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Competing Interests: C.B. served as a consultant for AbbVie, Celtrion, Ferring, Galapagos, Janssen, MSD, and Takeda. E.V.S. has served as speaker for AbbVie, Agave, AG Pharma, Alfasigma, Aurora Pharma, Cadigroup, Celltrion, Dr Falk, EG Stada Group, Fenix Pharma, Fresenius Kabi, Galapagos, Janssen, JB Pharmaceuticals, Innovamedica/Adacyte, Malesci, MayolyBiohealth, Omega Pharma, Pfizer, Reckitt Benckiser, Sandoz, SILA, Sofar, Takeda, Tillots, and Unifarco; has served as a consultant for AbbVie, Agave, Alfasigma, Biogen, Bristol Myers Squibb, Celltrion, Diadema Farmaceutici, Dr Falk, Fenix Pharma, Fresenius Kabi, Janssen, JB Pharmaceuticals, Merck & Co, Nestlé, Reckitt Benckiser, Regeneron, Sanofi, SILA, Sofar, Synformulas, Takeda, and Unifarco; and has received research support from Pfizer, Reckitt Benckiser, SILA, Sofar, Unifarco, and Zeta Farmaceutici. M.M. has received lecture fees and has been an Advisory Board member for Takeda, Galapagos, Biogen, Aurora Pharma, and AbbVie. F.A.C. served as consultant and advisory board member for Mundipharma, AbbVie, MS&D, Takeda, Janssen, Roche, and Celgene; has received lecture fees from AbbVie, Amgen, Ferring, Takeda, and Allergy Therapeutics; and has received unrestricted research grants from Giuliani, Sofar, MSD, Takeda, and AbbVie. G.B. served as speaker for AbbVie, Takeda, Galapagos, Lilly, and Janssen. A.V. has received lecture fees from and has been an advisory board member for Janssen-Cilag, Takeda, Pfizer, Ferring, MSD, Zambon, AbbVie, and Celltrion. F.S. has served as a lecturer for Sanofi. F.F. received consulting fees from Amgen, AbbVie, and Galapagos and lecture fees from Janssen and Pfizer; has served as an advisory board member; and/or received lecture grants from AbbVie, Biogen, Galapagos, Janssen, MSD, Pfizer, Takeda Pharmaceuticals. E.C. served as advisory board member for Takeda and AbbVie; and received lecture fees from AbbVie, Janssen, Galapagos, Ferring, Takeda. M.B.P. served as advisory board member and received lecture fee from MSD, AbbVie, Janssen, Pfizer, and Takeda. A.A. has been an advisory board member for Galapagos and consultant for AbbVie, Galapagos, Pfizer, Takeda, and Janssen. M.C. served as a speaker or advisory board member for Takeda, MSD, AbbVie, Shire, Fresenius, and Janssen. B.B. has served as a speaker for AbbVie, Agave, Alfasigma, AG Pharma, Janssen, MSD, Procise, Sofar, Takeda, and Unifarco. S.S. has received consultancy and lecture fees and has been an advisory board member for AbbVie, Arena, Ferring, Galapagos, Gilead, Janssen, MSD, Pfizer, and Takeda. P.B. has participated on advisory boards for Janssen and Takeda. A.A. has received consulting and/or advisory board fees from AbbVie, Allergan, Amgen, Arena, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Galapagos, Gilead, Janssen, MSD, Mylan, Nestlé, Pfizer, Protagonist Therapeutics, Roche, Samsung Bioepis, Sandoz, and Takeda; has received lecture and speaker bureau fees from AbbVie, Amgen, Arena, Biogen, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Galapagos, Gilead, Janssen, MSD, Mitsubishi Tanabe, Novartis, Pfizer, Roche, Samsung Bioepis, Sandoz, Takeda, and TiGenix; and has received research grants from Biogen, MSD, Pfizer, and Takeda. L.B. has received lecture fees, consultancy fees, or advisory board honoraria from Abbvie, Aliveda, Janssen, Noos, Pfizer, Pharmanutra, Takeda, and Zambon. S.D. received honoraria as a speaker, consultant, and/or advisory board member from AbbVie, Allergan, Amgen, AstraZeneca, Athos Therapeutics, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Enthera, Ferring, Gilead, Hospira, Inotrem, Janssen, Johnson & Johnson, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, TiGenix, UCB, and Vifor. G.F., M.M., G.B., A.M., C.C., M.C., L.C., V.C., A.S., and F.S.C. declare no conflict of interest.

Background and Aims: Inflammatory bowel disease (IBD) patients might experience disease-related malnutrition (DRM), but prevalence and risk factors are not well defined. The primary aim of the study was to define the prevalence of DRM and micronutrient deficiency in IBD patients; the secondary aim was to assess variables related to DRM., Materials and Methods: A multicenter, cross-sectional study was performed including consecutive adult IBD patients during a period of 2 weeks. Nutritional status was assessed with the body mass index (BMI) and the Malnutrition Universal Screening Tool. DRM was defined according to European Society for Clinical Nutrition and Metabolism guidelines., Results: Among the 295 enrolled patients, the prevalence of DRM was 23%, with no statistical difference between Crohn's disease and ulcerative colitis. Compared with well-nourished patients, patients with DRM showed higher rate of hospitalization in the previous month, were more often receiving systemic steroids, and had lower hemoglobin, albumin, and prealbumin levels and higher median C-reactive protein levels. At univariate logistic regression, current hospitalization, hospitalization in the previous month, low serum albumin, low BMI, high C-reactive protein, high Crohn's Disease Activity Index, and female sex were variables related to DRM. At the multivariate logistic regression, low BMI, current hospitalization and hospitalization in the previous month were significantly associated with DRM. In 23% of IBD patients, a deficiency of at least 1 micronutrient was observed, with no difference between ulcerative colitis and Crohn's disease., Conclusions: DRM and microelements malnutrition are frequent conditions in the IBD population. DRM seems to be associated with disease activity and hospitalization., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Inflammatory bowel disease (IBD) is a group of chronic multifactorial inflammatory disorders including two major entities: Crohn's disease (CD) and ulcerative colitis (UC). Preliminary evidence suggests that patients with IBD may be at increased risk of developing intestinal and extraintestinal cancers (EICs). Actually, little is known about the association between IBD and EICs, and there is ever-growing concern regarding the safety of immunomodulators and biological therapy, which may represent a risk factor for carcinogenesis., Aims: The aim of this review is to summarize the evidence regarding the association between IBD and EICs, the safety of immunomodulators and biological therapy and the management of immunomodulators and biologic agents in IBD patients with prior or current EICs., Results: IBD patients have a higher risk of developing different forms of extraintestinal solid organ tumors and hematological malignancies. Immunomodulators and biological therapy may increase the risk of developing some types of EICs and may be consciously used in patients with IBD and current or prior history of malignancy., Conclusions: Decisions regarding the use of immunomodulators or biological therapies should be made on an individual basis, considering a multidisciplinary approach involving oncologists.

