Asprosin contributes to vascular remodeling in hypertensive rats via superoxide signaling.

OBJECTIVE: Proliferation and migration of vascular smooth muscle cells (VSMCs) contribute to vascular remodeling. Asprosin, a newly discovered protein hormone, is involved in metabolic diseases. Little is known about the roles of asprosin in cardiovascular diseases. This study focused on the role and mechanism of asprosin on VSMC proliferation and migration, and vascular remodeling in a rat model of hypertension. METHODS AND RESULTS: VSMCs were obtained from the aortic media of 8-week-old male Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Asprosin was upregulated in the VSMCs of SHR. For in vitro studies, asprosin promoted VSMC proliferation and migration of WKY and SHR, and increased Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) activity, NOX1/2/4 protein expressions and superoxide production. Knockdown of asprosin inhibited the proliferation, migration, NOX activity, NOX1/2 expressions and superoxide production in the VSMCs of SHR. The roles of asprosin in promoting VSMC proliferation and migration were not affected by hydrogen peroxide scavenger, but attenuated by superoxide scavenger, selective NOX1 or NOX2 inhibitor. Toll-like receptor 4 (TLR4) was upregulated in SHR, TLR4 knockdown inhibited asprosin overexpression-induced proliferation, migration and oxidative stress in VSMCs of WKY and SHR. Asprosin was upregulated in arteries of SHR, and knockdown of asprosin in vivo not only attenuated oxidative stress and vascular remodeling in aorta and mesentery artery, but also caused a subsequent persistent antihypertensive effect in SHR. CONCLUSIONS: Asprosin promotes VSMC proliferation and migration via NOX-mediated superoxide production. Inhibition of endogenous asprosin expression attenuates VSMC proliferation and migration, and vascular remodeling of SHR.

Phase Transition and Luminescent Property Change Induced by Different Organic Cations in One-Dimensional Double Perovskites.

Double perovskites (DPs) have attracted attention in the field of luminescence due to their inherent broadband emission of self-trapping excitons. In this work, we choose [(CH3)3NCH2CHCH2]+ and [CH3CHOHCH2NH2]+ as organic cations to synthesize two new organic-inorganic hybrid DPs, [(CH3)3NCH2CHCH2]2KInCl6 (1) and [CH3CHOHCH2NH2]2KInCl6 (2). The [KCl6]3- and [InCl6]3- octahedra are interchangeably connected by sharing two opposite faces, forming a one-dimensional coordination chain. Each K atom coordinates with six chlorine atoms in 1, while it coordinates with two oxygen atoms in addition to the six chlorine atoms in 2. The coordination between ions K and O in compound 2 may have significantly reduced its luminescence. As a result, compound 1 shows bright-yellow light with a quantum yield of more than 90%, while 2 shows weak blue light with a quantum yield of only 0.98%. In addition, different from no phase transition found in 2, 1 undergoes a reversible phase transition at 324/307 K in the heating-cooling cycle. Through structural and spectral analysis and density functional theory calculation, we conclude that the larger degree of [InCl6]3- octahedral distortion and the larger anion distance (In···In) also cause the PLQY of compound 1 to be higher than that of compound 2.

Insights Into Colorectal Cancer Screening: A Multidatabase Cohort Study of Over 1.5 Million Taiwanese.

INTRODUCTION: Colorectal cancer (CRC) remains a significant public health concern. This study aims to provide a comprehensive understanding of the effectiveness of fecal immunochemical test (FIT) screening on CRC incidence and mortality, leveraging the scale of over 1.5 million randomly selected Taiwanese and more than 11.7 million person-years of follow-up. METHODS: This prospective cohort study merges data from 3 robust Taiwanese health databases: the CRC screening program, cancer registration, and death registration databases. Incidence and mortality rates of CRC were calculated based on age, sex, urbanization, and past screening status. Cox proportional hazard models were used to assess the association between screening statuses and CRC incidence or mortality, adjusting for age, sex, and urbanization levels. Statistical analysis of the data was conducted in 2021-2022. RESULTS: FIT screening was associated with a 33% reduction in CRC incidence and a 47% reduction in mortality. The study identified a dose-response relationship between the fecal hemoglobin concentration (f-HbC) levels and CRC risk. Participants with consistent FIT-negative results had significantly reduced CRC incidence and mortality risks, while those with one or more positive FIT results faced increased risks. Notably, compliance with follow-up examinations after a positive FIT significantly lowered mortality risk. CONCLUSIONS: This large-scale study validates the efficacy of FIT screening in reducing CRC incidence and mortality. It offers a nuanced understanding of how various screening statuses impact CRC risks, thus providing valuable insights for public health strategies aimed at CRC prevention.

