Efficacy of spesolimab for the treatment of generalized pustular psoriasis flares across pre-specified patient subgroups in the Effisayil 1 study.

Effisayil 1 was a multicentre, randomized, double-blind, placebo-controlled study of the anti-interleukin (IL)-36 receptor monoclonal antibody, spesolimab, in patients presenting with a generalized pustular psoriasis (GPP) flare. Previously published data from this study revealed that within 1 week, rapid pustular and skin clearance were observed in patients receiving spesolimab versus placebo. In this pre-specified subgroup analysis, the efficacy of spesolimab was evaluated according to patient demographic and clinical characteristics at baseline in patients receiving spesolimab (n = 35) or placebo (n = 18) on Day 1. Efficacy was by assessed by achievement of primary endpoint (Generalized Pustular Psoriasis Physician Global Assessment [GPPGA] pustulation subscore of 0 at Week 1) and key secondary endpoint (GPPGA total score of 0 or 1 at Week 1). Safety was assessed at Week 1. Spesolimab was found to be efficacious and had a consistent and favourable safety profile in patients presenting with a GPP flare, regardless of patient demographics and clinical characteristics at baseline.

Occupational Fall Risk Assessment Tool for older workers.

BACKGROUND: No easy-to-use fall risk assessment tools have been devised to assess occupational fall risk in older workers. AIMS: To develop an Occupational Fall Risk Assessment Tool (OFRAT) and report its predictive validity and reliability in older workers. METHODS: The baseline fall risk assessment was completed by 1113 participants aged ≥60 years who worked ≥4 days/month in Saitama, Japan. Participants were followed up for falls during occupational activities for 1 year, and 30 participants were assessed twice for test-retest reliability. The following assessment measures were summed to form the OFRAT risk score: older age, male sex, history of falls, physical work participation, diabetes, use of medications increasing fall risk, reduced vision, poor hearing, executive dysfunction and slow stepping. The scores were then classified into four grades (0-2 points: very low, 3 points: low, 4 points: moderate and ≥5 points: high). RESULTS: During follow-up, 112 participants fell 214 times during work. The negative binomial regression model showed that participants with higher grades had a higher incidence rate ratio [95% confidence interval] for falls than those with very low grades (low: 1.64 [1.08-2.47], moderate: 4.23 [2.82-6.34] and high: 6.12 [3.83-9.76]). The intraclass correlation coefficient for risk score was 0.86 [0.72-0.93], and the weighted kappa coefficient for grade assessment was 0.74 [0.52-0.95]. CONCLUSIONS: The OFRAT is a valid and reliable tool for estimating the occupational fall risk in older workers. It may assist occupational physicians implement strategies to prevent falls in this group.

Efficacy of influenza vaccine (Fluvax) in cancer patients on treatment: a prospective single arm, open-label study.

PURPOSE: Influenza virus infection has significant morbidity and mortality in patients with medical co-morbidities who are also immunosuppressed. The efficacy of the seasonal influenza vaccine has not been well studied in patients receiving chemotherapy. We assessed the efficacy of seasonal influenza vaccine in patients with non-haematological malignancy on active treatment (chemotherapy and targeted therapy). METHODS: A prospective single arm, open label study with 53 patients with non-haematological cancers recruited during the 2011 and 2012 influenza seasons. Participants had one dose of 2011/2012 trivalent vaccine containing strains A/California/7/2009(H1N1), A/Perth/16/2009 (H3N2) and B/Brisbane/60/2008 (Fluvax) prior to or in-between treatment cycles. Haemagglutination inhibition antibody (HIA) titres in serum were measured at baseline 3, 6 and 24 weeks. Primary endpoint: seroconversion rate (SCR) at 3 weeks. Secondary endpoints: late SCR at 6 weeks. rate of sustained sero-protection titres (SPR) at 24 weeks. Seroconversion was defined as postvaccination ≥ 4-fold increase in HIA titre and sero-protection defined as a HIA ≥ 1:40. RESULTS: The SCR at 3 weeks were 35%, 30% and 22.5% to the H1N1, H3N2 and B/Bris strains, respectively. There were no new cases of late SC at 6 weeks or 24 weeks. The SPR at 3 weeks were 72.5%, 65% and 40%, respectively, to H1N1, H3N2 and B/Bris. The SPR at 24 weeks to H1N1, H3N2 and B/Bris were 40%, 52.5% and 17.5%, respectively. CONCLUSIONS: Patients on various solid tumour treatments achieve sero-protection rate congruent with the general population. The sero-protection HIA titres were not sustained at 24 weeks postvaccination.

