Search

The strong cell killing effect of high linear energy transfer (LET) carbon ions is dependent on lethal DNA damage. Our recent studies suggest that induction of clusters of double-strand breaks (DSBs) in close proximity is one of the potential mechanisms. However, the relationship between LET, the degree of DSB clustering and the cell killing effect of carbon ions remains unclear. Here, we used high-resolution imaging technology to analyze the volume of γH2AX foci induced by monoenergetic carbon ions with a clinically-relevant range of LET (13–100 keV/μm). We obtained data from 3317 γH2AX foci and used a gaussian function to approximate the probability (p) that 1 Gy-carbon ions induce γH2AX foci of a given volume (vth) or greater per nucleus. Cell killing effects were assessed in clonogenic assays. The cell killing effect showed high concordance with p at vth = 0.7 μm3 across various LET values; the difference between the two was 4.7% ± 2.2%. This relationship was also true for clinical carbon ion beams harboring a mixed LET profile throughout a spread-out Bragg peak width (30–120 mm), with the difference at vth = 0.7 μm3 being 1.6% ± 1.2% when a Monte Carlo simulation-derived dose-averaged LET was used to calculate p. These data indicate that the cell killing effect of carbon ions is predictable by the ability of carbon ions to induce γH2AX foci containing clustered DSBs, which is linked to LET, providing the biological basis for LET modulation in the planning of carbon ion radiotherapy.

Background: Fulminant myocarditis presentation (FMP) is a rare and severe presentation of myocarditis. The natural history of FMP and its clinical features associated with poor outcomes are incompletely understood because there is a lack of generalizable evidence. Methods: This multicenter retrospective cohort study included patients hospitalized with histologically proven myocarditis who underwent catecholamine or mechanical support from 235 cardiovascular training hospitals across Japan between April 2012 and March 2017. Clinical features and the prognostic predictors of death or heart transplantation within 90 days on the basis of clinical and pathologic findings were determined using the Kaplan-Meier method, log-rank test, and Cox regression analysis. Results: This study included 344 patients with histologically proven FMP (median age, 54 years; 40% female). The median follow-up was 600 days (interquartile range, 36 to 1599 days) and the cumulative risk of death or heart transplantation at 90 days was 29% (n=98). Results from multivariable Cox regression analysis showed that older age, nonsinus rhythm, low left ventricular wall motion ( Conclusions: The results from analyses of data from this multicenter registry demonstrated that patients with FMP are at a higher risk of death or heart transplantation in real-world settings. These observations inform which clinical and pathologic findings may be useful for prognostication in FMP. Registration: URL: https://www.umin.ac.jp/ctr ; Unique identifier: UMIN000039763.

Implantations of leadless pacemakers in the septum lower the risk of cardiac perforation. However, the relationship between the implantation site and the success rate, complication rate, and pacemaker parameters are not well-investigated.Patients who underwent leadless pacemaker implantation with postprocedural computed tomography (CT) between September 2017 and November 2020 were analyzed. Septum was targeted with fluoroscopic guidance with contrast injection. We divided patients into two groups based on the implantation site confirmed by CT: septal and non-septal, which included the anterior/posterior edge of the septum and free wall. We compared the complication rates and pacemaker parameters between the two groups.A total of 67 patients underwent CT after the procedure; among them, 28 were included in the septal group and 39 were included in the non-septal group. The non-septal group had significantly higher R wave amplitudes (6.5 ± 3.3 vs. 9.7 ± 3.9 mV, p = .001), lower pacing threshold (1.0 ± 0.94 vs. 0.63 ± 0.45 V/0.24 ms, p = .02), and higher pacing impedance (615 ± 114.1 vs. 712.8 ± 181.3 ohms, p = .014) after the procedure compared to the septal group. Cardiac injuries were observed in four patients (one cardiac tamponade, one possible apical hematoma, two asymptomatic pericardial effusion), which were only observed in the non-septal group.Leadless pacemaker implantation may be technically challenging with substantial number of patients with non-septal implantation when assessed by CT. Septal implantation may have a lower risk of cardiac injury but may lead to inferior pacemaker parameters than non-septal implantation.

