Search

OBJECTIVE: To explore susceptibility loci associated with uveitis in Behçet's disease (BD).METHODS: We conducted a 2-stage study, consisting of a genome-wide association study (GWAS) stage and a replication stage, in a Chinese population. The GWAS stage included 978 cases with BD-related uveitis and 4,388 controls, and the replication stage included 953 cases with BD-related uveitis and 2,129 controls. Luciferase reporter analysis and chromatin immunoprecipitation assay were performed to explore the functional role of susceptibility genetic variants near ZMIZ1.RESULTS: Three independent HLA alleles (HLA-B51 [3.75 × 10-190 ], HLA-A26 [1.50 × 10-18 ], and HLA-C0704 [3.44 × 10-16 ]) were identified as having a genome-wide association with BD-related uveitis. In the non-HLA region, in addition to confirming 7 previously reported loci, we identified 22 novel susceptibility variants located in 16 loci. Meta-analysis of the Chinese cohort consisting of 1,931 cases and 6,517 controls and a published Japanese cohort of 611 cases and 737 controls showed genome-wide significant associations with ZMIZ1, RPS6KA4, IL10RA, SIPA1-FIBP-FOSL1, and VAMP1. Functional experiments demonstrated that genetic variants of ZMIZ1 were associated with enhanced transcription activity and increased expression of ZMIZ1.CONCLUSION: This GWAS study identified a novel set of genetic variants that are associated with susceptibility to uveitis in BD. These findings enrich our understanding of the contribution of genetic factors to the disease.

We have applied our amplitude-modulated flow analysis concept to extend the dynamic range to saturated analytical signals. Sample solution, the flow rate FS of which is periodically varied with a triangular control signal Vc, is merged with a reagent solution delivered at a constant flow rate FR. While the total flow rate FT is kept constant, a diluent with FT – (FS + FR) flow rate is aspirated from the third channel. The analytical signal Vd obtained downstream is processed by fast Fourier transform to obtain the amplitudes of the wave components in Vd. When the sample concentration CS is low, Vd shows a triangular profile like Vc; the sum of the amplitudes ΣA is proportional to CS. When CS is high, Vd shows a trapezoidal profile because of the Vd saturation. A linear calibration curve can also be obtained for such saturated signals by plotting CSΣA against CS. The proof of the concept is validated by applying it to spectrophotometric determinations of a dye (Methylene Blue) and colored complexes of Fe2+−phenanthroline and Fe3+−Tiron.

Objectives This study aimed to determine the clinical efficacy of apremilast for oral ulcers (OUs), extra-oral manifestations, and overall disease activity in patients with Behçet’s disease (BD). Methods A systematic literature search was performed in PubMed, Embase, Cochrane Library, and Web of Science Core Collection. Studies assessing the treatment effects of apremilast in BD were included. The odds ratios (ORs) of being symptom-free for individual manifestations and mean difference (MD) of Behçet’s Disease Current Activity Form (BDCAF) scores were calculated with 95% confidence intervals (CIs) at 12 and 24 weeks using a random-model meta-analysis. Results Of 259 screened articles, eight were included. After 12 weeks of apremilast treatment the OR of symptom-free was as followings: OUs, 45.76 (95% CI, 13.23–158.31); genital ulcers, 4.56 (95% CI, 2.47–8.44); erythema nodosum, 3.59 (95% CI, 1.11–11.61); pseudofolliculitis, 2.81 (95% CI, 1.29–6.15); and arthritis, 3.55 (95% CI, 1.71–7.40). Furthermore, BDCAF scores at 12 weeks were significantly reduced (MD=−1.38; −1.78 to −0.99). However, the proportion of oral-ulcer-free patients increased at 24 weeks (OR = 14.88; 4.81 to 46.07). Conclusions The currently accumulated data indicate an improvement in mucocutaneous and articular symptoms by short-term apremilast treatment in patients with BD.

We investigated the efficacy and safety of adalimumab (ADA) treatment for chronic recurrent Vogt-Koyanagi-Harada (VKH) patients with sunset glow fundus (SGF).Medical records of 50 chronic recurrent VKH patients with SGF who received ADA treatment for more than 6 months were retrospectively reviewed.The mean age of chronic recurrent VKH patients with SGF was 55.9 ± 14.4 years, and the male/female ratio was 26/24. Before ADA treatment, the mean daily dose of systemic corticosteroids was 16.5 ± 12.7 mg, and 22 patients (44%) were under immunosuppressors. LogMAR visual acuity (VA), flare counts, subfoveal choroidal thickness (SFCT), indocyanine green angiography scores, and corticosteroid and cyclosporine doses were significantly reduced by ADA treatment at 6 months compared to baseline. Among all parameters, flare count was significantly related to LogMAR VA. LogMAR VA was significantly related to flare counts but not to SFCT nor to ICGA scores. ADA treatment was continued in 94%.ADA was shown to be effective in achieving remission of chronic recurrent VKH disease with SGF refractory to conventional treatments, and was generally well tolerated with few serious adverse events.

