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A 67-year-old man presented to our hospital with vomiting. Esophagogastroduodenoscopy revealed duodenal stenosis and atypical epithelium. A tumor in the pancreatic head, about 30mm in size, involving the superior mesenteric artery and a superior mesenteric vein was identified using abdominal contrast computed tomography (CT). Locally advanced pancreatic cancer was diagnosed in the patient through an endoscopic biopsy. Due to the duodenal stenosis complication, duodenal stent placement was conducted. After stent placement, oral intake was resumed, and improvement of the systemic condition led to chemotherapy (modified FOLFIRINOX). After chemotherapy, CT revealed decreased carcinoma progression and vascular invasion. Conversion surgery was improved, and R0 resection was achieved. Our study showed that duodenal stent placement could enhance prognosis;as a result, it was regarded as a good choice for multidisciplinary therapy.
Subject(s)
Duodenal Obstruction , Pancreatic Neoplasms , Stents , Humans , Male , Aged , Pancreatic Neoplasms/surgery , Pancreatic Neoplasms/diagnostic imaging , Duodenal Obstruction/etiology , Duodenal Obstruction/surgery , Duodenal Obstruction/diagnostic imagingABSTRACT
BACKGROUND: Endoscopic healing (EH) is a therapeutic target in ulcerative colitis (UC). However, even patients who have achieved EH relapse frequently. AIMS: To investigate the association between recent steroid use and relapse risk in UC patients with EH. METHODS: This multi-centre cohort study included 1212 UC patients with confirmed EH (Mayo endoscopic subscore ≤1). We excluded patients with current systemic steroid use or history of advanced therapy. We divided patients into a recent steroid group (last systemic steroid use within 1 year; n = 59) and a non-recent or steroid-naïve group (n = 1153). We followed the patients for 2 years to evaluate relapse, defined as induction of systemic steroids or advanced therapy. We used logistic regression to estimate the odds ratio (OR) of relapse. RESULTS: Relapse occurred in 28.8% of the recent steroid group and 5.6% of the non-recent/steroid-naïve group (multi-variable-adjusted OR 5.53 [95% CI 2.85-10.7]). The risk of relapse decreased with time since the last steroid use: 28.8% for less than 1 year after steroid therapy, 22.9% for 1 year, 16.0% for 2 years and 7.9% beyond 3 years, approaching 4.0% in steroid-naïve patients. (ptrend <0.001). CONCLUSIONS: Even for patients with UC who achieved EH, the risk of relapse remains high following recent steroid therapy. Physicians need to consider the duration since last steroid use to stratify the relapse risk in UC patients with EH.
Subject(s)
Colitis, Ulcerative , Recurrence , Steroids , Humans , Colitis, Ulcerative/drug therapy , Male , Female , Adult , Middle Aged , Steroids/therapeutic use , Cohort Studies , Risk Factors , Colonoscopy , Time Factors , Wound Healing/drug effects , Treatment OutcomeABSTRACT
BACKGROUND: Endoscopic healing is generally defined as Mayo endoscopic subscore (MES) ≤1 in ulcerative colitis (UC). However, patients with an MES of 1 are at higher relapse risk than those with an MES of 0. This study evaluated the therapeutic efficacy of proactive dose escalation of oral 5-aminosalicylic acid (5-ASA) in UC patients with an MES of 1. METHODS: An open-label, randomized controlled trial was conducted in 5 hospitals between 2018 and 2022. Ulcerative colitis patients in clinical remission under oral 5-ASA therapy and diagnosed as having an MESâ ofâ 1 were enrolled. Patients receiving maintenance therapy other than 5-ASA and immunomodulator were excluded. Patients were randomly assigned in a 1:1 ratio to receive either a dose-escalated (intervention) or constant dose (control) of 5-ASA. Concomitant immunomodulator was used as the stratification factor in the randomization. The primary end point was relapse within 1 year. The subgroup analysis was stratified for the use of immunomodulators. RESULTS: The full analysis set included 79 patients (39 intervention and 40 control). Immunomodulators were used in 20 (25.3%) patients. Relapse was less in the intervention group (15.4%) than the control group (37.5%; P = .026). In the subgroup with concomitant immunomodulators, relapse was also less in the intervention group (10.0%) than the control group (70.0%; P = .020). In patients without immunomodulators, the difference was not significant between 2 groups (intervention, 17.2%; control, 26.7%; P = .53). CONCLUSIONS: Dose escalation of 5-ASA reduced relapse within 1 year in UC patients in clinical remission with an MES of 1.
