Clinical Background and Coronary Artery Lesions Characteristics in Japanese Patients With Acute Coronary Syndrome Suffering Major Bleeding.

Background: Although the clinical factors that predict major bleeding in Western patients with acute coronary syndrome (ACS) are becoming elucidated, they have not been fully investigated, especially coronary lesion characteristics, in a Japanese population. Methods and Results: ACS patients (n=1,840) were divided into a "bleeding group" and a "no-bleeding group," according to whether they had major bleeding during the 2-year follow-up period, to investigate the prognostic effect of bleeding and the predictive factors of bleeding. Among them, patients who underwent primary percutaneous coronary intervention with optical coherence tomography (OCT) guidance (n=958) were examined to identify the effect of coronary lesion characteristics on bleeding. Of the 1,840 enrolled patients, 124 (6.7%) experienced major bleeding during the 2-year follow-up period. Incidence of cardiovascular death during the 2-year follow-up period was significantly higher among patients with major bleeding (26.4% vs. 8.5%, P=0.001). OCT examination showed that disrupted fibrous cap (DFC: 68% vs. 48%, P=0.014) and calcified plaque (63% vs. 42%, P=0.011) were more prevalent in the bleeding group. DFC was a predictor of major bleeding in the multivariate Cox proportional hazards analyses (hazard ratio 2.135 [95% confidence interval 1.070-4.263], P<0.001). Conclusions: ACS patients with major bleeding had poorer cardiac outcomes. Advanced atherosclerosis at the culprit lesion influences the higher incidence of major bleeding in ACS patients.

Relationship between the Residual Cesium Body Contents and Individual Behaviors among Evacuees from Municipalities near the Fukushima Daiichi Nuclear Power Plant.

ABSTRACT: To support estimations of early individual internal doses to residents who suffered from the 2011 accident at the Fukushima Daiichi Nuclear Power Plant (FDNPP), we have sought to use whole-body counter (WBC) measurement results of subjects who lived in municipalities neighboring the FDNPP at the time of the accident. These WBC measurements started several months after the accident; the targeted radionuclides were 134Cs and 137Cs. Our previous study had analyzed the relationship between the residual Cs contents of individuals and evacuation behaviors in the period immediately after the accident for residents of Namie-town, one of the most radiologically affected municipalities. Those results suggested that the first major release event at the FDNPP on 12 March 2011 caused significant exposure, particularly to those who delayed evacuation on that day. The present study expanded its scope to include subjects from four towns neighboring the FDNPP (Namie, Futaba, Okuma, and Tomioka) to gather additional evidence of the exposure that took place on 12 March 2011. Additionally, we investigated the relationship between individual cesium doses and subjects' destinations following the largest release event on 15 March 2011. The study population was 1,145 adults. We first divided the subjects into two evacuation groups depending on the distance from the FDNPP and their evacuation whereabouts (25-km boundary) as of 15:00 on 12 March 2011: the G1 group (≥25 km) and the G2 group (<25 km). We further divided these two subject groups into seven subgroups based on the subjects' destinations as of 0:00 on 16 March 2011. Our four main findings are as follows. (1) The 137Cs detection rate was significantly different between the G1 and G2 groups of Namie-town and Futaba-town but not for those of Okuma-town and Tomioka-town. This result corresponds to the plume passage (flowing toward the northwest to the north) in the afternoon of 12 March 2011 and supports our previous study. (2) The upper-percentile committed effective doses (CEDs) of the G2 groups were higher than those of the G1 groups for all four towns, although the between-group difference varied with the town. The highest CEDs were found in the G2 group of Futaba-town, and the lowest CEDs were in the Namie-town G1 group: 0.16 mSv and 0.04 mSv at the 90th percentile, respectively. The CEDs for both the G1 and G2 groups were relatively high for Okuma-town and Tomioka-town compared to those of the G1 group of Namie-town, although the former subjects were expected to be less exposed on 12 March 2011 and then evacuated to remote places, as did the residents of the other towns. (3) The CEDs of the G1 subgroup that evacuated outside Fukushima Prefecture were extremely low, suggesting that these subjects were little exposed on both 12 and 15 March 2011. However, the CEDs of the same G1 subgroup were rather higher than those of the corresponding G2 subgroup for Futaba-town and Okuma-town. We thus speculate that the WBC measurements were likely to have been affected by the contamination occurring in the second-round temporary re-entry (except for the Namie-town residents). (4) The analyses of the Namie-town evacuees indicated that the area including the middle and northern parts of Fukushima Prefecture was relatively more affected by the major release event on 15 March 2011. In conclusion, the early cesium intake due to the FDNPP accident remained detectable in the WBC measurements of certain present subjects; however, further analyses of the available data are necessary for a full understanding of the WBC measurement results.