Objectives: Comparative trials among biological drugs for the treatment of ulcerative colitis (UC) provided conflicting results. After patent expire of infliximab originator, adalimumab, infliximab biosimilar, golimumab and vedolizumab have been approved in Italy.We compared the efficacy of these four biologics in UC according to the concept of continuous clinical remission (CCR)., Methods: In a retrospective, multicentre study, all UC patients treated with adalimumab, infliximab biosimilar, golimumab or vedolizumab between 2014 and 2019 were included. All drugs were compared to each other according to the 1-year CCR rate, defined as Mayo partial score ≤2, with bleeding subscore = 0, without any relapse or optimization with dose escalation, topical treatments or steroid use after first clinical remission., Results: Four-hundred sixteen patients (adalimumab = 90, infliximab biosimilar = 105, golimumab = 79, vedolizumab = 142) were included. CCR was achieved in similar percentages among the groups (33%, 37%, 28%, 37%, respectively). All drugs were equivalent in biologic-naive patients, while vedolizumab was better than a second anti-TNFα in prior anti-TNFα agent failures. No differences were found according to type of adverse events or severe adverse events., Conclusions: Based on a strict definition of clinical remission, all biologics appear equally effective at 1 year. Changing to vedolizumab is more effective than switching to another anti-TNFα in TNFα failures., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Data regarding double switching from originator infliximab (IFX) to IFX biosimilars in inflammatory bowel diseases (IBDs) are lacking. The purpose of this study was to evaluate the safety and efficacy of switching from originator IFX to CT-P13 and subsequently to SB2 (double switch) in patients with IBD. Patients undergoing IFX-double switch in eight Centers in Lombardy (Italy) from November 2018 to May 2019 were retrospectively analyzed. The IFX discontinuation rate, incidence and type of adverse events (AEs), and clinical remission rate were recorded. A comparison with a control group of patients with IBD single-switched from originator IFX to CT-P13 was performed, before and after an inverse probability of treatment weighting (IPTW)-based propensity score analysis. Fifty-two double-switched patients with IBD were enrolled. The 24- and 52-week proportions of patients continuing on IFX therapy following the second switch (CTP13 → SB2) were 98% (95% confidence interval [CI] 94%-100%) and 90% (95% CI 81%-99%), respectively. Four patients experienced a total of five AEs, all graded 1-3 according to Common Terminology Criteria for Adverse Events (CTCAE). No infusion reactions were observed. The 24-week and follow-up end clinical remission rates following the second switch were 94% and 88%, respectively. No differences were observed in the safety and efficacy outcomes by comparing the double-switch group with a single-switch group of 66 patients with IBD; all these results were confirmed by IPTW-adjusted analysis. The study suggests both the safety and efficacy of the double switch from originator IFX to CT-P13 and SB2 in patients with IBD is maintained. This strategy may be associated with potential cost implications., (© 2021 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Background and Aim: Since the outbreak of COVID-19, concerns have been raised as to whether inflammatory bowel disease (IBD) patients under biologic therapy may be more susceptible to the disease. This study aimed to determine the incidence and outcomes of COVID-19 in a large cohort of IBD patients on biologic therapy., Methods: This observational retrospective multicenter study collected data about COVID-19 in IBD patients on biologic therapy in Italy, between February and May 2020. The main end-points were (i) to assess both the cumulative incidence and clinical outcome of COVID-19, according to different biologic agents and (ii) to compare them with the general population and a cohort IBD patients undergoing non-biologic therapies., Results: Among 1816 IBD patients, the cumulative incidence of COVID-19 was 3.9 per 1000 (7/1816) with a 57% hospitalization rate and a 29% case-fatality rate. The class of biologic agents was the only risk factor of developing COVID-19 (P = 0.01). Non-gut selective agents were associated with a lower incidence of COVID-19 cases, related symptoms, and hospitalization (P < 0.05). Compared with the general population of Lombardy, an overall lower incidence of COVID-19 was observed (3.9 vs 8.5 per 1000, P = 0.03). Compared with 565 IBD patients on non-biologic therapies, a lower rate of COVID-19 symptoms was observed in our cohort (7.5% vs 18%, P < 0.001)., Conclusions: Compared with the general population, IBD patients on biologic therapy are not exposed to a higher risk of COVID-19. Non-gut selective agents are associated with a lower incidence of symptomatic disease, supporting the decision of maintaining the ongoing treatment., (© 2021 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background and Aims: Restructuring activities have been necessary during the lockdown phase of the coronavirus disease 2019 (COVID-19) pandemic. Few data are available on the post-lockdown phase in terms of health-care procedures in inflammatory bowel disease (IBD) care, and no data are available specifically from IBD units. We aimed to investigate how IBD management was restructured during the lockdown phase, the impact of the restructuring on standards of care and how Italian IBD units have managed post-lockdown activities., Methods: A web-based online survey was conducted in two phases (April and June 2020) among the Italian Group for IBD affiliated units within the entire country. We investigated preventive measures, the possibility of continuing scheduled visits/procedures/therapies because of COVID-19 and how units resumed activities in the post-lockdown phase., Results: Forty-two referral centres participated from all over Italy. During the COVID-19 lockdown, 36% of first visits and 7% of follow-up visits were regularly done, while >70% of follow-up scheduled visits and 5% of first visits were done virtually. About 25% of scheduled endoscopies and bowel ultrasound scans were done. More than 80% of biological therapies were done as scheduled. Compared to the pre-lockdown situation, 95% of centres modified management of outpatient activity, 93% of endoscopies, 59% of gastrointestinal ultrasounds and 33% of biological therapies. Resumption of activities after the lockdown phase may take three to six months to normalize. Virtual clinics, implementation of IBD pathways and facilities seem to be the main factors to improve care in the future., Conclusion: Italian IBD unit restructuring allowed quality standards of care during the COVID-19 pandemic to be maintained. A return to normal appears to be feasible and achievable relatively quickly. Some approaches, such as virtual clinics and identified IBD pathways, represent a valid starting point to improve IBD care in the post-COVID-19 era.