Purpose Although infliximab (IFX) decreases the risk of blindness due to refractory uveitis in patients with Behcet's disease (BD), there are no standard criteria for IFX switching or withdrawal. To evaluate the effect of IFX switching in patients with BD in long-term remission, a prospective, single-arm intervention trial was conducted, switching from IFX to cyclosporine A (CYA). Study design A prospective open-label study. Methods Eligible patients met the following criteria: administration of IFX without concomitant immunosuppressants for more than 5 years with no episodes of ocular attacks, no retinal vasculitis on fluorescein fundus angiography, negative C-reactive protein in serum, and no extraocular lesions at the time of IFX withdrawal. CYA 5 mg/kg/day was administered from 6 weeks after IFX withdrawal. The primary outcome was the rate of readministration of tumor necrosis factor inhibitors at 1 year after IFX withdrawal. Results Three of 45 BD patients treated with IFX for refractory uveitis were included in the study. At 1 year after withdrawal of IFX, no patient had experienced any ocular attacks or needed readministation of IFX. However, extraocular lesions, such as recurrent oral ulcers, folliculitis, and recurrent fevers, occurred in all patients. Liver or renal dysfunction, which may have been caused by CYA, was also observed in all patients. Conclusions Although no ocular attacks were observed for at least 1 year after IFX withdrawal, this prospective study indicates that IFX withdrawal should be considered carefully, even for patients in long term remission of ocular and extraocular lesions.

A multicenter randomized controlled trial was conducted to compare the effectiveness of incisional and nonincisional surgical techniques for treating lower lid epiblepharon in children. The study included 89 eyes from 50 children aged 3–15 years (mean, 7.5 ± 2.4 years) with clinically significant moderate lower lid epiblepharon. Patients were randomly assigned to either incisional (modified Hotz procedure with lid margin splitting; 45 eyes of 25 patients) or nonincisional (44 eyes of 25 patients) surgery groups. Treatment outcomes were evaluated 6 months after surgery and classified into three grades: well-corrected, no ciliary touch, and superficial keratitis; under-corrected, ciliary touch, and superficial keratitis; and over-corrected, eyelid ectropion, and insufficient eyelid closure. Changes in astigmatism were compared between the two techniques after surgery. Incisional surgery provided a significantly higher percentage (77.8%) of well-corrected treatment results (P = 0.026; odds ratio, 2.88; 95% confidence interval, 1.07–8.22) than nonincisional surgery (55.4%). The mean change in astigmatism pre and post surgery was − 0.24 ± 0.42 and − 0.01 ± 0.47 D in the incisional and nonincisional surgery groups, respectively. The improvement in astigmatism 6 months after surgery was significantly higher in the incisional surgery group than in the nonincisional surgery group (P = 0.008). The incisional surgical treatment for epiblepharon in children resulted in a higher number of well-corrected patients, indicating an absence of both ciliary touch and superficial keratitis as well as statistically significant improvements in astigmatism correction.

This paper reports the direct analysis of polymer components in the airborne particulates collected on quartz filters by pyrolysis (Py)-GC/MS. The airborne microplastics (AMPs) were collected with three classification stages depending on different aerodynamic diameters using a multi-nozzle cascade impact (MCI) sampler. The quartz filter holding AMPs was punched directly into several pieces without pretreatment procedures. Three pieces were introduced into a sample cup, and Py-GC/MS measurements were done to analyze AMPs. Evolved gas analysis (EGA) of AMPs showed the volatilization of phthalates, the generation of sulfur dioxide and nitrogen oxide, and the thermal decomposition of polymer components as the heating temperature increased. In thermal desorption (TD)-GC/MS prior to Py-GC/MS, polycyclic aromatic hydrocarbons were detected in addition to phthalates and some aliphatic carboxylic acids. The following Py-GC/MS results indicated the presence of polyethylene, polypropylene (PP), polystyrene (PS), styrene-butadiene rubber (SBR), and natural rubber in AMPs. Among these polymers, PS, PP, and SBR were quantified using the indicator ions of their characteristic pyrolysis products. The analytical results showed that PS and PP seem to accumulate in the smaller aerodynamic diameter stage, while SBR appears to collect in the larger one. The analytical method using Py-GC/MS described herein is a powerful one that requires no pretreatment of the AMP samples.

