Search

Gabrio Bassotti,1,2 Alessandro Fruganti,3 Giovanni Maconi,4 Pierfrancesco Marconi,5 Katia Fettucciari5 1Department of Medicine and Surgery, Gastroenterology, Hepatology & Digestive Endoscopy Section, University of Perugia, Perugia, Italy; 2Gastroenterology & Hepatology Unit, Santa Maria della Misericordia Hospital, Perugia, Italy; 3School of Biosciences and Veterinary Medicine, University of Camerino, Macerata, Italy; 4Department of Biomedical and Clinical Sciences, Gastroenterology Unit, “L. Sacco” Hospital, University of Milano, Milano, Italy; 5Department of Medicine and Surgery, Biosciences & Medical Embryology Section, University of Perugia, Perugia, ItalyCorrespondence: Gabrio BassottiDepartment of Medicine and Surgery, Gastroenterology, Hepatology & Digestive Endoscopy Section, University of Perugia, Perugia, ItalyEmail gabassot@tin.itAbstract: Clostridioides difficile infection is widespread throughout countries and represents an important cause of nosocomial diarrhoea, with relatively high morbidity. This infection often occurs in patients with inflammatory bowel diseases and may complicate their clinical picture. Here, we propose, on the basis of evidence from basic science studies, that in patients affected by inflammatory bowel diseases, this infection might be facilitated by a derangement of the enteric glial cell (EGC) network caused by the effects of proinflammatory cytokines, such as tumour necrosis factor alpha and interferon gamma, which enhance the cytotoxic effects of C. difficile toxin B on EGCs. This hypothesis, if confirmed, could open the door to alternative treatment approaches to fight C. difficile infection.Keywords: Clostridioides difficile infection, cytokines, inflammatory bowel diseases, interferon gamma, tumour necrosis factor alpha

Purpose: Alimentary tract duplications (ATDs) are rare congenital lesions often associated with anomalies such as spinal, urinary and GI tract malformations. The purpose of this study was to report the experience of a single center with ATDs in children, focusing on the natural history, associated malformations, and their impact on patient management., Methods: We performed a retrospective analysis over 14 years, collecting prenatal, clinical, surgical, and follow-up data. We focus on associated anomalies prenatal and postnatal management, and outcomes., Results: Sixty-three patients with ATD (thirty-six females, twenty-seven males, aged 1 day to 14 years) were enrolled in this study. Prenatal diagnosis was made in 22 patients (35%), of whom 8 showed compression signs. Elective surgery was performed at a mean age of 1.5 years in prenatally diagnosed cases. The others presented symptoms at a mean age of 5.2 years (55.5%) or were detected incidentally (9.5%) at a mean age of 10.7 years. In four patients (6.3%), we identified multiple duplications, and ten cases (15.8%) were found with associated anomalies., Conclusion: The wide spectrum of clinical appearance of ATDs and a comprehensive knowledge of human embryology might define surgical management, which should always be patient-tailored and respectful of the child's development., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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.

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., Competing Interests: Conflict of interest The Authors have no conflict of interest to declare. No specific funding. This work was supported by the Italian Group for Inflammatory Bowel Diseases (IG-IBD); the Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia; and the University of Pavia, Pavia, Italy. No specific funding was obtained., (Copyright © 2024. Published by Elsevier Ltd.)

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., Competing Interests: Conflict of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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.

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.

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.

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.