Efficacy of dotinurad in patients with severe renal dysfunction.

BACKGROUND: Although hyperuricemia is associated with the progression of chronic kidney disease (CKD), a reduction in CKD progression by uric acid (UA)-lowering therapy has been controversial. Recently, dotinurad, a uricosuric drug with selective urate reabsorption inhibitory properties, has been developed. However, its efficacy in lowering serum UA levels and its effects on renal function in patients with severe renal dysfunction are unclear. Thus, this study aimed to determine the effects of dotinurad on renal function in patients with severe renal dysfunction. METHODS: Data from 53 outpatients with hyperuricemia who newly received dotinurad between December 2020 and October 2022 were retrospectively analyzed. The mean baseline estimated glomerular filtration rate (eGFR) was 38.7 ± 17.0 mL/min/1.73 m2. The patients were divided into three groups based on their baseline eGFR: eGFR < 30 (n = 17), 30 ≤ eGFR < 45 (n = 17), and eGFR ≥ 45 (n = 19). RESULTS: The mean follow-up period was 9.8 ± 4.5 (range, 3-21) months. Serum UA levels significantly decreased in all groups. Although eGFR did not significantly change in patients with 30 ≤ eGFR < 45 and eGFR ≥ 45 (P = 0.918 and P = 0.535, respectively), it improved significantly in patients with eGFR < 30 (P = 0.032). The proportion of patients with improved eGFR was significantly higher in patients with eGFR < 30 (P = 0.038) than in patients with 30 ≤ eGFR < 45 and eGFR ≥ 45. In the multivariate logistic regression analysis, baseline eGFR < 30 and achieving a serum UA level of ≤ 6.0 mg/dL were significantly associated with improved eGFR (P = 0.033 and P = 0.015, respectively). CONCLUSIONS: Dotinurad may have UA-lowering effects and the potential to improve kidney function in patients with severe renal dysfunction.

Influence of short-lived radioiodines other than 131I on screening direct thyroid measurements with TCS-172 NAI(TL) survey meters.

In a nuclear emergency, one of the actions taken for the sake of public is to monitor thyroid exposure to radioiodines. Japan's Nuclear Regulation Authority recently published a report on such monitoring and proposed direct thyroid measurements with conventional NaI(Tl) survey meters (e.g. Hitachi model TCS-172) as a primary screening method. A previous study proposed screening levels (SLs) used in these simplified measurements as the net reading values of the TCS-172 device. Age-specific SLs were derived from a thyroid equivalent dose of 100 mSv due to the inhalation intake of 131I. This study addressed the possible influence of short-lived iodine isotopes other than 131I on the simplified measurements. In preparation for such measurements, the responses of the device for 132I as an ingrowth component from 132Te, 133I, 134I and 135I in the thyroid were evaluated by numerical simulations using age-specific stylized phantoms in addition to those obtained for 131I in the previous study. The radioactivity ratios of the relevant isotopes were taken from the inventory data of the Fukushima Daiichi Nuclear Power Plant. The results were used to predict the net readings of the device when 132Te-132I and 133I as well as 131I were inhaled at 24 or 72 h after the shutdown of a nuclear power plant. In these cases, the signals from 132Te-132I and 133I become undetectable a couple of days after intake, which could lead to underestimations of the thyroid dose. To estimate the thyroid dose accurately from the simplified measurements, it is necessary to identify the exact time of intake after the shutdown and the actual physiochemical property of 132Te that affects the thyroid uptake of 132I.

Improvement of spectral analysis using a NaI(Tl) scintillation spectrometer to evaluate ambient gamma dose rates from primordial radionuclides.

