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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.)

Histidine photooxygenation has been the subject of extensive investigation for many years. The intricate nature of histidine distinguishes it from other amino acids, as its side chain readily undergoes changes in charge state and tautomerization in response to pH, and the polarity of the imidazole ring inverts upon oxidation. This complexity gives rise to a diverse range of oxidation products and mechanisms, posing challenges in their interpretation. This review aims to provide a thorough overview of the chemistry involved in histidine photooxygenation, encompassing a comprehensive analysis of resulting products, mechanisms engaged in their formation, and analytical techniques that have contributed to their identification. Additionally, it explores a wide range of applications stemming from this transformation, offering valuable insights into its practical implications in fields such as materials science, biomedical research, and drug development. By bridging the existing gap in literature, this review serves as a resource for understanding the intricacies of histidine photooxygenation and its diverse ramifications., (© 2023 The Authors. The Chemical Record published by The Chemical Society of Japan and Wiley-VCH GmbH.)

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.)

Objective: To identify the risks of myocarditis or pericarditis after vaccination with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccines in Japan., Methods: We conducted an observed-to-expected analysis (OE analysis) of spontaneous reports of suspected adverse events from pharmaceutical companies, calculating rate ratios with myocarditis and pericarditis after the vaccination of the mRNA vaccines Comirnaty (BNT162b2) and Spikevax (mRNA-1273) and expected rate of myocarditis and pericarditis in the population before the COVID-19 pandemic. These reports dated from 17/2/2021 to 14/11/2021 and from 22/5/2021 to 14/11/2021 for Comirnaty and Spikevax, respectively. The observed-to-expected ratios (OE ratios) for each vaccine were estimated by age groups and sex., Results: We identified 281 and 195 cases of myocarditis or pericarditis for Comirnaty and Spikevax, respectively, which were administrated 163,059,502 and 31,768,352 doses for Comirnaty and Spikevax until the 14th of November 2021, respectively. The OE ratios were statistically significantly higher in adolescent and young adult males in their age of teens and twenties after the second dose in a two-dose series [Comirnaty in teens male: 6.15 (95% CI, 2.26-21.98), Comirnaty in twenties male: 2.86 (95% CI, 1.13-8.38), Spikevax in teens male: 41.59 (95% CI, 5.64-43,281.94), Spikevax in twenties male: 16.84 (95%CI, 6.77-57.49)]., Conclusions: Risks of myocarditis and pericarditis following SARS-CoV-2 mRNA vaccines in Japan seems to be significantly elevated for adolescent and young adult males., (© 2022. The Author(s), under exclusive licence to The Drug Information Association, Inc.)

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.)

Purpose Implants made of anodized-hydrothermally treated commercially pure titanium with a nanotopographic surface structure (SA-treated c.p.Ti) may advantageously promote contact osteogenesis during the early stages of healing. We hypothesized that utilizing SA-treated c.p.Ti with dental pulp stem cells (DPSCs) might improve osteoconduction during the process of osseointegration. This in vitro study investigated the effect of initial adhesion of DPSCs to SA-treated c.p.Ti compared with conventional c.p.Ti and anodic oxide (AO) c.p.Ti.Methods DPSCs were obtained from the mandibular incisors of Sprague-Dawley rats and cultured without osteogenic induction medium on c.p.Ti, AO c.p.Ti, and SA-treated c.p.Ti disks for up to 14 days. The morphology, proliferation, and differentiation of DPSCs were assessed by scanning electron microscopy, an MTT assay, and Alizarin Red S staining, respectively. A real-time quantitative polymerase chain reaction was used to quantify the mRNA expression of osteocalcin, osteopontin, and bone sialoprotein.Results On all disks, the DPSCs appeared flattened with the formation of extensions over time. The filopodium-like extensions were closely bound to the SA-treated c.p.Ti surface. The proliferation of DPSCs was not significantly different among the c.p.Ti treatments. However, DPSCs on SA-treated c.p.Ti showed the greatest mRNA levels of osteopontin, osteocalcin, and bone sialoprotein, as well as increased Alizarin Red S staining.Conclusions The results of the present in vitro study demonstrate that the surface properties of SA-treated c.p.Ti disks enhance osteogenic differentiation of DPSCs and may facilitate mineralized matrix formation on SA-treated c.p.Ti implant surfaces, which can enhance early bone regeneration.

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.

The importance of continuous monitoring of skin hydration in daily life, to aid in the diagnosis of skin diseases, is rising. Electrodes that can be worn directly on the skin are attracting attention as an effective means. However, they should not inhibit natural water evaporation from the skin and should not cause inflammation or irritation even if they are attached to the body for long periods of time. In this study, nanomesh electrodes that have previously been reported to exhibit high biocompatibility are also found to exhibit high water vapor permeability, resulting in properties that prevent skin dampness. Furthermore, the skin impedance measured using nanomesh electrodes is found to correlate with the hydration level of skin measured using existing medical equipment. This study provides a new approach to measure skin hydration in conditions close to bare skin., (© 2020 Wiley-VCH GmbH.)

