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Masahito Katsuki,1,2 Maiko Nanri,3 Yuki Miyakoshi,4 Shuto Gobo,4 Akihito Koh,2 Shin Kawamura,2 Senju Tachikawa,2 Ryo Matsukawa,2 Kenta Kashiwagi,5 Mitsuhiro Matsuo,6 Fuminori Yamagishi7 1Department of Neurosurgery and Headache Outpatient, Japanese Red Cross Suwa Hospital, Nagano, Japan; 2Department of Neurosurgery, Itoigawa General Hospital, Niigata, Japan; 3Nurse-Senka, SMS Corporation, Tokyo, Japan; 4Creatone, Regnition, Saitama, Japan; 5Department of Neurology, Itoigawa General Hospital, Niigata, Japan; 6Department of Anesthesiology, Toyama University Hospital, Toyama, Japan; 7Department of Surgery, Itoigawa General Hospital, Niigata, JapanCorrespondence: Masahito Katsuki, Department of Neurosurgery, Japanese Red Cross Suwa Hospital, 5-11-50, Kogandori, Suwa, Nagano, 392-0027, Japan, Tel/Fax +81-0266-52-6111, Email ktk1122nigt@gmail.comIntroduction: Headache is a common public health problem, but its burden could be avoided by raising headache awareness and the appropriate use of acute medication and prophylactic medication. Few reports on raising headache awareness in the general public have been reported, and there are no reports on headache awareness campaigns through social networking services (SNS), or social media, in Japan. We prospectively performed a headache awareness campaign from March 2022 through 2 SNS, targeting nurse and wind instrumental musicians, because they are with high headache prevalence.Methods: Through the 2 SNS, the article and video were distributed, respectively. The article and video described the 6 important topics for the general public about headaches, which were described in the Clinical Practice Guideline for Headache Disorders 2021. Just after reading or watching them as e-learning, we performed online questionnaire sheets to investigate the awareness of the 6 topics through the 2 SNS. The awareness of the 6 topics before and after the campaign was evaluated.Results: In the SNS nurse-senka, we obtained 1191 responses. Women comprised 94.4%, and the median (range) age was 45 (20 to 71) years old. Headache sufferers were 63.8%, but only 35.1% had consulted doctors. In the SNS Creatone, we got the response from 134 professional musicians, with 77.3% of women. The largest number of respondents were in their 20s (range 18– 60 years old). Headache sufferers were 87.9%. Of them, 36.4% had consulted doctors, 24.2% were medication-overuse headache. The ratios of individuals who were aware of the 6 topics significantly increased from 15.2%-47.0% to 80.4– 98.7% after the online questionnaire in both SNS (p < 0.001, all).Conclusion: E-learning and online survey via SNS can improve headache awareness.Keywords: awareness, education, medication-overuse headache, migraine, online, prevention, social networking services, social media

Background: We previously demonstrated that higher simple guideline-directed medical therapy (GDMT) scores (comprising renin-angiotensin system inhibitors, β-blockers, mineralocorticoid antagonists, and sodium-glucose cotransporter 2 inhibitors) at discharge were correlated with improved prognosis in heart failure (HF) patients. HF readmissions are linked to adverse outcomes, emphasizing the need for enhanced optimization of GDMT., Methods and Results: Using the simple GDMT score, we evaluated the effect of revising and modifying in-hospital GDMT on the prognosis of patients with HF readmissions. In this retrospective analysis of 2,100 HF patients, we concentrated on 1,222 patients with HF with reduced ejection/moderately reduced ejection fraction, excluding patients with HF with preserved ejection fraction, on dialysis, or who died in hospital. A higher current GDMT score was associated with better HF prognosis. Of the 1,222 patients in the study, we analyzed 372 cases of rehospitalization, calculating the simple GDMT scores at admission and discharge. Patients were divided into groups according to score improvement. Multivariate analysis showed a significant association between improved in-hospital simple GDMT score and the composite outcome (HF readmission+all-cause mortality; hazard ratio 0.459; 95% confidence interval 0.257-0.820; P=0.008). Even after propensity score matching to adjust for background, among rehospitalized patients, those with an improved in-hospital simple GDMT score had a better prognosis., Conclusions: Our results highlight the potential of robust interventions and score elevation during hospitalization leading to improved outcomes.

