Successful Fistula Closure After Treatment with Colostomy and Infliximab in a Patient with Ulcerative Colitis Complicated by Rectovaginal Fistula.

The patient was a 50-year-old Japanese woman who was diagnosed with total-colitis-type ulcerative colitis (UC) at the age of 26 years. She was treated with mesalazine and azathioprine, and her disease activity was well controlled. At the age of 50 years, the patient was experiencing fever, abdominal pain, diarrhea, bloody stool, and anal pain, which led to a diagnosis of a relapse of UC. Although steroid therapy was administered and tended to improve her symptoms, fecaloid vaginal discharge occurred, and rectovaginal fistula (RVF) was confirmed. Colostomy was performed, and infliximab was initiated as maintenance therapy for UC. All symptoms improved, and RVF closure was confirmed 6 months after the initiation of infliximab. To date, she has been free from relapse of UC. There have been only a few reports of UC complicated by RVF, and this condition is often difficult to treat. To the best of our knowledge, no other case of UC complicated by RVF in which the fistula was closed after treatment with colostomy and infliximab has been previously reported; thus, our report of the present case is valuable to the literature.

Identifying Kawasaki Disease With a Low Coronary Artery Aneurysm Risk.

INTRODUCTION: Kawasaki disease (KD) patients with a high risk of coronary artery aneurysm (CAA) development are well characterized and targeted for intensified primary intravenous immunoglobulin (IVIG) treatment. However, the characteristics of KD patients with a low CAA risk are less well-known. METHODS: The present study was a secondary analysis of Prospective Observational study on STRAtified treatment with Immunoglobulin plus Steroid Efficacy for Kawasaki disease (Post RAISE), a multicenter, prospective cohort study of KD patients in Japan. The target of the analysis was patients with a Kobayashi score <5 who were predicted to respond to IVIG. The incidence of CAA during the acute phase, the primary outcome, was assessed based on all echocardiographic evaluations performed between week 1 (days 5-9) and month 1 (days 20-50) after the start of primary treatment. Multivariable logistic regression was used to identify the independent risk factors of CAA during the acute phase, based on which a decision tree was created to identify a subpopulation of patients with KD with a low CAA risk. RESULTS: Multivariate analysis found that a baseline maximum Z score >2.5, age <12 months at fever onset, nonresponsiveness to IVIG, low neutrophils, high platelets and high C-reactive protein were independent predictors of CAA during the acute phase. The decision tree created by using these risk factors identified 679 KD patients who had a low incidence of CAA during the acute phase (4.1%) and no medium or large CAA. CONCLUSIONS: The present study identified a KD subpopulation with a low CAA risk comprising around a quarter of the entire Post RAISE cohort.

Risk Factors Associated with Perineal and Vaginal Lacerations and Vaginal Removal in Total Laparoscopic Hysterectomy.

Objectives: This study aimed to identify risk factors associated with perineal and vaginal lacerations related to vaginal removal during total laparoscopic hysterectomy (TLH). Materials and Methods: We retrospectively assessed 134 patients who underwent TLH, of whom 44 (32.8%) had vaginal lacerations. Results: Univariate analysis revealed that for patients with myomas and adenomyosis, gonadotropin-releasing hormone agonist use and myomas with a transverse diameter of ≥5 cm were significant risk factors, while multiparity (vaginal delivery) was a protective factor for perineal and vaginal lacerations. Moreover, multivariate analysis indicated that multiparity was the only statistically significant protective factor. For cervical intraepithelial neoplasia, endometrial cancer, and endometrial hyperplasia, only a uterine transverse diameter of ≥5 cm was a significant risk factor for perineal or vaginal lacerations. Conclusion: For patients with large myomas, multiple vaginal delivery was a protective factor, and in patients with normal-sized uteri, a uterine transverse diameter of ≥5 cm was a risk factor for perineal or vaginal lacerations.

