PubMed | Japan Community Healthcare Organization JCHO Gunma Chuo Hospital, JCHO Tokyo Joto Hospital, Saitama Medical Center, JCHO Hokkaido Hospital and 10 more.
Type: Journal Article | Journal: Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy | Year: 2016
We surveyed the status of community-acquired infections involving four extended-spectrum -lactamase (ESBL)-producing bacteria (Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Proteus mirabilis) isolated from clinical specimens from 11 social insurance hospitals in Japan in 2012. These are member hospitals of the Japan Community Healthcare Organization, an independent administrative hospital organization. The isolation rates for E.coli, K.pneumoniae, K.oxytoca, and P.mirabilis were 14.0% (165/1176), 3.3% (16/480), 3.1% (4/130), and 15.9% (17/107), respectively. The CTX-M-9 group, the most frequently detected genotype, was found in 77.0% (127/165) of E.coli and 43.8% (7/16) of K.pneumoniae isolates. Among K.oxytoca isolates, 75% (3/4) were the CTX-M-1 group, and all 17 P.mirabilis strains were the CTX-M-2 group. ESBL-producing bacteria isolation rates in each hospital ranged from 5.8% to 21.5% (median 9.5%), and the proportion of community-acquired infections among ESBL-producing bacteria isolates ranged from 1.6% to 30.8% (median 11.4%) in each hospital. Overall, the rates of ESBL-producing bacterial infection in all community-acquired infections and in all hospital infections were 10.6% (115/1081) and 10.7% (87/812), respectively. The ESBL-producing bacteria are not limited to certain regions or hospitals but are spreading in communities throughout Japan.
PubMed | University of Minnesota, Kobe City Medical Center General Hospital, Tokyo Metropolitan Hiroo Hospital, Harvard University and 11 more.
Type: | Journal: International journal of cardiology | Year: 2016
Renal dysfunction is a common comorbidity in acute heart failure (AHF) patients. The prognostic significance of early treatment with tolvaptan in AHF patients complicated with renal dysfunction has not been elucidated.Post hoc analysis was performed on a randomized clinical study for prespecified prognostic endpoints and prespecified subgroups. 217 AHF patients with renal dysfunction (eGFR 15 to 60mL/min/1.73m(2)) were randomized within 6h from hospitalization to either tolvaptan treatment for 2days or conventional treatment. The primary outcome was the combined endpoint of all-cause death and HF readmission.During follow-up (636days, median) 99 patients experienced combined endpoint and 53 patients died. There was no significant difference in event-free survival rate for either the combined events (Log-rank: P=0.197) or all-cause death (Log-rank: P=0.894) between tolvaptan and conventional groups. In prespecified subgroup analysis, in patients whose BUN/creatinine ratio was above the median (>20), tolvaptan significantly reduced the risk of combined events (HR: 0.52, 95% CI: 0.30-0.91, P=0.021) with a significant interaction (P value for interaction=0.045). Likewise, in patients whose eGFR was 30mL/min/1.73m(2) or above, tolvaptan reduced the risk of combined events (HR: 0.54, 95% CI: 0.32-0.90, P=0.017) with a significant interaction (P value for interaction=0.015).Short-term use of tolvaptan in acute-phase in AHF with renal dysfunction showed a neutral effect on prognosis. Patients with relatively preserved renal function and relatively high BUN/creatinine ratios are potentially favorable subgroups for treatment with tolvaptan.
Yoshimura N.,Tokyo Yamate Medical Center |
Watanabe M.,Tokyo Medical and Dental University |
Motoya S.,Sapporo Kosei General Hospital |
Tominaga K.,Dokkyo Medical University |
And 4 more authors.