Molecular detection of fungal and bacterial DNA from pustules in patients with palmoplantar pustulosis: special focus on Malassezia species.

BACKGROUND: Palmoplantar pustulosis (PPP) is a distinct, chronic skin disorder characterized by intraepidermal pustules on the palms and soles. It is hypothesized that microorganisms on the skin might induce the symptoms of PPP via inflammatory cell activation. However, the microbiota has not been studied in detail because of the assumption that the pustules in PPP are sterile. AIM: To elucidate the role of microorganisms in pathogenesis of PPP. METHODS: PCR analysis was performed of microbial DNA fragments in the pustules of patients with PPP. The sequence of the D1/D2 LSU 26s rRNA gene and that of the 16S rRNA gene was used for fungal and bacterial DNA detection, respectively. RESULTS: In total, 71 samples were carefully collected from the pustules of patients with PPP. Fungal DNA bands were detected in 68 samples, and fungi including Malassezia spp. were identified in 30 of 71 samples (42.3%). Malassezia restricta was the most frequently encountered fungus (14/71; 19.7%). However, bacterial DNA was not detected by the methods used. Furthermore, identical fungal DNA was not detected in the outer lid of the pustules, suggesting that the fungi detected within the pustule did not derive from contamination via the skin surface. CONCLUSIONS: In the present study, we demonstrated for the first time that certain pustules in patients with PPP contain fungal DNA fragments, especially those of Malassezia spp. Our findings provide new insights on the role of skin microbiota in the pathogenesis of PPP.

The risk of interstitial lung disease during biological treatment in Japanese patients with psoriasis.

BACKGROUND: With the increasing use of biological agents for the treatment of psoriasis, the numbers of patients with interstitial lung disease (ILD) associated with biologics have also increased. Many of these cases were associated with tumour necrosis factor (TNF)-α inhibitors, but cases associated with other families of biologics have also been reported in Japan. AIM: To analyse the background factors of patients who developed ILD, and to discuss better management of biological treatment. METHOD: We reviewed 246 patients with psoriasis who were treated with biological agents in our department to identify any pulmonary adverse events (AEs). Data on patients who developed ILD were extracted to analyse background factors, clinical type of psoriasis, time to onset of ILD, pre-existing ILD, smoking habit and prescribed drugs. RESULTS: Pulmonary AEs were seen in 22 cases, of which 11 were diagnosed as drug-induced ILD. The causative drugs were mainly TNF-α inhibitors, accounting for eight cases (six treated with infliximab, two with adalimumab). The remaining three cases were associated with secukinumab, ustekinumab and ixekizumab (n = 1 each). Notably, these three cases also had a history of drug-induced ILD. CONCLUSION: Patients with a history of drug-induced ILD seem to be more susceptible to developing another ILD induced by biologics, even if treated with interleukin-17 inhibitors. Thorough screening of risk factors and evaluation for eligibility, and careful monitoring during treatment are the best solutions to avoid serious pulmonary AE. Early detection and precise diagnosis of pulmonary AEs, especially differentiation from infectious diseases, is essential for managing biological treatment.

Primary solitary fibrous tumour of the prostate: A case report and literature review.