In-situ measurements by gamma-ray spectrometry using a NaI(Tl) scintillation spectrometer are performed to discriminate primordial and artificial radionuclides contributing to ambient gamma dose rates in the living environment to quantify prolonged influence of nuclear accidents. However, low energy resolution of the spectrometer causes poor discrimination in the measurements at high-dose-rate points, which leads to overestimation of ambient gamma dose rate from the primordial radionuclides. The present study clarified that photon fluxes originating from 40K and 214Bi were affected by the presence of 134Cs, whereas those from 208Tl were independent of it. In addition, the absorbed dose rates in air were strongly correlated with the 208Tl photon fluxes. These findings indicate that 208Tl photon fluxes can be used to evaluate absorbed dose rates in air from the primordial radionuclides. When estimated from the 208Tl photon fluxes only, the absorbed dose rates in air in Namie Town and Okuma Town, locations affected by the Fukushima Dai-ichi Nuclear Power Plant accident, were 19-71 and 20-47 nGy h-1, respectively.

Response of personal dosemeters on various age-specific anthropometric phantoms under external irradiation applied to areas affected by the 2011 Fukushima Daiichi nuclear accident.

We experimentally obtained the responses of two personal dosemeters (PDs, D-shuttle and Dose-i) attached on five age-specific phantoms under rotational irradiation geometry, which simulated an environment that was radiologically affected by the 2011 Fukushima nuclear accident using of a 137Cs source. Although the PD responses showed an angular phase shift by the PD position on the phantoms, the angular dependence was small when the contamination was widely distributed. The PD responses decreased as much as ~10% with the increase in the phantoms' body size. Although there were ~17% variations in the PD/ADE (ambient dose equivalent) ratio depending on the different PDs, this variation was due to the fact that D-shuttle was calibrated with the inclusion of a safety margin. The PD/ADE ratios were similar to the effective dose to ADE ratios for corresponding age-specific phantoms. Our results suggest that these two PDs can provide reasonable estimates for age-dependent effective doses.

Development of a new integrated IN-VIVO counting system at the QST.

A new in-vivo counting system that functions as both a whole-body counter (WBC) and a lung counter (LC) was developed at the QST to enhance its dose assessment capability. This paper presents an overview of this system and the results of its performance tests. For use of the system as a WBC, three high purity germanium (HPGe) detectors installed in a 20-cm-thick iron shielding chamber are linearly arrayed over a subject lying on the bed, whereas two of the three HPGe detectors are placed over the subject's chest from side to side when using the system as an LC. The new in-vivo system was calibrated using three de-facto phantoms owned by the QST: an adult-male BOttle Manikin ABsorption (BOMAB) phantom, a Lawrence Livermore National Laboratory (LLNL) phantom and a Japan Atomic Energy Research Institute (JAERI) phantom. Monte Carlo simulations were also performed to determine an optimum location for the three detector array in the WBC mode and revealed that the peak efficiency for the BOMAB phantom (662 keV) was little varied as long as the middle detector was placed above the thorax and abdomen parts of the phantom. The calculated peak efficiencies agreed well with the observed peak efficiencies for photons with energies over 100 keV. For lung counting, a tentative Minimum Detectable Activity of 241Am was evaluated as 9.5 Bq for a counting time of 30 minutes, and a Japanese male subject with an average chest wall thinness (2.27 cm). The developed system is now ready for use.

The new QST bioassay laboratory in Chiba, Japan.

Japan's National Institutes for Quantum Science and Technology (QST) was designated as the core radiation emergency medical support center by the country's Nuclear Regulation Authority (NRA) in 2019. One of the main missions of the QST is to maintain and improve its dose assessment capability for radiation-exposed individuals. Toward the goal of effectively fulfilling this mission, a new facility-the Dose Assessment Building for Advanced Radiation Emergency Medicine-was constructed at the Chiba base of the QST in 2020. An integrated bioassay laboratory was installed in this facility for assessing subjects' internal doses, along with a new integrated in vivo counter. The bioassay capability of the new laboratory is currently expected to screen 5-10 persons simultaneously assuming internal contamination with actinides such as Pu, Am/Cm and U, although this is dependent on the specific contamination circumstances.

