourished or at risk for malnutrition. The aim of this study, conducted by the Federation of Associations of Hospital Internists (FADOI) and the Italian Society of Artificial Nutrition and Metabolism (SINPE) was to assess the nutritional management of internal medicine inpatients in Italy, to identify critical issues and formulate practical proposals to improve nutritional treatment. METHODS: From February to April 2021, FADOI and SINPE conducted a national web-based survey, including a 13 multiple-choice item questionnaire related to three key areas: screening and assessment of malnutrition and associated/overlapping sarcopenia and dysphagia; specialist consultations; and management of nutritional support. RESULTS: Responding to the questionnaire were 266 physicians among FADOI members (10.76%). Screening for malnutrition is performed with validated tests, within standardized care pathways, or routinely, only by 22% of participants. Global Leadership Initiative on Malnutrition criteria for diagnosis of malnutrition are little used (20%). Screening for sarcopenia was insufficient as the systematic use of assessment tools (handgrip/chair test) was minimal (3%). Screening for dysphagia is not a routine procedure for at-risk patients according to 33% of participants. Systematic involvement of clinical nutrition services/units in the management of malnourished/sarcopenic patients was reported by only 17% of internists. CONCLUSIONS: To overcome the critical issues that emerged from the present study, FADOI and SINPE experts proposed practical solutions to promote the application of the most recent guidelines and to improve awareness and sensitivity to nutritional management in internal medicine real-life settings.

Long-term real-life efficacy and safety of infliximab and adalimumab in the treatment of inflammatory bowel diseases outpatients.

BACKGROUND: Infliximab and adalimumab are widely used for the treatment of Crohn's disease and ulcerative colitis. AIM: To compare the long-term efficacy and safety of infliximab and adalimumab in a large cohort of Crohn's disease and ulcerative colitis patients reflecting real-life clinical practice. METHODS: Seven hundred twelve patients were retrospectively reviewed, 410 with Crohn's disease (268 treated with adalimumab and 142 with infliximab; median follow-up 60 months, range, 36-72) and 302 with ulcerative colitis (118 treated with adalimumab and 184 with infliximab; median follow-up 48 months, range, 36-84). RESULTS: In Crohn's disease, clinical remission was maintained in 75.0% of adalimumab vs. in 72.5% of infliximab patients (P = 0.699); mucosal healing and steroid-free remission were maintained in 49.5% of adalimumab vs. 63.9% of infliximab patients (P = 0.077) and in 77.7% of adalimumab vs. 77.3% in infliximab group (P = 0.957), respectively. In ulcerative colitis, clinical remission was maintained in 50.0% of adalimumab vs. 65.8% of infliximab patients (P < 0.000); mucosal healing and steroid-free remission were maintained in 80.6% of adalimumab vs. 77.0% of infliximab patients (P = 0.494) and in 90.2% of adalimumab vs. 87.5% of infliximab patients (P = 0.662), respectively. At the multivariate analysis, ileocolonic location and simple endoscopic score for Crohn's disease >10 were predictors of failure in Crohn's disease; treatment with adalimumab, BMI ≥30 and Mayo score >10 were predictors of failure in ulcerative colitis. infliximab was more likely to cause adverse events than adalimumab (16.6 vs. 6.2%, P < 0.000). CONCLUSION: Both adalimumab and infliximab are effective in long-term outpatients management of inflammatory bowel diseases. Adalimumab had a lower rate of adverse events.

Acute Diverticulitis Is at Significant Risk of Malnutrition: an Analysis of Hospitalized Patients in a Medicine Department.

BACKGROUND AND AIM: The Nutritional Risk Security (NRS2002) System is recommended for hospitalized patients in order to assess their nutritional status. However, studies assessing large-scale systematic screening policies are lacking. The aim of this study was to assess the feasibility of implementing a screening strategy concerning all admissions for diverticular disease (DD) of the colon in the Department of Medicine of a Tertiary Hospital. METHODS: All patients suffering from acute diverticulitis (AD) and admitted to the Medicine Department from January 1st to 31 December 2017, were pre-screened by NRS2002 System by the nursing staff of the Nutritional team at the day of the admission. If the pre-screening was positive, the patients were referred to a supplementary assessment performed by a dietician. RESULTS: The global number of admissions in the observational period was 4,667 and 133 patients suffered from AD. A positive pre-screening test was recorded in 97 (72.9%) patients: a NRS2002 score > 3, describing a severe impaired nutritional status was found in 61 patients (62.9%). All 97 patients with a NRS2002 positive screening received initial nutritional support by oral supplements (17 patients, 17.52%) or enteral nutrition (22 patients, 22.68%) or total parenteral nutrition (58 patients, 59.8%). The mean length of hospital stay for all 133 patients was 6,9 days. However, the length of hospital stay was significantly longer for patients with a positive NRS2002, with a mean of 18 days (p= 0.01) Conclusions: A large number of hospitalized patients due to AD are at nutritional risk and have a significantly longer hospital stay.

