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Objectives: In the phase 3 JAVELIN Renal 101 trial in patients with advanced renal cell carcinoma (aRCC), objective response rate (ORR) and progression-free survival (PFS) were significantly improved in patients treated with first-line avelumab plus axitinib vs sunitinib. Here we evaluate real-world outcomes with first-line avelumab plus axitinib in Japanese patients with aRCC., Methods: In this multicenter, noninterventional, retrospective study, clinical data from patients with aRCC treated with first-line avelumab plus axitinib between December 2019 and December 2020 in Japan were reviewed. Endpoints included ORR and PFS per investigator assessment, and time to treatment discontinuation (TTD)., Results: Data from 48 patients (median age, 69 years) from 12 sites were analyzed. Median follow-up was 10.4 months (range, 2.6-16.5), and median duration of treatment was 7.4 months (range, 0.5-16.5). International Metastatic RCC Database Consortium risk category was favorable, intermediate, or poor in 16.7%, 54.2%, and 29.2% of patients, respectively. The ORR was 48.8% (95% CI, 33.3%-64.5%), including complete response in 3/43 patients (7.0%). Thirteen patients (27.1%) had disease progression or died, and median PFS was 15.3 months (95% CI, 9.7 months - not estimable). At data cutoff, 24 patients (50.0%) were still receiving avelumab plus axitinib, and median TTD was 15.2 months (95% CI, 7.4 months - not estimable). Three patients (6.3%) received high-dose corticosteroid treatment for immune-related adverse events, and 8 (16.7%) received treatment for infusion-related reactions., Conclusions: We report the first real-world evidence of the effectiveness and tolerability of first-line avelumab plus axitinib in Japanese patients with aRCC. Results were comparable with the JAVELIN Renal 101 trial., (© 2023 The Authors. International Journal of Urology published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Urological Association.)

We report the case of a 48-year-old man who presented with fatigue and weight loss. A local physician observed elevated alkaline phosphatase levels, anemia, thrombocytopenia, and renal dysfunction. Fever also appeared, and the patient was admitted to our hospital. Computed tomography revealed hepatosplenomegaly, pleural and ascitic fluid, and left axillary lymphadenopathy. Bone marrow biopsy indicated hyperplasia with increased megakaryocytes and reticulin fibrosis. Axillary lymph node biopsy showed Castleman's disease-like features. Liver biopsy revealed proliferation of reticulin fibrosis. Therefore, TAFRO syndrome was diagnosed and treatment with 1 mg/kg prednisolone was started. Anemia and thrombocytopenia improved, and after 24 weeks of treatment, serum hyaluronic acid and type IV collagen decreased to the normal range. Bone marrow biopsy after 18 weeks of treatment showed decreased reticular fibers. In TAFRO syndrome, improvement of liver and bone marrow fibrosis can be expected with adequate intervention, and serum hyaluronic acid and type IV collagen are useful for evaluating fibrosis.

Purpose: To evaluate 10-year outcome of infliximab (IFX) treatment for uveitis in Behçet disease (BD) patients using a standardized follow-up protocol., Design: Retrospective longitudinal cohort study., Participants: 140 BD uveitis patients treated with IFX enrolled in our previous study., Methods: Medical records were reviewed for demographic information, duration of IFX treatment, number of ocular attacks before IFX initiation, best corrected visual acuity (VA) at baseline and 1, 2, 3, 4, 5, and 10 years after IFX initiation, uveitis recurrence after IFX initiation and main anatomical site, concomitant therapies, and adverse events (AEs)., Main Outcome Measures: 10-year IFX continuation rate and change in LogMAR VA., Results: Of 140 BD patients, 106 (75.7%) continued IFX treatment for 10 years. LogMAR VA improved gradually after initiation of IFX, and the improvement reached statistical significance from 2 years of treatment. Thereafter, significant improvement compared with baseline was maintained until 10 years, despite a slight deterioration of logMAR VA from 5 years. However, eyes with worse baseline decimal VA < 0.1 showed no significant improvement from baseline to 10 years. Uveitis recurred after IFX initiation in 50 patients (recurrence group) and did not recur in 56 (non-recurrence group). Ocular attacks/year before IFX initiation was significantly higher in the recurrence group (2.82 ± 3.81) than in the non-recurrence group (1.84 ± 1.78). In the recurrence group, uveitis recurred within 1 year in 58% and within 2 years in 74%. Seventeen patients (34%) had recurrent anterior uveitis, 17 (34%) had posterior uveitis, and 16 (32%) had panuveitis, with no significant difference in VA outcome. In addition, logMAR VA at 10 years did not differ between the recurrence and non-recurrence groups. AEs occurred among 43 patients (30.7%), and 24 (17.1%) resulted in IFX discontinuation before 10 years., Conclusions: Among BD patients with uveitis who initiated IFX, approximately 75% continued treatment for 10 years, and their VA improved significantly and was maintained for 10 years. Uveitis recurred in one-half of the patients, but visual acuity did not differ significantly from the patients without recurrence., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Takeuchi, Usui, Namba, Keino, Takeuchi, Takase, Kamoi, Hase, Ito, Nakai, Maruyama, Kobayashi, Mashimo, Sato, Ohguro, Hori, Okada, Sonoda, Mizuki and Goto.)

