Radiological outcome after treatment of juvenile flatfeet with subtalar arthroereisis: a matched pair analysis of 38 cases comparing neurogenic and non-neurogenic patients.

PURPOSE: Therapy of juvenile neurogenic flatfoot (JNF) with subtalar arthroereisis (SA) is currently under critical clinical investigation. In this retrospective matched pair analysis, the radiological outcome after arthroereisis in paediatric patients with infantile cerebral palsy and JNF was compared with children with juvenile flatfeet (JF) without neurological diseases. METHODS: From October 2007 to April 2018 80 patients with 149 flatfeet underwent surgery with SA. Inclusion criteria were: 1) JNF or JF with age at surgery ≤ 13 years; 2) treatment with SA; 3) presence of three sets of biplane radiographs (preoperative, postoperative and follow-up (FU)). The radiographs were analyzed for: 1) navicular-cuboidal-index (NCI); 2) talocalcaneal angle anteroposterior; 3) talocalcaneal angle lateral; 4) calcaneal-pitch (CP); and 5) talometatarsal-index (TMTI). Following this, 25 patients with 38 flatfeet could be included. RESULTS: The mean age at SA of the JNF group was 9.2 years (JF group: 9.3 years) and the mean time of FU was 35.2 months (JF group: 39.4 months). In comparison with preoperatively, a significant decrease of the NCI was seen in both groups (p = ≤ 0.05 and p = ≤ 0.001) in the FU radiographs. The analysis of CP and TMTI in the JF group also resulted in a significant improvement (p = ≤ 0.001 and p = ≤ 0.05). Overall, the comparison between the JNF and JF group showed no significant differences in regard to the analyzed postoperative parameters. CONCLUSION: Based on this data, treatment of flatfeet by SA in patient with neurological disorders shows an improvement of radiological parameters comparable with neurologically unimpaired patients and might be considered as additional treatment option. LEVEL OF EVIDENCE: IV.

A Polymorphism rs6726395 in Nrf2 Contributes to the Development of Emphysema-Associated Age in Smokers Without COPD.

INTRODUCTION: Several studies have reported that single nucleotide polymorphisms (SNPs) in the gene encoding NF-E2-related factor 2 (Nrf2) contribute to airflow limitations in smokers without COPD. Although small airway lesions and emphysema contribute cooperatively to airflow limitation, the relationship between Nrf2 SNPs and the development of emphysema in smokers without COPD is not well understood. METHODS: Healthy subjects who underwent an annual health checkup with computed tomography (CT) of the chest at Osaka City University Hospital were prospectively recruited. The percentage of low-attenuation area (%LAA) on chest CT was quantified, and correlations between %LAA, Nrf2 SNP [rs6726395 (G/A)] genotypes, and clinical characteristics were examined. RESULTS: A total of 245 subjects without COPD [non-/light-smoker: 153 (62.4%) and smoker: 92 (37.6%)] were enrolled. The %LAA in the upper lung field was higher than that in the lower lung field (p < 0.001). The %LAA in smokers was significantly higher than that in non-/light-smokers (p = 0.021). The %LAA showed significant but weak correlation with age in all subjects (r = 0.141, p = 0.028). Divided by genotype, the %LAA of the upper lung field was significantly correlated with age in smokers with genotype GG (wild type) (r = 0.333, p = 0.022), but was not significantly correlated with age in smokers with genotype AG/AA. These correlations were not observed in non-/light smokers. CONCLUSION: A polymorphism rs6726395 in Nrf2 can contribute to the development of emphysema-associated aging in smokers. The Nrf2 SNP may be a predictive factor for smoking-induced emphysema, and genotyping of Nrf2 SNP may serve as biomarker for emphysema prevention.

Poorer radiological outcome after delayed diagnosis and treatment in human position in Fettweis plaster cast in 93 unstable hip joints type D, III and IV according to Graf.

