Purpose: The long-term efficacy and safety of infliximab (IFX) in Japanese children with inflammatory bowel disease (IBD) remain unclear. This study aimed to examine the longterm outcomes of IFX treatment in Japanese children with IBD. Methods: We retrospectively recruited patients aged <16 years who were diagnosed with ulcerative colitis (UC) or Crohn’s disease (CD) at Kurume University Hospital in Japan between 2011 and 2022 and examined the effectiveness and safety of IFX. We characterized the responses to IFX as primary response, primary nonresponse (PNR), secondary loss of response (sLOR), or still receiving IFX. Results: Among the 77 enrolled patients with UC (median age, 10 years) and 48 with CD (median age, 12 years), 55 (27 with UC and 28 with CD) received IFX treatment. IFX treatment was significantly more common in patients with CD (58.3%) than in those with UC (35.1%;p=0.016). The PNR was significantly greater in patients with UC (18.5%) than in those with CD (0.0%; p=0.023), as was the sLOR (UC, 51.9%; CD, 21.4%; p=0.026). The likelihood of continuing IFX treatment during follow-up (median, 38 months) was significantly higher in patients with CD (71.4%) than in those with UC (29.6%; p=0.003). Adverse events resulting in the discontinuation of IFX occurred in 3.6% of the patients; one patient with CD developed leukemia, and the other had a serious infusion reaction. Conclusion The long-term durability of IFX in Japanese pediatric patients with IBD was inadequate in UC compared with CD. Serious adverse events in 3.6% of patients required discontinuation.

An 89-year-old woman presented to the hospital with a chief complaint of fever and hematuria. Computed tomography revealed left hydronephrosis due to bladder cancer, along with common bile duct stones and marked dilation of the bile duct. Endoscopic ultrasonography-guided choledochoduodenostomy was attempted, but the common bile duct could not be visualized in close proximity to the duodenum. Instead, due to the gastroduodenal deformity, the common bile duct was in close proximity with the gastric antrum; therefore, the common bile duct was selected for puncture from the gastric antrum using a 19-gauge needle. However, the gastric wall and scope became separated during the dilation maneuver, making it difficult to dilate the fistula using a 6-Fr dilator and a 4-mm-diameter balloon dilation catheter, although it was possible to insert a tapered catheter with a 3.5-Fr tip under a 0.025-inch guidewire into the bile duct. The use of a stiff 0.035-inch guidewire allowed blunt dilation up to 9-Fr with a dilator, while simultaneously maintaining the distance between the gastric wall and the scope. Using this method, a 10-mm-diameter, 12-cm-long, partially covered metal stent was deployed successfully between the common bile duct and the posterior wall of the gastric antrum. Endoscopic ultrasonography-guided choledochogastrostomy (EUS-CGS) risks separating the gastrointestinal and biliary tracts during or after the procedure. In this case, the stiff guidewire enabled successful completion of the biliary procedures; thus, this guidewire can be used to safely manage difficult cases of EUS-CGS involving dilation of the fistula and stent deployment.

Background/Aims: Bowel urgency is an important symptom for quality of life determination in patients with ulcerative colitis (UC). Few clinical studies have focused on bowel urgency as an efficacy endpoint. Budesonide foam enema has shown efficacy for clinical and endoscopic improvement in mild-to-moderate UC. We evaluated the improvement of clinical symptoms (bowel urgency), safety, and treatment impact of twice-daily budesonide foam enema on the quality of life in patients with UC. Methods: This open-label, multicenter, prospective observational study comprised a 4-week observation period assessing the effectiveness and safety of twice-daily budesonide foam enema. Mild-to-moderate UC patients who had bowel urgency were included. Patients collected data daily in an electronic patient-reported outcome system or logbooks. The primary endpoint was the rate of resolution of bowel urgency at the end of the 4-week observation period. The rate of bowel incontinence was also assessed. Results: Sixty-one patients were enrolled. Of patients with a final evaluation, the rate of resolution of bowel urgency was 58.5% (31/53; 95% confidence interval, 44.1%–71.9%). Bowel urgency decreased over time, with a significant difference observed on day 7 versus day 0. Bowel incontinence showed a decreasing trend from day 5, with a significant difference confirmed on day 12 versus day 0. The clinical remission rate was 64.4% (38/59; 95% confidence interval, 50.9%–76.4%). One adverse event not related to budesonide rectal foam occurred. Conclusions The findings suggest that bowel urgency can be improved early with twice-daily budesonide foam enema. No new safety signals were observed.