Aberrant aggregates of amyloid-β (Aβ) and tau protein (tau), called amyloid, are related to the etiology of Alzheimer disease (AD). Reducing amyloid levels in AD patients is a potentially effective approach to the treatment of AD. The selective degradation of amyloids via small molecule-catalyzed photooxygenation in vivo is a leading approach; however, moderate catalyst activity and the side effects of scalp injury are problematic in prior studies using AD model mice. Here, leuco ethyl violet (LEV) is identified as a highly active, amyloid-selective, and blood-brain barrier (BBB)-permeable photooxygenation catalyst that circumvents all of these problems. LEV is a redox-sensitive, self-activating prodrug catalyst; self-oxidation of LEV through a hydrogen atom transfer process under photoirradiation produces catalytically active ethyl violet (EV) in the presence of amyloid. LEV effectively oxygenates human Aβ and tau, suggesting the feasibility for applications in humans. Furthermore, a concept of using a hydrogen atom as a caging group of a reactive catalyst functional in vivo is postulated. The minimal size of the hydrogen caging group is especially useful for catalyst delivery to the brain through BBB., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Aims: The guideline-directed medical therapy (GDMT) has been recommended for heart failure (HF) with reduced ejection fraction (HFrEF) based on the accumulating clinical evidence. However, it is difficult to implement all the trial-proven medications for every patient in the real world., Methods and Results: A simple GDMT score was created, according to the combination of GDMT drugs (renin-angiotensin system inhibitors, beta-blockers, mineralocorticoid receptor antagonists, and sodium-glucose transporter 2 inhibitors) administration and their dosage (0-9 points). Its impact on the prognosis of HF patients was investigated. Admitted HF patients [HFrEF and HF with mildly reduced ejection fraction (HFmrEF), n = 1054] were retrospectively analysed (excluding those with in-hospital death and dialysis). A simple GDMT score ≥5, but not the number of medications, was significantly associated with a reduction of all-cause death, HF readmission, and composite outcome (HF readmission and all-cause death) (P < 0.001). Subgroup analysis showed that almost all groups with a simple GDMT score of 5 or higher had a better prognosis., Conclusions: The developed simple GDMT score was associated with prognosis in HFrEF and HFmrEF patients. Even if all four drugs cannot be introduced for some reason, a regimen with a simple GDMT score ≥5 may lead to a prognosis in HF patients., (© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: The efficacy of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in patients with acute chronic heart failure (HF) is increasingly being reported. However, it is not clear when SGLT2i should be initiated in patients with acute decompensated HF (ADHF) after hospitalization. We retrospectively analyzed ADHF patients with newly prescribed SGLT2i. Methods and Results: Among the 694 patients hospitalized due to HF between May 2019 and May 2022, data were extracted for 168 patients with newly prescribed SGLT2i during the index hospitalization. These patients were divided into 2 groups: and early group (92 patients who started SGLT2i within 2 days of admission) and a late group (76 patients who started SGLT2i after 3 days). Clinical characteristics were comparable between the 2 groups. The date of cardiac rehabilitation initiation was significantly earlier in the early than late group (2.5±1.2 vs. 3.8±2.2 days; P<0.001). Hospital stay was significantly shorter in the early group (16.4±6.5 vs. 24.2±16.0 days; P<0.001). Although there were significantly fewer HF readmissions within 3 months in the early group (2.1% vs. 10.5%; P=0.044), the association disappeared in a multivariate analysis including clinical confounders. Conclusions: Early initiation of SGLT2i may shorten hospital stays., (Copyright © 2023, THE JAPANESE CIRCULATION SOCIETY.)

Aims: The aim of this study was to compare the diagnostic performance of the nutritional indicators, the mini nutritional assessment-short form (MNA-SF), the geriatric nutritional risk index (GNRI), and the controlling nutritional status (CONUT), in heart failure (HF) patients., Methods and Results: Nutritional status was prospectively assessed by the aforementioned three nutritional indicators in 150 outpatients with HF who were then followed for 1 year. The prevalence of patients with the nutritional risk as assessed by the MNA-SF, GNRI, and CONUT scores was 50.0%, 13.3%, and 54.0%, respectively. There was slight agreement of nutritional risk assessment between the MNA-SF and GNRI scores (κ coefficient = 0.16), as well as the GNRI and CONUT scores (κ = 0.11), but poor agreement between the MNA-SF and CONUT scores (κ = -0.09). The CONUT score had the lowest area under the curve (AUC) for the identification of low body weight, low muscle mass, and low physical function among the three indicators (all P < 0.05). Compared with the MNA-SF score, both the GNRI and CONUT scores had lower AUCs for the identification of reduced dietary intake and weight loss (all P < 0.05). There was no significant difference in predicting all-cause mortality or HF rehospitalization among the three indicators. The prescription of statins reduced the diagnostic performance of the CONUT score, as the CONUT score includes cholesterol level assessment., Conclusions: Of the three indicators, the diagnostic ability of the MNA-SF score was the highest, and that of the CONUT score was the lowest, for the assessment of HF patient nutritional status. The CONUT score may misrepresent nutritional status, particularly in patients receiving statins., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Acute coronary syndrome (ACS) patients with solid lesions often require predilatation before stenting. Predilatation with high pressure may increase the risk of distal embolism, whereas direct stenting increases the risk of stent underexpansion. We recently reported that, in severely calcified lesions, using a cutting balloon (CB) can provide greater acute gain compared with other scoring balloons. Therefore, we hypothesized that predilatation with CB may reduce the incidence of distal embolism in ACS patients with solid lesions. Methods and Results: This study retrospectively analyzed data for 175 ACS patients who required predilatation, either with a conventional balloon (n=136) or CB (n=39). The occurrence of distal embolism was significantly lower in the CB than conventional balloon group (10.3% vs 32.4%, respectively; P=0.007). Multivariate analysis showed that the occurrence of distal embolism was positively associated with Thrombolysis in Myocardial Infarction (TIMI) grade and the presence of attenuated plaque, but negatively associated with the use of a CB. To support this clinical observation, we compared thrombus dispersal using a CB and non-compliant balloon in an ex vivo experimental model using a pseudo-thrombus. In this model, pseudo-thrombus dispersal was significantly smaller when a CB rather than non-compliant balloon was used (1.8±1.0% vs 2.6±1.2%, respectively; n=20, for each; P=0.002). Conclusions: In ACS patients with solid lesions that require predilatation, predilatation with a CB may reduce the incidence of distal embolism., Competing Interests: R.M. has received honoraria for lectures from Abbott Japan LCC, Boston Scientific, and TERUMO. The remaining authors have no conflicts of interest to declare., (Copyright © 2022, THE JAPANESE CIRCULATION SOCIETY.)

