Digestive Diseases最新文献

Introduction: Infliximab (IFX) is a standard, inpatient salvage therapy for the treatment of refractory acute severe ulcerative colitis (ASUC). Remicade™ is the originator IFX. Its biosimilar Renflexis™ offers a reduced cost structure. We performed a cost-minimization analysis to compare costs with Remicade™ and Renflexis™ for the inpatient treatment of ASUC.

Methods: Retrospective clinical and financial data were obtained from 34 inpatients with refractory ASUC who received Renflexis™ (n = 17) or Remicade™ (n = 17) between 2019 and 2021. Clinical data included admission and discharge laboratory values. Financial data included a decision support drug cost (DSDC), constituting the total cost associated with inpatient IFX administration, and total inpatient cost of care. The following equation generated a ratio (rDSDC) representing the percentage of drug cost (or DSDC) of the total inpatient cost of care, after controlling for IFX dose and length of stay: [DSDC of IFX/Number of Units of IFX] ÷ [Total Inpatient Cost of Care/Length of Stay in Days]. Median and non-parametric Wilcoxon ranked sum test were used for analyzing patient demographics, clinical, and financial data.

Results: No differences were found in baseline or discharge clinical parameters. The median unadjusted ratio of DSDC to total inpatient cost of care was 0.387 versus 0.241 in the Remicade™ versus Renflexis™ groups (p = 0.0025), respectively, representing an absolute difference of ∼14%. Median adjusted rDSDC were 0.04 versus 0.024 in the Remicade™ versus Renflexis™ groups, respectively, representing a relative cost reduction of ∼40% (p = 0.0001).

Discussion: The unadjusted absolute cost reduction and adjusted relative cost reduction were, respectively, 14% and 40% in the Renflexis™ group as compared to Remicade™, when treating inpatient ASUC. Our calculation included median DSDC as a percentage of the total inpatient cost of care, controlling for IFX dose and length of stay. This reduced cost structure promotes use of Renflexis™ for ASUC inpatients and may reduce costs systemically.

Background: Liver transplantation (LT) is the only effective therapy for end-stage liver diseases, but some patients usually present with serious infection and immune rejection. Those with immune rejection require long-term administration of immunosuppressants, leading to serious adverse effects. Mesenchymal stem cells (MSCs) have various advantages in immune regulation and are promising drugs most likely to replace immunosuppressants.

Summary: This study summarized the application of MSCs monotherapy, its combination with immunosuppressants, MSCs genetic modification, and MSCs derivative therapy (cell-free therapy) in LT. This may deepen the understanding of immunomodulatory role of MSCs and promote the application of MSCs in immune rejection treatment after LT.

Key messages: MSCs could attenuate ischemia-reperfusion injury and immune rejection. There is no consensus on the effects of types and concentrations of immunosuppressants on MSCs. Although genetically modified MSCs have contributed to better outcomes to some extent, the best modification is still unclear. Besides, multiple clinical complications developed frequently after LT. Unfortunately, there are still few studies on the polygenic modification of MSCs for the simultaneous treatment of these complications. Therefore, more studies should be performed to investigate the potency of multi-gene modified MSCs in treating complications after LT. Additionally, MSC derivatives mainly include exosomes, extracellular vesicles, and conditioned medium. Despite therapeutic effects, these three therapies still have some limitations such as heterogeneity between generations and that they cannot be quantified accurately.

Introduction: We investigated the hemostatic effect and safety of a hemostatic peptide solution for the treatment of gastrointestinal bleeding requiring emergency endoscopy.

Methods: We retrospectively examined the patient backgrounds, hemostatic results, and procedural safety in patients who were treated with a hemostatic peptide solution for hemostasis during emergency endoscopies for gastrointestinal bleeding. All hemostatic procedures were performed by nonexpert physicians with less than 10 years of endoscopic experience. All of the cases were treated at a single institution over the months from January 2022 to January 2023.

Results: Twenty-six consecutive patients (17 males and 9 females) with a median age of 74 (45-95) years were included. Their conditions requiring emergency endoscopy were melena in 8 patients, hematochezia in 2, hematemesis in 8, anemia in 6, and bleeding during esophagogastroduodenoscopy in 2. The sites of bleeding were the esophagus in 3 patients, the stomach in 17, the duodenum in 3, the small intestine in 2, and the colon in 1. Hemostasis was obtained with another hemostasis device used in conjunction with the hemostatic peptide solution in 13 cases and with the hemostatic peptide solution alone in 13 cases. The hemostasis success rate was 100%, with no complications. Rebleeding occurred within 1 week in 4 cases.

Conclusion: Hemostasis with the hemostatic peptide solution was safe and provided a temporary high hemostatic effect in emergency gastrointestinal endoscopy.

