Search

Naoyuki Akashi,1 Tomio Umemoto,1 Hodaka Yamada,2 Takayuki Fujiwara,3 Kei Yamamoto,1 Yousuke Taniguchi,1 Kenichi Sakakura,1 Hiroshi Wada,1 Shin-ichi Momomura,1 Hideo Fujita1 1Division of Cardiovascular Medicine, Jichi Medical University Saitama Medical Center, Saitama, Japan; 2Division of Endocrinology and Metabolism, Jichi Medical University Saitama Medical Center, Saitama, Japan; 3Department of Cardiovascular Medicine, The University of Tokyo Hospital, Tokyo, JapanCorrespondence: Tomio Umemoto, Division of Cardiovascular Medicine, Jichi Medical University Saitama Medical Center, 1-847 Amanuma-cho, Omiya-ku, Saitama, 330-8503, Japan, Tel +81-48-647-2111, Fax +81-48-648-5188, Email to-ume@omiya.jichi.ac.jpPurpose: Dipeptidyl peptidase-4 (DPP-4) inhibitors increase endothelial progenitor cells (EPCs) in peripheral blood circulation. However, the underlying mechanisms and effects on vascular endothelial function remain unclear. We evaluated whether the DPP-4 inhibitor teneligliptin increases circulating EPCs by inhibiting stromal-derived factor-1α (SDF-1α) and improves flow-mediated vascular dilatation (FMD) in type 2 diabetes mellitus patients with acute coronary syndrome (ACS) or its risk factors.Patients and Methods: This single-center, open-label, prospective, randomized controlled trial evaluated 17 patients (hemoglobin A1c ≤ 7.5% and peak creatinine phosphokinase < 2000 IU/mL) with ACS or a history of ACS or multiple cardiovascular risk factors. Metabolic variables of glucose and lipids, circulating EPCs, plasma DPP-4 activity, and SDF-1α levels, and FMD were evaluated at baseline and 28 ± 4 weeks after enrollment. Patients were randomly assigned to either the teneligliptin (n = 8) or control (n = 9) groups.Results: The DPP-4 activity (∆− 509.5 ± 105.7 vs ∆32.8 ± 53.4 μU/mL) and SDF-1α levels (∆− 695.6 ± 443.2 vs ∆11.1 ± 193.7 pg/mL) were significantly decreased after 28 weeks in the teneligliptin group than those in the control group. The number of EPCs showed an increasing trend in the teneligliptin treated group; albeit this did not reach statistical significance. Glucose and lipid levels were not significantly different between the groups before and after 28 weeks. However, FMD was significantly improved in the teneligliptin group when compared to the control group (∆3.8% ± 2.1% vs ∆− 0.3% ± 2.9%, P=0.006).Conclusion: Teneligliptin improved FMD through a mechanism other than increasing the number of circulating EPCs.Keywords: endothelial progenitor cell, teneligliptin, DPP-4 inhibitor, flow-mediated dilation, type 2 diabetes mellitus

Takashi Fujiwara,1,2 Chisato Miyakoshi,3 Takashi Kanemitsu,4 Yasuyuki Okumura,5 Hironobu Tokumasu2,6 1Department of Management, Clinical Research Center, Kurashiki Central Hospital, Okayama, Japan; 2Department of Public Health Research, Kurashiki Clinical Research Institute, Okayama, Japan; 3Department of Pediatrics, Kobe City Medical Center General Hospital, Hyogo, Japan; 4Medical Affairs Division, Chugai Pharmaceutical Co., Ltd, Tokyo, Japan; 5Department of Psychiatry and Behavioral Science, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan; 6Real World Data Co., Kyoto, JapanCorrespondence: Takashi FujiwaraDepartment of Management, Clinical Research Center, Kurashiki Central Hospital, 1-1-1 Miwa, Kurashiki City, Okayama, JapanTel +81-86-422-0210Fax +81-86-421-3424Email tf14817@kchnet.or.jpPurpose: Routinely collected data are useful for epidemiological study in hemophilia, but few studies validated the algorithm accuracy. We aimed to develop and validate algorithms to identify patients with hemophilia A and hemophilia A-related events.Patients and Methods: This validation study compared data from medical chart reviews to a database of routinely collected health data, including claims data and discharge abstracts, and especially electronic medical records (EMR), at a single Japanese hospital (Kurashiki Central Hospital) using a stratified sampling method. Two physicians reviewed the charts for all patients at high risk for hemophilia A, and randomly sampled patients with moderate risk. Diagnostic accuracy was determined based on sensitivity, specificity, positive predictive value (PPV), and negative predictive value.Results: There were 1,033,845 eligible patients, of whom 31 had a diagnosis of hemophilia A. ICD-10 diagnosis code D66 in the EMR identified hemophilia A with a sensitivity of 93.5% (95% confidence interval: 78.6– 99) and PPV of 61.7% (95% confidence interval: 46.4– 75.5). The administration of ≥ 10,000 units/month of factor VIII products, as documented in the EMR, identified 81.3% of patients with prophylactic factor replacement therapy. The ICD-10 diagnosis code for intracranial bleeding in the EMR identified 75.0% of patients with intracranial bleeding, but those of gastrointestinal bleeding and major joint bleeding identified only 11.1% and 1.7%, respectively.Conclusion: We developed and validated algorithms to identify congenital hemophilia A and hemophilia A-related events. Hemophilia A could be identified with high sensitivity and PPV, but it was still challenging to identify hemophilia A-related events.Keywords: congenital hemophilia, electronic health record, positive predictive value, sensitivity, validation study