Background: The full impact of the intake of citrus fruits on the risk of depression in individuals with chronic heart failure (HF) is unknown. Here, we examined the associations between the estimated habitual intakes of citrus fruits and depressive symptoms in patients with chronic HF., Methods: We enrolled 150 stable outpatients with chronic HF who had a history of worsening HF. To assess the patients' daily dietary patterns, we used a brief self-administered diet-history questionnaire to calculate the daily consumption of foods and nutrients. To assess the patients' mental state, we used a nine-item Patient Health Questionnaire (PHQ-9)., Results: Twelve patients (8%) were identified as having moderate-to-severe depression (PHQ-9 score ≥10). The patients with PHQ-9 ≥10 had lower daily intakes of citrus fruits compared to those with no or mild depressive symptoms (PHQ-9 <10). The daily intakes of various antioxidants, including vitamin C, β-carotene, and β-cryptoxanthin, all of which are abundant in citrus fruits, were reduced in the patients with PHQ-9 ≥10, accompanied by higher serum levels of 8-isoprostane (an oxidative stress marker). A multivariate logistic regression analysis using forward selection showed that a lowered daily intake of citrus fruits was an independent predictor of the comorbidity of moderate-to-severe depression in patients with chronic HF, after adjustment for age, gender, and the hemoglobin value., Conclusions: A lower daily consumption of citrus fruits was associated with higher prevalence of depression in patients with chronic HF. Our findings support the hypothesis that a daily consumption of citrus fruits has a beneficial effect on the prevention and treatment of depression in chronic HF patients., (Copyright © 2021. Published by Elsevier Ltd.)

Aims: It has been reported that congestive heart failure (CHF) readmission has not decreased in the last decade. It is also reported that CHF readmission is likely to occur shortly after discharge. We investigated whether an early follow-up at outpatient care within 2 weeks after discharge affects the long-term readmission rate and prognosis., Methods and Results: We reviewed consecutive 1002 patients admitted to our hospital due to CHF. Two-hundred and fifty-nine patients who died in-hospital or were transferred to another hospital or readmitted within 2 weeks were excluded and 743 of discharged patients were analysed. We extracted contributing variables associated with heart failure (HF) readmission and the composite adverse outcome (all cause death or HF readmissions) by univariate and multivariate analysis. Multivariate analysis showed that the early follow-up was independently associated with freedom from HF readmission and the composite outcome. We divided these patients into two groups, with/without early follow-up and performed a propensity score-matching analysis (n = 259 each). HF readmission during 2 year follow-up was significantly less in the early follow-up group [P = 0.02, hazard ratio (HR) = 0.647, 95% confidence interval (CI) = 0.447-0.935] as well as the composite outcome was less in the early follow-up group (P = 0.01, HR = 0.643, 95% CI = 0.456-0.908). Medication adjustments were done in only 33.2% of the patients. Rates of HF readmissions were comparable regardless of whether or not medication adjustment was done at the early follow-up (P = 0.505, HR = 1.208, 95% CI = 0.692-2.106)., Conclusions: The present study demonstrates that an early follow-up approach after discharge in CHF patients may improve the long-term prognosis. These results may not depend on medication adjustment but rather on modifying patient factors early after discharge., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Extracellular vesicles (EVs) are known to be secreted by various cells. In particular, mesenchymal stem cell (MSC)-derived EVs (MSC-EVs) have tissue repair capacity and anti-inflammatory properties. Dental pulp stem cells (DPSCs), which are MSCs isolated from pulp tissue, are less invasive to the body than other MSCs and can be collected from young individuals. In this study, we investigated the efficacy of EVs secreted by DPSCs (DPSC-EVs) for bone formation., Methods: DPSC-EVs were isolated from the cell culture medium of DPSCs. DPSC-EVs were unilaterally injected along with collagen (COL), beta-tricalcium phosphate (β-TCP) or hydroxyapatite (HA) into rat calvarial bone defects. The effects of DPSC-EVs were analyzed by micro-computed tomography (micro-CT) and histological observation., Results: Micro-CT showed that administration of DPSC-EVs with the abovementioned scaffolds resulted in bone formation in the periphery of the defects. DPSC-EVs/COL specifically resulted in bone formation in the center of the defects. Histological observation revealed that DPSC-EVs/COL promoted new bone formation. Administration of DPSC-EVs/COL had almost the same effect on the bone defect site as transplantation of DPSCs/COL., Conclusions: These results suggest that DPSC-EVs may be effective tools for bone tissue regeneration.

