High-intensity focused ultrasound（HIFU）can non-invasively irradiate inside the body. However, when used to treat fetuses, it can cause thermal burns of the mother’s abdominal wall at the skin interface. This study was carried out to determine whether a modified HIFU transducer enabling split-aperture irradiation can prevent thermal burns. Two HIFU transducers were compared: a conventional transducer using full-aperture irradiation and a modified transducer using split-aperture irradiation. The modified transducer was divided into six sectors for split-aperture irradiation and had a larger surface area and a smaller F number（focal length/aperture diameter）than the conventional transducer. HIFU was delivered to eight sites on the left and right leg of a three-month-old baby pig under general anesthesia, and the sites were assessed for thermal burning by two or more dermatologists. The same person performed all irradiations. Full-aperture irradiation with the conventional transducer caused deep dermal burns at all target sites, while split-aperture irradiation with the modified transducer caused only epidermal burns or superficial dermal burns. Split-aperture irradiation using a modified HIFU transducer with six sectors and a smaller F number reduces the severity of skin burns, and thus will improve the safety of HIFU therapy.

View full abstract

An increase in epicardial adipose tissue（EAT）in the left atrium（LA）predicts the progression of atrial fibrillation（AF）and AF recurrence after pulmonary vein catheter ablation（CA）. We hypothesized that EAT in the right atrium（RA）is also associated with the progression of AF and post-CA AF recurrence. Using 128-slice multidetector computed tomography, EAT volume and atrial volume were measured 3-dimensionally before CA in 68 patients who had proven AF（paroxysmal AF, 42; persistent AF, 26; mean age, 65±11 years; 42.6％ female）with successful CA and 21 volunteers with sinus rhythm（age, 63±13 years; 52.3％ female）. In both atria, EAT and atrial volumes were largest in patients with persistent AF, followed, in order, by those with paroxysmal AF, and then healthy volunteers（P＜0.001）. Increased EAT and atrial volumes in both atria predicted persistent AF（P＜0.001）. Fifteen patients had AF recurrence（22.1％）during the 2-year period after CA. Increased EAT volume in both atria were independent predictors for AF recurrence, and a RA EAT volume≥6.2ml was an independent predictor, with a hazard ratio of 5.47（95％ confidence interval, 1.2-24.3; P=0.03）. The combination of EAT and atrial volume in both atria was a more powerful independent prognostic factor, with a hazard ratio of 4.8（95％ confidence interval, 1.7-3.7; P=0.003）, and a sensitivity of 60％ in 9 of 15 patients, and specificity of 81.1％ in 43 of 53 patients,（P=0.003）. RA EAT is associated with the progression of AF and post-CA AF recurrence.

View full abstract

Long-term cognitive effects following acute lymphoblastic leukemia treatment have been reported for Caucasians; however, these data remain unclear for other ethnicities and the treatment of other cancers. Here, we assessed cognitive function in Japanese childhood cancer survivors. This study enrolled 53 Japanese survivors of childhood cancer （mean age, 9.5 years; 36 boys and 17 girls）. We evaluated performance-based cognitive function using the Wechsler Intelligence Scale for Children-Fourth Edition （WISC-Ⅳ）. Deviation intelligence quotients （IQ） for verbal comprehension （VC）, perceptual reasoning （PR）, processing speed （PS）, and working memory （WM） were compared with the standardized mean and standard deviation （SD; 100 and 15, respectively）. We classified patients into three groups depending on the cumulative methotrexate （MTX） dose （none, 1–19g/m², and＞20g/m²）. Full-scale IQ was within normal range at 104.8 （SD, 12.9）, although there were significant differences among the four WISC–Ⅳ index scores （P＜0.001）. The PS score （97.1±15.5） was significantly lower than the VC （107.2±15.8） and PR （105.3±14.2） scores （both P＜0.005）. WM performance decreased in an MTX dose-dependent manner （107.8, 102.6, and 96.5 for none, 1–19g/m², and higher than 20g/m², respectively; P=0.05）. Japanese childhood cancer survivors, including those in the non-MTX group, demonstrated significant PS impairment. High-dose MTX treatment might be associated with neurocognitive deficiencies, particularly in WM. Although current treatments are associated with high cure rates, future research and interventions are required to improve cognitive function in these patients.

