Quality of life after brain injury-overall scale, Japanese version: assessment of reliability and validity.

This study analyzed the linguistic and psychometric validation of the Japanese version of the Quality of Life after Brain Injury-Overall Scale (QOLIBRI-OS) consisting of six items which cover several TBI-relevant domains. We hypothesized that the Japanese version has good reliability, convergent validity, and divergent validity, compared with its long version, the 37-item QOLIBRI. The QOLIBRI-OS Japanese version was forward and back-translated from the English version. In total, 129 individuals participated in this study after experiencing a traumatic brain injury and attending clinics, rehabilitation centers, and support centers in Japan. The structure of the QOLIBRI-OS was investigated by confirmatory factor analyses and compared with the QOLIBRI. Only one factor was extracted, and a model with one underlying factor had a good fit. The QOLIBRI-OS showed good-to-excellent internal consistency and test-retest reliability. The QOLIBRI-OS was positively correlated with the QOLIBRI, Short Form Health Survey-36 version 2, and Glasgow Outcome Scale Extended, and negatively correlated with the Hospital Anxiety and Depression Scale. The results suggest that the QOLIBRI-OS Japanese version is a reliable and valid tool for assessing disease-specific health-related QOL in individuals after traumatic brain injury in Japan.

Gene and Induced Pluripotent Stem Cell Therapy for Retinal Diseases.

Given the importance of visual information to many daily activities, retinal degenerative diseases-which include both inherited conditions (such as retinitis pigmentosa) and acquired conditions (such as age-related macular degeneration)-can have a dramatic impact on human lives. The therapeutic options for these diseases remain limited. Since the discovery of the first causal gene for retinitis pigmentosa almost three decades ago, more than 250 genes have been identified, and gene therapies have been rapidly developed. Simultaneously, stem cell technologies such as induced pluripotent stem cell-based transplantation have advanced and have been applied to the treatment of retinal degenerative diseases. Here, we review recent progress in these expanding fields and discuss the potential for precision medicine in ophthalmic care.

Fluoroscopic predictors of acceptable capture threshold during the implantation of the micra transcatheter pacing system.

INTRODUCTION: Few predictors of low capture threshold before the deployment of the Micra transcatheter pacing system (Micra TPS) have been determined. We aimed to identify fluoroscopic predictors of an acceptable capture threshold before Micra TPS deployment. METHODS: Sixty patients were successfully implanted with Micra TPS. Before deployment, gooseneck appearance of the catheter shaft was quantified using the angle between the tangent line of the shaft and the cup during diastole in the right anterior oblique (RAO) view. The direction of the device cup toward the ventricular septum was evaluated using the angle between the cup and the horizontal plane in the left anterior oblique (LAO) view. RESULTS: Of the 95 deployments we evaluated, 56 achieved an acceptable capture threshold of ≤2.0 V at 0.24 ms. In this acceptable threshold group, the deflection angle of the gooseneck shaft was significantly larger and the device cup was placed more horizontally with a lower elevation angle compared with those in the high threshold group. A deflection angle of ≥6° and an elevation angle of ≤30° were identified as the predictors of an acceptable capture threshold after deployment. An acceptable capture threshold was achieved in 24/31 (77.4%) patients in whom either angle criterion was satisfied at the first deployment. CONCLUSIONS: Diastolic gooseneck appearance of the delivery catheter in the RAO view or near-horizontal direction in the LAO view predicts an acceptable capture threshold after deployment. The shape of the delivery catheter before deployment should be evaluated using multiple fluoroscopic views to ensure successful implantation of Micra TPS.

Ocular biometry with swept-source optical coherence tomography-based optical biometer in Japanese patients with EYS-related retinitis pigmentosa: a retrospective study.