Malnutrition is highly prevalent in patients with heart failure (HF), but the precise impact of dietary energy deficiency on HF patients' clinical outcomes is not known. We investigated the associations between inadequate calorie intake and adverse clinical events in 145 stable outpatients with chronic HF who had a history of hospitalization due to worsening HF. To assess the patients' dietary pattern, we used a brief self-administered diet-history questionnaire (BDHQ). Inadequate calorie intake was defined as <60% of the estimated energy requirement. In the total chronic HF cohort, the median calorie intake was 1628 kcal/day. Forty-four patients (30%) were identified as having an inadequate calorie intake. A Kaplan-Meier analysis revealed that the patients with inadequate calorie intake had significantly worse clinical outcomes including all-cause death and HF-related hospitalization during the 1-year follow-up period versus those with adequate calorie intake (20% vs. 5%, p < 0.01). A multivariate logistic regression analysis showed that inadequate calorie intake was an independent predictor of adverse clinical events after adjustment for various factors that may influence patients' calorie intake. Among patients with chronic HF, inadequate calorie intake was associated with an increased risk of all-cause mortality and rehospitalization due to worsening HF. However, our results are preliminary and larger studies with direct measurements of dietary calorie intake and total energy expenditure are needed to clarify the intrinsic nature of this relationship.

Background: The aim of this study was to assess specialty-related differences in the treatment for patients with acute heart failure (AHF) in the acute phase and subsequent prognostic differences. Methods and Results: We analyzed hospitalizations for AHF in REALITY-AHF, a multicenter prospective registry focused on very early presentation and treatment in patients with AHF. All patients were classified according to the medical specialty of the physicians responsible for contributed most to decisions regarding the initial diagnosis and treatment after the emergency department (ED) arrival. Patients initially managed by emergency physicians (n=614) or cardiologists (n=911) were analyzed. After propensity-score matching, vasodilators were used less often by emergency physicians than by cardiologists at 90 min after ED arrival (29.8% vs. 46.1%, P<0.001); this difference was also observed at 6, 24, and 48 h. Cardiologists administered furosemide earlier than emergency physicians (67 vs. 102 min, P<0.001). However, the use of inotropes, noninvasive ventilation, and endotracheal intubation were similar between groups. In-hospital mortality did not differ between patients managed by emergency physicians and those managed by cardiologists (4.1% vs. 3.8%, odds ratio 1.12; 95% confidence interval 0.58-2.14)., Conclusions: Despite differences in initial management, no prognostic difference was observed between emergency physicians and cardiologists who performed the initial management of patients with AHF.

