Sex Differences in Cardiovascular Disease-Related Hospitalization and Mortality in Japan　- Analysis of Health Records From a Nationwide Claim-Based Database, the Japanese Registry of All Cardiac and Vascular Disease (JROAD).

BACKGROUND: The prevalence of cardiovascular disease (CVD) is rising in Japan with its aging population, but there is a lack of epidemiological data on sex differences in CVD, including acute coronary syndrome (ACS), acute heart failure (AHF), and acute aortic disease.Methods and Results: This retrospective study analyzed data from 1,349,017 patients (January 2012-December 2020) using the Japanese Registry Of All Cardiac and Vascular Diseases database. ACS patients were youngest on average (70.5±12.9 years) and had the lowest female proportion (28.9%). AHF patients had the oldest mean age (79.7±12.0 years) and the highest proportion of females (48.0%). Acute aortic disease had the highest in-hospital mortality (26.1%), followed by AHF (11.5%) and ACS (8.9%). Sex-based mortality differences were notable in acute aortic disease, with higher male mortality in Stanford Type A acute aortic dissection (AAD) with surgery (males: 14.2% vs. females: 10.4%, P<0.001) and similar rates in Type B AAD (males: 6.2% vs. females: 7.9%, P=0.52). Aging was a universal risk factor for in-hospital mortality. Female sex was a risk factor for ACS and acute aortic disease but not for AHF or Types A and B AAD. CONCLUSIONS: Sex-based disparities in the CVD-related hospitalization and mortality within the Japanese national population have been highlighted for the first time, indicating the importance of sex-specific strategies in the management and understanding of these conditions.

The real-world clinical decisions of physicians in the management of Takayasu arteritis and giant cell arteritis in Japan: A cross-sectional web-questionnaire survey.

OBJECTIVES: To access the real-world clinical management of physicians who treat Takayasu arteritis (TAK) and giant cell arteritis (GCA) after the publication of the Japanese Circulation Society (JCS) 2017 Guidelines for the Management of Vasculitis Syndrome. METHODS: This descriptive, cross-sectional study utilized self-administered electronic questionnaires, which were answered in February 2022 by physicians treating TAK or GCA and registered with Macromill Inc. RESULTS: The 329 survey respondents comprised 110 cardiologists, 110 rheumatologists, 34 cardiovascular surgeons, 24 surgeons, 35 internal medicine physicians, 13 nephrologists, and 7 pediatricians. The 2017 JCS Guidelines were the most commonly referenced information source for resolving clinical questions, accessed by 70% of respondents. Ophthalmoscopy was performed in only 50% of patients with TAK, and in 70% for GCA. The median percentages of patients who underwent 18F-fluorodeoxyglucose-positron emission tomography/computed tomography for TAK and GCA patients were 23% and 20% at diagnosis, respectively, and 10% each at follow-up within 12 months. Tocilizumab was the most frequently used medication in combination with glucocorticoids for both TAK and GCA, especially in remission induction therapy for relapsed patients. CONCLUSIONS: The majority of physician treating TAK and GCA referred to the 2017 JCS guidelines. This report clarified the current clinical practice for large vessel vasculitis in Japan, providing information for the next revision of the guidelines.

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.

Demographic Traits, Clinical Status, and Comorbidities of Patients With Thromboangiitis Obliterans in Japan.

BACKGROUND: The latest demographics, clinical and living conditions, and comorbidities of patients with thromboangiitis obliterans (TAO) in Japan are unknown.Methods and Results: We conducted a retrospective cross-sectional survey using the annual database of the Japanese Ministry of Health, Labour and Welfare medical support system for patients with TAO between April 2013 and March 2014. This study included 3,220 patients (87.6% male), with current age ≥60 years in 2,155 patients (66.9%), including 306 (9.5%) patients aged ≥80 years. Overall, 546 (17.0%) had undergone extremity amputation. The median interval from onset to amputation was 3 years. Compared with never smokers (n=400), 2,715 patients with a smoking history had a higher amputation rate (17.7% vs. 13.0%, P=0.02, odds ratio [OR]=1.437, 95% confidence interval [CI]=1.058-1.953). A lower proportion of workers and students was seen among patients after amputation than among amputation-free patients (37.9% vs. 53.0%, P<0.0001, OR=0.542, 95% CI=0.449-0.654). Comorbidities, including arteriosclerosis-related diseases, were found even in patients in their 20-30 s. CONCLUSIONS: This large survey confirmed that TAO is not a life-threatening but an extremity-threatening disease that threatens patients' professional lives. Smoking history worsens patients' condition and extremity prognosis. Long-term total health support is required, including care of extremities and arteriosclerosis-related diseases, social life support, and smoking cessation.

