A 1-year follow-up study on checkpoint inhibitor-induced colitis: results from a European consortium.

BACKGROUND: Data regarding the clinical outcome of patients with immune checkpoint inhibitor (ICI)-induced colitis are scant. We aimed to describe the 12-month clinical outcome of patients with ICI-induced colitis. MATERIALS AND METHODS: This was a retrospective, European, multicentre study. Endoscopy/histology-proven ICI-induced colitis patients were enrolled. The 12-month clinical remission rate, defined as a Common Terminology Criteria for Adverse Events diarrhoea grade of 0-1, and the correlates of 12-month remission were assessed. RESULTS: Ninety-six patients [male:female ratio 1.5:1; median age 65 years, interquartile range (IQR) 55.5-71.5 years] were included. Lung cancer (41, 42.7%) and melanoma (30, 31.2%) were the most common cancers. ICI-related gastrointestinal symptoms occurred at a median time of 4 months (IQR 2-7 months). An inflammatory bowel disease (IBD)-like pattern was present in 74 patients (77.1%) [35 (47.3%) ulcerative colitis (UC)-like, 11 (14.9%) Crohn's disease (CD)-like, 28 (37.8%) IBD-like unclassified], while microscopic colitis was present in 19 patients (19.8%). As a first line, systemic steroids were the most prescribed drugs (65, 67.7%). The 12-month clinical remission rate was 47.7 per 100 person-years [95% confidence interval (CI) 33.5-67.8). ICI was discontinued due to colitis in 66 patients (79.5%). A CD-like pattern was associated with remission failure (hazard ratio 3.84, 95% CI 1.16-12.69). Having histopathological signs of microscopic colitis (P = 0.049) and microscopic versus UC-/CD-like colitis (P = 0.014) were associated with a better outcome. Discontinuing the ICI was not related to the 12-month remission (P = 0.483). Four patients (3.1%) died from ICI-induced colitis. CONCLUSIONS: Patients with IBD-like colitis may need an early and more aggressive treatment. Future studies should focus on how to improve long-term clinical outcomes.

Effect of Periodontitis and Periodontal Therapy on Oral and Gut Microbiota.

Mounting evidence indicates that periodontitis-related oral bacteria may contribute to gut microbial dysbiosis. This clinical study aimed to explore the oral-gut microbial signatures associated with periodontitis and to longitudinally evaluate the effect of periodontal treatment on the oral and gut microbial composition. Stool and saliva samples from generalized stage III/IV periodontitis patients (n = 47) were collected and analyzed by 16S ribosomal RNA gene amplicon sequencing, before and 3 mo after steps I to II of periodontal therapy. Periodontally healthy matched subjects (n = 47) were used as controls. Principal component analysis was carried out to identify oral-gut microbial profiles between periodontitis patients at baseline and healthy subjects; periodontitis samples were longitudinally compared before and after treatment. ß-Diversity of gut microbial profiles of periodontitis patients before treatment significantly differed from healthy controls (P < 0.001). Periodontal therapy was associated with a significant change in gut microbiota (P < 0.001), with post-treatment microbial profiles similar to healthy volunteers. A higher abundance of Bacteroides, Faecalibacterium, Fusobacterium, and Lachnospiraceae was noted in fecal samples of periodontitis patients at baseline compared to healthy controls. In contrast, Lactobacillus was the only genus more abundant in the latter. Additionally, periodontal therapy led to a parallel reduction in the salivary carriage of periodontal pathobionts, as well as gut Bacteroides, Lachnoclostridium, Lachnospiraceae, Oscillospiraceae, and Ruminococcaceae, to levels similar to healthy controls. Collectively, discriminating oral-gut microbial signatures of periodontitis were found. Periodontal treatment both mitigated oral dysbiosis and altered gut microbial composition, signifying potential broader implications for gastrointestinal health and disease.

Severe ulcerative colitis: predictors of response and algorithm proposal for rescue therapy.

BACKGROUND: There is no agreeing if rescue therapy can avoid short-term colectomy in patients treated for severe steroid-refractory ulcerative colitis. AIMS: The aim of our study was to identify predictors of response to infliximab and cyclosporine A. METHODS: In this cross-sectional study, 49 patients with severe ulcerative colitis were included. Response to therapy was defined as three or more point reductions in Mayo score after 6 months of treatment and avoidance of colectomy after 1 year. The predictors analysed were gender, age, time from ulcerative colitis diagnosis, months of steroid or/and azathioprine therapy before onset of the severe phase, smoking habits, extension of the disease, laboratory analyses and Mayo score. RESULTS: Patients treated with infliximab showed a statistically significant higher response rate in case of moderate Mayo score (P = 0.04). Ex-smokers had very low chance of response to infliximab (P = 0.03). In the group treated with cyclosporine A, patients with C-reactive protein >3 mg/L had a response rate significantly higher than those with C-reactive protein <3 mg/L (P = 0.03); those with negative C-reactive protein and moderate Mayo score did not responded to therapy, while in the ones with elevated C-reactive protein and/or severe Mayo score, 15 versus 4 responded (P = 0.008). CONCLUSIONS: Our data suggest that cyclosporine A is advisable in ex-smokers. In never smokers or active smokers, infliximab can be prescribed in case of Mayo score ≤10 and/or negative CRP, while cyclosporine A is indicated in case of Mayo score >10 and positive CRP.

Endoscopic ultrasound in the preoperative staging of gastric cancer: key messages for surgeons.