Gastroenterology | Year: 2015
Background & Aims AJM300 is an orally active small-molecule antagonist of the α4 integrin subunit. We performed a randomized trial to investigate the efficacy and safety of AJM300 in patients with active ulcerative colitis (UC). Methods In a double-blind, placebo-controlled, phase 2a study, 102 patients with moderately active UC (Mayo Clinic scores of 6-10, endoscopic subscores ≤2, and rectal bleeding subscores ≤1) who had inadequate response or intolerance to mesalamine or corticosteroids were randomly assigned to receive AJM300 (960 mg) or placebo 3 times daily for 8 weeks. The primary end point was a clinical response at week 8, defined as a decrease in Mayo Clinic score of at least 3 points and a decrease of at least 30% from baseline, with a decrease in the rectal bleeding subscore of at least 1 point or an absolute rectal bleeding subscore of 0 or 1. Results Clinical response rates were 62.7% and 25.5% at week 8 in the AJM300 group and placebo group, respectively (odds ratio [OR] = 5.35; 95% confidence interval [CI]: 2.23-12.82; P =.0002). Rates of clinical remission (Mayo Clinic score ≤2 and no subscore >1) were 23.5% and 3.9% in the AJM300 group and placebo groups, respectively (OR = 7.81; 95% CI: 1.64-37.24; P =.0099), and rates of mucosal healing (endoscopic subscores of 0 or 1) were 58.8% and 29.4% (OR = 4.65; 95% CI: 1.81-11.90; P =.0014). No serious adverse event, including progressive multifocal leukoencephalopathy, was observed, although more investigations are needed to confirm the safety profile of this drug. Conclusions AJM300 was well tolerated and more effective than placebo in inducing clinical response, clinical remission, and mucosal healing in patients with moderately active UC. ClinicalTrials.jp no: JapicCTI-132293. © 2015 AGA Institute.
Okochi Y.,Tokyo Yamate Medical Center |
Tokuda H.,Tokyo Yamate Medical Center
Japanese Journal of Chest Diseases | Year: 2016
Respiratory tract infections in compromised hosts now pose problems in a variety of medical fields, as a result of the development of treatments for autoimmune diseases, transplantation therapy, among others, which involve the administration of immunosup- presants or biologic agents. Their pathogenesis is diverse, ranging from common bacterial infections to opportunistic infections. The appropriate prophylaxes for many respiratory tract infections are unclear, and early diagnosis and empiric treatment is required for all of them. In recent years, therapeutic strategies for compromised hosts have been developed against specific infections, such as pneumococcal pneumonia, tuberculosis, aspergillosis, and Pneumocystis pneumonia.
PubMed | Fukuoka University, Kyushu University, Sapporo Kosei General Hospital, Toho University and 2 more.
Type: Journal Article | Journal: Journal of gastroenterology | Year: 2016
Crohns disease (CD) and ulcerative colitis (UC) are two major forms of inflammatory bowel disease (IBD). Meta-analyses of genome-wide association studies (GWAS) have identified 163 susceptibility loci for IBD among European populations; however, there is limited information for IBD susceptibility in a Japanese population.We performed a GWAS using imputed genotypes of 743 IBD patients (372 with CD and 371 with UC) and 3321 controls. Using 100 tag single-nucleotide polymorphisms (SNPs) (P<510(-5)), a replication study was conducted with an independent set of 1310 IBD patients (949 with CD and 361 with UC) and 4163 controls. In addition, 163 SNPs identified by a European IBD GWAS were genotyped, and genetic backgrounds were compared between the Japanese and European populations.In the IBD GWAS, two East Asia-specific IBD susceptibility loci were identified in the Japanese population: ATG16L2-FCHSD2 and SLC25A15-ELF1-WBP4. Among 163 reported SNPs in European IBD patients, significant associations were confirmed in 18 (8 CD-specific, 4 UC-specific, and 6 IBD-shared). In Japanese CD patients, genes in the Th17-IL23 pathway showed stronger genetic effects, whereas the association of genes in the autophagy pathway was limited. The association of genes in the epithelial barrier and the Th17-IL23R pathways were similar in the Japanese and European UC populations.We confirmed two IBD susceptibility loci as common for CD and UC, and East Asian-specific. The genetic architecture in UC appeared to be similar between Europeans and East Asians, but may have some differences in CD.