IL-23 past, present, and future: a roadmap to advancing IL-23 science and therapy.

Interleukin (IL)-23, an IL-12 cytokine family member, is a hierarchically dominant regulatory cytokine in a cluster of immune-mediated inflammatory diseases (IMIDs), including psoriasis, psoriatic arthritis, and inflammatory bowel disease. We review IL-23 biology, IL-23 signaling in IMIDs, and the effect of IL-23 inhibition in treating these diseases. We propose studies to advance IL-23 biology and unravel differences in response to anti-IL-23 therapy. Experimental evidence generated from these investigations could establish a novel molecular ontology centered around IL-23-driven diseases, improve upon current approaches to treating IMIDs with IL-23 inhibition, and ultimately facilitate optimal identification of patients and, thereby, outcomes.

Projected Time for the Elimination of Cervical Cancer Under Various Intervention Scenarios: Age-Period-Cohort Macrosimulation Study.

BACKGROUND: The World Health Organization aims for the global elimination of cervical cancer, necessitating modeling studies to forecast long-term outcomes. OBJECTIVE: This paper introduces a macrosimulation framework using age-period-cohort modeling and population attributable fractions to predict the timeline for eliminating cervical cancer in Taiwan. METHODS: Data for cervical cancer cases from 1997 to 2016 were obtained from the Taiwan Cancer Registry. Future incidence rates under the current approach and various intervention strategies, such as scaled-up screening (cytology based or human papillomavirus [HPV] based) and HPV vaccination, were projected. RESULTS: Our projections indicate that Taiwan could eliminate cervical cancer by 2050 with either 70% compliance in cytology-based or HPV-based screening or 90% HPV vaccination coverage. The years projected for elimination are 2047 and 2035 for cytology-based and HPV-based screening, respectively; 2050 for vaccination alone; and 2038 and 2033 for combined screening and vaccination approaches. CONCLUSIONS: The age-period-cohort macrosimulation framework offers a valuable policy analysis tool for cervical cancer control. Our findings can inform strategies in other high-incidence countries, serving as a benchmark for global efforts to eliminate the disease.

Enhanced visible light photocatalytic performance of carbon and oxygen co-doped carbon nitride with a three-dimensional structure: Performance and mechanism study.

As a cost-effective photocatalyst, carbon nitride (g-C3N4) holds tremendous promise for addressing energy shortages and environmental pollution. However, its application is limited by disadvantages such as low specific surface area and easy recombination of photogenerated electron-hole pairs. This study introduces C and O co-doped g-C3N4 with a three-dimensional (3D) structure achieved through a straightforward one-step calcination process, demonstrating excellent photocatalytic activity of hydrogen production and oxytetracycline degradation, with superoxide radicals as the primary active species. We propose a plausible enhanced mechanism based on systematic characterizations and density functional theory calculations. The 3D structure confers a substantial specific surface area, enhancing both the adsorption area and active sites of catalysts while bolstering structural stability. Co-doping optimizes the band structure and electric conductivity of the catalyst, facilitating rapid migration of photogenerated charges. The synergistic effects of these enhancements significantly elevate the photocatalytic performance. This study presents a convenient and feasible method for the preparation of dual-regulated photocatalysts with outstanding performance.

A three-dimensional liquid diode for soft, integrated permeable electronics.