View full abstract

Heart failure （HF） is a common disease in elderly patients, particularly in those presenting as readmission for worsening HF. While recent studies have revealed mortality-associated factors in this population, little is known about prognostic factors associated with worsening HF. To investigate this clinical evidence gap in patients aged over 75 years, we retrospectively investigated 165 patients hospitalized for HF at Showa University Hospital, of whom 65 （39.4％） were readmitted for worsening HF. We extracted the candidate variables based on univariate analysis, and then elucidated the independent prognostic factors by multivariate analysis. Compared with non-readmitted patients, readmitted patients with worsening HF had lower left ventricular ejection fraction （LVEF） （39％ vs. 50％, P＝0.002） and body mass index （BMI） （19.9kg/m² vs. 21.4kg/m², P＝0.007）, higher levels of B-type natriuretic peptide （BNP） （478pg/ml vs. 198pg/ml, P＜0.001）, and heart rate （HR） （71.0 beats/min vs. 67.0 beats/min, P＝0.021） upon discharge during the primary admission. Multivariate logistic analysis identified LVEF ＜40％, BMI ＜21kg/m², BNP ≥500pg/ml, Charlson score ≥3, and HR ≥70 beats/min upon initial discharge as independent prognostic factors. Based on these factors, readmission for worsening HF was more frequent in those with our proposed risk score of ≥3.0 than in those with a risk score ＜3.0 （P＜0.001）, and we suggested five prognostic factors for HF patients over 75 years old. Our proposed risk score combines these factors and might predict readmission for worsening HF in the elderly population.

View full abstract

Survivors of ventricular fibrillation out-of-hospital cardiac arrest（VF-OHCA）due to potentially reversible causes such as acute coronary syndrome（ACS）, vasospastic angina and electrolyte abnormalities are considered low risk for recurrent arrhythmia. Accordingly, implantable cardioverter-defibrillator therapy is not routinely recommended in such patients. We investigated the risk of mortality and the value of ICD therapy for VF-OHCA. Among 2,248 cardiopulmonary arrest patients presenting at our hospital, we retrospectively investigated 110 patients with VF-OHCA who were admitted for treatment. We divided the patients based on ICD（n＝71） or No-ICD status（n＝39）, and on reversible cause（n＝70） or irreversible cause（n＝40）. The groups were compared for baseline characteristics, mortality and ICD therapies. Patients with a reversible cause had a significantly lower rate of ICD implantation than those with an irreversible cause（P＝0.03）. Males in the ICD group presented more frequently than those in the No-ICD group, and cardiac mortality in patients with acute coronary syndrome was significantly lower with ICD therapy than without ICD（P＝0.04）. The rate of appropriate ICD therapies with a reversible cause was 28％, and the first ICD therapy was highest within 1 year post-implantation. Patients with VF-OHCA due to a reversible cause remain at high risk of recurrent ventricular arrhythmias, suggesting that ICD implantation is a reasonable approach in such cases.

View full abstract

This study aimed to clarify whether native coronary artery（CA） calcification before index percutaneous coronary intervention（PCI） has an impact on the effectiveness of drug-coated balloon（DCB） angioplasty for the treatment of in-stent restenosis（ISR）. 100consecutive patients with 166ISR lesions underwent quantitative coronary angiography（QCA） before and after index PCI and before and after DCB angioplasty for ISR. CA calcification before index PCI was assessed by angiography and results were analyzed to reveal the predictive values for target lesion revascularization（TLR） and major adverse cardiac events（MACE）. During 1.03±1.03years of follow-up, TLR occurred in 44lesions（26.5%） and MACE in 33 patients（33%）. On multivariate analysis, CA calcification before index PCI（p=0.016）, and % diameter of stenosis（%DS）≥73%（p=0.023） and minimal lumen diameter（MLD）<0.65mm（p=0.001） before DCB angioplasty were independent predictors for TLR after DCB angioplasty. MACE was also associated with CA calcification before index PCI（p=0.01）, and %DS≥73%（p=0.001） and MLD<0.65mm（p=0.01） before DCB angioplasty, but only %DS≥73% before DCB angioplasty was an independent predictor for MACE after DCB angioplasty（p=0.039）. The combination of CA calcification before index PCI and these QCA factors before DCB angioplasty was an independent and more powerful predictor for MACE than the QCA factors alone（p<0.001）. Thereafter, the combination of CA calcification and %DS≥73% before DCB angioplasty stratified the risk of MACE after DCB angioplasty（p<0.05）. CA calcification before index PCI, as well as anatomical information at ISR, have an impact on outcome after DCB angioplasty for ISR.

View full abstract

Emergency department（ED）crowding due to frequent visitors increases medical costs and endangers the safety of patients who need prompt treatment. Although some studies have examined the social background of frequent visitors to the ED, there are few comprehensive studies of factors related to frequent ED visits in Japan. The present study examined whether public assistance status, age, and underlying conditions are associated with frequent visits to the ED. Subjects in this study were patients over 20 years of age who visited the ED of General Medicine in Showa University Hospital in Tokyo, Japan, from April 1, 2014, to March 31, 2015（n＝6,182）. Information regarding sex, age, public insurance, hypertension, diabetes mellitus, dyslipidemia, chronic obstructive pulmonary disease, cancer, dysuria, bronchial asthma, and chronic kidney disease was collected using a patient database created from medical and hospital records. Based on a previous study, subjects who visited the ED four or more times were defined as frequent visitors, while those who visited the ED less than four times were considered infrequent visitors. Logistic regression analysis was performed to calculate odds ratios（ORs）and 95％ confidence intervals（CIs）for frequent ED visits. Receipt of public assistance significantly increased the OR for frequent visits（4.26, 95％ CI: 1.90-9.56）, even after adjusting for sex, age, and potential confounding factors（OR: 3.89, 95％ CI: 1.62-9.35）. The current study found a significant association between frequent ED visits and the receipt of public assistance. Emergency physicians and medical practitioners need to share information with outpatient physicians and welfare officers and work together with patients to address their specific medical and social vulnerabilities.

