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Purpose To describe the clinical features of severe recurrent fibrovascular proliferation after intravitreal bevacizumab injections and laser photocoagulation for aggressive posterior retinopathy of prematurity. Methods This retrospective, nonrandomized case series reviewed the medical and ophthalmic records in the referral hospital and our hospital. Patients Four patients (seven eyes) with aggressive posterior retinopathy of prematurity. Results The patients were referred for vitrectomy with/without lensectomy for recurrent fibrovascular proliferation with a tractional retinal detachment after combined intravitreal bevacizumab injections and laser photocoagulation. Three patients were born at 22 weeks or 23 weeks' gestational age and one patient at 29 weeks' gestational age. Preoperatively, fluorescein angiography images showed all eyes had tractional retinal detachment from regrowth of fibrovascular proliferation 3 months to 5 months after the intravitreal bevacizumab injection and abnormal retinal vasculature; four eyes had a broad ischemic retina. Postoperatively, four eyes had retinal attachment and three eyes a total retinal detachment. Neovascular glaucoma developed in five of the seven eyes during the clinical course. Conclusion Severe fibrovascular proliferation may recur due to widespread retinal ischemia with capillary dropout and abnormal vasculature after failed combined intravitreal bevacizumab and laser photocoagulation therapy as the initial treatment for aggressive posterior retinopathy of prematurity. Careful follow-up is important especially after anti-vascular endothelial growth factor treatment, with recognition that severe reactivation is possible.

OBJECTIVES Controlled donation after circulatory death (cDCD) donors are becoming a common source of organs for transplantation globally. However, the graft survival rate of cDCD abdominal organs is inferior to that of organs from brain-dead donors. The rapid retrieval (RR) technique is used by most donor organ procurement teams. The abdominal normothermic regional perfusion (A-NRP) technique has been implemented to minimize warm ischaemic damage to the abdominal organs. However, there is limited information on the effect of A-NRP on the quality of the donor lungs. This study aimed to compare lung transplantation outcomes using lungs procured from cDCD donors using the A-NRP and abdominal RR techniques. METHODS A single-centre retrospective analysis of consecutive transplant recipients of cDCD lungs from June 2013 to December 2019 was performed. The recipients were divided into 2 cohorts according to the abdominal procurement technique used. The recipient and donor characteristics (age, sex, cause of brain injury, warm ischaemic time, diagnosis, lung allocation score and other factors), incidence of primary graft dysfunction and early survival were monitored. RESULTS Twenty-eight consecutive lung transplantation recipients were identified (median age 59 years; 61% male); 14 recipients received lungs using the A-NRP and 14 using abdominal RR for abdominal organ retrieval. There were no significant differences in the baseline characteristics, primary graft dysfunction (P = 0.70), hospital mortality (P = 1.0) and 1-year survival rate (P = 1.0) between the 2 groups. CONCLUSIONS No difference was observed in lung transplantation outcomes irrespective of the abdominal organ procurement technique used (A-NRP or abdominal RR).

OBJECTIVES We reviewed the incidence of coronavirus disease 2019 cases and the postoperative outcomes of patients who had thoracic surgery during the beginning and at the highest point of transmission in our community. METHODS We retrospectively reviewed patients who had undergone elective thoracic surgery from 12 February 2020 to 30 April 2020 and were symptomatic or tested positive for severe acute respiratory syndrome coronavirus 2 infection within 14 days after surgery, with a focus on their complications and potential deaths. RESULTS Out of 101 surgical procedures, including 57 primary oncological resections, 6 lung transplants and 18 emergency procedures, only 5 cases of coronavirus disease 2019 were identified, 3 in the immediate postoperative period and 2 as outpatients. All 5 patients had cancer; the median age was 64 years. The main virus-related symptom was fever (80%), and the median onset of coronavirus disease 2019 was 3 days. Although 80% of the patients who had positive test results for severe acute respiratory syndrome coronavirus 2 required in-hospital care, none of them were considered severe or critical and none died. CONCLUSIONS These results indicate that, in properly selected cases, with short preoperative in-hospital stays, strict isolation and infection control protocols, managed by a dedicated multidisciplinary team, a surgical procedure could be performed with a relatively low risk for the patient., Since the outbreak of the novel coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, China [1], over 4.9 million cases have been diagnosed around the world [2].

Purpose To examine the usefulness of red channel fundus imaging to detect the ischemic status in eyes with central retinal vein occlusion (CRVO). Methods Ultra-widefield (UWF) fundus images were obtained from 42 eyes with CRVO. Twenty-one eyes were ischemic, and 21 eyes were non-ischemic. Rubeosis was found in 11 ischemic eyes. UWF images were split into red and green channels using ImageJ software. Both the color and red channel images were used to predict the presence or absence of ischemia when examined by masked graders. The sensitivity and specificity of UWF imagings for the detection of ischemia were calculated in Group A (total 42 eyes), Group B (32 eyes excluding non-rubeotic ischemic CRVO) and Group C (31 eyes excluding rubeotic ischemic CRVO), respectively. Moreover, a linear mixed model was conducted to investigate the relationship between the type of images and the accuracy of prediction in each group. Results No significant difference in the sensitivity of color fundus imaging was seen between Group A and Group B. By contrast, a significant difference in the sensitivity of red channel imaging was seen between Group A and Group B (p = 0.031). The accuracies of the predictions were not associated with the type of image in Group A and Group B, but were significantly associated in Group C (p = 0.026). Conclusions UWF red channel imaging enabled more accurate detection of the ischemic status, compared with color fundus images, especially in non-rubeotic CRVO eyes.