PURPOSE: In this study the course of unstable hips after successful treatment with Fettweis plaster of Paris (POP) is examined. Special focus will be given to age at beginning of treatment and initial hip type. METHODS: The development of 93 unstable hips treated between November 2001 and April 2015 was examined. Inclusion criteria were: 1) unstable hips with successful treatment with Fettweis POP; 2) presence of two pelvic radiographs (12 to 24 months and 24 to 48 months). We analyzed: 1) the initial ultrasound hip type according to Graf; 2) the average age at first and second radiograph; 3) the Tönnis classification: normal findings (< 1 SD), slightly (1 SD to 2 SD) and severely dysplastic hips (> 2 SD). RESULTS: In all, there were 14 hips type D, 41 hips type III and 38 hips type IV. Mean age of the first radiograph was 13.9 months and of the second 28.5 months. The first radiograph showed: (< 1 SD): 36, (1 SD to 2 SD): 34, (> 2 SD): 23 hips, the second radiograph: (< 1 SD): 33, (1 SD to 2 SD): 19, (> 2 SD): 30 hips. With subdivision at the start of treatment at age eight or fewer weeks 2/16 hips (12.5%) and with initiation of the treatment more than eight weeks 22/77 (26.0%) deteriorated. During the course between first and second radiograph a total of 35.7% of initial hip type D, 19.5% of type III and 23.7% of type IV deteriorated. CONCLUSION: Radiograph controls after treatment with Fettweis POP show poorer outcome after delaying the start of treatment more than 8 weeks. These findings were independent of the initial ultrasound hip type. Regular radiograph controls of all hip types treated for unstable hips are justified to detect residual dysplasia. LEVEL OF EVIDENCE: IV.

Safety and efficacy of guselkumab in Japanese patients with moderate-to-severe plaque psoriasis: a randomized, placebo-controlled, ascending-dose study.

BACKGROUND: The interleukin (IL)-23/IL-17 pathway is central in the pathogenesis of psoriasis. The favourable efficacy and safety of guselkumab, an IL-23-specific monoclonal antibody, has been demonstrated in global phase III studies of plaque psoriasis. OBJECTIVES: To evaluate the safety, efficacy and pharmacokinetics of single-dose subcutaneous guselkumab in Japanese patients with moderate-to-severe plaque psoriasis. METHODS: Patients with ≥ 10% of total body surface area involvement and a Psoriasis Area and Severity Index (PASI) ≥ 12 were randomized (5 : 1) to receive guselkumab or placebo in four cohorts of this double-blind, placebo-controlled, single ascending-dose, single-centre study. Safety, pharmacokinetics and clinical response were monitored at baseline and specific time points over a 24-week follow-up period. RESULTS: To week 24, 55% (11/20) of patients in the guselkumab group and 50% (2/4) in the placebo group experienced ≥1 adverse event (AE). No deaths, serious AEs or AEs leading to treatment discontinuation were reported. Maximum clinical response was seen at week 16 with PASI 75 (≥ 75% improvement from baseline PASI) response in two of five (10 mg), four of five (30 mg and 300 mg) and three of five (100 mg) patients; and PASI 90 (≥ 90% improvement from baseline PASI) in zero of five (10 mg), three of five (30 mg), two of five (100 mg) and three of five (300 mg) patients. Mean maximum serum concentration (Cmax ) and area under the curve from time zero to infinity values increased in a dose-proportional manner with a mean terminal half-life of 15·6-17·6 days and median time to reach Cmax of 4-6 days. CONCLUSIONS: Guselkumab was generally well-tolerated and exhibited sustained high levels of clinical response in Japanese patients with moderate-to-severe psoriasis.

Note: Optimization of magnifying a polarization angle with Littrow layout blazed gratings.

Magnification of a polarization angle with Littrow layout gratings has been developed. High magnification with a factor of 7.7 using two gratings in Littrow layout was experimentally proved. The magnification range was investigated by calculation at a wavelength of 10.6 µm. The method can be applied for a high magnification factor >30. Larger groove numbers and smaller blaze angles are suitable for the large magnification. Statistical fluctuation of the diffracted polarization angle is compared with that of the incident polarization angle.

Design of tangential viewing phase contrast imaging for turbulence measurements in JT-60SA.

A tangential viewing phase contrast imaging system is being designed for the JT-60SA tokamak to investigate microturbulence. In order to obtain localized information on the turbulence, a spatial-filtering technique is applied, based on magnetic shearing. The tangential viewing geometry enhances the radial localization. The probing laser beam is injected tangentially and traverses the entire plasma region including both low and high field sides. The spatial resolution for an Internal Transport Barrier discharge is estimated at 30%-70% of the minor radius at k = 5 cm-1, which is the typical expected wave number of ion scale turbulence such as ion temperature gradient/trapped electron mode.