Predictive potential of age-group cut-off values of N-terminal pro-brain natriuretic peptide in Kawasaki disease.

BACKGROUND: The relationship between serum N-terminal pro-brain natriuretic peptide (NT-proBNP) and the clinical features of patients with Kawasaki disease (KD) has been the subject of research. Recent studies have revealed that serum NT-proBNP levels vary with age. We therefore aimed to determine the utility of age-stratified cut-off values for NT-proBNP in predicting coronary artery lesions (CALs) in patients with KD. METHODS: We retrospectively assessed the electronic medical records of patients who were hospitalized for KD or incomplete KD between January 1, 2015, and August 31, 2019. The patients were divided into high and normal NT-proBNP groups using age-stratified cut-off based on serum NT-proBNP levels measured immediately before KD treatment initiation. RESULTS: The study comprised 242 cases, including 71 and 171 cases in high and normal NT-proBNP groups, respectively. Thirty-seven of them (15.3%) were resistant to treatment; 15 (6.2%) had CALs, with a higher incidence in the high NT-proBNP group than in the normal NT-proBNP group. On multivariate logistic regression analysis, high serum NT-proBNP levels were significantly correlated to CALs (OR, 9.76; 95% CI, 2.64-36.2). On logistic regression analysis to compare the predictive accuracy of the age-stratified and fixed cut-off for CALs, the age-stratified cut-off values showed a larger area under the receiver operating characteristic curve than fixed cut-off value. CONCLUSIONS: Based on age-stratified cut-off values for serum NT-proBNP, high NT-proBNP levels at the time of diagnosis were significantly associated with CALs in patients with KD. Higher predictive accuracy for CALs of the age-stratified cut-off values was also suggested.

Risk Factors of Coronary Artery Aneurysms in Kawasaki Disease with a Low Risk of Intravenous Immunoglobulin Resistance: An Analysis of Post RAISE.

OBJECTIVE: To detect risk factors of coronary artery aneurysm (CAA) development in patients with Kawasaki disease determined to have a low risk for resistance to primary intravenous immunoglobulin (IVIG) treatment based on the Kobayashi score. STUDY DESIGN: This study included 1757 predicted IVIG responders from Prospective Observational study on STRAtified treatment with Immunoglobulin plus Steroid Efficacy for Kawasaki disease (Post RAISE), a large-scale, multicenter, prospective cohort study of Kawasaki disease in Japan. Predicted IVIG responders were defined as patients with Kawasaki disease with a Kobayashi score of <5, a predictive scoring system for IVIG resistance created in Japan. The primary outcome was CAA development at 1 month after disease onset. CAA was defined as a Z score of ≥2.5. Multivariable logistic regression was used to identify the independent risk factors of CAA. The variables for inclusion were identified based on univariate analysis results and previously reported risk factors of CAA. RESULTS: Among 1632 patients who had complete coronary outcome data, CAA developed in 90 patients (5.5%) at 1 month after disease onset. Multivariable analysis found that a baseline maximum Z score of >2.5, age of <12 months at fever onset, and nonresponsiveness to IVIG were significant, independent risk factors of CAA development at 1 month after disease onset. Among the risk factors, a baseline maximum Z score of >2.5 was most strongly associated with CAA development (OR, 7.1; 95% CI, 4.1-12.2; P ≤ .001). CONCLUSIONS: Predicted IVIG responders with CAA risk factors identified in this study may be candidates for future clinical trials of intensified primary IVIG treatment with prednisolone, cyclosporine or infliximab.

Evaluation of a Kawasaki Disease Risk Model for Predicting Coronary Artery Aneurysms in a Japanese Population: An Analysis of Post RAISE.

