A novel online calculator based on clinical features and hematological parameters to predict total skin clearance in patients with moderate to severe psoriasis.

BACKGROUND: Treatment responses to biologic agents vary between patients with moderate to severe psoriasis; while some patients achieve total skin clearance (TSC), a proportion of patients may only experience partial improvement. OBJECTIVE: This study was designed to identify potential predictors for achieving TSC in psoriasis patients treated with IL-17 inhibitors. It also aimed to develop an easy-to-use calculator incorporating these factors by the nomogram to predict TSC response. METHODS: A total of 381 patients with psoriasis receiving ixekizumab were included in the development cohort and 229 psoriasis patients who initiated secukinumab treatment were included in the validation cohort. The study endpoint was achieving TSC after 12 weeks of IL-17 inhibitors treatment, defined as the 100% improvement in Psoriasis Area and Severity Index (PASI 100). Multivariate Cox regression analyses and LASSO analysis were performed to identify clinical predictors and blood predictors respectively. RESULTS: The following parameters were identified as predictive factors associated with TSC: previous biologic treatment, joint involvement, genital area affected, early response (PASI 60 at week 4), neutrophil counts and uric acid levels. The nomogram model incorporating these factors achieved good discrimination in the development cohort (AUC, 0.721; 95% CI 0.670-0.773) and validation cohort (AUC, 0.715; 95% CI 0.665-0.760). The calibration curves exhibited a satisfactory fit, indicating the accuracy of the model. Furthermore, the decision curve analysis confirmed the clinical utility of the nomogram, highlighting its favorable value for practical application. Web-based online calculator has been developed to enhance the efficiency of clinical applications. CONCLUSIONS: This study developed a practical and clinically applicable nomogram model for the prediction of TSC in patients with moderate to severe psoriasis. The nomogram model demonstrated robust predictive performance and exhibited significant clinical utility. Trial registration A multi-center clinical study of systemic treatment strategies for psoriasis in Chinese population;ChiCTR2000036186; Registered 31 August 2020; https://www.chictr.org.cn/showproj.html?proj=58256 .

The role of ultrasound in screening subclinical psoriatic arthritis in patients with moderate to severe psoriasis.

OBJECTIVE: To identify patients in the subclinical psoriatic arthritis (Sub-PsA) phase by ultrasound (US) and provide a solution to screen them. METHODS: A total of 490 participants with moderate-to-severe psoriasis were evaluated. Among them, 384 participants without arthritis symptoms were enrolled into the silent psoriasis group and 106 participants with arthritis symptoms, called prodromal/active PsA phase, were enrolled into the clinical PsA group. Another 80 non-psoriasis participants were enrolled into the control group. Each participant received clinical assessments and US examinations of 60 joints, 38 tendons, and 40 entheses. We compared the incidences of synovio-enthesitis, synovitis, tenosynovitis, erosion, and dactylitis detected on US among the three groups. Subsequently, on the basis of significant US findings, we distinguished Sub-PsA from psoriasis alone (PsO) in the silent psoriasis group and analyzed the clinical characteristics, mainly including basic clinical characteristics, body surface area (BSA), and Psoriasis Area and Severity Index (PASI) score. RESULTS: Only synovio-enthesitis significantly differed between the control group and the silent psoriasis group (1.3% vs. 16.1%, p < 0.001). The knee was the most commonly involved site of synovio-enthesitis (79.0%). Taking synovio-enthesitis as the standard, 16.1% of silent psoriasis participants and 12.7% of all psoriasis participants were in the Sub-PsA phase. Furthermore, there were no differences in BSA and PASI among the three phases of PsO, Sub-PsA, and prodromal/active PsA. CONCLUSIONS: Since the psoriasis patients in Sub-PsA phase was as high as 12.7% in all patients with moderate-to-severe psoriasis, US-detected synovio-enthesitis was recommended routinely for screening them regardless of arthritis symptoms, especially in the lower limbs. KEY POINTS: • Synovio-enthesitis on ultrasound was significantly associated with subclinical psoriatic arthritis, especially in the lower limbs. • Routine ultrasound evaluation could help screen psoriasis patients in the subclinical psoriatic arthritis phase, which was as high as 12.7% in all psoriasis patients.