Introduction Controlled donation after circulatory-death donors (cDCD) are becoming a frequent source of lungs grafts worldwide. Conversely, lung transplantations (LTx) from uncontrolled donors (uDCD) are sporadically reported. We aimed to review our institutional experience using both uDCD and cDCD and compare to LTx from brain death donors (DBD). Methods This is a retrospective analysis of all LTx performed between January 2013- December 2019 in our institution. Donor and recipient characteristics were collected and univariate, multivariate and survival analyses were carried out comparing the three cohorts of donors. Results A total of 239 (84.7%) LTx were performed from DBD, 29 (10.3%) from cDCD and 14 (5%) from uDCD. There were no statistically significant differences in primary graft dysfunction grade 3 at 72 hours, 30- and 90-day mortality, need for extracorporeal membrane oxygenation after procedure, ICU and hospital length of stay, airway complications, CLAD incidence or survival at 1 and 3 years after transplant (DBD: 87.1% and 78.1%; cDCD: 89.7% and 89.7%; uDCD: 85.7% and 85.7%, respectively; p=0.42). Short- and mid-term outcomes are comparable between the three types of donors. Conclusions These findings may encourage and reinforce all types of donation after circulatory-death programmes as a valid and growing source of suitable organs for transplantation.

Background Idiopathic multicentric Castleman disease (iMCD) is a rare polyclonal lymphoproliferative disease caused by the overrepresentation of interleukin-6 (IL-6). Tocilizumab (TCZ) is a humanized monoclonal antibody that binds to the IL-6 receptor and is approved for the treatment of iMCD. The efficacy and tolerability of TCZ in patients with iMCD undergoing lung transplantation (LTx) remain unknown. Case presentation We present the case of a 48-year-old iMCD patient with end-stage lung disease (ESLD) who was successfully treated with cadaveric single-LTx. Intravenous TCZ was used to stabilize the iMCD patient every 2 weeks, except for withdrawal immediately after LTx. At 32 month post-transplant, the patient remained asymptomatic without evidence of rejection, development of de novo donor-specific antibody (DSA), and recurrent iMCD in the native lung. Conclusions Single-LTx can be a feasible treatment option for ESLD caused by iMCD. TCZ can be used safely and may be beneficial in recipients with iMCD, and TCZ in combination with usual immunosuppression can be helpful in stabilizing iMCD patients pre- and post-LTx.

OBJECTIVES Most transplant centres use donation after brain death (DBD) criteria to assess the quality of controlled donation after circulatory death (cDCD) lungs. However, research on the relationship between DBD extended criteria and cDCD lung transplantation outcomes is limited. We investigated the outcomes of using DBD extended criteria donor organs in cDCD lung transplantation, compared to the standard criteria cDCD lung transplantation. METHODS A retrospective chart review of consecutive cDCD lung referrals to Hospital Universitario Puerta de Hierro-Majadahonda from June 2013 to December 2019 was undertaken. Donors were divided into standard and extended criteria groups. Early outcomes after lung transplant were compared between these groups using the Kaplan–Meier method and log-rank test. RESULTS Thirty out of 91 cDCD donor lung offers were accepted for transplantation, of which 11 were from standard criteria donors and 19 were extended criteria donors. The baseline characteristics of the 2 recipient groups were similar. There were no differences in the rates of grade 3 primary graft dysfunction at 72 h after lung transplantation (21% vs 18%), duration of mechanical ventilation (48 h vs 36 h), total intensive care unit stay (10 days vs 7 days) and 1-year survival (89% vs 90%). CONCLUSIONS Carefully selecting cDCD lungs from outside the standard acceptability criteria may expand the existing donor pool with no detrimental effects on lung transplantation outcomes.

To describe the clinical features and treatment outcomes of severe retinopathy in eyes with incontinentia pigmenti (IP) of infants within a few months of birth. Retrospective clinical study. Six eyes of three patients (6-day-old girl, 5-month-old girl, and 14-day-old boy) with IP were examined and treated under general anesthesia. Ophthalmologic examinations were performed including images from wide-angle fluorescein angiography (FA), swept-source optical coherence tomography (OCT), and OCT angiography (OCTA). Ophthalmoscopy showed prominent vascular tortuosity in five eyes, retinal hemorrhages in four eyes, and incomplete vascular development in two eyes. FA showed extensive avascularity including the posterior pole of the retina in all cases except one eye. Prompt and intensive laser photocoagulation stabilized the pre-proliferative severe retinopathy in five eyes; however, foveal structure and vessel anomalies were detected in three of six eyes by OCT and two of five eyes by OCTA. Severe retinopathy in the neonatal period and infancy was present not only in the periphery but also in the posterior pole including the fovea, which might be related to retinal vascular maldevelopment. It is, therefore, recommended that wide-angle fundus FA examination be performed in the early postnatal period to detect early signs of severe retinopathy in infants with IP.

Purpose To report the outcomes of autologous neurosensory retinal transplant as a primary treatment for patients with large chronic macular holes and evaluate the safety and feasibility of the procedure. Design Retrospective study, consecutive case series. Methods We reviewed seven patients with a primary chronic large macular hole, who underwent autologous neurosensory retinal transplant. Mean preoperative minimum and maximum hole diameters were 643 µm and 1214 µm, respectively. Changes in visual acuity were measured postsurgery, and optical coherence tomography, fluorescein angiography, and microperimetry-3 were analyzed after the procedure. Results Closure of the macular hole was achieved in all seven eyes in the study. At 1 year post-surgery, there was significant improvement in mean visual acuity (LogMAR 1.10 vs. 0.68, P = 0.001). Optical coherence tomography showed that all grafts had formed attachments to the retinal epithelial cells of the recipient retina. Mean preoperative ellipsoid zone defect was 1,089 ± 403.8 µm (range, 918-1,329 µm) which further decreased to 921 ± 129.1 µm (range, 670-1,201 µm) at final follow up (P = 0.09). Microperimetry-3 testing indicated retinal sensitivity in the graft in five eyes. Conclusion Autologous retinal transplantation may help rebuild the macular structure resulting in functional improvement for eyes with primary chronic large macular hole.

