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Objectives: We have developed an image-guided surgical system based on invisible near-infrared fluorescent light. Presently, the only clinically available near-infrared fluorophore is indocyanine green, which fluoresces at approximately 800 nm and is used for coronary angiography. Our objective was to determine whether methylene blue, already US Food and Drug Administration approved for other indications, has useful near-infrared fluorescence properties for image-guided cardiac surgery. Methods: The optical properties of methylene blue were measured after dissolution in 100% serum. Biodistribution and clearance were quantified in organs and tissue after intravenous bolus injection of 2 mg/kg methylene blue in 3 rats. Coronary arteriography and cardiac perfusion were imaged in real time after intravenous bolus injection of 1 mg/kg methylene blue in 5 pigs with coronary obstructions. Coronary angiography and acute thrombi were assessed by using 800-nm fluorophores, indocyanine green, and IR-786–labeled platelets, respectively. Results: The peak absorbance and emission of methylene blue as a near-infrared fluorophore occur at 667 nm and 686 nm, respectively. After intravenous injection, methylene blue provides highly sensitive coronary angiography. A lipophilic cation, methylene blue is extracted rapidly into tissue, with myocardium displaying unusually high uptake. Methylene blue permits real-time visualization and quantitative assessment of myocardial perfusion. Because of absent spectral overlap, use of 2 independent fluorophores in our imaging system permits simultaneous quantification of perfusion, venous drainage, and/or intravascular thrombi. Conclusions: Methylene blue is an effective near-infrared fluorophore that provides direct visualization of coronary arteriography and cardiac perfusion. In conjunction with approximately 800-nm near-infrared fluorophores, important functional assessments during cardiac surgery are also possible. [Copyright &y& Elsevier]

Objectives: To investigate the cost-effectiveness of abatacept (ABA) as first-line (1L) therapy in Japanese rheumatoid arthritis (RA) patients using data from the Institute of Rheumatology, Rheumatoid Arthritis database., Methods: A decision-analytic model was used to estimate the cost per American College of Rheumatology response of at least 50% improvement (ACR50) responder and per patient in Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) remission from a Japanese healthcare payers' perspective over a 2-year time horizon. Clinical characteristics of patients on ABA-1L were matched with those of patients on ABA second or later line (2L+) or tumour necrosis factor inhibitor (TNFi)-1L directly or using propensity scores. Resource utilisation and medical costs were calculated from the Japan Medical Data Center claims database. Parameter uncertainty was addressed by sensitivity and subgroup analyses (age, treatment duration, Japanese version of Health Assessment Questionnaire [J-HAQ] score)., Results: Incremental costs per member per month (ΔPMPM) for ABA-1L versus TNFi-1L and ABA-2L+ were -1,571 Japanese Yen (JPY) and 81 JPY, respectively. For ABA-1L versus TNFi-1L, ΔPMPM by ACR50 response was -11,715 JPY and by CDAI and SDAI remission 11,602 JPY and 47,003 JPY, respectively. Corresponding costs for ABA-1L were lower for all outcome parameters versus those for ABA-2L+. Scenario analyses showed that ABA-1L was cost-effective over TNFi-1L in patients <65 years for any outcome. Furthermore, ABA-1L was cost-effective over ABA-2L+ for all outcomes in patients with age <65 years, disease duration <5 years and J-HAQ ≥1.5., Conclusions: ABA-1L demonstrated a favourable cost-effectiveness profile in RA patients, accruing savings for the Japanese healthcare