Objectives: COVID-19 has rapidly become a major health emergency worldwide. Patients with IBD are at increased risk of infection, especially when they have active disease and are taking immunosuppressive therapy. The characteristics and outcomes of COVID-19 in patients with IBD remain unclear., Design: This Italian prospective observational cohort study enrolled consecutive patients with an established IBD diagnosis and confirmed COVID-19. Data regarding age, sex, IBD (type, treatments and clinical activity), other comorbidities (Charlson Comorbidity Index (CCI)), signs and symptoms of COVID-19 and therapies were compared with COVID-19 outcomes (pneumonia, hospitalisation, respiratory therapy and death)., Results: Between 11 and 29 March 2020, 79 patients with IBD with COVID-19 were enrolled at 24 IBD referral units. Thirty-six patients had COVID-19-related pneumonia (46%), 22 (28%) were hospitalised, 7 (9%) required non-mechanical ventilation, 9 (11%) required continuous positive airway pressure therapy, 2 (3%) had endotracheal intubation and 6 (8%) died. Four patients (6%) were diagnosed with COVID-19 while they were being hospitalised for a severe flare of IBD. Age over 65 years (p=0.03), UC diagnosis (p=0.03), IBD activity (p=0.003) and a CCI score >1 (p=0.04) were significantly associated with COVID-19 pneumonia, whereas concomitant IBD treatments were not. Age over 65 years (p=0.002), active IBD (p=0.02) and higher CCI score were significantly associated with COVID-19-related death., Conclusions: Active IBD, old age and comorbidities were associated with a negative COVID-19 outcome, whereas IBD treatments were not. Preventing acute IBD flares may avoid fatal COVID-19 in patients with IBD. Further research is needed., Competing Interests: Competing interests: CB received lecture fees from Takeda, AbbVie and Janssen. SS received lecture fees from Takeda Pharmaceuticals and Janssen Pharmaceuticals and served as a consultant and a member of Advisory Boards for AbbVie and Janssen Pharmaceuticals. AV received lecture fees from Takeda and AbbVie and served as consultant for MSD, Pfizer and Janssen. MA received consulting fees from Nikkiso Europe and lecture fees from Janssen, Abbvie and Pfizer. CR reports personal fee from Abbvie, Janssen Cilag, MSD, Recordati, Takeda and Vifor. FC served as consultant and a member of advisory board for Mundipharma, AbbVie, MS&D, Takeda, Janssen, Roche, Celgene and received lecture fees from AbbVie, Amgen, Ferring, Takeda, Allergy Therapeutics and unrestricted research grants from Giuliani, Sofar, MSD, Takeda, AbbVie. FB served as a member of advisory board for Biogen and Janssen, Takeda, Celgene, Mundipharma, AbbVie and MSD. FC served as consultant and a member of advisory board for Mundipharma, AbbVie, MS&D, Takeda, Janssen, Roche, Celgene and received lecture fees from AbbVie, Amgen, Ferring, Takeda, Allergy Therapeutics. DGR served as consultant and received lecture fees from Janssen, Ferring, Errekappa. SD served as a speaker, consultant and advisory board member for Schering-Plough, Abbott (AbbVie) Laboratories, Merck, UCB Pharma, Ferring, Cellerix, Millenium Takeda, Nycomed, Pharmacosmos, Actelion, Alfa Wasserman, Genentech, Grunenthal, Pfizer, AstraZeneca, Novo Nordisk, Cosmo Pharmaceuticals, Vifor and Johnson and Johnson. MCF received fees as member of advisory boards and participation to sponsored symposia from AbbVie, Takeda, Jannsen-Cilag, Pfizer, Sandoz. AA served as a consultant for AbbVie, Allergan, Amgen, Biogen, Bristol Myers Squibb, Celgene, Celltrion, Ferring, Gilead, Janssen, Lilly, MSD, Mylan, Pfizer, Roche, Samsung Bioepis, Sandoz and Takeda; MD served as a speaker, consultant and advisory board member for AbbVie, Takeda, Janssen, Norgine, Pfizer, MSD, Celltrion, Roche, Gilead, Bioclinica, Ferring, SOFAR, Chiesi, Zambon. GF received consultancy fees from Ferring, MSD, AbbVie, Takeda, Janssen, Amgen, Sandoz, Samsung Bioepis, Celltrion., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

The gut microbiota is a complex and dynamic ecosystem with a strong influence on the host's health. Several factors can modify the gut's bacterial composition, often leading to the onset of intestinal dysbiosis. Therefore, it is essential not only to evaluate the quantitative bacterial changes occurring in the human microbiota but also to characterize relationships existing among all the microorganisms. This study aimed to evaluate the impact of bowel cleansing on the fecal microbiota network by highlighting differences between fecal microflora before and after colonoscopy, and luminal samples during colonoscopy. Fecal and luminal samples, previously analyzed by mean of Next-Generation Sequencing (NGS) for their bacterial abundance, were further processed by a method based on Artificial Neural Network (ANN) architecture. The bowel lavage had a strong effect on the intestinal microbiota network, leading to significant changes in the distribution of different bacterial hubs potentially involved in the microbiota homeostasis. Furthermore, the fecal and luminal microbiota showed a different bacterial network, characterized by distinct microbial hubs. In particular, the latter seemed to be rich in potentially pathogenic bacteria which, in physiological conditions, are counteracted by fecal microorganisms.

Background: Percutaneous endoscopic gastrostomy (PEG) is the most common endoscopic procedure used to provide nutritional support., Aim: To prospectively evaluate the mortality and complication incidences after PEG insertion or replacement., Methods: All patients who underwent PEG insertion or replacement were included. Details on patient characteristics, ongoing therapies, comorbidities, and indication for PEG placement/replacement were collected, along with informed consent form signatures. Early and late (30-day) complications and mortality were assessed., Results: 950 patients (47.1% male) were enrolled in 25 centers in Lombardy, a region of Northern Italy. Patient mean age was 73 years. 69.5% of patients had ASA status 3 or 4. First PEG placement was performed in 594 patients. Complication and mortality incidences were 4.8% and 5.2%, respectively. The most frequent complication was infection (50%), followed by bleeding (32.1%), tube dislodgment (14.3%), and buried bumper syndrome (3.6%). At multivariable analysis, age (OR 1.08 per 1-year increase, 95% CI, 1.0-1.16, p = 0.010) and BMI (OR 0.86 per 1-point increase, 95% CI, 0.77-0.96, p = 0.014) were factors associated with mortality. PEG replacement was carried out in 356 patients. Thirty-day mortality was 1.8%, while complications occurred in 1.7% of patients., Conclusions: Our data confirm that PEG placement is a safe procedure. Mortality was not related to the procedure itself, confirming that careful patient selection is warranted., (Copyright © 2019 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Introduction: Endoscopy has a key role in the management of inflammatory bowel disease (IBD). It is helpful in the diagnosis, in case of relapse, refractoriness, before therapeutic changes, after surgery as well as in the assessment of mucosal healing and in the surveillance of colo-rectal cancer. IBD patients are intended to undergo several times the examination during their lifespan. Bowel preparation and sedation highly contribute to high-quality colonoscopy. Areas covered: Few studies addressed preparation and sedation in the field of IBD. In this review, we focused our attention on the available evidences about bowel preparation and sedation in patients with IBD. Expert commentary: In recent years, the goal of medical treatment in IBD is shifting from clinical improvement in symptoms towards mucosal healing. High-quality endoscopy will gain even more importance in the management of IBD. It is important to locate the most effective preparation and the best sedation in patient with IBD to perform a high-quality endoscopy.

Objective: An adequate bowel preparation is essential for a successful colonoscopy, but to date, only scarce information exists on the impact of the bowel cleansing on the gut microbiota, in particular, 1 month after the procedure., Patients and Methods: Through 16S rDNA Ion Torrent profiling of fecal samples of 10 patients, we evaluated changes that occurred in the gut microbiota composition immediately after a 4 liter polyethylene glycol-based (SELG Esse) bowel lavage and 1 month thereafter. We studied the gut microbiota at the phylum, class, and family level., Results: At the phyla level, we found a significant decrease in Firmicutes abundance and an increase in Proteobacteria abundance immediately after the colon cleansing and 1 month after the colonoscopy, whereas, at the class level, a significant increase in γ-Proteobacteria immediately after the colonoscopy was observed. Interestingly, 1 month after the endoscopic examination, this bacterial class was decreased 2.5-fold compared with samples before colonoscopy, as well as α-Proteobacteria. At the family level, a significant reduction in Lactobacillaceae and an increase in Enterobacteriaceae abundance were observed immediately after the colonoscopy, whereas 1 month after the bowel cleansing, these families were significantly lower compared with samples collected before the colonoscopy. Moreover, the abundance of Rikenellaceae and Eubacteriaceae has been observed to be significantly higher compared with samples collected before the bowel lavage. Finally, Streptococcaceae were increased 4.0-fold 1 month after the bowel lavage compared with fecal samples collected before the colonoscopy., Conclusion: We provide clear evidence that, in normal individuals, a high-volume polyethylene glycol bowel cleansing preparation has a long-lasting effect on the gut microbiota composition and homeostasis, in particular, with a decrease in the Lactobacillaceae abundance, a population of protective bacteria. Further studies are required to assess whether these changes have any metabolic, immunological, or clinical consequence.

