Efficacy and safety of plasma exchange in interstitial lung diseases with anti-melanoma differentiation-associated 5 gene antibody positive clinically amyopathic dermatomyositis.

OBJECTIVE: Clinically amyopathic dermatomyositis (CADM) patients frequently develop refractory interstitial lung disease (ILD), with a poor prognosis. We aimed to verify the efficacy and safety of plasma exchange (PE) treatment for ILD in CADM. METHOD: A retrospective case-control study was conducted to compare clinical outcomes with and without PE treatment in CADM-ILD patients refractory to combination therapy of high-dose glucocorticoids, calcineurin inhibitors, and cyclophosphamide. Among 19 enrolled patients, 11 were further treated with PE. We compared survival rates and other clinical characteristics. PE consisted of either fresh-frozen plasma or albumin as a replacement solution. RESULTS: Basal clinical characteristics at diagnosis, including age, gender, serum ferritin, Krebs von den Lungen-6 (KL-6), C-reactive protein, and respiratory function tests, did not differ between the two groups. The survival rate for treatment with PE was higher than for treatment without PE (91% and 50%, respectively, p < 0.05). Among PE-treated patients, anti-melanoma differentiation-associated gene-5 (anti-MDA-5) antibody titre, ferritin, and KL-6 as serological activity markers were sustainably reduced only after initiating PE. Therapeutic intervention with PE reduced the frequency of exacerbation of ILD requiring methylprednisolone pulse therapy. The occurrence of bacterial, fungal, and cytomegalovirus infection did not differ between the groups with and without PE, and adverse events associated with PE resolved with appropriate intervention. CONCLUSION: Combination therapy with PE was associated with an improved survival rate, and may be effective for the management of refractory ILD in CADM patients. A personalized therapeutic strategy including PE could be introduced for fatal rapidly progressive ILD.

W-band millimeter-wave back-scattering system for high wavenumber turbulence measurements in LHD.

A 90 GHz W-band millimeter-wave back-scattering system is designed and installed for measuring electron scale turbulence (k⊥ρs ∼ 40). A metal lens relay antenna is used for in-vessel beam focusing, and a beam diameter of less than 40 mm is achieved in the plasma core region. This antenna can be steered at an angle of 159° ± 6°, which almost covers the plasma radius. The estimated size of the scattering volume is ∼105 mm at the edge and 135 mm at the core, respectively. A 60 m corrugated waveguide is used to achieve a low transmission loss of ∼8 dB. A heterodyne detection system for millimeter-wave circuits with probing power modulation can distinguish the scattered signal from background noise.

Associations of PD-L1, PD-L2, and HLA class I expression with responses to immunotherapy in patients with advanced sarcoma: post hoc analysis of a phase 1/2 trial.

BACKGROUND: Although immunotherapy is thought to be a promising cancer treatment, most patients do not respond to immunotherapy. In this post hoc analysis of a phase 1/2 study, associations of programmed death ligand 1 (PD-L1), PD-L2, and HLA class I expressions with responses to dendritic cells (DCs)-based immunotherapy were investigated in patients with advanced sarcoma. METHODS: This study enrolled 35 patients with metastatic and/or recurrent sarcomas who underwent DC-based immunotherapy. The associations of PD-L1, PD-L2, and HLA class I expressions in tumor specimens, which were resected before immunotherapy, with immune responses (increases of IFN-γ and IL-12) and oncological outcomes were evaluated. RESULTS: Patients who were PD-L2 (+) showed lower increases of IFN-γ and IL-12 after DC-based immunotherapy than patients who were PD-L2 (-). The disease control (partial response or stable disease) rates of patients who were PD-L1 (+) and PD-L1 (-) were 0% and 22%, respectively. Disease control rates of patients who were PD-L2 (+) and PD-L2 (-) were 13% and 22%, respectively. Patients who were PD-L1 (+) tumors had significantly poorer overall survival compared with patients who were PD-L1 (-). No associations of HLA class I expression with the immune response or oncological outcomes were observed. CONCLUSIONS: This study suggests that PD-L1 and PD-L2 are promising biomarkers of DC-based immunotherapy, and that addition of immune checkpoint inhibitors to DC-based immunotherapy may improve the outcomes of DC-based immunotherapy.

Downward Terrestrial Gamma-Ray Flash Observed in a Winter Thunderstorm.