Assessment of Fecal Microbiota and Fecal Metabolome in Symptomatic Uncomplicated Diverticular Disease of the Colon.

GOAL: The aim of this study was to assess fecal microbiota and metabolome in a population with symptomatic uncomplicated diverticular disease (SUDD). BACKGROUND: Whether intestinal microbiota and metabolic profiling may be altered in patients with SUDD is unknown. PATIENTS AND METHODS: Stool samples from 44 consecutive women [15 patients with SUDD, 13 with asymptomatic diverticulosis (AD), and 16 healthy controls (HCs)] were analyzed. Real-time polymerase chain reaction was used to quantify targeted microorganisms. High-resolution proton nuclear magnetic resonance spectroscopy associated with multivariate analysis with partial least-square discriminant analysis (PLS-DA) was applied on the metabolite data set. RESULTS: The overall bacterial quantity did not differ among the 3 groups (P=0.449), with no difference in Bacteroides/Prevotella, Clostridium coccoides, Bifidobacterium, Lactobacillus, and Escherichia coli subgroups. The amount of Akkermansia muciniphila species was significantly different between HC, AD, and SUDD subjects (P=0.017). PLS-DA analysis of nuclear magnetic resonance -based metabolomics associated with microbiological data showed significant discrimination between HCs and AD patients (R=0.733; Q=0.383; P<0.05, LV=2). PLS analysis showed lower N-acetyl compound and isovalerate levels in AD, associated with higher levels of A. municiphila, as compared with the HC group. PLS-DA applied on AD and SUDD samples showed a good discrimination between these 2 groups (R=0.69; Q=0.35; LV=2). SUDD patients were characterized by low levels of valerate, butyrate, and choline and by high levels of N-acetyl derivatives and U1. CONCLUSIONS: SUDD and AD do not show colonic bacterial overgrowth, but a significant difference in the levels of fecal A. muciniphila was observed. Moreover, increasing expression of some metabolites as expression of different AD and SUDD metabolic activity was found.

Interactions between Innate Immunity, Microbiota, and Probiotics.

The term "microbiota" means genetic inheritance associated with microbiota, which is about 100 times larger than the guest. The tolerance of the resident bacterial flora is an important key element of immune cell function. A key role in the interaction between the host and the microbiota is played by Paneth cell, which is able to synthesize and secrete proteins and antimicrobial peptides, such as α/ß defensins, cathelicidin, 14 ß-glycosidases, C-type lectins, and ribonuclease, in response to various stimuli. Recent studies found probiotics able to preserve intestinal homeostasis by downmodulating the immune response and inducing the development of T regulatory cells. Specific probiotic strain, as well as probiotic-driven metabolic products called "postbiotics," has been recently recognized and it is able to influence innate immunity. New therapeutic approaches based on probiotics are now available, and further treatments based on postbiotics will come in the future.

Accuracy of Rapid Fecal Calprotectin Test in Monitoring Inflammatory Bowel Diseases Under Treatment with TNFα Antagonists.