Introduction: The objective of this study was to evaluate esophageal varices (EVs) as predictors of poor prognosis with low tolerability after balloon-occluded retrograde transvenous obliteration (BRTO) in patients with overt hepatic encephalopathy (HE).

Methods: This study retrospectively enrolled 107 patients who underwent BRTO for uncontrollable overt HE. The enrolled patients were divided into two groups based on the presence of EVs using propensity matching. The present study assessed the technical success rate and safety of BRTO in both the groups. Further, the event-free survival, HE-free survival, and the overall survival (OS) were compared between the two groups. Event-free survival was defined as the time period during which the patients did not developed complications related to portal hypertension, including EVs, hepatic ascites, and portal vein thrombosis.

Results: After propensity matching, the EV and non-EV groups had 37 and 36 patients, respectively. Only 1 patient experienced an unsuccessful procedure in the EV group. Procedure-related adverse events in the EV group and non-EV group occurred in 11 and 7 patients, respectively (p = 0.417). The event-free survival after BRTO in the EV and non-EV group were 1,283 (95% CI: 798-1,767) days and 2,257 (1,722-2,792) days, respectively. Event-free survival was significantly worse in the EV group than in the non-EV group (p = 0.014). Furthermore, the EV group experienced worse OS than the non-EV group (p = 0.001 and p < 0.001, respectively).

Conclusions: The presence of EVs could potentially be associated with a higher risk of adverse outcomes or mortality after BRTO treatment in individuals with HE.

Introduction: There is no evidence that a positive breath test is a good predictor of the success of a carbohydrate-restricted diet. Our objective was to investigate whether patients in whom lactose intolerance (LIT) or fructose intolerance (FIT) is diagnosed by validated symptom measurement respond to diet.

Methods: Patients referred for evaluation of LIT or FIT underwent hydrogen/methane breath testing (malabsorption test) and symptom measurement with the adult Carbohydrate Perception Questionnaire (aCPQ, intolerance test) before and after 50 g lactose or 25 g fructose. Patients with a positive aCPQ received instructions on specific diets and supplements. Severity of abdominal pain, bloating, diarrhoea, flatulence, and nausea were measured using a visual analogue scale (VAS) before (VAS1, mm) and after (VAS2, mm) diet. The change in VAS for individual symptoms and overall symptoms after diet is expressed as deltaVAS (mm) and as change relative to VAS1 (%).

Results: Forty-one patients were included (23 LIT, 8 FIT, 10 LIT+FIT). Eight patients had negative breath tests (no malabsorption). After 2 months of diet, the overall VAS and the individual symptoms decreased (p < 0.001). Overall VAS1 and the VAS1 for individual symptoms correlated significantly with the decrease in deltaVAS (mm) after diet. Nineteen patients (46%) had total recovery, and additional 13 patients (32%) had improvement of >50%. Response to diet was independent of breath test results.

Conclusion: This uncontrolled and unblinded study suggests that patients with carbohydrate intolerance diagnosed by aCPQ benefit significantly from diet, independent of the presence of malabsorption. Controlled studies are required to confirm these results in larger patient groups.

Background: Primary sclerosing cholangitis (PSC) is a chronic cholestatic disease of unknown etiology characterized by biliary inflammation and periductal fibrosis. The gut microbiota plays a crucial role in the pathogenesis of PSC by regulating bile acid metabolism, inflammation, and immune response. On the other hand, liver disease progression affects the composition of the gut microbiota, fostering these mechanisms in a mutual detrimental way.

Summary: Recent evidences described a specific pro-inflammatory microbial signature in PSC patients, with an overall reduced bacterial diversity and the loss of beneficial metabolites such as short-chain fatty acids. As effective therapies for PSC are still lacking, targeting the gut microbiota offers a new perspective in the management of this disease. To date, antibiotics, fecal microbiota transplantation, and probiotics are the most studied gut microbiota-targeted intervention in PSC, but new potential strategies such as vaccines and bacteriophages represent possible future therapeutic horizons.

Key messages: In this review, we focus on the role of the gut microbiota in PSC, considering its pathogenetic and prognostic role and the therapeutic implications.

Introduction: Superficial non-ampullary duodenal epithelial tumors (SNADETs) include low-grade adenoma (LGA) and high-grade adenoma or carcinoma (HGA/Ca) and are classified into two different epithelial subtypes, gastric-type (G-type) and intestinal-type (I-type). We attempted to distinguish them by endoscopic characteristics including magnifying endoscopy with narrow-band imaging (M-NBI).

