Search

Objectives This study assesses the clinical relevance of dipeptidyl peptidase 4 (DPP4) membrane exopeptidase as a biomarker of inflammatory bowel disease (IBD). A spike-and-recovery approach of DPP4 in fecal samples was used to compare two different methods for protein extraction, followed by a stability assessment. Methods Fecal samples of healthy volunteers spiked with known concentrations of recombinant DPP4 were processed using a standard manual extraction protocol and the CALEX® protocol. The two methods were compared by quantification of fecal DPP4 by ELISA, followed by Bland-Altman analysis. For the stability assays DPP4 was extracted from fecal samples and stored under different conditions of temperature and time after collection. Results In general, the levels of spiked DPP4 in stool samples were lower with the manual protocol than in those obtained with the CALEX® method; this trend was corroborated by Bland-Altman analysis. Nonetheless, variability was within the acceptable limits for both protocols. In the stability assessment, no statistically significant differences were found between the results obtained under the different storage conditions. Conclusions Both manual and CALEX® protocols provided equal extraction ability of DPP4 from stool samples. In addition, DPP4 provided flexibility in terms of sample storage enabling the accurate assessment of samples delivered up to a week before analysis.

Background: Molecular therapy with sorafenib remains the mainstay for advancedstage hepatocellular carcinoma. Notwithstanding, treatment efficacy is low, with few patients obtaining long-lasting benefits due to the high chemoresistance rate. Objective: To perform, for the first time, an overview of the literature concerning the role of adenosine triphosphate-binding cassette (ABC) transporters in sorafenib therapy for hepatocellular carcinoma. Methods: Three online databases (PubMed, Web of Science, and Scopus) were searched, from inception to October 2020. Study selection, analysis, and data collection were independently performed by two authors. Results: The search yielded 224 results; 29 were selected for inclusion. Most studies were pre-clinical, using HCC cell lines; three used human samples. Studies highlight the effect of sorafenib in decreasing ABC transporters expression. Conversely, it is described the role of ABC transporters, particularly multidrug resistance protein 1 (MDR-1), multidrug resistance-associated proteins 1 and 2 (MRP-1 and MRP-2) and ABC subfamily G member 2 (ABCG2) in sorafenib pharmacokinetics and pharmacodynamics, being key resistance factors. Combination therapy with naturally available or synthetic compounds that modulate ABC transporters may revert sorafenib resistance by increasing absorption and intracellular concentration. Conclusion: A deeper understanding of ABC transporters’ mechanisms may provide guidance for developing innovative approaches for hepatocellular carcinoma. Further studies are warranted to translate the current knowledge into practice and paving the way to individualized therapy.

currently, most endoscopy software only provide limited statistics of past procedures, while none allows extrapolating patterns. To overcome this need, the authors applied business analytic models to predict future demand and need for endoscopists in a tertiary hospital endoscopy unit.a query to the endoscopy database was done to retrieve demand from 2015 to 2021. The graphical inspection allowed inferring trend and seasonality, perceiving the impact of the COVID-19 pandemics, and selecting the best forecasting models. Considering COVID-19's impact in 2020's second quarter, data for esophagogastroduodenoscopy (EGD) and colonoscopy was estimated using linear regression of historical data. The actual demand in the first 2 quarters of 2022 was used to validate the models.during the study period 53886 procedures were requested. The best forecasting models were: i) simple seasonal exponential smoothing for EGD, colonoscopy, and percutaneous endoscopic gastrostomy (PEG); ii) double exponential smoothing for capsule endoscopy and deep enteroscopy and iii) simple exponential smoothing for endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS). The mean average percentage error ranged from 6.1% (EGD) to 33.5% (deep enteroscopy). Overall, 8788 procedures were predicted for 2022. The actual demand in the first 2 quarters of 2022 was within the predicted range. Considering the usual time allocation for each technique, 3.2 full-time equivalent endoscopists (40 hours-dedication to endoscopy) will be required to perform all procedures in 2022.the incorporation of business analytics into the endoscopy software and clinical practice may enhance resource allocation, improving patient-focused decision-making and healthcare quality.