Background Anti-aminoacyl-tRNA synthetase (ARS) antibodies have been detected in patients with polymyositis/dermatomyositis (PM/DM) and are especially correlated with interstitial lung disease (ILD). The aim of this study was to clarify the clinical features of patients with anti-ARS antibody positive idiopathic interstitial pneumonias (IIPs). Methods Patients were classified into three groups: 1) IIP with anti-ARS antibodies (ARS(+)IIP), 2) IIP without anti-ARS antibodies (ARS(−)IIP), and 3) PM/DM-associated ILD with anti-ARS antibodies (ARS(+)PM/DM-ILD). Clinical characteristics were compared retrospectively between the ARS(+)IIP group and the ARS(−)IIP group or ARS(+)PM/DM-ILD group. Results Eighteen ARS(+)IIP, 284 ARS(−)IIP, and 20 ARS(+)PM/DM-ILD patients were enrolled. The ARS(+)IIP group was significantly older and the male sex was predominant, had a lower prevalence of signs of connective tissue disease, differences in HRCT findings and patterns, and higher KL-6 levels compared to the ARS(+)PM/DM-ILD group. The findings in the bronchoalveolar lavage fluid (BALF) showing lymphocytosis and a lower CD4/CD8 ratio were similar between the two groups. However, the ARS(+)IIP group had significantly lower percentage of sputum, higher prevalence of mechanic's hand, higher KL-6 levels, lower percentage of vital capacity in the pulmonary function test, and lower CD4/CD8 ratio in BALF, compared to the ARS(−)IIP group. Conclusions The present study demonstrated that features of pulmonary involvement were similar to those in the ARS(+)PM/DM-ILD group; however, some differences including HRCT findings and higher KL-6 levels suggest that ARS(+)IIP has severe ILD compared with ARS(+)PM/DM-ILD. Further prospective studies with a larger number of patients will elucidate the exact role of anti-ARS antibodies in IIPs.

Purpose This study investigated the relationship between retinal artery angle and visual function in eyes with idiopathic epiretinal membrane (ERM). Methods Ultra-wide field fundus imaging was conducted to analyze ERM and normal contralateral eyes. In addition to the logMAR visual acuity (VA) measurement, the average of the vertical and horizontal metamorphopsia scores (Mave) was measured using m-Charts for each eye. We calculated the retinal artery angle (Yugami correlated angle [YCA]) in all the examined eyes using ImageJ software. The YCAs were then compared between the ERM and normal contralateral eyes. Additionally, the relationship between YCA and visual function was investigated in the ERM eyes. Results Data from 40 patients with ERM were analyzed. The mean age of the participants was 67.1 ± 8.1 years. The YCA was significantly smaller in the ERM eyes, compared with the contralateral eyes (P < 0.001, respectively; Wilcoxon signed rank test). Among age, axial length, YCAs, central retinal thickness (CRT), and central choroidal thickness (CCT), the optimal model for logMAR VA included age, YCA, and CRT. On the other hand, the optimal model for Mave included YCA and CCT. Conclusions The retinal artery angle may be useful for predicting visual function in eyes with ERM. Translational Relevance Our established quantitative measurements in fundus photography have potential clinical use in predicting visual function in ERM.

Purpose To investigate the associations between visual function and the optical coherence tomography (OCT) parameters in eyes with idiopathic epiretinal membrane (ERM). Methods Thirty-nine consecutive eyes with ERM were enrolled. In addition to OCT parameters, such as central retinal thickness (CRT), the area of gap between the ERM and the retinal surface (SUKIMA) was newly defined and calculated from the vertical and horizontal OCT images (SUKIMAv and SUKIMAh). The average of SUKIMAv and SUKIMAh (SUKIMAave) was used for the statistical analysis. The vertical and horizontal metamorphopsia scores (MV, MH) and the average of MV and MH (Mave) were also used for the analysis. Results The Mave was not significantly associated with logMAR visual acuity (VA) (P = 0.57, linear regression analysis). Analysis using second-order bias-corrected Akaike information criterion model selection identified the age, CRT, and SUKIMAave as being associated with logMAR VA. On the other hand, among the OCT parameters, SUKIMAave and CRT were associated with the Mave. In addition, there was a significant relationship between SUKIMAh and MV (P = 0.011) and between SUKIMAv and MH (P = 0.0014). Conclusions We identified SUKIMA as a novel OCT parameter that is useful to predict both VA and metamorphopsia in patients with ERM.

Purpose To report the clinical and genetic findings of a male toddler who presented bilateral bullous retinoschisis with a novel RS1 mutation. Observations This is an observational case report of a patient referred to our hospital with esotropia. A comprehensive ophthalmic examination was performed with the boy (age, 1 year 4 months) under general anesthesia that included fundus examinations, fluorescein angiography (FA), swept-source optical coherence tomography (SS-OCT), and full-field electroretinography (FF-ERG). Genetic analysis of the coding region in the RS1 gene was performed by Sanger sequencing for the patient and mother. There was a family history of X-linked retinoschisis (XLRS). Fundus examinations and FA showed bullous retinoschisis bilaterally in the inferior retina. The SS-OCT images showed two kinds of schisis in the inner nuclear layer (INL) and more proximally. In general, the inner plexiform layer, ganglion cell layer, and retinal nerve fiber layer are in the proximal INL; however, in this case there was hyperreflective tissue with a rough surface instead of normal retinal layers. In addition, in the schisis cavity between the hyperreflective tissue and separated retina, a number of hyperreflective fiber-like strands arose from the hyperreflective tissue and extended to the schisis cavity. During the follow-up period, the bullous retinoschisis collapsed spontaneously in the right eye. FF-ERG showed a reduced b-wave and relatively preserved a-wave in all components. Genetic analysis showed a novel RS1 mutation (c.185_186insT, p.E62DfsX24 in exon 4) in the patient and mother. Conclusions and importance We report the detailed retinal structure in a genetically identified case of bullous retinoschisis. The notable finding was that the cavity of bullous retinoschisis contained a number of fiber-like strands as observed in the cavity of typical retinoschisis.