Background: Although liver dysfunction is one of the common complications in patients with acute heart failure (AHF), no integrated marker has been defined. The albumin-bilirubin (ALBI) score has recently been proposed as a novel, clinically-applicable scoring system for liver dysfunction. We investigated the utility of the ALBI score in patients with AHF compared to that for a preexisting liver dysfunction score, the Model of End-Stage Liver Disease Excluding prothrombin time (MELD XI) score., Methods: We evaluated ALBI and MELD XI scores in 1,190 AHF patients enrolled in the prospective, multicentre Registry Focused on Very Early Presentation and Treatment in Emergency Department of Acute Heart Failure study. The associations between the two scores and the clinical profile and prognostic predictive ability for 1-year mortality were evaluated., Results: The mean MELD XI and ALBI scores were 13.4±4.8 and -2.25±0.48, respectively. A higher ALBI score, but not higher MELD XI score, was associated with findings of fluid overload. After adjusting for pre-existing prognostic factors, the ALBI score (HR 2.11, 95% CI: 1.60-2.79, p<0.001), but not the MELD XI score (HR 1.02, 95% CI: 0.99-1.06, p=0.242), was associated with 1-year mortality. Likewise, area under the receiver-operator-characteristic curves for 1-year mortality significantly increased when the ALBI score (0.71 vs. 0.74, p=0.020), but not the MELD XI score (0.71 vs. 0.72, p=0.448), was added to the pre-existing risk factors., Conclusions: The ALBI score is potentially a suitable liver dysfunction marker that incorporates information on fluid overload and prognosis in patients with AHF. These results provide new insights into heart-liver interactions in AHF patients., (Copyright © 2019 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

The a3 isoform of vacuolar-type proton-pumping ATPase (V-ATPase) is essential for bone resorption by osteoclasts. Although more than 90 mutations of the human a3 gene have been identified in patients with infantile malignant osteopetrosis, it is unclear whether they lead to osteoclast dysfunction. We have established an in vitro assay to induce osteoclasts from spleen macrophages derived from a3-knockout mice. Here, we examined the effects of these mutations in a3-knockout osteoclasts. We were interested in four mutations, two short deletions and two missense mutations, previously identified in the a3 cytosolic domain. a3 harboring either of the two short deletions was hardly expressed in osteoclasts and calcium phosphate resorption was impaired. On the other hand, osteoclasts expressing a3 with either of the two missense mutations exhibited no defects. Specifically, expression levels of the mutant proteins, V-ATPase assembly, and calcium phosphate resorption activity were similar to those of the wild type. Moreover, these missense mutants interacted with Rab7, a small GTPase that regulates lysosomal trafficking. These results suggest that the short deletions impair a3 expression and thus disrupt V-ATPase subunit assembly essential for bone resorption, while the missense mutations do not cause osteoclast dysfunction without an additional mutation(s) or impair resorption of bone, but not of calcium phosphate., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Cutting balloons (CBs) and other scoring balloons are known to be useful for plaque modification in heavily calcified lesions. There have been some reports of the efficacy of these balloons compared to conventional balloons. However, there have been no reports exploring which balloon is most effective among these three types of balloons. We, therefore, compared these three balloons with respect to effectiveness in plaque modification of calcified lesions. We retrospectively investigated 201 cases using these three balloons from April 2015 to December 2017. Of these cases, 156 with severe calcified lesions that had undergone intravascular ultrasound (IVUS) or optical frequency domain imaging (OFDI) were enrolled. The ratio of severe calcified lesion was higher in the CB group than in the groups of other balloons (p = 0.001), and IVUS and OFDI showed that a CB was more effective in plaque modification than the other balloons. The acute gain (minimum stent diameter minus minimum lumen diameter) and acute cross-sectional area (CSA) gain (minimum stent area minus minimum lumen area) were both larger in the CB group than in the others, and the stent symmetry index (minimum stent diameter/maximum stent diameter) showed that the CB group more closely approximated a perfect circle than the other groups (p = 0.0001, 0.006 and 0.002 for the acute gain, acute CSA gain and the stent symmetry index). Similar results were obtained in cases without rotational atherectomy. These data suggest that CB is more effective for plaque modification in cases of severe calcified lesions than other scoring balloons.

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.

We recently reported that the early initiation of tolvaptan in congestive heart failure shortened the hospital stay and reduced the rate of in-hospital death. However, whether or not these results apply to elderly patients with congestive heart failure is unclear. We performed a sub-analysis of our previous study. Among the 102 patients in that study, we retrospectively analyzed the elderly patients >75 years of age treated with tolvaptan. First, we analyzed the efficacy of early tolvaptan use in these patients. We then compared the efficacy and the safety of all tolvaptan use between elderly and younger patients. There were no significant differences in the baseline clinical parameters between the early- and late-tolvaptan-use elderly patients, except for the serum blood nitrogen urea. However, the early use of tolvaptan was also associated with the earlier initiation of ambulatory cardiac rehabilitation, a shorter hospital stay, and a lower rate of in-hospital death in elderly congestive heart failure patients. Furthermore, there were no significant differences in the occurrence of worsening renal failure and hypernatremia. The early use of tolvaptan in elderly patients was also associated with a shorter hospital stay and reduced mortality. We also confirmed the safety of tolvaptan in elderly patients. It might, therefore, be beneficial to consider administering tolvaptan early in elderly patients with heart failure, just as in younger patients.

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.)

Tolvaptan is an oral antagonist of arginine vasopressin receptor 2 that has been approved in Japan to reduce congestive symptoms in patients with heart failure refractory to loop diuretics. However, it is unknown whether the early use of tolvaptan results in better clinical outcomes. We retrospectively analyzed 102 consecutive patients with decompensated heart failure treated with tolvaptan at our hospital. A given patient was defined as a responder when the maximum urine volume was greater than 150 % of that observed before tolvaptan use. A logistic regression analysis revealed that the early use of tolvaptan (within 3 days after admission) was an independent factor associated with tolvaptan responsiveness. There were no significant differences in the baseline clinical parameters between the early and late tolvaptan use groups. However, the early use of tolvaptan was associated with higher tolvaptan responsiveness, a shorter duration of carperitide infusion, earlier initiation of ambulatory cardiac rehabilitation, shorter hospital stay, lower rate of in-hospital death. The early use of tolvaptan was associated with a shorter hospital stay and reduced mortality in our retrospective cohort. It might therefore be beneficial to consider administering tolvaptan earlier in patients with heart failure.

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.)