Note: Magnification of a polarization angle with a Littrow layout brazed grating.

A new method to magnify a small polarization angle with brazed gratings has been developed. In the method, difference in diffraction efficiency for S and P polarization components is used. The magnification dependence on the incident angle can be small by arranging the grating in Littrow layout. A magnification with a factor ~2.7 has been demonstrated for a 10.6 µm CO2 laser beam as expected from a calculation. The method is applicable in many polarimetry fields.

Longitudinal monitoring of CYP3A activity in patients receiving 3 cycles of itraconazole pulse therapy for onychomycosis.

WHAT IS KNOWN AND OBJECTIVE: Itraconazole, a CYP3A inhibitor, is used for the treatment for onychomycosis with a three-cycle pulse therapy over 3 months, but its effects on in vivo CYP3A activity during the entire course remain unknown. METHODS: Urinary 6ß-hydroxycortisol/cortisol ratios were determined in 19 patients with onychomycosis, before therapy, during three cycles of itraconazole pulse therapy (200 mg twice daily for a week in each monthly cycle) and at 3 month after completion of therapy. RESULTS AND DISCUSSION: The mean 6ß-hydroxycortisol/cortisol ratio was reduced by 68% from baseline (P < 0·05) after the 1st pulse dosing, but the inhibitory effect appeared to be resolved before the next pulse dosing and at 3 months post-treatment. The magnitude of inhibition appeared in proportion to the baseline CYP3A activity. WHAT IS NEW AND CONCLUSION: The inhibitory effect of itraconazole pulse therapy on the in vivo CYP3A activity appears clinically relevant at the end of each cycle, but the inhibition resolves, on average, within 3 weeks.

Development of automated 3-dimensional tissue fabrication system Tissue Factory - Automated cell isolation from tissue for regenerative medicine.

We have developed a new automated cell isolation system as one of the modules of automated cell sheet production system named Tissue-Factory (T-Factory). This system enables isolation of the target cells from tissue. Using this new system, we successfully isolated skeletal myoblast from skeletal muscle tissue. The cell isolation system makes us stably prepare cell suspension from each tissue automatically and safely. Isolation of skeletal myoblasts will contribute to labor-saving cell cultivation and operational stability, and lead further process in tissue engineering and regenerative medicine.

Fully automatic rapid DNA Ploidy Analyzer for intraoperative rapid diagnosis support.

Frozen section studies are a useful method to rapidly define tumor malignancy and identify the extent of surgical resection. However, diagnosis with a frozen section is qualitative and sometimes difficult. Therefore a quantitative method for grading tumors is desired. We have already reported a technique of intraoperative flow cytometry (iFC) that supports intraoperative histopathological examination of frozen sections. In this study, we report an advanced system named "Fully Automatic Rapid DNA Ploidy Analyzer" with a tissue pretreatment function and a freeze-dried reagent kit for cell staining. To evaluate our system, we analyzed samples from glioma patients who underwent open surgery for brain tumors. We observed obvious difference of the Malignancy Index (MI) between neoplastic and perilesional brain tissue (26.0 ±22.1% and 4.1 ±2.5%, respectively, P<0.001). Cut-off level for identification of the tumor in the biopsy specimen was 6.8% which provided 86% sensitivity and 81% specificity. We also obtained a good correlation between the MI and histological grade (WHO grading). Our new system also enabled finishing the process from sample preparation to the end of analysis in ten minutes or less. These results demonstrate that our fully automatic rapid DNA ploidy analyzer is feasible for rapid determination of glioma presence in a surgical biopsy sample.

SU-E-I-63: Performance Study of An Electron-Tracking Compton Camera for Medical Imaging.