BACKGROUND: This study aimed to identify the features of ocular biometry in patients with EYS-related retinitis pigmentosa using IOLMaster 700. METHODS: We retrospectively reviewed the medical records of patients with retinitis pigmentosa. Patients with records of the following were included: (1) ocular biometry measurements using the IOLMaster 700 and (2) genetic diagnostic tests. Axial length, keratometry, anterior chamber depth, aqueous depth, lens thickness, central corneal thickness (CCT), and corneal diameter (white to white) measurements were extracted. Based on keratometry measurements, (1) standard keratometric astigmatism, (2) posterior corneal astigmatism, and (3) total corneal astigmatism were obtained. Demographics and biometric parameters were compared between patients with EYS-related retinitis pigmentosa and other patients with retinitis pigmentosa. RESULTS: A total of 86 eyes of 44 patients (23 females and 21 males; mean age: 47.7 years) with retinitis pigmentosa were included. Of these, 18 were identified as having EYS variants. CCT was significantly thinner (P < 0.001) and the posterior corneal curvature at the steepest meridian was significantly smaller (P = 0.024) in patients with EYS-related retinitis pigmentosa than in other patients with retinitis pigmentosa. The magnitudes of all corneal astigmatism measurements was higher in patients with EYS-related RP, although these differences were not statistically significant. CONCLUSION: Patients with EYS-related retinitis pigmentosa had unique features in ocular biometry, such as thinner central corneal thickness and smaller posterior corneal curvature radius at the steepest meridian compared with other patients with retinitis pigmentosa. The findings suggest that patients with retinitis pigmentosa have different ocular dimension features among the different causative genes.

Perception of genetic testing among patients with inherited retinal disease: Benefits and challenges in a Japanese population.

Inherited retinal disease (IRD) is clinically and genetically heterogeneous. Awareness of the importance of genetic testing for IRD in the clinical setting is increasing with the recent development of new therapeutic strategies, such as gene therapy. Here, the perception of genetic testing, including its benefits and potential challenges, among patients with IRD was investigated to establish strategies for IRD genetic testing and counseling practices that can meet the requirements of the patients in Japan. An anonymous self-administered questionnaire was distributed to 275 patients with IRD who underwent genetic testing after clinical consultation and genetic counseling to investigate the motivations for genetic testing, benefits, challenges, status of communication of results to family, and attitude to timing of genetic testing. In total, 228 (82.9%) responses were analyzed. Several major motivations for genetic testing were identified, including gaining information on future treatment options and clarification of the inheritance pattern, among others. No association was found between the sharing of results with family members and the results of genetic testing. Moreover, according to patients who received positive results, the benefits of genetic testing included information on the inheritance pattern, additional information on the diagnosis, and mental preparation for the future. Even patients who received negative or inconclusive (variant of uncertain significance) results reported certain informative and psychological benefits. Altogether, these findings suggest that provisions for genetic testing and genetic counseling are necessary within a certain period after clinical diagnosis and it is necessary to facilitate appropriate family communication about genetic testing results while paying attention to the background of family relationships. Moreover, the benefits of genetic testing can be influenced by the careful interpretation and information provided on the test results during genetic counseling and consultation.

Optogenetic Therapy for Visual Restoration.

Optogenetics is a recent breakthrough in neuroscience, and one of the most promising applications is the treatment of retinal degenerative diseases. Multiple clinical trials are currently ongoing, less than a decade after the first attempt at visual restoration using optogenetics. Optogenetic therapy has great value in providing hope for visual restoration in late-stage retinal degeneration, regardless of the genotype. This alternative gene therapy consists of multiple elements including the choice of target retinal cells, optogenetic tools, and gene delivery systems. Currently, there are various options for each element, all of which have been developed as a product of technological success. In particular, the performance of optogenetic tools in terms of light and wavelength sensitivity have been improved by engineering microbial opsins and applying human opsins. To provide better post-treatment vision, the optimal choice of optogenetic tools and effective gene delivery to retinal cells is necessary. In this review, we provide an overview of the advancements in optogenetic therapy for visual restoration, focusing on available options for optogenetic tools and gene delivery methods.

Peptide Derivatives of Retinylamine Prevent Retinal Degeneration with Minimal Side Effects on Vision in Mice.