Wearable electronics with great breathability enable a comfortable wearing experience and facilitate continuous biosignal monitoring over extended periods1-3. However, current research on permeable electronics is predominantly at the stage of electrode and substrate development, which is far behind practical applications with comprehensive integration with diverse electronic components (for example, circuitry, electronics, encapsulation)4-8. Achieving permeability and multifunctionality in a singular, integrated wearable electronic system remains a formidable challenge. Here we present a general strategy for integrated moisture-permeable wearable electronics based on three-dimensional liquid diode (3D LD) configurations. By constructing spatially heterogeneous wettability, the 3D LD unidirectionally self-pumps the sweat from the skin to the outlet at a maximum flow rate of 11.6 ml cm-2 min-1, 4,000 times greater than the physiological sweat rate during exercise, presenting exceptional skin-friendliness, user comfort and stable signal-reading behaviour even under sweating conditions. A detachable design incorporating a replaceable vapour/sweat-discharging substrate enables the reuse of soft circuitry/electronics, increasing its sustainability and cost-effectiveness. We demonstrated this fundamental technology in both advanced skin-integrated electronics and textile-integrated electronics, highlighting its potential for scalable, user-friendly wearable devices.

Coupled Stable Isotope Tracing and Sulfamic Acid Reduction (SIT-SAR) Method to Determine the Ammonia and Nitrite Oxidation Rates in Water and Sediments.

Herein, a method was developed to measure the ammonia oxidation rate (Ra) and the nitrite oxidation rate (Rn) of water and sediment samples using a coupled stable isotope tracing and sulfamic acid reduction (SIT-SAR) method. 15NH4+ was used as a tracer to determine the ammonia oxidation rates (Ra) by calculating the concentrations of produced 15NO2- and 15NO3- during incubation, while 15NO2- was used as a tracer to determine the nitrite oxidation rates (Rn) by calculating the increase of 15NO3- during incubation. 15NO2- was chemically reduced to 29N2 with 15 mmol·L-1 sulfamic acid (SA). 15NO3- was first reduced to 15NO2- with a zinc-cadmium reducing agent, and then 15NO2- was subsequently reduced to 29N2 with SA. The produced 29N2 was measured by a membrane inlet mass spectrometer (MIMS). Under optimized experimental conditions, this method provides a sensitive (detection limit: 0.5 µmol·L-1) and precise (relative standard deviation: 4.80% for 15NO2-, 3.82% for 15NO3-) approach to quantify the concentrations of 15NO2- (0.5-150 µmol·L-1) and 15NO3- (0.5-120 µmol·L-1) in water and sediment samples over a wide range of salinities (0-30‰) with excellent calibration curves (R2 ≥ 0.999). This method was a successful application to estuarine water and sediments along the salinity gradient. Overall, the SIT-SAR method provided a rapid, accurate, and cost-effective means to determine Ra and Rn simultaneously.

Efficacy of psychosocial interventions to reduce affective symptoms in sexual and gender minorities: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Lesbian, gay, bisexual, transgender, and queer/questioning (LGBTQ) individuals are more likely than cisgender heterosexuals to experience mental, physical, and sexual health issues. A promising contemporary strategy to address the issue of affective symptoms in sexual and gender minorities (SGM) is psychosocial intervention. OBJECTIVE: To systematically evaluate the effect of psychosocial interventions on the improvement of affective symptoms in SGM, and to provide a reference for the implementation of effective psychological interventions for SGM with affective symptoms. METHODS: Between the date of database construction until December 10, 2022, a computerized search of the English-language literature published both nationally and worldwide was done. 8 literature databases and 3 additional gray databases were searched. We gathered randomized controlled trials that used psychological interventions for SGM. To evaluate risk bias in included papers in accordance with Cochrane cooperation criteria, we used Review Manager 5.4 software. In conjunction with post-test and follow-up data, mean differences were standardized using Stata 12.0 software. Subgroup analysis was used to investigate the cause of heterogeneity. The study was conducted strictly in accordance with PRISMA guidelines, and it was registered on the PROSPERO platform (CRD42023408610). RESULTS: This review covered 18 research, and 14 studies were included in the meta-analysis. A total of 1194 study cases, including 706 cases from the control group and 488 cases from the experimental group, were included in these investigations. Compared to the control group, the psychosocial intervention group had significantly lower levels of depression (standardized mean difference (SMD) = -0.17;95% CI = [-0.30, -0.04]; p = 0.012) and anxiety (SMD = -0.22; 95% CI = [-0.41, -0.04]; p = 0.01), but no significant differences were found for distress (SMD = -0.19; 95% CI = [-0.45,0.07]; p = 0.021). CONCLUSION: According to this study, psychosocial interventions helped lessen the symptoms of depression and anxiety in SGM but had no significant effect on their psychological distress. To assess the impact of psychological intervention on SGM, more randomized controlled trials with larger sample sizes and numerous follow-up times should be done.