Background: Patients with rheumatoid arthritis (RA) are at an increased risk of osteoporosis and vertebral fractures. This study aimed to investigate factors associated with vertebral fractures and treatment goals to prevent new vertebral fractures in patients with RA. Methods: The database used in this study included outpatient data of RA patients at the authors’ hospital of RA patients taken from 2018 to 2022. The patients underwent annual imaging evaluations to assess parameters, including bone mineral density of the lumbar spine (LS; L2-4), total hip, and femoral neck, as well as vertebral fractures. Vertebral fractures were evaluated using radiographic images of the T8 to L5 vertebrae. Results: The prevalence rates of new vertebral fractures in 2018–2019, 2019–2020, 2020– 2021, and 2021–2022 were 2.0%, 1.3%, 2.3%, and 2.0%, respectively. The presence of existing vertebral fractures was associated with new vertebral fractures (p=0.003; odds ratio, 0.241; 95% confidence interval, 0.093–0.624). The cut-off T-score values for the LS for new vertebral fractures in patients with or without pre-existing vertebral fractures were -0.7 (sensitivity, 40.9%; specificity, 100%) and -1.4 (sensitivity, 69.0%; specificity, 62.5%), respectively. Conclusions The presence of pre-existing vertebral fractures is an independent factor associated with new vertebral fractures. It is important to tailor treatment goals based on the presence or absence of vertebral fractures to effectively prevent new fractures.

Background/Aims: Pathological evaluation is crucial for diagnosing biliary lesions and determining appropriate treatment strategies. However, tissue sampling via the transpapillary route can be difficult. In this study, we aimed to assess the efficacy and safety of a novel tapered-tip sheath system for tissue sampling from biliary strictures. Methods: This single-center, randomized, parallel-group clinical trial included patients aged 20 to 85 years admitted to Kyoto University Hospital for biliary strictures. The patients were randomly assigned (1:1) to a new or conventional method group. The primary outcome was technical success of biopsy at the target bile duct using the assigned method, as determined in accordance with the intention-to-treat principle. Adverse events were assessed in all eligible patients. Results: Fifty-six patients were assessed for eligibility between September 2020 and March 2023; 50 patients were enrolled. The patients were randomly divided into the new (n=25) method group and the conventional (n=25) method group. Technical success was achieved in 96.0% (24/25) and 48.0% (12/25) of patients in the new and conventional method groups, respectively (risk ratio, 2.00; 95% confidence interval [CI], 1.32 to 3.03; risk difference, 48.0%; 95% CI, 27.0% to 69.0%; p<0.001). Adverse events occurred in 4.0% (1/25) and 36.0% (9/25) of patients in the new and conventional method groups, respectively (risk ratio, 0.11; 95% CI, 0.02 to 0.81; risk difference, –32.0%; 95% CI, –52.3% to –11.7%; p=0.005). Conclusions The novel tapered-tip sheath system is a promising option for precisely and safely delivering biopsy forceps to target sites, thereby facilitating the diagnosis of biliary strictures.

Autoimmune pancreatitis (AIP), which is considered the pancreatic expression of a systemic immunoglobulin G4-related disease, is characterized by excessive infiltration of plasmacytes bearing immunoglobulin G4 and a unique form of fibrosis in multiple organs. This relatively new disease entity has garnered great attention from clinicians, but its pathophysiology remains poorly understood. Recent discoveries indicate that plasmacytoid dendritic cell activation followed by robust production of type I interferon and interleukin-33 plays a key role in driving chronic fibro-inflammatory responses in both murine and human AIP. Furthermore, the compositional alterations in the gut microbiota, known as intestinal dysbiosis, triggered plasmacytoid dendritic cell-driven pathogenic type I interferon responses. Intestinal dysbiosis is associated with a breakdown in intestinal barrier function; thus, we examined whether the latter condition affects the development of experimental AIP. Our recent research has revealed that intestinal barrier disruption worsens experimental AIP by facilitating the translocation of pathogenic bacteria, such as Staphylococcus sciuri, to the pancreas from the gut. These results indicate the “gut-pancreas axis” underlies the immunopathogenesis of AIP, and the maintenance of intestinal barrier integrity can prevent the worsening of AIP by inhibiting pancreatic colonization by harmful gut bacteria. In this mini review, the interactions between AIP development and gut microbiota are discussed with the aim of providing useful information not only for researchers but also for clinicians.

Photobiomodulation (PBM), a noninvasive phototherapy that utilizes wavelengths between red and near-infrared light, has emerged as a promising approach for controlling inflammation by modulating macrophage polarization. This review investigates the therapeutic potential of PBM in treating ENT-specific inflammatory conditions, such as chronic rhinosinusitis and otitis media, focusing on its effects on macrophage phenotypes and evidence from preclinical studies. By promoting mitochondrial activity, increasing adenosine triphosphate production, and modulating reactive oxygen species, PBM has been shown to shift macrophages from a pro-inflammatory to an anti-inflammatory phenotype. Studies have demonstrated that PBM enhances tissue repair, reduces inflammatory markers, and promotes wound healing. Moreover, PBM facilitates the polarization of M2 macrophages, a crucial factor in resolving mucosal inflammation in the nasal, pharyngeal, and middle ear cavities, as well as restoring tissue homeostasis. The anti-inflammatory effects of PBM are attributed to its ability to influence several molecular mechanisms involved in inflammation regulation, particularly in ENT organ tissues, where recurrent inflammation can lead to chronic conditions such as otitis media or sinusitis. Furthermore, this review compares PBM to competing methods for reprogramming macrophages and treating inflammation, highlighting its advantages of minimal toxicity, simplicity, and precision in controlling ENT immune responses.

