Clinical Characteristics and Treatment Outcomes of Patients With Newly Diagnosed Takayasu Arteritis in Japan During the First 2 Years of Treatment　- A Nationwide Retrospective Cohort Study.

BACKGROUND: This study aimed to clarify recent clinical features and treatment outcomes in Japanese patients with newly diagnosed Takayasu arteritis (TAK) during the first 2 years of treatment. METHODS AND RESULTS: A nationwide multicenter retrospective cohort study for TAK was implemented to collect data between 2007 and 2014. The primary outcome of the study was clinical remission at Week 24. Of the 184 participants registered, 129 patients with newly diagnosed TAK were analyzed: 84% were female and the mean age at onset was 35 years. Clinical symptoms at diagnosis were mostly associated with large-vessel lesions. Frequent sites of vascular involvement included the carotid artery, subclavian artery, aortic arch, and descending aorta. The mean initial dose of prednisolone administered was 0.68 mg/kg/day, and 59% and 17% of patients received immunosuppressive drugs and biologics, respectively, by Week 104. Clinical remission at Week 24 and sustained clinical remission with daily prednisolone at ≤10 mg at Week 52 were achieved in 107 (82.9%) and 51 (39.5%) patients, respectively. The presence of signs and symptoms linked to large-vessel lesions was associated with failure to achieve sustained clinical remission at Week 52. CONCLUSIONS: We elucidated the clinical characteristics, treatment outcomes, and factors associated with failure to achieve sustained clinical remission in patients with newly diagnosed TAK in Japan during the first 2 years of treatment.

Establishing clinical remission criteria for giant cell arteritis: Results of a Delphi exercise carried out by an expert panel of the Japan Research Committee of the Ministry of Health, Labour, and Welfare for Intractable Vasculitis.

OBJECTIVE: To develop a proposal for giant cell arteritis remission criteria in order to implement a treat-to-target algorithm. METHODS: A task force consisting of 10 rheumatologists, 3 cardiologists, 1 nephrologist, and 1 cardiac surgeon was established in the Large-vessel Vasculitis Group of the Japanese Research Committee of the Ministry of Health, Labour and Welfare for Intractable Vasculitis to conduct a Delphi survey of remission criteria for giant cell arteritis. The survey was circulated among the members over four reiterations with four face-to-face meetings. Items with a mean score of ≥4 were extracted as items for defining remission criteria. RESULTS: An initial literature review yielded a total of 117 candidate items for disease activity domains and treatment/comorbidity domains of remission criteria, of which 35 were extracted as disease activity domains (systematic symptoms, signs and symptoms of cranial and large-vessel area, inflammatory markers, and imaging findings). For the treatment/comorbidity domain, ≤5 mg/day of prednisolone 1 year after starting glucocorticoids was extracted. The definition of achievement of remission was the disappearance of active disease in the disease activity domain, normalization of inflammatory markers, and ≤5 mg/day of prednisolone. CONCLUSION: We developed proposals for remission criteria to guide the implementation of a treat-to-target algorithm for giant cell arteritis.

Diamond-like carbon coating to inner surface of polyurethane tube reduces Staphylococcus aureus bacterial adhesion and biofilm formation.

Staphylococcus aureus is one of the main causative bacteria for polyurethane catheter and artificial graft infection. Recently, we developed a unique technique for coating diamond-like carbon (DLC) inside the luminal resin structure of polyurethane tubes. This study aimed to elucidate the infection-preventing effects of diamond-like carbon (DLC) coating on a polyurethane surface against S. aureus. We applied DLC to polyurethane tubes and rolled polyurethane sheets with our newly developed DLC coating technique for resin tubes. The DLC-coated and uncoated polyurethane surfaces were tested in smoothness, hydrophilicity, zeta-potential, and anti-bacterial properties against S. aureus (biofilm formation and bacterial attachment) by contact with bacterial fluids under static and flow conditions. The DLC-coated polyurethane surface was significantly smoother, more hydrophilic, and had a more negative zeta-potential than did the uncoated polyurethane surface. Upon exposure to bacterial fluid under both static and flow conditions, DLC-coated polyurethane exhibited significantly less biofilm formation than uncoated polyurethane, based on absorbance measurements. In addition, the adherence of S. aureus was significantly lower for DLC-coated polyurethane than for uncoated polyurethane under both conditions, based on scanning electron microscopy. These results show that applying DLC coating to the luminal resin of polyurethane tubes may impart antimicrobial effects against S. aureus to implantable medical polyurethane devices, such as vascular grafts and central venous catheters.

