Background: and Purpose To assess the long-term outcomes of intracranial dural arteriovenous fistula (DAVF) treated with stereotactic radiosurgery (SRS) alone or embolization and SRS (Emb-SRS) and to develop a grading system for predicting DAVF obliteration. Methods: This multi-institutional retrospective study included 200 patients with DAVF treated with SRS or Emb-SRS. We investigated the long-term obliteration rate and obliteration-associated factors. We developed a new grading system to estimate the obliteration rate. Additionally, we compared the outcomes of SRS and Emb-SRS by using propensity score matching. Results: The 3- and 4-year obliteration rates were 66.3% and 78.8%, respectively. The post-SRS hemorrhage rate was 2%. In the matched cohort, the SRS and Emb-SRS groups did not differ in the rates of obliteration (P=0.54) or post-SRS hemorrhage (P=0.50). In multivariable analysis, DAVF location and cortical venous reflux (CVR) were independently associated with obliteration. The new grading system assigned 2, 1, and 0 points to DAVFs in the anterior skull base or middle fossa, DAVFs with CVR or DAVFs in the superior sagittal sinus or tentorium, and DAVFs without these factors, respectively. Using the total points, patients were stratified into the highest (0 points), intermediate (1 point), or lowest (≥2 points) obliteration rate groups that exhibited 4-year obliteration rates of 94.4%, 71.3%, and 60.4%, respectively (P<0.01). Conclusions SRS-based therapy achieved DAVF obliteration in more than three-quarters of the patients at 4 years of age. Our grading system can stratify the obliteration rate and may guide physicians in treatment selection.

BACKGROUND/AIMS: The pharmacokinetics of tacrolimus (TAC) is known to be largely influenced by single-nucleotide polymorphisms (SNPs) in CYP3A5. Patients starting TAC require careful dose adjustment, owing to the wide range of optimal dosages, depending on their CYP3A5 expression status. Here, we evaluated whether individualization of TAC dosages based on CYP3A5 SNPs would improve its therapeutic efficacy in ulcerative colitis. METHODS: Twenty-one patients were prospectively treated, with their initial dosage adjusted according to their CYP3A5 status (0.1, 0.15, and 0.2 mg/kg/day for CYP3A5*3/*3, CYP3A5*1/*3, and CYP3A5*1/*1, respectively). Their clinical outcomes were compared with those of patients treated with a fixed dose (0.1 mg/kg/day). RESULTS: The first blood trough level of CYP3A5 expressors, CYP3A5*1/*3 or CYP3A5*1/*1, and the overall rate in achieving the target blood trough level within a week in the individualized-dose group were significantly higher than those in the fixed-dose group (5.15±2.33 ng/mL vs. 9.63±0.79 ng/mL, P=0.035 and 12.5% vs. 66.7%, P=0.01). The remission rate at 2 weeks in the expressors was as high as that in the nonexpressors, CYP3A5*3/*3, in the individualized-dose group. CONCLUSIONS: Individualized TAC treatment is effective against ulcerative colitis regardless of the CYP3A5 genotype.
Colitis, Ulcerative ; Cytochrome P-450 CYP3A ; Genotype ; Humans ; Pharmacokinetics ; Polymorphism, Single Nucleotide ; Prospective Studies ; Tacrolimus ; Ulcer