In lung transplantation, unexpected pulmonary emboli, including thrombi and fat, have been observed with high probability and are associated with potential primary graft dysfunction. We evaluated a new perfusion method using warm retrograde flushing that removes more fat than conventional cold retrograde flushing. We developed a novel porcine donor model for pulmonary fat embolism by administering autologous fat in the left pulmonary artery. The left pulmonary artery and the left superior and inferior pulmonary veins were cannulated for flushing and collecting these solutions. After flushing, the left lung was reperfused under observation for 3 h. Two groups underwent warm and cold additional retrograde flush (WS; warm solution group, CS; cold solution group). The fat removal rate in the antegrade flush was equal in both groups (3.0 ± 0.6% vs 3.0 ± 0.4%, p = 0.46); however, the rate was significantly greater in the WS group in retrograde flush (25.2 ± 3.2% vs 8.0 ± 1.4%, p = 0.01). Histology with Oil Red O staining and its software analysis showed more residual fat in the CS group (0.12 ± 0.01% vs 0.38 ± 0.07%, p = 0.01). There was no significant difference in the pulmonary function and hemodynamics during the 3-h period after reperfusion. Warm retrograde perfusion can remove more fat from lung grafts with fat embolism in a porcine donor model.

Donor-derived cell-free DNA (dd-cf-DNA) has been shown to be an informative biomarker of rejection after lung transplantation (LT) from deceased donors. However, in living-donor lobar LT, because small grafts from blood relatives are implanted with short ischemic times, the detection of dd-cf-DNA might be challenging. Our study was aimed at examining the role of dd-cf-DNA measurement in the diagnosis of primary graft dysfunction and acute rejection early after living-donor lobar LT. Immediately after LT, marked increase of the plasma dd-cf-DNA levels was noted, with the levels subsequently reaching a plateau with the resolution of primary graft dysfunction. Increased plasma levels of dd-cf-DNA were significantly correlated with decreased oxygenation immediately (p = 0.022) and at 72 hours (p = 0.046) after LT. Significantly higher plasma dd-cf-DNA levels were observed in patients with acute rejection (median, 12.0%) than in those with infection (median, 4.2%) (p = 0.028) or in a stable condition (median, 1.1%) (p = 0.001). Thus, measurement of the plasma levels of dd-cf-DNA might be useful to monitor the severity of primary graft dysfunction, and plasma dd-cf-DNA could be a potential biomarker for the diagnosis of acute rejection after LT.

Background Idiopathic pulmonary fibrosis (IPF) is a chronically progressive lung disease with exceptionally poor prognosis. While lung transplantation (LTx) is considered the last-resort therapeutic option, dismal waitlist mortality still hampers the salvage of patients with IPF. Pirfenidone, originally designed for IPF treatment, has increasingly been utilized. This study aimed to evaluate whether Pirfenidone could influence outcomes of patients with IPF on the Japanese LTx waitlist. Methods This retrospective single-center cohort study included 25 consecutive patients with IPF who were registered as LTx candidates at our institution between July 1999 and August 2016. Patients with a history of pretransplant Pirfenidone therapy (Pirfenidone group) were compared with those with no history (non-Pirfenidone group). Results In total, 6 (24%) patients received Pirfenidone as pretransplant therapy for 45.2 (range, 18.6–66.8) months. During the treatment period, the Pirfenidone group achieved a significant reduction in the decline rate of the forced vital capacity (-6.2% vs. -0.3%, p = 0.04) and a lower lung allocation score (31 vs. 41, p = 0.013) compared with the non-Pirfenidone group. The Pirfenidone group exhibited 100% waitlist survival three years after registration that was comparable to other indications, and 66% of the patients were still alive at the time of organ availability. No patient in the Pirfenidone group developed Pirfenidone-related surgical complications postoperatively. Conclusions Patients with IPF successfully managed with long-term Pirfenidone therapy achieved favorable outcomes after LTx registration, comparable to other patients with LTx indications. The tolerability to antifibrotic therapy can be a predictor of waitlist survival.

PURPOSE: When patients are mechanically ventilated for more than 5 days, they are usually declined as donors for lung transplantation (LTx); thus, the long-term outcomes of LTx from such donors remain unclear. We investigated the feasibility of LTx from donors that had been mechanically ventilated for prolonged periods. METHODS: The subjects of this retrospective comparative investigation were 31 recipients of LTx from donors who had been mechanically ventilated for RESULTS: The median duration of donor mechanical ventilation was 3 days in the short-term group and 8.5 days in the long-term group. However, other than the difference in the duration of donor ventilation, there were no significant differences in the clinical characteristics of the donors or recipients between the groups. The overall survival rate after LTx was comparable between the long-term group and short-term group (5-year survival rate, 66.6% vs. 75.2%). CONCLUSION: The potential inclusion of donors who have been on mechanical ventilation for more than 5 days could be a feasible strategy to alleviate donor organ shortage.

PURPOSE: Glucocorticoids are used to prevent chronic lung allograft dysfunction (CLAD) after lung transplantation (LT). Our study was aimed at assessing the association between the glucocorticoid-induced transcript 1 gene (GLCCI1) variant, which modulates glucocorticoid sensitivity, and the postoperative lung function and development of CLAD after LT. METHODS: A total of 71 recipients of LT were genotyped for the GLCCI1 variant (rs37972) and divided into three groups: the homozygous mutant allele (TT) group, the heterozygous mutant allele (CT) group, and the wild-type allele (CC) group. The results of pulmonary function tests were compared with the postoperative baseline values. RESULTS: The total lung capacity (TLC) in the TT group was significantly lower than that in the CC group at 3 years after LT (P = 0.029). In the recipients of cadaveric LT, the TLC and forced expiratory volume in 1 s in the TT group were significantly lower than those in the CC groups, resulting in a significant worse CLAD-free survival at 3 years after LT (P = 0.016). CONCLUSION: The GLCCI1 variant was associated with a significant decrease of the TLC at 3 years after LT and the development of CLAD at 3 years, especially in patients undergoing cadaveric LT.