Background The effectiveness of Crohn’s disease treatments for inducing histological outcomes has not been addressed systematically. We performed a systematic review and meta-analysis of randomized controlled trials in Crohn’s disease to assess the impact of therapies on mucosal histopathology. Methods Databases (MEDLINE, CENTRAL, Web of Science, EMBASE) were searched for randomized controlled trials including adult patients and evaluating histological outcomes. Risk of bias was evaluated using the Critical Appraisal Skills Programme. Histological outcomes, pooled frequencies, pooled odds ratios, and standard mean differences of the histological scores were compared between the intervention and placebo groups using a random-effects model. Results Out of 2070 records, 10 studies were included. The quality of the studies ranged from moderate to high, but they were clinically and methodologically diverse. All interventions were superior to placebo. Histological response was achieved by 68% of patients, and 38% achieved remission. Pooled odds ratio for histological remission in patients receiving intervention vs placebo was 4.14 (95% CI, 2.28-7.50; I2 0%; P < .01). Heterogeneity in histological response estimates was significant, and subgroup analysis of the odds ratio results was limited by the low number of studies per group. The standard mean difference of histological scores was higher for patients receiving intervention in both induction and maintenance studies (−2.95; 95% CI, −4.17 to −1.74; I2 83% P < .00; and −2.58; 95% CI, −3.89 to −1.27; I2 56% P < .00). Conclusions Crohn’s disease therapies are effective for achieving histological outcomes. Adherence to recently published consensus on histopathology harmonization assessment in Crohn’s disease would facilitate adequate comparison between studies in the future.

Background The roles dipeptidyl peptidase 4 (DPP4), aminopeptidase N (APN), and their substrates in autoimmune diseases are being increasingly recognized. However, their significance in inflammatory bowel diseases (IBD) is not entirely understood. This systematic review aims to discuss the pathophysiological processes related to these ectopeptidases while comparing findings from preclinical and clinical settings. Methods This review was conducted according to the PRISMA guidelines. We performed a literature search in PubMed, SCOPUS, and Web of Science to identify all reports from inception until February 2020. The search included validated animal models of intestinal inflammation and studies in IBD patients. Quality assessment was performed using SYRCLE’s risk of bias tool and CASP qualitative and cohort checklists. Results From the 45 included studies, 36 were performed in animal models and 12 in humans (3 reports included both). Overall, the methodological quality of preclinical studies was acceptable. In animal models, DPP4 and APN inhibition significantly improved intestinal inflammation.Glucagon-like peptide (GLP)-1 and GLP-2 analogs and GLP-2-relase-inducing drugs also showed significant benefits in recovery from inflammatory damage. A nonsignificant trend toward disease remission with the GLP-2 analog teduglutide was observed in the sole interventional human study. All human studies reported an inverse correlation between soluble DPP4/CD26 levels and disease severity, in accordance with the proposal of DPP4 as a biomarker for IBD. Conclusions The use of DPP4 inhibitors and analogs of its substrates has clear benefits in the treatment of experimentally induced intestinal inflammation. Further research is warranted to validate their potential diagnostic and therapeutic applications in IBD patients.

This case demonstrates the utility of the "purse string" to close large defects and shows that optical diagnosis may have pitfalls in evaluating the invasion of neoplastic lesions, particularly large ones.

The authors report a case of a 62-year-old male presenting to the emergency department with hematochezia. Urgent colonoscopy revealed numerous diverticula in the sigmoid colon, two of them inverted. Oozing bleeding from a visible vessel was identified on the top of the most distal inverted diverticulum. An over-the-scope clip was released after suction into the transparent cap and successful hemostasis was achieved.

A 55-year-old woman with cirrhosis was admitted for acute decompensation caused by portal vein thrombosis. Ten days later, the patient presented melena. Esophagogastroscopy revealed two gastric polyps, both with bleeding stigmata. One of the polyps was removed with a diathermic loop, after adrenalin injection, while in the other the "ligate and let go" technique was applied, after biopsy. A "metallic tulip-bundle" technique, combining through the scope and over-the-scope clips, was applied for hemostasis. This case underlines how the combination of various endoscopic techniques may be useful to manage upper gastrointestinal bleeding, especially in patients with important comorbidities.