Establishing clinical remission criteria and the framework of a treat-to-target algorithm for Takayasu arteritis: Results of a Delphi exercise carried out by an expert panel of the Japan Research Committee of the Ministry of Health, Labour and Welfare for intractable vasculitis.

OBJECTIVES: To develop a proposal for remission criteria and a framework for a treat-to-target (T2T) algorithm for Takayasu arteritis (TAK). METHODS: A study group of the large-vessel vasculitis group of the Japanese Research Committee of the Ministry of Health, Labour and Welfare for Intractable Vasculitis consists of 10 rheumatologists, 5 cardiologists, 1 nephrologist, 1 vascular surgeon, 1 cardiac surgeon, and 2 paediatric rheumatologists. A Delphi survey of remission criteria items was circulated among the study group over four reiterations. To develop the T2T algorithm, the study group conducted four face-to-face meetings and two rounds of Delphi together with three patients. RESULTS: Initial literature review resulted in a list of 117 candidate items for remission criteria, of which 56 items with a mean score of ≥4 (0-5) were extracted including disease activity domains and treatment/comorbidity domains. The study group provided six overarching principles for the T2T algorithm, two recommendations on treatment goals, five on evaluation of disease activity and imaging findings including positron emission tomography-computed tomography, and two on treatment intensification. CONCLUSIONS: We developed a T2T algorithm and proposals for standardised remission criteria by means of a Delphi exercise. These will guide future evaluation of different TAK treatment regimens.

Genetic determinants and an epistasis of LILRA3 and HLA-B*52 in Takayasu arteritis.

Takayasu arteritis (TAK) is a systemic vasculitis with severe complications that affects the aorta and its large branches. HLA-B*52 is an established susceptibility locus to TAK. To date, there are still only a limited number of reports concerning non-HLA susceptibility loci to TAK. We conducted a genome-wide association study (GWAS) and a follow-up study in a total of 633 TAK cases and 5,928 controls. A total of 510,879 SNPs were genotyped, and 5,875,450 SNPs were imputed together with HLA-B*52. Functional annotation of significant loci, enhancer enrichment, and pathway analyses were conducted. We identified four unreported significant loci, namely rs2322599, rs103294, rs17133698, and rs1713450, in PTK2B, LILRA3/LILRB2, DUSP22, and KLHL33, respectively. Two additional significant loci unreported in non-European GWAS were identified, namely HSPA6/FCGR3A and chr21q.22. We found that a single variant associated with the expression of MICB, a ligand for natural killer (NK) cell receptor, could explain the entire association with the HLA-B region. Rs2322599 is strongly associated with the expression of PTK2B Rs103294 risk allele in LILRA3/LILRB2 is known to be a tagging SNP for the deletion of LILRA3, a soluble receptor of HLA class I molecules. We found a significant epistasis effect between HLA-B*52 and rs103294 (P = 1.2 × 10-3). Enhancer enrichment analysis and pathway analysis suggested the involvement of NK cells (P = 8.8 × 10-5, enhancer enrichment). In conclusion, four unreported TAK susceptibility loci and an epistasis effect between LILRA3 and HLA-B*52 were identified. HLA and non-HLA regions suggested a critical role for NK cells in TAK.

Impact of postoperative remote infection on length of stay and medical costs in hospitals in Japan.