The technique of pneumonectomy, back-table lung preservation, double-sleeve resection and reimplantation of basal segments (the Oto procedure) has been proposed as a useful technique for the management of locally advanced central lung cancer with short-term follow-up. We report the long-term outcomes of 5 consecutive patients who underwent the Oto procedure.

Autoantibodies specific for idiopathic inflammatory myopathy (myositis-specific autoantibodies (MSAs)) are clinically useful biomarkers to help the diagnosis of polymyositis/dermatomyositis (PM/DM). Many of these are also associated with a unique clinical subset of PM/DM, making them useful in predicting and monitoring certain clinical manifestations. Classic MSAs known for over 30 years include antibodies to Jo-1 (histidyl transfer RNA (tRNA) synthetase) and other aminoacyl tRNA synthetases (ARS), anti-Mi-2, and anti-signal recognition particle (SRP). Anti-Jo-1 is the first autoantibodies to ARS detected in 15-25 % of patients. In addition to anti-Jo-1, antibodies to seven other aminoacyl tRNA synthetases (ARS) have been reported with prevalence, usually 1-5 % or lower. Patients with any anti-ARS antibodies are associated with anti-synthetase syndrome characterized by myositis, interstitial lung disease (ILD), arthritis, Raynaud's phenomenon, and others. Several recent studies suggested heterogeneity in clinical features among different anti-ARS antibody-positive patients and anti-ARS may also be found in idiopathic ILD without myositis. Anti-Mi-2 is a classic marker for DM and associated with good response to steroid treatment and good prognosis. Anti-SRP is specific for PM and associated with treatment-resistant myopathy histologically characterized as necrotizing myopathy. In addition to classic MSAs, several new autoantibodies with strong clinical significance have been described in DM. Antibodies to transcription intermediary factor 1γ/α (TIF1γ/α, p155/140) are frequently found in DM associated with malignancy while anti-melanoma differentiation-associated gene 5 (MDA5; CADM140) are associated with clinically amyopathic DM (CADM) complicated by rapidly progressive ILD. Also, anti-MJ/nuclear matrix protein 2 (NXP-2) and anti-small ubiquitin-like modifier-1 (SUMO-1) activating enzyme (SAE) are recognized as new DM-specific autoantibodies. Addition of these new antibodies to clinical practice in the future will help in making earlier and more accurate diagnoses and better management for patients.

A photothermal film (PTF) with densely assembled gold nanoparticle-fixed beads on a polymer substrate is fabricated. Remarkably, a temperature rise higher than 40 °C is achieved in the PTF with only 100 seconds of artificial solar irradiation, and the output power of the thermoelectric device was enhanced to be one order higher than that without PTF. These results will pioneer a rapid solar thermoelectric device.

Semiconductor DFB (Distributed feedback) laser diodes with an operating wavelength of 1064 nm, which is suitable for pulse-on-demand fiber laser, have been developed. The stable performance of CW and nanosecond/picosecond pulsed operation is reviewed. By applying gain-switching operation with a simple direct modulation technique, 50-ps pulse generation with a stable spectral single-mode property was obtained. For the efficient amplification of the obtained 50-ps pulse, a monolithic semiconductor optical amplifier (SOA) was integrated into the DFB lasers. An improved peak power of 300 mW at 50-ps pulse was observed with limited optical noise injection when the synchronous modulation technique of the DFB and the SOA was employed. Short cavity lasers showed a high-frequency response compared to the original DFB lasers and achieved a short pulse width of 13 ps by standard gain-switched operation.

Senescence marker protein-30 (SMP30) decreases androgen-independently with aging and is a lactone-hydrolyzing enzyme gluconolactonase (GNL) that is involved in vitamin C biosynthesis. In the present study, bone properties of SMP30/GNL knockout (KO) mice with deficiency in vitamin C synthesis were investigated to reveal the effects of SMP30/GNL and exogenous vitamin C supplementation on bone formation. Mineral content (BMC) and mineral density (BMD) of the mandible and femur of SMP30/GNL KO and wild-type mice at 2 and 3 months of age with or without vitamin C supplementation were measured by dual-energy X-ray absorptiometry. Body and bone weight of both age groups decreased and became significantly lower than those of wild-type mice. The bones of SMP30/GNL KO mice were rough and porous, with BMC and BMD significantly below wild-type. Oral supplementation with vitamin C eliminated differences in body weight, bone weight, BMC, and BMD between SMP30/GNL KO and wild-type mice at each age. These results indicate that bone degeneration in SMP30/GNL KO mice was caused by lack of vitamin C, and that this mouse strain is an appropriate model for bone metabolism in humans, which have no ability to synthesize vitamin C.