Introduction: In the treatment of upper GI endoscopy-negative patients with heartburn and epigastric pain or burning, antacids, antireflux agents, and mucosal protective agents are widely used, alone or as add-on treatment, to increase response to proton-pump inhibitors, which are not indicated in infancy and pregnancy and account for significant cost expenditure., Methods: In this randomized, controlled, double-blind, double-dummy, multicenter trial assessing the efficacy and safety of mucosal protective agent Poliprotect (neoBianacid, Sansepolcro, Italy) vs omeprazole in the relief of heartburn and epigastric pain/burning, 275 endoscopy-negative outpatients were given a 4-week treatment with omeprazole (20 mg q.d.) or Poliprotect (5 times a day for the initial 2 weeks and on demand thereafter), followed by an open-label 4-week treatment period with Poliprotect on-demand. Gut microbiota change was assessed., Results: A 2-week treatment with Poliprotect proved noninferior to omeprazole for symptom relief (between-group difference in the change in visual analog scale symptom score: [mean, 95% confidence interval] -5.4, -9.9 to -0.1; -6.2, -10.8 to -1.6; intention-to-treat and per-protocol populations, respectively). Poliprotect's benefit remained unaltered after shifting to on-demand intake, with no gut microbiota variation. The initial benefit of omeprazole was maintained against significantly higher use of rescue medicine sachets (mean, 95% confidence interval: Poliprotect 3.9, 2.8-5.0; omeprazole 8.2, 4.8-11.6) and associated with an increased abundance of oral cavity genera in the intestinal microbiota. No relevant adverse events were reported in either treatment arm., Discussion: Poliprotect proved noninferior to standard-dose omeprazole in symptomatic patients with heartburn/epigastric burning without erosive esophagitis and gastroduodenal lesions. Gut microbiota was not affected by Poliprotect treatment. The study is registered in Clinicaltrial.gov (NCT03238534) and the EudraCT database (2015-005216-15)., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Introduction: We assessed the prevalence and clinical outcomes of segmental colitis associated with diverticulosis (SCAD) in patients with newly diagnosed diverticulosis., Methods: A 3-year international, multicenter, prospective cohort study was conducted involving 2,215 patients., Results: SCAD diagnosis was posed in 44 patients (30 male patients; median age: 64.5 years; prevalence of 1.99%, 95% confidence interval, 1.45%-2.66%). Patients with SCAD types D and B showed worse symptoms, higher fecal calprotectin values, needed more steroids, and reached less likely complete remission., Discussion: Although SCAD generally had a benign outcome, types B and D were associated with more severe symptoms and worse clinical course., (Copyright © 2023 by The American College of Gastroenterology.)

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.

Maintenance of plasma glucose (PG) homeostasis is due to a complex network system. Even a minor fall in PG activates multiple neuroendocrine actions promoting hormonal, metabolic and behavioral responses, which prevent and ultimately recover hypoglycemia, primarily neuroglycopenia. Among these responses, gastric emptying (GE) plays an important role by coordinated mechanisms which regulate transit and absorption of nutrients through the small intestine. A bidirectional relationship between GE and glycemia has been established: GE may explain the up to 30-40 % variance in glycemic response following a carbohydrate-rich meal. In addition, acute and chronic hyperglycemia induce deceleration of GE after meals. Hypoglycemia accelerates GE, but its role in counterregulation has been poorly investigated. The role of GE as a counterregulatory mechanism has been confirmed in pathophysiological conditions, such as gastroparesis or following recurrent hypoglycemia. Therefore, it could represent an "ancestral" mechanism, highly conservative and effective in all individuals, conditions and clinical contexts. Recent guidelines recommend GLP-1 receptor agonists (GLP-1RAs) either as the first injectable therapy for type 2 diabetes mellitus or in combination with insulin. Considering the potential impact on GE, it would be important to study subjects on GLP-1 RAs during hypoglycemia, to establish whether a possible deceleration of GE impairs glucose counterregulation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background and Aims: The Diverticular Inflammation and Complication Assessment (DICA) classification and the Combined Overview on Diverticular Assessment (CODA) were found to be effective in predicting the outcomes of Diverticular Disease (DD). We ascertain whether fecal calprotectin (FC) can further aid in improving risk stratification., Methods: A three-year international, multicentre, prospective cohort study was conducted involving 43 Gastroenterology and Endoscopy centres. Survival methods for censored observations were used to estimate the risk of acute diverticulitis (AD) in newly diagnosed DD patients according to basal FC, DICA, and CODA. The net benefit of management strategies based on DICA, CODA and FC in addition to CODA was assessed with decision curve analysis, which incorporates the harms and benefits of using a prognostic model for clinical decisions., Results: At the first diagnosis of diverticulosis/DD, 871 participants underwent FC measurement. FC was associated with the risk of AD at 3 years (HR per each base 10 logarithm increase: 3.29; 95% confidence interval, 2.13-5.10) and showed moderate discrimination (c-statistic: 0.685; 0.614-0.756). DICA and CODA were more accurate predictors of AD than FC. However, FC showed high discrimination capacity to predict AD at 3 months, which was not maintained at longer follow-up times. The decision curve analysis comparing the combination of FC and CODA with CODA alone did not clearly indicate a larger net benefit of one strategy over the other., Conclusions: FC measurement could be used as a complementary tool to assess the immediate risk of AD. In all other cases, treatment strategies based on the CODA score alone should be recommended., (© 2023 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Many colorectal diseases depend on complex interactions between several pathophysiological factors, including the intestinal microbiota. In recent years, the widespread use of antibiotics has been recognized as a main cause of intestinal dysbiosis and a favouring factor for Clostridioides difficile infection. The latter, in addition, causes infectious diarrhoea, pseudomembranous colitis, and toxic megacolon by means of its toxins (A and, especially, B), is characterized by frequent relapses; thus, its persistence in a host may be long-lasting. Based on recent experimental evidence, here we analyse the possibility that, similarly to other bacteria, Clostridioides difficile may be considered a potential carcinogen for colorectal cancer., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Clostridioides difficile ( C. difficile ), responsible for 15-25% of gastrointestinal infections, causes health problems mainly due to the toxic activity of toxins A and B (Tcds). These are responsible for its clinical manifestations, including diarrhea, pseudomembranous colitis, toxic megacolon and death, with a mortality of 5-30% in primary infection, that increase following relapses. Studies on Tcd-induced cell death have highlighted a key role of caspases, calpains, and cathepsins, with involvement of mitochondria and reactive oxygen species (ROS) in a complex signaling pathway network. The complex response in the execution of various types of cell death (apoptosis, necrosis, pyroptosis and pyknosis) depends on the amount of Tcd, cell types, and Tcd receptors involved, and could have as initial/precocious event the alterations in calcium homeostasis. The entities, peculiarities and cell types involved in these alterations will decide the signaling pathways activated and cell death type. Calcium homeostasis alterations can be caused by calcium influx through calcium channel activation, transient intracellular calcium oscillations, and leakage of calcium from intracellular stores. These increases in cytoplasmic calcium have important effects on all calcium-regulated molecules, which may play a direct role in several cell death types and/or activate other cell death effectors, such as caspases, calpains, ROS and proapoptotic Bcl-2 family members. Furthermore, some support for the possible role of the calcium homeostasis alteration in Tcd-induced cell death originates from the similarity with cytotoxic effects that cause pore-forming toxins, based mainly on calcium influx through plasma membrane pores.