Background: Acute heart failure (AHF) is a life-threatening disease requiring urgent treatment, including a recommendation for immediate initiation of loop diuretics., Objectives: The authors prospectively evaluated the association between time-to-diuretic treatment and clinical outcome., Methods: REALITY-AHF (Registry Focused on Very Early Presentation and Treatment in Emergency Department of Acute Heart Failure) was a prospective, multicenter, observational cohort study that primarily aimed to assess the association between time to loop diuretic treatment and clinical outcome in patients with AHF admitted through the emergency department (ED). Door-to-furosemide (D2F) time was defined as the time from patient arrival at the ED to the first intravenous furosemide injection. Patients with a D2F time <60 min were pre-defined as the early treatment group. Primary outcome was all-cause in-hospital mortality., Results: Among 1,291 AHF patients treated with intravenous furosemide within 24 h of ED arrival, the median D2F time was 90 min (IQR: 36 to 186 min), and 481 patients (37.3%) were categorized as the early treatment group. These patients were more likely to arrive by ambulance and had more signs of congestion compared with the nonearly treatment group. In-hospital mortality was significantly lower in the early treatment group (2.3% vs. 6.0% in the nonearly treatment group; p = 0.002). In multivariate analysis, earlier treatment remained significantly associated with lower in-hospital mortality (odds ratio: 0.39; 95% confidence interval: 0.20 to 0.76; p = 0.006)., Conclusions: In this prospective multicenter, observational cohort study of patients presenting at the ED for AHF, early treatment with intravenous loop diuretics was associated with lower in-hospital mortality. (Registry focused on very early presentation and treatment in emergency department of acute heart failure syndrome; UMIN000014105)., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Aneurysms affecting the aorta are a common condition associated with high mortality as a result of aortic dissection or rupture. Investigations of the pathogenic mechanisms involved in syndromic types of thoracic aortic aneurysms, such as Marfan and Loeys-Dietz syndromes, have revealed an important contribution of disturbed transforming growth factor (TGF)-β signaling., Objectives: This study sought to discover a novel gene causing syndromic aortic aneurysms in order to unravel the underlying pathogenesis., Methods: We combined genome-wide linkage analysis, exome sequencing, and candidate gene Sanger sequencing in a total of 470 index cases with thoracic aortic aneurysms. Extensive cardiological examination, including physical examination, electrocardiography, and transthoracic echocardiography was performed. In adults, imaging of the entire aorta using computed tomography or magnetic resonance imaging was done., Results: Here, we report on 43 patients from 11 families with syndromic presentations of aortic aneurysms caused by TGFB3 mutations. We demonstrate that TGFB3 mutations are associated with significant cardiovascular involvement, including thoracic/abdominal aortic aneurysm and dissection, and mitral valve disease. Other systemic features overlap clinically with Loeys-Dietz, Shprintzen-Goldberg, and Marfan syndromes, including cleft palate, bifid uvula, skeletal overgrowth, cervical spine instability and clubfoot deformity. In line with previous observations in aortic wall tissues of patients with mutations in effectors of TGF-β signaling (TGFBR1/2, SMAD3, and TGFB2), we confirm a paradoxical up-regulation of both canonical and noncanonical TGF-β signaling in association with up-regulation of the expression of TGF-β ligands., Conclusions: Our findings emphasize the broad clinical variability associated with TGFB3 mutations and highlight the importance of early recognition of the disease because of high cardiovascular risk., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Recently, there has been increasing concern about adverse health effects of exposure to desert dust events. However, the association between dust and the incidence of ischemic heart diseases is unknown. The aim of the present study was to elucidate whether Asian dust (AD), a windblown sand dust originating from mineral soil in China and Mongolia, is associated with the incidence of acute myocardial infarction (AMI)., Methods and Results: We investigated the data regarding hospitalization because of AMI among 3068 consecutive patients from 4 AMI centers in Fukuoka, Japan, and data for AD from April 2003 to December 2010. We applied a time-stratified case-crossover design to examine the association between AD and the incidence of AMI. Using a conditional logistic regression analysis, we estimated the odds ratios of AMI associated with AD after controlling for ambient temperature and relative humidity. The occurrence of AD events 0 to 4 days before the day of admission was significantly associated with the incidence of AMI. In particular, the occurrence of AD 4 days before admission was significantly associated with the onset of AMI., Conclusions: These data suggest that exposure to AD a few days before symptom onset is associated with the incidence of AMI., (© 2014 American Heart Association, Inc.)