Safe and effective molecular therapeutics for prophylactic treatment of retinal degenerative diseases are greatly needed. Disruptions in the clearance of all-trans-retinal (atRAL) by the visual (retinoid) cycle of the retina can lead to the accumulation of atRAL and its condensation products known to initiate progressive retinal dystrophy. Retinylamine (Ret-NH2) and its analogues are known to be effective in lowering the concentration of atRAL within the eye and thus preventing retinal degeneration in mouse models of human retinopathies. Here, we chemically modified Ret-NH2 with amino acids and peptides to improve the stability and ocular bioavailability of the resulting derivatives and to minimize their side effects. Fourteen Ret-NH2 derivatives were synthesized and tested in vitro and in vivo. These derivatives exhibited structure-dependent therapeutic efficacy in preventing light-induced retinal degeneration in Abca4-/-Rdh8-/- double-knockout mice, with the compounds containing glycine and/or L-valine generally exhibiting greater protective effects than Ret-NH2 or other tested amino acid derivatives of Ret-NH2. Ret-NH2-L-valylglycine amide (RVG) exhibited good stability in storage; and effective uptake and prolonged retention in mouse eyes. RVG readily formed a Schiff base with atRAL and did not inhibit RPE65 enzymatic activity. Administered by oral gavage, this retinoid also provided effective protection against light-induced retinal degeneration in Abca4-/-Rdh8-/- mice. Notably, the treatment with RVG had minimal effects on the regeneration of 11-cis-retinal and recovery of retinal function. RVG holds promise as a lead therapy for effective and safe treatment of human retinal degenerative diseases.

Non-viral Gene Therapy for Stargardt Disease with ECO/pRHO-ABCA4 Self-Assembled Nanoparticles.

Stargardt disease (STGD) is an autosomal recessive retinal disorder caused by a monogenic ABCA4 mutation. Currently, there is no effective therapy to cure Stargardt disease. The replacement of mutated ABCA4 with a functional gene remains an attractive strategy. In this study, we have developed a non-viral gene therapy using nanoparticles self-assembled by a multifunctional pH-sensitive amino lipid ECO and a therapeutic ABCA4 plasmid. The nanoparticles mediated efficient intracellular gene transduction in wild-type (WT) and Abca4-/- mice. Specific ABCA4 expression in the outer segment of photoreceptors was achieved by incorporating a rhodopsin promoter into the plasmids. The ECO/pRHO-ABCA4 nanoparticles induced substantial and specific ABCA4 expression for at least 8 months, 35% reduction in A2E accumulation on average, and a delayed Stargardt disease progression for at least 6 months in Abca4-/- mice. ECO/plasmid nanoparticles constitute a promising non-viral gene therapy platform for Stargardt disease and other visual dystrophies.

A ROCK Inhibitor Promotes Graft Survival during Transplantation of iPS-Cell-Derived Retinal Cells.

Currently, retinal pigment epithelium (RPE) transplantation includes sheet and single-cell transplantation, the latter of which includes cell death and may be highly immunogenic, and there are some issues to be improved in single-cell transplantation. Y-27632 is an inhibitor of Rho-associated protein kinase (ROCK), the downstream kinase of Rho. We herein investigated the effect of Y-27632 in vitro on retinal pigment epithelium derived from induced pluripotent stem cells (iPS-RPE cells), and also its effects in vivo on the transplantation of iPS-RPE cell suspensions. As a result, the addition of Y-27632 in vitro showed suppression of apoptosis, promotion of cell adhesion, and higher proliferation and pigmentation of iPS-RPE cells. Y-27632 also increased the viability of the transplant without showing obvious retinal toxicity in human iPS-RPE transplantation into monkey subretinal space in vivo. Therefore, it is possible that ROCK inhibitors can improve the engraftment of iPS-RPE cell suspensions after transplantation.

Left Atrial Reverse Remodeling Following the Modified Box Isolation with Centerline in Patients with Persistent Atrial Fibrillation.

Esophageal injury is a rare but serious complication of atrial fibrillation (AF) ablation. To minimize esophageal injury, our persistent AF (PerAF) protocol involves complete left atrial posterior wall (LAPW) and pulmonary vein (PV) isolation (box isolation), with a centerline away from the esophagus. However, there has been a concern that extensive LA isolation might deteriorate LA function. There has been a paucity of data on LA remodeling after box isolation. Therefore, we compared LA size pre- and post-box isolation with an LAPW centerline in patients with PerAF.Patients who underwent catheter ablation (CA) for PerAF between November 2016 and December 2018 were retrospectively evaluated.The LAPW, including all PVs, was completely isolated in 105 consecutive patients (75 men; mean age: 68 ± 10 years) with PerAF, including 58 patients with long-standing PerAF. During a follow-up of 660 ± 332 days, 76 patients (72%) were arrhythmia-free. The LA dimension (38 ± 6 mm versus 42 ± 7 mm; P < 0.0001) and volume index (38 ± 13 mL/m2 versus 47 ± 14 mL/m2; P < 0.0001) at 6 months post-ablation were significantly decreased in patients who maintained sinus rhythm compared to pre-ablation. In patients with recurrent AF/atrial tachycardia (AT), these parameters were also significantly decreased (P < 0.001, respectively).Box isolation with a posterior centerline has no esophageal complications and a high clinical success rate in patients with PerAF. Reverse remodeling could be achieved even when using extensive isolation of the PV and LAPW in patients with PerAF.