PURPOSE: To analyze the impact of postoperative remote infections (PRIs) on medical expenditure. METHODS: The subjects of this retrospective study were 338 patients who had undergone gastroenterological surgery at one of the 20 Japanese institutions within the Japan Society for Surgical Infection (JSSI) and mainly authorized as educational institutions. The patients were allocated to 169 pairs of those with a PRI (PRI (+) group) matched with those without a PRI (PRI (-) group). PRIs included pneumonia, urinary tract infection (UTI), catheter-associated blood stream infection (CA-BSI), and antibiotic-associated enteritis. RESULTS: SSI developed in 74 of the 338 patients (22 without PRI and 52 with PRI). The SSI incidence was significantly higher in the PRI (+) group (p < 0.001). The difference in the median postoperative length of hospital stay was 15 days, indicating a significant prolongation in the PRI (+) group (p < 0.001). The PRI (+) group also had a higher rate of inter-hospital transfer (p < 0.01) and mortality (p < 0.001). Similarly, the difference in median postoperative medical fees was $6832.3, representing a significant increase in the PRI (+) group (p < 0.001). CONCLUSIONS: The postoperative length of hospital stay is longer and the postoperative medical expenditure is higher for patients with a PRI than for those without a PRI.

[Treatment Strategy for Aortic Arch Aneurysms to Minimize the Complications:Which should be Chosen, Endovascular Treatment or Open Repair?]

The technologies of endovascular treatment for aortic pathologies have progressed rapidly, and endovascular treatment for thoracic pathologies has gained widespread acceptance, and there has been a significant increase in the number of thoracic pathologies treated by thoracic endovascular aortic repair (TEVAR) over the last decade. The initial results of TEVAR such as operative mortality and morbidities have been good and acceptable. Therefore, indication of TEVAR has expanded along with the improvement of techniques and devices. However, as its mid-term and long-term results became available, complications including stroke, endoleaks and consequent aneurysm rupture have become apparent. Open repair is still the important treatment option because its results are acceptable and durable. This article provides an treatment strategy of aortic arch aneurysms to minimize the complications.

Current Trends in Epidemiology and Clinical Features of Thromboangiitis Obliterans in Japan　- A Nationwide Survey Using the Medical Support System Database.

BACKGROUND: The epidemiology and clinical features of thromboangiitis obliterans (TAO) in Japan have not been updated extensively.Methods and Results:This retrospective study used the Japanese Ministry of Health, Labour and Welfare (JMHLW) medical support system database and associated health insurance data. The number of medical financial support recipients registered as TAO patients and estimated prevalence of TAO decreased from fiscal year (FY) 2000 (10,089 and 7.95 [95% confidence interval, CI: 7.79-8.10] per 100,000 population) to FY 2010 (7,147 and 5.58 [95% Cl: 5.45-5.71] per 100,000) and leveled off until 2014. The prevalence of TAO among patients with peripheral arterial occlusive diseases declined from 7.15% (95% Cl: 7.00-7.31) in FY 2008 to 6.12% (95% Cl: 5.98-6.26) in FY 2014. Clinicodemographic features were obtained from 89 new recipients in FY 2013 and 2014: 12 (13%) women, 36 (40%) aged ≥50 years, 26 (29%) had probable onset age ≥50 years, 7 (8%) were non-smokers, and 12 (13%) had arteriosclerosis-related comorbidities. The symptoms were similar regardless of registration age, smoking history, or sex. Although 40 (45%) had digit ulcers, only 12 (13%) fulfilled Shionoya's criteria. They rarely had infrapopliteal lesions combined with upper extremity involvement or phlebitis. CONCLUSIONS: The prevalence of TAO has decreased in Japan. In the current diagnosis of TAO, various clinical characteristics including late onset, arteriosclerotic factors, non-smoking, or mild symptoms should be considered.

[Initial Clinical Experience of the Herbal Medicine Inchinkoto for Refractory Hyperbilirubinemia Following Open-heart Surgery].

We retrospectively assessed our initial clinical experience of the herbal medicine Inchinkoto for refractory hyperbilirubinemia following open-heart surgery. Six patients developed hyperbilirubinemia in an acute phase after surgery and their maximum total bilirubin levels were 6.4~26.4 mg/dl( mean:13.1± 8.2 mg/dl). They were initially treated with ursodeoxycholic acid and/or Stronger Neo-Minophagen C containing monoammonium glycyrrhizinate, glycine, aminoacetic acid, and L-cysteine hydrochloride hydrate. These treatments, however, were ineffective, and Inchinkoto was introduced at 5~34 day (mean:13.3±11.3 days) after surgery. Hyperbilirubinemia improved in all patients after the introduction of Inchinkoto:1 day after in 1 case, 2 days after in 2 cases, 3 days after in 2 cases, and 4 days after in 1 case. These results indicate the potential of Inchinkoto to attenuate refractory hyperbilirubinemia following cardiac surgery with cardiopulmonary bypass.