PubMed | Tokyo Women's Medical University, Tohoku Rosai Hospital, Torii Clinic., Keio University and 8 more.
Type: | Journal: Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society | Year: 2017
The risk of developing colorectal cancer is higher in patients with ulcerative colitis (UC) than in the general population. Guidelines recommend surveillance colonoscopy (SCS) to reduce mortality; however, few studies have assessed physicians adherence to guidelines. This study was aimed to clarify the current status of SCS and adherence to guidelines through the characteristics of cancer/dysplasia surveillance for UC patients in Japan.A questionnaire was mailed to 541 physicians who attended meetings on inflammatory bowel disease.The respondents encountered a median of 100 UC cases. Thirty percent of the respondents had never managed a UC patient with cancer. Fifty-one percent of the respondents had never diagnosed colorectal cancer with UC. Forty-seven percent of the respondents considered total colitis and left-sided colitis as indications for SCS, and 38% performed SCS regardless of the disease extent. Sixty-three percent of the respondents started SCS at 7-10 years after UC onset, whereas 20% started SCS at 3 years or less. Fifty-two percent of the respondents obtained targeted biopsies only, and chromoendoscopy was employed by 49% of the respondents as a special technique for surveillance. The median number of biopsies at SCS was 5 per patient; it was 3 among patients performed by physicians who obtained targeted biopsies only and 7 among those performed by physicians who obtained step biopsies and targeted biopsies (p < 0.0001).A considerable proportion of the respondents did not follow the guidelines when selecting patients for surveillance and performing SCS. This article is protected by copyright. All rights reserved.
PubMed | Tokyo Women's Medical University, Showa University, Hyogo College of Medicine, Sapporo Kosei General Hospital and 5 more.
Type: | Journal: Journal of gastroenterology and hepatology | Year: 2016
Ulcerative colitis (UC) is a chronic inflammatory disease of the colon with an intractable, recurrent course. Although the goal of UC therapy has recently been to target mucosal healing, the molecular mechanism of mucosal healing remains unknown. In this study, we aimed to elucidate the molecular dynamics related to the proliferation and differentiation of intestinal epithelial cells (IECs) during cytapheresis therapy in a short duration.Endoscopy was performed in 26 patients with UC in multicentre hospitals, and biopsy specimens were collected from the rectum before and within two weeks after leukocytapheresis (LCAP). The expression of representative proteins in IECs and pathological findings were compared before and after LCAP.The expression of caudal type homeobox 2 (CDX2) and a hairy-related protein 1 (HES1) markedly increased after LCAP. Patients with endoscopic improvement after LCAP showed the expression of CDX2 before LCAP. Moreover, the number of goblet cells significantly increased after LCAP. Patients without endoscopic improvement after LCAP did not show the expression of CDX2 before LCAP. However, the expression of CDX2 markedly increased after LCAP.This study suggests that cytapheresis might induce CDX2 expression without affecting the cell proliferation; thus, resulting in mucosal healing with goblet cell restoration.
PubMed | Tokyo Yamate Medical Center, Tokyo University of Science, Center Hospital of the National Center for Global Health and Medicine Center Hospital and RIKEN
Type: Journal Article | Journal: Osteoarthritis and cartilage | Year: 2016
The aim of this work was to characterize the genome-wide DNA methylation profile of cartilage from three regions of tibial plateau isolated from patients with primary knee osteoarthritis (OA), providing the first DNA methylation study that reflects OA progression.The unique model system was used to section three regions of tibial plateau: the outer lateral tibial plateau (oLT), the inner lateral tibial plateau (iLT) and the inner medial tibial plateau (iMT) regions which represented the early, intermediate and late stages of OA, respectively. Genome-wide DNA methylation profile was examined using Illumina Infinium HumanMethylation450 BeadChip array. Comparisons of the iLT/oLT and iMT/oLT groups were carried out to identify differentially methylated (DM) probes (DMPs) associated with OA progression. DM genes were analyzed to identify the gene ontologies (GO), pathways, upstream regulators and networks.No significant DMPs were identified in iLT/oLT group, while 519 DMPs were identified in iMT/oLT group. Over half of them (68.2%) were hypo-methylated and enriched in enhancers and OpenSea. Upstream regulator analysis identified many microRNAs. DM genes were enriched in transcription factors, especially homeobox genes and in Wnt/-catenin signaling pathway. These genes also showed changes in expression when analyzed with expression profiles generated from previous studies.Our data suggested the changes in DNA methylation occurred at the late stage of OA. Pathways and networks enriched in identified DM genes highlighted potential etiologic mechanism and implicated the potential cartilage regeneration in the late stage of knee OA.