The accurate measurement of the 3D dose distribution of carbon-ion beams is essential for safe carbon-ion therapy. Although ionization chambers scanned in a water tank or air are conventionally used for this purpose, these measurement methods are time-consuming. We thus developed a rapid 3D dose-measurement tool that employs a silver-activated zinc sulfide (ZnS) scintillator with lower linear energy transfer (LET) dependence than gadolinium-based (Gd) scintillators; this tool enables the measurement of carbon-ion beams with small corrections. A ZnS scintillator sheet was placed vertical to the beam axis and installed in a shaded box. Scintillation images produced by incident carbon-ions were reflected with a mirror and captured with a charge-coupled device (CCD) camera. A 290 MeV/nucleon mono-energetic beam and spread-out Bragg peak (SOBP) carbon-ion passive beams were delivered at the Gunma University Heavy Ion Medical Center. A water tank was installed above the scintillator with the water level remotely adjusted to the measurement depth. Images were recorded at various water depths and stacked in the depth direction to create 3D scintillation images. Depth and lateral profiles were analyzed from the images. The ZnS-scintillator-measured depth profile agreed with the depth dose measured using an ionization chamber, outperforming the conventional Gd-based scintillator. Measurements were realized with smaller corrections for a carbon-ion beam with a higher LET than a proton. Lateral profiles at the entrance and the Bragg peak depths could be measured with this tool. The proposed method would make it possible to rapidly perform 3D dose-distribution measurements of carbon-ion beams with smaller quenching corrections.

Background Catheter ablation for paroxysmal supraventricular tachycardia (PSVT) is an established treatment, but the effect of deep sedation on PSVT inducibility remains unclear. Aim We sought to examine PSVT inducibility and outcomes of catheter ablation under deep sedation using adaptive servo ventilation (ASV). Methods We retrospectively evaluated consecutive patients who underwent catheter ablation for PSVT under deep sedation (Propofol + Dexmedetomidine) with use of ASV. Anesthetic depth was controlled with BIS™ monitoring, and phenylephrine was administered to prevent anesthesia‐induced hypotension. PSVT induction was attempted in all patients using extrastimuli at baseline, and after isoproterenol (ISP) infusion when necessary. Results PSVT was successfully induced in 145 of 147 patients, although ISP infusion was required in the majority (89%). The PSVT was atrioventricular nodal reentrant tachycardia (AVNRT) in 77 (53%), atrioventricular reciprocating tachycardia (AVRT) in 51 (35%), and atrial tachycardia (AT) in 17 (12%). A higher ISP dose was required for AT compared to other PSVT (AVNRT: 0.06 (IQR 0.03‐0.06) vs AVRT: 0.03 (0.02‐0.06) vs AT: 0.06 (0.03‐0.12) mg/h, P = .013). More than half (51%) of the patients developed hypotension requiring phenylephrine; these patients were older. Acute success was obtained in 99% (patients with AVNRT had endpoints with single echo on ISP in 46%). Long‐term success rate was 136 of 144 (94%) (AVNRT 96%, AVRT 92%, and AT 93%). There were no complications related to deep sedation. Conclusions Deep sedation with use of ASV is a feasible anesthesia strategy for catheter ablation of PSVT with good long‐term outcome. PSVT remains inducible if ISP is used., Deep sedation with use of ASV is a feasible anesthesia strategy for catheter ablation of PSVT with good long‐term outcome. PSVT remains inducible if ISP is used.

Optimization studies of feed drive system parameters of machine tools are gaining attention. Majority of the studies use the weighted sum of several evaluation indices regarding machine behavior as the objective function. However, there is no clear guideline for designing those weights, which are currently configured empirically. To address this problem, this study has optimized acceleration/deceleration parameters of a milling table with various weight configurations by using a machine tool simulator. Optimized parameters showed clear relationships between the weights related to the magnitude of acceleration and the positional accuracy. That enables weight configuration design to meet various users’ needs.