BACKGROUND: Age-related musculoskeletal diseases are becoming increasingly burdensome in terms of both individual quality of life and medical cost. We intended to establish a large population-based cohort study to determine environmental, lifestyle, and genetic risk factors of musculoskeletal and other age-related diseases, and to clarify the association between vitamin D status and such diseases. METHODS: We targeted 34,802 residents aged 40-74 years living in areas of northern Niigata Prefecture, including Sekikawa Village, Awashimaura Village, and Murakami City (Murakami region). The baseline questionnaire survey, conducted between 2011 and 2013, queried respondents on their lifestyle and environmental factors (predictors), and self-reported outcomes. Plasma 25-hydroxyvitamin D (25[OH]D) concentration, an indicator of vitamin D status, was determined with the Liaison® 25OH Vitamin D Total Assay. The primary outcome of this study was osteoporotic fracture; other outcomes included age-related diseases including knee osteoarthritis, perception of chronic pain, dementia, and long-term care insurance use. Mean ages of men and women were 59.2 (SD = 9.3, N = 6907) and 59.0 (SD = 9.3, N = 7457) years, respectively. From the blood samples provided by 3710 men and 4787 women, mean 25(OH)D concentrations were 56.5 (SD = 18.4) nmol/L (22.6 ng/mL) and 45.4 (SD = 16.5) nmol/L (18.2 ng/mL), respectively. DISCUSSION Follow-up surveys are planned every 5 years for 15 years, and incident cases of our targeted diseases will be followed at hospitals and clinics in and nearby the cohort area. We anticipate that we will be able to clarify the association between vitamin D status and multiple disease outcomes in a Japanese population.
Aged ; Aging ; Cohort Studies ; Epidemiologic Research Design ; Female ; Humans ; Incidence ; Japan ; epidemiology ; Male ; Middle Aged ; Musculoskeletal Diseases ; epidemiology ; prevention & control ; Predictive Value of Tests ; Quality of Life ; Risk Factors ; Vitamin D ; analogs & derivatives ; blood

BACKGROUND/AIMS: Mesalazine is an effective drug for treating ulcerative colitis (UC), but causes allergic symptoms in a few cases. Therefore, the objective of this study was to evaluate the usefulness of the drug-induced lymphocyte stimulation test (DLST) for the diagnosis of mesalazine allergy. METHODS: Patients with UC treated with mesalazine with or without a history of associated adverse events (AEs) were enrolled at Kyorin University Hospital from July 2016 to April 2017. RESULTS: The DLST was performed in 104 patients with UC, of which 24 had a history of AEs due to mesalazine treatment. The control value of DLST was 337.4±296.3 counts per minute (cpm) in the AE+ group and 408.0±371.9 cpm in the AE− group. The measured value of DLST was 578.8±424.7 cpm in the AE+ group and 476.5±471.8 cpm in the AE− group. The stimulation index (SI) was 243.9%±291.1% in the AE+ group and 119.8%±53.0% in the AE− group. The SI value and DLST positivity were significantly higher in the AE+ group than in the AE− group (P=0.030 and P=0.029, respectively). The test sensitivity and specificity were 0.240 and 0.805, respectively, and the false-positive and false-negative rate was 0.195 and 0.760, respectively. CONCLUSIONS: The DLST for mesalazine showed low sensitivity and high specificity, suggesting that it may be useful for the definitive diagnosis of allergy to mesalazine.
Colitis, Ulcerative ; Diagnosis ; Humans ; Hypersensitivity* ; Lymphocyte Activation* ; Lymphocytes* ; Mesalamine* ; Sensitivity and Specificity

BACKGROUND/AIMS: Endoscopic placement of self-expandable metal stents (SEMSs) has emerged as a palliative treatment for malignant gastric outlet obstruction (GOO). Although covered SEMSs can prevent tumor ingrowth, frequent migration of covered SEMSs may offset their advantages in preventing tumor ingrowth. METHODS: We conducted this multicenter, single-arm, retrospective study at six tertiary referral centers to evaluate the safety and efficacy of a partially covered SEMS with an uncovered large-bore flare at the proximal end as an antimigration system in 41 patients with symptomatic malignant GOO. The primary outcome was clinical success, and the secondary outcomes were technical success, stent dysfunction, adverse events, and survival after stent placement. RESULTS: The technical and clinical success rates were 100% and 95%, respectively. Stent dysfunctions occurred in 17 patients (41%), including stent migration in nine (23%), tumor ingrowth in one (2%), and tumor overgrowth in four (10%). Two patients (5%) developed adverse events: one pancreatitis and one perforation. No procedure-related death was observed. CONCLUSIONS: A novel partially covered SEMS with a large-bore flare proximal end was safe and effective for malignant GOO but failed to prevent stent migration. Further research is warranted to develop a covered SEMS with an optimal antimigration system.
Gastric Outlet Obstruction* ; Humans ; Palliative Care ; Pancreatitis ; Retrospective Studies ; Self Expandable Metallic Stents ; Stents* ; Tertiary Care Centers

