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Background and Purpose: Despite the widespread adoption of various preventive measures since the spread of COVID-19, there remains a lack of consensus on universally acknowledged best practices. However, the significance of vaccination has risen to prominence as a paramount preventive strategy. Numerous investigations have demonstrated vaccine effectiveness against the omicron strain in severe disease and symptomatic disease, however, the scope of research pertaining to vaccine effectiveness in preventing infection is presently limited. Therefore, the current study aimed to evaluate COVID-19 mRNA (Pfizer-BioNTech BNT162b2 or Moderna mRNA-1273) vaccine effectiveness in preventing infection., Methods: We conducted a test-negative case-control study using a dataset of 117,335 individuals. These data were collected through the COVID-19 J-SPEED form in the PCR center at Hiroshima Prefecture, Japan from 1 February to 17 March 2022. We estimated propensity score matching for vaccine status based on participants' demographic characteristics. Subsequently, odds ratio was calculated from logistic regression to determine the association between vaccination status and test positivity rate adjusting for symptoms, exposure to close contact, and previous infection history. Vaccine effectiveness was defined as (1 -aORs) ×100%., Results: The PCR test positivity rates were 7.9%, 4.5%, and 2.8% for the non-vaccinated (non-vaccinated, vaccinated with a single dose, and vaccinated with two doses less than 14 days ago), vaccinated with two doses (vaccinated over 14 days ago), and three doses, respectively. In unadjusted and adjusted analyses, vaccine effectiveness of two doses against infection were 38.5% (95% confidence interval [CI]: 32.8%-43.8%) and 34.7% (95%CI: 28.4%-40.4%), respectively, compared to non-vaccinated group. Vaccine effectiveness of three doses were 33.8% (95%CI: 25.0%-41.5%) and 26.4% (95%CI: 16.4%-35.2%), respectively, compared to those vaccinated with two doses., Conclusions: These results illustrate the protective effect of mRNA vaccines against Omicron strain infections and emphasize the significance of completing the suggested vaccination schedule., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Yumiya et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Continued study of risk factors can inform future pandemic preparedness and response. We aimed to determine the potential risk factors of COVID-19 severity among patients admitted to the hospital during the Delta- and Omicron-dominant periods., Methods: We utilized the J-SPEED-style COVID-19 Hospital version, a pre-administered questionnaire, to collect data from hospitals in Hiroshima Prefecture between 8 August 2021 and 19 April 2022., Results: During the Delta-dominant period, patients aged over 65 (OR = 2.59, 95% CI = 1.75-3.84), males (OR = 1.42, 95% CI = 1.12-1.81) and with BMI exceeding 25 (OR = 1.99, 95% CI = 1.57-2.52), diabetes (OR = 2.03, 95% CI = 1.40-2.95), and those with fewer than two doses of vaccine (OR = 2.39, 95% CI = 1.46-3.91) were at a greater risk of severe COVID-19 compared to those without these risk factors. During the Omicron-dominant period, significantly greater severity was observed among patients over 65 years old (OR = 3.89, 95% CI = 2.95-5.12), males (OR = 1.76, 95% CI = 1.40-2.21), those with high blood pressure (OR = 1.30, 95% CI = 1.02-1.65), and mental disorder (OR = 2.22, 95% CI = 1.69-2.92) compared to patients without these risks., Conclusions: Our findings indicate that risk factors vary across different SARS-CoV-2 variants. Examining variant-specific risk factors for COVID-19 severity can aid policymakers, public health specialists, and clinicians in prioritizing screening, treatment, and vaccination efforts, especially during potential healthcare resource shortages.

More than 200 million COVID-19 survivors have lasting symptoms after recovering, but the duration and related risk factors remain uncertain. This study focused on all 6551 patients diagnosed with COVID-19 at a medical institution in Hiroshima from March 2020 to July 2022. In November 2022, a questionnaire survey was conducted regarding post-COVID symptoms and their duration. The prevalence and duration of post-COVID symptoms were illustrated using the Kaplan-Meier method. Risk factors for symptoms lasting over 3 months and interfering with daily life were assessed via multivariate logistic regression. A total of 2421 survivors responded: 1391 adults, 1030 children, median age 34 years (IQR 9-55), 51·2% male, 36·7% hospitalized, median time from infection to the survey was 295 days (IQR 201-538). Upon their initial recovery, the prevalence of post-COVID symptoms was 78·4% in adults and 34·6% in children. Three months later, the rates were 47·6% and 10·8%. After over one year, they were 31·0% and 6·8%. Regarding symptoms interfere with daily life, 304 people (12.6%) experienced symptoms lasting for over three months, with independent risk factors including age, being female, diabetes mellitus, infection during the Delta period, and current smoking. There was no significant association between vaccination history and post-COVID symptoms., (© 2024. The Author(s).)