Objective. Dosimetric commissioning of treatment planning systems (TPS) focuses on validating the agreement of the physical dose with experimental data. For carbon-ion radiotherapy, the commissioning of the relative biological effectiveness (RBE) is necessary to predict the clinical outcome based on the radiation quality of the mixed radiation field. In this study, we proposed a approach for RBE commissioning using Monte Carlo (MC) simulations, which was further strengthen by RBE validation based on linear energy transfer (LET) measurements. Approach. First, we tuned the MC simulation based on the results of dosimetric experiments including the beam ranges, beam sizes, and MU calibrations. Furthermore, we compared simulated results to measured depth- and radial-LET distributions of the 430 MeV u−1 carbon-ion spot beam with a 1.5 mm2, 36 μm thick silicon detector. The measured dose-averaged LET (LETd) and RBE were compared with the simulated results. The RBE was calculated based on the mixed beam model with linear-quadratic parameters depending on the LET. Finally, TPS-calculated clinical dose profiles were validated through the tuned MC-based calculations. Main results. A 10 keV μm−1 and 0.15 agreement for LETd and RBE, respectively, were found between simulation and measurement results obtained for a 2σ lateral size of 430 MeV u−1 carbon-ion spot beam in water. These results suggested that the tuned MC simulation can be used with acceptable precision for the RBE and LET calculations of carbon-ion spot beam within the clinical energy range. For physical and clinical doses, the TPS- and MC-based calculations showed good agreements within 1.0% at the centre of the spread-out Bragg peaks. Significance. The tuned MC simulation can accurately reproduce the actual carbon-ion beams, and it can be used to validate the physical and clinical dose distributions calculated by TPS. Moreover, the MC simulation can be used for dosimetric commissioning, including clinical doses, without LET measurements.

Background It is unclear whether pacing maneuver at the end of catheter ablation for atrial fibrillation (AF) predicts recurrence of atrial tachyarrhythmia postintervention. Objective To investigate whether the predictive value of incremental pacing maneuver after catheter ablation for AF depends on the pacing cycle length and type of AF. Methods This study included 298 consecutive patients who underwent initial catheter ablation for nonvalvular AF (61% paroxysmal AF [PAF], 39% persistent AF [PeAF]). Rapid atrial pacing was performed at the end of the procedure. We analyzed minimum coupling interval (CI) of pacing, arrhythmia‐inducibility, and atrial tachyarrhythmia recurrence in patients with PAF and PeAF. Results Patients were divided into the following three groups according to their response to pacing maneuver: AF‐inducible (inducible group; n = 86), noninducible at CI ≥200 ms (non‐CI ≥200 group; n = 100), and noninducible at CI, When patients were divided into three groups according to the response to pacing maneuver (inducible, non‐inducible at coupling interval [CI] ≥ 200 ms, and non‐inducible at CI < 200 ms), significant difference in atrial tachyarrhythmia free survival were observed (panel A). However, when paroxysmal atrial fibrillation (PAF) and persistent atrial fibrillation (PeAF) were analyzed separately, significant deference was observed only in PeAF (panel B and C).

Background Venous bleeding complication is often observed after catheter ablation of atrial fibrillation (AF), but the risk factors remain unclear. Methods We retrospectively evaluated 570 consecutive patients who underwent catheter ablation of AF from April 2012 to March 2017. After the procedure, the sheaths were removed, and hemostasis was obtained by manual compression followed by application of rolled gauze with elastic bandage and continuous pressure to the puncture site. We evaluated the risk factors for venous bleeding complications defined as hemorrhage from the puncture site that needed recompression after removal of the elastic bandage and rolled gauze. Results After excluding 11 patients because of missing data, 559 patients (395 [70.7%] men, mean age: 65.6 ± 8.7 years) were included for analysis. Venous bleeding complication was observed in 213 patients (38.1%). In the multivariate logistic regression analysis, low body mass index (BMI; odds ratio [OR] 0.95, 95% CI 0.90‐1.00, P = .04), short compression time (OR 0.77, 95% CI 0.68‐0.88, P, We retrospectively evaluated 570 consecutive patients who underwent catheter ablation of atrial fibrillation. The risk factors for venous bleeding complications were analyzed. Low BMI, short compression time, and antiplatelet therapy were found to be the significant risk factors.

重粒子を用いた治療技術にはその高度化に伴い、高い空間分解能やエネルギー弁別機能を備えた、より高度な線量評価が必要となっている。既存電離箱で対応できない複雑な線量評価における需要に対し、放射線耐性に優れた4H-SiCショットキーバリアダイオード(SBD)に着目した検討がおこなわれている。しかしながら、粒子パルスを計数する既存の計測体系では、1Mpps 程度の低い照射量領域のみで動作が可能であった。これに対し、本研究では、リアルタイムで計測可能な放射線誘起過渡電流 (Radiation Induced Current: RIC) に着目し、RICを対象とした測定法によって炭素線を測定することで、治療線量強度において微細な空間分解能で線量分布を測定する手法の開発を行った。, 応用物理学会春季学術講演会