The efficacy and safety of dupilumab for the treatment of atopic dermatitis among Chinese patients in clinical practice: A single-center retrospective study.

Little real-work data regarding the efficacy and safety of dupilumab in the treatment of atopic dermatitis (AD) is available at present. To assess the efficacy and safety of dupilumab at 12 weeks in the treatment of AD in clinical routine clinical practice. A retrospective, single-centre study of adult patients with moderate to severe AD treated with dupilumab for 12 weeks in China. In total, 60 patients (48 male, 12 female; mean age: 53.2 ± 15.6) were enrolled in this retrospective study. These patients exhibited a mean AD disease course of 10.6 years (6.0), 30% exhibited a family history of allergies, and 31 (51.7%) had one or more allergic comorbidities. Following dupilumab treatment for 12 weeks, 83.3% and 42% of patients had achieved EASI-50 and EASI-75, respectively. Overall, adverse events (AEs) were reported by 15% of patients, with the most common being conjunctivitis, injection site reactions, and herpes simplex virus infections. Laboratory testing after 12 weeks revealed pronounced decreases in both circulating eosinophil counts (from 0.6 (0.1-2.8) to 0.3 (0.1-9.7) 109 /L) and total IgE concentrations (from 327 (2.46-2500) to 230 (47.6-2200) U/ml) in these patients. These real-world data reaffirm the safety and efficacy of dupilumab as a treatment for moderate-to-severe AD among Chinese patients in clinical practice.

Measure microbial activity driven oxygen transfer in membrane aerated biofilm reactor from supply side.

This short communication demonstrates for the first time a solely microbial activity driven oxygen influx across a microporous hollow fibre membrane via tracking changes in volume and gas composition of entrapped air supply. A U-shape manometer was used to directly reflect gas influx due to microbial activities. A pressure difference of several hundred pascal was created to draw oxygen while 25 mg-N/L of ammonium was oxidized into nitrite by active biofilm at a hydraulic retention time of 6 h. Calibrated and normalized gas compositions before and after the experiment were processed to unveil the gas exchange and estimate the actual oxygen influx across the membrane. A solely microbial activity driven oxygen influx of 10.7 mg O2/m2/h was observed. Measuring oxygen transfer from supply side provides a more straight-forward perspective on the role of active biofilm in membrane aerated biofilm reactor. The capability of the microbial activity to uptake oxygen on its own could potentially lead to greater energy savings in some MABR applications when strict aeration control is not needed.

Interleukin-33 alleviates psoriatic inflammation by suppressing the T helper type 17 immune response.

Psoriasis is a chronic inflammatory skin disease with unclear pathogenesis. Interleukin-33 (IL-33) is highly expressed in patients with psoriasis, but its role in psoriasis is unknown. The aim of this study was to investigate the possible role of IL-33 in the pathogenesis and treatment of psoriasis. IL-33 expression was determined using enzyme-linked immunosorbent assay, real-time fluorescent quantitative polymerase chain reaction and immunohistochemical staining. CD4+ T cells were sorted using magnetic beads and treated with or without IL-33. Imiquimod (IMQ) was used to induce psoriatic inflammation in mice. The frequency of immune cells was determined using flow cytometry. The cytokine level in mouse skin was measured using cytometric bead array. Our results showed that IL-33 was highly expressed in the lesional skin and serum of patients with moderate-to-severe plaque psoriasis. IL-33 inhibited the expression of IL-17 in CD4+ T cells of psoriasis patients. Subcutaneous injection of IL-33 alleviated the IMQ-induced psoriatic inflammation in mice, reduced tumor necrosis factor-α and IL-23 expression, and decreased the proportion of T helper type 17 (Th17) cells in the skin-draining lymph nodes in the mice. Our results suggest that IL-33 plays a protective role in the pathogenesis of psoriasis by suppressing Th17 cell differentiation and function. The potential therapeutic effect of IL-33 in treating psoriasis warrants further investigation.