Objectives: The present study investigates the diagnosis and prediction of COVID-19 based on clinical symptoms, and corresponding difference between the Delta- and Omicron-dominant periods, using data collected at polymerase chain reaction (PCR) centers in Hiroshima Prefecture, Japan., Methods: Data was collected using a J-SPEED-style COVID-19 standard data collection form. The analysis was done in two directions: calculating the likelihood ratio that clinical symptoms will manifest in "infected" versus "non-infected" individuals and calculating the diagnostic odds ratio (OR) of infection for those who have symptoms compared to those without symptoms., Results: COVID-19 was more strongly associated with smell and taste disorders during the Delta-dominant period, and muscle pain during the Omicron-dominant period. An age-specific analysis of likelihood and diagnostic ORs found cold-like symptoms had the lowest ability to diagnose COVID-19, and the lowest predictability of COVID-19 with children during both periods. The likelihood and diagnostic ORs of other symptoms for COVID-19 were highest in adults and lowest in those over 65., Conclusion: Symptoms are an important indicator of COVID-19, but the association between specific symptoms and COVID-19 is dependent on the dominant variant of the virus., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Although drug-coated balloon (DCB)-based stent-less percutaneous coronary intervention (PCI) for de-novo lesions has attracted more attention, outcomes of the DCB procedure for hemodialysis (HD) patients are reported to be inferior to those for non-HD patients, similarly to drug-eluting stent (DES). Recent several reports have shown that rotational atherectomy (RA) followed by DCB treatment (RA/DCB) could be an option of revascularization strategy particularly for calcified de-novo lesions even in the new-generation DES era; however, efficacy of the RA/DCB procedure for HD patients remains unclear., Methods: A total of 47 consecutive cases (53 lesions) undergoing RA/DCB for de-novo lesions were enrolled. According to the presence/absence of HD at baseline, the 47 cases were divided into the HD cases (N.=16) and the non-HD cases (N.=31), and the 53 lesions were divided into the HD lesions (N.=20) and the non-HD lesions (N.=33)., Results: The HD cases had a significantly lower prevalence of dyslipidemia and smoking than the non-HD cases. Final RA burr size, DCB diameter used, and angiographic success rate of PCI did not significantly differ between the 2 groups. Preprocedural, post-procedural, and follow-up QCA parameters were also similar between the 2 groups. Twelve-month clinical outcomes were comparable between the 2 groups., Conclusions: Mid-term outcomes of stent-less PCI using RA/DCB for de-novo lesions in HD patients might be comparable to those in non-HD patients, suggesting efficacy of pretreatment of RA prior to DCB treatment in HD patients.

It is crucial to provide mental health care following a disaster because the victims tend to experience symptoms such as anxiety and insomnia during the acute phase. However, little research on mental health during the acute phase has been conducted, and reported only in terms of the temporal transition of the number of consultations and symptoms. Thus, the aim of the study was to examine how mental health care needs are accounted for in the overall picture of disaster relief and how they change over time. Using data from the Japanese version of Surveillance in Post-Extreme Emergencies and Disasters (J-SPEED), we assessed the mental health of injured and ill patients to whom Emergency Medical Teams (EMTs) were providing care during the acute period of a disaster. Approximately 10% of all medical consultations were for mental health issues, 83% of which took place within the first 2 weeks after the disaster. The findings showed that, from the start of the response period to the 19th response day, the daily proportion of mental health problems declined substantially, and then gradually increased. Such a V-shaped pattern might be helpful for identifying phase changes and supporting the development of EMT exit strategies.

This study aimed to exercise the Sanger sequencing strategy for screening of variants among confirmed COVID-19 cases and validate our strategy against NGS strains in Hiroshima retrieved from GISAID. A total of 660 samples from confirmed COVID-19 cases underwent screening for variants by Sanger-based partial sequencing to the targeted spike gene (nt22,735~nt23,532) using an in-house-developed primer set. The identification of variants was done by unique checkpoints of base nucleotide changes in the targeted spike gene. Moreover, we amplified one full-length genome using Sanger method and an in-house-developed primer library. Using NGS strains of the same sampling period from GISAID, a phylogenetic tree was constructed to examine the distribution pattern of variants in Hiroshima and to validate our Sanger method. The modified primer set provided 100% validation and 99.2% amplification. PANGO Lineage R.1 was detected in late in the third wave, followed by Alpha (B.1.1.7) domination in the fourth wave, Delta (B.1.617.2) domination in the fifth wave, and Omicron (B.1.1.529) domination in the sixth wave, and there was no significant difference in viral copies between variants ( p = 0.09). The variants showed different transmission patterns, but the distribution of variants is consistent to that shown by the phylogenetic tree. The Sanger method also provided successful amplification of the full-length genome of the SARS-CoV-2 virus. Our Sanger sequencing strategy was useful for the screening of SASR-CoV-2 variants without the need for full-genome amplification. The modified primer set was validated to use universally, which allows an understanding of the variants' distribution in real time and provides the evidence for policy-making and the formulation or modification of preventive strategies.

Introduction: Rainfall-induced floods and landslides accounted for 20.7% of all disaster events in Japan from 1985 through 2018 and caused a variety of health problems, both directly and indirectly, including injuries, infectious diseases, exacerbation of pre-existing medical conditions, and psychological issues. More evidence of health problems caused by floods or heavy rain is needed to improve preparedness and preventive measures; however, collecting health data surrounding disaster events is a major challenge due to environmental hazards, logistical constraints, political and economic issues, difficulties in communication among stakeholders, and cultural barriers. In response to the West Japan Heavy Rain in July 2018, Emergency Medical Teams (EMTs) used Japan - Surveillance in Post-Extreme Emergencies and Disasters (J-SPEED) as a daily reporting template, collecting data on the number and type of patients they treated and sending it to an EMT coordination cell (EMTCC) during the response., Study Objective: The aim of the study was to conduct a descriptive epidemiology study using J-SPEED data to better understand the health problems during floods and heavy rain disasters., Methods: The number and types of health problems treated by EMTs in accordance with the J-SPEED (Ver 1.0) form were reported daily by 85 EMTs to an EMTCC, where data were compiled during the West Japan Heavy Rain from July 8 through September 11, 2018. Reported items in the J-SPEED form were analyzed by age, gender, area (prefecture), and time period., Results: The analysis of J-SPEED data from the West Japan Heavy Rain 2018 revealed the characteristics of a total of 3,617 consultations with the highest number of consultations (2,579; 71.3%) occurring between Day 5 and Day 12 of the 65-day EMT response. During the response period, skin disease was the most frequently reported health event (17.3%), followed by wounds (14.3%), disaster stress-related symptoms (10.0%), conjunctivitis (6.3%), and acute respiratory infections (ARI; 5.4%)., Conclusion: During the response period, skin disease was the most frequently reported health event, followed by wounds, stress, conjunctivitis, and ARIs. The health impacts of a natural disaster are determined by a variety of factors, and the current study's findings are highly context dependent; however, it is expected that as more data are gathered, the consistency of finding will increase.