payers., Competing Interests: ET reports consulting fees from AbbVie Japan GK, Asahi Kasei Corp., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., Mitsubishi Tanabe Pharma Co., Mochida Pharmaceutical Co., Pfizer Japan Inc. and Takeda Pharmaceutical Co., Ltd. and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AbbVie Japan GK, Astellas Pharma Inc., Asahi Kasei Corp., Ayumi Pharmaceutical Co., Bristol-Myers Squibb Co., Celltrion Healthcare Japan Co, Ltd., Chugai Pharmaceutical Co., Ltd., Daiichi-Sankyo, Inc., Eisai Co., Ltd., Eli Lilly Japan K.K., GlaxoSmithKline K.K., Kyowa Pharma Chemical Co., Ltd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Mochida Pharmaceutical Co., Nippon Kayaku Co., Ltd., Pfizer Japan Inc., Takeda Pharmaceutical Co., Ltd., Teijin Pharma Ltd. and UCB Japan Co., Ltd. EI reports consulting fees from Pfizer Japan Inc., Bristol-Myers Squibb Co., Ltd., Nippontect Systems Co., Ltd. and RCR Co., Ltd. AS is an employee of Medilead, Inc., which was commissioned to perform this study analysis by Tokyo Women’s Medical University. JN was employed by ICON plc. for this study. CP is an employee of ICON plc. and reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Bristol-Myers Squibb Co., Ltd. DD is an employee of Bristol-Myers Squibb Co., Ltd. and reports stock or stock options from Bristol-Myers Squibb Co., Ltd. YY is an employee of Bristol-Myers Squibb Co., Ltd. MO reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Chugai Pharmaceutical Co., Ltd., Sentan Igaku-Sha Ltd., Asahi Kasei Corp., Bunkodo Co., Ltd., Maruho Co., Ltd., Medical view Co., Ltd. and Kagakuhyoronsya Co., Ltd. KI reports consulting fees from Zimmer Biomet Holdings, Inc.; payment or honoraria for speakers bureaus from AbbVie, Astellas Pharma Inc., Ayumi Pharmaceutical Co., Bristol-Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Ltd., Daiichi-Sankyo, Inc., Janssen Pharmaceutical K.K., Eli Lilly Japan K.K, Pfizer Japan Inc., Takeda Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co. and UCB Japan Co. and for participation on a Data Safety Monitoring Board or Advisory Board from Gilead Sciences, Inc.; and unrestricted grant to Division of Multidisciplinary Management of Rheumatic Diseases from Ayumi Pharmaceutical Co., Chugai Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Mochida Pharmaceutical Co., Ltd, Nippon Kayaku Co., Ltd. and Teijin Pharma Ltd. HY reports consulting fees and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Teijin Pharma Ltd., Eisai Co., Ltd., YLBio, Pfizer Japan Inc., Astellas Pharma Inc., Mitsubishi Tanabe Pharma Co., Bristol-Myers Squibb Co., Ltd., AbbVie Japan GK, Ayumi Pharmaceutical Co., Boehringer, Chugai Pharmaceutical Co., Ltd., Daiichi-Sankyo, Inc., Kaken, Nippon Kayaku Co., Ltd., Novartis, Ono, Taisyo-Toyama, Takeda, Torii Pharmaceutical Co., Ltd., UCB Japan Co., Ltd. and MSD. MH reports research grants from Bristol-Myers Squibb K.K.; grants or contracts from AbbVie Japan GK, Kaken Pharmaceutical Co. Ltd., Asahi Kasei Corp., Mitsubishi Tanabe Pharma Co., Astellas Pharma Inc., Nippon Kayaku Co., Ltd., Ayumi Pharmaceutical Co., Taisho Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Takeda, Daiichi-Sankyo, Inc., Pfizer Japan Inc. and Eisai Co., Ltd.; consulting fees from AbbVie Japan GK and Bristol-Myers Squibb K.K. and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AbbVie GK, Nippon Kayaku Co., Ltd., Ayumi Pharmaceutical Co., Nippon Shinyaku Co., Ltd., Bristol-Myers Squibb K.K., Ltd., Pfizer Japan Inc., Chugai Pharmaceutical Co., Mitsubishi Tanabe Pharma Co., Eisai Co., Ltd., UCB Japan Co., Ltd., Eli Lilly Japan K.K., Gilead Sciences Inc. and Janssen Pharmaceutical K.K. MA, KS, ES, NS and RY have no conflicts of interest to report., (Copyright: © 2022 Tanaka et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)