Exploring the multifaceted impact of lanthanides on physiological pathways in human breast cancer cells.

Lanthanum (La) and cerium (Ce), rare earth elements with physical properties similar to calcium (Ca), are generally considered non-toxic when used appropriately. However, their ions possess anti-tumor capabilities. This investigation explores the potential applications and mechanisms of LaCl3 or CeCl3 treatment in triple-negative breast cancer (TNBC) cell lines. TNBC, characterized by the absence of estrogen receptor (ERα), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) expression, is prone to early metastasis and resistant to hormone therapy. Our results demonstrate that La/Ce treatment reduces cell growth, and when combined with cisplatin, it synergistically inhibits cell growth and the PI3K/AKT pathway. La and Ce induce oxidative stress by disrupting mitochondrial function, leading to protein oxidation. Additionally, they interfere with protein homeostasis and induce nucleolar stress. Furthermore, disturbance in F-actin web formation impairs cell migration. This study delves into the mechanism by which calcium-like elements La and Ce inhibit breast cancer cell growth, shedding light on their interference in mitochondrial function, protein homeostasis, and cytoskeleton assembly.

11B NMR of the Morphological Evolution of Traditional Chinese Medicine Borax.

This article applies nuclear magnetic resonance technology to the study of boron-containing traditional Chinese medicine, in order to explore the morphological evolution of boron elements in traditional Chinese medicine. Borax is a traditional Chinese medicine with anti-corrosion, anti-inflammatory, antibacterial, and anticonvulsant effects. It is made by boiling, removing stones, and drying borax minerals like borate salts. This article introduces an 11B nuclear magnetic resonance method for identifying and characterizing boron-containing compounds in TCM. We applied this technology to borax aqueous solutions in different chemical environments and found that with boron mixed in the form of SP2 hybridization in equilateral triangles and SP3 hybridization in equilateral tetrahedra, the pH changes in alkaline environments significantly affected the ratio of the two. At the same time, it was found that in addition to the raw material peak, boron signals of other boron-containing compounds were also detected in 20 commercially available boron-containing TCM preparations. These new boron-containing compounds may be true pharmaceutical active ingredients, and adding them directly to the formula can improve quality and safety. This article describes the detection of 11B NMR in boron-containing traditional Chinese medicine preparations. It is simple, non-destructive, and can provide chemical fingerprint studies for boron-containing traditional Chinese medicine.

The possibility of visualizing TGF-ß1 expression in ApoE-/- mice atherosclerosis using MR targeted imaging.

BACKGROUND: Endothelial TGF-ß1 signaling is a primary driver of atherosclerosis-associated vascular inflammation. Targeted imaging and inhibition of the expression of TGF-ß1 may reduce the atherosclerotic vessel wall inflammation and stop the progression of atherosclerotic plaque. PURPOSE: To investigate the possibility of the anti-TGF-ß1-ultrasmall superparamagnetic iron oxide (USPIO) specific probe as an imaging marker for the expression of TGF-ß1 in ApoE-/- mice atherosclerosis detected with 7.0-T magnetic resonance imaging (MRI). MATERIAL AND METHODS: Here, 70 ApoE-/- mice on a high-fat diet served as the experimental group and 30 C57BL/6 mice on a normal diet served as the control group. The morphology of plaques was viewed by H&E staining, and the expression and distribution of TNC and TGF-ß1 were detected by immunohistochemical staining. Another 40 mice in the experimental group were classified into a targeted group, which was administrated an anti-TGF-ß1-USPIO probe, and the pure group, which was injected with pure USPIO. RESULTS: The 7.0-T MRI showed that the relative signal intensity (rSI) changes of the targeted group decreased more than those of the pure group (-19.34 ± 0.68% vs. -5.61 ± 0.57%; P < 0.05). Histopathological analyses demonstrated expression of TGF-ß1 in atherosclerotic plaque formation progression from 10 to 28 weeks. The MR images of the expression of TGF-ß1 in atherosclerosis correlated well with the pathological progression of atherosclerotic plaque formation. CONCLUSIONS: Anti-TGF-ß1-USPIO could provide a useful molecular imaging tool for detecting and monitoring the expression of TGF-ß1 in atherosclerotic plaques by MRI.