Ulcerative colitis (UC) has been the focus of numerous observational studies over the years and a common strategy employed in their design is the use of composite and aggregate outcomes.This systematic review and meta-analysis aims to identify composite and aggregate outcomes of observational studies in UC and to evaluate how the number and type of variables included and the length of follow-up affect the frequency of patients that achieve these outcomes.A systematic literature search was carried out using MEDLINE [via PubMed], Scopus, and Web of Science online databases. Observational studies that included UC patients and reported composite or aggregate outcomes were identified. A set of variables considered to be representative of progressive or disabling UC was defined, the proportion of patients attaining the outcomes was determined and a random-effects meta-analysis was performed by dividing the identified studies into subgroups according to different criteria of interest.A total of 10,264 records were identified in the systematic search, of which 33 were retained for qualitative analysis and 20 were included in the meta-analysis. The mean frequency for composite outcomes was 0.363 [95% confidence interval (CI) 0.323-0.403]. The frequency of composite outcome for the subgroup of studies that included the variable "Biologics" was significantly higher than for those in which this variable was not reported [0.410; 95% CI 0.364-0.457 versus 0.298; 95% CI 0.232-0.364; p = 0.006]. Composite outcomes were also more frequent as the follow-up duration increased.The frequency of composite outcomes in observational studies of UC is dependent on the specific identity of the variables being reported. Moreover, longer follow-up periods are associated with higher frequencies of composite outcomes. The evidence provided here is useful for the design of future observational studies of UC that aim to maximize the frequency of patients that achieve composite outcomes.

Small-bowel capsule endoscopy (SBCE) and device-assisted enteroscopy (DAE) are essential in obscure GI bleeding (OGIB) management. However, the best timing for such procedures remains unknown. This meta-analysis aimed to compare, for the first time, diagnostic and therapeutic yields, detection of active bleeding and vascular lesions, recurrent bleeding, and mortality of "early" versus "nonearly" SBCE and DAE.MEDLINE, ScienceDirect, and Cochrane Central Register of Controlled Trials were searched to identify studies comparing early versus nonearly SBCE and DAE. Random-effects meta-analysis was performed; reporting quality was assessed.From 1974 records, 39 were included (4825 patients). Time intervals for the early approach varied, within 14 days in SBCE and 72 hours in DAE. The pooled diagnostic and therapeutic yields of early DAE were superior to those of SBCE (7.97% and 20.89%, respectively; P .05). The odds for active bleeding (odds ratio [OR], 5.09; IThe role of small-bowel studies in the early evaluation of OGIB is unquestionable, impacting diagnosis, therapeutic intervention, and prognosis. Comparative studies are still needed to identify optimal timing.

Current analysis systematically reviews data available in the literature on the anti-bacterial activity of Annona muricata extracts (AME) against Staphylococcus aureus and Escherichia coli. Search was undertaken at four electronic databases and studies’ quality were assessed. Results were summarized and Minimum Inhibitory Concentration (MIC) of AME (versus antimicrobial control) against S. aureus and E. coli was the main datum analyzed. The initial database search yielded 2,433 results. We selected 14 studies and four were used for meta-analysis. The MIC ranged between 156 μg/mL and 1,024 μg/mL against S. aureus and between 256 μg/mL and 1,024 μg/mL against E. coli. The different strains of E. coli studied were more sensitive to AME than those of S. aureus. The differences mean concentrations and standard deviations between AME and antimicrobials were 101.91 and 946.05 for E. coli, and 388.90 and 970.61 for S. aureus respectively. The heterogeneity of data is highlighted. Different methodologies were used, several studies didn’t include antibiotics as control, antibiotics were different and various concentrations of extracts were tested. Studies showed possibilities of the plant under analysis as a source of new phytochemical compounds against microorganisms. info:eu-repo/semantics/publishedVersion