Objectives: The management of acute type A aortic dissection complicated by coma remains controversial. We previously reported an excellent rate of recovery of consciousness provided aortic repair was performed within 5 hours of the onset of symptoms. This study evaluates the early and long-term outcomes using this approach., Methods: Between August 2003 and July 2013, of the 241 patients with acute type A aortic dissection brought to the Japanese Red Cross Kobe Hospital and Hyogo Emergency Medical Center, 30 (12.4%) presented with coma; Glasgow Coma Scale was less than 11 on arrival. Surgery was performed in 186 patients, including 27 (14.5%) who were comatose. Twenty-four comatose patients underwent successful aortic repair immediately (immediate group). Their mean age was 71.0 ± 11.1 years, Glasgow Coma Scale was 6.5 ± 2.4, and prevalence of carotid dissection was 79%. For brain protection, deep hypothermia with antegrade cerebral perfusion was used, and postoperative induced hypothermia was performed. Neurologic evaluations were performed using the Glasgow Coma Scale, National Institutes of Health Stroke Scale, and modified Rankin Scale., Results: In the immediate group, the time from the onset of symptoms to arrival in the operating theater was 222 ± 86 minutes. Hospital mortality was 12.5%. Full recovery of consciousness was achieved in 79% of patients in up to 30 days. Postoperative Glasgow Coma Scale and National Institutes of Health Stroke Scale improved significantly when compared with the preoperative score (P < .05), and postoperative activities of daily living independence (modified Rankin Scale <3) was achieved in 50% of patients. The mean follow-up period was 56.5 months, and the cumulative survival was 48.2% after 10 years. Cox proportional hazards regression analysis indicated that immediate repair (hazard ratio, 4.3; P = .007) was the only significant predictor of postoperative survival over a 5-year period., Conclusions: The early and long-term outcomes as a result of immediate aortic repair for acute type A aortic dissection complicated by coma were satisfactory., (Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Background: Coronary risk factors for the onset of acute coronary syndrome (ACS), including polyunsaturated fatty acids (PUFAs), in younger adult patients may be different from those in older patients., Methods and Results: We enrolled 578 patients who underwent coronary angiography at Fukuoka Saiseikai Hospital, and divided them into a younger adult group (YG) (<50 years, n=47) and a middle-aged older group (OG) (≥50 years, n=531). In a multivariate analysis, lower levels of high-density lipoprotein cholesterol and the ratio of eicosapentaenoic acid (EPA) to arachidonic acid (AA) (EPA/AA), and less aspirin, oral hypoglycemic agent, and calcium channel blocker (CCB) use were independent risk factors for ACS in all patients. In YG, lower levels of EPA/AA and less angiotensin II receptor blocker/angiotensin-converting enzyme inhibitor use were the independent risk factors. In OG, smoking, lower levels of EPA/AA, less aspirin and CCB use were the risk factors. While lower levels of EPA/AA was the only risk factor for ACS that was common to all patients, YG and OG, docosahexaenoic acid/AA was not associated with ACS in YG and OG., Conclusions: Lower level of EPA/AA is a common critical risk factor for ACS in middle-aged older patients as well as younger adult patients. Some of the risk factors for the onset of ACS in younger patients were different from those in older patients., (Copyright © 2013 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Aims: Depression often coexists with cardiovascular disease, such as hypertension and heart failure, in which sympathetic hyperactivation is critically involved. Reduction in the brain sigma-1 receptor (S1R) functions in depression pathogenesis via neuronal activity modulation. We hypothesized that reduced brain S1R exacerbates heart failure, especially with pressure overload via sympathetic hyperactivation and worsening depression., Methods and Results: Male Institute of Cancer Research mice were treated with aortic banding and, 4 weeks thereafter, fed a high-salt diet for an additional 4 weeks to accelerate cardiac dysfunction (AB-H). Compared with sham-operated controls (Sham), AB-H showed augmented sympathetic activity, decreased per cent fractional shortening, increased left ventricular dimensions, and significantly lower brain S1R expression. Intracerebroventricular (ICV) infusion of S1R agonist PRE084 increased brain S1R expression, lowered sympathetic activity, and improved cardiac function in AB-H. ICV infusion of S1R antagonist BD1063 increased sympathetic activity and decreased cardiac function in Sham. Tail suspension test was used to evaluate the index of depression-like behaviour, with immobility time and strain amplitude recorded as markers of struggle activity using a force transducer. Immobility time increased and strain amplitude decreased in AB-H compared with Sham, and these changes were attenuated by ICV infusion of PRE084., Conclusion: These results indicate that decreased brain S1R contributes to the relationship between heart failure and depression in a mouse model of pressure overload.

Background: Management of acute type A aortic dissection (AADA) complicated by coma remains controversial. We analyzed our experience in managing AADA complicated by coma to determine the relationship of duration of preoperative coma to postoperative neurological recovery., Methods and Results: Between September 2003 and October 2010, 181 patients with AADA were treated, including 27 presenting with coma (Glasgow Coma Scale <11) on arrival. Twenty-one patients were repaired immediately (immediate group); time from onset of symptoms to operating room was <5 hours. For brain protection, deep hypothermia with antegrade cerebral perfusion was used, and postoperative therapeutic hypothermia with magnesium treatment was performed. Six patients initially were managed medically, and 3 of them were followed by eventual repair because time from onset was >5 hours (delayed group). The preoperative National Institutes of Health Stroke Scale score was 31.4 ± 6.6 in the immediate group and 28.3 ± 9.5 in the delayed group. Hospital mortality was 14% in the immediate group and 67% in the delayed group. Full recovery of consciousness was achieved in 86% of patients in the immediate group and in 17% in the delayed group. In immediate group, the postoperative National Institutes of Health Stroke Scale score significantly improved to 6.4 ± 8.4, cumulative survival rate was 71.8% in 3 years, and independence in daily activities was achieved in 52% (11/21)., Conclusions: Aortic repair, if performed immediately from the onset of symptoms, showed satisfactory recovery of consciousness and neurological function in patients with AADA complicated by coma. In this patient population, immediate aortic repair is warranted.