Organ Damage and Quality of Life in Takayasu Arteritis　- Evidence From a National Registry Analysis.

BACKGROUND: Takayasu arteritis, affecting primarily young women, damages large arteries and organs. We examined the impact of disease duration and sex on organ damage and quality of life using Japan's Intractable Disease Registry.Methods and Results: After refining data, 2,013 of 2,795 patients were included in the study. Longer disease duration was related to a lower prevalence of disease activity symptoms, a higher prevalence of organ damage, and a higher proportion of patients requiring nursing care. Compared with men, women tended to have an earlier onset age, exhibiting longer disease duration. A higher proportion of women had aortic regurgitation and required nursing care. The proportion of female patients in employment was lower than that of the general female population, whereas no difference was observed between male patients and the general male population. Logistic regression analysis revealed that age at surveillance, brain ischemia, visual impairment/loss, and ischemic heart disease were significant factors associated with high nursing care needs (Level ≥2, with daily activity limitations). CONCLUSIONS: Early diagnosis and effective treatment, particularly to prevent brain ischemia, visual impairment, and ischemic heart disease, may improve the quality of life of patients with Takayasu arteritis, especially women.

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.

Endoscopic Treatment of Colo-Colonic Intussusception in a Patient with Peutz-Jeghers Syndrome.

A 19-year-old man with a history of Peutz-Jeghers syndrome (PJS) and two previous partial small bowel resections because of intussusception presented with lower abdominal pain. Computed tomography (CT) showed concentric multilayer and cord-like structures in the transverse colon. Colo-colonic intussusception was suspected and he was hospitalized. After two therapeutic enemas were unsuccessful, a colonoscopy was performed. The intussusception was reduced and a 40-mm transverse colon polyp with a thick stalk was resected. After the procedure, his abdominal pain was relieved and he was discharged on the sixth hospital day. This case and several previous reports suggest that PJS polyps with tumor diameter exceeding 30 mm and location in the transverse or sigmoid colon can cause intussusception. Endoscopic treatment should be considered for these lesions.

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.

Intraoperative collection of autologous platelet-rich plasma from the cardiopulmonary bypass circuit upon initiation of extracorporeal circulation.

OBJECTIVES: The aim of this study is to evaluate the possibility of the autologous platelet-rich plasma (PRP) collection from the cardiopulmonary bypass (CPB) circuit and to evaluate its effect on the aggregative function. METHODS: For seventy-two patients undergoing cardiac surgery with CPB, an autologous PRP was prepared using the Haemonetics Component Collection System® by drawing blood from the CPB circuit immediately after CPB was established. The blood samples were taken at three points for examination, A: beginning of surgery, B: immediately after heparin reversal with protamine following discontinuation of CPB, C: after the collected autologous PRP was returned to the patient. Platelet count and platelet aggregation ability were analyzed. RESULTS: The mean platelet count in autologous PRP was 5.5 (range: 3-14) units. Platelet count decreased by 115.0 (±27.3) × 1000/µl from A to B and increased by 27.3 ± 17.2 (× 1000/µl) from B to C. When platelet aggregation was measured by Adenosine Diphosphate (ADP) 3.0 µM, it decreased by 42.6% ± 12.1% from A to B and increased by 8.7% ± 7.4% from B to C. CONCLUSIONS: Autologous PRP can be safely collected by drawing blood from the CPB circuit, platelet count and aggregation ability significantly decreased after CPB including autologous PRP collection. Some improvement was detected in the number of the platelets count and platelet aggregation ability by administrating an autologous PRP even if autologous PRP is collected from CPB circuit. TRIAL REGISTRATION: UMI-CTR, UMIN000023776 . Registered 1 October 2016.

Treatment of ventricular septal perforation caused by blunt trauma using the right ventricle approach: A case report.

Traumatic ventricular septal perforation (VSP) is a rare condition that can occur following chest trauma and can lead to heart failure. Herein, a case of VSP caused by blunt chest trauma successfully closed using the double-patch technique via the right ventricle after medial sternotomy is presented. This case report highlights the necessity of emergency surgery in the acute phase of traumatic VSP if heart failure is difficult to control. This technique was useful for acute surgery. .

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.

Associated factors of poor treatment outcomes in patients with giant cell arteritis: clinical implication of large vessel lesions.