A radiation-tolerant silicon carbide (SiC) based dosimeter was developed for the measurement of linear energy transfer (LET) distributions along the Bragg curve for pristine and spread-out Bragg peak (SOBP) clinical carbon beam. Since the conventional ionized chamber is not suitable and effective for LET measurement, several energy-dispersive dosimeters are being developed and tested in the clinical field. While most of the detector lacks radiation hardness against carbon beam, we have utilized wide-bandgap semiconductors of SiC with different epitaxial layers from 25, 69, and 170 μm as a dosimeter for the clinical carbon field at Gunma University Heavy Ion Medical Center (GHMC). LET spectra were obtained not only for pristine carbon beams with an energy of 290 MeV/n but also SOBP conditions. It was confirmed through the changes in LET distribution, primally carbons and fragments are identified, and those energy depositions are successfully obtained by the fabricated SiC dosimeter. The distribution of relative biological effectiveness (RBE) was estimated from LET through biological estimation models. Results suggested that SiC-based dosimeter is successful in being utilized in the detailed characterization of the clinical carbon therapy field.

This study aimed to explore the prognostic factors associated with acute radiation dermatitis (ARD). A normal tissue complication probability (NTCP) model for ARD in patients with head and neck cancer treated with carbon ion radiation therapy was developed.A total of 187 patients were included in the analysis, and the endpoint was ≥grade 2 ARD. The biological and physical dose-surface parameters associated with ARD were used in the logistic regression model. The mean areas under the receiver operating characteristic curve in the internal cross-validation and Akaike's corrected Information Criterion were examined for model evaluation and selection. The multivariate logistic regression NTCP models were established based on factors with weak correlation.Tumor volume, planning target volume to the skin, radiation technique and all dose-surface parameters were significantly associated with ARD (P.05). Models with high performance for grade 2 to 3 ARD were constructed. The most significant prognostic predictors were SNTCP models for ARD may provide a basis for the development of individualized treatment strategies and reduce the incidence of severe ARD in patients with head and neck cancer receiving carbon ion radiation therapy. Furthermore, biological and physical dose-surface parameter-based models are comparable. However, further validation with more evaluation parameters is warranted.

Purpose The purpose of this study was to study the field size effect on the estimated Relative Biological Effectiveness (RBE) for carbon scanning beam irradiation. Methods A silicon-on-insulator (SOI) microdosimeter system developed by the Centre for Medical Radiation Physics, University of Wollongong, Australia, was used for lineal-energy measurements (microdosimetric quantity). The RBE values were derived based on the modified microdosimetric kinetic model (MKM) at different depths in a water phantom in the scanning carbon beam for various scanned areas. Results Our study shows that the difference in RBE values derived from the SOI microdosimeter measurements with the MKM model and from the Treatment Planning System (TPS). The difference of the RBE values is within 6.5 % at the peak point of the spread-out Bragg Peak (SOBP) region. Compared to the spot-beam, RBE values obtained in the scanned-beam with a larger scanned area of 1.0 × 1.0 cm2 have better agreement with which estimated by the TPS. Conclusions This study shows the possibility of using the SOI microdosimeter system as a quality assurance (QA) tool for RBE evaluation in carbon-pencil beam scanning radiotherapy.

The His-Purkinje system (HPS) is known to be involved in the reentrant circuit of ventricular tachycardia (VT), even in patients with structural heart disease.1, 2, 3 Catheter ablation may be an effective strategy for this entity; however, there is a potential risk of conduction delay or even high-degree atrioventricular (AV) block. Therefore, detailed understanding of the reentry circuit is crucial. However, the mechanism and role of HPS in this entity are debatable. We experienced a case of post–myocardial infarction VT with involvement of the HPS demonstrating a change in QRS morphology without termination, which provided us clues for understanding the mechanisms underlying this type of VT.

Although angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) have been recommended for patients with heart failure, their clinical and prognostic impact in the very acute phase of acute heart failure (AHF) is unclear, mainly because data on their safety and efficacy are lacking. This study was a post hoc analysis of the REALITY-AHF trial. Patients with AHF who did not take an ACEI or ARB at admission were enrolled. Patients who received these medications within 48 h of admission were categorized as the ACEI/ARB group, and all other patients were categorized as the no ACEI/ARB group. The primary endpoint was a composite of all-cause death and heart failure readmission within 1 year of admission. Of the 1682 patients in the REALITY-AHF cohort, 900 were enrolled in this study, and 288 (32%) were included in the ACEI/ARB group. After propensity score matching, 152 pairs were evaluated, and no significant difference was found for in-hospital mortality, worsening renal function, or length of hospital stay. The ACEI/ARB group had significantly higher event-free survival (hazard ratio 0.51; 95% confidence interval 0.32–0.82; p = 0.006). Early initiation of ACEIs/ARBs within 48 h of admission for hospitalized patients with AHF was not associated with adverse events and correlated with improved outcomes at 1 year from admission.