A novel proteasome deubiquitinase inhibitor, VLX1570, has been highlighted as a promising therapeutic agent mainly for lymphoid neoplasms and solid tumors. We examined in vitro effects of VLX1570 on eight myeloid and three lymphoid leukemia cell lines. From cell culture studies, 10 out of 11 cell lines except K562 were found to be susceptible to VLX1570 treatment and it inhibited cell growth mainly by apoptosis. Next, to identify the signaling pathways associated with apoptosis, we performed gene expression profiling using HL‐60 with or without 50 nmol/L of VLX1570 for 3 hours and demonstrated that VLX1570 induced the genetic pathway involved in “heat shock transcription factor 1 (HSF1) activation”, “HSF1 dependent transactivation”, and “Regulation of HSF1 mediated heat shock response”. VLX1570 increased the amount of high molecular weight polyubiquitinated proteins and the expression of HSP70 as the result of the suppression of ubiquitin proteasome system, the expression of heme oxygenase‐1, and the amount of phosphorylation in JNK and p38 associated with the generation of reactive oxygen species (ROS) induced apoptosis and the amount of phosphorylation in eIF2α, inducing the expression of ATF4 and endoplasmic reticulum (ER) stress dependent apoptosis protein, CHOP, and the amount of phosphorylation slightly in IRE1α, leading to increased expression of XBP‐1s in leukemia cell lines. In the present study, we demonstrate that VLX1570 induces apoptosis and exerts a potential anti‐leukemic effect through the generation of ROS and induction of ER stress in leukemia cell lines., VLX1570 induces apoptosis mainly through reactive oxygen (ROS) stress signaling and unfolded protein response pathway under endoplasmic reticulum (ER) stress. Regarding ER stress, VLX1570 activated the protein kinase RNA‐like endoplasmic reticulum kinase signaling pathway, leading to ER stress‐dependent apoptosis. As another pathway, excess accumulation of polyubiquitinated proteins on the mitochondria induces ROS generation, followed by phosphorylation of JNK and p38, leading to caspases‐dependent apoptosis.

The standard addition method is a powerful tool to eliminate matrix interferences and enables accurate determinations, but it is time-consuming and labor-intensive. This paper proposes a feedback standard addition method coupled flow injection analysis, FB-SAM/FIA, for the rapid and accurate determination of trace interest in seawater samples. This approach automatically prepares spiked samples by feeding back the peak height in the fiagram, thus significantly improving the sample throughput compared to the manual standard addition method. Spectrophotometric determination of NO2- with the Griess assay was used as an evaluation model. The proposed technique demonstrated a sample throughput of 3 samples/h, ranging from 0.0050 mg L-1 (LOD) to 0.125 mg L-1 NO2-. The accuracies of NO2- determination with FB-SAM/FIA and an absolute calibration method were tested using natural seawater and pseudo-seawater samples containing 0.040 mg L-1 NO2- in 0, 1, 2, 3, and 4% sodium chloride media. With the absolute calibration method, the calculated concentration increased with an increase in salinity, reaching an overestimation of about 40%. On the other hand, FB-SAM/FIA suppressed the errors in the range of -7.8% to 1.3% and applied successfully to the determination of NO2- in the natural seawater samples.

Microfluidic devices are widely used in lipid nanoparticle (LNP)-based vaccines and nanomedicine research. These devices should be stiff enough to withstand the high flow rate for the mass production of LNPs, and malleable enough to use when fabricating complicated microchannel or micromixer structures, such as stag-gering herringbone micromixers. Due to the limitations of the available fabrication methods, optimal micro -fluidic devices have not yet been developed. In this study, we report the development of a glass-based microfluidic device based on the invasive Lipid Nanoparticle Production (iLiNP) device (R) reported previously. The LNP size controllability of glass-based iLiNP device was similar to that of the poly(dimethylsiloxane) (PDMS)-based iLiNP device, and the glass-iLiNP device was used for mRNA-loaded LNP production with ionizable lipids used for COVID-19 mRNA vaccines. We also demonstrate a piling-and numbering-up strategy based on glass-iLiNP device. The iLiNP unit composed of five-layered microchannels was fabricated by piling-up each glass-iLiNP device followed by parallelization (numbering-up) for the mass production of LNPs. This iLiNP system can produce LNPs with sizes ranging between 20 and 60 nm at a flow rate of 20-50 mL/min, and its performance is comparable to that of the commercially available microfluidic system like NanoAssemblr (R).

Purpose To identify novel susceptibility loci for high myopia. Design Genome-wide association study (GWAS) followed by replication and meta-analysis. Participants A total of 14 096 samples from East and Southeast Asian populations (2549 patients with high myopia and 11 547 healthy controls). Methods We performed a GWAS in 3269 Japanese individuals (1668 with high myopia and 1601 control participants), followed by replication analysis in a total of 10 827 additional samples (881 with high myopia and 9946 control participants) from Japan, Singapore, and Taiwan. To confirm the biological role of the identified loci in the pathogenesis of high myopia, we performed functional annotation and Gene Ontology (GO) analyses. Main Outcome Measures We evaluated the association of single nucleotide polymorphisms with high myopia and GO terms enriched among genes identified in the current study. Results We identified 9 loci with genome-wide significance (P Conclusions The current study identified 6 novel loci associated with high myopia and demonstrated an important role of the nervous system in the disease pathogenesis. Our findings give new insight into the genetic factors underlying myopia, including high myopia, by connecting previous findings and allowing for a clarified interpretation of the cause and pathophysiologic features of myopia at the molecular level.