Methods: Various endoscopic and M-NBI findings of 286 SNADETs were retrospectively reviewed and compared between G- and I-types and histological grades. M-NBI findings were divided into four patterns based on the following vascular patterns; absent, network, intrastructural vascular (ISV), and unclassified. Lesions displaying a single pattern were classified as mono-pattern and those displaying multiple patterns as mixed-pattern. Lesions showing CDX2 positivity were categorized as I-types and those showing MUC5AC or MUC6 positivity were categorized as G-types based on immunohistochemistry.

Results: Among 286 lesions, 23 (8%) were G-type and 243 (85%) were I-type. More G-type lesions were located oral to papilla (91.3 vs. 45.6%, p < 0.001), and had protruding morphology compared to those of I-types (65.2 vs. 14.4%, p < 0.001). The major M-NBI pattern was ISV in G-type (78.2 vs. 26.3%, p < 0.001), and absent for I-type (0 vs. 34.5%, p = 0.003). Three endoscopic characteristics; location oral to papilla, protruding morphology, and major M-NBI pattern (ISV) were independent predictors for G-type. Mixed-pattern was more common in HGA/Ca than LGA for I-type (77.0 vs. 58.8%, p = 0.01); however, there was no difference for those in G-type.

Conclusion: Endoscopic findings including M-NBI are useful to differentiate epithelial subtypes.

Introduction: Identifying novel treatment strategies for patients with ulcerative colitis (UC) and at risk of relapse is critical. The objective of this study was to assess the efficacy of beclomethasone dipropionate (BDP) in lowering fecal calprotectin (FC) levels in UC patients in clinical remission and at risk of relapse.

Methods: This multicenter study comprised a double-blind, randomized, placebo-controlled phase (part I) and an open-label, non-randomized phase (part II). Eligible participants with UC in clinical remission treated with 5-aminosalicylic acid and with FC levels ≥250 μg/g were randomized to receive 5 mg/day of BDP or placebo for 4 weeks (part I). At week 5, patients with FC ≥100 μg/g were treated with 5 mg/day of BDP for 4 weeks (part II), and FC levels were tested at week 9.

Results: Forty-three patients were randomized: 22 received BDP (group A) and 21 placebo (group B). At week 4, 13 patients (59.1%) in group A and 3 (17.6%) in group B had FC levels <100 μg/g (p value = 0.010). In the double-blind phase of the study, no patient relapsed in group A and 4 in group B (p value = 0.049). Both treatment groups showed a favorable safety profile, with the most common adverse events being gastrointestinal disorders.

Conclusion: In this multicenter, randomized clinical trial including patients with UC in clinical remission but with elevated FC, BDP was efficacious in reducing FC and well-tolerated.

Introduction: Gastric cancer (GC) remains a global health challenge, and H. pylori infection is a main risk factor for noncardia GC. The present study aimed to investigate the association between single nucleotide polymorphisms (SNPs) in mammalian sterile 20-like kinase 1 (MST1) and MST2, H. pylori (H. pylori) infection, and the risk of noncardia gastric cancer (GC).

Methods: A case-control study was conducted using enzyme-linked immunosorbent assay (ELISA) and TaqMan method to detect the titer of anti-H. pylori antibody in normal human serum and genotype 9 SNPs of MST1 and MST2 genes among 808 samples. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between SNPs and H. pylori infection, as well as the risk of noncardia gastric cancer in codominant, dominant, overdominant, recessive, and log-additive genetic models. Haplotypes were constructed using the Haploview 4.2 software.

Results: The CC genotype of MST2 SNP rs10955176 was associated with a reduced risk of H. pylori infection compared to the TT + CT genotype. None of other SNPs were associated with H. pylori infection. The TT genotype of MST2 SNP rs7827435 was associated with a reduced risk of noncardia gastric cancer compared to the AA + AT genotype. None of the SNPs were associated with noncardia gastric cancer. There were no associations between haplotypes and H. pylori infection or the risk of noncardia gastric cancer.

Conclusions: The CC genotype of rs10955176 and the TT genotype of rs7827435 may serve as protective factors against H. pylori infection and noncardia gastric cancer risk, respectively.

Background: Chronic hepatitis B (CHB) infection is still a major global public health problem, with nearly two billion patients. Although current antiviral drugs can inhibit viral replication and reduce hepatitis B virus (HBV) related complications, it is difficult to achieve clinical endpoints due to drug resistance.

Summary: Immune checkpoint inhibitors (ICIs) are an important strategy to reverse T-cell exhaustion, and rebuilding an effective functional T-cell response is a promising immunomodulatory approach for CHB patients. However, ICIs may lead to viral reactivation or immune-related adverse effects. There are still many controversies in the application of ICIs in treating patients with CHB.

Key messages: This article reviews the research progress of ICIs in CHB infection and related issues. The goal of this paper was to summarize the possible impact of new therapies for CHB with the aim of reducing potential clinical risks.