Therapeutic Advances in Gastroenterology最新文献

Background: It remains unclear whether visceral adipose tissue (VAT) can predict the response of patients with Crohn's disease (CD) to anti-tumour necrosis factor-α (anti-TNF-α) therapy.

Objectives: This study aimed to investigate whether VAT predicts the efficacy of infliximab (IFX) for different sites of CD and its relationship with serum TNF-α levels and IFX serum trough concentration.

Design: This is a multicentre retrospective study.

Methods: Patients with CD treated with IFX from January 2014 to January 2021 were included. The perimeter of the visceral adipose area was obtained by a Computed Tomography (CT) scan. Participants were classified according to the lesion site (L₁, L₂, and L₃) and visceral fat area. The participants were divided into colon-uninvolved non-visceral obesity (L₁-VAT_L), colon-uninvolved visceral obesity (L₁-VAT_H), colon-involved non-visceral obesity (L₂ + L₃-VAT_L), and colon involved visceral obesity (L₂ + L₃-VAT_H) groups. The end points of this study were set as disease remission status at 6 and 12 months.

Results: The final cohort included 140 patients. Regarding efficacy at 6 and 12 months, there was a significant difference between L₁-VAT_L (73.8% versus 36.8%, p = 0.006) and L₁-VAT_H (81.0% versus 47.4%, p = 0.008) groups. In the analysis of serum TNF-α levels and IFX serum trough concentrations, there was a significant difference between L₁-VAT_L and L₁-VAT_H (59.5 pg/mL versus 236.0 pg/mL, p_TNF-α = 0.006), (10.0 μg/mL versus 0.4 μg/mL, p_IFX = 0.000), and L₁-VAT_H and L₂ + L₃-VAT_H (78.7 pg/mL versus 118.6 pg/mL, p_TNF-α = 0.031), (0.4 μg/mL versus 6.40 μg/mL, p_IFX = 0.017).

Conclusion: In L₁ patients, the VAT level predicted the efficacy of IFX, with high VAT values indicating poor efficacy. The VAT level may be a useful radiological marker to predict the efficacy of IFX in patients with various types of CD.

During the past 3 years, the coronavirus disease 2019 (COVID-19) pandemic has had a great impact on people all over the world. However, it has become evident that disease manifestations and severity differ across age groups. Most children have a milder disease course than adults but possibly more pronounced gastrointestinal (GI) symptoms. Given the child's developing immune system, the impact of COVID-19 on disease development may differ compared to adults. This study reviews the potential bi-directional relationship between COVID-19 and GI diseases in children, focusing on common pediatric conditions such as functional GI disorders (FGID), celiac disease (CeD), and inflammatory bowel disease (IBD). Children with GI diseases, in general, and CeD and IBD, in particular, do not seem to have an increased risk of severe COVID-19, including risks of hospitalization, critical care need, and death. While infections are considered candidate environmental factors in both CeD and IBD pathogenesis, and specific infectious agents are known triggers for FGID, there is still not sufficient evidence to implicate COVID-19 in the development of either of these diseases. However, given the scarcity of data and the possible latency period between environmental triggers and disease development, future investigations in this field are warranted.

Background: Videocapsule endoscopy (VCE) and double-balloon enteroscopy (DBE) are part of the diagnostic and therapeutic work-up of indications other than suspected small bowel bleeding (OSBB). The literature is currently lacking studies describing these procedures in this particular setting.

Objectives: We assessed the clinical impact of VCE and DBE in a large monocentric cohort of OSBB patients, as compared to a control group of suspected small bowel bleeding (SSBB) patients who underwent enteroscopy over the same period.

Design: Monocentric, retrospective, cohort study.

Methods: We collected the data of consecutive patients with OSBB undergoing VCE and/or DBE from March 2001 to July 2020. The demographic and clinical parameters of the patients, technical characteristics, and adverse events for each procedure were collected. The impact of VCE and DBE was defined in terms of diagnostic yield (DY). The patients were subdivided according to the main indication into four groups: celiac disease, Crohn's disease (CD), neoplasia, and persistent gastrointestinal symptoms.