Dose escalation of 5-aminosalicylic acid for ulcerative colitis reduced relapse rate in patients in clinical remission with a Mayo endoscopic subscore of 1. The therapeutic efficacy was more evident in those whom immunomodulators were used.
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BACKGROUND: This study evaluated the effectiveness of NUDT15 codon 139 genotyping in optimizing thiopurine treatment for inflammatory bowel disease (IBD) in Japan, using real-world data, and aimed to establish genotype-based treatment strategies. METHODS: A retrospective analysis of 4628 IBD patients who underwent NUDT15 codon 139 genotyping was conducted. This study assessed the purpose of the genotyping test and subsequent prescriptions following the obtained results. Outcomes were compared between the Genotyping group (thiopurine with genotyping test) and Non-genotyping group (thiopurine without genotyping test). Risk factors for adverse events (AEs) were analyzed by genotype and prior genotyping status. RESULTS: Genotyping test for medical purposes showed no significant difference in thiopurine induction rates between Arg/Arg and Arg/Cys genotypes, but nine Arg/Cys patients opted out of thiopurine treatment. In the Genotyping group, Arg/Arg patients received higher initial doses than the Non-genotyping group, while Arg/Cys patients received lower ones (median 25 mg/day). Fewer AEs occurred in the Genotyping group because of their lower incidence in Arg/Cys cases. Starting with < 25 mg/day of AZA reduced AEs in Arg/Cys patients, while Arg/Arg patients had better retention rates when maintaining ≥ 75 mg AZA. Nausea and liver injury correlated with thiopurine formulation but not dosage. pH-dependent mesalamine reduced leukopenia risk in mesalamine users. CONCLUSIONS: NUDT15 codon 139 genotyping effectively reduces thiopurine-induced AEs and improves treatment retention rates in IBD patients after genotype-based dose adjustments. This study provides data-driven treatment strategies based on genotype and identifies risk factors for specific AEs, contributing to a refined thiopurine treatment approach.
Subject(s)
Azathioprine , Genotype , Inflammatory Bowel Diseases , Mercaptopurine , Pyrophosphatases , Humans , Pyrophosphatases/genetics , Female , Male , Retrospective Studies , Adult , Middle Aged , Mercaptopurine/therapeutic use , Mercaptopurine/adverse effects , Inflammatory Bowel Diseases/drug therapy , Inflammatory Bowel Diseases/genetics , Japan , Azathioprine/adverse effects , Azathioprine/therapeutic use , Young Adult , Aged , Immunosuppressive Agents/therapeutic use , Immunosuppressive Agents/adverse effects , Adolescent , Risk Factors , Codon , Nudix HydrolasesABSTRACT
Indigo naturalis is an effective treatment for ulcerative colitis. However, long-term use of indigo naturalis causes adverse events, such as pulmonary hypertension. The natural history of patients with ulcerative colitis who discontinued indigo naturalis after induction therapy is unknown. Moreover, the clinical features of patients who relapsed within 52 weeks after the discontinuation of indigo naturalis are unclear. This study aimed to assess the clinical outcomes of patients with ulcerative colitis after discontinuation of indigo naturalis and to identify potential markers responsible for relapse. This single-center retrospective study investigated the follow-up of 72 patients who achieved a clinical response 8 weeks after indigo naturalis treatment. We observed relapse in patients with ulcerative colitis after the discontinuation of indigo naturalis. We analyzed the factors predicting long-term outcomes after discontinuation of indigo naturalis. Relapse was observed in 24%, 57%, and 71% of patients at 8, 26, and 52 weeks, respectively. There were no predictive markers in patients who relapsed within 52 weeks after the discontinuation of indigo naturalis. The ulcerative colitis relapse rate after indigo naturalis discontinuation was high. Follow-up treatment is required after the discontinuation of indigo naturalis in patients with ulcerative colitis.