Long-Term Safety of Guselkumab in Patients with Psoriatic Disease: An Integrated Analysis of Eleven Phase II/III Clinical Studies in Psoriasis and Psoriatic Arthritis.

INTRODUCTION: The benefit/risk profiles of biologics can be affected by comorbidities, certain demographic characteristics, and concomitant medications; therefore, it is important to evaluate the long-term safety profiles of biologics across broad patient populations. Guselkumab was well tolerated and efficacious across individual pivotal clinical studies in adults with moderate-to-severe psoriasis and/or active psoriatic arthritis (PsA). OBJECTIVES: The objective of the current analysis was to evaluate guselkumab safety in a large population of patients with psoriatic disease by pooling adverse event (AE) data from 11 phase II/III studies (seven in psoriasis; four in PsA). METHODS: Guselkumab was generally administered as 100 mg subcutaneous injections at Week 0, Week 4, then every 8 weeks (Q8W) in psoriasis studies and at Week 0, Week 4, then every 4 weeks (Q4W) or Q8W in PsA studies. Safety data were summarized for the placebo-controlled period (Weeks 0-16 in psoriasis; Weeks 0-24 in PsA) and through the end of the reporting period (up to 5 years in psoriasis; up to 2 years in PsA). Using the integrated data, incidence rates of key AEs were determined post hoc, adjusted for duration of follow-up, and reported per 100 patient-years (PYs). AE rates were also determined in subgroups of patients defined by sex, age, body mass index (BMI), and prior biologic use. RESULTS: During the placebo-controlled period, 1061 patients received placebo (395 PYs) and 2257 received guselkumab (856 PYs). Through the end of the reporting period, 4399 guselkumab-treated patients contributed 10,787 PYs of follow-up. During the placebo-controlled period, in the guselkumab and placebo groups, respectively, rates of AEs were 281 versus 272/100 PYs, and infections were 76.0 versus 72.2/100 PYs. Rates of serious AEs (5.6 vs. 7.8/100 PYs), AEs leading to discontinuation (4.9 vs. 6.6/100 PYs), serious infections (1.0 vs. 2.3/100 PYs), malignancy (0.59 vs. 0.25 patients/100 PYs), and major adverse cardiovascular events (MACE; 0.35 vs. 0.25/100 PYs) were low and comparable between guselkumab and placebo. Among guselkumab-treated patients, safety event rates through the end of the reporting period were numerically lower than or comparable with rates observed during the placebo-controlled period: AEs, 164/100 PYs; infections, 61.2/100 PYs; serious AEs, 5.4/100 PYs; AEs leading to discontinuation, 1.8/100 PYs; serious infections, 1.0/100 PYs; malignancy, 0.6/100 PYs; and MACE, 0.3/100 PYs. No AEs of Crohn's disease, ulcerative colitis, or active tuberculosis were reported among guselkumab-treated patients. In the psoriasis studies, no opportunistic infections were reported among guselkumab-treated patients. Three AEs of opportunistic infections were reported in guselkumab-treated patients with PsA (0.14/100 PYs; all after Week 52 in DISCOVER-2). AE rates were largely consistent across subgroups of guselkumab-treated patients defined by sex, age, BMI, and prior biologic use. CONCLUSIONS: In this analysis of 4399 guselkumab-treated patients with psoriatic disease followed for 10,787 PYs, guselkumab had a favorable AE profile. AE rates were similar between guselkumab- and placebo-treated patients and were consistent throughout long-term guselkumab treatment and across broad subgroups of patients with psoriatic disease. CLINICAL TRIALS REGISTRATIONS: Clinicaltrials.gov identifiers: NCT01483599, NCT02207231, NCT02207244, NCT02203032, NCT02905331, NCT03090100, NCT02325219, NCT02319759, NCT03162796, NCT03158285, and NCT03796858.