This study aimed to develop the feasible and effective universal screening strategy of the notable SARS-CoV-2 variants by Sanger Sequencing Strategy and then practically applied it for mass screening in Hiroshima, Japan. A total of 734 samples from COVID-19 confirmed cases in Hiroshima were screened for the notable SARS-CoV-2 variants (B.1.1.7, B.1.351, P.1, B.1.617.2, B.1.617.1, C.37, B.1.1.529, etc.). The targeted spike region is amplified by nested RT-PCR using in-house designed primer set hCoV-Spike-A and standard amplification protocol. Additionally, randomly selected 96 samples were also amplified using primer sets hCoV-Spike-B and hCoV-Spike-C. The negative amplified samples were repeated for second attempt of amplification by volume-up protocol. Thereafter, the amplified products were assigned for Sanger sequencing using corresponding primers. The positive amplification rate of primer set hCoV-Spike-A, hCoV-Spike-B and hCoV-Spike-C were 87.3%, 83.3% and 93.8% respectively for standard protocol and increased to 99.6%, 95.8% and 96.9% after second attempt by volume-up protocol. The readiness of genome sequences was 96.9%, 100% and 100% respectively. Among 48 mutant isolates, 26 were B.1.1.7 (Alpha), 7 were E484K single mutation and the rest were other types of mutation. Moreover, 5 cluster cases with single mutation at N501S were firstly reported in Hiroshima. This study indicates the reliability and effectiveness of Sanger sequencing to screen large number of samples for the notable SARS-CoV-2 variants. Compared to the Next Generation Sequencing (NGS), our method introduces the feasible, universally applicable, and practically useful tool for identification of the emerging variants with less expensive and time consuming especially in those countries where the NGS is not practically available. Our method allows not only to identify the pre-existing variants but also to examine other rare type of mutation or newly emerged variants and is crucial for prevention and control of pandemic., (© 2022. The Author(s).)

Introduction: Japan recently experienced two major heavy rain disasters: the West Japan heavy rain disaster in July 2018 and the Kumamoto heavy rain disaster in July 2020. Between the occurrences of these two disasters, Japan began experiencing the wave of the coronavirus disease 2019 (COVID-19) pandemic, providing a unique opportunity to compare the incidence of acute respiratory infection (ARI) between the two disaster responses under distinct conditions., Sources for Information: The data were collected by using the standard disaster medical reporting system used in Japan, so-called the Japan-Surveillance in Post-Extreme Emergencies and Disasters (J-SPEED), which reports number and types of patients treated by Emergency Medical Teams (EMTs). Data for ARI were extracted from daily aggregated data on the J-SPEED form and the frequency of ARI in two disasters was compared., Observation: Acute respiratory infection in the West Japan heavy rain that occurred in the absence of COVID-19 and in the Kumamoto heavy rain that occurred in the presence of COVID-19 were responsible for 5.4% and 1.2% of the total consultation, respectively (P <.001)., Analysis of Observation and Conclusion: Between the occurrence of these two disasters, Japan implemented COVID-19 preventive measures on a personal and organizational level, such as wearing masks, disinfecting hands, maintaining social distance, improving room ventilation, and screening people who entered evacuation centers by using hygiene management checklists. By following the basic prevention measures stated above, ARI can be significantly reduced during a disaster.

Background: This longitudinal study aimed to determine chronological changes in the seroprevalence of prior SARS-CoV-2 infection, including asymptomatic infections in Hiroshima Prefecture, Japan., Methods: A stratified random sample of 7,500 residents from five cities of Hiroshima Prefecture was selected to participate in a three-round survey from late 2020 to early 2021, before the introduction of the COVID-19 vaccine. The seroprevalence of anti-SARS-CoV-2 antibodies was calculated if at least two of four commercially available immunoassays were positive. Then, the ratio between seroprevalence and the prevalence of confirmed COVID-19 cases in Hiroshima was calculated and compared to the results from other prefectures where the Ministry of Health, Labour and Welfare conducted a survey by using the same reagents at almost the same period., Results: The numbers of participants in the first, second, and third rounds of the survey were 3025, 2396, and 2351, respectively and their anti-SARS-CoV-2 antibodies seroprevalences were 0.03% (95% confidence interval: 0.00-0.10%), 0.08% (0.00-0.20%), and 0.30% (0.08-0.52%), respectively. The ratio between the seroprevalence and the prevalence of confirmed COVID-19 cases in Hiroshima was 1.2, which was smaller than that in similar studies in other prefectures., Conclusions: The seroprevalence of anti-SARS-CoV-2 antibodies in Hiroshima increased tenfold in a half year. The difference between seroprevalence and the prevalence of confirmed COVID-19 cases in Hiroshima was smaller than that in other prefectures, suggesting that asymptomatic patients were more actively detected in Hiroshima.