BACKGROUND: To ensure quality and stability, monitoring systems are recommended to analyze pharmaceutical manufacturing processes. OBJECTIVE: This study was performed to predict powder X-ray diffraction (PXRD) patterns of formulation powders through attenuated total reflectance (ATR)-infrared (IR) spectroscopy in a nondestructive manner along with chemometrics. RESULTS: Caffeine anhydrate, acetaminophen, and lactose monohydrate were grinded at six weight ratios. The six sample groups were evaluated using ATR-IR spectroscopy and PXRD analysis. Partial least squares models were constructed to predict the PXRD intensities of the samples from the ATR-IR spectra. The prediction accuracy on the prepared PLS regression models was as high as R2 = 0.993. CONCLUSIONS: Linear relationships were obtained between the prediction data set and reference PXRD intensity at each degree. 2D PLS regression coefficient analysis enabled the analysis of the correlation between PXRD patterns and IR spectra.

To determine the real-world short-term efficacy and safety of apremilast for Behçet’s disease (BD). The study included patients who received apremilast for refractory oral ulcers in addition to meeting International Study Group criteria for BD or the revised International Criteria for Behçet’s Disease. To assess the efficacy of apremilast, Behçet’s disease current activity form (BDCAF) and patients’ self-perception of their disease activity were monitored for three months. The disease phenotypes, laboratory data, concomitant medication use, and adverse events were also investigated. Fourteen BD patients were included in the study. Concomitant drug use were as follows: colchicine 92.9%, prednisolone 21.4%, immunosuppressants 28.6%, and tumor-necrosis inhibitor 14.3%. Oral ulcers and BDCAF scores at 3 months showed significant improvement compared to baseline. Adverse events during the study were diarrhea (n = 3, 21.4%), nausea (n = 3, 21.4%), music hallucination (n = 1, 7.1%), and branch retinal vein occlusion (n = 1, 7.1%). Apremilast was discontinued in 1 patient (7.1%) due to nausea. Significant improvement in oral ulcer and BDCAF with apremilast was confirmed in real-world BD patients after 3 months. The combination of colchicine and apremilast appears to be well tolerated in BD in the short-term.

We investigated efficacy and safety of adalimumab (ADA) treatment for exacerbation or recurrence of Vogt-Koyanagi-Harada (VKH) patients. Medical records of 70 VKH patients who received ADA treatment for more than 6 months were retrospectively investigated. The mean age of VKH patients was 54.8 ± 15.1 years, and male/female ratio was 34/36, and sunset glow fundus was observed in 71.4%. Subfoveal choroidal thickness, indocyanine green angiography scores, and corticosteroid and cyclosporine doses were significantly reduced by ADA treatment for 6 months compared to baseline, while LogMAR and flare counts were also improved without being statistically significant. Adverse events were observed in 17.1%, in which tuberculosis was at 7.14% and psoriasis was at 2.86%; however, ADA treatment was continued in 91.4%. ADA was shown to be effective to achieve remission of VKH disease refractory to conventional treatments and was generally well tolerated with few serious adverse events.

Mountain observatories at high altitudes, far from local anthropogenic emission sources, are considered ideal for monitoring temporal variations of tropospheric air pollutants. During August 17–21 in 2013, we measured sulfur dioxide and nitric acid concentrations in the free troposphere at the top (3776 m a.s.l.) of Mt. Fuji, Japan. A parallel plate wet denuder-ion chromatographic system was used for the online measurement with 15 min temporal resolution. The continuous observations were successfully achieved without any problems. Of the samples collected, 97.8% of sulfur dioxide and 75.7% of nitric acid were above the limits of quantification. The average gas concentrations ± standard deviation (n = 408) were 0.106 ± 0.377 ppbv for sulfur dioxide and 0.015 ± 0.014 ppbv for nitric acid, respectively. Episodic elevations of sulfur dioxide concentration were recorded from August 20 to 21. Backward trajectory analyses indicated that the high-temporal resolution monitor detected the volcanic sulfur dioxide from Mt. Sakurajima, located 857 km from the sampling point. High-time-resolved observations in the free troposphere proved useful for source identification of air pollutants.

Introduction This study examined the usefulness of basic fibroblast growth factor impregnated collagen-gelatin sponge (bFGF-CGS) in reconstructive surgery for various acute skin defects including deep dermal burns, facial full-thickness skin defects, and finger amputations as the first clinical application. Methods Reconstructive surgery was performed in two stages with bFGF-CGS in 8 male subjects, ranging in age from 6 to 84 years, with acute full-thickness skin defects. Following the adequate debridement of the defect, surgeons prepared a bFGF-CGS with bFGF solution at a dose of 7–14 mg/cm2 approximately 10 min just before application and then secured the bFGF-CGS in place with non-absorbable sutures. Second-stage wound closure was performed with autologous skin grafting following adequate dermis-like tissue regeneration at the site postoperatively. Follow-up was continued for 6 months. Results Of the 8 subjects, the mean duration from the adequate vascularization of the dermis-like tissue until the second-stage autologous skin graft was 22 ± 4 days. Wound closure was achieved in all cases; the mean duration until wound closure was 32 ± 8 days. During the 6-month follow-up period, no wound infection, recurrent skin ulceration, and no exposure of tendon, bone, and cartilage were observed, and there were no cases of indirectly restricted range of motion from postoperative scar contracture and none with disfiguring scars. Conclusion The authors achieved favorable outcomes following reconstructive surgery with a hybrid artificial dermis impregnated with bFGF for treating acute full-thickness skin defects. bFGF-CGS serves as a convenient regenerative device requiring no specialized medical facilities., Highlights • This study examined the usefulness of bFGF-impregnated collagen gelatin sponge for skin defects. • bFGF-CGS achieved wound closure with acute full-thickness skin defects in a short period of time. • bFGF-CGS is a convenient device without requiring specialized medical facilities.