Purpose: The 2010 Lung Allocation Score (LAS) version considers the estimated survival benefit offered by lung transplantation (LTx) and uses 6-minute Walk Test (6MWT) distance as a dichotomous covariate of whether an individual can walk more than 150 ft or 45.7 m in 6 min. This study aimed to provide evidence that 6MWT gives no clinically meaningful information to be used in the current LAS for candidates to LTx with cystic fibrosis (CF)., Materials and Methods: We collected data from 6MWTs performed since 2003 at our CF centre. A joint model was fitted to describe the effect of changes in walked distance on the hazard of LTx or death., Results: Up to 2019, 552 6MWTs were performed on 163 individuals with CF. None of the individuals included walked for less than 45.7 m during the 6MWT. Based on the joint modelling, the association of walked distance with the hazard ratio (HR) of LTx or death was significant (HR 0.99, 95% Credible Interval [CI]: 0.99 to 1.00)., Conclusions: When adopted dichotomously for LAS calculation, walked distance does not add any useful information about exercise capacity. Longitudinal trajectories of walked distance may provide complementary information about prognosis in individuals with CF.Implications for rehabilitationDichotomized walked distance does not contribute to lung allocation score in candidates to lung transplantation with cystic fibrosisChanges in the longitudinal trajectory of walked distance can be clinically meaningful for prognostication.Sensitive outcomes to be incorporated in the lung allocation scoring system for individuals with CF are yet needed to catch rapid falls in functional capacity.

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.

Mucosal healing (MH) is the main treatment target in ulcerative colitis (UC) and Crohn's disease, and it is defined by the combination of complete endoscopic and histologic remission. The complete resolution of mucosal inflammation should be confirmed by histology but its assessment is not always univocal. Neutrophil infiltration represents the unique histological marker in discriminating the active vs. quiescent phases of the disease, together with crypt injuries (cryptitis and crypt abscesses), erosions, and ulcerations. On the contrary, basal plasmacytosis is not indicative of activity or the remission of inflammatory bowel diseases (IBDs) but instead represents a diagnostic clue, mostly at the onset. Several histological scoring systems have been developed to assess grade severity, particularly for UC. However, most are complex and/or subjective. The aim of this review was to summarize available scores, their characteristics and limitations, and to present the advantages of a simplified mucosa healing scheme (SHMHS) based on neutrophils and their distribution in the gut mucosa. Finally, we overview future developments including artificial intelligence models for standardization of disease assessments and novel molecular markers of inflammation with potential application in diagnostic practice.