Biokinetic model analysis with DTPA administration for a case of accidental inhalation of actinides in Japan.

Accidental inhalation intake of plutonium isotopes and 241Am occurred at a Pu research facility in Japan in 2017, and the five workers involved in this accident were treated by the administration of Ca/Zn-diethylenetriaminepentaacetic acid (DTPA). For the worker who was most internally exposed, the therapy was continued over 1 y after the accident. Urinary samples collected before and after each administration were subject to bioassay to evaluate the efficacy of the dose reduction. This study performed numerical analyses using a biokinetic model dealing with 241Am-DTPA with reference to the European Coordinated Network on Radiation Dosimetry approach, which assumes that the complex of actinides and Ca/Zn-DTPA is generated in the designated compartments in the biokinetic model. The results of the model prediction well captured the trend of the observed urinary excretion in the long-term bioassay and would be useful to evaluate the efficacy of the Ca/Zn-DTPA administration for the worker involved in the accident.

Uncertainties associated with direct thyroid measurements using an NaI(Tl) survey meter: the effect of anatomical differences among individuals.

Photon detectors utilised for direct thyroid measurements to determine the radioiodine content in the thyroid are normally calibrated using a phantom that mimics the human neck, including the thyroid. However, such measurements are necessarily subject to uncertainty because of the difference between the phantom and the real human subject and also the morphological differences among individuals. In this study, personal voxel phantoms were created from magnetic resonance images of the necks of 24 adult volunteers (15 males and 9 females), and numerical simulations using these phantoms were performed to examine the variation in a conversion factor (131I kBq in the thyroid per µSv h-1) for a conventional NaI(Tl) survey meter among the individuals and also to confirm the suitability of reference Japanese voxel phantoms as a calibration standard for such measurements. As a result, it was found that the conversion factor obtained from the reference Japanese male (female) phantom was 1.29 (1.18) times larger than the average conversion factor for the male (female) subjects, suggesting that the conversion factors of the reference Japanese adult male and female phantoms would generally overestimate the 131I thyroidal contents and that the thyroid volume would be one of the factors influencing the conversion factor. This study also revealed a wide difference in the thyroid volume among individuals, which would be of concern when performing specific dose assessments for heavily exposed persons.

Screening levels of TCS-172 NaI(Tl) survey meters used for direct thyroid measurements in nuclear disasters.

It is a challenging task to establish a feasible and robust method for the population monitoring of individuals' thyroid exposure following an accidental intake of radioiodines in a nuclear emergency, because of the time restriction. The authors previously proposed a method for such monitoring to obtain as many reliable human data as possible and one of the components is simplified measurements by conventional NaI(Tl) survey meters that are intended to be used for the initial triage to identify significantly exposed individuals and get an overall picture of the exposure levels in a target population in a timely manner. This study determined screening levels (SLs) for a conventional NaI(Tl) survey meter (model TCS-172, Hitachi, Japan) using the conversion factor (131I kBq in the thyroid per µSv h-1) that were obtained from experiments and simulations with age-specific phantoms. The results demonstrated that the derived SLs for 100 mSv thyroid equivalent dose were as follows: 0.2 µSv h-1 (SL1) for the age group ≤ 5-y-olds, 0.5 µSv h-1 (SL2) for the 10- and 15-y-old age groups and 1.0 µSv h-1 (SL3) for adults. These SLs would be reasonably available within 1 week after the intake of 131I on the safe side.

Rapid measurement of actinides in urine by mass and alpha spectrometric methods.

To provide timely information for prompting decision-making in emergency radiation therapy, we developed simple and rapid mass and alpha spectrometric methods for urinary bioassays to determine ultra-trace actinide isotopes. For the mass spectrometric method, after organic matter decomposition, LaF3/CaF2 co-precipitation and chromatographic purification using 2 ml of AG MP-1 M anion exchange resin, U and Pu isotopes were measured in a 20-ml urine sample by inductively coupled plasma-mass spectrometry. In the alpha spectrometric method, after organic matter decomposition, iron hydroxide co-precipitation and chromatographic purification using 2 ml of TEVA and 2 ml of DGA resin cartridges, Pu, U and Am/Cm isotopes were measured in a 500-ml urine sample by alpha spectrometry. These alpha and mass spectrometric methods were then applied for participation in the 2020 intercomparison organized by the Association for the PROmotion of Quality COntrol in RADiotoxicological Analysis (PROCORAD), France, for method validations.