Radiological and Physiological Predictors of IPF Mortality.

Background and Objectives: Idiopathic pulmonary fibrosis (IPF) has a variable clinical course, which ranges from being asymptomatic to progressive respiratory failure. The purpose of this study was to evaluate the novel clinical parameters of IPF patients who receive an anti-fibrotic agent. Materials and Methods: From January 2011 to January 2021, we identified 39 IPF patients at Okinawa Chubu Hospital. Clinical information was obtained, such as laboratory data, pulmonary function test (PFT) results, and chest images, including of soft tissue thickness and the high-resolution computed tomography (HRCT) pattern at diagnosis. Results: The mean age was 72.9 ± 7.0 (53-85); 27 patients were men and 12 were women. The mean body mass index was 25.1 ± 3.9 (17.3-35). Twenty-four were active smokers and the median number of packs per year was 20. Regarding laboratory findings, mean white blood cell (WBC), lactate dehydrogenase (LDH), and Krebs Von den Lungen-6 (KL-6) values were 7816 ± 1859, 248 ± 47, and 1615 ± 1503, respectively. In PFT, the mean percent predicted FVC, percent predicted total lung capacity, percent predicted functional residual capacity (FRC), and percent predicted diffusion capacity of the lung for carbon monoxide (DLco) were 66.8 ± 14.9%, 71.8 ± 13.7%, 65 ± 39.6%, and 64.6 ± 27.9%, respectively. In chest radiological findings, soft tissue thickness at the right 9th rib was 26.4 ± 8.8 mm. Regarding chest HRCT patterns, 15 showed the definite usual interstitial pneumonia (UIP) pattern, 16 showed the probable UIP pattern, and eight showed the indeterminate for UIP pattern. In the treatment, 24 patients received pirfenidone and 15 patients took nintedanib. The mean observation period was 38.6 ± 30.6 months and 24 patients died. The median survival time was 32.4 months (0.9-142.5). Multivariate analysis adjusted for age showed that both soft tissue thickness [Hazard ratio (HR): 0.912, 95% confidence interval (CI): 0.859-0.979, p-value: 0.009] and percent FRC [HR: 0.980, 95% CI: 0.967-0.992, p-value: 0.002] were robust predictors of IPF mortality. Conclusions: In IPF patients treated with anti-fibrotic agents, both soft tissue thickness at the right 9th rib shown on the chest radiograph and %FRC can be novel predictors of IPF mortality.

Lipocalin 2 Plays an Important Role in Regulating Inflammation in Retinal Degeneration.

It has become increasingly important to understand how retinal inflammation is regulated because inflammation plays a role in retinal degenerative diseases. Lipocalin 2 (LCN2), an acute stress response protein with multiple innate immune functions, is increased in ATP-binding cassette subfamily A member 4 (Abca4) -/- retinol dehydrogenase 8 (Rdh8) -/- double-knockout mice, an animal model for Stargardt disease and age-related macular degeneration (AMD). To examine roles of LCN2 in retinal inflammation and degeneration, Lcn2-/-Abca4-/-Rdh8-/- triple-knockout mice were generated. Exacerbated inflammation following light exposure was observed in Lcn2-/-Abca4-/-Rdh8-/- mice as compared with Abca4-/-Rdh8-/- mice, with upregulation of proinflammatory genes and microglial activation. RNA array analyses revealed an increase in immune response molecules such as Ccl8, Ccl2, and Cxcl10 To further probe a possible regulatory role for LCN2 in retinal inflammation, we examined the in vitro effects of LCN2 on NF-κB signaling in human retinal pigmented epithelial (RPE) cells differentiated from induced pluripotent stem cells derived from healthy donors. We found that LCN2 induced expression of antioxidant enzymes heme oxygenase 1 and superoxide dismutase 2 in these RPE cells and could inhibit the cytotoxic effects of H2O2 and LPS. ELISA revealed increased LCN2 levels in plasma of patients with Stargardt disease, retinitis pigmentosa, and age-related macular degeneration as compared with healthy controls. Finally, overexpression of LCN2 in RPE cells displayed protection from cell death. Overall these results suggest that LCN2 is involved in prosurvival responses during cell stress and plays an important role in regulating inflammation during retinal degeneration.