Background Previous studies have indicated that the appendix may be a priming site of ulcerative colitis (UC). Appendectomy is inversely associated with the development of UC, and is suggested to have a beneficial effect on the disease course in patients with refractory disease. Objective The aim of the current study was to assess histological features of appendices from patients with UC and their clinical relevance. Methods Patients with UC in remission and active UC (therapy refractory) that underwent appendectomy between 2012 and 2019 were included. Histological features of UC appendices were compared to those of patients with acute appendicitis and colon carcinoma. The Robarts Histopathology Index (RHI) was used to assess appendiceal inflammation. In patients with active UC, histological and clinical characteristics were compared between patients with and without endoscopic response following appendectomy. Results In total, 140 appendix specimens were assessed (n = 35 UC remission, n = 35 active UC, n = 35 acute appendicitis, n = 35 colon carcinoma). Histological features of appendices from UC patients looked like UC rather than acute appendicitis. The presence of active appendiceal inflammation was comparable between patients in remission versus active disease (53.7% vs. 46.3%, p = 0.45) and limited versus extensive disease (58.5% vs. 41.5%, p = 0.50). Endoscopic response (Mayo 0–1) following appendectomy, assessed in 28 therapy refractory patients, was more frequently seen in patients with higher RHI scores (RHI > 6: 81.8% vs. RHI ≤ 6: 9.1%, p = 0.03) and limited disease (proctitis/left sided 63.6% vs. pancolitis 36.4%, p = 0.02). Conclusion The presence of active appendiceal inflammation is common in UC and does not correlate with colonic disease activity. More than 50% of UC patients in remission showed active histological disease in the appendix. Favorable response to appendectomy for refractory UC was seen in cases with ulcerative appendicitis. These findings might support the role of the appendix as a pivotal organ in UC.

Several potassium channels (KCs) have been described throughout the gastrointestinal tract. Notwithstanding, their contribution to both physiologic and pathophysiologic conditions, as inflammatory bowel disease (IBD), remains underexplored. Therefore, we aim to systematically review, for the first time, the evidence on the characteristics and modulation of KCs in intestinal epithelial cells (IECs). PubMed, Scopus, and Web of Science were searched to identify studies focusing on KCs and their modulation in IECs. The included studies were assessed using a reporting inclusiveness checklist. From the 745 identified records, 73 met the inclusion criteria; their reporting inclusiveness was moderate-high. Some studies described the physiological role of KCs, while others explored their importance in pathological settings. Globally, in IBD animal models, apical KCa1.1 channels, responsible for luminal secretion, were upregulated. In human colonocytes, basolateral KCa3.1 channels were downregulated. The pharmacological inhibition of K2P and Kv influenced intestinal barrier function, promoting inflammation. Evidence suggests a strong association between KCs expression and secretory mechanisms in human and animal IECs. Further research is warranted to explore the usefulness of KC pharmacological modulation as a therapeutic target.

Background The incidence of inflammatory bowel disease (IBD) continues to rise worldwide and despite the advances on pharmacotherapy, the etiopathogenesis of Crohn's disease (CD) and ulcerative colitis (UC) remains underexplained. In this context, the migratory waves of the last decades created a challenging setting to analyze the evolution of IBD prevalence and to infer its triggering factors. Objective Our study aimed to overview the literature regarding IBD prevalence and phenotype in first- and secondgeneration migrants. Methods A non-systematic review was performed following electronic (PubMed and Web of Science) and manual searches on relevant topics. Results Overall, first-generation migrants tend to maintain the IBD risk of the native country. On the following generation, the risk tends to converge to that of the destination country. Earlier age at migration modulates IBD risk, suggesting that the degree of exposure to environmental and socio-economic factors can be decisive for disease progression. In general, CD needs more time to reach a disease burden similar to that of the host country, indicating that UC may be more affected by nongenetic factors and genetic-nongenetic interactions. Conclusion IBD phenotypes and natural history vary in migrants and according to ethnicity; however, the trends are not consensual among cohorts. Further studies are warranted to analyze the effect of environmental risk factors in different ethnic groups, providing background to move towards identification of at-risk individuals, prevention and earlier diagnosis of IBD.

Antibacterial resistance has become a challenging situation worldwide. The increasing emergence of multidrug-resistant pathogens stresses the need for developing alternative or complementary antimicrobial strategies, which has led the scientific community to study substances, formulas or active ingredients used before the antibiotic era. Honey has been traditionally used not only as a food, but also with therapeutic purposes, especially for the topical treatment of chronic-infected wounds. The intrinsic characteristics and the complex composition of honey, in which different substances with antimicrobial properties are included, make it an antimicrobial agent with multiple and different target sites in the fight against bacteria. This, together with the difficulty to develop honey-resistance, indicates that it could become an effective alternative in the treatment of antibiotic-resistant bacteria, against which honey has already shown to be effective. Despite all of these assets, honey possesses some limitations, and has to fulfill a number of requirements in order to be used for medical purposes.