With the widespread and increasing number of cases of Coronavirus Disease (2019) globally, countries have been taking preventive measures against this pandemic. However, there is no universal agreement across cultures on whether wearing face masks are an effective physical intervention against disease transmission. We investigated the relationship between mask wearing and COVID-19 among close contacts of COVID-19 patients in the Hiroshima Prefecture, Japan. In the Hiroshima Prefecture, a COVID-19 form adapted from the reporting form, "Japanese Surveillance in Post-Extreme Emergencies and Disasters", was developed to collect data from COVID-19 patients' close contacts under active epidemiological surveillance at Public Health Centers. The relative risk of COVID-19 for mask users versus non-mask users was calculated. A total of 820 interviewees were included in the analysis and 53.3% of them responded that they wore masks. Non-mask users were infected at a rate of 16.4%, while mask users were infected at a rate of 7.1%. Those who wore masks were infected at a rate of 0.4 times that of those who did not wear masks. (RR = 0.4, 95%CI = 0.3-0.6; Adjusted RR = 0.6, 95%CI = 0.3-0.9). These findings implied that COVID-19 could be avoided to a certain degree by wearing a mask.

Background: In this study, we performed molecular characterization of SARS-CoV-2 strains in Hiroshima and its mutation pattern between the first and second waves of the outbreak., Method: A total of 55 nasal swab samples from the first wave in Hiroshima and 13 from the second wave were examined quantitatively by RT-qPCR and qualitatively by nested PCR using specific primers. Four samples from each wave underwent next-generation sequencing and phylogenetic tree analysis including controls and all sequences retrieved in Japan from GISAID and GenBank. Subsequently, mutations were examined., Results: Viral load ranged 7.85 × 101-1.42 × 108 copies/ml. Of 68 samples, one was Asian type-O, 65 were European type-GR, and 2 were undetectable. Phylogenetic tree analysis indicated that Japan was infected with various Asian strains (L, S, V, O) from January through April. By second week of March, European strains (G, GH, GR) had appeared, and GR strains became predominant after mid-March. The first case in Hiroshima was classified as Asian strain O, and the rest were GR strains. Then, second wave of GR strains appeared independently with 11-15 base mutations. Comparing the first- and second-wave GR strains, mutation rate was 1.17-1.36 × 10-3 base substitutions per site per year; in addition, amino acid changes occurred at S1361P and P3371S in ORF1a, A314V in ORF1b, and P151L in N. All seven GR strains were D614G variants with R202K and G203R mutations in N. A single-nucleotide insertion in ORF8 that causes a defect in ORF8 protein was found in one isolate (S66) from the second wave., Conclusion: Our findings reveal the evolutionary hierarchy of SARS-CoV-2 in Japan. The predominant D614G variants and a new form of ORF8 deletion in Hiroshima provide the clue for role of viral factor in local outbreaks of SARS-CoV-2., Competing Interests: The authors have declared that no competing interests exist.

Background: Several recent reports have shown that a stentless interventional procedure using rotational atherectomy followed by drug-coated balloon (DCB) treatment (RA/DCB) is a potent revascularization therapy for calcified de novo lesions even in the new-generation drug-eluting stent era; however, the role of the RA/DCB procedure for noncalcified de novo lesions remains unclear., Methods: A total of 47 consecutive patients (53 lesions) who underwent RA/DCB for coronary de novo lesions were enrolled. According to the presence or absence of severe calcification at target lesions on fluoroscopy, the 47 patients were divided into the noncalcified cases (n = 12) and the calcified cases (n = 35), and the 53 lesions were divided into the noncalcified lesions (n = 14) and the calcified lesions (n = 39)., Results: The noncalcified cases tended to have a higher frequency of bleeding risk and had a significantly lower prevalence of dual antiplatelet therapy compared with the calcified cases. The main lesion-specific factors for the RA/DCB procedure among the noncalcified lesions were presence of left circumflex coronary artery ostial lesion. The final burr size, DCB diameter used, and angiographic success rate did not significantly differ between the 2 groups. The noncalcified lesions had a larger reference diameter and a shorter lesion length than the calcified lesions, whereas acute gain and late lumen loss did not differ between the 2 groups. Nine-month clinical outcomes were comparable between the 2 groups., Conclusions: Under drug-eluting stent-unsuitable clinical or lesion conditions, acute and midterm outcomes of RA/DCB for noncalcified de novo lesions might be comparable with those for calcified de novo lesions., (© 2021 The Authors.)