Background/Aims: Biliary complications are a leading cause of morbidity after liver transplantation, but can be reduced using real-time assessment of the biliary tree. This study described a novel technique for performing ex vivo cholangioscopy during cold static storage and normothermic machine perfusion (NMP) to assess the biliary tree before liver transplantation. Methods: Human donor livers, which were considered unsuitable for transplantation, were perfused at 36ºC using a modified commercial ex vivo perfusion system. Ex vivo cholangioscopy was performed using a SpyGlass Discover system. Cholangioscopy was performed during cold static storage and after 12 hours in NMP. Bile duct biopsies and confocal microscopy were performed. Results: Ex vivo cholangioscopy was performed on eight grafts. During cold static storage, luminal debris was visualized throughout the biliary tree. After 12 hours of reperfusion, the bile ducts appeared hyperemic, heterogeneous, and mottled. Confocal microscopy confirmed perfusion of biliary microvasculature. Conclusions We describe the first use of ex vivo cholangioscopy to assess the biliary tree before liver transplantation. This real-time technique can be used to assess biliary trees during cold static storage and NMP. In addition, cholangioscopy-based interventions can be used to better assess intrahepatic bile ducts.

Purpose: The long-term efficacy and safety of infliximab (IFX) in Japanese children with inflammatory bowel disease (IBD) remain unclear. This study aimed to examine the longterm outcomes of IFX treatment in Japanese children with IBD. Methods: We retrospectively recruited patients aged <16 years who were diagnosed with ulcerative colitis (UC) or Crohn’s disease (CD) at Kurume University Hospital in Japan between 2011 and 2022 and examined the effectiveness and safety of IFX. We characterized the responses to IFX as primary response, primary nonresponse (PNR), secondary loss of response (sLOR), or still receiving IFX. Results: Among the 77 enrolled patients with UC (median age, 10 years) and 48 with CD (median age, 12 years), 55 (27 with UC and 28 with CD) received IFX treatment. IFX treatment was significantly more common in patients with CD (58.3%) than in those with UC (35.1%;p=0.016). The PNR was significantly greater in patients with UC (18.5%) than in those with CD (0.0%; p=0.023), as was the sLOR (UC, 51.9%; CD, 21.4%; p=0.026). The likelihood of continuing IFX treatment during follow-up (median, 38 months) was significantly higher in patients with CD (71.4%) than in those with UC (29.6%; p=0.003). Adverse events resulting in the discontinuation of IFX occurred in 3.6% of the patients; one patient with CD developed leukemia, and the other had a serious infusion reaction. Conclusion The long-term durability of IFX in Japanese pediatric patients with IBD was inadequate in UC compared with CD. Serious adverse events in 3.6% of patients required discontinuation.

Purpose: The long-term efficacy and safety of infliximab (IFX) in Japanese children with inflammatory bowel disease (IBD) remain unclear. This study aimed to examine the longterm outcomes of IFX treatment in Japanese children with IBD. Methods: We retrospectively recruited patients aged <16 years who were diagnosed with ulcerative colitis (UC) or Crohn’s disease (CD) at Kurume University Hospital in Japan between 2011 and 2022 and examined the effectiveness and safety of IFX. We characterized the responses to IFX as primary response, primary nonresponse (PNR), secondary loss of response (sLOR), or still receiving IFX. Results: Among the 77 enrolled patients with UC (median age, 10 years) and 48 with CD (median age, 12 years), 55 (27 with UC and 28 with CD) received IFX treatment. IFX treatment was significantly more common in patients with CD (58.3%) than in those with UC (35.1%;p=0.016). The PNR was significantly greater in patients with UC (18.5%) than in those with CD (0.0%; p=0.023), as was the sLOR (UC, 51.9%; CD, 21.4%; p=0.026). The likelihood of continuing IFX treatment during follow-up (median, 38 months) was significantly higher in patients with CD (71.4%) than in those with UC (29.6%; p=0.003). Adverse events resulting in the discontinuation of IFX occurred in 3.6% of the patients; one patient with CD developed leukemia, and the other had a serious infusion reaction. Conclusion The long-term durability of IFX in Japanese pediatric patients with IBD was inadequate in UC compared with CD. Serious adverse events in 3.6% of patients required discontinuation.