PURPOSE: Conventional gamma-ray detector, PET and SPECT, have the limitation of energy and field of view. These limitations are major problems of studying for a new medical imaging. Therefore, we have developed the new imaging detector which is an electron-tracking Compton camera (ETCC). METHODS: A reconstruction method of Compton camera (CC) is using the physics principle. Because of using physics principle, CC can have a wide energy dynamic range and wide field of view. Conventional CC, however, cannot catch Compton recoil electron tracks, and this is one of the reasons of low imaging power. We have developed a time projection chamber (TPC) using micro pixel chamber (µPIC) as the new detector for ETCC. The µPIC is 2-dimensional gaseous detector and this position resolution is less than 400 µm. Using this detector, ETCC can get electron tracks which are generated from Compton scattering. In this paper, we show the prototype ETCC performance and imaging results. RESULTS: ETCC achieved a wide energy dynamic range (200-1300keV) and wide field of view (3 steradian). Also we succeeded in imaging new imaging reagents using mice as follows; (1) F-18-FDG (511 keV) and I-131-MIBG (364 keV) simultaneous imaging for double clinical tracer imaging, (2) Zn-65- porphyrin (1116 keV) imaging for high energy gamma-ray imaging and, (3) imaging of some minerals (Mn-54, Zn-65) in mice and so on. And we succeeded in 3-D imaging which has imaged only one direction using one head camera. CONCLUSIONS: We have developed the ETCC for new medical imaging device and succeeded in imaging the some imaging reagents. We started to develop the new ETCC which can image the mouse within 30 min. Thus, this detector has the possibility of new medical imaging.

New automatic cell isolation system for flow cytometry: cell isolation unit and staining reagent kit.

Flow cytometry is well-known cell analysis method and useful to gain quantitative information from cells in blood, however, it is not widely used for solid tissues in clinical settings. This is partly because it takes a long time to prepare samples and the operation can be complicated. To resolve these problems, we developed a new automatic cell isolation system which consists of cell isolation unit and staining reagent kit specialized for flow cytometry. With this new system, cell isolation can be done more rapidly and easily. By using this method, we could determine optimum condition to disintegrate porcine colon tissue and stain cells stably in 6 minutes. This result indicates that our method can provide analysis data within 10 minutes. We also evaluated our method in colorectal cancer patients, and the result was promising. All the data suggests that this method can support and facilitate rapid diagnosis.

Surfactant protein C G100S mutation causes familial pulmonary fibrosis in Japanese kindred.

Several mutations in the surfactant protein C (SP-C) gene (SFTPC) have been reported as causing familial pulmonary fibrosis (FPF). However, the genetic background and clinical features of FPF are still not fully understood. We identified one Japanese kindred, in which at least six individuals over three generations were diagnosed with pulmonary fibrosis. We examined the patients radiologically and histopathologically and sequenced their SFTPC and ABCA3 genes. We also established a cell line stably expressing the mutant gene. All the patients had similar radiological and histopathological characteristics. Their histopathological pattern was that of usual interstitial pneumonia, showing numerous fibroblastic foci even in areas without abnormal radiological findings on chest high-resolution computed tomography. No child had respiratory symptoms in the kindred. Sequencing of SFTPC showed a novel heterozygous mutation, c.298G>A (G100S), in the BRICHOS domain of proSP-C, which co-segregated with the disease. However, in the ABCA3 gene, no mutation was found. In vitro expression of the mutant gene revealed that several endoplasmic reticulum stress-related proteins were strongly expressed. The mutation increases endoplasmic reticulum stress and induces apoptotic cell death compared with wild-type SP-C in alveolar type II cells, supporting the significance of this mutation in the pathogenesis of pulmonary fibrosis.

Development of cell culture monitoring system and novel non-contact pH measurement.

This paper describes a cell culture monitoring system for regenerative medicine. To realize this monitoring system, a new culture vessel and a removable measurement unit were proposed. The measurement unit was installed in the culture vessel and it was used to measure important cell culture parameters (e.g., temperature, CO(2) level, and pH). Thus, the status of the culture could be monitored. In addition, we developed a novel noninvasive method based on spectrophotometry for measuring pH. This method is a non-contact method that permits noninvasive and contamination-free pH measurement. The spectroscopic pH measurements agreed well with pH measurements using an electrode. The error was within 0.02; thus, the new pH measurement method is sufficiently accurate for cell culture. This new system is expected to contribute to advances in tissue engineering and regenerative medicine.

Temporomandibular joint and 3.0 T pseudodynamic magnetic resonance imaging. Part 1: evaluation of condylar and disc dysfunction.