Objectives: We investigated angiographic and clinical outcomes in patients with de novo lesions undergoing rotational atherectomy (RA) followed by drug-coated balloon (DCB) dilation (RA/DCB)., Background: Implantation of drug-eluting stent (DES) has been a mainstay of the interventional treatment of coronary artery disease (CAD); however, there still remain several DES-unsuitable clinical/lesion conditions. Nowadays DCB for de novo lesions has attracted more attention, and RA, which tends not to cause major dissection but to debulk intima, might be one of suitable pre-treatments before DCB., Methods and Results: Thirty patients (34 lesions) undergoing RA/DCB for de novo lesions were enrolled. Clinical/lesion background included severe calcification, calcified nodule, inlet/outlet of aneurysm, ostial lesion, severe thrombocytopenia, bleeding tendency, and/or sequelae of Kawasaki disease. The largest burr size used was 1.83 ± 0.23 mm, and the mean DCB diameter was 2.71 ± 0.47 mm. Angiographic success was obtained in 94% of the lesions. No acute closure but 1 no reflow occurred. Repeat angiography (mean, 6.6 months after procedure) was performed for 19 lesions. Frequency of binary restenosis was 21.1%, and late lumen loss was 0.34 ± 0.30 mm. During a mean follow-up period of 13.1 months, 6 deaths (2 sudden deaths, 1 cardiac death, 3 non-cardiac deaths), 2 strokes, and 2 target lesion revascularizations were observed., Conclusions: Stent-less PCI using RA/DCB might be an alternative revascularization therapy for CAD patients complicated with DES-unsuitable conditions., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest regarding the content of the manuscript., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Even in the drug-eluting stent era, ostial lesion of the right coronary artery (RCA) still remains therapeutic challenge for interventional cardiologists. Case Series Case 1 (76 y.o. male) with angina on effort underwent transradial stent-less percutaneous coronary intervention (PCI) using rotational atherectomy (RA) followed by drug-coated balloon (DCB) dilation alone (RA/DCB) against a calcified de novo RCA ostial lesion. Case 2 (86 y.o. female) with recurrent unstable angina and hemodialysis underwent transfemoral RA/DCB against a severe repeat in-stent restenosis probably due to calcified nodule in the RCA ostium. In the both patients, PCI was successfully completed under intravascular ultrasound imaging (IVUS) guidance without complications. Follow-up CAG performed 4-5 months after the procedure revealed no significant lumen narrowing in the both RCA ostial lesions., Conclusions: The both cases suggest that stent-less PCI using RA/DCB under IVUS might be an alternative revascularization therapy of choice for calcified RCA ostial lesions., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective The purpose of the present study was to examine the relationship between thrombocytopenia at baseline and in-hospital outcomes in unselected patients undergoing elective percutaneous coronary intervention (PCI) in Japan. Methods Among a total of 1,247 consecutive elective PCI-treated patients, patients with a baseline platelet count 150,000-449,000/μL and 50,000-149,000/μL were assigned to the normal platelet (n=1,009) and thrombocytopenia (n=226) groups, respectively. The thrombocytopenia group was further divided into the mild thrombocytopenia (100,000-149,000/μL, n=187) and moderate thrombocytopenia (50,000-99,000/μL, n=39) groups. Results The angiographic success rate of PCI and in-hospital mortality rate did not differ to a statistically significant extent between the normal platelet and thrombocytopenia groups or between the mild thrombocytopenia and moderate thrombocytopenia groups, whereas the moderate thrombocytopenia group had a significantly higher rate of access site-related bleeding complications than the normal platelet group. According to a multivariate analysis, moderate thrombocytopenia was an independent predictor of access site-related bleeding complications. Conclusion Among patients with mild to moderate thrombocytopenia, elective PCI might be feasible and effective in the short term; however, more attention should be paid to access site-related bleeding complications, particularly in patients with moderate thrombocytopenia.

A 77-year-old man was referred to our hospital for angina on effort. Coronary angiography and computed tomography demonstrated a single coronary artery arising from the right sinus of Valsalva. The left circumflex coronary artery (LCx) anomalously deriving near from the ostium of right coronary artery exhibited severe stenosis in the bifurcation of the obtuse marginal branch. Although the bifurcation lesion still remains a therapeutic challenge for guide extension catheter (GEC)-based percutaneous coronary intervention, under the guidance of intravascular ultrasound imaging, we successfully implanted an everolimus-eluting stent at the bifurcated LCx lesion and performed kissing balloon inflation using 0.014- and 0.010-inch systems through GECs.

Background: Experiences of rotational atherectomy (RA) followed by drug-coated balloon (DCB) dilation alone (RA/DCB) for de novo coronary artery lesion have been limited., Case Series: Case 1 (65 year-old male) with silent myocardial ischemia and hemodialysis had old anterior myocardial infarction and intact LM/LCx, and underwent RA/DCB against a diffuse calcified lesion in the proximal LAD and a tandem lesion in the proximal RCA. Case 2 (88 year-old female) with post-infarction unstable angina had severe thrombocytopenia and anemia due to myelodysplastic syndrome (platelet 6000/μL, hemoglobin 8.3 g/dL), and underwent RA/DCB against a severe stenosis in the mid LCx after transfusions. Case 3 (47 year-old male) with silent myocardial ischemia due to possible sequelae of Kawasaki disease underwent RA/DCB against a restenotic lesion at the in-let of the calcified aneurysm in the proximal LAD. In all of the patients, PCI was successfully completed under optical frequency domain imaging (OFDI) without complications. Follow-up CAG performed 6-7 months after the procedure revealed no restenosis in case 1 and case 3, and all of the 3 cases have been free of cardiovascular/hemorrhagic events for 11-37 months since the last stent-less procedures., Conclusions: These cases suggest that RA/DCB under OFDI might be an alternative stent-less revascularization therapy of choice for patients who may be unsuitable for drug-eluting stent implantation., (Copyright © 2018 Elsevier Inc. All rights reserved.)

An 83-year-old man presented with recurrent acute coronary syndrome (ACS) at the left main coronary artery (LMCA) complicated with ostial chronic total occlusion (CTO) in the right coronary artery (RCA) (RCA-CTO). At the first LMCA-ACS approximately 1 year earlier, he had undergone LMCA-crossover stenting with a biolimus-eluting stent in the presence of RCA-CTO. At the second LMCA-ACS, we angiographically confirmed severe in-stent restenosis in the distal LMCA, in addition to angled severe stenosis in the just proximal LCx, and performed primary PCI for the LMCA bifurcation lesion under intra-aortic balloon pumping support. Because of difficulty in crossing a guidewire through the just proximal LCx lesion, we first performed rotational atherectomy against the LMCA in-stent eccentric lesion. After successfully crossing the guidewire into the LCx, we added balloon dilation with kissing balloon inflation followed by alternate drug-coated balloon dilation. An eight-month follow-up coronary angiography revealed no further vessel narrowing in the LMCA bifurcation lesion.