Angiotensin-converting enzyme 2 (ACE2) has been highlighted for its role as a receptor for SARS-CoV-2, responsible for the current COVID-19 pandemic. This review summarizes current knowledge about ACE2 as a multifunctional protein, focusing on its relevance in inflammatory bowel disease (IBD). As an enzyme, ACE2 may be protective in IBD because it favors the counter-regulatory arm of the renin-angiotensin system or deleterious because it metabolizes other anti-inflammatory/repairing elements. Meanwhile, as a receptor for SARS-CoV-2, the impact of ACE2 expression/activity on infection is still under debate because no direct evidence has been reported and, again, both protective and deleterious pathways are possible. Research has shown that ACE2 regulates the expression of the neutral amino acid transporter B0AT1, controlling tryptophan-associated intestinal inflammation and nutritional status. Finally, intact membrane-bound or shed soluble ACE2 can also trigger integrin signaling, modulating the response to anti-integrin biologic drugs used to treat IBD (such as vedolizumab) and fibrosis, a long-term complication of IBD. As such, future studies on ACE2 expression/activity in IBD can improve monitoring of the disease and explore an alternative pharmacological target.

Background and Aims Interest in histology for ulcerative colitis [UC] has increased recently. This systematic review and meta-analysis aims to assess, for the first time, whether histological outcomes are more informative than endoscopic and clinical outcomes in distinguishing the impact of intervention over placebo in induction trials. Methods MEDLINE, ScienceDirect and Cochrane Central Register of Controlled Trials were searched to identify randomized placebo-controlled trials [RCTs] enrolling moderate-to-severe UC patients. Studies were assessed using the Quality Assessment Tool for Studies with Diverse Designs. We analysed the pooled proportion of patients achieving clinical, endoscopic and histological remission and response after a pharmacological intervention and compared the results with those of placebo-treated patients by using a random-effects model. Results From 889 identified records, 13 RCTs were included. The odds ratio [OR] for remission was higher in patients receiving intervention than in those under placebo for clinical (OR 2.13, 95% confidence interval [CI] 1.33–3.43), endoscopic [OR 1.46, 95% CI 0.19–11.18] and histological remission [OR 1.85, 95% CI 1.20–2.84]. Significant differences were observed for all response outcomes [clinical: OR 2.27, 95% CI 1.84–2.85; endoscopic: OR 2.16, 95% CI 1.51–3.10; histological: OR 3.63, 95% CI, 1.41–9.36]. No significant heterogeneity existed; no subgroup effects were found for duration of the induction or histological scale [p > 0.05]. Clinical and histological remission and endoscopic response were concordant in discriminating interventions from placebo. Conclusion Histological outcomes are informative in trials of moderate-to-severe UC. Further studies analysing histology at the end of induction are needed to confirm its relevance in distinguishing the efficacy of an intervention over placebo in comparison to clinical and endoscopic outcomes and to explore its prognostic value.

The increasing knowledge on ulcerative colitis' pathophysiology has contributed to the expansion of the therapeutic arsenal for this condition. However, to date, 25-40% of patients with ulcerative colitis remain primary or secondary non-responders to therapy, and up to 10% need to eventually undergo a colectomy. Janus kinase inhibitors block cytokine signalling involved in the pathogenesis of several inflammatory conditions. Tofacitinib is the first drug of this class approved for moderate-to-severely active ulcerative colitis in patients for whom disease worsened and those who did not improve with conventional therapy (aminosalicylates, corticosteroids and immunosuppressants) or monoclonal antibodies. We aimed to review the main aspects and concerns related to the current use of tofacitinib and to explore its future application.

Background The relative proportion of inflammation and fibrosis in a stricture is highly relevant in defining the clinical approach for Crohn’s disease [CD] patients. Whereas transmural inflammation in CD can be accurately estimated by cross-sectional imaging, evaluating the extent and severity of fibrosis still requires surgical pathology of intestinal resection specimens. This study systematically reviewed all existing transmural histopathological scoring systems developed for the assessment of inflammation and/or fibrosis in CD. Methods A systematic review of histopathological scoring systems for the assessment of transmural inflammation and/or fibrosis in CD, focusing on originally developed scoring systems. Risk of bias, methodological quality, and operating or psychometric properties [validity, reliability, responsiveness, and feasibility] of each histological scoring system were analysed. Results A total of 29 original scoring systems were included in this review. Three scoring systems were highlighted as the most widely reproduced, one aimed at assessing inflammation only and two aimed at assessing inflammation and fibrosis. These scores were more widely reproduced probably due to their ease of application in clinical studies. Two highly comprehensive scores were identified, showing good operating properties and high methodological quality, as well as the lowest risk of bias; these should, therefore, be further validated in clinical research studies. Conclusions This study reviewed all existing transmural histopathological scoring systems for the assessment of inflammation and/or fibrosis in CD and identified the most reliable and accurate scores for clinical research and clinical practice settings.