[Clinical Efficacy of Prone Positioning in Elderly Patients with Respiratory Failure after Thoracic Aortic Surgery].

In order to demonstrate the clinical efficacy of prone positioning(PP), we reviewed 2 elderly patients with respiratory failure who underwent thoracic aortic surgery. Case 1:An 80-year-old man with true thoracic aortic aneurysm (TAA) underwent total arch replacement under moderate hypothermia. Two days after surgery, PP was conducted for 3 hours to treat atelectasis and poor oxygenation. His respiratory state and oxygenation subsequently improved and he was weaned from ventilator assistance. Case 2:An 82-year-old woman with early thrombosed acute type A aortic dissection and cardiac tamponade underwent emergency primary repair of the ascending aorta under moderate hypothermia. Six days after surgery, PP was conducted for approximately 3 hours to improve oxygenation. She was weaned from the ventilator 7 days after surgery. The clinical courses of both cases after PP were uneventful. In order to improve the respiratory state of elderly patients after TAA surgery, PP is effective and useful.

Surgical Outcomes of Isolated Coronary Artery Bypass Grafting for Acute Coronary Syndrome　- Based on the Japan Adult Cardiovascular Surgery Database.

BACKGROUND: The present study aimed to clarify the current use and outcomes of coronary artery bypass grafting (CABG) for acute coronary syndrome (ACS) based on the Japan Adult Cardiovascular Surgery Database (JACVSD) in stratified risk categories, and also to provide guidance on selection of optimal surgical strategies for ACS.Methods and Results:From January 2008 through December 2012, 7,867 isolated CABG procedures for ACS were identifiedfrom the JACVSD. Patients were stratified into 3 subgroups (<2%, 2-9.9%, ≥10%) according to preoperative risk estimations based on this database. Off- and on-pump CABG surgical outcomes were evaluated in each subgroup. Off-pump CABG (OPCAB) was the predominant surgical strategy in all subgroups. The proportion of on-pump beating CABG increased in the higher-risk groups. Although average observed mortality rates were compatible with preoperative estimated risk in all subgroups, those after OPCAB were significantly lower in the medium (2-9.9%) risk group with lower incidence of major complications. In the low (<2%) and high (≥10%) risk groups, observed mortality rates did not show statistically significant differences between off- and on-pump CABG. CONCLUSIONS: In this study in Japan, OPCAB was mainly performed in patients with ACS, particularly those with estimated risk <10%, with lower mortality rates, whereas on-pump beating CABG was selected for higher-risk patients with ACS, with reasonable mortality rates.

Current Clinical Features of New Patients With Takayasu Arteritis Observed From Cross-Country Research in Japan: Age and Sex Specificity.

BACKGROUND: The clinical features of newly diagnosed Japanese patients with Takayasu arteritis and its age or sex specificities are unknown. METHODS AND RESULTS: We analyzed information from nationwide registration forms submitted by patients with Takayasu arteritis between April 2001 and March 2011 as part of a research program by the Japanese Ministry of Health, Labor and Welfare. Among the 7779 patients who submitted their forms, 1372 newly registered patients with Takayasu arteritis were enrolled; 83.8% were female. The median age at onset was 35 years, which was significantly higher in male patients (median, 43.5 years) than in female patients (median, 34 years; P<0.001). Local symptoms and findings were most commonly observed in the cervicobrachial area, with more complaints in the head or neck than in the upper limbs. Approximately 85% of the patients had vascular involvements in the aortic arch or its major branches; many young female patients had localized lesions. Although male patients had extensive aortic lesions or aneurysms with more complications, localized abdominal lesions were relatively more frequent in male patients with age at onset >40 years than in other age-sex groups. Disease statuses were severe in patients who registered at ≥1 year after onset. CONCLUSIONS: The proportions of male patients and patients with elderly onset increased in newly diagnosed patients with Takayasu arteritis. Their clinical and angiographic features differed according to onset age and sex.