Koji Akeda, Norihiko Takegami, Junichi Yamada, Tatsuhiko Fujiwara, Akinobu Nishimura, Akihiro Sudo Department of Orthopaedic Surgery, Mie University Graduate School of Medicine, Tsu, JapanCorrespondence: Koji AkedaDepartment of Orthopaedic Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu City, Mie, 514-8507, JapanTel +81-59-231-5022Fax +81-59-231-5211Email k_akeda@clin.medic.mie-u.ac.jpPurpose: Central sensitization (CS) is defined as the increased responsiveness of nociceptive neurons in the central nervous system to normal or subthreshold afferent input. CS has been proposed as an underlying mechanism of chronic pain in musculoskeletal disorders including low back pain (LBP). A Central Sensitization Inventory (CSI) has recently been developed for screening participants with CS. However, the association of CS with chronic LBP (cLBP) in the general population remains unknown. The purpose of this study was to investigate the association of CS with cLBP using the CSI in a population-based cohort of a Japanese mountain village.Participants and Methods: Participants aged more than 50 years were recruited from the inhabitants of a mountain village in Japan. Participants completed the following patient-reported outcome measures. Severity of CS was assessed by the CSI. LBP intensity was measured on a numerical rating scale (NRS). Health-related quality of life (QOL) was measured using the EuroQol 5-dimension (EQ-5D), EuroQol-visual analogue scales (EQ-VAS), and the Oswestry Disability Index (ODI). The association of CS and each parameter was statistically evaluated.Results: A total of 272 participants (average age: 72.1 years-old) were analyzed in this study, and 28.3% had cLBP. Average NRS, ODI and CSI scores were significantly higher in the cLBP group than in the without LBP (LBP−) group. There was a significant correlation between CSI and NRS scores (r=0.34, P< 0.0001), ODI (r=0.60, P< 0.0001), EQ5D (r=− 0.55, P< 0.0001) and EQ-VAS (r=− 0.52, P< 0.0001). A multiple regression analysis identified that ODI, EQ-VAS and age were factors significantly associated with CSI.Conclusion: The results of this study suggest that CS is involved in the pathological condition of cLBP in the local residents of a Japanese mountain village.Keywords: central sensitization, low back pain, Central Sensitization Inventory, general population

Precise fluorescence-guided surgery (FGS) for pancreatic cancer has the potential to greatly improve the outcome in this recalcitrant disease. To achieve this goal, we have used genetic reporters to color code cancer and stroma cells in a patient-derived orthotopic xenograft (PDOX) model. The telomerase-dependent green fluorescent protein (GFP)-containing adenovirus OBP-401 was used to label the cancer cells of a pancreatic cancer PDOX. The PDOX was previously grown in a red fluorescent protein (RFP) transgenic mouse that stably labeled the PDOX stroma cells bright red. The color-coded PDOX model enabled FGS to completely resect the pancreatic tumors including stroma. Dual-colored FGS significantly prevented local recurrence, which bright-light surgery or single-color FGS could not. FGS, with color-coded cancer and stroma cells has important potential for improving the outcome of recalcitrant-cancer surgery.

JLab E12-19-002 Experiment is planned to measure the Λ-binding energies of 3ΛH [Jπ = 1/2+ or 3/2+(T = 0)] and 4ΛH (1+) at JLab Hall C. The expected accuracy for the binding-energy measurement is |ΔBtotal Λ | ≃ 70 keV. The accurate spectroscopy for these light hypernuclei would shed light on the puzzle of the small binding energy and short lifetime of 3ΛH, and the chargesymmetry breaking in the ΛN interaction. We aim to perform the experiment in 2025.