Positive association between insulin resistance and fatty liver disease in psoriasis: evidence from a cross-sectional study.

Background: Fatty liver disease (FLD) is a common comorbidity of psoriasis and is often referred to as non-alcoholic fatty liver disease (NAFLD). However, the role of inflammation or insulin resistance (IR) in FLD is inconclusive. The study aims to explore whether FLD in psoriasis patients is more related to insulin resistance or systemic inflammation level. Methods: Data for this study were collected from the Shanghai Psoriasis Effectiveness Evaluation Cohort, a prospective cohort that examines psoriasis characteristics in the Chinese population. IR was assessed using the triglyceride glucose (TyG) and TyG-body mass index (TyG-BMI) indicators. Systemic non-specific inflammation was assessed using the neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), and systemic immune inflammation index (SII). Results: The analysis included a total of 647 patients. Subsequent logistic regression analysis revealed that NLR, dNLR, and SII were not significantly associated with FLD in psoriasis patients, while TyG and TyG-BMI showed significant associations with FLD. Subgroup analysis indicated that in the majority of subgroups, TyG and TyG-BMI were significantly associated with FLD, particularly TyG-BMI. Excluding individuals with methotrexate and acitretin resulted in consistent findings with the main analysis. Further analysis revealed a significantly higher diagnosis rate of metabolic-associated fatty liver disease (MAFLD) compared to NAFLD. Conclusions: Metabolic factors play a crucial role in FLD in patients with psoriasis, and TyG and TyG-BMI are potential predictors of FLD. Therefore, MAFLD can be recommend as a term to describe FLD in psoriasis patients. Trial registration: https://www.chictr.org.cn/showproj.html?proj=58256, identifier ChiCTR2000036186. A multi-center clinical study of systemic treatment strategies for psoriasis in Chinese population. Registered 31 August 2020.

Mainstream nitrogen removal in membrane aerated biofilm reactor at minimal lumen pressure.

Nitrogen removal via anammox is a promising and sustainable solution in mainstream wastewater treatment. To maintain stable anammox process, competitors of anammox bacteria should be suppressed while cooperators need to be favoured. This study demonstrated a synchronous aerobic and anaerobic ammonium removal process in a membrane aerated biofilm reactor (MABR) under minimal lumen pressure. By adjusting the lumen pressure, aerobic and anaerobic ammonium oxidation rate can be synchronized to minimize interference of nitrite oxidizing bacteria (NOB) by limiting NOB's access to both oxygen and nitrite. Long-term performance indicated that PN/A in MABR could be achieved at zero positive aeration pressure. Furthermore, by connecting two MABRs in series, high total nitrogen (TN) removal efficiency of 71.1% ± 5.3% was attained with a TN removal rate of 30.1 ± 3.2 mg-N/L/d. The organic carbon present in the wastewater reduced the nitrate concentration in the effluent while not affecting the overall nitrogen removal efficiency and rate. Real-time qPCR analysis suggested that the abundance of amoA gene was relatively stable while K-strategist Nitrospira 16S rRNA gene did not surge in the long-term operation. High throughput sequencing showed that Candidatus Brocadia and uncultured anaerobic ammonium oxidizing bacteria from Chloroflexi were the most abundant anammox taxa. Denitrifiers, such as Denitratisoma may be responsible to reduce the nitrate in the effluent.

NOB suppression strategies in a mainstream membrane aerated biofilm reactor under exceptionally low lumen pressure.