PubMed | Red Cross, Fukuoka University, Tokyo Medical and Dental University, Osaka City General Hospital and 13 more.
Type: Journal Article | Journal: Journal of Crohn's & colitis | Year: 2016
The efficacy of azathioprine for Crohns disease under adalimumab treatment remains obscure.In an open-labelled prospective study, we evaluated the efficacy of adalimumab with and without azathioprine in patients with active Crohns disease, who were nave to biologics and thiopurines. The patients were randomly assigned to subcutaneous administration of adalimumab [monotherapy group] or to exactly the same schedule of adalimumab with azathioprine [25-100mg daily] [combination group] for 52 Weeks. The primary endpoint was clinical remission at WWeek 26. We also evaluated the score for simple endoscopic severity of Crohns disease before the therapy and at WWeeks 26 and 52.A total of 176 patients were randomized to either the monotherapy group [n = 85] or to the combination group [n = 91]. Eighteen patients [21.2%] from the monotherapy group and 7 patients [7.7%] from the combination group withdrew owing to active disease, and 15 patients [16.5%] from the combination group and 1 patient [1.2%] from the monotherapy group withdrew due to side effects of the medications. Non-responder imputation analysis revealed that the remission rate at WWeek 26 did not differ between the monotherapy group and the combination group [71.8% vs 68.1%; OR 0.84, p = 0.63]. The rate of endoscopic improvement at WWeek 26 was significantly higher in the combination group [84.2%, n = 57] than in the monotherapy group [63.8%, n = 58] [p = 0.019].The clinical efficacy of a combination of adalimumab and azathioprine at WWeek 26 did not differ from that of adalimumab monotherapy in patients with Crohns disease nave to both medications.
PubMed | Red Cross, Tokyo Medical and Dental University, Yokosuka Kyosai Hospital, Tokyo Yamate Medical Center and Machida Municipal Hospital
Type: | Journal: Artificial organs | Year: 2016
Off-pump coronary artery bypass grafting (OPCAB) in patients with acute myocardial infarction (AMI) is difficult because of circulatory deterioration during displacement of the heart. At our institution, we performed minimally circulatory-assisted on-pump beating coronary artery bypass grafting (MICAB) in these patients. During MICAB, support flow was controlled at a minimal level to maintain a systemic blood pressure of approximately 100 mmHg and a pulmonary arterial systolic pressure of <30 mmHg, providing optimal pulsatile circulation for end-organ perfusion and prevention of heart congestion. From September 2006 to March 2012, MICAB was performed in 37 patients. Either emergent or urgent MICAB was performed in 27 patients following AMI because of hemodynamic instability during reconstruction. Elective MICAB was performed in the remaining 10 patients because of dilated left ventricle (LV) or small target coronary arteries. The details of bypass grafts, perioperative renal function, and early and mid-term morbidity and mortality were compared between the patients who received MICAB and the 37 consecutive patients who underwent OPCAB during the study period at our hospital. The assist flow indices (actual support flow/body surface area) during anastomosis to the left anterior descending artery, left circumflex artery, and right coronary artery were 0.950.48 L/min/m