During a winter thunderstorm on 24 November 2017, a strong burst of gamma rays with energies up to ∼10 MeV was detected coincident with a lightning discharge, by scintillation detectors installed at the Kashiwazaki-Kariwa Nuclear Power Station at sea level in Japan. The burst had a subsecond duration, which is suggestive of photoneutron production. The leading part of the burst was resolved into four intense gamma-ray bunches, each coincident with a low-frequency radio pulse. These bunches were separated by 0.7-1.5 ms, with a duration of ≪1 ms each. Thus, the present burst may be considered as a "downward" terrestrial gamma-ray flash (TGF), which is analogous to upgoing TGFs observed from space. Although the scintillation detectors were heavily saturated by these bunches, the total dose associated with them was successfully measured by ionization chambers, employed by nine monitoring posts surrounding the power plant. From this information and Monte Carlo simulations, the present downward TGF is suggested to have taken place at an altitude of 2500±500 m, involving 8_{-4}^{+8}×10^{18} avalanche electrons with energies above 1 MeV. This number is comparable to those in upgoing TGFs.

Antibacterial coating of implants: are we missing something?

Implant-related infection is one of the leading reasons for failure in orthopaedics and trauma, and results in high social and economic costs. Various antibacterial coating technologies have proven to be safe and effective both in preclinical and clinical studies, with post-surgical implant-related infections reduced by 90% in some cases, depending on the type of coating and experimental setup used. Economic assessment may enable the cost-to-benefit profile of any given antibacterial coating to be defined, based on the expected infection rate with and without the coating, the cost of the infection management, and the cost of the coating. After reviewing the latest evidence on the available antibacterial coatings, we quantified the impact caused by delaying their large-scale application. Considering only joint arthroplasties, our calculations indicated that for an antibacterial coating, with a final user's cost price of €600 and able to reduce post-surgical infection by 80%, each year of delay to its large-scale application would cause an estimated 35 200 new cases of post-surgical infection in Europe, equating to additional hospital costs of approximately €440 million per year. An adequate reimbursement policy for antibacterial coatings may benefit patients, healthcare systems, and related research, as could faster and more affordable regulatory pathways for the technologies still in the pipeline. This could significantly reduce the social and economic burden of implant-related infections in orthopaedics and trauma. Cite this article: C. L. Romanò, H. Tsuchiya, I. Morelli, A. G. Battaglia, L. Drago. Antibacterial coating of implants: are we missing something? Bone Joint Res 2019;8:199-206. DOI: 10.1302/2046-3758.85.BJR-2018-0316.

Morphometric geometrical analysis to determine the centre of the acetabular component placement in Crowe type IV hips undergoing total hip arthroplasty.

AIMS: We analyzed the acetabular morphology of Crowe type IV hips using CT data to identify a landmark for the ideal placement of the centre of the acetabular component, as assessed by morphometric geometrical analysis, and its reliability. PATIENTS AND METHODS: A total of 52 Crowe IV hips (42 patients; seven male, 35 female; mean age 68.5 years (32 to 82)) and 50 normal hips (50 patients; eight male, 42 female; mean age 60.7 years (34 to 86)) undergoing total hip arthroplasty were retrospectively identified. In this CT-based simulation study, the acetabular component was positioned at the true acetabulum with a radiological inclination of 40° and anteversion of 20°. Acetabular shape and the position of the centre of the acetabular component were analyzed by morphometric geometrical analysis using the generalized Procrustes analysis. RESULTS: The acetabular shapes of Crowe IV hips were distinctively triangular; the ideal position of the centre of the acetabular component was superior on the posterior bony wall. The first and second relative warps explained 34.2% and 18.4% of the variance, respectively, compared with that of 28.6% and 18.0% in normal hips. We defined the landmark as one-third the distance from top on the posterior bony wall in Crowe IV hips. The average distance from the centre of the acetabular component was 5.6 mm. CONCLUSION: Crowe IV hips are distinctively triangular; the point one-third from the top on the posterior bony wall was a useful landmark for placing the acetabular component.

Microwave frequency comb Doppler reflectometer applying fast digital data acquisition system in LHD.

We succeeded in increasing the radial observation points of the microwave frequency comb Doppler reflectometer system from 8 to 20 (or especially up to 45) using the high sampling rate of 40 GS/s digital signal processing. For a new acquisition system, the estimation scheme of the Doppler shifted frequency is constructed and compared with the conventional technique. Also, the fine radial profile of perpendicular velocity is obtained, and it is found that the perpendicular velocity profile is consistent with the E × B drift velocity one.

Long-term patient survival after the surgical treatment of bone and soft-tissue metastases from renal cell carcinoma.