The world is currently facing the sea level rise due to climate change. And we are facing many sorts of problems of energy, water, food, garbage, air pollution and so on. Fortunately, however, 70% of the earth’s surface is covered with the ocean. The ocean has a tremendous capacity and a big influence on the global environment and the sustainability of human beings. We Shimizu are heading new challenges for the better future utilizing the potential of the ocean. “Green Float” is a new model for eco friendly Mega Floating City. The Green Float concept embodies two areas of innovation. The one is “Green innovation” and the other is “Float innovation”. By integrating “Green Innovation” and “Float Innovation”, a super high value-added Mega Floating City can be realized. In order to perform a basic verification of the technology, several hydraulic float model experiments and numerical computations about wind waves and tsunamis were conducted. We got a public third party’s certification concerning about “structural safety of floating building”. In addition, we continue to research and development the “City Grid System (city Cell, Module, Unit) of mega float city” based on Green Float.

Under industrial scenarios, high-speed motion is an important factor in increasing productivity. In this paper, a linear variable structured elastic actuator (LVSEA) is proposed for high-speed linear motion. The LVSEA consists of a geared motor, an electromagnetic clutch, a ball screw, compression springs, and a flange. The clutch is located between the geared motor and the ball screw. The clutch disconnects the geared motor from the ball screw. The compression springs are located between a housing and the flange of the ball screw. The spring stores elastic energy using the geared motor via the ball screw and the clutch. The stored elastic energy is released as kinetic energy by disconnecting the ball screw from the geared motor. On the load side, low inertia and low friction are achieved by disconnecting the ball screw from the geared motor, and high-speed movement is thereby realized. In the experiment, the velocity of a conventional ball screw system driven by the geared motor was 0.014 m/s. By contrast, the velocity of the LVSEA was 0.898 m/s. Therefore, the LVSEA could move faster than the conventional system. We verified repeating motions to reciprocate from position to position of the LVSEA and the conventional system. The average reciprocating time of the LVSEA was 4.76 s. By contrast, the average reciprocating time of the conventional system was 8.74 s. Therefore, the repeating motion of the LVSEA was faster than that of the conventional system.

Non-infectious uveitis associated with Vogt-Koyanagi-Harada (VKH) disease or sarcoidosis is commonly treated with systemic corticosteroids (SCS). We assessed the use of SCS for non-infectious uveitis relapses in Japanese clinical practice.Multicenter, retrospective chart review (UMIN Clinical Trial Registry; UMIN000032390).One hundred fifty-seven patients (15- ≤ 75 years; 103 VKH disease, 54 sarcoidosis) given SCS to treat a relapse of non-infectious intermediate, posterior, or panuveitis accompanying VKH disease or sarcoidosis were studied (August 2011-December 2018). SCS dose and duration, concomitant medications, subsequent relapses, and steroid-related adverse drug reactions (ADRs) were analyzed for 12 months after target relapse treatment. Relationships between background factors and total SCS dose were analyzed (logistic regression).Mean (± SD) total SCS dose over 12 months after target relapse treatment was 3874 ± 2775 mg, and was higher in patients with immunosuppressants than in those without (4575 mg vs 3496 mg). Immunosuppressant use was the only factor significantly associated with higher total SCS dose (p = 0.0196). Mean duration of SCS treatment for relapse was 318.7 ± 89.3 days. Only 29.3% of patients were steroid-free after 12 months; the percentage was higher in patients without immunosuppressants (36.3% vs 16.4%). Subsequent relapse was experienced by 39.5% of patients, and 13.4% had a steroid-related ADR (mostly glaucoma or diabetes).In Japanese clinical practice, many patients with recurrent uveitis accompanying VKH disease or sarcoidosis received SCS for relapse for ≥ 300 days, suggesting that reducing corticosteroids is challenging in patients with difficulty suppressing inflammation.

The aim of this study was to predict Differential Scanning Calorimetry (DSC) curves of pharmaceutical direct compression model tablet by chemometrics using Raman spectroscopy, measured in a nondestructive and contact-free manner. Theophylline anhydrate, theophylline hydrate, and micro-crystalline cellulose were ground and mixed with a mortar and pestle to obtain various formulations. The tablets were then measured with a handheld Raman spectrometer. DSC curves of the ground powder were measured, and the first-order derivative DSC curves were calculated. The Partial Least Squares (PLS) models were constructed to predict the calories at each temperature from the Raman spectra, and the regression vector of the constructed PLS models was plotted with 2D mapping (Raman wavenumber, Temperature, Regression coefficient). This mapping system allowed for the analysis of the correlations between Raman shift and DSC endothermic peaks.