An 89-year-old woman appeared to have acute coronary syndrome at the left main trunk (LMT) complicated with severe aortic stenosis, moderate-severe mitral regurgitation, depressed left ventricular (LV) function, and multivessel disease. Because of sustained hypotension even under intra-aortic balloon pumping support during emergency coronary angiograhy, we performed primary percutaneous coronary intervention solely for the LMT lesion using a bare metal stent, leading to recovery from the shock state. On the second hospital day, based on our heart-team consensus, we performed aortic valve replacement and coronary artery bypass grafting surgery, and added edge-to-edge repair (Alfieri stitch) of the mitral valve, resulting in complete revascularization and dramatically improved LV function.

Aim: National medical projects are carried out according to medical care plans directed by the Medical Care Act of Japan. In order to improve Japanese perinatal medical care, it is necessary to determine the factors that might influence perinatal outcome., Methods: Statistical data of births and perinatal deaths were obtained for all municipalities in Japan from 2008 to 2012 from the Portal Site of Official Statistics of Japan (e-Stat). The perinatal mortality of all 349 Japanese secondary medical care zones was calculated. The number of neonatal intensive care units (NICUs), maternal-fetal intensive care units (MFICUs), pediatricians and obstetricians in 2011 were also obtained from e-Stat. Nine secondary medical care zones in two prefectures, Fukushima (7) and Miyagi (2) were excluded to eliminate the influence of the 2011 Great East Japan Earthquake., Results: The 340 secondary medical care zones were divided into three groups according to population size and density: metropolis, provincial city, and depopulation. The number of secondary medical care zones in each group were 52, 168, and 120, respectively. The secondary medical care zones in the depopulation group had fewer pediatricians and significantly fewer NICUs and MFICUs than the metropolis group, but there was no significant difference in perinatal mortality. The only independent risk factor for high perinatal mortality, determined by multivariable analysis, was the absence of an NICU (P = 0.011)., Conclusions: To consider directions in perinatal medical care, planned arrangement and appropriate access to NICUs is indispensable., (© 2016 Japan Society of Obstetrics and Gynecology.)

A J-shaped or U-shaped curve phenomenon might exist between systolic blood pressure (SBP) or pulse pressure (PP) at admission and in-hospital mortality in Japanese patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI). However, data regarding a relationship between mean blood pressure (MBP) at admission and in-hospital outcome in AMI patients undergoing primary PCI are still lacking in Japan.A total of 1,413 primary PCI-treated AMI patients were classified into quintiles based on admission MBP (< 79 n = 283, 79-91 n = 285, 92-103 n = 285, 104-115 n = 279, and ≥ 116 mmHg n = 281). Patients with MBP < 79 mmHg had a significantly higher in-hospital mortality, while mortality was not significantly different among the other quintiles: 16.6% (< 79), 4.9% (79-91), 3.9% (92-103), 3.2% (104-115), and 5.0% (≥ 116 mmHg). On multivariate analysis, Killip class ≥ 3 at admission, LMT or multivessels as culprit lesions, admission MBP < 79 mmHg, and age were independent positive predictors of in-hospital mortality, whereas hypercholesterolemia and TIMI 3 flow before/after PCI were negative predictors, while the other MBP categories were not.These results suggest that admission MBP < 79 mmHg might be associated with in-hospital death, and the in-hospital prognostic effects of MBP, the steady component of blood pressure, at admission might be different from those of SBP or PP, the pulsatile component of blood pressure, at admission in Japanese AMI patients undergoing primary PCI.

Rotational atherectomy with/without low-pressure balloon dilation has been a mainstay of interventional treatment for stenosis due to the coronary sequelae of Kawasaki disease (KD). Here, we report a restenosis case of probable coronary sequelae of KD treated with rotational atherectomy with low-pressure 2.5-mm balloon dilation 6 months previously. Under the guidance of optical frequency domain imaging, we performed rotational atherectomy followed by 2.5-mm drug-coated balloon (DCB) dilation for an atherosclerotic restenosis at the inlet of a calcified aneurysm in the proximal left anterior descending coronary artery. Coronary angiography 6 months later showed no apparent progression of vessel narrowing, and we could defer repeat intervention. The present case suggests that rotational atherectomy followed by DCB dilation could be an alternative revascularization therapy of choice in coronary KD sequelae complicated with atherosclerosis.

Acute myocardial infarction (AMI) at left main trunk (LMT) is a deteriorated condition with high in-hospital morbidity and mortality; however, detailed data regarding AMI patients with LMT as culprit lesion (LMT-AMI patients) undergoing primary percutaneous coronary intervention (PCI) has been still limited. Using the AMI-Kyoto Multi-Center Risk Study database, clinical background, angiographic findings and results of primary PCI were retrospectively compared between primary PCI-treated LMT-AMI patients without in-hospital death (survivors, n = 21) and those with in-hospital death (non-survivors, n = 19). The survivors had higher values of estimated glomerular filtration rate (eGFR) and systolic blood pressure at admission and lower prevalence of Killip grade 4 than the non-survivors. Pre-procedural thrombolysis in myocardial infarction (TIMI) flow grade ≥2 at the initial coronary angiography (CAG) and post-procedural TIMI flow grade 3 at the final CAG were more frequent in the survivors, compared with the non-survivors. In contrast, age and gender did not differ significantly between the two groups. On multivariate analysis, higher eGFR and Killip grade 4 at admission were found to be independent in-hospital prognostic factors in the LMT-AMI patients. Admission eGFR and Killip grade 4 are tightly associated with in-hospital prognosis in LMT-AMI patients undergoing primary PCI.