Results: A total of 611 VCEs and 387 DBEs were performed for OSBB. The main indications were complicated celiac disease and CD. The DYs of VCE and DBE overall were 53 and 61.7%, respectively, with some variance among the four groups. We report no statistical differences in the DY of VCE and DBE in SSBB vs OSBB (57.7% vs 53%, p = 0.0859 and 68.8% vs 61.7%, p = 0.0582, respectively). OSBB patients were significantly younger than those with SSBB. However, similarly to SSBB (k = 0.059), poor agreement between the enteroscopic techniques was found in the OSBB population (k = 0.109). The safety of both procedures in OSBB was comparable to that in SSBB patients.

Conclusion: VCE and DBE are effective and safe in suspected OSBB, where their role is similar to that in SSBB, their main indication.

Background: The endoscopic submucosal dissection (ESD) is a technically demanding and time-consuming procedure, with an increased risk of adverse events compared to standard endoscopic resection techniques. The main difficulties are related to the instability of the operating field and to the loss of traction. We aimed to evaluate in a pilot trial a new endoscopic platform [tissue retractor system (TRS); ORISE, Boston scientific Co., Marlborough, MA, USA], designed to stabilize the intraluminal space, and to provide tissue retraction and counter traction.

Method: We prospectively enrolled all consecutive patients who underwent an ESD for sigmoid/rectal lesions. The primary outcome was the rate of technical feasibility. Further technical aspects such as en-bloc and R0 resection rate, number of graspers used, circumferential incision time, TRS assemblage time, submucosal dissection time, and submucosal dissection speed were provided. Clinical outcomes (recurrence rate and adverse events) were recorded as well.

Results: In all, 10 patients (M/F 4/6, age: 70.4 ± 11.0 years old) were enrolled. Eight out of 10 lesions were located in the rectum. Average lesion size was 31.2 ± 2.7 mm, and mean lesion area was 1628.88 ± 205.3 mm². The two sigmoid lesions were removed through standard ESD, because the platform assemblage failed after several attempts. All rectal lesions were removed in an en-bloc fashion. R0 resection was achieved in 7/8 (87.5%) patients in an average procedure time of 60.5 ± 23.3 min. None of the patients developed neither intraprocedural nor postprocedural adverse events.

Conclusion: TRS-assisted ESD is a feasible option when used in the rectum, with promising result in terms of efficacy and safety outcomes. Nevertheless, our pilot study underlines few technical limitations of the present platform that need to be overcome before the system could be widely and routinely used.

Background: Acid sensitivity can be altered in patients with gastroesophageal reflux disease (GERD). Secondary peristalsis helps clear gastro-esophageal refluxate and residual ingested food bolus.

Objectives: The aim of this study was to investigate the associations among acid sensitivity, esophageal mucosal integrity, chemical clearance, and secondary peristalsis before and after esophageal acid infusion.

Design: This was an investigator-initiated, prospective, cross-sectional study.

Methods: Adult reflux patients underwent high resolution manometry and 24 h impedance-pH monitoring off acid suppression to identify GERD phenotypes, including non-erosive reflux disease (NERD), reflux hypersensitivity (RH), and functional heartburn (FH). Secondary peristalsis was assessed using five rapid 20 mL air injections into the esophagus before and after infusion of hydrochloric acid (0.1 N) into the mid-esophagus. Conventional acid infusion parameters recorded included lag time, intensity rating, and sensitivity score. Chemical clearance was evaluated using the post-reflux swallow-induced peristaltic wave (PSPW), and mucosal integrity was assessed by the mean nocturnal baseline impedance (MNBI) derived from impedance-pH monitoring.

Results: A total of 88 patients (age 21-64 years, 62.5% women) completed the study including 12 patients with NERD, 45 with RH, and 31 with FH. There was no significant difference in acid infusion parameters between patients with NERD, RH, and FH. Upon acid infusion, patients who exhibited successful secondary peristalsis had longer lag time, higher MNBI, and shorter bolus contact time than those without secondary peristalsis. Meanwhile, patients with intact PSPW demonstrated significantly higher intensity ratings in response to acid perfusion and higher MNBI than those with impaired PSPW. The lag time correlated positively with MNBI (r = 0.285; p = 0.007).

Conclusion: In conclusion, the protective effect of esophageal secondary peristalsis and chemical clearance on esophageal mucosal integrity was demonstrated. Concerning acid sensitivity, longer lag time in patients with intact secondary peristalsis may be attributed to better esophageal mucosal integrity, while stronger intensity ratings may have a greater tendency to induce PSPW and protect esophageal mucosal integrity.