BACKGROUND: In hospitalized heart failure patients, a poor diuretic response (DR) during the first days of hospital admission is associated with worse outcomes. However, it remains unknown whether diuretic response in the first hours has similar prognostic value. Moreover, data on the sequential change in DR during hospital admission are lacking.METHODS AND RESULTS: DR (urine output per 40 mg furosemide-equivalent diuretics dose) was measured from 0 to 6 hours (DR6), 6 to 48 hours (DR6-48), and 0 to 48 hours (DR48) of the patient's arrival to the emergency department (ED) in 1551 patients with AHF (mean age 78 years old; 56% were male; and 48% were de-novo patients with heart failure). Patients with a poor DR within the first 6 hours were older age, had worse renal function and were already on diuretic treatment before admission. DR6 was only weakly correlated with DR6-48 (Spearman's rho=0.273; pCONCLUSION: Both DR measured within the first 6 hours of ED arrival and DR measured during the first 48 hours in patients with AHF have similar prognostic value, although they were moderately correlated. Changes in DR over time provide additional prognostic information.

Radiochromic films are useful as dosimeters in high-precision radiotherapy owing to their high spatial resolution. However, when a particle beam is measured using a radiochromic film, the dose cannot be estimated accurately because the film darkness varies with variations in linear energy transfer (LET). This paper proposes a novel method for estimating the LET and the dose based on the film darkness. In this method, after a high-LET particle beam, such as a carbon-ion beam, was incident on the film, the film was digitized and its net optical density was determined. Further, the non-linearity of the film response curve between the dose and the darkness, depending on LET, was used. Then, calibration curves were created using 290 MeV u−1 mono energetic carbon-ion beams. We used LETs of 20, 50, 100, and 150 keV µm−1 and a physical dose of 2–14 Gy. The calibration curves were approximated for each LET using a quadratic function. The correlations between the coefficients of the quadratic function and the LET were also obtained. To verify the proposed method, the films were irradiated under 12 different conditions corresponding to various depths and doses. Four depths of −2, −5, −10, and −20 mm with respect to the Bragg peak, and three different preset values were used for the film measurements. The films were analyzed in four groups, where each group comprised films irradiated at the same depth. The LETs obtained from the film analysis, ordered from the upstream of the beam, were 20, 41, 56, and 97 keV µm−1, and the doses for the lowest preset value were 3.95, 4.07, 4.03, and 3.99 Gy for the four groups. The LETs obtained from the film analysis increased toward the Bragg peak, and the doses measured in the ionization chamber were almost equal to 4 Gy.

AimsThe prognostic impact of worsening renal function (WRF) in patients with acute heart failure (AHF) remains under debate. Successful decongestion might offset the negative impact of WRF, but little is known about indicators of successful decongestion in the very acute phase of AHF. We hypothesized that decongestion as evaluated by the percent reduction in brain natriuretic peptide (BNP) could identify relevant prognostic implications of WRF in the very acute phase of AHF.Methods and resultsData on 907 consecutive hospitalized patients with AHF in the REALITY-AHF study (age: 78±12 years; 55.1% male) were analyzed. Creatinine and BNP were measured at baseline and 48 hours from admission. WRF was defined as an increase in creatinine >0.3 mg at 48 hours from admission. The primary endpoint was 1-year all-cause mortality. Patients were divided into four groups according to the presence/absence of WRF and a BNP reduction higher/lower than the median: no-WRF/higher-BNP-reduction (n = 390), no-WRF/lower-BNP-reduction (n = 397), WRF/higher-BNP-reduction (n = 63), and WRF/lower-BNP-reduction groups (n = 57). Kaplan-Meier curve analysis showed that the WRF/lower-BNP-reduction group had a worse prognosis than the other groups. In a Cox regression analysis, only the WRF/lower-BNP-reduction group had higher mortality compared to the no-WRF/higher-BNP-reduction group (hazard ratio: 3.34, pConclusionIn the very acute phase of AHF, BNP reduction may aid in identifying relevant prognostic significance of WRF.