BACKGROUND: Relapses frequently occur in giant cell arteritis (GCA), and long-term glucocorticoid therapy is required. The identification of associated factors with poor treatment outcomes is important to decide the treatment algorithm of GCA. METHODS: We enrolled 139 newly diagnosed GCA patients treated with glucocorticoids between 2007 and 2014 in a retrospective, multi-center registry. Patients were diagnosed with temporal artery biopsy, 1990 American College of Rheumatology classification criteria, or large vessel lesions (LVLs) detected by imaging based on the modified classification criteria. Poor treatment outcomes (non-achievement of clinical remission by week 24 or relapse during 52 weeks) were evaluated. Clinical remission was defined as the absence of clinical signs and symptoms in cranial and large vessel areas, polymyalgia rheumatica (PMR), and elevation of C-reactive protein (CRP) levels. A patient was determined to have a relapse if he/she had either one of the signs and symptoms that newly appeared or worsened after achieving clinical remission. Re-elevation of CRP without clinical manifestations was considered as a relapse if other causes such as infection were excluded and the treatment was intensified. Associated factors with poor treatment outcomes were analyzed by using the Cox proportional hazard model. RESULTS: Cranial lesions, PMR, and LVLs were detected in 77.7%, 41.7%, and 52.5% of the enrolled patients, respectively. Treatment outcomes were evaluated in 119 newly diagnosed patients who were observed for 24 weeks or longer. The mean initial dose of prednisolone was 0.76 mg/kg/day, and 29.4% received any concomitant immunosuppressive drugs at baseline. Overall, 41 (34.5%) of the 119 patients had poor treatment outcomes; 13 did not achieve clinical remission by week 24, and 28 had a relapse after achieving clinical remission. Cumulative rates of the events of poor treatment outcomes in patients with and without LVLs were 47.5% and 17.7%, respectively. A multivariable model showed the presence of LVLs at baseline was significantly associated with poor treatment outcomes (adjusted hazard ratio [HR] 3.54, 95% CI 1.52-8.24, p = 0.003). Cranial lesions and PMR did not increase the risk of poor treatment outcomes. CONCLUSION: The initial treatment intensity in the treatment algorithm of GCA could be determined based upon the presence or absence of LVLs detected by imaging at baseline.

[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.

Effects of Catheter Tip Location on the Spread of Sensory Block Caused by a Continuous Thoracic Paravertebral Block: A Prospective, Randomized, Controlled, Double-Blind Study.

Single injections in the anterior region of the thoracic paravertebral space (TPVS) have been reported to generate a multisegmental longitudinal spreading pattern more frequently than those in the posterior region of the TPVS. In this trial, we examined the hypothesis that a continuous thoracic paravertebral block (TPVB) administered through a catheter inserted into the anterior region of the TPVS allows a wider sensory block dispersion. Fifty consecutive patients undergoing video-assisted thoracic surgery were enrolled. Before the surgery, an infusion catheter was inserted into the TPVS through a needle placed adjacent to either the parietal pleura (group A) or internal intercostal membrane (group P) using an ultrasound-guided intercostal transverse approach according to a randomized allocation schedule. A chest radiograph was obtained postoperatively after injection of 10 mL of radiopaque dye through the catheter. Thereafter, 20 mL of 0.375% levobupivacaine was injected via the catheter, followed by commencement of continuous TPVB with 0.25% levobupivacaine at 8 mL/h. The primary outcome was the number of blocked dermatomes at 24 h after surgery. The secondary outcomes included radiopaque dye spreading patterns, the number of segments reached by the radiopaque dye, the number of blocked dermatomes at 2 h after surgery, and pain scores. The median (interquartile range [range]) number of blocked dermatomes 24 h after surgery was 3 (2.75-4 [1-6]) in group A (n = 22) and 2 (1.5-3 [0-7]) in group P (n = 25; p = 0.037). No significant differences in the other outcomes were found between the groups. In conclusion, a continuous TPVB administered using a catheter supposedly inserted into the anterior region of the TPVS allows a wider sensory block dispersion than a catheter inserted into the posterior region of the TPVS. This trial is registered with the UMIN Clinical Trials Registry (UMIN000018578).

Utility of skin perfusion pressure values with the Society for Vascular Surgery Wound, Ischemia, and foot Infection classification system.