Simple Interrupted Suturing for Redo Mitral Valve Replacement.

BACKGROUND: An evaluation was made of the early clinical outcomes and efficacies of simple interrupted suturing (SIS) for redo mitral valve replacement (MVR). METHODS: Among 336 mitral valve surgery patients at the authors' institution between April 2000 and May 2014, a total of 21 redo MVR using SIS (12 women, nine men; mean age 67±11 years; range 32-80 years) participated in the study. Surgical indications for redo MVR were paravalvular leakage (PVL) in 10 patients, prosthetic valve endocarditis in five, mechanical valve thrombosis in three, and structural valve deterioration (SVD) of the bioprosthesis in three. The number of previous surgeries was one in 10 patients, two in seven, and three in four. With regards to surgical technique, sharp dissection was initially performed on one side of the previous prosthetic sewing cuff, and the overall sewing cuff was thereafter completely removed following leaflet detachment. SIS (mean number of sutures 32.5 ± 3.0; range: 28-40 sutures) was performed to implant the new prosthesis, without exposing the rough surface of the previous mitral valve annulus, thereby allowing for eventual implantation of the same-sized or larger-sized prosthesis. RESULTS: The surgical procedure was successfully performed in all patients without any serious complications. Bioprostheses were selected for 11 patients, and mechanical valves for 10. Sixteen patients (76.2%) received a new prosthesis that was the same size as or larger than the previous prosthesis. Operative mortality within 30 days was 4.8%, which was similar to that of primary MVR in the same period (n = 83; 2.4%; p = 0.57). Recurrent PVL was detected in only one patient, who underwent a fourth surgery for SVD of the bioprosthesis. CONCLUSIONS: SIS for redo MVR may allow for the implantation of larger prostheses, and this novel maneuver may achieve acceptable early clinical outcomes.

Socioeconomic effects of surgical site infection after cardiac surgery in Japan.

PURPOSE: Surgical site infection (SSI) increases medical costs and prolongs hospitalization; however, there has been no multicenter study examining the socioeconomic effects of SSI after cardiovascular surgery in Japan. METHODS: A retrospective 1:1 matched, case-controlled study on hospital stay and health care expenditure after cardiovascular surgery was performed in four hospitals. Patients selected for the study had undergone coronary artery bypass grafting and/or valve surgery between April, 2006 and March, 2008. Data were obtained for 30 pairs of patients. RESULTS: The mean postoperative stay for the SSI group was 49.1 days, being 3.7 times longer than that for the non-SSI group. The mean postoperative health care expenditure for the SSI group was ¥ 2,763,000 (US$27,630), being five times higher than that for the non-SSI group. Charges for drug infusion and hospitalization for inpatient care were significantly higher for the SSI group than for the non-SSI group. The increased health care expenditure was mainly attributed to the cost of antibiotics and antimicrobial agents. CONCLUSION: SSI after cardiovascular surgery not only prolonged the length of hospital stay, but also increased medical expenditure. Thus, the prevention of SSI after cardiovascular surgery is of great socioeconomic importance.

[SUBFASCIAL ENDOSCOPIC PERFORATOR VEIN SURGERY IN THE TREATMENT OF SEVERE VARICOSE VEINS].

Surgical treatment of severe varicose veins (CEAP classification : C4b-C6) should involve not only interruption of incompetent superficial veins to prevent venous regurgitation due to valve incompetence but also interruption of incompetent perforator veins. Subfascial endoscopic perforator vein surgery (SEPS) is performed via a small skin incision and involves interruption of perforator veins by the insertion of an endoscope into the subfascial space. SEPS produces good surgical outcomes: it is accurate in detecting and transecting perforator veins; has a low frequency of surgical wound complications; prevents lipodermatosclerosis and formation of pigmented skin lesions; and is minimally invasive compared with Linton's operation. Thus, SEPS is an excellent procedure for patients with incompetent perforator veins. SEPS has been covered by the Japanese national health insurance system since April 2014, and it is expected that SEPS will be further developed and become more widespread in use.