Congenital dysfibrinogenemias are characterized by biosynthesis of a structurally abnormal fibrinogen molecule that exhibits reduced functional levels compared with the level of fibrinogen antigen. To date a large number of mutations have been identified in patients with dysfibrinogenemia. Mutations occurring at the thrombin cleavage site (Arg16-Gly17 in the mature alpha-chain) at the amino-terminal end of the fibrinogen alpha chain are a common cause of the disease. These mutations causing abnormal fibrin polymerization are associated with different phenotypes. Here, we report the identification of a novel heterozygous missense mutation of Glycine 17 (Gly17Asp) in a female patient with mild bleeding manifestations, and compare it with other previously reported mutations also resulting in abnormal knob A.

The following on proton pump inhibitors (PPIs) and chemoprevention in relation to Barrett's esophagus includes commentaries on 48-h pH monitoring, pH-impedence, bile acid testing, dyspepsia, long/short segment Barrett's esophagus, nonerosive reflux disease (NERD), functional heartburn, dual-release delivery PPIs, immediate-release PPIs, long-term PPI use, prokinetic agents, obesity, baclofen, nocturnal acid breakthrough, nonsteroidal anti-inflammatory drugs (NSAIDs), and new PPIs., (© 2011 New York Academy of Sciences.)

Background: The prevalence of gastro-oesophageal reflux disease symptoms in physicians, as compared to that of the general population, is not known., Methods: We submitted a validated Italian version of a simple questionnaire (Reflux Disease Questionnaire) to 490 physicians and 430 controls to assess: (i) the presence, frequency and severity of gastro-oesophageal reflux disease symptoms in the two populations; (ii) how the self-assessment of troublesome gastro-oesophageal reflux disease symptoms by physicians correlate with a pathological Reflux Disease Questionnaire, judged on the basis of a total Reflux Disease Questionnaire score >or=8., Results: A valid and complete questionnaire was obtained in 456/490 (93.1%) physicians and 367/430 (85.3%) controls. Between the two groups there were no differences in terms of total Reflux Disease Questionnaire score or individual items, with the only exception of "severity of burning feeling behind breastbone" which was significantly higher in the physician group. An excellent correlation was found between the self-assessment by physician and the total Reflux Disease Questionnaire score., Conclusions: The prevalence of gastro-oesophageal reflux disease symptoms among Italian doctors is not different from that reported by a matched control group, and that their ability in self-assessing a troublesome gastro-oesophageal reflux disease is optimal.

Background/aims: The reflux disease questionnaire (RDQ) is a very simple questionnaire based on only 12 questions that can be answered and evaluated quickly in a primary care setting, which was already found to be valid and reliable in the diagnosis of gastroesophageal reflux disease (GERD). As an English and a German version of the RDQ exist, but not an Italian one, we aimed at translating the RDQ into Italian and evaluating its reliability for the use of Italian-speaking GERD patients., Patients/methods: For the purpose of linguistic validation, we translated backward and forward the original RDQ into Italian and again into English. For the purpose of assessing internal consistency, test-retest, and interrater reliability, 130 GERD patients were used, of whom 57 patients had an endoscopic oesophagitis of grade A to C according to the Los Angeles classification and 63 patients had uninvestigated GERD symptoms but with a frequency of heartburn and/or regurgitation at least twice a week., Results: After professional translation, the Italian RDQ was judged to retain fully the meaning of the original RDQ. Internal consistency, as judged by the (Cronbach's alpha) was satisfactory, with an overall RDQ scale alpha=0.86 (minimum acceptable value=0.70). Test--retest reliability (Spearman coefficient) was again found to be optimal, with individual item values ranging between 0.74 (for 'pain in the upper stomach: frequency') and 0.90 (for 'burning feeling behind breastbone: severity'). Finally, the correlation coefficient was 0.96 for the total scale and a range of 0.85-0.98 for individual items, indicating extremely satisfactory concordance., Conclusions: The Italian RDQ appears to be a simple, reproducible, and reliable tool for the diagnosis of GERD. We believe that this questionnaire is well suited for use, both in primary care settings and in epidemiological studies, in particular for the assessment of so-called typical symptoms.

Aim: To assess the late outcome of teen-agers with a previous history of recurrent abdominal pain (RAP) or irritable bowel syndrome (IBS)., Methods: A group of 67 children with RAP referred to the department from January 1986 to December 1995 was followed up between 5 and 13 years after the initial diagnosis by means of a structured telephone interview. We hypothesized that those patients with persistent adult IBS-like symptoms would be significantly more likely to report a family history of IBS in comparison with adults with no persistent abdominal complaint., Results: Out of the 52 trackable subjects, 15 were found to present IBS-like symptoms at follow-up (29%) whereas the majority (37 subjects) did not. Subjects with IBS-like symptoms were almost three times more likely to present at least one sibling with similar symptoms compared to subjects not complaining (40.0% vs 16.0%), respectively (P < 0.05 at Student t test). Subjects with IBS-like symptoms also reported a higher prevalence of extra-intestinal symptoms, such as back pain, fibromyalgia, headache, fatigue and sleep disturbances., Conclusion: The study confirms previous observations indicating that pediatric RAP can predict later development of IBS. The latter appears to be greatly influenced by intrafamilial aggregation of symptoms, possibly through the learning of a specific illness behavior.

Objective: Reactive regional lymph node enlargement is a frequent ultrasonographic finding in patients with Crohn's disease. However, the prevalence of this condition and its clinical significance are unknown. This study assesses the prevalence of enlarged regional mesenteric lymph nodes and its clinical significance in Crohn's disease, and in particular whether there is a correlation between the sonographic detection of enlarged regional lymph nodes and the degree of clinical or biochemical activity of the disease., Material and Methods: A total of 240 in- and outpatients with Crohn's disease underwent intestinal ultrasound to assess the presence of enlarged regional lymph nodes as well as the thickness and echopattern of the bowel wall, the site and extent of Crohn's disease and the presence of stenosis, fistulas and abscesses. Demographic, clinical and biochemical parameters were also collected for each patient. A multivariate model by means of multiple regression analysis was used to identify independent variables linked to regional lymph node enlargement., Results: Enlarged regional lymph nodes were detected ultrasonographically in 25.4% of Crohn's disease patients. The presence of regional lymph nodes showed a weak correlation with both clinical and biochemical Crohn's disease activity. Regional lymph nodes were found more frequently in young patients (50% of patients < 30 years, 18% of patients between 30 and 50 yrs, and 7% of patients > 50 yrs; p<0.0001) and in patients with a shorter disease duration. Enlarged regional lymph nodes were strongly correlated with internal fistulas and intra-abdominal abscesses. The multiple regression analysis showed that age, duration of disease and presence of internal fistulas were the best independent predictive factors linked to the presence of enlarged mesenteric lymph nodes., Conclusions: The sonographic detection of enlarged regional lymph nodes is more frequent in young patients, which suggests an earlier phase of Crohn's disease and the presence of septic complications such as fistulas and abscesses, but this is of limited valued in assessing disease activity.