OBJECTIVE: The addition of skin perfusion pressure (SPP) might enhance the predictive value of the Society for Vascular Surgery Wound, Ischemia, and foot Infection (WIfI) classification system. The purpose of the present study was to evaluate the SPP for each WIfI classification stage among patients with foot wounds by cross-referencing the results of prospectively monitored limb outcomes and to derive the SPP criteria that could be combined with other measurements to grade ischemia for the WIfI classification. METHODS: From July 2015 to June 2017, patients with foot wounds that met the WIfI classification criteria were prospectively enrolled. We assessed the limbs using the WIfI ischemia grade without measuring the transcutaneous oxygen pressure but measured the SPP. After monitoring for 1 year, the predictability of the WIfI stages was analyzed according to whether the limbs had not healed (unchanged or worsened wounds, minor or major amputation, all-cause death) or had healed (improved or healed wounds) by comparing stages 1 and 2 with stages 3 and 4. We also statistically analyzed the SPP values that could be the boundary values between each ischemia grade and reevaluated the predictability of the WIfI stages with the boundary SPP values. RESULTS: We enrolled a total of 91 limbs for 76 patients (mean age, 70.5 ± 12.0 years). The mean SPP values stratified by ischemia grade 0 to 3 were 52.1, 41.1, 27.1, and 18.8 mm Hg, respectively (an SPP of <30 mm Hg indicates severe ischemia). After monitoring for 1 year, 19 of 48 limbs in stage 1 and 2 and 35 of 43 in stage 3 and 4 were in the nonhealed group and 29 limbs in stage 1 and 2 and 8 limbs in stage 3 and 4 were in the healed group. The SPP boundary values between each ischemia (I) grade were calculated as 45 mm Hg for I-0/I-1, 35 for I-1/I-2, and 25 for I-2/I-3. When jointly using the boundary SPP values, the ischemia grade changed for 23 limbs, altering the distribution of the WIfI stages and limb outcomes: 11 of 38 limbs in stage 1 and 2 and 43 of 53 in stage 3 and 4 were transferred to the nonhealed group. The sensitivity, efficiency, and negative predictive value of WIfI staging improved when staging with SPP: from 65% to 80%, 70% to 77%, and 60% to 71%, respectively. CONCLUSIONS: The SPP boundary values that could be used with ischemia grade in the WIfI classification were identified as 45, 35, and 25 mm Hg. The addition of SPP could improve the accuracy of the evaluation.

Toe-Brachial Index in the Second Toe: Substitutability to Toe-Brachial Index in the Great Toe and Ankle-Brachial Index.

Objective: Toe-brachial index (TBI) is usually measured in the great toe (TBI-1). However, this is not always possible. To determine the usefulness of TBI measurement in the second toe (TBI-2), we examined the relation between systolic pressure in the second toe (toe pressure [TP-2]) and that in the great toe (TP-1) and evaluated the association between TBI and ankle-brachial index (ABI). Materials and Methods: We retrospectively analyzed patients who underwent a series of measurements of TBI-2, TBI-1, and ABI using an automatic oscillometric device at Kawasaki Medical School Hospital, Japan in 2012. Results: We evaluated 114 feet without severe ischemia symptoms in 57 patients (median age: 73 years). TP-2 was similar to TP-1 (correlation coefficient [r] = 0.769, 95% confidence interval [CI]: 0.681-0.836, p <0.001). ABI showed a mild correlation with TBI-2 (r = 0.463, 95% CI: 0.303-0.598, p <0.001) and a moderate correlation with TBI-1 (r = 0.586, 95% CI: 0.450-0.696, p <0.001). The TBIs of 0.65 and 0.5 corresponded to the ABIs of about 1.0 and 0.9, respectively, in both toes. Conclusion: TBI-2 measurement can be considered as an acceptable substitute to TBI-1 or ABI measurement to assess the patients in whom ABI and TBI-1 cannot be measured.

Positioning for Endovenous Laser Ablation: Comparative Study with Thigh Stripping.

We performed a comparative study of surgical outcomes and venous functions between endovenous laser ablation with a 980-nm diode laser (EV group) and thigh stripping (ST group). There were no severe complications and initial success rates were 100% in both groups. In the EV group, preoperative symptoms improved in 94.3% of cases, the venous occlusion rate was 98%, and endovenous heat induced thrombosis had occurred in 11.9% (Class 3: 0.7%) at 12 months after the operation. Although comparative study of postoperative venous function by air plethysmography showed significant improvement in both groups, there was less recovery of postoperative venous function in the EV than in the ST group. (This article is a translation of J Jpn Coll Angiol 2015; 55: 13-20.).