Background/Aims: Recent studies suggested a favorable effect of indigo naturalis (IN) in inducing remission for refractory ulcerative colitis (UC), however, the maintenance effect of IN for patients with UC remains unknown. Therefore, we conducted a prospective uncontrolled open-label study to analyze the efficacy and safety of IN for patients with UC. Methods: Patients with moderate to severe active UC (clinical activity index [CAI] ≥ 8) took 2 g/day of IN for 52 weeks. CAI at weeks 0, 4, 8, and 52 and Mayo endoscopic subscore (MES) and Geboes score (GS) at weeks 0, 4, and 52 were assessed. Clinical remission (CAI ≤ 4), mucosal healing (MES ≤ 1), and histological healing (GS ≤ 1) rates at each assessment were evaluated. Overall adverse events (AEs) during study period were also evaluated. The impact of IN on mucosal microbial composition was assessed using 16S ribosomal RNA gene sequences. Results: Thirty-three patients were enrolled. The rates of clinical remission at weeks 4, 8, and 52 were 67%, 76%, and 73%, respectively. The rates of mucosal healing at weeks 4 and 52 were 48% and 70%, respectively. AEs occurred in 17 patients (51.5%) during follow-up. Four patients (12.1%) showed severe AEs, among whom 3 manifested acute colitis. No significant alteration in the mucosal microbial composition was observed with IN treatment. Conclusions One-year treatment of moderate to severe UC with IN was effective. IN might be a promising therapeutic option for maintaining remission in UC, although the relatively high rate of AEs should be considered.

Background/Aims: This study aimed to assess the efficacy of a novel aerosol-exposure protection (AP) mask in preventing coronavirus disease in healthcare professionals during upper gastrointestinal endoscopy and to evaluate its clinical feasibility. Methods: In Study 1, three healthy volunteers volitionally coughed with and without the AP mask in a cleanroom. Microparticles were visualized and counted with a specific measurement system and compared with and without the AP mask. In Study 2, 30 patients underwent endoscopic resection with the AP mask covering the face, and the SpO2 was measured throughout the procedure. Results: In Study 1, the median number of microparticles in volunteers 1, 2, and 3 with and without the AP mask was 8.5 and 110.0, 7.0 and 51.5, and 8.0 and 95.0, respectively (p<0.01). Using the AP mask, microparticles were reduced by approximately 92%. The median distances of microparticle scattering without the AP mask were 60, 0, and 68 in volunteers 1, 2, and 3, respectively. In Study 2, the mean SpO2 was 96.3%, and desaturation occurred in three patients. Conclusion The AP mask could provide protection from aerosol exposure and can be safely used for endoscopy in clinical practice.

Background/Aims: Probe-based confocal laser endomicroscopy (pCLE) requires the administration of intravenous (IV) fluorescein. This study aimed to determine the optimal dose of IV fluorescein for both upper and lower gastrointestinal (GI) tract pCLE. Methods: Patients 20 to 79 years old with gastric high-grade dysplasia (HGD) or colorectal neoplasms (CRNs) were enrolled in the study. The dose de-escalation method was employed with five levels. The primary endpoint of the study was the determination of the optimal dose of IV fluorescein for pCLE of the GI tract. The reduced dose was determined based on off-line reviews by three endoscopists. An insufficient dose of fluorescein was defined as the dose of fluorescein with which the pCLE images were not deemed to be visible. If all three endoscopists determined that the tissue structure was visible, the doses were de-escalated. Results: A total of 12 patients with gastric HGD and 12 patients with CRNs were enrolled in the study. Doses were de-escalated to 0.5 mg/kg of fluorescein for both non-neoplastic duodenal and colorectal mucosa. All gastric HGD or CRNs were visible with pCLE with IV fluorescein at 0.5 mg/kg. Conclusions In the present study, pCLE with IV fluorescein 0.5 mg/kg was adequate to visualize the magnified structure of both the upper and lower GI tract.

Background/Aims: Probe-based confocal laser endomicroscopy (pCLE) requires the administration of intravenous (IV) fluorescein. This study aimed to determine the optimal dose of IV fluorescein for both upper and lower gastrointestinal (GI) tract pCLE. Methods: Patients 20 to 79 years old with gastric high-grade dysplasia (HGD) or colorectal neoplasms (CRNs) were enrolled in the study. The dose de-escalation method was employed with five levels. The primary endpoint of the study was the determination of the optimal dose of IV fluorescein for pCLE of the GI tract. The reduced dose was determined based on off-line reviews by three endoscopists. An insufficient dose of fluorescein was defined as the dose of fluorescein with which the pCLE images were not deemed to be visible. If all three endoscopists determined that the tissue structure was visible, the doses were de-escalated. Results: A total of 12 patients with gastric HGD and 12 patients with CRNs were enrolled in the study. Doses were de-escalated to 0.5 mg/kg of fluorescein for both non-neoplastic duodenal and colorectal mucosa. All gastric HGD or CRNs were visible with pCLE with IV fluorescein at 0.5 mg/kg. Conclusions In the present study, pCLE with IV fluorescein 0.5 mg/kg was adequate to visualize the magnified structure of both the upper and lower GI tract.