Integrating the aeration-efficient membrane aerated biofilm reactor (MABR) with anaerobic ammonium oxidation (anammox) could yield further reduction in energy in wastewater treatment facilities. However, nitrite oxidizing bacteria (NOB) suppression remained challenging due to the absence of intrinsic inhibition factors in mainstream conditions. This study investigated selective NOB suppression strategies in MABR under <5 kPa lumen pressure. Three MABRs were seeded from different seeding sludge, and operated under various ammonium loading rates, aeration pressure, and temporary inhibitory shock conditions. The three reactors were operated for 170-456 days depending on studied parameters. The results showed that higher ammonium loading could create a substrate-oxygen imbalance and quickly contain emergent NOB activity when aeration pressure was not excessive. In addition, lowering of aeration pressure reversed nitrite oxidizing activities without affecting ammonium oxidizing bacteria (AOB). Cultivating partial nitritation biofilm under zero positive aeration pressure slowed down the growth of NOB yet resulted in self-induced anammox activities. With the aid of temporary free ammonia (FA)/free nitrous acid (FNA) treatment, full-nitrifying biofilm could be transformed to stable partial nitritation biofilm. More than 84% nitrite accumulation ratio (NAR) was sustained during stable operation in each reactor together with an ammonium removal rate of more than 100 mg-N/L/d. Microbial analysis revealed that Nitrosomonas was the main AOB taxon in the three reactors while K-strategist Nitrospira showed presence despite low nitrite oxidizing activities. Under zero positive pressure, proliferation of Nitrospira was much slower while Candidatus Brocadia was self-induced. Furthermore, Nitrospira showed downturn after temporary inhibition treatment.

Efficacy and safety of biologics targeting IL-17 and IL-23 in the treatment of moderate-to-severe plaque psoriasis: A systematic review and meta-analysis of randomized controlled trials.

Numerous biologics are currently licensed for the treatment of psoriasis, including new drugs targeting interleukin-17 (IL-17) and interleukin-23 (IL-23). This meta-analysis evaluated the short-term (12-16 weeks) efficacy and safety of biologics targeting IL-17 and IL-23 in the treatment of moderate-to-severe plaque psoriasis. Twenty-one randomized clinical trials met the defined inclusion criteria. Our results showed that Ixekizumab (160 mg wk0 + 80 mg q2w) had the greatest probability of achieving both PASI 75 (RR 21.32, 95% CI 15.48-29.36, P < 0.00001) and PASI 90 response (RR 59.76, 95% CI 32.41-110.19, P < 0.00001) at the primary endpoint times, followed by Ustekinumab and Secukinumab. Regarding the safety profile, Tildtakizumab (200 mg, q4w) was safest (RR 0.88, 95% CI 0.78-0.99, P = 0.04), while Ixekizumab (160 mg wk0 + 80 mg q2w) showed highest risk for one or more AE (RR 1.26, 95% CI 1.15-1.38, P < 0.00001). However, there was no significant difference between the two biologics regarding one or more SAEs. Comparing to the biologics targeting IL-23, the pooled effect size favored the biological agents targeting IL-17 in terms of the PASI 75 (PASI 75: RR 17.28, 95% CI 14.51-20.58, P < 0.00001) and PASI 90 (RR 37.19, 95% CI 26.91-51.41, P < 0.00001). The rate of overall AEs was significantly higher (P < 0.00001) in biologics targeting the IL-17 (RR 1.18, 95% CI 1.12-1.24, P < 0.00001) compared to biologics targeting IL-23 (RR 0.97, 95% CI 0.91-1.04, P = 0.44), and with respect to one or more SAEs, no difference was seen between biologics targeting IL-17 and IL-23. This meta-analysis found that Ixekizumab was the most effective short-term treatment, but was ranked as the most risk therapeutic choice among the biologics involved in this study, while Tildtakizumab was the best alternative in the case of safety. Furthermore, it demonstrated that biologics inhibiting IL-17 were superior to biologics targeting IL-23 in terms of the efficacy, but posed higher risk at the same time. This study might help the clinicians and guideline developers to choose the optimal one among these biologics for the treatment of moderate-to-severe plaque psoriasis.