Sarcoidosis is a major cause of granulomatous uveitis but rarely manifests as multiple choroidal granulomas. This report describes the use of enhanced depth imaging optical coherence tomography (EDI-OCT) to visualize changes occurring in multiple choroidal granulomas during treatment. The patient was a 36-year-old Japanese man with histopathologically confirmed sarcoidosis, who was examined using EDI-OCT and showed multiple yellowish-white subretinal lesions in the peripapillary region and the arcade of the right eye. EDI-OCT revealed homogeneous hyporeflective choroidal lesions with choriocapillaris thinning, consistent with a diagnosis of choroidal granulomas. Subretinal fluid adjacent to one of the peripapillary choroidal lesions was also apparent. EDI-OCT during oral prednisolone administration revealed a decrease in lesion size at as early as 3 weeks and complete resolution of the lesions after 6 months of treatment. However, 2 months after prednisolone discontinuation, EDI-OCT revealed recurrence of choroidal granulomas in the peripapillary region and the arcade of the right eye. After injection of triamcinolone acetonide into the posterior sub-Tenon’s capsule (sub-Tenon’s injection), EDI-OCT demonstrated a reduction in granuloma lesion size within 3 months of the injection. EDI-OCT allowed detailed morphologic visualization of the choroidal granulomas caused by sarcoidosis. This imaging technique was useful for monitoring changes in granuloma size in response to steroid administration and for early detection of recurrence. Injection of triamcinolone acetonide into the posterior sub-Tenon’s capsule was as effective as oral prednisolone for the treatment of choroidal granulomas.

A successful outcome after lung transplant was achieved using lungs donated from a teenage boy who underwent prolonged mechanical ventilation. The donor experienced hypoxic brain damage and was declared brain dead 324 days after tracheal intubation. At the time of referral, the donor's lungs revealed diffuse radiologic infiltration and atelectasis but excellent function, with a PaO2/FiO2 ratio of 450. The lungs were transplanted to a 10-year-old girl with bronchiolitis obliterans. She developed grade 2 primary graft dysfunction, but recovered quickly. She is doing well and has not experienced any other critical adverse events 12 months after lung transplantation.

Charge-trapping nonvolatile memories have received considerable attention as a promising candidate for the future data storages in communication and multimedia applications. In this architecture, electron and hole trapping phenomena by point defects distributed in charge trapping dielectric layers, such as silicon nitrides, are commonly used to memorize data. Recently, we have proposed the application of SiCN films with a low-dielectric constant (low-k) and a narrow band gap to the charge trapping layers [1]. The relative dielectric constant of SiCN films is 4.8-4.9, which is lower than that of silicon nitride films. Charges trapped in the low-k SiCN charge trapping layer induce the larger threshold voltage shift in MISFETs as compared with those trapped in the silicon nitride layer. In addition, the band gap of SiCN films is 3 to 4 eV, which is narrower than that of silicon nitride films (~5 eV). The narrower band gap of the charge trapping layer reduces the energy barrier for carrier injection into the layer. Thus, the low-k and narrow-band gap SiCN films would yield higher programming and erasing speeds and reduced power consumption. In the present study, we conducted a comparative study on charge trapping characteristics of the SiCN and silicon nitride films. Two types of film structures were fabricated on p-type (100) silicon substrates: (A) a SiOX-SiCN-SiO2 film and (B) a SiOX-SiNX-SiO2 film. In the both types of films, a tunnel oxide film of 2.4 nm in thickness was first formed using rapid thermal oxidation. A 31.5-nm-thick SiCN film with the relative dielectric constant of 4.8-4.9 was grown at 400 °C using a PECVD technique. A 30.4-nm-thick SiNX film was grown at 600 °C using a LPCVD technique. A blocking oxide film of 17.3 nm was grown using a PECVD technique. Finally, an aluminum film was deposited to form the gate electrode. After electrons or holes were injected into the charge trapping layers, the flat-band voltage shifts ΔVFBwere measured. Figure 1 shows the programming and erasing characteristics under the gate biases of +14.3 V and -15.1 V. The programming and erasing speeds in the SiOX-SiCN-SiO2 structure were obviously higher than those in the SiOX-SiNX-SiO2 structure. In the programming operation, the higher programming speed in the SiCN sample was mainly attributed to the low-dielectric constant of the SiCN film. In the erasing operation, the hole trapping speed in the SiCN sample was higher than that in the SiNX sample. The higher erasing speed in the SiCN sample arose from the higher hole trapping speed and the low-dielectric constant of the SiCN film. Figure 2 shows the retention characteristics of the SiOX-SiCN-SiO2 and SiOX-SiNX-SiO2 structures. The extrapolated 10-year memory window of the SiCN sample was wider than that of the SiNXsample. The SiCN films can be employed as the charge trapping layer of advanced nonvolatile memories. References: [1] K. Kobayashi, S. Naito, S. Nakiri and Y. Ito, ECS Trans. 58(5) (2013) 81.

It is known that the collisions caused by lane departure events account for range of percentages among the countries studied. To help prevent such collisions, the Lane Departure Warning (LDW) system has started to be introduced in production vehicles, but there is little research on its benefits and limitations so far. In this paper we performed an in-depth analysis of the collisions and driver-related essential variables for the lane-departure collision scenarios and demonstrated the benefit estimation process. The benefit of the LDW system is estimated by comparing lane departure events when the vehicle has no LDW, and how they change with the addition of LDW. The event without LDW was modeled in 5 phases: (1) before departure, (2) starting of the departure, (3) departed the lane, (4) at the impact with an object, and, (5) after the impact. "An extensive analysis was conducted of traffic crash data compiled by the Institute for Traffic Accident Research and Data Analysis (ITARDA). The results of this analysis were used to create models of each phase of an LDW event. The Advanced Safety System & Traffic REaltime Evaluation Tool (ASSTREET), which is based on Monte-Carlo Simulation, was then used to simulate a variety of collision types. The results of these simulations were validated by comparing the distributions of fatality, serious injury, minor injury and no injury that they generated to crash statistics for Japan. Then, the effect of the LDW system was added to the lane departure events. The drivers' response delay to the LDW and the possible reactions were measured in a driving simulator test. The comparison between events with and without LDW clearly shows which cases could be prevented by the use of LDW and the ones that could not be avoided, thereby, providing us with important guidelines to improve the system performance. Language: en