Potential Predictors of Poor Prognosis among Critical COVID-19 Pneumonia Patients Requiring Tracheal Intubation.

Coronavirus disease 2019 (COVID-19) is a global public health concern that can be classified as mild, moderate, severe, or critical, based on disease severity. Since the identification of critical patients is crucial for developing effective management strategies, we evaluated clinical characteristics, laboratory data, treatment provided, and oxygenation to identify potential predictors of mortality among critical COVID-19 pneumonia patients. We retrospectively utilized data from seven critical patients who were admitted to our hospital during April 2020 and required mechanical ventilation. The primary endpoint was to clarify potential predictor of mortality. All patients were older than 70 years, five were men, six had hypertension, and three ultimately died. Compared with survivors, non-survivors tended to be never smokers (0 pack-years vs. 30 pack-years, p = 0.08), to have higher body mass index (31.3 kg/m2 vs. 25.3 kg/m2, p = 0.06), to require earlier tracheal intubation after symptom onset (2.7 days vs. 5.5 days, p = 0.07), and had fewer lymphocytes on admission (339 /µL vs. 518 /µL, p = 0.05). During the first week after tracheal intubation, non-survivors displayed lower values for minimum ratio of the partial pressure of oxygen to fractional inspiratory oxygen concentration (P/F ratio) (44 mmHg vs. 122 mmHg, p < 0.01) and poor response to intensive therapy compared with survivors. In summary, we show that obesity and lymphopenia could predict the severity of COVID-19 pneumonia and that the trend of lower P/F ratio during the first week of mechanical ventilation could provide useful prognostic information.

Truncating Variants Contribute to Hearing Loss and Severe Retinopathy in USH2A-Associated Retinitis Pigmentosa in Japanese Patients.

USH2A is a common causal gene of retinitis pigmentosa (RP), a progressive blinding disease due to retinal degeneration. Genetic alterations in USH2A can lead to two types of RP, non-syndromic and syndromic RP, which is called Usher syndrome, with impairments of vision and hearing. The complexity of the genotype-phenotype correlation in USH2A-associated RP (USH2A-RP) has been reported. Genetic and clinical characterization of USH2A-RP has not been performed in Japanese patients. In this study, genetic analyses were performed using targeted panel sequencing in 525 Japanese RP patients. Pathogenic variants of USH2A were identified in 36 of 525 (6.9%) patients and genetic features of USH2A-RP were characterized. Among 36 patients with USH2A-RP, 11 patients had syndromic RP with congenital hearing problems. Amino acid changes due to USH2A alterations were similarly located throughout entire regions of the USH2A protein structure in non-syndromic and syndromic RP cases. Notably, truncating variants were detected in all syndromic patients with a more severe retinal phenotype as compared to non-syndromic RP cases. Taken together, truncating variants could contribute to more serious functional and tissue damages in Japanese patients, suggesting important roles for truncating mutations in the pathogenesis of syndromic USH2A-RP.

Sector retinitis pigmentosa: Report of ten cases and a review of the literature.

Purpose: To describe the genotypes and phenotypes of ten patients with sector retinitis pigmentosa (RP). We also review previously reported mutations associated with sector RP and provide a discussion of possible underlying pathophysiological mechanisms. Methods: Patients underwent detailed ophthalmologic examinations, fundus photography, fundus autofluorescence (FAF) imaging, spectral-domain optical coherence tomography (SD-OCT), as well as visual field and electroretinographic testing. All patients underwent genetic testing to identify the molecular etiology of their disease. Results: A total of ten patients were studied. Among these patients, nine had mutations in RHO (c.677T>C; p.Leu226Pro (novel), c.68C>A; p.Pro23His, c.808A>C; p.Ser270Arg, c.44A>G; p.Asn15Ser, and c.325G>A; p.Gly109Arg), and one patient had a mutation in RPGR (c.3092_3093delAG; p.Glu1031Glyfs*47). All patients with missense mutations in RHO had visual acuities (VAs) better than 20/30 and showed a retained foveal ellipsoid zone and overlying retinal structures. The patient with the c.3092_3093delAG deletion in RPGR had VA of 20/60 oculus dexter (OD) and 20/400 oculus sinister (OS), as well as significant foveal thinning and contour atrophy. All patients showed pigmentary changes, or marked atrophy along the inferior arcades, or both. This pattern of degeneration corresponded to hypo- and hyperFAF and superior visual defects. Conclusions: Sector RP is an uncommon form of RP in which only one or two retinal quadrants display clinical pathological signs. The great majority of cases result from mutations in RHO. The present data confirmed previously reported phenotypic manifestations of sector RP. Inferior retinal quadrants are possibly more severely affected due to greater light exposure.