Subject(s)
Colitis, Ulcerative , Drugs, Chinese Herbal , Humans , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/chemically induced , Indigo Carmine , Retrospective Studies , Drugs, Chinese Herbal/pharmacology , RecurrenceABSTRACT
Introduction: Whether white blood cell (WBC) counts are predictors for the effectiveness of thiopurine treatment in ulcerative colitis (UC) has been inconclusive in previous studies with small sample sizes. We investigated the association between WBC counts and future relapses in UC patients in a large-scale multi-center study. Methods: This retrospective cohort study enrolled a total of 723 UC patients in remission from 33 hospitals and followed up for 3 years. Relapse was defined as a need for treatment intensification. The risk of relapse was compared among patients with the baseline WBC counts <3,000/µL (N = 31), 3,000-4,000/µL (N = 167), 4,000-5,000/µL (N = 241), and ≥5,000/µL (N = 284) using a Cox regression model analysis. Moreover, exploratory analyses were conducted to identify other factors predicting relapse. Results: During a median follow-up period of 1,095 (interquartile range, 1,032-1,119) days, relapse occurred in 17.2% (125/723). In a crude analysis, WBC counts were not associated with relapse; hazard ratios (HRs) (95% confidence interval [CI]) were 1.50 (0.74-3.06), 1.02 (0.66-1.59), and 0.67 (0.43-1.05) in WBC <3,000/µL, 3,000-4,000/µL, and 4,000-5,000/µL groups, respectively (WBC ≥5,000/µL group, as reference). Multivariable-adjusted analyses showed similar results; HRs (95% CI) were 1.21 (0.59-2.49), 1.08 (0.69-1.69), and 0.69 (0.44-1.07), in <3,000/µL, 3,000-4,000/µL, and 4,000-5,000/µL groups, respectively. In the exploratory analyses, thiopurine use <1 year and a mean corpuscular volume <90 fL were predictors for relapse. Discussion/Conclusion: WBC counts were not predictors for future relapses in patients with UC treated with thiopurine as a maintenance therapy.
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Introduction: A large proportion of small bowel lesions in Crohn's disease (CD) may exist beyond the reach of ileocolonoscopy and there is no gold standard imaging modality to screen them, suggesting the need for optimal biomarkers. We aimed to compare the usefulness of C-reactive protein (CRP), faecal calprotectin (FC), and leucine-rich alpha-2 glycoprotein (LRG) in determining small bowel lesions of CD. Methods: This was a cross-sectional observational study. CRP, FC, and LRG were prospectively measured in patients with quiescent CD who underwent imaging examinations (capsule or balloon-assisted endoscopy, magnetic resonance enterography, or intestinal ultrasound) selected by the physician in clinical practice. Mucosal healing (MH) of the small bowel was defined as a lack of ulcers. Patients with a CD activity index >150 and active colonic lesions were excluded. Results: A total of 65 patients (27, MH; 38, small bowel inflammation) were analysed. The area under the curve (AUC) of CRP, FC, and LRG was 0.74 (95% confidence interval: 0.61-0.87), 0.69 (0.52-0.81), and 0.77 (0.59-0.85), respectively. The AUC of FC and LRG in a subgroup of 61 patients with CRP <3 mg/L (26, MH; 32, small bowel inflammation) was 0.68 (0.50-0.81) and 0.74 (0.54-0.84), respectively. The cut-off of 16 µg/mL of LRG showed the highest positive predictive value of 1.00 with specificity of 1.00, while negative predictive value was highest (0.71) with sensitivity of 0.89 at the cut-off of 9 µg/mL. Conclusion: LRG can accurately detect and/or exclude the small bowel lesions with two cut-off values.