INTRODUCTION: Solitary fibrous tumour (SFT) is a rare mesenchymal tumour with intermediate malignant potential. Although this tumour arises in several sites, prostatic SFT is an extremely rare neoplasm and may prove confusing owing to the lack of clinical experience because of tumour rarity. The diagnosis may be further difficult because SFTs can manifest positive immunoreactivity for CD34 and progesterone receptor, which are known markers of prostatic stromal tumours. Herein, we describe a case of prostatic SFT that was difficult to differentiate from a prostatic stromal tumour of uncertain malignant potential because of positive immunoreactivity to CD34 and progesterone receptor. CASE REPORT: A 40-year-old Japanese man presented with lower abdominal pain. Computed tomography revealed a prostatic mass; furthermore, prostate core needle biopsy revealed proliferating bland spindle cells, without necrosis or prominent mitoses. Tumour cells were positive for CD34 and progesterone receptor on immunohistochemical analysis; thus, a prostatic stromal tumour of uncertain malignant potential was initially suspected. However, as the tumour cells showed positive immunoreactivity for STAT6, the final diagnosis was an SFT of the prostate. The patient underwent tumour resection, and at the 6-month postoperative follow-up, neither local recurrence nor distant metastasis occurred. CONCLUSION: For an accurate diagnosis of an SFT of the prostate, STAT6 immunohistochemistry should be conducted for all mesenchymal tumours of the prostate. When STAT6 immunohistochemical analysis is unfeasible, pathologists should be aware that the morphological and immunohistochemical characteristics of SFT variable from case to case and diagnose with combined analysis of several immunohistochemical markers.

Long-term efficacy and safety of ixekizumab in Japanese patients with erythrodermic or generalized pustular psoriasis: subgroup analyses of an open-label, phase 3 study (UNCOVER-J).

BACKGROUND: Erythrodermic and generalized pustular psoriasis are rare, difficult to treat forms of psoriasis. In previous reports, we documented 24- and 52-week findings of an open-label, phase 3 trial (UNCOVER-J) of ixekizumab in Japanese patients with erythrodermic or generalized pustular psoriasis; most patients responded to treatment and maintained response through 52 weeks. OBJECTIVE: To assess the long-term (>3 years) efficacy and safety of ixekizumab in Japanese patients with erythrodermic or generalized pustular psoriasis. METHODS: These subgroup analyses were of a partial population of patients from UNCOVER-J (NCT01624233; Sponsored by Eli Lilly and Company), specifically those with erythrodermic psoriasis (N = 8) or generalized pustular psoriasis (N = 5). These patients received 160 mg ixekizumab at Week 0, ixekizumab 80 mg every 2 weeks through Week 12, and ixekizumab 80 mg every 4 weeks thereafter up to Week 244. This regimen is consistent with the regimen approved in Japan for plaque, erythrodermic, and generalized pustular psoriasis and psoriatic arthritis. Efficacy assessments included Global Improvement Score (GIS), Psoriasis Area and Severity Index (PASI), dermal symptoms (for patients with generalized pustular psoriasis), Dermatology Life Quality Index (DLQI) and Itch Numeric Rating Scale (NRS). Safety assessments included treatment-emergent adverse events and adverse events of special interest. RESULTS: Most patients had a GIS of resolved or improved from Week 12 onwards, and all patients had early and sustained improvement in PASI and dermal symptom (generalized pustular psoriasis only) scores. Mean improvements in DLQI and Itch NRS at Week 12 were sustained through Week 244. Ixekizumab was well tolerated over 3 years of treatment in patients with erythrodermic psoriasis or generalized pustular psoriasis, and no new safety concerns were identified. CONCLUSION: These findings suggest that ixekizumab can be an effective long-term treatment option for erythrodermic or generalized pustular psoriasis.

Sézary syndrome managed with histone deacetylase inhibitor followed by anti-CCR4 monoclonal antibody.