This systematic review aimed to assess the efficacy of the current approach to tissue traction during the endoscopic submucosal dissection (ESD) of superficial esophageal cancer, early gastric cancer, and colorectal neoplasms.We performed a systematic electronic literature search of articles published in PubMed and selected comparative studies to investigate the treatment outcomes of tractionassisted versus conventional ESD. Using the keywords, we retrieved 381 articles, including five eligible articles on the esophagus, 13 on the stomach, and 12 on the colorectum. A total of seven randomized controlled tri-als and 23 retrospective studies were identified. Clip line traction and submucosal tunneling were effective in re-ducing the procedural time during esophageal ESD. The efficacy of traction methods in gastric ESD varied in terms of the devices and strategies used depending on the le-sion location and degree of submucosal fibrosis. Several prospective and retrospective studies utilized traction de-vices without the need to reinsert the colonoscope. When pocket creation is included, the traction devices and methods effectively shorten the procedural time during colorectal ESD. Although the efficacy is dependent on the organ and tumor locations, several traction techniques have been demonstrated to be efficacious in facilitating ESD by maintaining satisfactory traction during dissection.

Background/Aims: The accurate assessment of the depth of invasion of early gastric cancer (EGC) is critical to determine the most appropriate treatment option. However, it is difficult to distinguish shallow submucosal (SM1) invasion from deeper submucosal (SM2) invasion. We investigated the diagnostic performance of endoscopic ultrasonography (EUS) using a miniature probe for EGC with suspected SM invasion. Methods: From April 2008 to June 2018, EGCs with suspected SM invasion were analyzed retrospectively. The EGCs examined by a 20 MHz high-frequency miniature probe was included in our study. Esophago-gastric junction cancers and patients treated by chemotherapy before resection were excluded. The sensitivity and specificity for the detection of SM2 invasion by EUS were compared with those of white light imaging (WLI).Additionally, factors related to depth underestimation or overestimation were investigated using multivariate analysis. Results: A total of 278 EGCs in 259 patients were included in the final analysis. The sensitivity and specificity for SM2 or deeper by EUS were 73.7% (87/118) and 74.4% (119/160), respectively. The sensitivity and specificity by WLI were 47.5% (56/118) and 68.1% (109/160), respectively. The sensitivity of EUS was significantly superior to that of conventional endoscopy (p<0.01). Multivariate analysis revealed that an anterior location of the EGC was an independent risk factor for underestimation by EUS (odds ratio, 3.3; 95% confidence interval, 1.1 to 9.8; p=0.03). Conclusions The depth diagnostic performance for EGCs with suspected SM invasion using EUS was satisfactory and superior to that of conventional endoscopy. Additionally, it is important to recognize factors that may lead to misdiagnosis in thoselesions.

We added Kampo medicine (Japanese traditional herbal medicine) to disease-­modifying anti-­rheumatic drugs (DMARDs) to treat rheumatoid arthritis (RA) in 41 patients. After 1 year, disease activity assessments showed improvement in the number of tender joints and DAS 28-­CRP, and Boolean remission increased from 3 cases to 6 cases. However, 16 of 41 patients had an insufficient therapeutic effect with Kampo medicine ; therefore, their DMARD treatment was strengthened. Disease activity in the 16 patients with strengthened DMARD therapy (Western group) was compared with that in the 25 patients who did not require strengthened DMARD therapy (Kampo group). The Western group had high disease activity at the beginning of Kampo medicine, and a year later CRP and DAS 28­-CRP improved. In the Kampo group, disease activity was relatively good at the beginning of Kampo medicine, and patient global assessment (PGA) improved. We believe that combination therapy, with DMARDs controlling synovitis and Kampo medicine improving PGA, is an effective way to achieve Boolean remission.

