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Summary: Background: The Psoriasis Area and Severity Index (PASI) represents the gold standard for psoriasis severity assessments but is limited by its subjectivity and low intra‐ and inter‐rater consistency. Objectives: To investigate the precision and reproducibility of automated, computer‐guided PASI measurements (ACPMs) in comparison with three trained physicians. Methods: This was a comparative observational study assessing ACPMs attained by automated total‐body imaging and computerized digital image analysis in a cohort of 120 patients affected by plaque psoriasis of various severities. The level of agreement between ACPMs and physicians' PASI measurements was calculated by the intraclass correlation coefficient (ICC). The reproducibility of ACPMs in comparison with physicians' PASI measurements was investigated by performing two successive 'repeat PASI calculations' in the same patients. Results: The agreement between ACPMs and physicians' PASI calculations in 120 fully evaluable patients was high (ICC 0·86, 95% confidence interval 0·80–0·90, mean absolute difference 2·5 PASI points). Repeat ACPMs to measure the reproducibility showed an excellent ICC of 0·99 (95% confidence interval 0·98–0·99) with a mean absolute difference of 0·5 PASI points. The ACPMs thus outperformed the three physicians for intrarater reliability (mean ICC 0·86). Conclusions: The results of this first clinical study investigating ACPMs in 120 patients with psoriasis indicate a similar precision and higher reproducibility in comparison with trained physicians. Limitations arise from poorly observable body sites and from patients unable to attain predefined postures during automated image acquisition. What's already known about this topic? The Psoriasis Area and Severity Index (PASI) is the standard for psoriasis severity assessments but is limited by its subjectivity and low reproducibility. What does this study add? Automated computer‐guided PASI measurements (ACPMs) agreed with the results of trained physicians and outperformed the physicians in terms of reproducibility.ACPMs provide a first step towards a higher standardization and reproducibility of PASI measurements. Linked Comment:  Garcia‐Doval and Albrecht. Br J Dermatol 2019; 180:260–261. Respond to this article [ABSTRACT FROM AUTHOR]

Physiological changes during normal pregnancy are characterized by an inflammatory immune response and insulin resistance. Therefore, we hypothesize that gestational diabetes mellitus ( GDM) may be caused by an inappropriate adaption of the maternal immune system to pregnancy. In this study we examined the role of regulatory T cell ( Treg) differentiation for the development of GDM during pregnancy. We used six-colour flow cytometric analysis to demonstrate that the total CD4+ CD127low+/− CD25+ forkhead box protein 3 ( Fox P3+) Treg pool consists of four different Treg subsets: naive CD45 RA+ Tregs, HLA-DR− CD45 RA− memory Tregs ( DR− Tregs) and the highly differentiated and activated HLA- DRlow+ CD45 RA− and HLA- DRhigh+ CD45 RA− memory Tregs ( DRlow+ and DRhigh+ Tregs). Compared to healthy pregnancies, the percentage of CD4+ CD127low+/− CD25+ Fox P3+ Tregs within the total CD4+ T helper cell pool was not different in patients affected by GDM. However, the suppressive activity of the total CD4+ CD127low+/− CD25+ Treg pool was significantly reduced in GDM patients. The composition of the total Treg pool changed in the way that its percentage of naive CD45 RA+ Tregs was decreased significantly in both patients with dietary-adjusted GDM and patients with insulin-dependent GDM. In contrast, the percentage of DR−-memory Tregs was increased significantly in patients with dietary-adjusted GDM, while the percentage of DRlow+ and DRhigh+ memory Tregs was increased significantly in patients with insulin-dependent GDM. Hence, our findings propose that alterations in homeostatic parameters related to the development and function of naive and memory Tregs may cause the reduction of the suppressive capacity of the total Treg pool in GDM patients. However, as this is an exploratory analysis, the results are only suggestive and require further validation. [ABSTRACT FROM AUTHOR]

Background: The SYNCHRONOUS-study investigates simultaneous ASV-ablation with great saphenous vein (GSV) treatment in endovenous laser ablation (EVLA) for preventing varicose vein recurrence. This sub-study examines complication rates associated with prophylactic ASV-ablation., Methods: Among 1173 patients with refluxing GSV, 604 underwent GSV-ablation only, and 569 received additional ASV-ablation. Complication rates were compared over 6 months., Results: Approximately 80% of patients were complication-free with minor bruising and dysesthesia being most common complications. After 6 months, additional prophylactic ASV-ablation did not increase the rate of complications compared to GSV-only treatment., Conclusion: The 6-months follow-up data suggests that prophylactic ASV-closure, alongside GSV-treatment, is safe, with similar complication rates to GSV-only EVLA., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

This paper outlines the development and psychometric evaluation of the Fears and Worries at Nighttime-Young Children (FAWN-YC) scale; a parent-rated measure for children aged 3-5 years. Based on previous literature, it was hypothesised that the measure would be represented by a six-factor solution, with four clusters of fear types and two behavioural manifestations of fears. Exploratory factor analysis (EFA; N = 436) and confirmatory factor analysis (CFA; N = 383), resulted in a final 17 items that loaded onto 3 factors: Nighttime Fear Focus (8 items, α = 0.92), Bedtime/Sleep Avoidance and Interference (5 items, α = 0.90), and Dark Fear (4 items, α = 0.88). Evidence of convergent validity was found through strong associations between the total score and subscales of the FAWN-YC with measures of child anxiety, fear, sleep, externalizing and conduct problems. Furthermore, there was support for divergent validity (through a very weak to no relationship with a measure of prosocial behaviours), and evidence for temporal stability was also established with 2-week test-retest reliability. Overall, the results provide strong preliminary evidence for the reliability and validity of the FAWN-YC total score and subscales. Implications for the use of the measure in research and clinical practice are discussed., (© 2024. The Author(s).)