We encountered a case of exercise-induced chest pain after the implantation of sirolimus-eluting stents (SESs). She had no history of previous chest pain, and an exercise stress test just after the implantation of the SESs was negative without any symptoms. However, six months after the implantation of the SESs, she began to experience frequent episodes of severe chest pain on effort in spite of there being no significant coronary stenosis. Interestingly, severe coronary vasoconstriction was induced by an intracoronary administration of acetylcholine, and exercise stress testing revealed positive findings with chest pain and ST-T segment depression on ECG. An intensive treatment with two types of calcium channel blockers could readily and completely abolish the exercise-induced chest pain and ST-T segment depression on the ECG. In view of these findings, we presumed that coronary microvessel dysfunction and/or exercise-induced coronary vasoconstriction leading to myocardial ischemia had appeared 6 months after the implantation of the SESs. Although the pathogenesis of this phenomenon could not be completely elucidated, the anatomical and functional abnormalities of the coronary arteries associated with the implantation of the SESs may have been one of the most important mechanisms.

We encountered complications of septic shock and retroperitoneal hemorrhage which occurred after implantation of a retrievable Günther Tulip filter. A 79-year-old woman was diagnosed as right femoral vein thrombosis, and a retrievable Günther Tulip filter was deployed prior to a total knee replacement surgery. However, the patient developed septicemia due to Citrobacter freundii, followed by thrombocytopenia and retroperitoneal hemorrhage. A large hematoma was formed along the lateral side of the filter struts. We considered that the filter should be removed to control retroperitoneal hemorrhage and prevent secondary infection of the hematoma. Removal of the retrievable filter was effective in managing these complications.

Objective: Of 125 surgical patients with abdominal aortic aneurysm (AAA) treated from 1999, 11 patients with deep shock from ruptured AAAs who underwent aortic occlusion balloon catheter (AOBC) insertion before laparotomy were studied., Methods: With the patients under local anesthesia, the brachial artery was exposed and the balloon catheter was inserted into the thoracic aorta. The balloon was inflated halfway and pulled back gently to the orifice of the left subclavian artery, and was advanced with the aid of blood flow down to the abdominal aorta. After full inflation of the balloon, the catheter was pulled until the balloon was fixed at the proximal shoulder of the AAA., Results: AOBC insertion was completed within 16.1 +/- 5.1 minutes. Systolic blood pressure at presentation was 84.1 +/- 31.7 mm Hg, deteriorated to 60.9 +/- 15.4 mm Hg on arrival in the operating room, and increased significantly (P <.0001) to 123.4 +/- 25.3 mm Hg after AOBC insertion. The balloon burst in three patients. Embolic complications were observed in two patients. There were three deaths, two associated with the balloon bursting. In nine patients whose shock was successfully controlled by AOBC, operative mortality was 11%., Conclusion: Transbrachial arterial insertion of an AOBC may be useful to ameliorate hemorrhagic shock in patients with ruptured AAAs.

We describe the use of rib-cross thoracotomy and costal coaptation pins made with bioabsorbable poly-L-lactide for rib approximation. This thoracotomy provided an excellent intraoperative exposure of the entire descending aorta and thoracoabdominal aorta in patients with extended thoracoabdominal aortic aneurysm without increase in postoperative morbidity.

Background: Medical therapy for chronic pulmonary thromboembolism is limited, and surgical treatment has become more frequent recently. We have performed pulmonary thromboendarterectomy on 8 patients with chronic pulmonary thromboembolism accompanied by thrombophilia., Methods: The patients were 6 men and 2 women aged 21 to 56 years (mean, 35 years). Five patients had antiphospholipid syndrome, 2 had protein C deficiency, and 1 had congenital antithrombin III deficiency. The preoperative condition was New York Heart Association functional class III in 5 and class IV in 3. Hypoxemia, marked pulmonary hypertension (mean pulmonary artery pressure, 47+/-6.7 mm Hg), and low cardiac output were observed in all patients. After a median sternotomy, deep hypothermia was induced using a cardiopulmonary bypass, and pulmonary thromboendarterectomy in the bilateral pulmonary arteries was performed under intermittent circulatory arrest., Results: There were no operative deaths. Long-term respiratory management was needed postoperatively by 3 patients. In the remaining 5 patients, no reperfusion injury was observed. The arterial blood oxygen concentration improved, and the mean pulmonary pressure decreased to 16+/-5.5 mm Hg. The cardiac output also increased, and New York Heart Association functional class improved to I in 4 and II in 4 patients., Conclusion: Pulmonary thromboendarterectomy under deep hypothermic intermittent circulatory arrest was effective for chronic pulmonary thromboembolism accompanied by thrombophilia for which medical treatment is of limited value.