View full abstract

Knowing recent drug-resistant bacteria trends is important for proper antibacterial drug use to improve the prognosis of patients with infectious diseases and for public health. Because multiple quinolone antibacterial agents are simultaneously adopted in hospitals in Japan, we examined whether minimum inhibitory concentrations （MICs） against Haemophilus influenzae differ among quinolones. We determined MICs of six different quinolone antibacterial agents and performed molecular genetic analysis. We investigated β-lactamase-producing and β-lactamase-negative ampicillin-resistant（BLNAR）H. influenzae using the nitrocefin method in parallel. Overall, 144 clinical H. influenzae strains isolated at the Showa University Hospital between 2012 and 2017 were subjected to MIC determination for penicillin/quinolone antibacterial agents using the Clinical and Laboratory Standards Institute broth microdilution method. Amino acid mutations in the quinolone resistance-determining regions were analyzed in the isolates showing an MIC value ≥ 0.25µg/ml of quinolone antibacterial agents. BLNAR isolates increased from 2016 onward. Among quinolone antibacterial agents, all isolates remained susceptible to sitafloxacin. However, for moxifloxacin（MFLX）, strains with an MIC value＝0.5µg/ml were detected every year since 2013 except in 2015. Amino acid mutations were investigated in 17 isolates （11.8％） with MFLX MIC value≥ 0.25µg/ml and confirmed in 11 isolates （7.6％）, of which 9 contained GyrA mutations. The results demonstrated that MFLX was useful for predicting the presence of amino acid mutations and 0.25 was an appropriate MIC threshold for this purpose. This screening procedure may be effective for reducing the inappropriate use of quinolones and controlling the emergence of drug-resistant H. influenzae.

View full abstract

In this study, a highly sensitive method to simultaneously quantify the integrase strand transfer inhibitors （INSTIs） raltegravir, dolutegravir, elvitegravir, and bictegravir, which are recommended drugs in the HIV treatment guidelines, was established using liquid chromatography–tandem mass spectrometry （LC-MS/MS）. Raltegravir-d3 was used as the internal standard substance. The plasma samples were deproteinized with methanol and analyzed by LC-MS/MS. Chromatographic separation was performed using the gradient method with a mobile phase A （20mmol/l ammonium formate - water） and mobile phase B （20mmol/l ammonium formate - methanol）. In addition, an InertSustain C18 column （3µm, 100×2.1mm）, a flow rate of 0.45ml/min, and a measurement time of 10 minutes were used. The calibration curve showed linearity （r2＞0.9904） within the range of 0.5-1,250ng/ml, and the limit of quantification was 0.5ng/ml for all drugs. The mean intra- and inter-day accuracy was 99.6％±7.2％ and 101.0％±5.0％, respectively, and the coefficient of variation （CV） was ≤18.5％ and ≤10.3％, respectively. This method enables the highly sensitive simultaneous analysis of INSTIs and is useful for confirming the efficacy and safety of drugs in clinical practice.

View full abstract

Pentazocine is an intravenously administered preoperative analgesic, but patients occasionally experience nausea and vomiting as an adverse reaction to this drug. As nausea and vomiting may interfere with the patient’s postoperative rest, prevention of the reaction is necessary. This study aimed to survey postoperative nausea and vomiting（PONV）caused by pentazocine administered for catheter ablation. Patients receiving catheter ablation often experience pain during venipuncture and radiofrequency application, thus they are frequently placed under mild to deep sedation. Patients who underwent catheter ablation between February and July 2016 were analyzed retrospectively. The preoperative analgesic dose and PONV were assessed. In total, 256 subjects（177 males, mean age: 65.3±12.9 years）were analyzed of which 185（72.3％）underwent atrial fibrillation ablation. Of these, 134 subjects（52.3％）were administered 15mg pentazocine and 122 subjects（47.7％）were administered 30mg pentazocine, preoperatively. Patients who required additional sedative administration, as determined by the physician, during the procedure received either dexmedetomidine（205 subjects; 80.1％）or thiopental（218 subjects; 85.2％）. Investigation of postoperative nausea revealed that 8 subjects in the 15mg group（6.0％）and 21 subjects in the 30mg group（17.2％）experienced nausea, a significantly higher percentage in the 30mg group（p＝0.005）. Analysis of postoperative vomiting shows that 6 subjects in the 15mg group（4.5％）and 14 subjects in the 30mg group（11.5％）experienced postoperative vomiting, indicating a higher percentage in the 30mg group（p＝0.04）. Furthermore, the data indicate that being female is also an independent indicator of PONV. The results of this study suggest a relationship between pentazocine dose and PONV and that the incidence of PONV is directly related to an increased pentazocine dose.

View full abstract