Introduction: To evaluate the ability of intestinal ultrasound (IUS) in discriminating symptomatic uncomplicated diverticular disease (SUDD) among patients with abdominal symptoms including irritable bowel syndrome (IBS)., Methods: This observational, prospective study included consecutive patients classified into the following categories: (i) SUDD; (ii) IBS; (iii) unclassifiable abdominal symptoms; and (iv) controls, including asymptomatic healthy subjects and diverticulosis. The IUS evaluation of the sigmoid: assessed the presence of diverticula, thickness of the muscularis propria, and IUS-evoked pain, namely the intensity of pain evoked by compression with the ultrasound probe on sigmoid colon compared with an area of the left lower abdominal quadrant without underlying sigmoid colon., Results: We enrolled 40 patients with SUDD, 20 patients with IBS, 28 patients with unclassifiable abdominal symptoms, 10 healthy controls, and 20 patients with diverticulosis. Patients with SUDD displayed significantly ( P < 0.001) greater muscle thickness (2.25 ± 0.73 mm) compared with patients with IBS (1.66 ± 0.32 mm), patients with unclassifiable abdominal pain, and healthy subjects, but comparable with that of patients with diverticulosis (2.35 ± 0.71 mm). Patients with SUDD showed a greater (not significant) differential pain score than other patients. There was a significant correlation between the thickness of the muscularis propria and the differential pain score only for patients with SUDD ( r = 0.460; P : 0.01). Sigmoid diverticula were detected by colonoscopy in 40 patients (42.4%) and by IUS with a sensitivity of 96.0% and a specificity of 98.5%., Discussion: IUS could represent a useful diagnostic tool for SUDD, potentially useful in characterizing the disease and appropriately address the therapeutic approach., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Clostridioides difficile ( C. difficile ) is responsible for a high percentage of gastrointestinal infections and its pathological activity is due to toxins A and B. C. difficile infection (CDI) is increasing worldwide due to the unstoppable spread of C. difficile in the anthropized environment and the progressive human colonization. The ability of C. difficile toxin B to induce senescent cells and the direct correlation between CDI, irritable bowel syndrome (IBS), and inflammatory bowel diseases (IBD) could cause an accumulation of senescent cells with important functional consequences. Furthermore, these senescent cells characterized by long survival could push pre-neoplastic cells originating in the colon towards the complete neoplastic transformation in colorectal cancer (CRC) by the senescence-associated secretory phenotype (SASP). Pre-neoplastic cells could appear as a result of various pro-carcinogenic events, among which, are infections with bacteria that produce genotoxins that generate cells with high genetic instability. Therefore, subjects who develop IBS and/or IBD after CDI should be monitored, especially if they then have further CDI relapses, waiting for the availability of senolytic and anti-SASP therapies to resolve the pro-carcinogenic risk due to accumulation of senescent cells after CDI followed by IBS and/or IBD.

Percutaneous endoscopic gastrostomy is the method of choice to allow enteral access in patients requiring long-term enteral nutrition. However, although generally safe, percutaneous tube positioning may be plagued by several complications. Among these, the deterioration and/or deflation of balloons serving as internal bolster is particularly worrisome in that it may lead to gastrostomy cannulas dislocation. Of interest, such balloon deflation may occur in up to 30% of cases for apparently unexplained causes. Here, we provide a hypothesis that could explain some of these causes.

Background: Vedolizumab (VDZ) can be used to treat refractory ulcerative colitis (UC) and Crohn's disease (CD). We assessed whether there are differences in treating UC vs CD with VDZ., Research Design and Methods: Mayo score in UC and the Harvey-Bradshaw Index (HBI) in CD scored the clinical activity. Achievement and maintenance of clinical remission during the follow-up, and safety were the primary endpoints., Results: 729 patients (475 with UC and 254 with CD), median follow-up of 18 (IQR 6-36) months, were enrolled. Clinical remission at the 6 th month of treatment was achieved in 488 (66.9%) patients (74.4% in CD vs 62.9% in UC, p<0.002) while, during the follow-up, no difference was found (81.5% in the UC group and 81.5% pts in the CD group; p=0.537). The clinical remission at the 6 th month of treatment (p=0.001) and being naïve to biologics (p<0.0001) were significantly associated with prolonged clinical remission. The clinical response was significantly higher in UC (90.1%) vs CD (84.3%) (p=0.023), and surgery occurred more frequently in CD (1.9% in UC vs 5.1% in CD, p=0.016)., Conclusion: We found differences when using VDZ in UC vs CD in real life. These parameters can help the physician predict this drug's longterm efficacy.