Purpose: To investigate whether variants in the ARMC9 gene encoding KU-MEL-1 are associated with Vogt-Koyanagi-Harada (VKH) disease in a Japanese population.Methods: We recruited 380 Japane...

Uveitis is a generic term for inflammation of the uvea, which includes the iris, ciliary body, and choroid. Prevalence of underlying non-infectious uveitis varies by race and region and is a major cause of legal blindness in developed countries. Although the etiology remains unclear, the involvement of both genetic and environmental factors is considered important for the onset of many forms of non-infectious uveitis. Major histocompatibility complex (MHC) genes, which play a major role in human immune response, have been reported to be strongly associated as genetic risk factors in several forms of non-infectious uveitis. Behçet’s disease, acute anterior uveitis (AAU), and chorioretinopathy are strongly correlated with MHC class I-specific alleles. Moreover, sarcoidosis and Vogt-Koyanagi-Harada (VKH) disease are associated with MHC class II-specific alleles. These correlations can help immunogenetically classify the immune pathway involved in each form of non-infectious uveitis. Genetic studies, including recent genome-wide association studies, have identified several susceptibility genes apart from those in the MHC region. These genetic findings help define the common or specific pathogenesis of ocular inflammatory diseases by comparing the susceptibility genes of each form of non-infectious uveitis. Interestingly, genome-wide association of the interleukin (IL)23R region has been identified in many of the major forms of non-infectious uveitis, such as Behçet’s disease, ocular sarcoidosis, VKH disease, and AAU. The interleukin-23 (IL-23) receptor, encoded by IL23R, is expressed on the cell surface of Th17 cells. IL-23 is involved in the homeostasis of Th17 cells and the production of IL-17, which is an inflammatory cytokine, indicating that a Th17 immune response is a common key in the pathogenesis of non-infectious uveitis. Based on the findings from the immunogenetics of non-infectious uveitis, a personalized treatment approach based on the patient’s genetic make-up is expected.

Introduction Free flap lower extremity repair is associated with a high complication rate (>31%); higher rates are observed in more severe patients. In cases requiring prior systemic/local stabilization, delayed repair increases complication rate (+10% at 7 days): Negative-pressure Wound Therapy (NPWT) decreases complications but only when applied for less than 7 days. Recent limited evidence suggests that augmentation of NPWT with instillation for wound irrigation (NPWTi) might safely extend such window. This study hypothesizes that, through the combined cleansing effect of NPWT and instillation, NPWTi allows safe (low complication rate) delayed free flap repair in severe patients with Gustilo IIIb injuries (GIIIb). Methods A prospective case series was designed (inclusion criteria: GIIIb requiring microsurgical repair, severe patient/injury condition preventing immediate/early repair; exclusion criteria: allergy to NPWTi dressing). Patients received NPWTi (suction: 125 mmHg continuous; irrigation: NaCl 0.9%) until considered clinically ready for repair. Preoperative/postoperative complications (dehiscence, wound infection, bone non-union, osteomyelitis, flap failure) were monitored with clinical signs, imaging, and serum markers (CRP, WBC). Results Four patients (male: N = 4, female N = 1; Age: 59 [44–75] years-old) were treated. NPWTi was applied for 15.2 [9–28] days. No complication (0%) was observed preoperatively or postoperatively. Delayed repair occurred by latissimus dorsi musculocutaneous flap (N = 3), and anterolateral thigh flap (N = 2). All patients walked weight-bearing 12 [6–20] weeks after injury. Conclusions NPWTi seems to allow safe delayed free flap repair in patients with severe lower extremity injuries unable to undergo immediate/early repair.

Background We hypothesized that Behçet’s disease (BD) consists of several clinical subtypes with different severity, resulting in heterogeneity of the disease. Here, we conducted a study to identify clinical clusters of BD. Methods A total of 657 patients registered in the Yokohama City University (YCU) regional BD registry between 1990 and 2018, as well as 6754 patients who were initially registered in the Japanese Ministry of Health, Labour and Welfare (MHLW) database between 2003 and 2014, were investigated. The YCU registry data regarding the clinical manifestations of BD, human leukocyte antigen (HLA) status, treatments, and hospitalizations were analyzed first, followed by similar analyses of the MHLW for validation. A hierarchical cluster analysis was independently performed in both patient groups. Results A hierarchical cluster analysis determined five independent clinical clusters in the YCU cohort. Individual counterparts of the YCU clusters were confirmed in the MHLW registry. Recent phenotypical evolutions of BD in Japan, such as increased gastrointestinal (GI) involvement, reduced complete type according to the Japan Criteria, and reduced HLA-B51 positivity were associated with chronologically changing proportions of the clinical clusters. Conclusions In this study, we identified independent clinical clusters among BD patients in Japan and found that the proportion of each cluster varied over time. We propose five independent clusters namely “mucocutaneous”, “mucocutaneous with arthritis”, “neuro”, “GI”, and “eye.”