Robot-assisted laparoscopic partial nephrectomy (RAPN) is being used in Japan as a less invasive procedure. RENAL nephrometry (RN) score, Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) Classification and Simplified PADUA Renal (SPARE) nephrometry system are tumor-specific morphometry scoring systems used for predicting the difficulty of partial nephrectomy. Adherent perinephric fat (APF) is one of the patient-specific factors related to the difficulty of partial nephrectomy. Mayo Adhesive Probability (MAP) score measures the difficulty of partial nephrectomy due to APF. Whether these scoring systems were associated with perioperative outcome of RAPN was retrospectively analyzed in 57 patients who underwent RAPN by two experienced surgeons at our hospital from December 2016 to March 2020. Forty-five patients were male and 12 were female. The right side was resected in 25 and the left side in 32 patients. The approach was transperitoneal in 42 and retroperitoneal in 15 patients. There were significant correlations among RN, PADUA and SPARE scores, while MAP score was independent from the other scores. Warm ischemic time was significantly correlated with RN (r＝0.46, p＜0.001), PADUA (r＝0.45, p＜0.001) and SPARE scores (r＝0.44, p＜0.001). Time for console was significantly correlated with MAP score (r＝0.28, p＝0.035). In conclusion, RN and MAP scores might be useful parameters to predict warm ischemic time and time for console during RAPN, respectively.

Like many other countries, the economy and society of Japan have been deeply affected by the Covid-19 outbreak, and the fishery sector is no exception. This study takes an interdisciplinary approach to analyze the economic and social impacts of the pandemic on Japanese fisheries, gauging the extent and nature of the damages incurred from Covid-19 while helping to provide tailored post-recovery recommendations for the industry. Using results from an online survey questionnaire (N = 429) and compiling additional economic information from public sources, this study revealed the overwhelmingly negative changes in sales figures and overall financial security that survey participants experienced when compared to a year earlier. High-value and fresh fish species were also significantly affected in 2020 across Japan, in line with similar trends across the developed world. Aquaculture businesses were shown to be more vulnerable to the spread of Covid-19 than small-scale fishing operations, which tend to be more diverse and flexible. Bonding social capital was also shown to be important for mutual help and human well-being, especially among small-scale fishers. This "customary nature" of Japanese fisheries, at the same time, can be seen as a barrier to the transformation of the industry. Given these results, several policy implications are discussed to help fisheries stakeholders and their communities build back better from the Covid-19 pandemic., (© 2022 The Authors.)

Purpose: To compare the efficacy and safety of a combination therapy of prednisolone and cyclosporine and corticosteroid pulse therapy in Vogt-Koyanagi-Harada (VKH) disease., Study Design: A prospective, multicenter, randomized, non-inferiority trial., Methods: Patients of new-onset acute VKH disease at 11 centers in Japan between 2014 and 2018 were randomized to a combination (oral prednisolone 60 mg daily with gradual taper-off to 35 mg/day and cyclosporine 3 mg/kg/day) and corticosteroid (methylprednisolone 1000 mg for 3 days followed by oral prednisolone) groups, and were followed for 1 year., Results: Thirty-four were assigned to the combination and thirty-six patients to the corticosteroid group. Recurrence/worsening risk was 0.15 (95% confidence-interval [CI] 0.03-0.27) in the combination group and 0.25 (95% CI 0.11-0.39) in the corticosteroid group, with a risk difference of - 0.10 (90% CI - 0.27 to 0.06), demonstrating non-inferiority of the combination group with a non-inferiority margin of 0.20 (P = 0.0013). Serious adverse events occurred in three patients (two with hyponatremia and one with severe headaches) in the combination group and none in the corticosteroid group. Sunset glow fundus grades and cataract rates at 1 year were 0.57 (95% CI 0.42-71) and 4.3% in the combination group and 0.91 (95% CI 0.78-1.04) and 34.0% in the corticosteroid group, respectively., Conclusions: Combination therapy was noninferior to corticosteroid therapy with respect to recurrence/worsening risk. Notably, the recurrence/worsening risk, sunset glow fundus grade, and cataract rate were lower in the combination group than in the corticosteroid group., (© 2021. Japanese Ophthalmological Society.)