Cardiovascular Risk Factors and Culprit Plaque Characteristics in Women With Acute Coronary Syndromes.

Outcomes after myocardial infarction in women remain poor. The number of cardiovascular risk factors in women increase with age, however the relation between risk factors and culprit plaque characteristics in this population is poorly understood. The aim of the study was to investigate the relation between risk factors and culprit plaque characteristics in women with acute coronary syndrome (ACS). A total of 382 women who presented with ACS and underwent pre-intervention optical coherence tomography imaging of the culprit lesion were included in this analysis. The culprit plaques were categorized as plaque rupture, plaque erosion or calcified plaque, and then stratified by age and risk factors. The predominant pathology of ACS was plaque erosion in young patients (<60 years), which decreased with age (p <0.001). Current smokers had a high prevalence of plaque rupture (60%) and lipid plaque (79%). Women with diabetes tended to have more lipid plaque (70%) even at a young age. In women with hyperlipidemia, the prevalence of lipid plaques was modest in younger ages, but rose gradually with age (p <0.001). An increasing age trend for lipid plaque was also observed in women with hypertension (p = 0.03) and current smokers (p = 0.01). In conclusion, early treatment of risk factors such as diabetes in young women might be important before accelerated progression of atherosclerosis begins as age advances. Clinical trial registration: http://www.clinicaltrials.gov, NCT01110538, NCT03479723 and NCT02041650.

A preliminary report on retrospective dose assessment by FISH translocation assay in FDNPP Nuclear Emergency Worker Study (NEWS).

In Japan, a national project of longitudinal health care and epidemiological research (NEWS) was developed in 2014 to analyse the effects of radiation on human health for workers who responded to the Fukushima Dai-ichi nuclear emergency in 2011. In 2018, peripheral blood for chromosome translocation analysis was collected from 62 workers. Retrospective dose assessment was performed with fluorescence in situ hybridisation translocation (FISH-Tr) assay. The range of estimated doses by FISH-Tr assay was 0-635 mGy, in which 22 workers had estimated doses of more than 189 mGy. Biological dose estimates were five times higher in workers with physically measured total exposure recordings above 70 mGy. It is likely that smoking and medical exposure caused the discrepancy between estimated biological and physical total exposure doses. Thus, there is a possibility that retrospective biodosimetry assessment might over-estimate occupational exposures to workers exposed to chronic radiation during nuclear emergency work.

Early recurrence of attack after myocardial infarction with non-obstructive coronary arteries: a case report.

Background: Diagnostic strategies depend on non-standardized workup, and the causes of myocardial infarction with non-obstructive coronary arteries remain unclear for some patients. Intracoronary imaging is recommended for detecting the missed causes by coronary angiography. Myocardial infarction with non-obstructive coronary arteries is a heterogeneous entity; a meta-analysis of myocardial infarction with non-obstructive coronary artery studies demonstrated that all-cause mortality rate at 1 year is 4.7%, and its prognosis is not so favourable. Case summary: A 62-year-old man without remarkable medical history complained of acute chest pain at rest, which resolved at his arrival. Although echocardiography and electrocardiogram exhibited normal findings, the concentration of high-sensitive cardiac troponin T increased up to 0.384 from 0.04 ng/mL. Coronary angiography was performed, and mild stenosis of the proximal right coronary artery was detected. He was discharged without catheter intervention and medications as he reported no symptoms. He returned 8 days later because of inferoposterior ST-segment elevation myocardial infarction with ventricular fibrillation. Emergent coronary angiography showed that the mild stenosis of the proximal right coronary artery had progressed to total occlusion. Optical coherence tomography after thrombectomy revealed rupture of the thin-cap fibroatheroma and protruding thrombus. Discussion: Patients presenting with myocardial infarction with non-obstructive coronary arteries and plaque disruption and/or thrombus detected by optical coherence tomography do not show normal coronaries on coronary angiography. Aggressive investigation into plaque disruption using intracoronary imaging is recommended even if coronary angiography demonstrates mild stenosis to prevent a fatal attack for suspicious cases of myocardial infarction with non-obstructive coronary arteries.