Objectives No large-scale registration study has comprehensively evaluated the activities of daily living (ADL) in patients with Behçet’s disease. Methods The Japanese government provided us with a dataset of confirmed or suspected Behçet’s disease cases derived from ongoing national registration. ADL were categorized and analysed into four categories in patients who satisfied the International Criteria for Behçet’s Disease. Results Data from 2960 patients (men 38.9%, women 61.1%; median age 39 years) were assessed. While 1767 patients (59.7%) had normal ADL, the others had impaired ADL comprising limited but not assisted [n = 1058 (35.7%)], partially assisted [n = 116 (3.9%)] and fully assisted [n = 19 (0.6%)]. Logistic regression analysis showed that chronic ocular lesions [odds ratio (OR) 1.85 (95% CI 1.46, 2.35), P Conclusion Ocular lesions, neurological manifestations and arthritis affected ADL. Patients with ocular lesions or neurological manifestations more frequently required physical assistance.

We propose a novel concept for detecting color transition by the inner product (IP) of RGB unit vectors. A digital microscope-based detector and a Visual Basic program were developed in-house. The concept is applied to indicator-based flow titration. The IP is 1 or < 1 if the vector's direction is the same or different, respectively. The IP's change can be used as a criterion for the indicator's color transition. The present IP-based approach is simple, economical, and versatile because it is applicable to any color transition without selecting an analytical wavelength.

Purpose Guidelines and systematic reviews frequently warn of inhaled corticosteroid (ICS)-induced glaucoma. However, most of the published studies deny it. Methods We performed a systematic review of randomized, cohort, nested-case control, cross-sectional studies by using Meta-analyses of Observational Studies in Epidemiology statement. Four major databases, PubMed, EMBASE, Cochrane Search Manager, and the Web of Science Core Collection as well as meta-analysis were used. Studies comparing incidence, prevalence and intraocular pressure (IOP) between patients who were treated with and without ICSs were included. A random-model meta-analysis was performed using the inverse variance method. Results Out of 623 studies screened, 18 with 31,665 subjects were finally included. No significant difference between the 2 groups was observed for crude glaucoma incidence (odds ratio [OR], 0.95; 95% confidence interval [CI], 0.86-1.04; P = 0.26; I² = 0%; P for heterogeneity = 0.57) as a primary endpoint, adjusted glaucoma incidence (OR, 0.90; 95% CI, 0.65-1.24; P = 0.64), crude prevalence (OR, 1.82; 95% CI, 0.23-14.19; P = 0.57), adjusted prevalence (OR, 1.22; 95% CI, 0.50-2.96; P = 0.66), IOP change during ICS treatment (mean difference [MD] +0.01 mmHg; 95% CI, -0.19-0.20; P = 0.95), and single measurement IOP (MD +0.37 mmHg; 95% CI, -0.24-0.97; P = 0.23). Time-to-event analysis for glaucoma development as one of the secondary endpoints (adjusted hazard ratio, 0.52; 95% CI, 0.28-0.96) suggested a reverse association between ICS and glaucoma. Conclusions The ophthalmological side effects of ICSs, such as glaucoma and intraocular hypertension, should not be exaggerated. Trial registration University Hospital Medical Information Network Center Clinical Trial Registry Identifier: UMIN000040351.

Summary:. The authors describe a surgical treatment that optimally combined the use of the hydrosurgical system and a free multiperforator anterolateral thigh flap to prevent lower limb amputation in a severe case of necrotizing fasciitis. A 43-year-old woman was diagnosed with necrotizing fasciitis, and amputation was performed at the level of the metatarsal shafts with an emergency debridement using the hydrosurgical system. In the second reconstructive surgery, a free anterolateral thigh flap measuring 28 × 8 cm2 was harvested using the left thigh as the donor site and the vascular pedicle was made up of a total of 3 vessels, 2 perforating arteries from the descending branch of the lateral circumflex femoral artery, and 1 oblique branch from the lateral circumflex femoral artery. To thin the flap, we first resected as much subcutaneous fat as possible in the distal part of the flap (which would eventually cover the ankle joint) and ensured adequate residual volume of the proximal part of the flap (which would cover the metatarsal stumps). We then sutured the flap to the tissue defect on the left foot and then end-to-side anastomosing the lateral femoral circumflex artery and posterior tibial artery while the 2 veins were anastomosed to the posterior tibial veins under a microscope. Six months after the surgery, adequate flap volume was maintained over the metatarsal stumps with no postoperative complications such as infection or ulcer formation, and there were no other complications such as motor dysfunction at the donor site on the left thigh.