BACKGROUND: Anti-TNFα antibodies are effective in treating inflammatory bowel diseases (IBDs) unresponsive to the standard treatments. Information about the role of rapid fecal calprotectin (FC) in monitoring ambulatory IBD patients under treatment with anti-TNFα is lacking. Our aim was to assess the accuracy of rapid FC in monitoring those patients. METHODS: Seventy-two patients (38 males, 34 females, mean age 42.5 years, range 23-57 years), affected by ulcerative colitis (UC) (20 patients) or by Crohn's disease (CD) (52 patients) were treated with anti-TNFα antibodies. FC was assessed by a rapid semiquantitative test. RESULTS: With respect to the absence of clinical remission, FC test showed sensitivity of 71.8 %, specificity of 65.2 %, PPV of 41.8 %, and NPV of 86.9 %. In UC patients, FC test showed a sensitivity of 66.7 %, a specificity of 56.1 %, a PPV of 18.2 %, and a NPV of 92.0 %. In CD patients, FC test showed sensitivity of 70.6 %, specificity of 65.2 %, PPV of 50.0 %, and NPV of 81.8 %. With respect to the presence of endoscopic lesions, FC test showed sensitivity of 73.5 %, specificity of 96.0 %, PPV of 96.2 %, and NPV of 72.7 %. In UC patients, FC test showed sensitivity of 47.2 %, specificity of 84.6 %, PPV of 89.5 %, and NPV of 36.7 %. In CD patients, FC test showed sensitivity of 90.1 %, specificity of 79.7 %, PPV of 71.9 %, and NPV of 93.3 %. CONCLUSIONS: Diagnostic accuracy of rapid FC seems better in predicting persistence of endoscopic lesions than clinical remission in IBD patients under treatment with anti-TNFα.

Managing ambulatory ulcerative colitis patients with infliximab: a long term follow-up study in primary gastroenterology centers.

BACKGROUND: Infliximab (IFX) is the key treatment for ulcerative colitis (UC) unresponsive to standard treatments. The aim of the present study was to assess the efficacy and safety of IFX in treating ambulatory UC patients in primary gastroenterology centers. METHODS: One hundred and eighteen patients (65 M, 63 F, median age 34 years, range 19-71 years), affected by UC, were treated with IFX. Clinical efficacy, safety, mucosal healing (MH), and histological healing (HH) were assessed at a scheduled follow-up of 42 months. RESULTS: Percentage of patients with clinical remission persistence at 42-month follow-up was 70.4%. Colectomy occurred in only 3 patients (2.7%). At 42-month follow-up percentage of patients with MH was 44.6%, and percentage of patients with HH was 24.3%. HH at 6-month follow-up occurred in 13 out of 34 patients (38.2%) with C-reactive protein (CRP) <3 and in 8 out of 76 patients (10.5%) with CRP ≥ 3 (p=0.002). Side effects were reported in 16 patients (13.6%): infusion reactions occurred in 7 patients, other severe side-effects occurred in 3 patients, and opportunistic infections occurred in 3 patients (2.5%). Finally, 3 cancers (2.5%) occurred during the follow-up period (1 breast, 1 kidney and 1 rectal cancer). Both univariate and multivariate analyses showed Hb <11.5 g/dL and HH at 6-month follow-up to be significantly associated with treatment failure during follow-up. CONCLUSIONS: IFX seems to be effective and safe in long-term treatment of outpatients affected by UC.

Effectiveness and safety of infliximab and adalimumab for ambulatory Crohn's disease patients in primary gastroenterology centres.

BACKGROUND: Infliximab (IFX) and adalimumab (ADA) are the key treatments for Crohn's Disease (CD), unresponsive to standard treatments. Our aim was to compare the efficacy and safety of IFX and ADA in treating CD in clinical practice. METHODS: One hundred and twenty-six patients (61 M, 65 F, mean age 36.2 years, range 19-67 years), affected by CD, were treated with infliximab (IFX, 59 patients) or adalimumab (ADA, 66 patients). Clinical efficacy, mucosal healing (MH), histological healing (HH), and safety were assessed. MH was defined complicated if healing of ulcers occurred with deformation of bowel profile and/or complete colonoscopy was impossible because of scars. RESULTS: Patients were followed-up for 36 months. No difference was found between IFX and ADA in maintaining long-term clinical remission, MH and HH. Complicated MH was present in 17 (28.8%) patients in IFX group and in 7 (10.6%) patients in ADA group (p=0.012). In 9 (15.2%) patients in IFX group and 2 (3.0%) patients in ADA group colonoscopy was incomplete without cecal intubation or terminal ileum exploration (p=0.024). Side effects were similar in both groups. CONCLUSIONS: Both IFX and ADA seem to be effective and safe in long-term outpatient treatment of CD in clinical practice.

Efficacy, tolerability, and factors affecting the efficacy of the sequential therapy in curing Helicobacter pylori infection in clinical setting.