No evidence of thyroid consequences in seven nuclear workers at the Tokyo Electric Power Company Fukushima Daiichi Nuclear Power Plant accident: 10-year follow-up results of thyroid status.

Seven emergency nuclear workers, who had internal exposure due to an intake of radionuclides, mainly I-131, during the emergency response operation in March 2011, after the accident at the Tokyo Electric Power Company (TEPCO) Fukushima Daiichi Nuclear Power Plant (FDNPP), visited the National Institute of Radiological Sciences (NIRS) outpatient clinic for medical evaluation. They were followed up after their first visit for 10 years. The estimated committed equivalent doses to the thyroid were distributed between 3.2 to 1.2 × 10 Sv. This group thought to be received highest exposure at the accident. None of the workers had symptoms related to abnormal thyroid function. The examinations, including thyroid function tests and ultrasound, detected no abnormalities related to radiation exposure. However, there is a need for continuous monitoring of their thyroid status for longer periods in the future.

External Doses Available for Epidemiological Studies Related to the Fukushima Health Management Survey: First 4-month Individual Doses and Municipality-average Doses for the First Year.

BACKGROUND: One of the components of the Fukushima Health Management Survey (FHMS) is the Basic Survey, which estimates individual external doses for the first 4 months after the 2011 nuclear power plant accident. However, external exposure continues long-term. According to estimations by international organizations, the external dose during the first year accounts for a significant part of the long-term dose. Thus, the present study was intended to estimate the first-year doses by extrapolating the Basic Survey results. METHODS: For most municipalities of non-evacuated areas, ambient dose rate had been continuously measured for at least one designated point in each municipality after the accident. In the present study, a municipality-average dose received by residents for a period was assumed to be proportional to the ambient dose measured at the designated point of that municipality during the same period. Based on this assumption, 4-month municipality-average doses calculated from the Basic Survey results were extrapolated to obtain first-year doses. RESULTS: The extrapolated first-year doses for 49 municipalities in the non-evacuated areas had a good correlation with those estimated by UNSCEAR, although the extrapolated doses were generally higher (slope of the regression line: 1.23). The extrapolated municipality-average doses were in reasonable agreement (within 30%) with personal dosimeter measurements, suggesting that the extrapolation was reasonable. CONCLUSION: The present paper reports the first 4-month average doses for all 59 municipalities of Fukushima Prefecture and the extrapolated first-year doses for 49 municipalities. The extrapolated doses will be the basis for future epidemiological studies related to the FHMS.

Sex Differences in Culprit Plaque Characteristics Among Different Age Groups in Patients With Acute Coronary Syndromes.

BACKGROUND: Despite the significant decline in cardiovascular mortality in women over the past several decades, sex differences in the underlying pathology of acute coronary syndromes remain poorly understood. Previous postmortem studies have demonstrated sex differences in coronary plaque morphology with a higher prevalence of plaque erosion in young women and more plaque rupture in older women after menopause, whereas men showed no increase in prevalence of plaque rupture with age. However, in vivo data are limited. METHODS: This study included patients who presented with acute coronary syndrome and underwent preintervention optical coherence tomography imaging of the culprit lesion. The culprit plaque was categorized as plaque rupture, plaque erosion or culprit plaque with calcification, and stratified by age. Features of plaque vulnerability at culprit lesion were also analyzed. RESULTS: In 1368 patients (women=286), women and men had a similar distribution of culprit plaque morphology (plaque rupture versus plaque erosion). However, significant sex differences were found in the underlying mechanisms of acute coronary syndrome among different age groups: women showed a significant ascending trend with age in plaque rupture (P<0.001) and the features of plaque vulnerability such as lipid plaque (P<0.001), thin-cap fibroatheroma (P=0.005), and microstructures including macrophages, cholesterol crystals, and calcification (P=0.026). No trend was observed in men. CONCLUSIONS: Age related sex differences in culprit plaque morphology and vulnerability were identified in patients with acute coronary syndrome: prevalence of plaque rupture and vulnerability increased with age in women but not in men. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01110538 and NCT03479723.