Wearable and battery-free wound dressing system for wireless and early sepsis diagnosis.

Sepsis is a severe organ dysfunction typically caused by wound infection which leads to septic shock, organ failure or even death if no early diagnosis and property medical treatment were taken. Herein, we report a soft, wearable and battery-free wound dressing system (WDS) for wireless and real-time monitoring of wound condition and sepsis-related biomarker (procalcitonin [PCT]) in wound exudate for early sepsis detection. The battery-free WDS powered by near-field communication enables wireless data transmission, signal processing and power supply, which allows portable intelligent wound caring. The exudate collection associates with soft silicone based microfluidic technologies (exudate collection time within 15 s), that can filtrate contamination at the cell level and enable a superior filtration rate up to 95% with adopting microsphere structures. The battery-free WDS also includes state-of-the-art biosensors, which can accurate detect the pH value, wound temperature, and PCT level and thus for sepsis diagnosis. In vivo studies of SD rats prove the capability of the WDS for continuously monitoring wound condition and PCT concentration in the exudate. As a result, the reported fully integrated WDS provides a potential solution for further developing wearable, multifunctional and on-site disease diagnosis.

Astaxanthin-loaded polylactic acid-glycolic acid nanoparticles ameliorate ulcerative colitis through antioxidant effects.

Introduction: Astaxanthin (AST) is a type of carotenoid with strong antioxidant effects. However, the development and use of AST are limited by its water insolubility and low bioavailability. This study aims to investigate whether AST@PLGA can inhibit UC and reveal its possible mechanism. Methods: We tested the particle size, polydispersity index, and zeta potential of AST@PLGA. Then, the in vitro release and antioxidant capacity of AST@PLGA were tested. Finally, the mouse model of colitis was established and SOD, MDA, TNF-α, IL-1ß, IL-6 and P38 as well as ERK were detected from mice. Results: Particle size, polydispersity index and zeta potential of AST @PLGA were 66.78 ± 0.64 nm, 0.247 and -9.8 ± 0.53 mV, respectively, and were stable within 14 days. Then, it was observed that the AST@PLGA nanoparticles not only maintained the effect of AST but also had a sustained release effect. Experiments in mice showed that AST@PLGA effectively reduced MDA, TNF-α, IL-1ß and IL-6 levels and increased SOD levels. AST@PLGA also downregulated the protein expression of P38 and ERK. The results showed the positive protective effect of AST@PLGA in inhibiting acute colitis. Discussion: AST@PLGA nanoparticles have good stability and alleviating effect in colitis, which could be functional foods in the future.

Screening History and 7-Year Survival in 32,099 Colorectal Cancer Patients: A Population-Based Cohort Study.

Background: It is unclear whether colorectal cancer screening history, regardless of stage, is an independent predictor of survival, and if the screening advantage persists after diagnosis. 32 099 patients with colorectal cancer were enrolled in this population-based cohort study. Methods: We used data from the Taiwan Cancer Registry on patients with a first-time diagnosis of colorectal cancer between 2013 and 2015. In addition, we utilized data from a nationwide database of colorectal cancer screening programs to evaluate patients' screening histories, and sourced outcome data from the National Death Registry, tracking patients up to the last day of 2019. Results: Compared with fecal immunochemical testing (FIT)-positive patients with a follow-up examination, the adjusted hazard ratios (95% confidence intervals) for death from colorectal cancer were 1.40 (1.26-1.56) for FIT-positive patients without a follow-up examination, 1.63 (1.48-1.78) for FIT-negative patients, and 1.76 (1.65-1.89) for never screened patients. The adjusted hazard ratios for the FIT-positive patients with a follow-up examination increased when diagnosis was delayed by more than 12 months and were 1.2 after a 2-year delay. The adjusted hazard ratios for FIT-negative patients were approximately 2.0, decreased rapidly to 1.6, and stabilized after the 9th time-to-diagnosis month. Conclusion: In colorectal cancer patients, screening history prior to diagnosis is an independent prognostic factor, regardless of cancer stage or other variables. This study recommends that physicians take screening history into account during diagnosis to optimize follow-up and management for patients at higher risk.