Objective: To determine the prevalence of cytomegalovirus infection in patients with steroid-refractory ulcerative colitis who required colonic resection, and to assess its possible association with the use of immunosuppressive and steroid treatment and outcome after colectomy., Patients and Methods: The study included surgical specimens and related pre-operative endoscopic biopsy specimens of 77 consecutive ulcerative colitis patients (34 females) who underwent colectomy because of intractable steroid-refractory ulcerative colitis (55 patients), toxic megacolon (6 patients), dysplasia or cancer (7 patients) or loss of function of the colon (9 patients). Clinical features and current and past treatments were analysed. Haematoxylin and eosin and specific immunohistochemical staining for cytomegalovirus were used to detect inclusion bodies in all specimens., Results: Cytomegalovirus infection was found in 15 of 55 steroid-refractory ulcerative colitis patients (27.3%) and in 2 of 22 non-refractory patients (9.1%) (p=0.123). Only six patients had positive staining for cytomegalovirus in pre-operative endoscopic biopsy specimens. Detection of cytomegalovirus inclusion in biopsy specimens was not related to the number of biopsies or to time that had elapsed since colonoscopy and index surgery. Cytomegalovirus-positive patients were more likely to be on systemic corticosteroids (p=0.03). In contrast, current use and duration of immunosuppressive treatment, number of steroid cycles since diagnosis and in the last year, as well as chronic use of steroid in the last year were not significantly related to cytomegalovirus infection. Cytomegalovirus-positive patients did not receive antiviral therapy following proctocolectomy but did not show endoscopic or histological cytomegalovirus reactivation in the ileo-anal pouch and in the remaining bowel., Conclusions: Cytomegalovirus infection is frequently found in surgical specimens of patients with steroid-refractory ulcerative colitis and is more likely in patients on corticosteroid treatment. Cytomegalovirus infection is frequently unrecognised in pre-operative biopsy specimens, thus raising concerns about the accuracy of the available diagnostic tools. Unrecognised and untreated cytomegalovirus infection does not affect the outcome of ulcerative colitis patients following proctocolectomy.

Objective: Treatment of chronic functional constipation is difficult. Both oral and topical laxatives may fail to adequately relieve symptoms, and there is risk of adverse effects such as functional or structural changes in the intestine, together with electrolyte disturbances. The aim of this study was to evaluate the efficacy and safety of a suppository that combines sodium bicarbonate and potassium bitartrate in a polyethylene glycol base to generate approximately 175mL of carbon dioxide (CO(2)). This release distends the rectal ampulla, thereby stimulating peristalsis and a subsequent bowel movement., Patients and Methods: This was a prospective, crossover, double-blind, randomised, placebo-controlled, sequential study of outpatients with chronic functional constipation. Each patient received two suppositories of identical appearance, containing active drug or placebo. The sequence of active drug-placebo (sequence 1) or placebo-active drug (sequence 2) was randomised in groups of eight. The second suppository was taken 7 days after the first. The following parameters were evaluated and scored: evacuation time, type of evacuation, feeling of emptying of the rectal ampulla, stool characteristics, anal complaints, abdominal pain and overall patient assessment., Results: A total of 29 patients entered the study. According to a restricted sequential plan, a statistical significance (p < 0.05) in favour of the active drug was reached after 26 patients. A positive response within 30 minutes of introduction of the suppository occurred in 51.7% and 6.9% of patients treated with the active drug and placebo, respectively (p = 0.0003). Normal evacuation occurred in 65.5% and 24.1% of patients treated with the active drug and placebo, respectively (p = 0.004). Normal stool consistency was found in 44.8% and 7.2% of patients treated with the active drug and placebo, respectively (p = 0.04). Patient assessment of treatment as satisfactory occurred in 51.7% and 20.7% of subjects treated with the active drug and placebo, respectively (p = 0.029). Only a trend in favour of the active drug was observed with regard to feeling of incomplete evacuation, and active drug was comparable to placebo with regard to anal and abdominal tolerability, Conclusion: The CO(2)-releasing suppository may represent an alternative to rectal laxatives for the relief of chronic functional constipation. The data obtained in this study indicate that CO(2)-releasing suppositories may be usefully and safely employed in the treatment of patients at risk for electrolyte disorders such as the elderly or patients with renal or cardiovascular disorders.

Aim: Platelet-rich plasma (PRP) is a solution, usually in the form of a gel, with a high concentration of platelets (equal to double or three-fold normal reference values). This preparation also contains a high concentration of fibrinogen, a fundamental element for the release of numerous polypeptides (complementary factors) and above all for the induction of platelet degranulation and the consequent release of growth factors, which interact in a highly positive fashion with the bone metabolism at the host site. The biological benefit that PRP can give to tissues treated with the technique of major maxillary sinus augmentation thus appears undoubted., Methods: The series reported consists of 3 patients who were treated by major augmentation of the maxillary sinus associated with the use of a mixture consisting of PRP, beta-tricalcium phosphate (Cerasorb ) and autologous bone tissue., Results: All the patients were successfully treated and it was possible to detect tissue regeneration both horizontally and vertically (approximately 4 mm), with formation of high quality bone tissue, which subsequently enabled optimal osseointegration of the implants inserted., Conclusion: The introduction of PRP into the field of regenerative techniques has opened new horizons, especially in the branch of implantology. This mixture is able to reduce the quantity of autologous tissue harvested. The gel-like consistency also avoids the application and subsequent removal of a membrane, and in consequence the surgical trauma undergone by the patient is markedly reduced.

The aim of this study was to assess the epidemiology of syncope in unselected patients referred to an emergency room and eventually admitted to the clinical wards to perform a complete work-up, and to analyze the costs of hospitalization. The clinical charts of all patients referred for all causes to the emergency rooms of three hospitals in the Florence area during the year 2000 and of all patients admitted from the emergency rooms to the clinical wards with a diagnosis of lone-related (vasovagal) or disease-related syncope were revised. A total of 1,290 (3.36%) cases of syncope out of 38,330 presentations were registered; among these, 702 cases (1.83% of all presentations, 54% of all syncopes) were directly discharged, and 443 cases (1.14% of all presentations, 34% of all syncopes) were hospitalized. The remaining 149 cases (12% of all syncopes) refused admission. Following admission, 500 patients were discharged with the diagnosis of syncope: 115 lone-related (23%) and 385 disease-related syncopes (77%). A cost-benefit analysis of the hospitalized patients showed that admitting patients with lone syncope leads to an economical loss to the hospital., (Copyright 2002 S. Karger AG, Basel)

Background & Aims: The role of the interleukin (IL)-1 receptor antagonist (IL-1ra) in predisposing an individual to inflammatory bowel disease (IBD) is controversial. This study aimed to determine the association between intron 2 IL-1ra polymorphism and IBD by performing a multiethnic case-control study and to assess its functional significance., Methods: A total of 236 patients with ulcerative colitis (UC), 196 patients with Crohn's disease (CD), and 338 ethnically matched control patients treated at LAC-USC and Cedars-Sinai Medical Centers and the University of Milan Medical Center were genotyped for a variable length polymorphism in intron 2 of the IL-1ra gene (IL-1RN). Total IL-1ra protein production rates in peripheral blood mononuclear cells (PBMCs) were correlated with carriage of allele 2 of the IL-1RN gene (IL-1RN*2)., Results: In the LAC-USC group, UC patients (n = 60) had an increased frequency of at least 1 copy of IL-1RN*2 compared with controls (n = 129) (70% vs. 33%; P < 0.01; odds ratio [OR], 4.7). The frequency of IL-1RN*2 carriage in the Cedars-Sinai group was 59% in UC, 45% in CD, and 42% in controls (P < 0.01; OR, 2.0). A significant difference was observed only in the Jewish subgroup (P = 0.003; OR, 5.0). The association was not detected in UC or CD patients treated at the University of Milan. The ORs of 4.7 and 5.0 appear to be the highest reported in any UC population for any genetic markers. Further, carriage of IL-1RN*2 was associated with decreased production of total IL-1ra protein in cultured PBMCs from both UC patients and controls., Conclusions: These results provide further evidence that IL-1ra is important in the predisposition to UC, there may be genetic or pathogenetic heterogeneity between different ethnic groups, and UC and CD are genetically distinct diseases.