Background and aims Although 18F-fluorodeoxyglucose (FDG) uptake has emerged as a sensitive and reliable marker of atherosclerotic inflammation, its additive predictive value for future coronary disease in older subjects is unknown. The aim of this study was to test the prognostic value of aortic inflammation detected via FDG-positron emission tomography (PET)-computed tomography (CT) in older subjects. Methods We retrospectively utilized the records of 309 subjects aged over 65 years, without a history of coronary artery disease, who underwent 18F-FDG-PET-CT mostly due to the clinical suspicion of cancer, but eventually turned out to be cancer-free. Target-to-background ratio (TBR) was calculated at the ascending aorta. The endpoint was occurrence of coronary heart disease (CHD) events. Results During a median follow-up of 3.9 years, 28 subjects experienced CHD events and 12 patients died due to non-CHD causes. The highest TBR tertile was associated with a high CHD event rate, accounting for death due to non-CHD causes as a competing risk (Gray test, p = 0.005). In a Fine and Gray competing risk proportional hazard regression model, TBR was associated with significantly high CHD events independently of FRS, with a hazard ratio (HR) of 1.19 per 0.1 TBR increase (p Conclusions In older subjects with no history of malignant disease or overt coronary artery disease, arterial inflammation evaluated by FDG uptake provides information on future occurrence of coronary artery events.

OBJECTIVES Although cognitive impairment is common among patients with chronic heart failure (HF), the accuracy with which caregivers can recognize it is unknown. This study aimed to examine the degree to which subjective and objective evaluations coincide. METHODS Cognitive function was evaluated subjectively and objectively in 184 hospitalized patients aged 65 or older (82 ± 7.2 years old and 49% male) with HF, who were divided into three groups: (i) normal; (ii) mild cognitive impairment; and (iii) severe cognitive impairment. RESULTS The intrapatient agreement of the results of subjective and objective evaluations was tested, and weighted κ coefficients showed poor agreement (0.54, 95% confidence interval: 0.42-0.66, P < 0.001). CONCLUSION Subjective and objective cognitive function evaluations in older patients with HF are poorly concordant.

Background What happens to stent length when deployed in a coronary artery? It is the aim of this study. Results Consecutive 95 balloon-expandable stents (BES) were studied by intravascular ultrasound (IVUS) imaging. The stent length was measured from the longitudinal view in two ways: (1) edge-to-edge length (E-E) measured between distal and proximal stent frames located at one IVUS quadrant and (2) area-to-area length (A-A) measured between distal and proximal stent frames located at two or more IVUS quadrants. IVUS measurements were compared with the manufacturer-stated length (M-L). The median E-E length was significantly longer than M-L, 18.76 mm [interquartile range (IQR) 15.65–23.60] versus 18.00 mm (IQR 15.00–23.00), respectively, p p p p p = 0.01; pre-intervention minimal diameter of the external elastic membrane (EEM), p = 0.03; lesions present in the left anterior descending branch, p = 0.03; and M-L, p = 0.04. Conclusions In the present study, the length of BES measured by IVUS was significantly different from the manufacturer-stated length. In addition to the manufacturer length, other important factors such as lesion length, pre-intervention diameter of EEM, and affected vessel determine the stent length.