Background: Helicobacter pylori (H. pylori) is a group 1 carcinogen and the etiological agent of gastric diseases such as gastritis, ulcers, and gastric cancer. It infects approximately half of the world's population. Risk factors associated with H. pylori infection include socioeconomic status, lifestyle, and diet.

Objectives: This study aimed to evaluate the association between eating habits and H. pylori infection in patients from a reference hospital in Central Brazil.

Design: This cross-sectional study included 156 patients from 2019 to 2022.

Methods: Data were collected using a structured questionnaire on sociodemographic and lifestyle characteristics and a validated food frequency questionnaire. The H. pylori infection status (positive versus negative) was determined using the histopathological method. After grams/day, foods were stratified into tertiles of consumption (low, medium, and high). Simple and multiple binary logistic regression models were used in the analysis of odds ratios (ORs) and their respective 95% confidence intervals (CIs), with a 5% significance level.

Results: The prevalence of H. pylori infection was 44.2% (69/156 patients). Infected individuals had a mean age of 49.6 ± 14.6 years; 40.6% were men, 34.8% were aged 60 years or older, 42.0% were unmarried, 7.2% had higher education, 72.5% were non-white, and 30.4% were obese. In the H. pylori-positive group, 55.1% were alcohol drinkers and 42.0% were smokers. The results of multiple analyses showed that the chance of H. pylori infection was higher among male participants (OR = 2.25; CI = 1.09-4.68) and individuals with obesity (OR = 2.68; CI = 1.10-6.51). Participants with moderate consumption of refined grains (bread, cookies, cakes, breakfast cereal) (OR = 2.41; CI = 1.04-5.62) and fruits (OR = 2.53; CI = 1.08-5.94) were more likely to be infected.

Conclusion: In this study, male sex, obesity, and the consumption of refined grains and fruits were positively associated with H. pylori infection. Further research is needed to investigate this association and elucidate the underlying mechanisms.

Since the discovery of Helicobacter pylori (H. pylori) as the causative organism for gastric and duodenal ulcers four decades ago and subsequent recognition as class 1 gastric carcinogen, countless numbers of studies have been conducted and papers published, on the efficacy of various management strategies to eradicate the infection. In adults, a global consensus by the experts in the field concluded that H. pylori gastritis is an infectious disease and requires treatment irrespective of the presence or absence of symptoms due to the potential for serious complication like peptic ulcer disease and gastric neoplasia. However, although more than half the world's population harbors H. pylori, these serious complications occur only in a small minority of the infected population, even less so in childhood. More importantly, there is accumulating evidence for beneficial role of H. pylori against many chronic health conditions, from several epidemiological and laboratory studies. No doubt, eradication therapy is indicated in children with H. pylori-related peptic ulcer disease. Even though the pediatric guidelines from various learned societies recommend against a "test and treat" strategy, this is not always adhered to. With the accumulating evidence of the possible beneficial role of H. pylori, it is time to pause and think, are we causing more harm than good by eradicating H. pylori in every child who has this bug?

Background: Ustekinumab (UST) is indicated for the treatment of Crohn's disease (CD) and Ulcerative Colitis (UC). Despite having shown clinical effectiveness in the real world, some patients may lose response over time or need a higher dose to achieve it. In this context, UST intravenous (IV) maintenance has been proposed.

Objectives: The primary endpoint of our study was to evaluate the efficacy and safety of maintenance IV UST treatment in Inflammatory Bowel Disease (IBD) patients who present with partial response or loss of response to subcutaneous (SC) UST.

Design: We performed a monocentric observational retrospective study including patients with active IBD on maintenance treatment with IV UST.

Methods: The clinical response and remission was analyzed at week 12, defined as either Harvey-Bradshaw Index ⩽ 4 for CD or partial Mayo Score ⩽ 2 for UC. The reduction of objective markers of disease activity, fecal calprotectin, and C-reactive protein was evaluated. Moreover, UST trough levels were measured pre- and post-UST IV maintenance and any adverse events were assessed.