Aims: The aims of this study were to evaluate the long-term outcome of surgery for bone or soft-tissue metastases from renal cell carcinoma (RCC) and to determine factors that affect prognosis. Patients and Methods: Between 1993 and 2014, 58 patients underwent surgery for bone or soft-tissue metastases from RCC at our hospital. There were 46 men and 12 women with a mean age of 60 years (25 to 84). The mean follow-up period was 52 months (1 to 257). The surgical sites included the spine (33 patients), appendicular skeleton (ten patients), pelvis (eight patients), thorax (four patients), and soft tissue (three patients). The surgical procedures were en bloc metastasectomy in 46 patients (including 33 patients of total en bloc spondylectomy (TES)) and intralesional curettage in 12 patients. These patients were retrospectively evaluated for factors associated with prognosis. Results: The one-, three-, five-, ten-, and 15-year overall survival (OS) rates were 89%, 75%, 62%, 48%, and 25%, respectively. The median survival time (MST) was 127 months for en bloc metastasectomy and 54 months for intralesional curettage and bone grafting. The median survival time was 127 months for the spine, 140 months for lesions of the appendicular skeleton, and 54 months for the pelvis. Multivariate analysis showed that non-clear cell type RCC and metastases to more than two sites were independent risk factors for a poor prognosis. Conclusion: Patients with bone or soft-tissue metastases from a RCC have a reasonable prognosis, making surgical resection a viable option even in patients in whom the metastases are advanced. Cite this article: Bone Joint J 2018;100-B:1241-8.

Trigger mechanism for the abrupt loss of energetic ions in magnetically confined plasmas.

Interaction between a quasi-stable stationary MHD mode and a tongue-shaped deformation is observed in the toroidal plasma with energetic particle driven MHD bursts. The quasi-stable stationary 1/1 MHD mode with interchange parity appears near the resonant rational surface of q = 1 between MHD bursts. The tongue-shaped deformation rapidly appears at the non-resonant non-rational surface as a localized large plasma displacement and then collapses (tongue event). It curbs the stationary 1/1 MHD mode and then triggers the collapse of energetic particle and magnetic field reconnection. The rotating 1/1 MHD mode with tearing parity at the q = 1 resonant surface, namely, the MHD burst, is excited after the tongue event.

Appropriate hinge position for prevention of unstable lateral hinge fracture in open wedge high tibial osteotomy.

AIMS: Open wedge high tibial osteotomy (OWHTO) for medial-compartment osteoarthritis of the knee can be complicated by intra-operative lateral hinge fracture (LHF). We aimed to establish the relationship between hinge position and fracture types, and suggest an appropriate hinge position to reduce the risk of this complication. PATIENTS AND METHODS: Consecutive patients undergoing OWHTO were evaluated on coronal multiplanar reconstruction CT images. Hinge positions were divided into five zones in our new classification, by their relationship to the proximal tibiofibular joint (PTFJ). Fractures were classified into types I, II, and III according to the Takeuchi classification. RESULTS: Among 111 patients undergoing OWHTOs, 22 sustained lateral hinge fractures. Of the 89 patients without fractures, 70 had hinges in the zone within the PTFJ and lateral to the medial margin of the PTFJ (zone WL), just above the PTFJ. Among the five zones, the relative risk of unstable fracture was significantly lower in zone WL (relative risk 0.24, confidence interval 0.17 to 0.34). CONCLUSION: Zone WL appears to offer the safest position for the placement of the osteotomy hinge when trying to avoid a fracture at the osteotomy site. Cite this article: Bone Joint J 2017;99B10:1313-18.

Development of 2-D horn-antenna millimeter-wave imaging device (HMID) for the plasma diagnostics.

The two-dimensional (2-D) Horn-antenna Millimeter-wave Imaging Device (HMID) has been developed for the O-mode Microwave Imaging Reflectometry (O-MIR) in the Large Helical Device (LHD). The detectable frequency range of the HMID is 23-33 GHz, which corresponds to the cutoff electron density of 0.8-1.5 × 1019 m-3 in the O-MIR. The HMID is a 2-D imaging device that improves on the horn-antenna mixer array, which had been developed for the X-mode MIR in the LHD. In the HMID, the signal (RF) wave from the horn antenna is transmitted to the microstrip line by the finline transmitter, and this is mixed by the double-balanced-mixer with the local oscillation wave that is fed by a coaxial cable. By using the HMID, the MIR optical system can be significantly simplified.

Suppression of Trapped Energetic Ions Driven Resistive Interchange Modes with Electron Cyclotron Heating in a Helical Plasma.