Gastric cancer (GC) remains a frequent and important cause of cancer mortality worldwide. Many factors affect the prognosis of GC, but invasion and metastasis are the leading causes of death. Due to the various stage-oriented therapies available, after the diagnosis of GC it is important to determine the staging preoperatively in order to choose the appropriate management. GC staging is the workhorse of endoscopic ultrasound (EUS). EUS can distinguish the different wall layers of the gastrointestinal tract as well as assess regional lymph nodes. Furthermore, samples of suspicious lesions or lymph nodes can be obtained by means of EUS-guided fine-needle aspiration (EUS-FNA). In this narrative review, we highlight the current status of the usefulness of EUS for GC staging, with focus on early GC that still remains a diagnostic and therapeutic challenge. In particular, the possibility to ameliorate the accuracy of EUS, in this context, by using instruments with increased ultrasound frequency is emphasized.

Benefit of supplements in functional dyspepsia after treatment of Helicobacter pylori.

AIM: Functional dyspepsia, though benign, leads to deterioration of the quality of life and high costs for healthcare systems. The optimal therapy for functional dyspepsia is still to be defined because of its multifactorial pathogenesis. In an open multicentric study of patients with functional dyspepsia, we prospectively evaluated the benefit of treatment with a food supplement composed of sodium alginate, carbonate calcium, pineapple, papaya, ginger, α-galactosidase and fennel (Perdiges, Bioten Snc, Turin, Italy). METHODS: Ninety-one consecutive patients were included, suffering from functional dyspepsia, who had been previously submitted to therapy to eradicate the infection from Helicobacter pylori (H. pylori) and were waiting to perform the Urea Breath Test (UBT). The primary goal was to establish the percentage of patients who continued to abstain from proton pump inhibitors (PPI) as they waited to carry out the UBT, differentiating between patients who were treated (N.=55) with Perdiges and those who were not (N.=36). Our secondary goal was to document the differences within the 2 groups in terms of symptoms perceived between the start and end of the observation period. The wellness reported, during or in absence of treatment with Perdiges, was evaluated by the use of the VAS scale (Visual Analogical Scale) completed before the start of the treatment and after 30 days. RESULTS: All the patients treated with Perdiges (55/55, 100%) and 31/36 (86.1%) patients who were not (P=0.008) continued to abstain from PPI in the period awaiting the UBT. The VAS scale of those who took Perdiges improved on average by 1.78 points versus a worsening of 0.08 points of those who did not take it (P<0.0001). Furthermore, while among those who took Perdiges there was a statistically significant improvement (P<0.0001) in the VAS scale, between the baseline and the end of treatment, a worsening of 0.08 points (P=0.78) was noticed among the patients who did not take it. CONCLUSION: Perdiges is significantly effective in the period following treatment to eradicate the infection from H. pylori in patients with functional dyspepsia. This allows to reduce the need to use antisecretive drugs. Further randomised studies, with wide ranging case histories, must assess its long-term efficacy.

Osteopenia and osteoporosis in patients with new diagnosis of inflammatory bowel disease.

AIM: The decrease in bone density may occur as a result of inflammatory bowel disease (IBD). Studies conducted on this issue generally focused on treated IBD patients. It is thus difficult to discriminate the role of disease from the effect of therapy on bone density reduction. We evaluated the prevalence of osteopenia/osteoporosis and abnormalities in indices of bone metabolism in patients with newly diagnosed IBD. METHODS: Evaluation of dual-energy X-ray absorptiometry (DXA) at the lumbar spine and intact parathormone (PTH), 25-hydroxy vitamin D and urinary cross-links, on 37 (26 females, median age 35.6±14.5 years) consecutive patients. RESULTS: Sixteen of 37 patients (43%) had normal DXA, 17 (46%) were osteopenic and 4 (11%) osteoporotics. Most male patients >30 years (63%) old as well as young women (62%) had osteopenia/osteoporosis. Mean value of intact-PTH was significantly higher in women >50 years (55.0±18.1 pg/mL) compared with those aged 16-20 years (30.0±14.6 pg/mL) (P=0.042). Furthermore, there was a significant difference between mean value of 25-hydroxy vitamin D in women >50 years old (16.2±4.7 ng/mL) compared to those aged 21-30 years (26.6±7.9 ng/mL) (P=0.041). Intact-PTH was significantly higher in osteoporotic patients (55.7±12.7 pg/mL) compared to normal subjects (28.3±13.0 pg/mL) (P=0.0014). CONCLUSION: High prevalence of osteopenia/osteoporosis was observed in this population. On the basis of these data, we propose to perform DXA in male patients aged >30 years and in all women with new diagnosis of IBD.

Epilepsy and celiac disease: review of literature.

Celiac disease (CD) is a chronic, immune-mediated disorder, characterized by small intestinal malabsorption of nutrients after the ingestion of gluten by genetically susceptible individuals. The discovery of the wide variations in the nature and intensity of clinical presentation of CD has transformed its status, long considered a rare disease, to that of a common health problem. As patients with CD get older, they tend to present with complaints not directly referable to the gastrointestinal tract. Neurologic symptoms, caused by lesions of the central or peripheral nervous system occasionally occur in patients with CD and are poorly understood. This review focalizes on the present knowledge of the potential relationship between CD and epilepsy. The prevalence of CD among patients with epilepsy is not homogeneously distributed, probably because epilepsy encompasses a heterogeneous group of disorders. In fact, the clinical spectrum of epilepsy related to CD ranges from benign syndromes to intractable epilepsy. The precise mechanism of the potential association between CD and epilepsy is also still under discussion.