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Background and Aim: Crohn's disease (CD) often causes intractable diarrhea after intestinal resection. Anion exchange resins have been reported to be effective in patients with bile acid diarrhea after distal ileectomy; furthermore, bile acid metabolism has been implicated in the pathogenesis of CD. Therefore, we aimed to examine the effectiveness of colestimide in the management of postoperative CD, and to compare its impact between patients with and those without ileocecal resection. Methods: Postoperative CD patients prescribed colestimide for diarrhea between April 2017 and December 2020 were retrospectively evaluated for changes in the total Crohn's disease activity index (CDAI), each CDAI component including diarrhea frequency/week, albumin, and C-reactive protein (CRP) was evaluated before and after the administration of colestimide. Furthermore, comprehensive patient and physician assessments were reviewed from medical records during the first outpatient visit as a global clinical judgment after the initiation of colestimide therapy. Results: A total of 24 patients were included, of whom 17 had a previous history of ileocecal resection. Significant improvement was noted in CDAI and diarrhea frequency only in the ileocecal resection group (CDAI: 114.5 ± 52.7 and 95.4 ± 34.8, P < 0.05; diarrhea frequency/week 23.8 ± 14.1 and 15.4 ± 11.2, P < 0.05, respectively). There was no significant improvement in other CDAI components, albumin level, or CRP level in either group. In the global clinical judgment, 13 and 4 patients in the ileocecal and non-ileocecal resection groups, respectively, were judged as "effective," with an overall efficacy rate of 70.8%. Conclusion: Colestimide is effective for diarrhea in patients with postoperative CD, especially after ileocecal resection.
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BACKGROUND: The increasing incidence of older-onset ulcerative colitis (UC), which has a higher risk of surgery, is a global health issue. However, data regarding intravenous steroid treatment, one of the important treatment options to avoid surgery, for older-onset UC is lacking. AIMS: To evaluate the association between onset age and effectiveness of intravenous steroids in UC. METHODS: This retrospective multicentre (27 facilities) cohort study included moderate-to-severe hospitalised UC patients who underwent their first intravenous steroids between April 2014 and July 2019. The primary outcome was clinical remission at day 30, using two-item patient-reported outcome scoring. The key secondary outcomes were risks of surgery and adverse events (death, infection and venous thrombosis) within 90 days. A modified Poisson regression model was used for analysis. RESULTS: Overall, 467 UC patients (384 younger-onset and 83 older-onset) were enrolled. Clinical remission at day 30 was observed in 252 (65.6%) among younger-onset patients and 43 (51.8%) among older-onset patients (adjusted risk difference, -21.7% [95% CI, -36.1% to -7.2%]; adjusted risk ratio [ARR], 0.74 [95% CI, 0.59 to 0.93]). The risks of surgery and adverse events were higher in older-onset UC (20.5% vs. 3.1%; ARR, 8.92 [95% CI, 4.13 to 19.27], 25.3% vs. 9.1%; ARR, 2.19 [95% CI, 1.22 to 3.92], respectively). Four deaths occurred, all involving older-onset UC. The risks of infection and venous thrombosis were also higher in older-onset UC (18.1% vs. 8.6%, 7.2% vs. 0.5%, respectively). CONCLUSIONS: Older-onset was associated with a lower effectiveness of intravenous steroids with higher risks of surgery and adverse events in UC.