Scleritis involves inflammation of the sclera, which constitutes 75% of the wall of the eye. This pathology is often seen as an ocular lesion associated with systemic inflammatory diseases. Severe types of scleritis such as posterior scleritis require urgent immunosuppressive treatments, including molecularly targeted therapies to avoid permanent visual impairment. Which molecules should be selected as targets has remained unclear. To clarify the pathogenesis of scleritis and propose appropriate target molecules for therapy, we have established novel animal model of scleritis by modifying the Collagen-II Induced Arthritis (CIA) model. Immunization twice with collagen II emulsified with complete Freund's adjuvant (CFA) caused arthritis and scleritis. The clinical appearance resembled human diffuse scleritis. Histopathological analysis suggested that macrophages, plasma cells, deposition of immune complexes, and growth of blood and lymphatic vessels are involved in the pathogenesis of CIA-associated scleritis. In addition, we analysed the background diseases of posterior scleritis and responses to molecularly targeted therapies as a case series study. We inferred from both the animal model and case series study that targets should not be T cells, but factors inhibiting macrophage activity such as tumor necrosis factor (TNF) and interleukin (IL)-6, and molecules suppressing antibody-producing cells such as CD20 on B cells should be targeted by molecularly targeted therapies.

The patient was a 69-year-old man diagnosed with stage ⅣB lung adenocarcinoma with 95% programmed death- ligand 1 expression, and pembrolizumab monotherapy was initiated. The patient exhibited fatigue from the 12th course(36 weeks after treatment initiation) of treatment. Chest computed tomography revealed scattered ground-glass opacities in the upper lobes of both lungs, and he was subsequently diagnosed with interstitial pneumonia. Fatigue persisted even after a drug holiday from pembrolizumab, and the patient was diagnosed with hypopituitarism based on the results of endocrinological examinations. Rashes appeared on both legs 40 weeks after treatment initiation, which led to the patient being diagnosed with a drug-induced skin disorder. All the adverse events resolved upon treatment with hydrocortisone. Immune- related adverse events due to pembrolizumab may occur in multiple organs simultaneously.

Purpose: The posterior approach is widely used in femoral hemiarthroplasty. The major problem with this approach is the high risk of postoperative dislocation. A modified posterior approach, the conjoined tendon preserving posterior approach (CPP), was developed to reduce postoperative dislocations. The objective of this multicenter study was to evaluate the efficacy and safety of hemiarthroplasty performed using the CPP approach for femoral neck fractures., Methods: A total of 322 patients with femoral neck fracture, from 10 facilities, were prospectively studied. Bipolar hemiarthroplasty using the CPP approach was performed, using the same type of implants. Hip joint movement was not restricted following surgery, regardless of a patient's cognitive status. Final follow-up was performed 9.1 ± 1.5 months after surgery., Results: Hemiarthroplasty was undertaken in 320 patients using the CPP approach. The mean age, operative time, and intraoperative blood loss were 83.3 ± 7.4 years, 70.0 ± 22.7 min, and 134.8 ± 107.9 mL, respectively. No postoperative dislocations were observed during the study period. Intraoperative adverse events related to the hip joint included femoral fractures in five patients (1.6%) and trochanteric fractures in four patients (1.3%). Postoperative hip joint adverse events included a periprosthetic fracture in one patient (0.3%), deep infection in two patients (0.6%), and stem subsidence in one patient (0.3%). Postoperative deaths occurred in 23 patients (7.2%). One patient (0.3%) had a severe non-hip adverse event unrelated to surgery that prevented independent living, while five patients (1.6%) had a moderate non-hip adverse event that required treatment., Conclusion: The CPP approach prevented postoperative dislocation following femoral hemiarthroplasty in elderly patients, with no CPP-associated specific adverse events.