BACKGROUND: Slow-motion training, which comprises exercising using extremely slow-movements, yields a training effect like that of high-intensity training, even when the applied load is small. We developed a slow-training exercise program that allows elderly people to safely use their own body weight without a machine. Previously, it was confirmed that functional gait and lower limb muscle strength were improved by low-intensity training using bodyweight training for 3 months. This study evaluated the long-term effects of low-intensity training using body weight with slow-movements on the motor function of frail, elderly patients. METHODS: Ninety-six elderly men and women aged 65 years or older whose level of nursing care was classified as either support required (1 and 2) or long-term care required (care levels 1 and 2) volunteered to participate. Two facilities were used. Participants at the first facility used low-intensity training using body weight with slow-movements (low-stress training [LST] group, n = 65), and participants at another facility used machine training (MT group, n = 31). Exercise interventions were conducted for 12 months, once or twice per week, depending on the required level of nursing care. Changes in motor function were examined. RESULTS: Post-intervention measurements based on the results of the chair-stand test after 12 months showed significant improvements from pre-intervention levels (P < 0.0001) in the LST group and MT group. Although the ability of performing the Timed Up & Go test and the ability to stand on one leg with eyes open improved in both groups, no significant change was observed. When changes after 12 months were compared between the two groups, no significant difference was observed for any variables. CONCLUSIONS: Slow body weight training for 12 months without a machine improved the lower limb muscle strength. Therefore, it could have the same effects as training using a machine. TRIAL REGISTRATION UMIN000030853 . Registered 17 January 2018 (retrospectively registered).
Aged ; Aged, 80 and over ; Body Weight ; Exercise Therapy ; statistics & numerical data ; Female ; Frail Elderly ; statistics & numerical data ; Humans ; Japan ; Male ; Movement ; Prospective Studies

BACKGROUND: Slow-motion training, an exercise marked by extremely slow movements, yields a training effect like that of a highly intense training, even when the applied load is small. This study evaluated the effects of low-intensity bodyweight training with slow movement on motor function in frail, elderly patients. METHODS: Ninety-seven elderly men and women aged 65 years or older, whose level of nursing care was classified as either support required (1 and 2) or long-term care required (care level 1 and 2), volunteered to participate. Two facilities were used. Participants in the first facility used low-intensity bodyweight training with slow movement (the LST group, n = 65), and participants in another facility used machine training (the control group, n = 31). Exercises were conducted for 3 months, once or twice a week, depending on the required level of nursing care. Changes in motor function were examined. RESULTS: Post-exercise measurements showed significant improvements from the pre-exercise levels after 3 months, based on the results of the Timed Up and Go test (p = 0.0263) and chair-stand test (p = 0.0016) in the low-intensity exercise with slow movement and tonic force generation (LST) group. Although the ability to stand on one leg with eyes open tended to improve, no significant change was found (p = 0.0964). CONCLUSIONS: We confirmed that carrying out LST bodyweight training for 3 months led to improvements in ambulatory function and lower-limb muscle strength. In this way, it is possible that LST training performed by holding a bar or by staying seated on a chair contributes to improved motor function in elderly patients within a short time. TRIAL REGISTRATION UMIN000030853 . Registered 17 January 2018. (retrospectively registered).
Aged ; Aged, 80 and over ; Female ; Frail Elderly ; Humans ; Long-Term Care ; Male ; Motor Activity ; Movement ; Prospective Studies ; Resistance Training ; methods

BACKGROUND/AIMS: Nonalcoholic steatohepatitis (NASH) is prevalent in both economically developed and developing countries. Twenty percent of NASH progresses to cirrhosis with/without hepatocellular carcinoma, and there is an urgent need to find biomarkers for early diagnosis and monitoring progression of the disease. Using immunohistochemical and immunoelectron microscopic examination we previously reported that expression of matrix metalloproteinase-1 (MMP-1) increased in monocytes, Kupffer cells and hepatic stellate cells in early stage NASH. The present study investigated whether serum MMP-1 levels reflect disease activity and pharmaceutical effects in NASH patients. METHODS: We measured the serum levels of MMPs, tissue inhibitors of metalloproteinases (TIMPs), and several cytokines/chemokines in patients with histologically proven early and advanced stages of NASH and compared them with those in healthy controls. RESULTS: Serum MMP-1 levels in stage 1 fibrosis, but not in the more advanced fibrosis stages, were significantly higher than in healthy controls (P=0.019). There was no correlation between serum MMP-1 level and fibrosis stage. Serum MMP- 1 levels in NASH patients represented disease activity estimated by serum aminotransferase values during the follow-up period. In contrast, MMP-2, MMP-9 and TIMPs did not change with disease activity. Consistent with the finding that MMP-1 is expressed predominantly in monocytes and Kupffer cells, serum levels of monocyte chemotactic protein-1 and granulocyte-colony stimulating factor were significantly increased in NASH with stage 1 fibrosis. CONCLUSIONS: These results suggest that serum MMP-1 levels represent disease activity and may serve as a potential biomarker for monitoring the progression of NASH.
Biomarkers ; Carcinoma, Hepatocellular ; Chemokine CCL2 ; Cytokines ; Developing Countries ; Early Diagnosis ; Fibrosis* ; Follow-Up Studies ; Hepatic Stellate Cells ; Humans ; Kupffer Cells ; Liver Cirrhosis ; Matrix Metalloproteinase 1* ; Matrix Metalloproteinases ; Metalloproteases ; Monocytes ; Non-alcoholic Fatty Liver Disease*