Subject(s)
Colitis, Ulcerative , Administration, Intravenous , Aged , Cohort Studies , Colitis, Ulcerative/surgery , Humans , Retrospective Studies , Steroids/therapeutic useABSTRACT
BACKGROUND: Bowel ultrasonography is a non-invasive imaging tool that can repeatedly monitor ulcerative colitis (UC) activity. AIM: This study aimed to determine whether early transabdominal or transperineal ultrasonography changes can predict subsequent clinical response to induction therapy in patients with UC. METHODS: This single-centre prospective study explored ultrasonographic predictors for clinical remission (patient-reported outcome-2 ≤ 1 with no rectal bleeding subscore) at week 8 in patients with active UC who underwent induction therapy, in comparison with faecal calprotectin and C-reactive protein (measured at baseline, week 1 and week 8). Predictive factors were assessed using multivariable regression models and receiver-operating-characteristic curve analysis. RESULTS: A total of 100 patients were analysed, of which 54 achieved remission at week 8. Baseline biomarker and ultrasonographic-parameter values were not predictive of remission. Contrastingly, change from baseline to week 1 in rectal bowel wall thickness measured using transperineal ultrasonography was an independent predictor of remission by week 8 (adjusted odds ratio is associated with a 1-mm decrease: 1.90 [95% confidence interval, 1.22-2.95]). In a subgroup analysis of the patients who did not achieve remission in 1 week, the predictive value of change in rectal bowel wall thickness remained high (AUC = 0.77 [95% confidence interval, 0.61-0.88]). CONCLUSION: Improvement in rectal bowel wall thickness measured using transperineal ultrasonography at week 1 predicts treatment success and potentially facilitates decision making during the early course of induction therapy in UC.
Subject(s)
Colitis, Ulcerative , Colitis, Ulcerative/diagnostic imaging , Colitis, Ulcerative/drug therapy , Humans , Leukocyte L1 Antigen Complex , Prospective Studies , Remission Induction , UltrasonographyABSTRACT
BACKGROUND: Real-world big data studies using health insurance claims databases require extraction algorithms to accurately identify target population and outcome. However, no algorithm for Crohn's disease (CD) has yet been validated. In this study we aim to develop an algorithm for identifying CD using the claims data of the insurance system. METHODS: A single-center retrospective study to develop a CD extraction algorithm from insurance claims data was conducted. Patients visiting the Kitasato University Kitasato Institute Hospital between January 2015-February 2019 were enrolled, and data were extracted according to inclusion criteria combining the Tenth Revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10) diagnosis codes with or without prescription or surgical codes. Hundred cases that met each inclusion criterion were randomly sampled and positive predictive values (PPVs) were calculated according to the diagnosis in the medical chart. Of all cases, 20% were reviewed in duplicate, and the inter-observer agreement (Kappa) was also calculated. RESULTS: From the 82,898 enrolled, 255 cases were extracted by diagnosis code alone, 197 by the combination of diagnosis and prescription codes, and 197 by the combination of diagnosis codes and prescription or surgical codes. The PPV for confirmed CD cases was 83% by diagnosis codes alone, but improved to 97% by combining with prescription codes. The inter-observer agreement was 0.9903. CONCLUSIONS: Single ICD-code alone was insufficient to define CD; however, the algorithm that combined diagnosis codes with prescription codes indicated a sufficiently high PPV and will enable outcome-based research on CD using the Japanese claims database.
Subject(s)
Algorithms , Crohn Disease/diagnosis , Adult , Crohn Disease/drug therapy , Crohn Disease/surgery , Cross-Sectional Studies , Databases, Factual , Drug Prescriptions/statistics & numerical data , Female , Hospitals, University , Humans , Japan , Male , Middle Aged , Retrospective Studies , Surgical Procedures, Operative/statistics & numerical dataABSTRACT
A 28-year-old woman was hospitalized for cardiac tamponade caused by tuberculous pericarditis. She was taking ustekinumab (UST) for Crohn's disease. UST is not considered to significantly increase the risk of developing serious infections, including tuberculosis. However, there is still a risk of Mycobacterium tuberculosis reactivation. Therefore, for patients on concurrent UST and antituberculosis medication, a close collaboration among specialists in infectious diseases, cardiology, and gastroenterology is necessary.