We retrospectively investigated the clinical course of α1 blocker discontinuation in patients who had lower urinary tract symptoms with benign prostate hypertrophy (LUTS/BPH) and received combination therapy ofdutasteride and α1 blocker. Among the patients with LUTS/BPH who had been receiving combination therapy, those who wished to reduce the number ofprescribed drugs and discontinue the use of α1 blocker because ofsymptom improvement were recruited in this study. Symptom scores including International Prostate Symptom Score (IPSS) and overactive bladder symptom score (OABSS), parameters ofuroflowmetry and prostate volume (PV) were evaluated at the time of α 1 blocker discontinuation. Twenty-two patients discontinued the use of α 1 blocker. The mean PV at the time of α 1 blocker discontinuation was 43.2 ml, and the mean duration ofcombination therapy was 39.4 months. In 11 (50%) patients, dutasteride monotherapy without α1 blocker was maintained for a mean follow-up of 10.5 months (9-12 months) after α1 blocker discontinuation (Non-resumption group). In the other 11 patients (50%), α1 blocker was resumed because ofthe patient's request to resume the use of α1 blocker (Resumption group). The mean length ofdutasteride monotherapy was 4. 5 months (1-8 months) in the resumption group. Compared with the non-resumption group, IPSS total score and storage sub-score ofIPSS at the time of α1 blocker discontinuation were significantly higher in the resumption group. Based on the ROC curve, IPSS total score <16, IPSS voiding/storage symptom score <7, OABSS <7 and PV 54 ml or more at the time of α1 blocker discontinuation were predictors ofnon-resumption of α1 blocker. These results suggest that if LUTS is controlled by a long-term combination therapy ofdutasteride and α1 blocker and still PV is large enough, α1 blocker can be discontinued.

Sarcoidosis is a genetically complex systemic inflammatory disease that affects multiple organs. We present a GWAS of a Japanese cohort (700 sarcoidosis cases and 886 controls) with replication in independent samples from Japan (931 cases and 1,042 controls) and the Czech Republic (265 cases and 264 controls). We identified three loci outside the HLA complex, CCL24, STYXL1-SRRM3, and C1orf141-IL23R, which showed genome-wide significant associations (P < 5.0 × 10 -8 ) with sarcoidosis; CCL24 and STYXL1-SRRM3 were novel. The disease-risk alleles in CCL24 and IL23R were associated with reduced CCL24 and IL23R expression, respectively. The disease-risk allele in STYXL1-SRRM3 was associated with elevated POR expression. These results suggest that genetic control of CCL24, POR, and IL23R expression contribute to the pathogenesis of sarcoidosis. We speculate that the CCL24 risk allele might be involved in a polarized Th1 response in sarcoidosis, and that POR and IL23R risk alleles may lead to diminished host defense against sarcoidosis pathogens.

The eye is provided with immune protection against pathogens in a manner that greatly reduces the threat of inflammation-induced vision loss. Immune-mediated inflammation and allograft rejection are greatly reduced in the eye, a phenomenon called 'immune privilege'. Corneal tissue has inherent immune privilege properties with underlying three mechanisms: (1) anatomical, cellular, and molecular barriers in the cornea; (2) an immunosuppressive microenvironment; and (3) tolerance related to regulatory T cells and anterior chamber-associated immune deviation. This review describes the molecular mechanisms of the immunosuppressive microenvironment and regulatory T cells in the cornea that have been elucidated from animal models of ocular inflammation, especially those involving corneal transplantation, it also provides an update on immune checkpoint molecules in corneal and systemic immune regulation, and its relevance for dry eye associated with checkpoint inhibitor therapy.

Psoas muscle mass index (PMI) is related to sarcopenia. We examined whether PMI is associated with early complications after radical cystectomy. Seventy one male and 29 female patients who were 65 years old or older and who had undergone radical cystectomy at our hospital from April 2005 to March 2018 were retrospectively analyzed. Psoas muscle section area was measured manually on preoperative computed tomography (CT) scan and normalized by patient's height. Early postoperative complications of grade 3 or more occurred in 12 male (16.9%) and 5 female (17.2%) patients. PMI was lower in male patients who had early postoperative complications of grade 3 or more than in those without complications (5.61 vs 6.54 cm2 /m2, p=0. 08), although the difference was not statistically significant. There was suggested to be a relationship between early postoperative complications after radical cystectomy and preoperative PMI in elderly male patients.