　　A 48-year-old man with jaundice was referred to our hospital. Endoscopic retrograde cholangiography showed primary sclerosing cholangitis. Endoscopic biliary drainage was not successful because of highly viscous bile, so we performed percutaneous trans-gallbladder drainage (PTGBD), which was able to reduce the total serum bilirubin level from 8 to 10mg/ml. Subsequently, an indwelling drainage catheter was placed in the gallbladder for 13 months. However, liver atrophy worsened with the gradual progression of hepatic failure. Twelve months later, he complained of dyspnea. Computed abdominal tomography showed that the drainage catheter had perforated the diaphragm and become exposed to the chest cavity. In spite of intensive care, the patient died of liver failure while waiting for a liver transplant. Careful attention should be paid to the possibility of this serious complication in such patients.

A 72-year-old woman was admitted to our department with a diagnosis of severe aortic stenosis was also diagnosed Inherited antithrombin deficiency was also diagnosed after she suffered from a pulmonary thromboembolic event 10 years previously and had been taking warfarin since then. On admission, her antithrombin activity was 53% of normal, and her PT-INR level was maintained around 2.5. Preoperative management of anticoagulation therapy included discontinuation of warfarin, and supplementation of antithrombin with heparin infusion. On the day of operation, antithrombin activity was maintained above 80% by administering antithrombin, and aortic valve replacement with a mechanical valve prosthesis was carried out under standard cardiopulmonary bypass support using heparin. Heparin infusion was continued with antithrombin supplementation until PT-INR recovered to round 2.5 with warfarin. Her intra- and postoperative courses did not show any thromboembolic events, and she was discharged 14 days after the surgery.

This is a report on a case of delirium due to a small amount of ketamine with voriconazole. A 58 year old male was treated for multiple myeloma and hip pain due to an extramedullary tumor following the administration of oxycodone, and voriconazole was administrated for his suspected mycotic pneumonia. His pain was refractory, so we started the administration of a small dose of ketamine (4 mg/hr) for analgesia, added to oxycodone. About 30 hours later, the delirium appeared but he complained of worsening hip pain, so we added 2 mg of ketamine rapidly. Immediately after the additional administration of ketamine, his delirium became more serious. We think the reason why a small amount of ketamine induced delirium is an interaction of ketamine and voriconazole. Ketamine is metabolized to norketamine, which is thought to be more harmless than ketamine, by cytochrome P 450 (CYP) (a part of by CYP3A4) and voriconazole is an inhibitor of CYP3A4. In cases of patients treated with voriconazole, ketamine should be more carefully administrated.

Bacteremia from dental disease is the most important cause of infective endocarditis in patients with heart valve disease. However, the prevalence of dental disease in patients undergoing valve surgery has not been clarified. One hundred thirty-seven patients had a dental check-up before heart valve surgery, 82 patients (59.9%) had significant dental disease which could have caused bacteremia. All patients with the dental disease underwent extraction preoperatively. There was neither complication in extraction nor any influence on heart valve surgery. Postoperative hospital stay was not prolonged due to the extraction. During the mean follow-up period of 30 months, no infective endocarditis was seen. The prevalence of dental disease was high in patients undergoing heart valve surgery. Preoperative treatment of dental disease did not have a negative impact on the postoperative course and hospital stay in heart valve surgery.

1) The faculty development at each medical school from 2003 through 2005 was analysed.
2) The major themes in faculty development were problem based learning, tutorial, computer based testing, and clinical training.
3) Faculty development is considered an effective way to enhance the contributions of faculty members to medical education.