This paper proposes a novel method of verifying comprehensive driver model used for the evaluation of driving safety systems, which is achieved by coupling the traffic simulation and the driving simulator (DS). The method consists of three-step procedure. In the first step, an actual driver operates a DS vehicle in the traffic flow controlled by the traffic simulation. Then in the next step, the actual driver is replaced by a driver model and the surrounding vehicle maneuvers are replayed using the recorded data from the first step. Then, the maneuver by the driver model is compared directly with the actual driver's maneuver along the simulation time steps. For example, while turning right (in front of the oncoming traffic), the proposed verification method was applied to our driver-agent model of traffic simulation system ASSTREET (The Advanced Safety System & Traffic REaltime Evaluation Tool) to demonstrate that the proposed method provides a straightforward way of verifying the driver-agent model capability to reproduce the driving behavior including the subtle driving behaviors, such as safety confirmation, that can have significant impact on driving safety. The scheme of interactive connection of ASSTREET and a driving simulator is also described. Language: en

The start of warm ischemic time (WIT) of donor lungs in donation after cardiac death (DCD) is not clearly defined. We investigated the effect of donor pre-mortem hypotension and hypoxia to determine which physiologic factor is the determinant of WIT onset in controlled DCD lung transplantation.Twenty mechanically-ventilated donor pigs were placed in 4 groups (n = 5 each) and exposed to each of the pseudo-agonal conditions for 60 minutes: (1) control group, no intervention and optimum ventilation, followed by cardiac arrest; (2) hypotension (HT) group, controlled cardiac tamponade reducing systolic blood pressure to50 mm Hg, followed by cardiac arrest; (3) hypoventilation (HV) group, ventilation with room air at 5 breaths/min, followed by cardiac arrest; (4) non-circulation (NC) group, initial cardiac arrest, followed by a 60-minute standoff time. The lung graft was retrieved and the left lung was transplanted to the recipient. Graft function was evaluated for 4 hours after contralateral pulmonary artery ligation. The reperfusion injury was evaluated based on tissue cytokine expression, wet weight-to-dry weight ratio, and histology at the end of the reperfusion period.Impaired post-transplant graft function was seen in the HV group, which had significantly poorer oxygenation during the reperfusion period than the other groups (p0.001). The HV group also had higher tissue levels of interleukin-8 (p0.05), a higher wet weight-to-dry weight ratio (p0.05), and histologic findings of graft tissue injury than the control group. The difference in these parameters among the control, HT, and NC groups was not significant.Only pre-mortem hypoxia provoked by hypoventilation significantly impaired lung graft function in DCD lung transplantation. Ventilatory rather than circulatory deterioration can trigger the onset of warm ischemia.

てんかんと失神は一過性意識消失の原因として大きな割合を占める。両者の鑑別は重要であるが、てんかんと誤診されている失神の症例は未だに多く、誤診の原因について多数例で検討することが必要である。我々は当院のてんかん専門外来において、前医でてんかんと誤診されていた失神10症例について調査した。意識消失前に失神に多いとされる誘因があったのは9例、前駆症状を伴うものは7例であった。また、随伴症状としてけいれんなどの不随意運動が半数の5例で観察されており、失神に不随意運動を伴うconvulsive syncopeの存在が十分周知されていないことが示唆された。脳波は全ての症例で正常であったが、前医での脳波所見については十分な検討を行うことは出来なかった。誤診を少なくするには、誘因、前駆症状、随伴症状に着目した病歴聴取と、convulsive syncopeに留意することが重要であった。

アトピー性皮膚炎患者(AD)に対し, 外用療法と塩酸セチリジン内服を併用した場合の症状改善効果および患者評価によるそう痒およびquality of life(QOL)に対する影響をアトピー性皮膚炎重症度スコア, Visual Analogue Scale(VAS)およびDermatology Life Quality Index(DLQI)-base QOL質問票を用いて検討した。対象はAD患者19例(男性7例, 女性12例, 平均年齢28.4±13.6歳)で, 外用療法に加え塩酸セチリジン10mg/day を4週間投与した。軽度改善以上の改善率は2週後で50％, 4週後で80％であり, 中等度以上の改善率は2週後で16.7％, 4週後においては33.3％であった。患者評価によるそう痒のVASスコアおよびDLQI-base QOLスコアも経時的に有意な改善が認められた。これらの結果から, 外用薬と塩酸セチリジンを併用したことでADが改善され, 患者QOLに良好な影響をおよぼしたと考えた。

強直間代発作重積後に急速に認知障害が進行し、4カ月間にわたるもうろう状態の診断で、転院してきた症例を経験した。P3、O1、T5に頻発する鋭波、左posterior quadrant中心のPLEDs、またF3、C3を起始とする発作波などの多彩なてんかん性異常波が記録され、部分発作が頻回に出現していたことから、このもうろう状態は非けいれん性てんかん重積状態(NCSE）と診断した。MRI検査では左半球後部の広い範囲にFLAIR画像で高信号の領域を認め、またSPECTでは同部位の血流増加が見られたが、これらの部位はPLEDsの出現部位とほぼ一致していた。抗てんかん薬の調整により非けいれん性てんかん重積状態は消失し、脳波所見、MRI、SPECT所見も改善が認められた。本症例の可逆性のFLAIRの高信号は、てんかん発作が遷延したことによって焦点近傍の皮質に浮腫が生じた結果、出現していたと推測した。NCSEの診断と経過観察におけるMRIのFLAIR法とSPECTの有用性と限界について考察した。

Objectives This study was conducted to ascertain whether laboratory rats are an adequate animal model for aging oral cavity research, especially on occlusal tooth wear (OTW), which progresses with aging and causes abnormal occlusions. Mastication has been reported to relate to cognition in the elderly. Thus, it is important to care for the oral cavity, especially in the frail elderly, for the maintenance of all-round quality of life. Adequate and appropriate animal models are essential for basic and clinical research on the oral cavity. Methods Dried maxilla and mandible specimens from 98 young, aging or aged female F344/N rats were used. Results The levels of OTW of all molars were monitored with aging. The molar tooth began to wear at 1-month old (M) and progressed rapidly till 12 M. Subsequently, OTW progressed slowly till 30 M, and then rapidly again after 35 M. Conclusions This study showed that progress of OTW is well correlated with the entire life span of the rat, and suggested that the rat aged over 12 M would be an adequate animal model for research on OTW in middle-aged and elderly people.