Purpose: V-domain immunoglobulin suppressor of T cell activation (VISTA) is a novel immune checkpoint receptor and ligand for regulating T cell proliferation and cytokine production. The purpose of the present study was to determine the role of VISTA in the immune privilege of corneal allografts., Methods: Expression of VISTA mRNA in mouse eyes was assessed with reverse-transcription PCR. Corneas of C57BL/6 mice were orthotopically transplanted into the eyes of BALB/c wild-type recipients treated with anti-VISTA mAb, and graft survival was assessed. A separate set of BALB/c mice treated with anti-VISTA mAb or rat IgG received injection of C57BL/6 splenocytes into the anterior chamber, and induction of allospecific anterior chamber-associated immune deviation (ACAID) was assessed. CD4+ and CD8+ T cells in the spleen were assessed with flow cytometry., Results: VISTA mRNA was constitutively expressed in the cornea, and the expression of VISTA was localized to CD11b+ cells on the corneal stroma. Survival of allografts treated with anti-VISTA mAb was less than that of the control. ACAID was induced less efficiently in BALB/c mice treated with VISTA mAb. The proportions of CD8+ T cells and CD8+ CD103+ T cells (CD8+ T regulatory cells) in the spleen of BALB/c mice treated with anti-VISTA mAb were significantly lower than those of the control., Conclusions: VISTA may play an essential role in the acceptance of corneal allografts via involvement with allospecific ACAID, which suppresses T cell infiltration into the cornea.

Objectives: To examine the long-term outcomes of transurethral resection of the prostate., Methods: We retrospectively collected the data of patients who had undergone transurethral resection of the prostate before December 2010. Patients had been evaluated by urodynamics and the International Prostate Symptom Score preoperatively, and they were re-evaluated by using the International Prostate Symptom Score at the minimum 7 years after transurethral resection of the prostate. Patients who received any treatments to improve voiding symptoms were defined as having a relapse of voiding dysfunction. The Schäfer nomogram was used to assess the degree of obstruction and detrusor contractility. We assessed the change in International Prostate Symptom Score over time depending on obstruction (Schäfer grade 3-6) versus no obstruction (Schäfer grade 0-2), and normal detrusor contractility (strong and normal) versus detrusor underactivity (weak and very weak). Relapse rates of voiding dysfunction were determined using the Kaplan-Meier method., Results: A total of 39 patients were included. The mean age at transurethral resection of the prostate was 69.8 years, and the mean observation period after transurethral resection of the prostate was 114 months. During the observation period, eight patients (21%) were categorized as relapse of voiding dysfunction and the mean time to relapse was 4.2 years. Patients categorized as no obstruction or detrusor underactivity had a higher recurrence rate of voiding dysfunction with a statistical significance between those with versus without obstruction. Except for patients with relapse of voiding dysfunction, improvement of the International Prostate Symptom Score was maintained over a period of 10 years after transurethral resection of the prostate., Conclusions: Favorable long-term symptomatic outcome after transurethral resection of the prostate is likely in patients with urodynamic obstruction. Patients without urodynamic obstruction are likely to have a relapse of voiding symptoms and require additional treatments in the long term., (© 2019 The Japanese Urological Association.)

Corneal transplantation is the most successful solid organ transplantation performed in humans. The extraordinary success of orthotopic corneal allografts, in both humans and experimental animals, is related to the phenomenon of "immune privilege". Inflammation is self-regulated to preserve ocular functions because the eye has immune privilege. At present, three major mechanisms are considered to provide immune privilege in corneal transplantation: 1) anatomical, cellular, and molecular barriers in the cornea; 2) tolerance related to anterior chamber-associated immune deviation and regulatory T cells; and 3) an immunosuppressive intraocular microenvironment. This review describes the mechanisms of immune privilege that have been elucidated from animal models of ocular inflammation, especially those involving corneal transplantation, and its relevance for the clinic. An update on molecular, cellular, and neural interactions in local and systemic immune regulation is provided. Therapeutic strategies for restoring immune privilege are also discussed., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The patient was a 66-year-old man who had undergone ileocystoplasty and right nephrectomy at the age of 21 for the treatment of urinarytract tuberculosis. He had been receiving hemodialysis from the age of 58. Regular computed tomography (CT) examination at the age of 63 revealed a bladder mass, but the transurethral biopsyof the bladder mass did not reveal malignant findings. At the age of 66, his urine cytology indicated a suspicion of malignancy, and bladder tumor was detected by cystoscopy. The patient was referred to our hospital and we performed transurethral resection of the bladder tumor. Pathological diagnosis was papillaryadenocarcinoma. Because left lower ureteral cancer was also suspected byCT scan, we performed left nephroureterectomy and radical cystectomy. Pathological examination revealed adenocarcinoma of the reconstructed bladder. The patient remains free of disease for 1 year and 11 months after the operation. Forty-five cases of bladder cancer after enterocystoplasty have been reported in Japan. There are no guidelines for follow-up protocols after enterocystoplasty. A long-term follow-up is mandatory because of the possibilityof development of bladder malignancylong after the enterocystoplasty.