Arteriovenous fistula (AVF) after trans-radial catheterization is an extremely rare complication. A 61-year-old man experienced a painful swelling in the left radial punctured site. The findings of vascular ultrasound and angiography led to a diagnosis of an iatrogenic radial AVF. We performed continuous compression using a hemostatic band for 24 h after which the radial AVF completely disappeared without vessel occlusion, and no relapse occurred. Eight cases of catheterization-induced radial AVF have been mentioned in the literature, but the treatment has not been noninvasive in any case. This is the first report of an iatrogenic radial AVF that was noninvasively repaired using continuous low-pressure compression with a hemostatic band. < Learning objective: Arteriovenous fistula (AVF) after trans-radial catheterization is a rare complication. The literature reports only 8 cases of catheterization-induced radial AVF and no patient has been cured noninvasively. This is the first report of an iatrogenic radial AVF that was repaired noninvasively. We believe that continuous low-pressure compression using a hemostatic band is an effective therapeutic option for this complication.>.

"Heart Risk View" is the software to evaluate the cardiac event probability, and it is based on the results of the prospective cohort study (J-ACCESS). We examined the usefulness of this software. Study population consisted of 83 patients, who were diagnosed that cardiac event probability was over 20% by "Heart Risk View." During the follow-up period (596 +/- 356 days), cardiac event occurred in 23 patients (27.7%), including 7 patients death. No significant differences were observed in the ejection fraction by Quantitative Gated SPECT, total defect score calculated from SPECT, and the percentage of stress perfusion abnormality detected by SPECT between event and non-event groups. However, the percentage of cardiac revascularization therapy based on the SPECT was significantly lower in the event group (9 vs. 38%, p = 0.03). In conclusion, cardiac event probability calculated by "Heart Risk View" was reliable in our study cohort. Cardiac event strongly depended on the cardiac ischemia, for which the therapy was difficult because of lesion complexity or combined diseases.

Angiography is not always an accurate indicator of physiologically significant stenosis. We examined the usefulness of functional evaluation of coronary stenosis severity by determining the fractional flow reserve (FFR) using a pressure wire in patients who received hemodialysis with angiographically intermediate lesions. We recruited 44 patients with intermediate lesions; of these, 22 were undergoing hemodialysis while 22 were not. Quantitative coronary angiography (QCA) was performed to measure the minimal lumen diameter (MLD) and calculate the percent diameter stenosis (%DS). The FFR was calculated as the ratio of the coronary pressure at the distal stenotic site to the mean aortic pressure during maximum hyperemia. In each group, we investigated the relationship between the FFR and %DS and FFR and MLD. The patients in the hemodialysis group were significantly younger and had more calcified and type B2/C lesions than those in the non-dialysis group. Although the FFR was correlated with both %DS (r = 0.71, p < 0.01) and MLD (r = 0.58, p < 0.01) in the non-dialysis group, the FFR was not correlated with either MLD or %DS in the hemodialysis group. In the hemodialysis group, there was a discordance between the QCA- and FFR-based assessments of the severity of coronary stenosis. In patients receiving hemodialysis, both anatomical and functional assessments should be conducted to determine the physiological significance of the stenosis accurately.

Objective: Reactive oxygen species (ROS) are involved in the initial process of atherosclerosis, whereas it remains to be determined how atherogenic stimulus causes ROS-mediated proinflammatory reactions. Here, we focused on proline-rich tyrosine kinase (PYK2)-mediated ROS generation and examined how atherogenic stimulus causes early proinflammatory reactions., Methods and Results: PYK2-deficient (knockout [KO]) (PYK2-KO) mice were crossbred with apolipoprotein E (ApoE)-deficient (PYK2-KO/ApoE-KO) mice. PYK2-KO/ApoE-KO mice and endothelial cells (EC) were used for the study. Aortic atherogenic lesions in PYK2-KO/ApoE-KO mice were markedly decreased (55% versus ApoE-KO) after 8 weeks of a Western diet. Aortic PYK2 was activated as early as 7 days after the Western diet, when inflammatory cells were not yet activated. Addition of the proatherogenic oxidized phospholipid lysophosphatidylcholine caused activation of endothelial PYK2. Lysophosphatidylcholine-activated PYK2 induced NADPH oxidase-mediated ROS generation and ROS-mediated synthesis of tumor necrosis factor-α (TNFα), vascular cell adhesion molecule-1 (VCAM-1), monocyte chemotactic protein-1 (MCP-1), and p21Cip1/Ets-1. Neutralizing anti-TNFα antibody or knockdown of p21Cip1/Ets-1 system blocked the induction of VCAM-1 and MCP-1. PYK2 deficiency abolished these ROS-mediated proinflammatory reactions. Further analysis revealed that PYK2/ROS-mediated p21Cip1/Ets-1 activation upregulated the transcription of the MCP-1 gene in collaboration with p300 transcription coactivator., Conclusions: PYK2 is a key tyrosine kinase activated by high cholesterol exposure, which causes ROS-mediated TNFα release and induces TNFα-dependent expression of proinflammatory molecules via the p21Cip1/Ets-1/p300 transcription system.