The pathogenesis of ascites, a severe and the most frequent complication during cirrhosis, is still not completely understood, but present evidence indicates that portal hypertension principally triggers renal sodium and water retention. Ascites is associated with profound disturbances of splanchnic and systemic haemodynamics, which in turn may influence renal function. Within the kidney the balance between vasoconstricting and vasodilating factors is critical for the maintenance of renal function. As the disease progresses, vasoconstricting factors (mainly angiotensin II, catecholamines, thromboxane, leucotrienes and endothelins) prevail, probably due to the exhaustion of the vasodilating renal autacoid system (mainly prostaglandins). In this setting, vasoconstriction of the intrarenal vascular system induces marked and often irreversible sodium and water retention, leading to refractory ascites, a progressive rise in plasma creatinine levels and reduction of renal clearances (hepatorenal syndrome, HRS). This persistent renal hypoxia may also favour the occurrence of tubular damage due to several causes. A careful therapeutic approach is first based on sequential diuretic treatment (and the addition of adequate plasma expansion with human albumin for patients with diuretic resistant ascites), which may lead to control of ascites for years. However, when HRS occurs, all the proposed treatments (such as paracentesis, administration of renal vasodilators, systemic vasoconstrictors, calcium channel antagonists, TIPS, surgical portosystemic shunts) have been shown to moderately or temporarily improve renal function only, leaving liver transplantation as the only choice of treatment for patients.

Background/aims: Diuretic treatment of ascites could result in intravascular volume depletion, electrolyte imbalance and renal impairment. We investigated whether intravascular volume expansion with albumin exert beneficial effects in cirrhosis with ascites., Methods: In protocol 1, 126 cirrhotic inpatients in whom ascites was not relieved following bed rest and a low-sodium diet, were randomly assigned to receive diuretics (group A) or diuretics plus albumin, 12.5 g/day (group B). In protocol 2, group A patients continued to receive diuretics and group B diuretics plus albumin (25 g/week) as outpatients and were followed up for 3 years. End points were: disappearance of ascites, duration of hospital stay (protocol 1), recurrence of ascites, hospital readmission and survival (protocol 2)., Results: The cumulative rate of response to diuretic treatment of ascites was higher (p < 0.05) and hospital stay was shorter (20 +/- 1 versus 24 +/- 2 days, p < 0.05) in group B than in group A patients. After discharge, group B patients had a lower cumulative probability of developing ascites (19%, 56%, 69% versus 30%, 79% and 82% at 12, 24 and 36 months, p < 0.02) and a lower probability of readmission to the hospital (15%, 56%, 69% versus 27%, 74% and 79%, respectively, p < 0.02). Survival was similar in the two groups., Conclusions: Albumin is effective in improving the rate of response and preventing recurrence of ascites in cirrhotic patients with ascites receiving diuretics. However, the cost/benefit ratio was favorable to albumin in protocol 1 but not in protocol 2.

The liver plays a major role in the regulation of glucose metabolism: plasma glucose concentration is the result of peripheral glucose utilization and liver production. Several hormones, including insulin, glucagon, growth hormone, cortisol, and catecholamines contribute to the regulation of glucose metabolism by the liver. In this review, we examine hepatic glucose metabolism, in particular the actions of insulin and contrainsular hormones on glucose hepatic uptake and production in patients with diabetes or chronic liver disease. The most frequent patterns of hepatic involvement that take place during diabetes, i.e. nuclear glycogenesis, steatosis, portal fibrosis, and diabetic steatonecrosis, are discussed. Also considered are anomalies of glucose homeostasis observed in chronic liver disease, including glucose intolerance, diabetes, and hypoglycemias. There is a strong correlation between diabetes mellitus and the liver: diabetic patients have typical histological lesions, while several glucose metabolism alterations are commonly found in subjects with chronic liver disease. The pathogenesis of impaired glucose metabolism during chronic liver disease has not yet been fully understood: further clinical and experimental studies should clarify this issue.

Objective: Chronic infection by hepatitis B virus (HBV) and hepatitis C virus (HCV) is now recognized as a major cause of liver cirrhosis. This study was aimed at evaluating the natural history of the disease in a large series of Italian patients with HBV- and HCV-related cirrhosis without portal hypertension at entry., Methods: The clinical records of 405 patients (233 males, mean age 54 +/- 9 yr) with histologically proven cirrhosis (321 with HCV-related and 84 with HBV-related cirrhosis) and no clinical evidence of portal hypertension at entry were retrospectively examined to evaluate the occurrence of complications and the cumulative mortality rate during follow-up., Results: Patients had a mean follow-up of 8 +/- 3 yr. The cumulative survival rate was 99.1% at 5 yr, 76.8% at 10 yr, and 49.4% at 15 yr. The age-adjusted death rate was 3.14 and 2.84 times higher than in the general Italian population in men and women, respectively. Only the bilirubin level was an independent indicator of survival. Esophageal varices, ascites, jaundice, hemorrhage, hepatic encephalopathy, and hepatocellular carcinoma significantly reduced the survival rate (major complications), whereas thrombocytopenia, diabetes, and cholelithiasis did not affect survival (minor complications). The incidence of hepatocellular carcinoma was similar in patients with either HBV- or HCV-related disease and was quite frequent, especially in males., Conclusions: This study demonstrates that the course of virus-induced liver cirrhosis is not influenced by the etiology of the disease and that the occurrence of complications significantly shortens life expectancy. The longer survival rate observed in this study is probably due to the fact that cirrhosis was here recognized by liver biopsy in the absence of clinical evidence of portal hypertension.

