The Diagnosis and Management of Chronic Constipation in Italy: Results from a Survey Conducted among Italian Gastroenterologists.

Background: Chronic constipation (CC) is one of the most common disorders of gut-brain interaction (DGBI). The management of CC requires specific skills due to its complex and multifactorial pathophysiology and its multistep treatment. The aims of this study were to evaluate the availability and the use of diagnostic tools for CC in Italy and the therapeutic management of CC by Italian gastroenterologists (GEs). Methods: A survey was conducted during the 28th meeting of the Italian Federation of Digestive Disease Societies (FISMAD; Rome, Italy, 11-14 May 2022). The survey explored the presence of a clinic dedicated to DGBIs, the availability and the use of specific diagnostic tools, the routine use of digital rectal examination (DRE), and the therapeutic approach to CC by Italian GEs. Results: The survey was taken by 236 GEs. The most significant results were that 42% of respondents had a clinic dedicated to DGBI in their institute; DRE was regularly performed by 56.8% of GEs when evaluating a CC patient; young GEs (≤40 years) performed DRE less frequently than older ones (p < 0.001); anorectal manometry was available to 44.3% of GEs; balloon expulsion test (BET) was available to 19.1% of GEs; GEs with a clinic dedicated to DGBI had more frequent access to anorectal physiology testing (p < 0.001); diet and lifestyle advice were the most frequently prescribed treatments; and fiber and macrogol were the second and third most prescribed treatments, respectively. Conclusions: The survey provides an interesting picture of CC management by Italian GEs. The results are in line with previous data collected about 10 years ago among Italian GEs ("CHRO.CO.DI.T.E study"); DRE is still rarely performed by Italian GEs (particularly by young GEs). The availability of anorectal physiology testing is still limited, and BET, which could be easily performed in everyday clinical settings, is rarely performed. Lifestyle suggestions, macrogol and fiber are the preferred treatment, as recommended by all guidelines. These results will be useful to identify as yet unmet educational needs and critical issues to improve CC management.

Bowel movement alterations predict the severity of diverticular disease and the risk of acute diverticulitis: a prospective, international st.

Background/Aims: Patients with diverticular disease (DD) frequently have abnormal bowel movements. However, it is unknown whether the entity of these alterations is associated with the severity of DD. We aimed to assess bowel habits and their relationship with the severity of DD according to Diverticular Inflammation and Complication Assessment (DICA) classification, Combined Overview on Diverticular Assessment (CODA) score, and fecal calprotectin (FC). Methods: An international, multicenter, prospective cohort study was conducted in 43 centers. A 10-point visual analog scale (VAS) was used to assess the severity of constipation and diarrhea. The association of constipation and diarrhea with DICA classification, CODA score, and basal FC was tested using non-parametric tests. Survival methods for censored observations were applied to test the association of constipation and diarrhea with the incidence of acute diverticulitis over a 3-year follow-up. Results: Of 871 patients with DD were included in the study. Of these, 208 (23.9%) and 199 (22.9%) reported a VAS score for constipation and diarrhea at least 3 at baseline, respectively. Higher constipation and diarrhea scores were associated with increasing DICA classification, CODA score and basal FC (P< 0.001). Constipation and diarrhea scores were independently associated with an increased hazard of developing acute diverticulitis (hazard ratio [HR]constipation = 1.15 per 1-VAS point increase, 95% confidence interval [CI], 1.04-1.27; P=0.004; and HRdiarrhea =1.14; 95% CI, 1.03-1.26; P=0.014, respectively). Conclusions: In newly diagnosed patients with DD, higher endoscopic and combined scores of DD severity were associated with higher scores of constipation and diarrhea at baseline. Both constipation and diarrhea were independent prognostic factors of acute diverticulitis.

Claudin-2: A marker for a better evaluation of histological mucosal healing in inflammatory bowel diseases.

BACKGROUND: Histological mucosal healing has become a paramount target goal to achieve in the treatment of inflammatory bowel diseases. However, there is still a lack of agreement on the best way to reach this goal, since numerous histological scores are available worldwide. AIMS: We investigated whether claudin-2, a member of claudin family involved in the regulation of intestinal tight junctions, might be useful to assess the presence of active disease in patients with inflammatory bowel diseases. METHODS: Biopsies from 123 patients with ulcerative colitis, Crohn's disease, infectious colitides and irritable bowel syndrome patients where tested with immunohistochemistry for claudin-2. RESULTS: Claudin-2 appeared to be a very sensitive marker of disease activity in inflammatory bowel diseases, but was negative in the other kinds of patients. In addition, immunohistochemistry for claudin-2 showed good reproducibility by different pathologists. CONCLUSIONS: Should these findings be confirmed in more numerous cohorts of patients, and especially in those with minimal or focal residual disease activity, this simple assessment could be useful in the routine daily practice to facilitate the task of pathologists and clinicians in the diagnosis and management of patients with inflammatory bowel diseases.

PhosphoLipidome Alteration Induced by Clostridioides difficile Toxin B in Enteric Glial Cells.