New GABA modulators protect photoreceptor cells from light-induced degeneration in mouse models.

No clinically approved therapies are currently available that prevent the onset of photoreceptor death in retinal degeneration. Signaling between retinal neurons is regulated by the release and uptake of neurotransmitters, wherein GABA is the main inhibitory neurotransmitter. In this work, novel 3-chloropropiophenone derivatives and the clinical anticonvulsants tiagabine and vigabatrin were tested to modulate GABA signaling and protect against light-induced retinal degeneration. Abca4-/-Rdh8-/- mice, an accelerated model of retinal degeneration, were exposed to intense light after prophylactic injections of one of these compounds. Imaging and functional assessments of the retina indicated that these compounds successfully protected photoreceptor cells from degeneration to maintain a full-visual-field response. Furthermore, these compounds demonstrated a strong safety profile in wild-type mice and did not compromise visual function or damage the retina, despite repeated administration. These results indicate that modulating inhibitory GABA signaling can offer prophylactic protection against light-induced retinal degeneration.-Schur, R. M., Gao, S., Yu, G., Chen, Y., Maeda, A., Palczewski, K., Lu, Z.-R. New GABA modulators protect photoreceptor cells from light-induced degeneration in mouse models.

Nationwide epidemiologic study of norovirus-related hospitalization among Japanese older adults.

BACKGROUND: Older adults are vulnerable to hospitalization or death from norovirus infection, but the actual disease burden remains unknown. Therefore, we conducted a nationwide survey to estimate the number of inpatients with norovirus gastroenteritis and associated deaths among Japanese older adults. METHODS: We performed a nationwide two-step query targeting 4184 hospital departments selected from 17,575 departments using stratified random sampling according to the number of beds. We asked each department to complete a mail-back questionnaire on the annual numbers of inpatients with infectious gastroenteritis and associated deaths between administrative years 2012 and 2014, and the implementation status of norovirus infection testing. In a second query, we investigated the annual number of inpatients with norovirus gastroenteritis and associated deaths in departments that had reported infectious gastroenteritis inpatients in the first query. Clinical information was collected for inpatients with norovirus gastroenteritis in administrative year 2014. RESULTS: Norovirus testing for patients hospitalized for acute gastroenteritis was routinely conducted in 16% of the responding departments. Although half the departments responded that some acute gastroenteritis inpatients received such testing but others did not. In this situation, numbers of inpatients with norovirus gastroenteritis in Japan were estimated as 31,800 (95% CI: 25,700-37,900) in administrative year 2012, 21,600 (95% CI: 17,700-25,500) in administrative year 2013, and 15,700 (95% CI: 12,900-18,500) in administrative year 2014. The estimated number of associated deaths was approximately 600 in each administrative year. Factors associated with death included higher age, living in long-term care facilities, underlying illnesses such as chronic respiratory diseases, and complications such as aspiration pneumonia. CONCLUSIONS: The actual number of norovirus inpatient would be higher than the estimated here due to the low rate of routinely implemented norovirus testing. Considering Japan's rapidly aging society and the disease burden of norovirus infection among Japanese older adults, it is important to protect this high-risk population from norovirus infection.

Nationwide Survey of Pediatric Inpatients With Hand, Foot, and Mouth Disease, Herpangina, and Associated Complications During an Epidemic Period in Japan: Estimated Number of Hospitalized Patients and Factors Associated With Severe Cases.