The role of hepatitis B virus (HBV) and hepatitis C virus (HCV) as a major cause of chronic liver disease is now accepted worldwide. This study was aimed at evaluating the natural history of the disease in patients with virus-induced chronic active hepatitis or cirrhosis, and the influence played by age, sex and etiology, liver function tests and by the occurrence of different complications. We retrospectively examined the clinical records of 506 inpatients: 194 were affected by chronic active hepatitis (125 males, 69 females, mean age 45 +/- 11 years, 146 HCV- and 48 HBV-related), and 312 by cirrhosis without clinical evidence of portal hypertension (178 males, 134 females, mean age 53 +/- 9 years, 249 HCV- and 63 HBV-related). The occurrence of cirrhosis in the chronic active hepatitis group was then calculated, together with the occurrence of complications and the cumulative mortality rate of established cirrhosis. During follow-up 93 patients with chronic hepatitis developed cirrhosis. The cumulative probability of developing cirrhosis in this group was 6.64% at 5 years, 56.1% at 10 years and 86.8% at 15 years. These patients were therefore included in the cirrhosis group for the final analysis, so that a total of 405 cirrhotic patients were evaluated: these patients had a cumulative survival rate of 99.1% at 5, 76.8% at 10 and 49.4% at 15 years. Comparing the age-adjusted death rate of our patients with the general Italian population, we observed that in patients with liver cirrhosis it was 3.14 and 2.84 times higher in men and women, respectively. Bilirubin was an independent indicator of survival. Several complications, such as esophageal varices, ascites, jaundice, hemorrhage, hepatic encephalopathy and hepatocellular carcinoma significantly reduced the survival rate and were indicated as major complications, while thrombocytopenia, cholelithiasis and diabetes did not affect survival and thus were called minor complications. Incidence of hepatocellular carcinoma was very high especially in males, without correlation with etiology. In conclusion, the progression of virus-induced chronic active hepatitis to cirrhosis is not influenced by sex and etiology. Similarly, the different etiology does not modify the natural history of cirrhosis while the occurrence of one or more major complications significantly shortens survival. The longer survival rate observed in patients with cirrhosis included in this study is probably due to the selective inclusion of patients with early disease and no evidence of portal hypertension.

Over 2000 electrocution deaths were identified among U.S. construction workers from 1980 to 1991, with the highest mean annual crude mortality rate (2.5 per 100,000 people), and second highest mean age-adjusted rate (2.7 per 100,000 people) of all industries. Although the crude fatality rates showed a downward trend, construction workers are still about four times more likely to be electrocuted at work than are workers in all industries combined. Nearly 40% of the 5083 fatal electrocutions in all industries combined occurred in construction, and 80% were associated with industrial wiring, appliances, and transmission lines. Electrocutions ranked as the second leading cause of death among construction workers, accounting for an average of 15% of traumatic deaths in the industry from 1980 to 1991. The study indicates that the workers most at risk of electrical injury are male, young, nonwhite, and electricians, structural metal workers, and laborers. The most likely time of injury is 11 a.m. to 3 p.m. from June to August. Focusing prevention on these populations and characteristics through better methods of worker and supervisor electrical safety training, use of adequate protective clothing, and compliance with established procedures could minimize the average annual loss of 168 U.S. construction workers.

Patients with cirrhosis and ascites have high plasma levels of atrial (ANP) and brain (BNP) natriuretic peptides, two cardiac hormones released by the atria and ventricles, respectively. We evaluated renal hemodynamics, sodium excretion, and intrarenal sodium handling (lithium clearance method) in seven cirrhotic patients with ascites and avid sodium retention before, during, and after the infusion of synthetic human BNP, at the dose of 4 pmol/kg.min for 1 hour, which has been shown to increase renal plasma flow, glomerular filtration rate (GFR), and sodium excretion in healthy subjects without affecting systemic hemodynamics. Plasma BNP levels were 7.31 +/- 0.85 pmol/L in baseline conditions, and increased to 33.60 +/- 2.96 pmol/L at the end of the infusion (P < .01 vs. baseline). Urinary excretion of guanosine 3',5'-cyclic monophosphate (cGMP) also significantly increased during the infusion, indicating stimulation of natriuretic peptide receptors by BNP. BNP administration did not modify renal plasma flow, GFR, sodium excretion or tubular sodium reabsorption to any appreciable extent. Arterial pressure heart rate, plasma norepinephrine, and plasma renin activity (PRA) where also unchanged, whereas plasma aldosterone concentration showed a significant, 35% reduction at the end of the postinfusion period, ruling out the possibility that BNP-induced vasodilation might be responsible for failure of the peptide to induce a natriuretic response. Overactivity of antinatriuretic factors is probably the main determinant of the blunted natriuretic effect of BNP in these patients.

Background & Aims: Proinflammatory cytokines such as interleukin (IL) 1, IL-8, and tumor necrosis factor (TNF) have been implicated as primary mediators of intestinal inflammation. The aim of the present study was to determine the effects of a novel cytokine antagonist (CGP 47969A) in a rabbit model of acute colitis., Methods: Colitis was induced using the formalin-immune complex technique. Animals were pretreated intrarectally with CGP 47969A (30, 10, or 3 mg/kg), hydrocortisone (0.8 mg/kg), or vehicle (4 mL saline) 2 hours before the induction of colitis and twice daily thereafter until death 48 hours after the induction of colitis. The severity of inflammation of colonic tissue was assessed using histological analysis and myeloperoxidase activity assay, and IL-1 alpha, IL-8, TNF-alpha, and IL-1 receptor antagonist levels were determined., Results: Compared with vehicle, CGP 47969A (10 mg/kg) significantly reduced the acute inflammatory index by 58%, edema by 67%, necrosis by 99%, and myeloperoxidase activity by 49% (all P < 0.02) with efficacy similar to that of steroids. These effects were associated with a significant inhibition of colonic IL-1 alpha and IL-8 by 56% and 90%, respectively (p < 0.01)., Conclusions: Administration of CGP 47969A reduces inflammation and tissue damage in rabbit immune complex colitis through mechanisms involving the inhibition of mucosal proinflammatory cytokines.

We assessed the cardiovascular and renal effects of human brain natriuretic peptide (BNP) infused at a dose inducing an increase in plasma BNP to pathophysiologic levels, in eight hypertensive patients in a randomized, placebo-controlled, cross-over study. Left ventricular performance, cardiac output (echocardiography), heart rate, arterial pressure, glomerular filtration rate (GFR; creatinine clearance), sodium excretion, intrarenal sodium handling (lithium clearance method), and urine flow rate were measured in the infusion and postinfusion periods (1 h each), together with plasma BNP and the urinary excretion rate of cGMP. Plasma BNP levels increased from 2.90 +/- 0.74 to 36.43 +/- 5.51 pmol/L (P < .01) at the end of the infusion and were still elevated at the end of the postinfusion period (7.03 +/- 1.41 pmol/L, P < .05). The urinary excretion of cGMP was also significantly higher during BNP infusion. Left ventricular performance, cardiac output, arterial pressure, and peripheral vascular resistance were not affected by BNP. Peptide infusion induced a significant increase in GFR (placebo, 115 +/- 24; BNP, 147 +/- 19 mL/min), sodium excretion (placebo, 129 +/- 40; BNP, 243 +/- 60 mumol/min), and urine flow rate. All these effects were observed also in the postinfusion period. The natriuretic effect of BNP was attributable to both an increase in filtered sodium load and a reduction of distal sodium reabsorption. These results suggest that BNP may contribute to maintain renal function and sodium excretion in patients with essential hypertension.