BACKGROUND: Sequential therapy is currently suggested as first-line therapy in curing Helicobacter pylori infection, but results coming from its use in clinical practice are scarce. We evaluated the efficacy of this therapy regimen in our current clinical practice. METHODS: A retrospective study was conducted on 437 consecutive dyspeptic patients with proven H. pylori infection. Patients received a 10-day sequential therapy with proton pump inhibitor (PPI) plus amoxicillin 1 g for the first 5 days, followed by PPI, clarithromycin 500 mg, and tinidazole 500 mg for the remaining 5 days (all twice daily) plus PPI every day for further 4 weeks in case of active peptic ulcer or severe gastritis detected at endoscopy. One month after conclusion of therapy, endoscopy was performed in those patients for whom the examinations were clinically relevant. The remaining patients were checked by C-urea breath test. RESULTS: Three-hundred ninety-eight patients (91.08%; 95% confidence interval [CI], 87.91%-93.50%) were fully compliant, 19 patients (4.35%; 95% CI, 2.71%-6.83%) took less than 80% of the prescribed drugs, 11 patients (2.52%; 95% CI, 1.33%-4.60%) were withdrawn because of side effects, and 9 patients (2.06%; 95% CI, 1.01%-4.01%) were lost to follow-up. The H. pylori eradication was obtained in 395 (90.39%, 95% C.I. 87.14% to 92.91%) of 437 and in 362 of 437 (82.84%, 95% C.I. 78.90% to 86.19%) as per-protocol and intention-to-treat analyses, respectively. CONCLUSIONS: Sequential regimen seems to be a valid therapeutic strategy for the management of H. pylori infection in clinical practice.

Effect of gluten-free diet on pregnancy outcome in celiac disease patients with recurrent miscarriages.

PURPOSE: Available literature data show that celiac disease (CD) is a frequent cause of recurrent miscarriage. However, data are lacking for pregnancy outcome when the patient is on a gluten-free diet (GFD). A case-control study about the effect of GFD on pregnancy was conducted from 1995 to 2006. A cohort of 13 women (mean age 32 years, range 22-38 years) affected by CD with recurrent miscarriages was observed. In all of them several causes of miscarriage (gynecological, endocrine, hematological, etc.) were excluded. All patients were started on a gluten-free diet and were reassessed throughout a long-term follow-up period to evaluate the outcome of pregnancy. RESULTS: Six of 13 became pregnant (46.15%) as follows: 1 patient (7.69%) 1 year after GFD was started, 3 patients (23.07%) 2 years after GFD was started, 1 patient (7.69%) after 3 years, and finally 1 (7.69%) 4 years after GFD was started. Moreover, two patients (16.66%) had multiple pregnancies (one had had two childbirths and another had undergone three births within a 7-year follow-up period under GFD). CONCLUSIONS: GFD seems to favor a positive outcome of pregnancy in most CD patients with recurrent miscarriage.

The clinical picture of uncomplicated versus complicated diverticulitis of the colon.

PURPOSE: There is no consensus about the correct definition of uncomplicated diverticulitis (UD) in clinical practice. We evaluated therefore whether clinical picture of UD differs from complicated diverticulitis (CD). Fifty consecutive eligible patients (21 males, 29 females, mean age 63.6 years, range 47-75 years) were studied. Symptoms, the inflammatory indices, and Computerized Tomography (CT) scan of the abdomen were assessed at the time of admission. RESULTS: Thirty-nine patients classified were affected by UD and 11 patients by CD. CD patients showed more severe clinical picture than UD and required urgent Hospital admission. Conversely, most of the patients affected by UD were treated as outpatients. CD patients showed higher symptom scores than UD patients, except the parameter "diarrhea". All CD patients showed increases in all inflammatory indices. Conversely, all UD patients showed increased ESR, CRP and fibrinogen, but WBC and alpha1-acid glycoprotein were increased in only a few cases. CT scan in CD patients always showed signs of severe colonic and pericolonic inflammation. Conversely, UD patients often showed moderate localized signs of inflammation without complication. CONCLUSIONS: Clinical, laboratory, and radiological findings may easily differentiate uncomplicated from complicated diverticulitis of the colon. This integrated approach may be helpful in clinical settings.

Assessment of autonomic function in untreated adult coeliac disease.