Five-year Maintenance of Clinical Response and Consistent Safety Profile for Guselkumab in Asian patients with Psoriasis from VOYAGE 1 and VOYAGE 2.

INTRODUCTION: Guselkumab is a human monoclonal antibody against IL-23 used in the treatment of moderate-to-severe psoriasis. This post-hoc analysis evaluated the efficacy and safety of guselkumab in the Asian subpopulation of VOYAGE 1 and VOYAGE 2 through 5 years. METHODS: The proportions of guselkumab-treated Asian patients (VOYAGE 1 and 2) achieving Psoriasis Area and Severity Index (PASI) 90 and PASI 100, Investigator's Global Assessment (IGA) scores of 0/1 and 0, and Dermatology Life Quality Index (DLQI) scores of 0/1 (week 100 through week 252) were assessed. Non-responders were patients who met the treatment failure rules. Efficacy endpoints were analyzed using the as-observed methodology (no missing data imputation) for both studies and using non-responder imputation (for patients with any missing data) in VOYAGE 1. Safety outcomes were based on pooled data through week 252. RESULTS: Response rates through week 252 for 199 Asian patients in the guselkumab group in VOYAGE 1 and VOYAGE 2, respectively, were 76.8% and 80.6% (PASI 90), 26.8% and 38.7% (PASI 100), 64.3% and 87.1% (IGA 0/1), and 26.8% and 45.2% (IGA 0). DLQI (0/1) at week 252 was achieved by 52.7% of patients in VOYAGE 1 and 61.3% in VOYAGE 2, while DLQI (0) at week 252 was achieved by 32.7% of patients in VOYAGE 1 and 40.3% in VOYAGE 2. The safety profile was similar to the global population and remained consistent through 5 years. Asian patients were followed for a total of 814 patient-years (PY). Over 85% of the guselkumab-treated patients continued treatment through week 264. The rate of serious adverse events (AEs) at week 252 was 3.07/100 PY. Rates of AEs of interest were low: serious infections, 0.74/100 PY; nonmelanoma skin cancer (NMSC), no patients; malignancies other than NMSC, 0.12/100 PY; and no major adverse cardiovascular events (MACE). CONCLUSION: These analyses confirm a continuous response over 5 years, indicating that guselkumab shows therapeutic longevity in Asian patients requiring long-term treatment for moderate-to-severe psoriasis. TRIAL REGISTRATION: ClinicalTrials.gov identifiers: VOYAGE 1 [NCT02207231] and VOYAGE 2 [NCT02207244].

Psoriasis­a long-term condition that causes a skin rash with scaly, itchy patches (plaques)­is becoming more prevalent in Asia. To control symptoms of moderate-to-severe psoriasis and achieve a strong improvement in the patient's quality of life, continuous treatment is usually needed. Guselkumab is a medicine that targets specific parts of the immune system to treat moderate-to-severe psoriasis. It is important to understand the long-term benefits of guselkumab in Asian patient populations. Our study analyzed the data from two randomized clinical trials (called VOYAGE 1 and VOYAGE 2) that studied people with moderate-to-severe plaque psoriasis. We examined results for the 199 people from Asia, including Korea and Taiwan, who took part in these studies. Overall, 162 of the 184 (86.6%) people from Asia treated with guselkumab incorporated into these studies continued the treatment for 5 years. Patients treated with guselkumab showed effective clinical responses (improvements measured by clinicians), including high skin clearance, meaning a large reduction in skin surface area affected by psoriasis. On guselkumab, patients also reported improvements in their skin-related health-related quality of life. These improvements and the efficacy of guselkumab were maintained over 5 years of follow-up. The safety results for guselkumab in the Asian subpopulation were similar to those for the global population, showing low rates of serious adverse effects, as expected from this type of medicine. Overall, our study found a favorable benefit­risk profile with continuous guselkumab treatment for 5 years in Asian people with moderate-to-severe psoriasis. This highlights that guselkumab treatment allows long-lasting control of this disease.

