Digestive Diseases and Sciences最新文献

Background: The disorders of gut-brain interaction (DGBI) form a heterogeneous group of gastrointestinal disorders that, to date, have no organic basis. The role of oral health in the development of these disorders has not been explored.

Objective: The objective of this study was to examine the relationship between oral health and the DGBI.

Methods: Data obtained from 166 women with (n = 113) and without fibromyalgia (n = 55) during a prospective observational study conducted in New Zealand during 2022 was evaluated for correlations between oral health measures (WHO oral health questionnaire), and the DGBI (Rome IV survey).

Results: Of the 166 women enrolled in the study, 122 (73.5%) met criteria for at least one DGBI. Women who met criteria for any of the esophageal, gastroduodenal, bowel, and anorectal disorders had significantly lower oral health scores (p < 0.001). For 12 specific DGBI, oral health scores were significantly lower (p < 0.05). Oral health scores were inversely associated with the number of DGBI detected in each participant (ρ = - 0.590, p < 0.001, 95% CI [- 0.69, - 0.48]).

Conclusion: The results of this study suggest there is an association between the oral health and the presence, type, and number of DGBIs in women. Further research to examine the nature of this relationship is required.

Background: The armamentarium of medical therapies to treat inflammatory bowel disease (IBD) continues to grow, which has expanded treatment options, particularly after first biologic failure. Currently, there are limited studies investigating the predictive value of first biologic primary non-response (PNR) on subsequent biologic success. Our objective was to determine if PNR to the first biologic for IBD is predictive of response to subsequent biologic therapy.

Methods: A multicenter retrospective chart review study was performed with patients with IBD that received two or more biologics. PNR was defined as no clinical or symptomatic improvement after at least six weeks of treatment leading to cessation of drug. Patients who stopped their first biologic due to adverse side effects were classified in the intolerance group. Patients with initial significant response to biologic followed by a loss of response were classified as secondary loss of response (SLOR). Data analysis was performed with Python and Excel.

Results: Of the 249 patients that met inclusion criteria, there were 87 patients with PNR, 96 patients with SLOR, and 66 patients with intolerance to their first biologic exposure. Patients with ulcerative colitis (UC: 41.3%, p = 0.0083) and IBD-unclassified (IC: 56.3%, p = 0.0099) were found to have a significantly higher rate of primary non-response compared to patients with Crohn's disease (CD: 25.0%). Patients on adalimumab for their first biologic had a significantly (p = 0.0014) higher rate of PNR (42.7%, UC: 50.0%, CD: 32.7%) compared to those on infliximab (23.0%, UC: 31.0%, CD: 12.1%). Patients with PNR did not have a higher rate of second biologic nonresponse when compared to patients who had SLOR or intolerance to their first biologic. Univariate analyses demonstrated no difference in rates of response to second biologic when switching intra-class or out-of-class.

Conclusion: Ulcerative colitis and IBDU have higher rates of PNR compared to Crohn's disease, but still have high response rates to second biologic agents. Adalimumab may be a suboptimal initial biologic given its higher PNR rate compared to infliximab. Our results support that there is an equally likely chance of response to second biologic after first biologic PNR. Subanalyses evaluating intraclass and out-of-class medication switching showed similar success.

Background: Acute severe ulcerative colitis (ASUC) affects up to 25% of patients with UC and is associated with an increased risk of colectomy. Despite improvements in medical management, individual patient prognostication and risk stratification in ASUC remains challenging. We explored clinical, biochemical, and endoscopic factors as potential predictors for colectomy in patients hospitalized with ASUC.

Methods: A retrospective analysis of patients with ASUC as defined by Truelove and Witts criteria admitted to the Mount Sinai Hospital between 2011 and 2020 was conducted. Data on disease history, medication use, clinical symptoms, and laboratory results during admission for ASUC were included. Colectomy risk during hospitalization and within one year was assessed.

Results: We included 158 patients; 34 (21.5%) underwent colectomy during hospital admission and 41 (25.9%) within a year. On multivariable analysis, prior anti-TNF exposure (odds ratio [OR] 4.59, 95% confidence interval [CI] 1.57-13.4, P = 0.005), and biologic use at admission (OR 3.31, 95%CI 1.14-9.63, P = 0.028) were associated with an increased risk of 1-year colectomy. Conversely, mesalamine use at admission decreased this risk (OR 0.31, 95%CI 0.13-0.72, P = 0.006). Other risk factors included recent UC-related hospitalization (< 1 year of admission), higher bowel movement frequency after 3 days of treatment, low hemoglobin and albumin levels, and elevated CRP. Infliximab treatment was associated with decreased risk of urgent (OR 0.30, 95%CI 0.13-0.73, P = 0.007) and 1-year colectomy (OR 0.31, 95%CI 0.14-0.73, P = 0.007).

Conclusion: In patients with ASUC, prior anti-TNF exposure is linked to a higher risk of both short- and long-term colectomy, while recycling infliximab may reduce colectomy risk.