AIM: Some recent studies showed that alteration of upper-gut motility in coeliac disease may be related to dysfunction of autonomic nervous system. The aim of our study was to investigate whether autonomic nervous system was altered in untreated and unselected coeliac disease patients. METHODS: We studied 8 untreated and consecutive coeliac disease patients (2 males and 6 females, age range 37+/-14.5 years). Histological evaluation of duodenal mucosa, anti-gliadin antibodies (AGA), antiendomysial antibodies (EMA) and anti-tTG antibodies and sorbitol H2 breath test were performed in all patients. Extrinsic autonomic neuropathy was assessed by the standardized measurement of cardiovascular reflexes (lying-to-standing, Valsalva manoeuvre, deep breathing, sustained handgrip). The results obtained were compared with a healthy, asymptomatic control group (6 males and 7 females, age range 42.3+/-13.5 years). RESULTS: Coeliac patients exhibited a lower increase of PAS as a response to isometric effort, a reduction of spectral power LF as a response to clinostatic position, but without statistical significance. Also they showed a lower tolerance to orthostatic position, associated with a latent disequilibrium of sympathetic-vagal balance, a relative prevalence of parasympathetic component of the autonomic function. However, these results were not statistically significant when compared with control group (P = n.s.). And they were unchanged after 6 and 12 mo of gluten-free diet. CONCLUSION: This study failed to confirm a significant correlation between autonomic dysfunction and coeliac disease, yet we could not exclude a role of autonomic dysfunction in the genesis of systemic symptoms in some coeliacs.

High prevalence of small intestinal bacterial overgrowth in celiac patients with persistence of gastrointestinal symptoms after gluten withdrawal.

OBJECTIVE: Celiac disease is a gluten-sensitive enteropathy with a broad spectrum of clinical manifestation, and most celiac patients respond to a gluten-free diet (GFD). However, in some rare cases celiacs continue to experience GI symptoms after GFD, despite optimal adherence to diet. The aim of our study was to evaluate the causes of persistence of GI symptoms in a series of consecutive celiac patients fully compliant to GFD. METHODS: We studied 15 celiac patients (five men, 10 women, mean age 36.5 yr, range 24-59 yr) who continued to experience GI symptoms after at least 6-8 months of GFD (even if of less severity). Antigliadin antibody (AGA) test, antiendomysial antibody (EMA) test, and sorbitol H2-breath test (H2-BT), as well as esophagogastroduodenoscopy (EGD) with histological evaluation, were performed before starting GFD. Bioptic samples were obtained from the second duodenal portion during EGD, and histopathology was expressed according to the Marsh classification. To investigate the causes of persistence of GI symptoms in these patients, we performed AGA and EMA tests, stool examination, EGD with histological examination of small bowel mucosa, and sorbitol-, lactose-, and lactulose H2-breath tests. RESULTS: Histology improved in all patients after 6-8 months of GFD; therefore, refractory celiac disease could be excluded. One patient with Marsh II lesions was fully compliant to his diet but had mistakenly taken an antibiotic containing gluten. Two patients showed lactose malabsorption, one patient showed Giardia lamblia and one patient Ascaris lumbricoides infestation, and 10 patients showed small intestinal bacterial overgrowth (SIBO) by lactulose H2-BT. We prescribed a diet without milk or fresh milk-derived foods to the patient with lactose malabsorption; we treated the patients with parasite infestation with mebendazole 500 mg/day for 3 days for 2 consecutive wk; and we treated the patients with SIBO with rifaximin 800 mg/day for 1 wk. The patients were re-evaluated 1 month after the end of drug treatment (or after starting lactose-free diet); at this visit all patients were symptom-free. CONCLUSIONS: This study showed that SIBO affects most celiacs with persistence of GI symptoms after gluten withdrawal.

Assessment of orocaecal transit time in different localization of Crohn's disease and its possible influence on clinical response to therapy.