Current venous thromboembolism management and outcomes in Japan.

BACKGROUND: Epidemiology and clinical management of acute venous thromboembolism (VTE) are not readily available in Japan. METHODS AND RESULTS: The Japan VTE Treatment Registry (JAVA) is a multicenter cohort study of consecutive patients with an objectively confirmed, symptomatic acute pulmonary embolism (PE), symptomatic acute deep vein thrombosis (DVT), or asymptomatic acute proximal DVT. Of the 1,076 patients enrolled with acute VTE, 68.7% presented with an isolated DVT; 17.0% had PE alone; and 14.4% had both. VTE management was characterized by a high rate of inferior vena cava filter insertion (40.6%), frequent thrombolysis (21.1%), and sub-therapeutic unfractionated heparin-based anticoagulation, followed by warfarin prescription, mostly targeting an international normalized ratio of 2.0 (range, 1.5-2.5). During a mean observation period of 252.5 days, 29 recurrent cases of VTE were documented, yielding an incidence rate of 3.9 per 100 patient-years. A total of 123 patients died during the study period, corresponding to a rate of 16.6 deaths per 100 patient-years. The incidence of major bleeding was 3.2% per patient-year, including 2 fatal hemorrhages and 7 intracranial hemorrhages. CONCLUSIONS: VTE management in Japan is characterized by a highly aggressive strategy in the acute phase, in contrast to protocols that use low-level anticoagulation. The VTE recurrence rates in Japan and Western countries are similar, but mortality is higher in Japan, with significant variability depending on patient and management characteristics.

Preoperative chronic kidney disease as a strong predictor of postoperative infection and mortality after coronary artery bypass grafting.

BACKGROUND: The aim of this study was to determine the influence of preoperative kidney dysfunction (ie, chronic kidney disease (CKD)) on postoperative cardiovascular events, infection, acute kidney injury and hospital mortality in patients undergoing coronary artery bypass grafting (CABG). METHODS AND RESULTS: A multi-institutional retrospective study was performed at 14 hospitals of adult patients undergoing isolated CABG from 2007 to 2008 (n=1,522). We classified CKD level according to preoperative estimated glomerular filtration rate (eGFR): normal, eGFR >90 ml·min(-1)·1.73 m(-2); mild, eGFR 60-90 ml·min(-1)·1.73 m(-2); moderate, eGFR 30-59 ml·min(-1)·1.73 m(-2); and severe, eGFR <30 ml·min(-1)·1.73 m(-2), and assessed postoperative outcome. Preoperative CKD distribution was as follows: normal, n=121 (8%); mild, n=713 (47%); moderate, n=515 (34%); and severe, n=169 (11%). Risk of infection was strongly correlated with CKD level (normal, 3.3%; mild, 7.0%; moderate, 8.3%; severe, 17.0%; P<0.01). The risk of in-hospital death was also strongly correlated with CKD level (normal, 1.7%; mild, 1.0%; moderate, 1.6%; severe, 5.9%; P<0.01). On multivariate logistic regression analysis, CKD level was identified as a significant risk factor for postoperative infection, acute kidney injury, and in-hospital death. CONCLUSIONS: Advanced preoperative CKD is a strong predictor of postoperative infection, acute kidney injury and in-hospital death after CABG.

Endovascular Stent Graft Placement and Coil Embolization for Splenic Artery Aneurysm with an Anatomical Variant.

A 62-year-old woman with abdominal pain was diagnosed with a splenic artery aneurysm (SAA) and an anatomical variant in the splenic artery (SA) arising from the superior mesenteric artery (SMA) as its first branch. To treat the SAA, the draining artery and a small branch of the SAA were embolized, and then small-diameter stent grafts were deployed from SMA orifice, covering the aberrant origin of the SA and preserving the second branch of SMA. Intraoperative angiography confirmed successful exclusion of the SAA without endoleak or arterial dissection. The stent graft was patent and the aneurysm had shrunk 3.5 years after the operation.