BACKGROUND: Severe pediatric cases of hand, foot, and mouth disease (HFMD), herpangina (HA), and associated complications caused by enterovirus 71 (EV71) infection have brought substantial public health impact in Asia. This study aimed to elucidate the epidemiology of these pediatric cases in Japan. METHODS: A nationwide survey was conducted using stratified random sampling of hospital pediatric departments. We estimated the number of inpatients with HFMD, HA, and associated complications between April 1 and September 30, 2010, during which EV71 was circulating predominantly. Factors associated with severe cases with ≥7 days of admission, sequelae, or outcome of death were analyzed using multivariate logistic regression. RESULTS: During the 6-month epidemic period, the number of pediatric inpatients aged <15 years was about 2,900 (estimated cumulative incidence of hospitalized cases: 17.0 per 100,000 population). Severe cases were significantly associated with younger age. Compared to patients ≥5 years of age, the odds ratios (ORs) for <1 year of age and 1 to <3 years of age were 5.74 (95% confidence interval [CI], 2.14-15.4) and 2.94 (95% CI, 1.02-8.51), respectively. Elevated ORs for hyperglycemia (plasma glucose level of ≥8.3 mmol/L) on admission (OR 3.60; 95% CI, 0.94-13.8) were also observed. CONCLUSIONS: Disease burden of pediatric inpatients with HFMD, HA, and associated complications in Japan was described for the first time. During an EV71 epidemic, younger age and, suggestively, hyperglycemia may have been critical factors requiring more careful treatment.

Idiopathic Ventricular Arrhythmia Ablation Using Non-Fluoroscopic Catheter Visualization System.

A novel, sensor-based, electromagnetic, non-fluoroscopic catheter visualization (NFCV) system shows tracked catheters directly on pre-acquired fluoroscopy or cine loops. We aimed to evaluate the effectiveness of this system in the setting of catheter ablation for idiopathic premature ventricular contractions/ventricular tachycardia (i-PVC/VT).A total of 30 i-PVC/VT ablation procedures were performed using the NFCV system in conjunction with three-dimensional electroanatomic mapping system (3D-EMS) between January 2013 and April 2017. At the beginning of the procedure, cine loops of right and left anterior oblique views were obtained and replayed for subsequent mapping and ablation. Right ventriculography, aortography, or coronary angiography was performed, depending on the chamber of interest. We reviewed procedural parameters, comparing with the i-PVC/VT ablation procedure using conventional fluoroscopy (CvF) system (pre-, and post-NFCV implementation; 20 and 11 cases, respectively).I-PVC/VTs were successfully eliminated in 26 patients (87%) in the NFCV group and in 26 (84%) in the CvF group (P = 1.000). The procedure time in the NFCV group was comparable to that in the CvF group (119.8 versus 125.0 minutes, respectively, P = 0.868); the total fluoroscopy time was significantly shorter in the NFCV group (3.3 versus 16.6 minutes, P < 0.001). One patient in the CvF group experienced cardiac tamponade, requiring pericardial drainage. No major complications were encountered in the NFCV group.NFCV system, in conjunction with 3D-EMS, was safe and feasible for i-PVC/VT mapping and ablation. The system contributed to dramatically reduced fluoroscopy time, compared with CvF.

Protective Effect of Maternal Influenza Vaccination on Influenza in Their Infants: A Prospective Cohort Study.

Background: Infants <6 months of age are too young to receive influenza vaccine, despite being at high risk for severe influenza-related complications. Methods: To examine the effectiveness of maternal influenza vaccination in preventing influenza in their infants, we conducted a prospective cohort study of 3441 infants born at participating hospitals before the 2013-2014 influenza season. At the time of recruitment, their mothers completed a questionnaire about influenza vaccination status for the 2013-2014 season. A follow-up survey was conducted after the end of the 2013-2014 season to collect information regarding influenza diagnosis and hospitalization among infants. Results: During the 2013-2014 influenza season, 71 infants (2%) had influenza diagnosed, and 13 infants (0.4%) were hospitalized with influenza. Maternal influenza vaccination (especially prenatal vaccination) decreased the odds of influenza among infants. The effectiveness of prenatal vaccination was 61% (95% confidence interval, 16%-81%), whereas that of postpartum vaccination was 53% (-28%-83%). Although maternal influenza vaccination was also associated with a decreased odds of influenza-related hospitalization among infants, vaccine effectiveness (73%) did not reach statistical significance, owing to the limited number of infants hospitalized because of influenza. Conclusions: The present findings indicated that pregnant women and postpartum women should receive influenza vaccination to protect their infants.