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PURPOSE: Surgeon's tactile sense is restricted during laparoscopic surgery. We aim to develop a softness sensing probe for endometriosis. Identification of the boundary of the lesion through a tactile sensor during laparoscopic surgery can provide an appropriate cut line, reducing excessive cut. METHOD: We expand our acoustic reflection-based sensing to the proposed probe, which has three force-sensing points to measure the softness of the object. The compensation of the sensor posture with the three sensor outputs was additionally proposed. This sensor has a simple structure and no electrical elements in the part inserted into the body. The sensing principle was verified using the theoretical analysis. Fundamental experiment to make the estimation model and evaluation test with the simulated environment were conducted. RESULT: The fundamental experiment showed that different softness can be estimated and that leave-one-out cross-validation resulted that the root-mean-square-error of the softness estimation was 31.5 kPa within the range of 7.5° in the probe posture. Samples which have similar softness as normal and lesioned uterus were used for the evaluation test using laparoscopic box trainer and a general trocar. Six participants operated the sensor, and the results showed that the samples were significantly discriminated by the softness estimated. CONCLUSION: The experimental results showed that the sensor can estimate the softness while compensating the posture and discriminate model samples of normal and lesioned uterus in the simulated environment, indicating the possibility of boundary identification between normal and lesioned tissues during laparoscopic surgery of endometriosis.
Subject(s)
Acoustics , Endometriosis/surgery , Laparoscopy/instrumentation , Surgery, Computer-Assisted/instrumentation , Touch , Uterus/surgery , Computer Simulation , Elastic Modulus , Equipment Design , Female , Finite Element Analysis , Humans , Surgical Instruments , Young AdultABSTRACT
BACKGROUND AND AIM: 5-Aminosalicylic acid (5-ASA) is a fundamental treatment for mild-to-moderate ulcerative colitis (UC). 5-ASA is taken up into the colonic mucosa and metabolized to N-acetyl-5-ASA (Ac-5-ASA). Few studies have assessed whether mucosal 5-ASA and Ac-5-ASA concentrations are associated with endoscopic remission. This study aimed to investigate differences in 5-ASA and Ac-5-ASA concentrations according to endoscopic activity. METHODS: This single-center, prospective, cross-sectional study was conducted between March 2018 and February 2019. UC patients who were administered with 5-ASA medication for at least 8 weeks before sigmoidoscopy were enrolled. Mucosal 5-ASA and Ac-5-ASA concentrations were measured using liquid chromatography with tandem mass spectrometry. The primary endpoint was defined as the difference in mucosal concentrations of 5-ASA and Ac-5-ASA, according to the Mayo endoscopic subscore (MES). RESULTS: Mucosal concentrations were analyzed in 50 patients. In the sigmoid colon, the median 5-ASA concentration in patients with MES of 0 (17.3 ng/mg) was significantly higher than MES ≥ 1 (6.4 ng/mg) (P = 0.019). The median 5-ASA concentrations in patients with Ulcerative Colitis Endoscopic Index of Severity ≤ 1 (16.4 ng/mg) were also significantly higher than in patients with Ulcerative Colitis Endoscopic Index of Severity ≥ 2 (4.63 ng/mg) (P = 0.047). In the sigmoid colon, the concentration of Ac-5-ASA was higher in patients with MES of 0 (21.2 ng/mg) than in patients with MES ≥ 1 (5.81 ng/mg) (P = 0.022). CONCLUSIONS: The present study showed that mucosal Ac-5-ASA concentrations, as well as 5-ASA concentrations, are higher in UC patients with endoscopic remission. Ac-5-ASA may be useful for a biomarker of 5-ASA efficacy.