OBJECTIVES: This study describes an improved method for examining and diagnosing temporomandibular joint (TMJ) dynamics by 3.0 T pseudodynamic MRI. METHODS: Clinical observation and conventional static MRI of volunteers (one without and eight with TMJ arthrosis) were followed by 3.0 T pseudodynamic MRI in positions ranging from the mouth closed to mouth fully opened. Condylar head (Cd), articular disc anterior border (Da) and articular disc posterior border (Dp) were digitized on sagittal images to determine trajectory and velocity patterns. RESULTS: Patients were divided into three groups based on the presence or absence of dysfunction: Group 1, no dysfunction on the right or left side of the TMJ; Group 2, dysfunction on the right or left side of the TMJ; and Group 3, dysfunction on both the right and left sides of the TMJs. In 75% of patients (12 of 16 joints), pseudodynamic TMJ analysis was useful for determining a functional abnormality. Using a points system based on three trajectory and seven velocity patterns, discs with adhesion and perforation had significantly fewer points than discs with anterior displacement (with and without reduction) and discs with no abnormality (P = 0.019 < 0.05). CONCLUSIONS: Trajectory and velocity patterns based on 3.0 T pseudodynamic MRI identified the affected side and determined the extent of morbidity in the Cd as well as the Da and Dp. The typical abnormal movement pattern of discs with anterior displacement (with and without reduction) and pathological structural changes of the articular disc (such as adhesion and perforation) could be identified.

Temporomandibular joint and 3.0 T pseudodynamic magnetic resonance imaging. Part 2: evaluation of articular disc obscurity.

OBJECTIVES: This study examined the relationship between temporomandibular joint (TMJ) dysfunctions and obscurity grades of interpreted anterior and posterior borders of the articular disc (Da and Dp, respectively) by 3.0 T pseudodynamic MRI. METHODS: Da and Dp were classified into seven obscurity grades, and the Dp contour was classified into three types. The grades, types and TMJ function were compared by 3.0 T pseudodynamic MRI. RESULTS: Unobscured Da images at condylar positions posterior to the articular eminence were associated with normal TMJ function (P = 0.046 < 0.05). Unobscured Dp images at condylar positions anterior to the articular eminence were associated with normal TMJ function (P = 0.033 < 0.05). In addition, unobscured Dp images following flap insertion were associated with normal TMJ function (P = 0.043 < 0.05). There was no statistical relationship between Dp contour types and TMJ movement, but any change observed in the Dp contour during mouth opening was associated with abnormal TMJ function (P = 0.040 < 0.05). CONCLUSIONS: Grading of Da and Dp obscurity based on how well the areas were defined in the images, identifying the condylar positions in relation to the glenoid fossa and articular eminences, and observing the changes in Dp contour types were useful for diagnosing TMJ abnormalities.

Zeeman polarimetry measurement for edge current density determination using Li-beam probe on JT-60U.

Zeeman polarimetry system using Li-beam probe has been developed for the edge current density measurement in the JT-60U tokamak, which measures the polarization angle alpha (related to the pitch angle of the magnetic field) by means of photoelastic modulators, etalons, and phase sensitive detection using digital lock-in amplifiers with the accuracy in the alpha of Delta alpha approximately 0.1 degrees. The diagnostic has 20-channel viewing chords covering the plasma peripheral region of normalized minor radius r/a approximately 0.8-1 with a spatial resolution of up to approximately 1 cm. Li-beam injection with beam current of up to approximately 5 mA has been achieved. A new tuning method of the wavelength for the etalon has been demonstrated, scanning the beam acceleration voltage and keeping a beam current constant during a single shot. The peak wavelength of the etalon is adjusted in the direction to both blue- and redshifts by changing the angle of incidence and increasing the temperature, respectively. Time evolution of the edge current density profile has been determined for the current ramp experiment in the Ohmically heated discharges. In addition, the edge current density profile with the local peak of j(ped) approximately 0.15-0.25 MA/m(2) at r/a approximately 0.9 has been identified in the H-mode plasma, which is correlated with large pressure gradient in the pedestal region.

Multiple intravascular papillary endothelial hyperplasia affecting skin and bone.

We report a 75-year-old man with multiple recurrent black papules involving his entire body. In the course of 3 years, 20 lesions were resected, which were histologically confirmed as intravascular papillary endothelial hyperplasia (IPEH). A similar vascular lesion was found on his tibia. The occurrence of multiple IPEH affecting skin and bone is extremely rare. The patient's medical history included hepatitis C, hepatoma and associated coagulopathy. We suggest that this patient's multiple lesions were induced by microthrombus formation due to liver dysfunction.