OBJECTIVES: To test the performance of the Son risk score, which was created to predict coronary artery abnormalities from baseline variables in North American patients with Kawasaki disease. STUDY DESIGN: The dataset from Post RAISE, the largest prospective cohort study of Japanese patients with Kawasaki disease to date, was used for the present study. With high risk defined as ≥3 points, sensitivity, specificity, positive predictive value, and negative predictive value for coronary artery abnormality development were calculated. To evaluate the effect of each risk factor in the Son score, the OR and 95% CIs were calculated using logistic regression analysis with the presence of coronary artery abnormality at 1 month after disease onset. RESULTS: Post RAISE enrolled 2628 consecutive patients with Kawasaki disease, and 304 patients had a high-risk score, of whom 15.1% showed coronary artery abnormality. At the cutoff ≥3 points, the sensitivity was 37.7%, and the specificity was 87.2%. The maximum z score at baseline ≥2.0 (OR 3.5, 95% CI 2.3-5.2) and age <6 months at disease onset (OR 3.2, 95% CI 1.9-5.4), were significantly associated with coronary artery abnormality development. However, a high concentration of C-reactive protein was not associated with coronary artery abnormality. The area under the receiver operating characteristic curve for the Son score was 0.65 (95% CI 0.59-0.71). CONCLUSIONS: The Son score had insufficient sensitivity and good specificity in a Japanese cohort of patients with Kawasaki disease. Among the variables comprising the Son score, a large baseline z score and young age at disease onset were significant, independent predictors of coronary artery abnormality development.

Risk Factors of Coronary Artery Abnormalities and Resistance to Intravenous Immunoglobulin Plus Corticosteroid Therapy in Severe Kawasaki Disease: An Analysis of Post RAISE.

BACKGROUND: Coronary artery abnormalities (CAAs) still occur in patients with Kawasaki disease receiving intensified treatment with corticosteroids. We aimed to determine the risk factors of CAA development and resistance to intensified treatment in Post RAISE (Prospective Observational Study on Stratified Treatment With Immunoglobulin Plus Steroid Efficacy for Kawasaki Disease)-the largest prospective cohort of Kawasaki disease patients to date. METHODS: In Post RAISE, 2648 consecutive patients with Kawasaki disease were enrolled. The present study analyzed 724 patients predicted to be intravenous immunoglobulin (IVIG) nonresponders (Kobayashi score ≥5) who received intensified treatment consisting of IVIG plus prednisolone. The association between the baseline characteristics and CAA at 1 month after disease onset was examined. The association between the baseline characteristics and treatment resistance was also investigated. RESULTS: Maximum Z score at baseline ≥2.5 (odds ratio, 3.4 [95% CI, 1.5-7.8]), age at fever onset <1 year (odds ratio, 3.4 [95% CI, 1.6-7.4]), and nonresponsiveness to IVIG plus prednisolone treatment (odds ratio, 6.8 [95% CI, 3.3-14.0]) were independent predictors of CAA development. Nonresponsiveness to IVIG plus prednisolone was significantly associated with 8 baseline variables. Baseline total bilirubin (odds ratio, 1.4 [95% CI, 1.2-1.7]) was the only significant independent predictor other than the variables included in the Kobayashi score, enabling treatment resistance to be identified at diagnosis. The area under the ROC curve was 0.74 (95% CI, 0.69-0.79). At a cutoff point of 1.0, the sensitivity and specificity for predicting treatment resistance were 71% and 65%, respectively. CONCLUSIONS: In Post RAISE, younger age at fever onset, a larger maximum Z score at baseline, and nonresponsiveness to IVIG plus prednisolone were risk factors significantly associated with CAA development. Nonresponders were able to be identified at diagnosis based on the total bilirubin value. To prevent CAA, more intensified or adjunctive therapies using other agents, such as pulsed methylprednisolone, ciclosporin, infliximab, and Anakinra, should be considered for patients with these risk factors. Registration: URL: https://www.umin.ac.jp/ctr/; Unique identifier: UMIN000007133.

Decreased hemoglobin after initial treatment is associated with treatment resistance in Kawasaki disease in Kobayashi risk stratification.