Introduction: Inflammatory bowel disease (IBD) is a global health issue profoundly impacting quality of life. The United States accounts for nearly a quarter of the world's IBD patients, with the highest prevalence rates. This study aims to identify the demographic and regional trends of IBD-related mortality in the U.S. from 1999 to 2020.

Methodology: Our study utilized the CDC Wonder database to gather mortality data for IBD (Crohn's disease and ulcerative colitis) from 1999 to 2020. Results were presented as age-adjusted mortality rates (AAMR) per 100,000 population, with Joinpoint regression used to analyze trend changes and calculate annual percentage change (APC).

Results: A total of 62,310 IBD-related deaths were recorded. From 1999 to 2020, AAMR for Crohn's disease increased from 0.79 to 0.97, declining from 1999 to 2018 (APC: - 0.22) but surging from 2018 onwards (APC: 11.26). Women had a higher AAMR (0.81) compared to men (0.77). The highest rates were among non-Hispanic whites (0.86), followed by non-Hispanic blacks (0.48) and Hispanics (0.21). AAMR varied by state, ranging from 0.29 in Hawaii to 1.42 in Vermont. For ulcerative colitis, AAMR rose from 0.56 in 1999 to 0.63 in 2020, following a similar trend: a decline from 1999 to 2018 (APC: - 0.37) followed by an increase (APC: 12.21). State-specific AAMR ranged from 0.14 in Hawaii to 0.67 in Oregon.

Conclusion: This study highlights a decrease in AAMR for both diseases from 1999 to 2018, followed by significant increases from 2018 to 2020, indicating a need for targeted interventions.

Background: New diagnoses of inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), can highlight health system burden and potentially give clues to disease aetiology. This population-based study aimed to measure the annual incidence of IBD over six years (2018-2023) in the Canterbury region of New Zealand.

Methods: The medical records from public and private gastroenterology clinics were examined for new patients with a confirmed diagnosis of IBD from 1 January 2018 to 31 December 2023. Demographic and disease information (including the Montreal phenotype) was gathered in a secure database. Information was collected prospectively from 2021 to 2023 and retrospectively from 2018 to 2020.

Results: The incidence of IBD in 2023 was 30.1 per 100,000 person-years (95% CI 25.9-34.7), CD: 14.8 (95% CI 11.9-18.1), and UC: 14.5 (95% CI 11.7-17.7). The average age was 35.0 years (SD 17.2) and New Zealand European was the predominant ethnicity (83.4%), with smaller proportions of Māori (7.7%) and Pacific Islanders (1.7%). Between 2018 and 2023, the annual incidence of IBD was 32.4 per 100,000 person-years. The proportion of CD diagnosed each year decreased, and in 2023, the proportion of CD was equivalent (49%) to the proportion with UC.

Conclusions: The incidence of IBD in Canterbury remains high, and the rates appeared stable over the six years 2018-2023, consistent with the stabilizing incidence stage of the 4-stage epidemiological model of IBD. Māori and Pacific Island ethnicities contributed a small number of cases of IBD, but the rates of IBD in these groups were higher than in previous studies.

Background: The pathogenesis of hepatocellular carcinoma (HCC) emphasizes metabolic disorders. HCC patients showed abnormally low expression of Acyl-CoA dehydrogenase short chain (ACADS).

Objectives: This study aimed to elucidate the clinical significance and mechanistic role of ACADS in HCC.

Methods: We investigated the expression patterns and significance of ACADS in HCC by analyzing multiple public databases and clinical samples (Chip data). Immunohistochemistry was employed to observe the expression levels of ACADS in HCC tissues. In vitro experiments involved silencing or overexpressing ACADS in HCC cell lines, with protein expression levels determined by Western blotting. Functional validation included CCK-8, Transwell, and scratch wound healing assays. TOPFlash and FOPFlash reporter gene assays, co-immunoprecipitation, and immunofluorescence were used to explore the interaction between ACADS and β-catenin.

Results: ACADS was low expressed in HCC and was clinically associated with vascular invasion, TNM stage, and AFP levels. The low ACADS expression in HCC patients was negatively correlated with their survival. Overexpression of ACADS significantly suppressed the viability, migration, and invasive capacity of HCC cells, whereas silencing ACADS had the opposite effect. Mechanistically, co-immunoprecipitation experiments indicated that there was an interaction between ACADS and β-catenin. Overexpression of ACADS inhibited β-catenin activity and resulted in decreased nuclear β-catenin translocation and increased its cytoplasmic level. Immunofluorescence results also showed a decrease in β-catenin nuclear import following ACADS overexpression, whereas silencing ACADS led to an enhancement of its nuclear translocation.

Conclusion: ACADS emerges as a potentially valuable biomarker for HCC prognosis, exhibiting tumor-suppressive functions in HCC by participating in the regulation of β-catenin activity.