Subject(s)
Aminosalicylic Acids/metabolism , Colitis, Ulcerative/drug therapy , Intestinal Mucosa/metabolism , Mesalamine/therapeutic use , Sigmoidoscopy , Adult , Biomarkers/metabolism , Colitis, Ulcerative/diagnosis , Colitis, Ulcerative/metabolism , Colon, Sigmoid/metabolism , Cross-Sectional Studies , Female , Humans , Male , Mesalamine/metabolism , Middle Aged , Prospective Studies , Remission Induction , Treatment OutcomeABSTRACT
BACKGROUND/AIMS: 5-Aminosalicylic acid (ASA) causes intolerance reactions in some patients. This study was performed to examine the prognosis of patients with ulcerative colitis (UC) and 5-ASA intolerance, and to evaluate the potential interaction between 5-ASA intolerance and the intestinal microbiota. METHODS: We performed a retrospective cohort study of patients with UC who visited participating hospitals. The primary endpoint was to compare the incidence of hospitalization within 12 months between the 5-ASA intolerance group and the 5-ASA tolerance group. The secondary endpoint was to compare the risk of adverse clinical outcomes after the start of biologics between the 2 groups. We also assessed the correlation between 5-ASA intolerance and microbial change in an independently recruited cohort of patients with UC. RESULTS: Of 793 patients, 59 (7.4%) were assigned to the 5-ASA intolerance group and 734 (92.5%) were assigned to the 5-ASA tolerance group. The admission rate and incidence of corticosteroid use were significantly higher in the intolerance than tolerance group (P< 0.001). In 108 patients undergoing treatment with anti-tumor necrosis factor biologics, 5-ASA intolerance increased the incidence of additional induction therapy after starting biologics (P< 0.001). The 5-ASA intolerance group had a greater abundance of bacteria in the genera Faecalibacterium, Streptococcus, and Clostridium than the 5-ASA tolerance group (P< 0.05). CONCLUSIONS: In patients with UC, 5-ASA intolerance is associated with a risk of adverse clinical outcomes and dysbiosis. Bacterial therapeutic optimization of 5-ASA administration may be important for improving the prognosis of patients with UC.
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BACKGROUND: Indigo naturalis (IN) consists of ligands for the aryl hydrocarbon receptor and exhibits anti-inflammatory effects. Previously, we demonstrated that an 8-week treatment with oral IN is effective in inducing a clinical response in patients with ulcerative colitis (UC). Some UC patients with proctitis are refractory to topical mesalamine or corticosteroids and therefore require an alternative topical treatment. OBJECTIVES: We aimed to prospectively evaluate the safety and efficacy of IN suppositories in UC patients. METHOD: We performed an open-label, single-center, prospective pilot study from February 2018 to October 2018. A total of 10 patients with active UC, who had moderate to severe inflammation from the rectum to the sigmoid colon, were enrolled. The patients received a daily dose of 50 mg IN suppository for 4 weeks. The primary endpoint was safety at week 4. RESULTS: Although 1 patient experienced anal pain, no serious adverse events were observed. At week 4, the rates of clinical remission and mucosal healing were 30 and 40%, respectively. Mayo rectal bleeding subscores significantly improved after treatment (1.80 ± 0.13 vs. 0.90 ± 0.28; p = 0.009). Approximately 80% of the patients with a baseline Mayo endoscopic subscore in the rectum (r-MES) of 2 achieved mucosal healing, but those with a baseline r-MES of 3 did not. CONCLUSIONS: We found that 4 weeks of IN suppository can be tolerated by UC patients, but its efficacy was limited by the severity of the disease. Further investigation will be needed in order to confirm the optimum dose of IN suppository for patients with UC.
Subject(s)
Colitis, Ulcerative/drug therapy , Drugs, Chinese Herbal/administration & dosage , Induction Chemotherapy/methods , Proctitis/drug therapy , Administration, Topical , Adolescent , Adult , Aged , Colitis, Ulcerative/complications , Drugs, Chinese Herbal/adverse effects , Female , Gastrointestinal Hemorrhage/chemically induced , Humans , Induction Chemotherapy/adverse effects , Male , Middle Aged , Pilot Projects , Proctitis/etiology , Prospective Studies , Rectal Diseases/chemically induced , Severity of Illness Index , Suppositories , Treatment Outcome , Young AdultABSTRACT
BACKGROUND: We recently reported the efficacy of indigo naturalis (IN) in patients with active ulcerative colitis (UC) in a randomized controlled trial (INDIGO study). However, few studies have been conducted to investigate whether IN is effective even in treatment-refractory cases, such as in those with steroid dependency and anti-TNF refractoriness. METHODS: In the INDIGO study, 86 patients with active UC were randomly assigned to an IN group (0.5-2.0 g daily) or placebo group. The rate of clinical response (CR), mucosal healing (MH), and change in fecal calprotectin (FCP) levels was compared between refractory [patients with steroid-dependent disease, previous use of anti-TNF-α, and concomitant use of immunomodulators (IM)] and non-refractory patients. We also analyzed factors predicting CR and MH at week 8. RESULTS: The rates of CR of IN group were significantly higher than placebo group, even in patients with steroid-dependent disease (p < 0.001), previous use of anti-TNF-α (p = 0.002), and concomitant use of IM (p = 0.013). The rates of MH in IN group were significantly higher than in placebo group in patients with steroid-dependent disease (p = 0.009). In the IN group, median FCP levels, at week 8, were significantly lower than baseline in patients with steroid-dependent disease and patients with the previous use of anti-TNF-α (p < 0.001, respectively). Multivariate analysis indicated that the previous use of anti-TNF-α was not a predictive factor for CR and MH at week 8. CONCLUSIONS: In a sub-analysis of data from a randomized placebo-controlled trial, we found that IN may be useful even in patients with steroid-dependent disease and patients with the previous use of anti-TNF-α.