The resistive interchange mode destabilized by the resonant interaction with the trapped energetic ions is fully suppressed when the injected power of electron cyclotron heating exceeds a certain threshold. It is shown for the first time that the complete stabilization of the energetic-particle-driven mode without relaxing the energetic particle (EP) pressure gradient is possible by reducing the radial width of the eigenmodes δ_{w}, especially when δ_{w} narrows to a small enough value relative to the finite orbit width of EP.

Abrupt onset of tongue deformation and phase space response of ions in magnetically-confined plasmas.

An abrupt onset of the new tongue-shaped deformation of magnetic surface in magnetized plasmas, which was conjectured in since the 1960s but has not been observed, is experimentally identified just before an abrupt onset of a large-scale collapse event. Two novel properties of the event are identified. First, the transition of symmetry of perturbation (rather than a growth of linearly unstable MHD modes) was found to be a key for the onset of abrupt collapse, i.e., the transition of symmetry gives a new route to the collapse from stable state. Second, as a phase-space response of ions, the distortion from Maxwell-Boltzmann distribution of epithermal ions was observed for the first time.

Safe zone for transacetabular screw fixation using a Kerboull cross-plate: A CT-scan templating prospective study.

BACKGROUND: Implantation of Kerboull acetabular reinforcement cross-plates (Kerboull plate) carries a risk for injury to vascular structures and pelvic organs. To our knowledge, there is no study assessing anatomical assessment related to this risk with this specific design. Therefore, we performed a prospective study to answer the following four questions: 1) What is the minimum distance and angle between the plate and iliac vessels? 2) What is the distance between the plate and the inner cortex of the ilium? 3) What is the ratio of views with muscle tissue present on the inner surface of the ilium? 4) What are the boundaries of the safe zone for transacetabular screw fixation for a Kerboull plate? HYPOTHESIS: A safe zone for fixation screws would be defined by a narrow range of insertion angles. MATERIALS AND METHODS: This is a CT-based 3D templating prospective study. Simulations were performed for 18 patients fitted with a Kerboull plate. An original Kerboull plate (Stryker, Mahwah, NJ, USA) was placed at a 45° abduction angle relative to the X-axis (alignment A) and the palette was placed vertically to the X-axis (alignment B). We measured the distance from the centre of the plate to the inner surface of the cortex of the ilium, the shortest distance to vessels and the angle of existing vessels, and the ratio of muscles on the inner surface of the ilium. RESULTS: The shortest distance to the vascular structures increased with increasing angle of insertion of the fixation screws, 85.8±12.1mm for A and 111.4±12.0mm for B at 45°. The distance to the inner cortex was further increased for screws inserted in posterior direction. At insertion angles ≥40°, the screws passed through muscle before invading the pelvis in most cases. However, at anterior-posterior angle (AP angles) ≤-10°, the risk of direct insertion of screws into the sacroiliac joint increased. DISCUSSION: The safe zone for transacetabular screws would be insertion at an angle≥40°, with an AP angle between 0° and -10° (slight posterior direction). LEVEL OF EVIDENCE: Level IV prospective diagnostic study.

Reconstruction of high temporal resolution Thomson scattering data during a modulated electron cyclotron resonance heating using conditional averaging.

This paper provides a software application of the sampling scope concept for fusion research. The time evolution of Thomson scattering data is reconstructed with a high temporal resolution during a modulated electron cyclotron resonance heating (MECH) phase. The amplitude profile and the delay time profile of the heat pulse propagation are obtained from the reconstructed signal for discharges having on-axis and off-axis MECH depositions. The results are found to be consistent with the MECH deposition.

On-ground detection of an electron-positron annihilation line from thunderclouds.

Thunderclouds can produce bremsstrahlung gamma-ray emission, and sometimes even positrons. At 00:27:00 (UT) on 13 January 2012, an intense burst of gamma rays from a thundercloud was detected by the GROWTH experiment, located in Japan, facing the Sea of Japan. The event started with a sharp gamma-ray flash with a duration of <300 ms coincident with an intracloud discharge, followed by a decaying longer gamma-ray emission lasting for ∼60 s. The spectrum of this prolonged emission reached ∼10 MeV, and contained a distinct line emission at 508±3(stat.)±5(sys.) keV, to be identified with an electron-positron annihilation line. The line was narrow within the instrumental energy resolution (∼80keV), and contained 520±50 photons which amounted to ∼10% of the total signal photons of 5340±190 detected over 0.1-10 MeV. As a result, the line equivalent width reached 280±40 keV, which implies a nontrivial result. The result suggests that a downward positron beam produced both the continuum and the line photons.