A 70-year-old man presented to our clinic with a 10-year history of recurrent pruritic erythema and plaques on his trunk and limbs. Based on the pathological findings and monoclonal rearrangement of the T-cell receptor (TCR)-Cß1 gene, mycosis fungoides (T2N0M0B0 stage IB) was diagnosed. Despite combination therapy including histone deacetylase inhibitor (vorinostat), the symptoms slowly evolved into Sézary syndrome (SS; T4N1M0B2) over 4 years, with dense infiltrates due to atypical lymphocytes expressing CCR4 developing in the entire dermis. Anti-CCR4 monoclonal antibody (mogamulizumab) treatment was started. After seven courses, the CCR4-positive atypical lymphocytes decreased in the dermis to levels below those seen at the outset of treatment. To our knowledge, there is no previous report of a case of SS managed with vorinostat followed by mogamulizumab demonstrating such a remarkable change in the pathological state following treatment.

Analysis of treatment goal alignment between Japanese psoriasis patients and their paired treating physicians.

BACKGROUND: Appropriate goal-oriented treatment strategies are important for optimal treatment outcomes and may prevent under-treatment. As treatment goals vary by patient, a study to examine treatment goals is more meaningful when patients and their physicians are paired. There has not been any study that examines alignment between paired psoriasis patients and physicians in real-world clinical practice using skin clearance as a treatment goal indicator. OBJECTIVES: To evaluate treatment goal alignment between psoriasis patients and their paired physicians, and to quantitatively identify factors associated with goal misalignment. METHODS: The study was a nationwide multicenter cross-sectional observational study. Subjects were physician-reported moderate-to-severe psoriasis patients with a history of systemic treatments, directly paired with their treating physicians. Subjects completed surveys independently. Treatment goals included seven categories, and patient-physician pairs were grouped as 'aligned' or 'misaligned' when the answers were the same or different, respectively. RESULTS: A total of 425 pairs (mean response rate, 94.7%) of responses were collected from 54 sites (64.8% general practitioners or clinics; 35.2% university or large hospitals). Treatment goal misalignment was found in 67.9% of the patient-physician pairs. The misalignment was mainly 'patient predominant' (60.9%) indicating that patients had higher goals ('complete clearance') than physicians. In the multivariate logistic regression analyses, patients' treatment expectation for 'complete clearance' [odds ratio (OR): 1.927; 95% confidential interval (CI): 1.232-3.016] and physician rating of 'level of understanding on treatment options' being low (OR: 1.552, 95% CI; 1.082-2.227) were significant factors for treatment goal misalignment. CONCLUSIONS: The majority of treatment goal misalignment was found between paired psoriasis patients and their treating physicians in Japan. The most important contributing factors to misalignment were patients' treatment expectation for 'complete clearance' and physicians' rating of their patients' 'level of understanding on treatment options' being low.

Expression of thymidylate synthase (TS) and its prognostic significance in patients with cutaneous angiosarcoma.

Cutaneous angiosarcoma (CA) is extremely rare, and little is known about the biological significance of possible biomarkers for chemotherapeutic agents. Thymidylate synthase (TS) is an attractive target for cancer treatment in various human neoplasms. It remains unclear whether the expression of TS is associated with the clinicopathological features of CA patients. The aim of this study was to elucidate the relationship between TS expression and the clinicopathological significance in CA patients. Fifty-one patients with CA were included in this study. TS expression and Ki-67 labeling index were examined using immunohistochemical analysis. TS was positively expressed in 39% (20/51) of CA patients. No statistically significant prognostic factor was identified as a predictor of overall survival (OS) for all patients by univariate analysis, whereas a significant prognostic variable for progression free survival (PFS) was found to be the clinical stage. In addition, both univariate and multivariate analyses confirmed that positive expression of TS was a significant predictor of worse PFS in CA patients of clinical stage 1. CONCLUSION: Positive TS expression in CA was identified as a significant predictor of worse outcome in patients of clinical stage 1.

Prognostic impact of LAT1 and CD98 expression in cutaneous angiosarcoma.