Subject(s)
Colitis, Ulcerative/drug therapy , Drugs, Chinese Herbal/therapeutic use , Intestinal Mucosa/pathology , Wound Healing/drug effects , Adult , Colitis, Ulcerative/pathology , Feces/chemistry , Female , Humans , Immunologic Factors/therapeutic use , Leukocyte L1 Antigen Complex/analysis , Male , Middle Aged , Retreatment , Severity of Illness Index , Steroids/therapeutic use , Treatment Outcome , Tumor Necrosis Factor Inhibitors/therapeutic use , Young AdultABSTRACT
This study examined the relationship between the recognition of movement and actual movement during the standing long jump. A total of 11 healthy elementary school children from 10 to 11 years of age participated in this study. Participants conducted standing long jumps (the target movement) after receiving video instruction. They were then tested on their recognition of the target movement according to an image. A total of 12 markers were then attached to each participant to measure the actual movements taken during subsequent performances of the target movement. They were then tested on the recognition of their own movements (a self-evaluation). The results were as follows: maximum shoulder angle was observed prior to each jump; this became successively lower in the image review, actual movement, and self-evaluation procedures. Knee flexion angle successively decreased in the actual, target, self-evaluation, and image movements during the railway crossing procedure. While jumping, the maximum shoulder angle was significantly larger in the target movement than the actual (P < .01) movement, but the actual movement was significantly lower than the image (P < .001) and self-evaluation (P < .001) movements. The angle between the perpendicular from the acromion and the line segment connecting the acromion to the lateral malleolus successively decreased in the target, image, self-evaluation, and actual movements. Thus, there were obvious points at which it was either easier or more difficult for subjects to recognize movements. Points of relative ease and difficulty were also identified during performance of the target movement.
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This research aims to clarify the stride adjustment in the approach of the 400-m hurdles, and to examine the relationship with 400-m hurdle performance. Seven male 400-m hurdlers volunteered for this study. Participants ran three times from the start to the second hurdle. The standard deviation of toe-hurdle distance and standard deviation of stride length at each step from the start to the first hurdle were calculated. The maximum value of the standard deviation of toe-hurdle distance was defined as the position at which the athlete starts stride adjustment. The relationships between each variable, 400-m hurdle personal best, and the ratio of 400-m hurdle personal best and 400-m running personal best (400 m/400-m hurdles) were examined. Results concluded that standard deviation of toe-hurdle distance gradually increased after the start, reached the maximum value in the latter half of the approach section, and then decreased until the takeoff. Standard deviation of stride length increased significantly from 4 steps before the takeoff. From these trends, it was suggested that athletes seemed to start stride adjustment from the middle stage to the latter half of the approach by sensing stride error accumulation in the middle of the approach. The strides immediately before the takeoff were markedly involved in stride adjustment. Furthermore, the stride adjustment technique to reduce maximum accumulation error of stride evaluated in the approach section was considered associated with the smooth running of the entire 400-m hurdle race.