BACKGROUND: A study on orocaecal transit time (OCTT) in patients with different localizations of Crohn's disease (CD) is not available. Because slow-release drug formulations are increasingly available for the treatment, there is a concrete risk that delayed OCTT may impair the efficacy of these formulations. AIMS: We investigated OCTT before and after therapy using lactulose H2-breath test and we studied whether OCTT can influence the clinical response to therapy with slow-release mesalazine formulations in adult CD patients.(2) PATIENTS AND METHODS: We studied 45 adult patients with non-obstructive CD and Crohn's Disease Activity Index (CDAI) <200 (29 men, 16 women; mean age 42 years, range 22-73 years). Twenty patients had ileocolonic, 16 colonic and 9 ileal localization of CD. The control group consisted of 20 healthy subjects (13 men, seven women; mean age 53 years, range 22-71 years). After OCTT assessment, 29 patients were treated with time-dependent mesalazine 3.6 g/day, while 16 patients were treated with pH-dependent mesalazine 3.6 g/day. If bacterial overgrowth was detected, the patients were also treated with rifaximin 800 mg/day for 7 days. RESULTS: OCTT was delayed (120 min, range 115-210 min) in 30 of the 45 CD patients (67%). Four patients (9%) showed bacterial overgrowth, while OCTT was regular (82.5 min, range 75-90 min) in 11 patients (24%). In the control group, the mean OCTT was 88.2 min (range 75-135 min); (P<0.01). OCTT was more prolonged in ileal localization (182.2 min, range 150-210 min), rather than in patients with ileocolonic (122 min, range 75-180 min) or colonic (106 min, range 75-150 min) localization of CD; (P<0.01). Thirty-nine patients showed normal OCTT after starting therapy (83 min, range 75-105 min), while OCTT remained slightly delayed in the remaining patients (110 min, range 105-115 min); (P<0.01). CDAI was <100 (mean value 83) in all patients with reduction of OCTT to normal value 4 months after starting therapy, while it was >140 (mean value 143) in patients with a slight reduction but not normalization of OCTT respectively (five patients with ileal and one with ileocolonic localization of CD) with a statistically significant correlation between OCTT and CDAI (P<0.01). CONCLUSIONS: This study shows clearly for the first time that OCTT is not only delayed in patients with active CD, but also that it is prolonged in ileal and ileocolonic rather than colonic localization of CD. Moreover we obtained these results using a simple, sensitive, non-invasive and repeatable method, namely, a lactulose hydrogen breath test.

Efficacy and tolerability of ranitidine bismuth citrate plus amoxycillin and clarithromycin as first- or second-line therapy to cure Helicobacter pylori infection.

BACKGROUND/AIMS: Ranitidine bismuth citrate has recently been introduced for the treatment of H. pylori infection and obtains good eradication rates; however, eradication failures still appear in a considerable proportion of cases. The aim of this study was to compare the efficacy and tolerability of ranitidine bismuth citrate plus amoxycillin and clarithromycin as first- or second-line therapy to cure H. pylori infection. METHODOLOGY: We studied 423 consecutive H. pylori-positive patients. In 210 consecutive patients H. pylori infection was diagnosed for the first time (group A), while 213 consecutive patients were enrolled after failure of a first attempt to eradicate H. pylori (group B). All patients received ranitidine bismuth citrate 400 mg b.d. plus clarithromycin 500 mg b.d. and amoxycillin 1 g b.d. for seven days. H. pylori-status was evaluated by means of histology and rapid urease test at entry and by 13C-urea breath test in all patients one month after treatment. RESULTS: 410/423 patients completed the study (202/210 in group A and 208/213 in group B). Two patients of group A and 1 patient of group B were withdrawn from the study due to poor compliance, 6 group A patients and 4 group B patients were lost to follow-up. In group A, after the end of treatment, 181/202 patients were H. pylori-negative (per-protocol analysis: 89.60% [C.I. 95%: 82-95%]; on intention-to-treat analysis: 86.19% [C.I. 95%; 76-92%]), side-effects occurred in 29 patients (13.80%); they were severe in 2 patients and the patients were withdrawn from the study. In group B, after the end of treatment, 200/208 patients were H. pylori-negative (per-protocol analysis: 95.15% [C.I. 95%; 92-100%], on intention-to-treat analysis: 93.89% [C.I. 95%; 89-98%), side-effects occurred in 11 patients (5.13%); they were slight or mild and did not require discontinuation of the treatment. The results of group B were statistically better than group A, both in eradication rate (P < 0.01) as well as both side-effects provoked (P < 0.01). CONCLUSIONS: Ranitidine bismuth citrate-clarithromycin-amoxycillin is more effective when used as second-line therapy rather than when used as first-line therapy; second, ranitidine bismuth citrate-clarithromycin-amoxycillin shows lower and slighter side-effects when used as second-line therapy rather than when used as first-line therapy; finally, the excellent tolerability of ranitidine bismuth citrate + clarithromycin + amoxycillin influences positively the patients' compliance, both as first- and second-line therapy.