Background & Aims In addition to findings from endoscopy, histologic features of colon biopsies have been associated with outcomes of patients with ulcerative colitis (UC). We investigated associations between Geboes scores (a system to quantify structural changes and inflammatory activity in colon biopsies) and UC progression, and the time period over which this association is valid. Methods We analyzed data from 399 asymptomatic patients with UC enrolled in the ACERTIVE study, followed at 13 inflammatory bowel disease (IBD) centers in Portugal through 31 December 2019. Blood and stool samples were collected and analyzed, and all patients underwent sigmoidoscopy within 24 h of sample collection. We assessed baseline endoscopic status (Mayo endoscopic subscore), histologic features of 2 sigmoid and 2 rectal biopsies (Geboes score), and concentration of fecal calprotectin (FC). The primary outcome was UC progression (surgical, pharmacologic, and clinical events). We generated survival curves for 36 months or less and more than 36 months after biopsy according to Geboes score using the Kaplan-Meier method and compared findings with those from a log rank test. Cox regression was adjusted for Mayo endoscopic subscore, Geboes score, and level of FC; results were expressed as adjusted hazard ratios (HR) with 95% CIs. Results Patients with Geboes scores >2B.0, Geboes scores >3.0, or Geboes scores >4.0 had a higher frequency of, and a shorter time to UC progression, than patients with Geboes scores ≤2B.0, Geboes scores ≤3.0, or Geboes score ≤4.0 (P 2B.0, Geboes scores >3.0, or Geboes scores >4.0 compared with patients with Geboes scores ≤2B.0 (HR, 2.021; 95% CI, 1.158–3.526), Geboes scores ≤3.0 (HR, 2.007; 95% CI, 1.139–3.534), or Geboes scores ≤4.0 (HR, 2.349; 95% CI, 1.269–4.349), respectively, in the first 36 months after biopsy. Similar results were found for patients with concentrations of FC below 150 μg/g. Conclusions We found histologic features of colon biopsies (Geboes score) to be an independent risk factor for progression of UC in the first 36 months after biopsy.

Background and Aims Thiopurines are widely used in the management of inflammatory bowel diseases. However, their minimum effective dose and dose-response relationship remain undefined, and evidence about their use in clinical practice is mostly heterogeneous. This systematic review and meta-analysis aimed: i] to assess the clinical value of 6-thioguanine nucleotide thresholds; and ii] to compare mean 6-thioguanine nucleotide concentrations between patients in clinical remission vs. those with active disease. Methods A systematic literature search was carried out using four databases. Statistical heterogeneity was assessed with the I2 statistic followed by subgroup and sensitivity analyses. Odds ratios were computed using the random-effects model. Results A total of 1384 records were identified in the systematic search, of which 25 were retained for further analysis: 22 were used in the cut-off comparisons and 12 were used in the 6-thioguanine nucleotide mean differences analysis. The global odds ratio for remission in patients with 6-thioguanine nucleotide levels above the predefined thresholds was 3.95 (95% confidence interval [CI], 2.63-5.94; p < 0.001]. When considering the different thresholds individually, the odd ratios were significant for values above 235 pmol/8 × 108 and 250 pmol/8 × 108 red blood cells [2.25 and 4.71, respectively]. Mean 6-thioguanine nucleotide levels were higher among patients in clinical remission, with a pooled difference of 63.37 pmol/8 × 108 red blood cells [95% CI, 31.81-94.93; p < 0.001]. Conclusions This study reinforces the link between 6-thioguanine nucleotide levels and clinical remission in inflammatory bowel diseases, also exploring the validity of specific 6-thioguanine nucleotide thresholds to predict clinical outcomes.