Clinical utility of a novel anchor pronged clip for mucosal defect closure after colorectal endoscopic submucosal dissection (with video).

Background and study aims The MANTIS Clip (Boston Scientific) is a novel anchor pronged clip designed to enhance tissue grasping and facilitate the closure of defects in the gastrointestinal tract. This study evaluates the feasibility and effectiveness of the MANTIS Clip for closing mucosal defects following colorectal endoscopic submucosal dissection (C-ESD). Patients and methods A retrospective single-center study was conducted on patients who underwent C-ESD with MANTIS Clip closure from May 2023 to April 2024. The primary outcome measured was the complete closure success rate. Secondary outcomes included defect size, sustained closure rate, closure time, number of clips used, adverse events (AEs), and hospital stay duration. Results The MANTIS Clip was used in 52 cases. The complete closure rate was 98.1% (51/52), with a sustained closure rate of 96.1% (49/51). The median closed defect size was 32 mm, with the largest being 62 mm. The median closure time was 8 minutes. Typically, one MANTIS Clip per defect was used, with only one lesion requiring two clips. The median number of additional clips used was seven. AEs included one case of bleeding (1.9%) and one case of post-ESD coagulation syndrome (1.9%), both managed without extending hospital stays. The median C-reactive protein level on the first day post-ESD was 0.35 mg/dL and the median hospital stay was 5 days. Conclusions The MANTIS Clip is effective and practical for mucosal defect closure post-C-ESD, demonstrating high success and sustained closure rates with minimal complications. Future multicenter randomized trials are needed to further assess its efficacy and safety.

Proportion of Successful Lumbar Punctures in Infants Younger Than Three Months.

It is important to perform lumbar punctures (LPs) without a single traumatic tap in infants younger than three months owing to the risk of serious complications. The proportion of LPs in which clear cerebrospinal fluid (CSF) was obtained has been previously reported, but some of the procedures involved a traumatic tap. The present study aimed to identify the proportion of LPs in which clear CSF was obtained without a single traumatic tap and the factors associated with successful LPs in infants younger than three months. This retrospective, observational study included children younger than three months who underwent an LP in the pediatric emergency department between April 2018 and March 2021. The primary outcome was the proportion of successful LPs, defined as LPs obtaining clear CSF without a single traumatic tap. Multiple logistic regression analysis was used to identify factors related to successful LPs. Of 126 eligible patients, 121 were included. Among these, 83 (69%) were in the successful group. No factors significantly associated with successful LPs were found. Larger studies based on an accurate definition of successful LPs, such as that provided by this study, are needed to investigate related factors to increase the rate of successful LPs in this age group.

Intestinal barrier regulates immune responses in the liver via IL-10-producing macrophages.

The gut-liver axis is of clinical importance as a potential therapeutic target in a wide range of liver diseases; however, the mechanisms underlying interactions between microbial products and immune responses in the liver remain unknown. In this study, we demonstrated that IL-10-producing macrophages contribute to immune tolerance in the inflamed liver under intestinal barrier disruption in a murine tandem model of dextran sulfate sodium (DSS) colitis and concanavalin A (Con A) hepatitis. Intestinal barrier disruption protected mice from subsequent liver injury, and the severity of colitis directly affected susceptibility to such injury. The protective effect of DSS-Con A was canceled in gut-sterilized mice, suggesting that gut microbiota play a substantial role in this process. Altered gut microbiota and their metabolites, along with a disrupted intestinal barrier, directly gave rise to immunological permissiveness in the inflamed liver. We identified 1-methylnicotinamide (1-MNA) as a candidate metabolite capable of suppressing liver injury with the potential to induce IL-10-producing macrophages. Consistently, expression of nicotinamide N-methyltransferase, which converts nicotinamide to 1-MNA, was upregulated in the liver of DSS-Con A mice, and this effect was abrogated by gut sterilization. Collectively, our results provide a mechanistic insight into the regulation of immunological balance in the liver via the gut-liver axis.

Commensal Lactobacillus Controls Immune Tolerance during Acute Liver Injury in Mice.

Gut-derived microbial antigens trigger the innate immune system during acute liver injury. During recovery, regulatory immunity plays a role in suppressing inflammation; however, the precise mechanism underlying this process remains obscure. Here, we find that recruitment of immune-regulatory classical dendritic cells (cDCs) is crucial for liver tolerance in concanavalin A-induced acute liver injury. Acute liver injury resulted in enrichment of commensal Lactobacillus in the gut. Notably, Lactobacillus activated IL-22 production by gut innate lymphoid cells and raised systemic IL-22 levels. Gut-derived IL-22 enhanced mucosal barrier function and promoted the recruitment of regulatory cDCs to the liver. These cDCs produced IL-10 and TGF-ß through TLR9 activation, preventing further liver inflammation. Collectively, our results indicate that beneficial gut microbes influence tolerogenic immune responses in the liver. Therefore, modulation of the gut microbiota might be a potential option to regulate liver tolerance.