Members of the fibroblast growth factor (FGF) family have been clinically applied to the treatment of ischemic diseases because of their strong angiogenic actions. Although tissue ischemia is predominantly caused by atherosclerosis, the roles of endothelial FGF receptors (FGF-Rs) in atherosclerosis remain obscure. We generated endothelial cell (EC)-targeted constitutively active FGF-R2-overexpressing mice, using the Tie2 promoter (Tie2-FGF-R2-Tg), and crossed them with apolipoprotein E (ApoE)-deficient mice (ApoE-KO) to generate Tie2-FGF-R2-Tg/ApoE-deficient mice (Tie2-FGF-R2-Tg/ApoE-KO). After being fed a Western diet for 8 wk, the Tie2-FGF-R2-Tg/ApoE-KO demonstrated 2.0-fold greater atherosclerotic lesion area on the luminal surfaces of the aortas than the ApoE-KO (P < 0.01). The level of p21(Cip1) protein, a cell cycle inhibitor, in the FGF-R2-overexpressing EC was 2.5-fold greater than that in the wild-type (WT) EC at the baseline (P < 0.01). FGF-R2 overexpression in the EC resulted in increased expression of VCAM-1 and ICAM-1, acceleration of apoptosis, and decreased proliferative activity, all of which were normalized by small interfering RNA (siRNA)-mediated knockdown of p21(Cip1) (75% reduction in protein level, P < 0.01). Furthermore, the expression of PDGF-B and Egr-1, a PDGF/p21(Cip1)-inducible transcription factor, in the aortic endothelium of Tie2-FGF-R2-Tg/ApoE-KO was significantly greater than that in ApoE-KO. The proliferation of vascular smooth muscle cells in the aortic media of Tie2-FGF-R2-Tg/ApoE-KO was 2.0-fold higher than that in ApoE-KO (P < 0.01). Thus our study reveals that endothelial FGF-R2 signaling aggravates atherosclerosis by promoting p21(Cip1)-mediated EC dysfunction and cautions against the use of FGF for therapeutic angiogenesis in the setting of atherosclerosis.

Rationale: It has been reported that interleukin (IL)-1 is associated with pathological cardiac remodeling and LV dilatation, whereas IL-1beta has also been shown to induce cardiomyocyte hypertrophy. Thus, the role of IL-1 in the heart remains to be determined., Objective: We studied the role of hypertrophy signal-mediated IL-1beta/insulin-like growth factor (IGF)-1 production in regulating the progression from compensative pressure-mediated hypertrophy to heart failure., Methods and Results: Pressure overload was performed by aortic banding in IL-1beta-deficient mice. Primarily cultured cardiac fibroblasts (CFs) and cardiac myocytes (CMs) were exposed to cyclic stretch. Heart weight, myocyte size, and left ventricular ejection fraction were significantly lower in IL-1beta-deficient mice (20%, 23% and 27%, respectively) than in the wild type 30 days after aortic banding, whereas interstitial fibrosis was markedly augmented. DNA microarray analysis revealed that IGF-1 mRNA level was markedly (approximately 50%) decreased in the IL-1beta-deficient hypertrophied heart. Stretch of CFs, rather than CMs, abundantly induced the generation of IL-1beta and IGF-1, whereas such IGF-1 induction was markedly decreased in IL-1beta-deficient CFs. IL-1beta released by stretch is at a low level unable to induce IL-6 but sufficient to stimulate IGF-1 production. Promoter analysis showed that stretch-mediated IL-1beta activates JAK/STAT to transcriptionally regulate the IGF-1 gene. IL-1beta deficiency markedly increased c-Jun N-terminal kinase (JNK) and caspase-3 activities and enhanced myocyte apoptosis and fibrosis, whereas replacement of IGF-1 or JNK inhibitor restored them., Conclusions: We demonstrate for the first time that pressure-mediated hypertrophy and mechanical stretch generates a subinflammatory low level of IL-1beta, which constitutively causes IGF-1 production to maintain adaptable compensation hypertrophy and inhibit interstitial fibrosis.

Fibroblast growth factor receptor (FGFR) is expressed in a variety of cells and is involved in their proliferation/migration/survival. To elucidate FGFR-mediated specific action of vascular endothelial cells (ECs) on myocardial ischemia, we generated endothelium-targeted transgenic mice overexpressing constitutively active FGFR2 using Tie2 promoter (FGFR2-Tg). Infarct size, vessel formation and blood perfusion were significantly improved 28 days after myocardial infarction (MI) in FGFR2-Tg, compared with wild-type mice. Aortic ECs isolated from FGFR-Tg showed a marked increase in migratory capacity and tube formation. These in vitro angiogenic activities were blocked by PI3-kinase inhibitor. Whereas, parameters obtained from echocardiography were already improved at three days after MI. Cardiomyocyte apoptosis at the ischemic border zone was decreased in FGFR2-Tg (32.1%, p < 0.05) and cardiac mRNA expression of FGF2 (basic FGF) was also up-regulated (142%, p < 0.05) at 3 days after MI. 1% oxygen-mediated apoptosis was significantly inhibited in FGFR2-Tg-ECs and this inhibition was abolished by PI3-kinase inhibitor. FGFR2-Tg-ECs exposed to 1% oxygen exhibited enhanced phosphorylation of 416-Tyr-Src, 473-Ser-Akt, and HIF1alpha accumulation. The production of FGF2 was enhanced 2.1-fold in FGFR-Tg-ECs under 1% oxygen via the Src/Akt/HIF1alpha pathway, which induced the peri-vessel migration of vascular smooth muscle cells (VSMCs) and anti-apoptotic effects on VSMCs and cardiomyocytes. FGF receptor signaling in ECs promoted migration, survival and autocrine production of FGF2, leading to reduced infarct size, which is associated with anti-apoptotic action in the early stage and with enhanced angiogenesis in the late stage after MI.