L-type amino acid transporter 1 (LAT1) and CD98 are frequently expressed in various human cancers, and closely correlated with tumor aggressiveness and survival. However, little is known about the expression of LAT1 and CD98 in cutaneous angiosarcoma. The aim of this study is to investigate the clinicopathological significance of these markers in the dismal disease. A total of 52 patients with cutaneous angiosarcoma were retrospectively reviewed. Immunohistochemical staining of tumor specimens were evaluated using anti-LAT1, CD98 and Ki-67 antibodies. The rates of high expression for LAT1 and CD98 were 56% (29/52) and 79% (41/52), respectively. The frequency of high expression for CD98 was significantly higher than that for LAT1 (p=0.021). The low expression of CD98 was significantly associated with distant metastasis (p=0.044) and was identified as a significant prognostic predictor by multivariate analysis. The expression level of LAT1 was not significantly correlated with prognosis. The low expression of CD98 is a novel biomarker for predicting poor prognosis in patients with cutaneous angiosarcoma.

Efficacy of ixekizumab compared to etanercept and placebo in patients with moderate-to-severe plaque psoriasis and non-pustular palmoplantar involvement: results from three phase 3 trials (UNCOVER-1, UNCOVER-2 and UNCOVER-3).

BACKGROUND: Palmoplantar psoriasis has significant physical and emotional impact on patients and can be difficult to treat. OBJECTIVE: To evaluate the efficacy of ixekizumab in the treatment of patients with moderate-to-severe plaque psoriasis and moderate-to-severe non-pustular palmoplantar involvement. METHODS: In three phase 3, double-blind, placebo-controlled trials, patients with moderate-to-severe non-pustular plaque psoriasis [UNCOVER-1 (N = 1296), UNCOVER-2 (N = 1224), UNCOVER-3 (N = 1346)] were randomized to subcutaneous 80 mg ixekizumab every 2 or 4 weeks (Q2W, Q4W), after a 160-mg starting dose, or placebo through week 12. Additional UNCOVER-2 and UNCOVER-3 cohorts were randomized to 50 mg etanercept biweekly. Patients entering the open-label long-term extension (UNCOVER-3) received ixekizumab Q4W weeks 12-60. Moderate-to-severe palmoplantar involvement was defined as Palmoplantar Psoriasis Area and Severity Index (PPASI) ≥8. RESULTS: Twenty-eight percent of UNCOVER-1, UNCOVER-2 and UNCOVER-3 patients had baseline palmoplantar involvement (PPASI ≥0, n = 1092) and 9.1% (n = 350) had moderate-to-severe involvement, with mean baseline PPASI ~20, PASI ~24, and most (>60%) had static Physician's Global Assessment ≥4. Higher percentages of patients treated with ixekizumab vs. placebo or etanercept achieved PPASI 50 (approximately 80% vs. 32.9%, 67.8%; ixekizumab, placebo, etanercept, respectively) and PPASI 75 (approximately 70% vs. 18.8%, 44.1%; ixekizumab, placebo, etanercept, respectively) at week 12 (all P < 0.05). PPASI 100 was achieved by higher percentages of ixekizumab-treated patients vs. placebo (approximately 50% vs. 8.2%, P < 0.001) and ixekizumab Q2W-treated patients vs. etanercept (51.8% vs. 32.2%, P < 0.05). Outcomes were maintained or improved in patients continuing on ixekizumab Q4W through week 60. Differences between ixekizumab and placebo or etanercept were statistically significant as early as week 1. CONCLUSION: In a subpopulation analysis of patients from phase 3 trials with moderate-to-severe non-pustular palmoplantar involvement and moderate-to-severe plaque psoriasis, ixekizumab treatment resulted in greater and more rapid improvements than placebo and etanercept at week 12; improvements were sustained with continued treatment.

A linking bridge between histopathological analysis and molecular assay in microbiology.

No abstract available.

Development of an oncolytic HSV vector fully retargeted specifically to cellular EpCAM for virus entry and cell-to-cell spread.