Mami Ishihara, Akira Meguro, Mizuho Ishido, Masaki Takeuchi, Etsuko Shibuya, Nobuhisa Mizuki Department of Ophthalmology and Visual Science, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, JapanCorrespondence: Mami Ishihara; Akira Meguro Tel +81-45-787-2683Fax +81-45-781-9755Email mamitaiga7@gmail.com; akmeguro@yokohama-cu.ac.jpPurpose: Angiotensin-converting enzyme (ACE) is conventionally used as a biomarker in the diagnosis of uveitis associated with sarcoidosis, but its sensitivity is relatively low. In this study, we investigated whether serum soluble interleukin-2 receptor (sIL-2R) is also useful as a diagnostic marker, in addition to ACE, in the detection of uveitis associated with sarcoidosis.Patients and Methods: Data were analyzed from 126 patients with uveitis (52 sarcoidosis and 74 non-sarcoid uveitis) and 12 with primary intraocular lymphoma (PIOL) who had their serum sIL-2R and ACE levels measured.Results: Serum sIL-2R level was elevated in 69.2% of patients with sarcoid uveitis, 5.4% of those with non-sarcoid uveitis, and 16.7% of those with PIOL. The sensitivity and specificity of an elevated sIL-2R level for the detection of sarcoidosis were 69.2% and 93.0%, respectively. In contrast, serum ACE levels were elevated only in patients with sarcoid uveitis, with a sensitivity of 44.2% and specificity of 100%. Furthermore, serum sIL-2R and/or ACE level was elevated in 75.0% of patients with sarcoid uveitis, which is higher than those who had elevated serum ACE level only (44.2%, P = 0.0025). The sensitivity and specificity of elevated sIL-2R and/or ACE in detecting sarcoid uveitis were 75.0% and 93.0%, respectively. The PPV was 0.87, and the NPV was 0.86.Conclusion: Compared with the sensitivity of serum ACE levels alone, combined measurement of both serum sIL-2R and ACE levels improves sensitivity in the detection of uveitis associated with sarcoidosis. Nevertheless, serum ACE alone remains useful thanks to its high specificity in the differentiation of uveitis patients, with sarcoidosis from those without sarcoidosis.Keywords: sarcoid uveitis, soluble interleukin-2 receptors, sIL-2R, angiotensin-converting enzyme, ACE, primary intraocular lymphoma, PIOL

Background:. Pressure injuries (PIs) are common in hospitalized patients, with incidence exceeding 50% in high-risk patients. Immobilization causes a prolonged compression of vascular networks in tissues overlying bony prominences, leading to ischemia and ulceration. Traditionally, PIs are treated with a combination of surgical debridement and reconstruction. This approach can be invasive for debilitated patients who cannot tolerate prolonged surgeries and extensive tissue resection. Hydrosurgery uses high-pressure irrigation to low-invasively debride and cleanse wounds; its use has shown positive outcomes in burn and chronic wounds care. Here, we hypothesize that hydrosurgery allows low-invasive yet effective wound bed preparation in truncal PIs. Methods:. We conducted a single-center, prospective, uncontrolled case series. Inclusion criteria for this study were presence of a truncal PI (stage III or IV) and an American Society of Anesthesiologists physical status of ≥2 (no exclusion criteria). Measured outcomes included duration of hydrosurgery, postsurgical local (dehiscence, infection, seroma) or systemic complications in the first 30 days, and PI recurrence rate (6-month follow-up). Results:. Seven patients (3 sacral, 2 greater trochanteric, and 2 ischial tuberosity PIs) were enrolled for this study. Average duration of hydrosurgery was 12 minutes (±3.1). No local or systemic complications were observed at a 30-day follow-up (0/7, 0%). All flaps (6/7, 86%) and graft (1/7, 14%) reconstructions successfully survived, and no PI recurrence was reported within a 6-month follow-up (0/7, 0%). Conclusions:. Hydrosurgery seems to allow safe, low-invasive, and effective wound bed preparation in truncal PIs. Larger controlled trials are needed to confirm this preliminary evidence, to guide its broader adoption for improved care of high-risk patients with PIs.

Summary: Incisional hernia often complicates kidney transplant. However, there are few reports showing pitfalls after the repair of incisional hernia following living-donor kidney transplant. A 55-year-old man underwent living-donor kidney transplant from his wife at the Department of Urology at the authors’ hospital. He noticed abdominal distension 6 months postoperatively and was diagnosed with incisional hernia by computed tomography (CT) imaging. Clinical examination revealed the extensive distension of the right abdomen; noncontrast abdominal CT showed transverse colon, descending colon, and mesenteric prolapse through a hernial orifice measuring 11 × 14 cm, located slightly cranial to the anterior superior iliac spine. Repair was performed under general anesthesia the following day; the right thigh was the donor site. A pedicled anterolateral thigh flap from the donor site was used for abdominal wall reconstruction. He developed fever, and pain and swelling were noted in the right leg on postoperative day 14. Contrast-enhanced thoracic CT confirmed a diagnosis of pulmonary embolism (PE) and deep vein thrombosis. He was quickly started on an oral factor Xa inhibitor (edoxaban) and continuous intravenous heparin; contrast-enhanced thoracic CT on postoperative day 23 showed that PE had disappeared. At 6 months postoperatively, there was no recurrence of the venous thromboembolism or incisional hernia. The authors reported a case of incisional hernia repair after living-donor kidney transplant with a pedicled anterolateral thigh flap, complicated by deep vein thrombosis and PE. Adequate preoperative evaluation was required to determine optimal surgical techniques and preventive measures in cases with myriad thrombogenic risk factors.