Erythropoietin-producing hepatocellular receptor A2 (EphA2), is a receptor tyrosine kinase involved in cell-cell interactions. It is known to be overexpressed in various tumors and is associated with poor prognosis. EphA2 has been proposed as a target for theranostic applications. Low molecular weight peptide-based scaffolds with low nanomolar affinities have been shown to be ideal in such applications. Bicyclic peptides have emerged as an alternative to traditional peptides for this purpose, offering affinities comparable to antibodies due to their constrained nature, along with high tissue penetration, and improved stability compared to linear counterparts. This study presents the development and comprehensive in vitro and in vivo preclinical evaluation of BCY18469, a novel EphA2-targeting bicyclic peptide-based radiotheranostic agent. Methods: The EphA2-targeting Bicycle ® peptide BCY18469 was identified through phage-display and chemically optimized. BCY18469 was radiolabeled with 68 Ga, 177 Lu and 111 In. The physicochemical properties, binding affinity and internalization as well as specificity of the peptide were evaluated in vitro . In vivo PET/MR and SPECT/CT imaging studies were performed using [ 68 Ga]Ga-BCY18469 and [ 111 In]In-BCY18469, respectively, along with biodistribution of [ 177 Lu]Lu-BCY18469 up to 24 h post injection in HT1080- and PC-3-tumor bearing BALB/c nu/nu EphA2-overexpressing xenograft mouse models. Results: The EphA2-targeting bicyclic peptide BCY18469 showed high binding affinity toward human and mouse EphA2 (1.9 and 3.8 nM, respectively). BCY18469 specifically bound and internalized into EphA2-expressing HT1080 cells. Imaging studies showed high tumor enrichment at early time-points (SUV of 1.7 g/mL at 1 h p.i. and 1.2 g/mL at 2 h p.i. in PET/MRI, HT1080 xenograft) with tumor contrast as early as 5 min p.i. and kidney-mediated clearance. Biodistribution studies revealed high early tumor uptake (19.5 ± 3.5 %ID/g at 1 h p.i., HT1080 xenograft) with SPECT/CT imaging further confirming these findings (5.7 ± 1.5 %ID/g at 1 h p.i., PC-3 xenograft). Conclusion: BCY18469 demonstrated high affinity, specific targeting of EphA2, a favorable biodistribution profile, and clearance through renal pathways. These findings underscore the potentially important role of bicyclic peptides in advancing radiotheranostic approaches and encourage additional translational research., Competing Interests: Competing Interests: This work was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) DFG-grant 423813989/GRK2606 and DFG-grant 430609257/INST 39/1165-1, funding was also received from BicycleTx Limited. Anusha R. Regupathy, Ben Blakeman, Francesca Wood, Philip Huxley and Gemma E. Mudd were full time employees of Bicycle Therapeutics at the time in which the work was conducted, and all authors own/owned stock or stock options in Bicycle Therapeutics. GM is a named inventor on patent applications relating to compounds described in this work. All other authors have declared that no competing interest exists., (© The author(s).)