Background The values of n-3 and n-6 polyunsaturated fatty acids (PUFAs) like low eicosapentaenoic acid (EPA) /arachidonic acid (AA) ratio are known to be associated with cardiovascular events, however their relationship with coronary plaque vulnerability in acute myocardial infarction (AMI) is not revealed. Purpose We evaluated the relationship between n-3 and n-6 PUFAs and coronary plaque vulnerability assessed by optical coherence tomography (OCT) in AMI patients. Methods We investigated 79 AMI lesions (51 ST elevated myocardial infarction (STEMI) lesions and 28 non-STEMI lesions) that had undergone emergency percutaneous coronary intervention using OCT. Coronary plaque characteristics by OCT were compared with n-3 and n-6 PUFAs values which were measured on admission. Results Of all AMI lesions (n=79), 43 thin-cap fibroatheroma (TCFA) and 35 plaque rapture (PR) were detected by OCT. Lesions with TCFA had no significant relationship with n-3 and n-6 PUFAs values, whereas lesion with PR had significantly lower EPA values than those without (55.8±29.5 vs 74.3±37.1 μg/ml, p=0.018). Median low-density lipoprotein (LDL) cholesterol value was 117 (98–137) mg/dl and sub-analysis in patients who had lower LDL cholesterol values than median (n=39) revealed that EPA values were significantly lower in lesions with TCFA (56.3±30.9 vs 85.3±47.7 μg/ml, p=0.03). In STEMI patients, the values of EPA and EPA/AA ratio were significantly lower in lesions with TCFA (EPA: 55.5±22.8 vs 80.8±46.1 μg/ml, p=0.01; EPA/AA ratio: 0.34±0.16 vs 0.50±0.36, p=0.03). STEMI patients who had lower LDL cholesterol values Conclusion This study demonstrated that n-3 and n-6 PUFAs values were associated with coronary plaque vulnerability by OCT in AMI patients, especially in STEMI. These results suggest that n-3 and n-6 PUFAs may be residual risk markers of severe acute cardiovascular events in patients with low LDL cholesterol values.

This study aimed to assess dose distributions for stage I non-small cell lung cancer (NSCLC) with passive scattering carbon-ion radiotherapy (C-ion RT) using daily computed tomography (CT) images.We enrolled 10 patients with stage I NSCLC and acquired a total of 40 pre-fractional CT image series under the same settings as the planning CT images. These CT images were registered with planning CT images for dose evaluation using both bone matching (BM) and tumor matching (TM). Using deformable image registration, we generated accumulated doses. Moreover, the volumetric dose parameters were compared in terms of tumor coverage and lung exposure and statistical analyses were performed.Overall, 25% of 40 fractional dose distributions were unacceptable with BM, compared with 2.5% with TM (P 0.001). Using BM, three patients' accumulated dose distributions were unacceptable; however, all were satisfactory with TM (P 0.001). No differences were observed in water-equivalent path length (WEL). The required margins in patients with poor dose distribution were 5.9 and 4.4 mm for BM and TM, respectively.This study establishes that CT image-based TM is robust compared with conventional BM for both daily and accumulated dose distributions. The effects of changes in WEL seem to be limited. Hence, daily CT alignment is recommended for patients with stage I NSCLC receiving C-ion RT.

Background The effect of right ventricular (RV) septal pacing as opposed to RV apical pacing on prognosis in patients undergoing pacemaker implantation remains controversial. This study was performed to examine the clinical efficacy of RV septal pacing in a large cohort with medium-term follow-up and propensity-matched analysis. Methods A total of 982 consecutive patients with first pacemaker implantation between 2008 and 2013 at two centers in Japan (51.4% male, age 76.1±10.6years, 64.3% septal pacing, 94% preserved ejection fraction [EF]) were enrolled. Propensity matching successfully matched 446 patients into RV septal and apical pacing groups. The primary endpoint, a combination of all-cause death and hospitalization due to heart failure, was compared between the two groups. Results In the propensity-matched cohort, the primary endpoint was observed in 61 patients (13.7%) over a median follow-up period of 2.1years (interquartile range, 1.1–3.5years). The effects of septal pacing on prognosis were not statistically significant (hazard ratio [HR]=1.10, 95% confidence interval [CI]=0.60–2.04, P=0.752). No significant benefit of septal pacing was observed on all-cause death (HR=1.86, 95%CI=0.74–4.66, P=0.187) and heart failure hospitalization (HR=0.93, 95%CI=0.44–1.98, P=0.847) when assessed separately. Conclusion Septal pacing did not show medium-term advantages in prognosis in this large-scale retrospective cohort study with propensity matching of patients with predominantly preserved EF.

The presented data were obtained from 982 consecutive patients receiving their first pacemaker implantation with right ventricular (RV) lead placement between January 2008 and December 2013 at two centers in Japan. Patients were divided into RV apical and septal pacing groups. Data of Kaplan–Meier survival analysis and Cox regression analysis are presented. Refer to the research article “Implications of right ventricular septal pacing for medium-term prognosis: propensity-matched analysis” (Mizukami et al., in press) [1] for further interpretation and discussion. Keywords: RV septal pacing, RV non-apical pacing, Prognosis, Heart failure, Mortality, Data