On-treatment decrease of NKG2D correlates to early emergence of clinically evident hepatocellular carcinoma after interferon-free therapy for chronic hepatitis C.

BACKGROUND AND AIMS: Interferon (IFN)- free direct antiviral agents (DAAs) with rapid HCV eradication might evoke immunological reconstitutions, and some early recurrences of HCC after IFN-free DAAs have been reported. This study aimed to investigate whether natural killer group 2, member D (NKG2D) predicts early emergence of HCC after IFN-free DAAs. METHODS: We conducted a clinical practice-based observational study of 101 patients infected with genotype 1 HCV who received IFN-free (DAAs), and stratified them into those who did or did not develop early (i.e., during the 6-month surveillance period following treatment.) recurrence or occurrence of clinically evident HCC. We also analyzed the peripheral blood mononuclear cells, both before treatment and at end of treatment (EOT), of 24 of the patients who received IFN-free DAAs, and 16 who received IFN-combined protease inhibitor. RESULTS: We found early emergence of clinically evident HCC after IFN-free DAAs in 12 (12%) patients. Higher pre-treatment NKG2D expression, higher FIB-4 score, previous HCC history and failure to achieve sustained viral response were significant factors correlating to early HCC emergence. After IFN-free DAAs, a rapid decrease of NKG2D at EOT correlated with early HCC emergence in the IFN-free DAA-treated patients, but not in patients treated with the IFN-combined regimen. The decrease of NKG2D until EOT was predictive of early HCC emergence at a cut-off of -52% (AUC = 0.92). CONCLUSIONS: On-treatment decrease of NKG2D may be a useful predictor of early emerging HCC in patients treated with IFN-free DAAs.

Bone marrow-derived macrophages distinct from tissue-resident macrophages play a pivotal role in Concanavalin A-induced murine liver injury via CCR9 axis.

The fundamental mechanism how heterogeneous hepatic macrophage (Mφ) subsets fulfill diverse functions in health and disease has not been elucidated. We recently reported that CCR9+ inflammatory Mφs play a critical role in the course of acute liver injury. To clarify the origin and differentiation of CCR9+Mφs, we used a unique partial bone marrow (BM) chimera model with liver shielding for maintaining hepatic resident Mφs. First, irradiated mice developed less liver injury with less Mφs accumulation by Concanavalin A (Con A) regardless of liver shielding. In mice receiving further BM transplantation, CD11blowF4/80high hepatic-resident Mφs were not replaced by transplanted donors under steady state, while under inflammatory state by Con A, CCR9+Mφs were firmly replaced by donors, indicating that CCR9+Mφs originate from BM, but not from hepatic-resident cells. Regarding the mechanism of differentiation and proliferation, EdU+CCR9+Mφs with a proliferative potential were detected specifically in the inflamed liver, and in vitro study revealed that BM-derived CD11b+ cells co-cultured with hepatic stellate cells (HSCs) or stimulated with retinoic acids could acquire CCR9 with antigen-presenting ability. Collectively, our study demonstrates that inflammatory Mφs originate from BM and became locally differentiated and proliferated by interaction with HSCs via CCR9 axis during acute liver injury.

Simeprevir/pegylated interferon/ribavirin triple therapy for recurrent hepatitis C after living donor liver transplantation.

AIM: Simeprevir (SMV) is a protease inhibitor which demonstrates good tolerability and high antiviral response in patients with hepatitis C. The clinical outcomes of triple therapy using simeprevir, pegylated interferon and ribavirin (SMV/PEG IFN/RBV) for recurrent hepatitis C after living donor liver transplantation (LDLT) have not been well reported. In this study, we assessed the outcomes of patients with recurrent hepatitis C (genotype 1) after LDLT who received triple therapy at our hospital. METHODS: SMV/PEG IFN/RBV was administrated for 12 weeks (triple therapy), followed by another 12 weeks or extended period of PEG IFN/RBV (dual therapy). Virological response, interaction with calcineurin inhibitors and adverse events were retrospectively analyzed. RESULTS: Ten patients with recurrent hepatitis C after LDLT completed 12 weeks of triple therapy. Nine patients achieved rapid or early virological response, and one patient was a non-responder. The nine responders received subsequent dual therapy, and the duration of dual therapy was extended (24 to 36 weeks) in five cases. Although one patient was in relapse 8 weeks after completing the standard duration (12 weeks) of dual therapy, eight patients achieved sustained virological response for 12 weeks (SVR12). The SVR12 rate was 80%. Trough levels of calcineurin inhibitor did not show marked changes after introduction of SMV in all cases. There were no major adverse events associated with SMV. CONCLUSION: SMV treatment may be a safe and effective option for recurrent hepatitis C after LDLT.