Objective: Our goal was to investigate factors for mortality and cerebral outcome in patients with aneurysm of the aortic arch., Methods: From 1993 to 1996, 148 patients with aortic arch aneurysm underwent operations involving deep hypothermic circulatory arrest with retrograde cerebral perfusion. Age was 63.9 +/- 11.6 years (mean +/- standard deviation) and 52 patients were older than 70 years. Twenty-eight had acute aortic dissection. Twelve had ruptured aneurysms. Fourteen had redo operations. Seventy had aortic dissection. The aneurysms were caused by atherosclerosis in 123 patients and by other causes in 25. Median sternotomy was used in 92 and left thoracotomy in 56. Twenty-eight patients underwent replacement of the ascending aorta to the proximal arch, 62 had total arch replacement, 38 had distal arch replacement, 12 had simultaneous replacement of the distal arch and the descending aorta or thoracoabdominal aorta, and 8 had patch repair., Results: Fifteen (10.1%) early deaths occurred. New stroke occurred in six (4.0%) patients and transient delirium in 37 (25.0%). The duration of deep hypothermic circulatory arrest plus retrograde cerebral perfusion was 49 +/- 17 minutes, and it was more than 60 minutes in 36 patients. Patients awoke 7.5 +/- 8.2 hours after the operation. Logistic regression analysis demonstrated that risk factors for mortality were ruptured aneurysm, chronic obstructive pulmonary disease, arterial cannulation in the ascending aorta, and stroke. Risks for stroke were ruptured aneurysm and replacement of the distal arch. Risks for delirium were age older than 70 years and atherosclerotic aneurysm. Duration of circulatory arrest plus cerebral perfusion did not correlate with length of time before the patient regained consciousness. No difference was found in mortality, stroke, and delirium between patients with and those without more than 60 minutes of circulatory arrest and cerebral perfusion., Conclusion: Prolonged (> 60 minutes) deep hypothermic circulatory arrest with retrograde cerebral perfusion was not a risk factor for mortality and stroke in patients who underwent surgery for aneurysms of the aortic arch. However, the prevalence of transient delirium necessitates further investigations.

Background: Coagulation and fibrinolysis parameters were compared between two strategies of heparinization during cardiopulmonary bypass (CPB) in patients who underwent aortic surgery with deep hypothermic circulatory arrest (DHCA) and retrograde cerebral perfusion (RGCP) with aprotinin., Methods and Results: From January 1994 to January 1996, 94 patients underwent aortic surgery with DHCA with aprotinin; replacement of the ascending aorta took place in 14 patients, arch in 69, and descending aorta in 11. Two million units of aprotinin was administrated in the priming of CPB, and 3 mg/kg heparin was given before CPB. During CPB, 49 patients had an additional 1 mg/kg/h heparin regardless of activated clotting time (ACT) [group A], whereas 45 patients had an additional 1 mg/kg/h heparin when ACT was less than 500 seconds [group B]. ACT, PT, aPTT, fibrinogen, AT-3, plasminogen, alpha2-PI (plasmin inhibitor), fibrin/fibrinogen degradation products (FDP), DD (D dimer), TAT (thrombin-antithrombin complex), PIC (plasmin-plasmin inhibitor complex), beta-TG (thromboglobulin), and PF-4 (platelet factor-4) were assayed. No difference was detected between the two groups regarding the duration of operation, CPB, aortic cross-clamping, DHCA, RGCP, and time from the end of CPB to admission to ICU. The heparin dose was greater in group A, but the protamine dose was similar. There was no difference in bleeding after perfusion or in ICU. Levels of TAT, fibrinogen, and DD were lower in group A. PIC, alpha-PI, and FDP value showed no difference. PF-4 and beta-TG were lower in group A, and the platelet count at the end of operation and the day after the operation was higher in group A., Conclusions: Platelets were better preserved and activation of the coagulation system during CPB was less severe in patients who had a regular additional constant heparin regimen irrespective of ACT in surgery for the aortic aneurysm with DHCA and aprotinin usage. An accurate monitoring system for heparinization is necessary to maintain appropriate anticoagulation during CPB in patients who are undergoing aortic surgery with DHCA using aprotinin.

To clarify the role of squalene peroxide in the occurrence of skin damage from sunburn, the optimum condition of squalene peroxidation and the effect of squalene peroxide on cutaneous tissue were examined. Peroxidation of squalene was more easily induced than palmitoleic acid and oleic acid in the unsaturated lipid occurred in sebum. The peroxidation of squalene gradually occurred by U.V. irradation, and it is parallel to increases in the malonyldialdehyde production (production of lipoperoxide). This peroxidation easily carries out in the case of high temperature (40 degrees C than 30 degrees C), and in the case of low pH. Good correspondence was recognized among the spectrum of natural daylight, U.V. absorption spectrum of squalene and erythema curve. Squalene and its peroxide have an important role in the occurrence of sunburn, and/or protection from damage caused by U.V. irradiation.