Although hyponatremia on admission is a predictor of poor prognosis in acute heart failure (AHF) patients, little is known about the association between changes in sodium level in acute phase and in-hospital mortality. This study was performed to clarify the impact of sodium level improvement in the early phase on prognosis in AHF patients.A total of 882 consecutive hospitalized AHF patients were retrospectively enrolled in this study. Sodium levels were evaluated on days 1 and 3 of admission, and patients were classified into three groups: patients with hyponatremia on admission and day 3 (hypo-hypo group); patients with hyponatremia on admission and normonatremia on day 3 (hypo-normo group); and patients with normonatremia on admission (normo group).Hyponatremia (sodium ≤135 mEq/L) was observed in 14.3% of cases. In multivariate linear regression analysis, age (standardized beta=0.084), male gender (standardized beta=-0.072), history of ischemic heart disease (standardized beta=-0.069), baseline sodium level (standardized beta=-0.435), and tolvaptan use (standardized beta=0.093) were independent determinants of changes in sodium level from day 1 to day 3. In-hospital mortality rates were significantly higher in the hypo-hypo group (23.7%) and hypo-normo group (9.7%) than the normo group (6.9%) (p0.001). After adjustment for covariates, both hypo-normo (OR: 0.28, 95% CI: 0.08-0.93, p=0.038) and normo (OR: 0.42, 95% CI: 0.20-0.88, p=0.022) groups showed significantly lower in-hospital mortality rates than the hypo-hypo group.Early recovery from hyponatremia in AHF patients is associated with lower in-hospital mortality rate.

The acetylcholine (ACh) provocation test (ACh-test) is used for the diagnosis of vasospastic angina (VSA). However, subjects often show a moderate spasm (MS) response for which diagnosis of VSA is not definitive, and the clinical significance of this response is unknown. We assessed moderate coronary vasomotor response to the ACh test as an indicator of long-term prognosis. A total of 298 consecutive patients who underwent the ACh test for suspected VSA were retrospectively investigated. Coronary spasm severity after intracoronary administration of isosorbide dinitrate was evaluated by measuring epicardial coronary artery diameter reduction after ACh injection. Patients were divided into three groups according to the diameter reduction during the ACh test: severe spasm (SS) showing ≥75 % diameter reduction, MS showing ≥50 % diameter reduction, and others (N). In Kaplan-Meier analysis, the major adverse cardiac event (MACE) rates with a median follow-up of 4.6 years were significantly worse in SS (11.1 %) and MS (8.5 %) than N (1.9 %), (SS vs N; P = 0.009, MS vs N; P = 0.029). Significant difference in MACE rates was not observed between SS and MS (P = 0.534). Cox regression analysis revealed that MS remained an independent predictor of MACE after adjustment for other confounders (HR: 7.18, 95 % CI 1.42-36.4, P = 0.017). Patients with MS by ACh test had a cardiac event rate comparable with that of patients with SS and significantly worse than that of patients with normal vasomotor responses.

Background Pathological studies have suggested that acute coronary syndrome (ACS) may be caused by culprit lesions with intact fibrous cap (IFC), including plaque erosions. This study sought to evaluate the morphological features and clinical outcomes of patients with ACS caused by lesions with IFC. Methods A total of 318 patients with ACS who underwent optical coherence tomography (OCT) of a culprit lesion were investigated. The culprit lesions were categorized as follows: those with plaque rupture (PR group), those with an IFC (IFC group), and those with a massive thrombus precluding plaque visualization (MT group). Intravascular ultrasound (IVUS) was performed in 297 patients. Clinical follow-up data were collected regarding adverse cardiac events, including death, myocardial infarction, revascularization, and congestive heart failure requiring hospitalization. Results Culprit lesions were categorized into 141 RPs, 131 IFCs, and 46 MTs. IFC group exhibited a smaller remodeling index and less frequently attenuated plaques on IVUS. Three hundred and seven patients (96.5%) were followed for a median follow-up duration of 576 days. Adverse cardiac events were observed in 93 patients (30.3%). Kaplan–Meier analysis demonstrated a significantly lower event rate in IFC group compared with the RP and MT groups. Cox proportional hazard analysis demonstrated that an IFC and multivessel disease were independent predictors of adverse events [hazard ratio 0.57, 95% confidence interval (CI) 0.33–0.98, p = 0.043 and hazard ratio 1.72, 95% CI 1.09-2.73, p = 0.021]. Conclusions Culprit lesions with IFC showed smaller remodeling indices by IVUS, and were associated with better long-term prognosis compared with those with plaque rupture.