Clostridioides difficile (C. difficile) is responsible for a spectrum of nosocomial/antibiotic-associated gastrointestinal diseases that are increasing in global incidence and mortality rates. The C. difficile pathogenesis is due to toxin A and B (TcdA/TcdB), both causing cytopathic and cytotoxic effects and inflammation. Recently, we demonstrated that TcdB induces cytopathic and cytotoxic (apoptosis and necrosis) effects in enteric glial cells (EGCs) in a dose/time-dependent manner and described the underlying signaling. Despite the role played by lipids in host processes activated by pathogens, to counter infection and/or induce cell death, to date no studies have investigated lipid changes induced by TcdB/TcdA. Here, we evaluated the modification of lipid composition in our in vitro model of TcdB infection. Apoptosis, cell cycle, cell viability, and lipidomic profiles were evaluated in EGCs treated for 24 h with two concentrations of TcdB (0.1 ng/mL; 10 ng/mL). In EGCs treated with the highest concentration of TcdB, not only an increased content of total lipids was observed, but also lipidome changes, allowing the separation of TcdB-treated cells and controls into different clusters. The statistical analyses also allowed us to ascertain which lipid classes and lipid molecular species determine the clusterization. Changes in lipid species containing inositol as polar head and plasmalogen phosphatidylethanolamine emerged as key indicators of altered lipid metabolism in TcdB-treated EGCs. These results not only provide a picture of the phospholipid profile changes but also give information regarding the lipid metabolism pathways altered by TcdB, and this might represent an important step for developing strategies against C. difficile infection.

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

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

Ustekinumab safety and effectiveness in patients with ulcerative colitis: results from a large real-life study.

BACKGROUND: Ustekinumab (UST) is an interleukin-12/interleukin-23 receptor antagonist recently approved for treating ulcerative colitis (UC) but with limited real-world data. Therefore, we evaluated the effectiveness and safety of UST in patients with UC in a real-world setting. RESEARCH DESIGN AND METHODS: This is a multicenter, retrospective, observational cohort study. The primary endpoints were the clinical remission rate (partial Mayo score, PMS, ≤1) and the safety of UST. Other endpoints were corticosteroid-free remission (CSFR) rate, clinical response rate (PMS reduction of at least 2 points), and fecal calprotectin (FC) reduction at week 24. RESULTS: We included 256 consecutive patients with UC (M/F 139/117, median age 52). The clinical remission and clinical response rates at eight weeks were 18.7% (44/235) and 53.2% (125/235), respectively, and 27.6% (42/152) and 61.8% (94/152) at 24 weeks, respectively. At 24 weeks, CSFR was 20.3% (31/152), and FC significantly dropped at week 12 (p = 0.0004) and 24 (p = 0.038). At eight weeks, patients naïve or with one previous biologic treatment showed higher remission (p = 0.002) and clinical >response rates (p = 0.018) than patients previously treated with ≥ 2. Adverse events occurred in six patients (2.3%), whereas four patients (1.6%) underwent colectomy. CONCLUSION: This real-world study shows that UST effectively and safely treats patients with UC.

Pro-Inflammatory Cytokines Enhanced In Vitro Cytotoxic Activity of Clostridioides difficile Toxin B in Enteric Glial Cells: The Achilles Heel of Clostridioides difficile Infection?

Bacterial infections are characterized by an inflammatory response, which is essential for infection containment but is also responsible for negative effects on the host. The pathogen itself may have evolved molecular mechanisms to antagonize the antimicrobial effects of an inflammatory response and to enhance its pathogenicity using inflammatory response mediators, such as cytokines. Clostridioides difficile (C. difficile) infection (CDI) causes gastrointestinal diseases with markedly increasing global incidence and mortality rates. The main C. difficile virulence factors, toxin A and B (TcdA/TcdB), cause cytopathic/cytotoxic effects and inflammation. We previously demonstrated that TcdB induces enteric glial cell (EGC) apoptosis, which is enhanced by the pro-inflammatory cytokine tumor necrosis factor alpha plus interferon gamma (CKs). However, it is unknown whether CKs-enhanced TcdB cytotoxicity (apoptosis/necrosis) is affected by the timing of the appearance of the CKs. Thus, we simulated in vitro, in our experimental model with TcdB and EGCs, three main situations of possible interactions between TcdB and the timing of CK stimulation: before TcdB infection, concomitantly with infection, or at different times after infection and persisting over time. In these experimental conditions, which all represent situations of possible interactions between C. difficile and the timing of CK stimulation, we evaluated apoptosis, necrosis, and cell cycle phases. The CKs, in all of these conditions, enhanced TcdB cytotoxicity, which from apoptosis became necrosis when CK stimulation persisted over time, and was most relevant after 48 h of TcdB:EGCs interaction. Particularly, the enhancement of apoptosis by CKs was dependent on the TcdB dose and in a less relevant manner on the CK stimulation time, while the enhancement of necrosis occurred always independently of the TcdB dose and CK stimulation time. However, since in all conditions stimulation with CKs strongly enhanced the TcdB cytotoxicity, it always had a negative impact on C. difficile pathogenicity. This study might have important implications for the treatment of CDI.

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

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

Misinterpreting Diarrhea-Predominant Irritable Bowel Syndrome and Functional Diarrhea: Pathophysiological Highlights.

Irritable bowel syndrome with predominant diarrhea (IBS-D) and functional diarrhea (FD) are disorders of gut-brain interaction characterized by recurring symptoms which have a serious impact on the patient's quality of life. Their pathophysiology is far from being completely understood. In IBS-D growing evidence suggests that bile acid malabsorption (BAM) could be present in up to 30% of patients. Microscopic colitis (MC) is a well-known cause of watery diarrhea and some patients, at first, can be diagnosed as IBS-D or FD. Both BAM and MC are often responsible for the lack of response to conventional treatments in patients labelled as "refractory". Moreover, because BAM and MC are not mutually exclusive, and can be found in the same patient, they should always be considered in the diagnostic workout when a specific treatment for BAM or MC is unsatisfactory. In the present review the possible shared pathogenetic mechanisms between BAM and MC are discussed highlighting how MC can induce a secondary BAM. Moreover, a brief overview of the current literature regarding the prevalence of their association is provided.