Oncolytic herpes simplex virus (HSV) vectors have attracted increasing attention as novel anti-cancer agents. HSV entry is triggered by the binding of glycoprotein D (gD) to its receptors, such as herpesvirus entry mediator or nectin-1. We have recently reported the construction of a fully retargeted HSV platform that incorporates single-chain antibodies (scFv) into gD to mediate entry exclusively via tumor-associated antigens. In this study, we created an scFv directed against epithelial cell adhesion molecule (EpCAM), a recognized carcinoma-associated antigen, and inserted it into the retargeted HSV platform that is ablated for gD recognition of its canonical receptors and contains the entry-enhancing mutations in gB we previously identified. We observed that both initial entry and subsequent cell-to-cell spread of the retargeted virus were stringently dependent on cellular EpCAM expression. Interestingly, the retargeted virus developed larger plaques on some of the human tumor lines tested than the control virus bearing wild-type gD. Intratumoral injection of the retargeted virus revealed antitumor activity in a mouse xenograft model. These observations illustrate the versatility of our retargeted HSV platform as it allows expansion of the oncolytic virus toolbox for the treatment of diverse cancers.

Immediate Effects of Different Trunk Exercise Programs on Jump Performance.

The aim of this study was to investigate the immediate effects of trunk stabilization exercise (SE) and conventional trunk exercise (CE) programs on jump performance. 13 adolescent male soccer players performed 2 kinds of jump testing before and immediate after 3 experimental conditions: SE, CE, and non-exercise (NE). The SE program consisted of the elbow-toe, hand-knee, and back bridge, and the CE program consisted of the sit-up, sit-up with trunk rotation and back extension. Testing of a countermovement jump (CMJ) and rebound jump (RJ) were performed to assess jump performance. Jump height of the CMJ and RJ-index, contact time, and jump height of the RJ were analyzed. The RJ index was improved significantly only after SE (p=0.017). However, contact time and jump height did not improve significantly in the SE condition. Moreover, no significant interaction or main effects of time or group were observed in the CMJ. Consequently, this study showed the different immediate effect on the RJ between the SE and CE, and suggested the possibility that the SE used in this study is useful as a warm-up program to improve the explosive movements.

Effects of immersive virtual reality training on balance, gait and mobility in older adults: A systematic review and meta-analysis.

OBJECTIVE: To examine whether immersive virtual reality (VR) can improve balance, gait, mobility and fear of falling in older people. DATA SOURCES: MEDLINE, EMBASE, CINAHL, PsycINFO, ProQuest Central (Engineering and Computer Science) and reference lists of included articles. STUDY SELECTION: Randomised controlled trials that administered immersive VR training and assessed balance, gait and mobility outcomes in older adults without neurological disorders (mean age ≥ 65). Primary outcomes were standing balance (e.g. postural sway), multi-item balance scales (e.g. Berg Balance Scale), gait (e.g. gait speed) and mobility (e.g. Timed Up and Go test). Secondary outcomes comprised measures of enjoyment, fear of falling, adherence (e.g. dropout rate), feasibility/usability and adverse effects (e.g. motion sickness). RESULTS: Meta-analyses showed that immersive VR training significantly improved standing balance (SMD: 0.51, 95% CI: .15, 0.86, p = 0.005, I2 = 28% - 3 studies, n = 79) and performance on the Berg Balance Scale (MD: 2.36, 95% CI: 1.17, 3.56, p=0.0001, I2=0% - 4 studies, n = 190). No significant improvement in gait, mobility or fear of falling was found. Subgroup analyses revealed higher training doses (≥4.5 total hours) and VR interventions using non-head mounted displays were more likely to improve standing balance. No meta-analyses were conducted for enjoyment, adherence, feasibility/usability and adverse events. CONCLUSIONS: The findings indicate immersive VR has beneficial effects on balance, but not gait, mobility or fear of falling. Further research is required to examine these outcomes in trials that also include quantitative measurements of enjoyment, adherence, clinical feasibility, usability and adverse effects.