Background: Differentiating infections from sterile inflammation is crucial in early AP management.

Aim: This study aimed to assess the capability of Neutrophil-to-Lymphocyte Ratio (NLR) and procalcitonin to differentiate between sterile inflammation and infections in the first week of AP and to analyze the source, microbiological profile, and impact of infections in AP.

Methods: Consecutive patients presenting within 5 days of symptom onset were included. Microbiological profiles and serious adverse events (SAEs: in-hospital mortality or discharge in critical state) were analyzed. Blood count obtained at fever onset was used for calculating the NLR. The ability of NLR and procalcitonin to differentiate infections from sterile inflammation in the first week was assessed.

Results: Of 505 AP patients, 150 developed fevers. 48 (32%) had sterile inflammation, while 102 (68%) had infections. Most patients (n = 98, 65.3%) developed fever during the first week of illness (sterile inflammation (n = 43) and infections (n = 55)). NLR demonstrated good accuracy in differentiating infections from sterile inflammation in the first week (AUROC 0.70, p = 0.001), outperforming procalcitonin (AUROC 0.54, p = 0.58). Within infections (n = 102), 44 (43.1%) had infected pancreatic necrosis, 68 (66.7%) had extra-pancreatic infections, and 10 (9.8%) had both. Lower respiratory tract infection was the most common extra-pancreatic infection. Of 54 patients with culture-positive infections, 36 (66.7%) had grown multidrug-resistant (MDR) organisms. Fungal isolates were identified in 5 patients. Patients with infections had higher SAE incidence (21.6% vs. 4.2%, p = 0.007) than those with inflammation. The SAE incidence was higher with MDR infections than those without MDR (37.5% vs. 9.3%, p < 0.01).

Conclusions: Infections in AP occur early in the course of illness. NLR could serve as a reliable biomarker to distinguish infections from sterile inflammation in the early course of AP, aiding timely management. Patients with MDR infections have higher serious adverse outcomes.

Background: Treatment for primary biliary cholangitis (PBC) was defined by its singular relationship with ursodeoxycholic acid (UDCA) for decades. However, nearly 40% of patients fail to achieve adequate biochemical response with UDCA, necessitating second-line therapies.

Aims: The aim of our review was to assess the efficacy and safety of second-line therapies for PBC from phase three trials.

Methods: We conducted a systematic review of PubMed, Medline, and ClinicalTrials.gov for published phase three trial data of second-line PBC therapies.

Results: Four phase three clinical trial evaluating obeticholic acid, bezafibrate, seladelpar, and elafibranor, were identified. All trials but one defined the treatment endpoints of an alkaline phosphatase (ALP) less than 1.67 times the upper limit of normal (ULN), a 15% decrease of ALP from baseline, and normal total bilirubin (TB) after 12 months. All therapies demonstrated statistically significant achievement of primary endpoints relative to placebo. Reduction in ALP from baseline ranged from 113 to 133.9 U/L (- 34.6% to - 50%) across all trials. Primary endpoint treatment differences relative to placebo ranged between 31 and 47%. ALP normalization rates were described for three treatments and varied between 15 and 67% in treatment cohorts,compared to 0% to 2% of placebo cohorts. Only elafibranor and seladelpar demonstrated significant reduction in total 5D itch scale scores. Discontinuation rates across studies ranged from 1 to 14% due to adverse effects.

Conclusion: All reviewed therapies met their respective study endpoints. Effective second-line therapies area available and continue to receive long-term evaluation in patients with PBC.

Background: Although balloon enteroscopy-assisted ERCP and transgastric EUS-guided pancreatic duct drainage (EUS-PD) are treatment option for pancreaticojejunostomy anastomotic stricture (PJAS), they are often challenging with several limitations. This study aimed to examine the feasibility of transanastomotic forward-viewing EUS-PD (FVEUS-PD) via the afferent loop for PJAS after pancreaticoduodenectomy.

Methods: Ten consecutive patients with symptomatic PJAS who underwent FVEUS-PD between 2015 and 2021 were retrospectively evaluated. Study outcomes included technical and clinical success, adverse events, and recurrence rates associated with FVEUS-PD. A short dumbbell-shaped, fully covered metal stent was deployed in all cases, and the stent was removed 3 month after placement, after which it became stent-free.

Results: The technical success rate was 80% (8/10), and the scope could not reach the PJAS in two patients. Clinical success was achieved in all technically successful patients. No procedure-related adverse events observed. All patients were followed up for over three years after metal stent removal and becoming stent-free; the median follow-up period was 63 month. One patient developed symptomatic stricture recurrence 36 month after removal, with a stricture recurrence rate of 13% (1/8). The remaining patients did not experience any recurrence or late adverse events during the study period.

Conclusions: This study is the first to investigate FVEUS-PD, demonstrating promising technical feasibility with low adverse event and recurrence rates, potentially becoming a useful treatment option for PJAS.