Background: Defining hidradenitis suppurativa (HS) subtypes was previously limited by small sample sizes and poor interrater reliability; no study has investigated subtype treatment responses. The objective of this analysis was to characterize HS clusters in adult patients with moderate to severe HS and evaluate secukinumab treatment responses between clusters., Methods: Clusters were identified via an unsupervised machine learning clustering analysis using baseline data from the randomized, placebo-controlled SUNSHINE (NCT03713619) and SUNRISE (NCT03713632) phase 3 trials. To assess treatment responses, patients received secukinumab every 2 (SECQ2W) or 4 weeks (SECQ4W) or placebo, for 16 weeks, after which, placebo patients randomly switched to SECQ2W/SECQ4W, and SECQ2W/SECQ4W patients maintained their original treatment, until week 52. Baseline outcomes included patient characteristics, disease characteristics and severity, HS-associated comorbidities and previous treatment exposures. Treatment response was assessed via the HS clinical response (HiSCR), abscess and inflammatory nodule (AN) count, flares and NRS30 (skin pain)., Results: Based on baseline data, three clusters were identified from 1084 patients (Cluster 1: 54.1%, Cluster 2: 17.8%, Cluster 3: 28.1%). Cluster 1 was predominantly female (65.4%) and was characterized by milder HS. Cluster 2 had more patients from the Asia Pacific, Middle East and Africa region (58.5%) and was characterized by moderate HS. Cluster 3 had the highest rates of previous exposure to biologics (45.9%) and prior HS-related surgeries (47.5%) and was characterized by severe HS. SECQ2W and SECQ4W demonstrated efficacy versus placebo in all clusters at week 16; SECQ2W and SECQ4W efficacy was maintained to week 52. SECQ2W treatment showed a trend for greater efficacy versus SECQ4W in Cluster 3 through week 52., Conclusions: Three HS clusters were identified. Secukinumab demonstrated benefit over placebo in all clusters. However, patients with more severe disease may take longer to respond and more frequent secukinumab dosing may be required for these patients., Trial Registration: SUNSHINE (NCT03713619) and SUNRISE (NCT03713632)., (© 2024 The Author(s). Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Objectives: This study aimed to investigate the impact of post-interventional compression therapy on clinical outcomes after endovenous laser ablation (EVLA) of incompetent saphenous veins., Methods: This prospective, controlled, multicenter study in Germany involved 493 varicose vein patients followed-up for 6 months., Results: Compression therapy significantly reduced symptoms compared to no compression (VCSS: 1.4 ± 1.6 vs 2.2 ± 2.2; p = .007). Post-interventional therapy duration of up to 14 days was found to be most effective for improving patient-reported disease severity ( p < .001) and higher quality of life ( p = .001). Patient compliance was high (82%), and non-compliance was linked to worse disease severity (VCSS 1.4 ± 1.5 vs 2.1 ± 2.3, p = .009)., Conclusion: In conclusion, post-interventional compression therapy is beneficial by reducing symptoms and improving quality of life. High patient compliance with the therapy is observed, and non-compliance is associated with worse disease severity., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease associated with a substantial disease burden. Secukinumab has previously been reported to have sustained efficacy with a favourable safety profile in patients with moderate-to-severe HS. It is unknown whether prior biologic exposure affects the efficacy and safety of secukinumab., Objectives: To investigate the efficacy and safety of secukinumab in patients with moderate-to-severe HS based on prior exposure to -biologics., Methods: This was an analysis of the SUNSHINE and SUNRISE phase III trials of secukinumab in patients with moderate-to-severe HS. Patients were randomized at baseline to receive secukinumab every 2 (SECQ2W) or 4 weeks (SECQ4W), or placebo for 16 weeks. After week 16, patients on the SECQ2W and SECQ4W schedules remained on the same treatment regimen, while patients randomized to placebo were switched to either SECQ2W or SECQ4W up to week 52. Assessments based on prior exposure to biologics included Hidradenitis Suppurativa Clinical Response (HiSCR), abscess and inflammatory nodule (AN) count, flare rates, HS-related pain [numerical rating scale 30 (NRS30)], 