Autoantibodies to cellular constituents are the serological hallmark in systemic autoimmune rheumatic diseases (1). They are often associated with certain diagnosis, clinical features, or disease activity and considered as clinically useful biomarkers. Autoantibody immunoassays have been used extensively for over 50 years with continuous changes in technologies and antigens used. While standard enzyme-linked immunosorbent assay (ELISA) is still commonly used in practice, migration to multiplex immunoassays is the direction that many companies and laboratories are moving toward. Although multiplex assays have many advantages over conventional assays, there are also problems that may cause confusions among clinicians and researchers. In this Opinion Article, advantages and current problems in the use of multiplex immunoassays are discussed.

The aim of this research was to determine whether a rat was an adequate laboratory animal model for periodontal research on elderly humans. Thirty-two F344/NSlc female rats ranged between 30 and 1000 days of age were used. The alveolar bone loss around the molars was assessed by a morphometric method. A significant correlation was found between age and the amount of alveolar bone loss. For further analysis, the rats were grouped into four by age; 30-60 days, 220-430 days, 640-850 days, and more than 850 days. The means of alveolar bone loss were compared between age groups. It was found that the resorption of the alveolar bone around the molars of the rats continued until they were 1000-days-old, and this trend was stronger in the mandible than the maxilla. It was suggested that rats could be used as adequate laboratory animals for periodontal research.

Three strains of SAMs including SAMR1TA (SAMR1), SAMP6/Ta (SAMP6) and SAMP8/Ta (SAMP8) were monitored for their reproduction, pathology along the aging and survival under the housing condition of an aging farm at the National Institute for Longevity Sciences (NILS). Although the diet used at the NILS aging farm was different from that recommended by the Council for SAM Research, the low-protein diet, Labo MR Stock, did not disturb the reproduction of the SAMs. The strain differences among SAMs were clearly identified and the survival of each strain was far longer than previous reports. The housing system, including maintaining and breeding system, of the NILS aging farm was, thus, considered to be appropriate for the long-term observation and establishment of aged individuals in the laboratory strains of the rodents.

Object. Capillary hemangiomas are benign tumors or tumorlike lesions that originate from blood vessels and have rarely been reported to develop in the brain or spinal cord. The authors summarize the clinical and histological features of capillary hemangiomas of the central nervous system (CNS). Methods. The clinical features, imaging characteristics, and outcomes in 10 patients with CNS capillary hemangiomas were reviewed. Histological studies included immunostaining with CD31, α-smooth muscle actin, vascular endothelial growth factor, and Ki-67 antigen. Three patients with lesions in the brain presented with symptoms of increased intracranial pressure or seizures. Seven patients with lesions in the spinal cord presented with progressive sensorimotor disturbances of the lower limbs. Computerized tomography and magnetic resonance imaging demonstrated well-defined, enhancing lesions associated with marked perifocal edema. Angiography demonstrated hypervascular lesions, which have not recurred after resection. In two cases, multiple satellite lesions resolved after the systemic administration of steroid drugs or interferon-α. Histologically, all lesions were consistent with findings of capillary hemangioma of the skin or soft tissues. The CNS lesions differed significantly from other vascular neoplasms, such as hemangioendotheliomas, hemangiopericytomas, and hemangioblastomas. Conclusions. Capillary hemangiomas of the CNS are benign lesions that can be surgically removed and cured without adjuvant therapy.

Background: The purpose of the present study was to determine the effect of Helicobacter pylori eradication on the intensity of inflammation in the ulcerous mucosa by measuring the level of neutrophil-associated oxidants and to understand the role of mucosal inflammation in ulcer relapse from the viewpoints of the scarring stage and the H. pylori-infection status. The level of inflammation in the gastric mucosa after the eradication of H. pylori was examined using biopsy samples obtained from patients with gastric ulcers. Methods: Gastric mucosal specimens were endoscopically obtained before and after H. pylori-eradication therapy from 39 patients with gastric ulcers and a positive H. pylori-infection status. The level of neutrophil-derived oxidants was then measured in each sample using a luminol-dependent chemiluminescence (ChL) assay. Results: Chemiluminescence activity in the ulcer portion and the background gastric mucosa (antrum and corpus) was significantly reduced 3 months after successful therapy (n = 32). The ChL activity was further decreased 9 months after successful therapy, but the activity in the ulcer portion remained unchanged. In patients who did not respond to the H. pylori-eradication therapy (n = 7), the ChL activities were not altered in any mucosal portion after the therapy. Before the H. pylori-eradication therapy, a higher ChL activity was observed in open ulcer tissue than in scarred tissue. The ChL activity in the scarred tissue was reduced 3 months after the successful eradication of H. pylori; however, the ChL activity in the red scars was significantly higher than that in the white scars. The ChL level in the white scars was almost equivalent to that in the background mucosa 9 months after the completion of the H. pylori-eradication therapy. Conclusion: The eradication of H. pylori may reduce the level of oxidant production in gastric ulcers, promoting the prevention of ulcer recurrence. Furthermore, the presence of a red scar may indicate unstable healing, even after the successful eradication of H. pylori.

The authors operated on 61 tumors of the cervical spinal cord from 1980 to 2000, of which 15 were dumbbell tumors. Two were resected by anterior approach, 8 by posterior approach, and 7 by both the anterior and posterior approaches simultaneously. To preserve the alignment of neck, laminoplasty or partial laminectomy with bone graft was performed. The tumors were resected including the capsule to prevent recurrence, and gross total resection was achieved in 13 patients. There were no symptoms of recurrence.