Background: H. pylori and nonsteroidal anti-inflammatory drugs (NSAIDs) are major causes of gastroduodenal injury in man. We assessed the effect of daily NSAID ingestion on gastric histology and the interaction of H. pylori infection and NSAID ingestion on gross and histological injury and prostaglandin production., Methods: Fifty-two healthy volunteers with normal baseline endoscopy were randomly assigned to receive identical-appearing naproxen 500 mg b.d., etodolac 400 mg b.d., or placebo b.d. for 4 weeks. The number and size of all erosions and ulcers were recorded by endoscopy at weeks 1 and 4. Biopsies taken at baseline, week 1 and week 4 were assessed for H. pylori, histology and gastric prostaglandin E2 production., Results: No significant changes occurred with treatment in any histological feature in the three study groups or in H. pylori positive or negative subsets. Antral inflammation scores (scale, 0-6) for the NSAID group were: week 0--1.2 +/- 0.3; week 1--1.1 +/- 0.3; week 4--1.3 +/- 0.3; findings of 'chemical gastritis' were not seen. No significant difference in gross gastroduodenal injury (number or total surface area of ulcers or erosions) was seen between H. pylori positive and negative subjects in the three groups at week 1 or 4. Baseline prostaglandin E2 production was significantly higher in H. pylori positive subjects (2398 +/- 400 vs. 1064 +/- 255 pg/mg protein) and decreased significantly with 1 week of naproxen in H. pylori positive and negative subjects., Conclusions: NSAID ingestion does not cause diffuse histological injury. Any diffuse histological injury in the gastric mucosa is related to the presence of H. pylori, and this H. pylori-associated gastritis is not altered by NSAID ingestion. Furthermore, the development of gross gastroduodenal damage with 4 weeks of NSAID use is not influenced by underlying H. pylori infection.

The etiology and pathogenesis of inflammatory bowel disease (IBD) are unknown. Increasing evidence supports the theory that chronic IBD is the result of dysfunctional immunoregulation manifested by an inappropriate production of mucosal cytokines. The aim of the present study was to test the hypothesis that a specific mucosal imbalance of IL-1 and IL-1 receptor antagonist (IL-1ra) production plays an important role in the perpetuation and chronicity of intestinal inflammation. Total IL-1, IL-1ra, and the IL-1ra/IL-1 ratio were measured in freshly isolated intestinal mucosal cells, as well as in mucosal biopsies obtained from control, Crohn's disease, and ulcerative colitis patients. IL-1 alpha, IL-1 beta, and IL-1 ra were measured by specific non-cross-reacting radioimmunoassays and ELISA. A markedly significant decrease in the intestinal mucosal IL-1ra/IL-1 ratio was found in both Crohn's disease and ulcerative colitis patients when compared with control subjects (p < 0.01). The IL-1ra/IL-1 ratio correlated closely with the clinical severity of disease (r = -0.7846, p < 0.001). Furthermore, the observed decrease in the IL-1ra/IL-1 ratio was specific for IBD because a decreased IL-1ra/IL-1 ratio was not found in patients with self-limiting colitis. These results support the hypothesis that an imbalance between IL-1 and IL-1ra production is of pathogenic importance in chronic inflammatory diseases, including IBD.

Administration of exogenous interleukin-1 receptor antagonist (IL-1ra) is effective in reducing the severity of disease in animal models of acute inflammation. However, the function of endogenous IL-1ra in this process, is not yet known. We investigated the pathophysiological role of IL-1ra in a rabbit model of formalin-immune complex colitis. This model has previously been shown to be IL-1 mediated and a reduction in disease severity is observed with exogenous IL-1ra treatment. Colonic IL-1ra was found to be elevated subsequent to IL-1, and exceeded IL-1 levels 10-fold. Peak levels of IL-1ra preceded both the resolution of colitis and a significant decrease in IL-1 production. Administration of specific neutralizing antibodies against rabbit IL-1ra increased mortality and prolonged intestinal inflammatory responses. A significant increase in IL-1 alpha colonic tissue levels was also measured as a result of exogenous anti-IL-1ra treatment. These studies are the first demonstration that endogenous IL-1ra may play an important role in regulating the host's inflammatory response by counteracting the deleterious and possibly lethal effects of IL-1 produced during acute inflammation.

Background: In cirrhotic patients with ascites, captopril has deleterious effects on renal function, which have been referred to as captopril-induced arterial hypotension. The effects of this drug on renal function in cirrhosis were evaluated using low-dose captopril, thereby avoiding any change in arterial pressure., Methods: In a randomized, double-blind, placebo controlled, cross-over trial, the effects of 12.5 mg captopril on renal plasma flow, glomerular filtration rate (measured by radioisotopic techniques), and sodium excretion in healthy controls and cirrhotic patients with and without ascites were determined., Results: In healthy subjects, captopril only induced a significant, 18% increase in renal plasma flow. In contrast, glomerular filtration rate significantly decreased in patients with (from 108 +/- 7 to 78 +/- 9 mL/min) and without ascites (from 102 +/- 4 to 88 +/- 3 mL/min), whereas renal plasma flow did not change. Urinary sodium excretion also significantly decreased in ascitic patients (from 43.8 +/- 4.4 to 30.6 +/- 3.8 mumol/min)., Conclusions: These data suggest that angiotensin II contributes to maintain renal hemodynamics in cirrhosis with and without ascites.

Refractory ascites, that is ascites which cannot be mobilized by low sodium diet and maximal doses of diuretics (up to 400 mg spironolactone or potassium canrenoate and 160 mg furosemide per day), occurs in 5% of cirrhotic patients with ascites. The development of refractory ascites is mainly related to the progression of arterial vasodilation-mediated vascular underfilling and to the imbalance between reduced synthesis of renal vasodilating factors (especially renal prostaglandins) and extreme activation of vasoconstricting systems. Further features include increased sodium reabsorption in the proximal tubule and altered pharmacokinetics and pharmacodynamics of diuretics. In patients with impaired renal function (as is the case for most patients with refractory ascites), the marked reduction of renal perfusion and glomerular filtration rate, with the consequent decrease of filtered sodium load, becomes the main pathogenetic factor. The principal therapeutic options for refractory ascites include repeated paracentesis and implantation of the LeVeen shunt. Paracentesis is a rapid and safe procedure to remove ascites, but it does not correct sodium retention. Ascites recurrence, therefore, may occur after a brief interval. The LeVeen shunt allows for better long-term control of ascites, but severe complications may supervene, and shunt occlusion is common. Neither therapeutic procedure improves survival. Different experimental therapeutic procedures have been proposed. Administration of ornipressin corrects hyperdynamic circulation and improves renal function. Thromboxane synthase inhibitors, by reducing renal synthesis of thromboxane A2, potentiate the diuretic and natriuretic response to furosemide. More invasive procedures, including portosystemic shunt and transjugular intrahepatic stent, are rarely used in the treatment of refractory ascites.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma levels of brain natriuretic peptide, a recently identified cardiac hormone with natriuretic activity, were measured in 11 healthy subjects, 13 cirrhotic patients without ascites, 18 nonazotemic cirrhotic patients with ascites and 6 patients with cirrhosis, ascites and functional kidney failure. Plasma levels of brain natriuretic peptide were similar in healthy subjects and cirrhotic patients without ascites (5.56 +/- 0.65 and 7.66 +/- 0.68 fmol/ml, respectively). In contrast, cirrhotic patients with ascites, with and without functional kidney failure, had significantly higher plasma concentrations of brain natriuretic peptide (19.56 +/- 1.37 and 16.00 +/- 1.91 fmol/ml, respectively) than did healthy subjects and patients without ascites (p less than 0.01); no significant difference was found between the two groups of cirrhotic patients with ascites with respect to this parameter. In the whole group of cirrhotic patients included in the study, brain natriuretic peptide level was directly correlated with the degree of impairment of liver and kidney function, plasma renin activity and plasma levels of aldosterone and atrial natriuretic peptide. The results of this study indicate that brain natriuretic peptide is increased in cirrhotic patients with ascites and suggest that sodium retention in cirrhosis is not due to deficiency of this novel cardiac hormone.