The Epidemiology of Palmoplantar Pustulosis: An Analysis of Multiple Health Insurance Claims and Electronic Health Records Databases.

BACKGROUND: Palmoplantar pustulosis (PPP) is a chronic inflammatory condition characterized by sterile pustules on the palms and soles. This study evaluated the epidemiology of PPP using claims and electronic health record (EHR) databases. METHODS: Patients coded for PPP in the United States (US) and Japan from 2016 to 2020 were identified. Several PPP definitions were evaluated; the specific definition (≥ 2 visits coded for PPP, the second 31-730 days after diagnosis) was chosen for characterizing PPP epidemiology. Baseline characteristics and pre- and post-diagnosis treatments were summarized. Prevalence and incidence rates were analyzed by calendar year, sex, age, and database. RESULTS: Prevalence and incidence of PPP were higher in Japan than the US. PPP prevalence increased over time. PPP occurred predominantly in adulthood and was more common among women. Features of metabolic syndromes, anxiety, and depression were more common among US PPP patients. Consistently high baseline use of anti-bacterial, anti-inflammatory/anti-rheumatic, and obstructive airway disease treatments was observed among PPP patients. Potential miscoding or misclassification of PPP limited this analysis. Prevalence estimates from databases may differ from field- and population-based approaches. CONCLUSIONS: The burden of PPP was greater in Japan than in the US. Additional studies are needed to further elucidate PPP epidemiology worldwide.

Efficacy of Guselkumab in Treating Nails, Scalp, Hands, and Feet in Patients with Psoriasis and Self-reported Psoriatic Arthritis.

INTRODUCTION: The aim of this study was to evaluate guselkumab efficacy on regional psoriasis in a subset of psoriasis patients with a self-reported psoriatic arthritis (PsA) diagnosis. METHODS: In the phase 3 VOYAGE-1 and -2 studies, at week (W)0, patients with moderate-to-severe psoriasis were randomized to guselkumab 100 mg, placebo → guselkumab 100 mg at W16 through W44, or adalimumab 80 mg then 40 mg at W1 through W48 (VOYAGE-1) or W24 (VOYAGE-2). Pooled efficacy outcomes, including scalp-specific Investigator's Global Assessment (ss-IGA), hands and/or feet Physician's Global Assessment (hf-PGA), fingernail PGA (f-PGA), Nail Psoriasis Area and Severity Index (NAPSI), and Dermatology Life Quality Index (DLQI), were compared (nominal p-values) through W24 in patients with self-reported PsA diagnosis. Response rates/percentage improvement from baseline were determined, employing treatment failure rules and non-response/no improvement data imputation. RESULTS: A total of 76, 153, and 106 psoriasis patients with self-reported PsA were randomized to the placebo, guselkumab, or adalimumab groups, respectively; the baseline characteristics of patients in all three arms were comparable. At W16, a greater proportion of guselkumab- versus placebo-treated patients achieved ss-IGA 0/1 (80.6% vs. 22.7%, p < 0.001), hf-PGA 0/1 (68.9% vs. 14.8%, p < 0.001), f-PGA 0/1 (47.6% vs. 17.0%, p < 0.001), and DLQI 0/1 (45.6% vs. 2.7%, p < 0.001) responses; mean percentage NAPSI improvement was also greater with guselkumab (39.5% vs. 6.5%, p < 0.001). At W24, patients receiving guselkumab had higher ss-IGA 0/1 (77.5% vs. 58.5%, p = 0.003) and DLQI 0/1 (47.7% vs. 34.3%, p = 0.024) response rates versus those receiving adalimumab. Response rates/mean percentage improvements at W48 (VOYAGE-1) were numerically greater with guselkumab than adalimumab (e.g., NAPSI improvement: 75.6% vs. 60.9%). CONCLUSIONS: Guselkumab-treated patients with psoriasis and self-reported PsA showed meaningful improvements in nail, scalp, and palmoplantar psoriasis. TRIAL REGISTRATION: VOYAGE-1 (ClinicalTrials.gov Identifier: NCT02207231) and VOYAGE-2 (ClinicalTrials.gov Identifier: NCT02207244).