BACKGROUND: Although Kawasaki disease (KD) is known to cause anemia, the relationship between its prognosis and hemoglobin level is less well known. METHODS: We herein performed a secondary analysis of data from a previous study (Post-RAISE). Children aged 6 months to 2 years at the time of KD diagnosis were enrolled. Decreased hemoglobin was defined as a decrease > 10% on post-treatment day 2 compared with the level prior to the initial therapy. RESULTS: Of 1253 KD cases, treatment resistance was observed in 209 (17%) and was significantly more frequent in the decreased hemoglobin group (37/167 vs. 172/1086, P = 0.041). Multivariable logistic regression analysis revealed that decreased hemoglobin was associated with resistance to the initial treatment (odds ratio 1.53; 95% confidence interval 1.00-2.33; P = 0.048). CONCLUSIONS: Decreased hemoglobin was significantly associated with resistance to initial treatment in patients with KD.

Efficacy and safety of intravenous immunoglobulin plus prednisolone therapy in patients with Kawasaki disease (Post RAISE): a multicentre, prospective cohort study.

BACKGROUND: The RAISE study showed that additional prednisolone improved coronary artery outcomes in patients with Kawasaki disease at high risk of intravenous immunoglobulin (IVIG) resistance. However, no studies have been done to test the steroid regimen used in the RAISE study. We therefore aimed to verify the efficacy and safety of primary IVIG plus prednisolone. METHODS: We did a multicentre, prospective cohort study at 34 hospitals in Japan. We included patients diagnosed with Kawasaki disease according to the Japanese diagnostic criteria, and excluded those who were treated at other hospitals before being transferred to a participating hospital. Patients who were febrile at diagnosis received primary IVIG (2 g/kg per 24 h) and oral aspirin (30 mg/kg per day) until the fever resolved, followed by oral aspirin (5 mg/kg per day) for 2 months after Kawasaki disease onset. We stratified patients using the Kobayashi score into predicted IVIG non-responders (Kobayashi score ≥5) or predicted IVIG responders (Kobayashi score <5). For predicted non-responders, each hospital independently decided whether to add prednisolone (intravenous injection of 2 mg/kg per day for 5 days) to the primary IVIG treatment, according to their respective treatment policy, and we further divided these patients based on the primary treatment received. The primary endpoint was the incidence of coronary artery abnormalities determined by two-dimensional echocardiography at 1 month after the primary treatment in predicted non-responders treated with primary IVIG plus prednisolone. Coronary artery abnormalities were defined according to the criteria of the Japanese Ministry of Health and Welfare and of the American Heart Association (AHA). This study is registered with the University Hospital Medical Information Network Clinical Trials Registry, number UMIN000007133. FINDINGS: From July 1, 2012, to June 30, 2015, we enrolled 2628 patients with Kawasaki disease, of whom 724 (27·6%) were predicted IVIG non-responders who received IVIG plus prednisolone as primary treatment. 132 (18·2%) of 724 patients did not respond to primary treatment. Among patients with complete data, coronary artery abnormalities were present in 40 (incidence rate 5·9%, 95% CI 4·3-8·0) of 676 patients according to the AHA criteria or in 26 (3·8%, 2·5-5·6) of 677 patients according to the Japanese criteria. Serious adverse events were reported in 12 (1·7%) of 724 patients treated with primary IVIG plus prednisolone; two of these patients had hypertension and bacteraemia that was probably related to prednisolone. One patient died possibly due to severe inflammation from the Kawasaki disease itself. INTERPRETATION: Primary IVIG plus prednisolone therapy in this study had an effect similar to that seen in the RAISE study in reducing the non-response rate and decreasing the incidence of coronary artery abnormalities. A primary IVIG and prednisolone combination therapy might prevent coronary artery abnormalities and contribute to lowering medical costs. FUNDING: Tokyo Metropolitan Government Hospitals and the Japan Kawasaki Disease Research Center.