Results: We included 23 patients. Clinical remission at week 12 was achieved by 43.5% of the patients. The proportion of patients in clinical response after 12 weeks on UST IV maintenance was 82.6%. After a median follow-up of 9.3 months all patients remained on IV UST maintenance. No adverse events were recorded in any patient for the duration of the study.

Conclusions: IV UST maintenance treatment was able to recapture response in most of the patients who had lost response to SC maintenance.

Background: Therapeutic targets for ulcerative colitis (UC) and prediction models of antitumor necrosis factor (TNF) therapy outcomes have not been fully reported.

Objective: Investigate the characteristic metabolite and lipid profiles of fecal samples of UC patients before and after adalimumab treatment and develop a prediction model of clinical remission following adalimumab treatment.

Design: Prospective, observational, multicenter study was conducted on moderate-to-severe UC patients (n = 116).

Methods: Fecal samples were collected from UC patients at 8 and 56 weeks of adalimumab treatment and from healthy controls (HC, n = 37). Clinical remission was assessed using the Mayo score. Metabolomic and lipidomic analyses were performed using gas chromatography mass spectrometry and nano electrospray ionization mass spectrometry, respectively. Orthogonal partial least squares discriminant analysis was performed to establish a remission prediction model.

Results: Fecal metabolites in UC patients markedly differed from those in HC at baseline and were changed similarly to those in HC during treatment; however, lipid profiles did not show these patterns. After treatment, the fecal characteristics of remitters (RM) were closer to those of HC than to those of non-remitters (NRM). At 8 and 56 weeks, amino acid levels in RM were lower than those in NRM and similar to those in HC. After 56 weeks, levels of 3-hydroxybutyrate, lysine, and phenethylamine decreased, and dodecanoate level increased in RM similarly to those in HC. The prediction model of long-term remission in male patients based on lipid biomarkers showed a higher performance than clinical markers.

Conclusion: Fecal metabolites in UC patients markedly differ from those in HC, and the levels in RM are changed similarly to those in HC after anti-TNF therapy. Moreover, 3-hydroxybutyrate, lysine, phenethylamine, and dodecanoate are suggested as potential therapeutic targets for UC. A prediction model of long-term remission based on lipid biomarkers may help implement personalized treatment.

Background: Iron deficiency anemia (IDA) is a common extraintestinal manifestation of inflammatory bowel disease (IBD), affecting around one-third of patients.

Objective: To compare IBD progression and healthcare resource utilization in patients with and without a co-diagnosis of IDA in a real-world setting.

Design: A retrospective comparative study was conducted using Italian entities' administrative databases, covering 9.3 million health-assisted individuals.

Methods: Adult IBD patients diagnosed with ulcerative colitis and/or Crohn's disease were enrolled between January 2010 and September 2017. Within 12 months from IBD diagnosis, IDA was identified by at least one prescription for iron and/or IDA hospitalization and/or blood transfusion (proxy of diagnosis). IBD population was divided according to the presence/absence of IDA. Given the nonrandom patients' allocation, propensity score matching (PSM) was applied to abate potential unbalances between the groups. Before and after PSM, IBD progression (in terms of IBD-related hospitalizations and surgeries), and healthcare resource costs were assessed.

Results: Overall, 13,475 IBD patients were included, with an average age at diagnosis of 49.9 years, and a 53.9% percentage of male gender. Before PSM, 1753 (13%) patients were IBD-IDA, and 11,722 (87%) were IBD-non-IDA. Post-PSM, 1753 IBD-IDA patients were matched with 3506 IBD-non-IDA. Before PSM, IBD progression was significantly higher in IBD-IDA (12.8%) than in IBD-non-IDA (6.5%) (p < 0.001). After PSM, IBD progression and IBD-related hospitalizations were significantly (p < 0.001) more frequent in IBD-IDA patients (12.8% and 12.0%, respectively) compared to IBD-non-IDA (8.7% and 7.7%). Consistently, healthcare expenditures resulted significantly higher among IDA patients (p < 0.001), with an overall mean annual cost of €5317 compared to €2798 for patients without IDA. These results were confirmed after PSM matching, as the mean annual total cost/patient in IBD-IDA versus IBD-non-IDA were €3693 and €3046, respectively (p < 0.001).

Conclusion: In a real-life setting, IDA co-diagnosis in IBD patients was associated with disease progression and higher related economic burden.