55% reduction in the International Hidradenitis Suppurativa Severity Score System (IHS4-55), Dermatology Life Quality Index, EuroQol-5D and safety., Results: Overall, 1084 patients were randomized in the SUNSHINE and SUNRISE trials and included in this analysis; 255 (23.5%) were biologic-experienced [SECQ2W (n = 80); SECQ4W (n = 81); placebo (n = 94)] and 829 (76.5%) were biologic-naïve [SECQ2W (n = 281); SECQ4W (n = 279); placebo (n = 269)]. At week 16, responses were more efficacious for secukinumab than for placebo with regard to HiSCR in patients who were biologic-experienced {SECQ2W 37.0% [odds ratio (OR) 1.60, 95% confidence interval (CI) 0.83-3.08]; SECQ4W 38.8% [OR 1.67, 95% CI 0.86-3.22]; placebo 27.3%} and biologic-naïve [SECQ2W 45.6% (OR 1.64, 95% CI 1.15-2.33); SECQ4W 45.4% (OR 1.61, 95% CI 1.13-2.29); placebo 34.2%]. Similar results were observed for AN count, NRS30 and IHS4-55. The higher response seen at week 16 with secukinumab was sustained, with a trend toward improvement over time, through to week 52 in both subgroups. Additional efficacy was observed for quality-of-life assessments, and no differences in safety between subgroups were observed., Conclusions: Regardless of prior biologic exposure, secukinumab was efficacious in improving the signs and symptoms of HS. This finding positions secukinumab as the first option in patients who are biologic-naïve, as well as in patients who have previously been treated with other biologic therapy, based on individual patient needs., Competing Interests: Conflicts of interest C.C.Z. reports consultancy/advisory boards disease-­relevant honoraria from Boehringer Ingelheim, Incyte, InflaRx, Janssen, Novartis, Regeneron, Sanofi, UCB and Viatris; has received speaker fees from Almirall, Novartis and UCB; is President of the European Hidradenitis Suppurativa Foundation (EHSF) e.V., coordinator of the ALLOCATE Skin Group of the ERN-Skin, chair of the Acne/Rosacea/Hidradenitis Suppurativa Task Force group of the European Academy of Dermatology and Venerology (EADV), and Editor of EADV News. He is co-copyright holder of the International Hidradenitis Suppurativa Severity Score System (IHS4) on behalf of the EHSF e.V. His institution has received disease-relevant grants from Boehringer Ingelheim, InflaRx, Novartis and UCB for his participation as a clinical investigator. T.P. has received consulting fees from AbbVie, Almirall, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galderma, Incyte, Janssen, LEO Pharma, Novartis, Pfizer, Sanofi Genzyme, Sun Pharma, UCB and Vyne. D.P. reports consultancy, investigator, advisory board or data safety monitoring board honoraria from Bickel Biotechnology, Biofrontera, BMS, Dermira, LEO Pharma, US Novartis Pharmaceuticals, Pfizer, Regeneron and Sanofi. D.P.’s institution has received grants/research funding for the role of investigator from Almirall, Amgen, AOBiome, Asana Biosciences, Bickel Biotechnology, Celgene, Dermira, Eli Lilly, LEO Pharma, Menlo Therapeutics, Novartis Pharmaceuticals, Novo Nordisk, Ortho Dermatologics, Pfizer and Regeneron. M.B.W. is an employee of and stockholder in Novartis Ireland Ltd. A.O. has been principal investigator in clinical trials sponsored by AbbVie, Alfasigma, Almirall, Amgen, Difa Cooper, Celgene, Eli Lilly, Galderma, Janssen, Laboratori Farmacologici Milanesi, LEO Pharma, Novartis, Pfizer, Pierre Fabre, Regeneron, Sanofi, UCB Pharma and Boehringer Ingelheim. A.O.’s institution has received disease-relevant grants from AbbVie, Alfasigma, Almirall, Amgen, Difa Cooper, Celgene, Eli Lilly, Galderma, Janssen, Laboratori Farmacologici Milanesi, LEO Pharma, Novartis, Pfizer, Pierre Fabre, Regeneron, Sanofi, UCB Pharma and Boehringer Ingelheim. A.O. has received speaker fees from AbbVie, UCB, LEO Pharma, Novartis, Pfizer and Eli Lilly. M.S.A. has been the principal investigator for clinical trials funded by Novartis, Arcutis Biotherapeutics, Galderma Laboratories, Eli Lilly, AbbVie, Pfizer, Concert Pharmaceuticals, Dermira, UCB, Incyte, Boehringer Ingelheim, Amgen, Evelo Sciences, LEO Pharma, Bristol Myers Squibb, Dice Therapeutics, Kiniksa Pharmaceuticals, Zai Lab, Sanofi and Bausch Health; and has been on advisory boards for Amgen, AbbVie, Sanofi, Novartis, Incyte, Boehringer Ingelheim, UCB, Arcutis, Bristol Myers Squibb and Bausch Health. X.L. is an employee of Novartis Pharma Co., Ltd. China. L.U., A.L.M., I.A. and I.L. are employees and stockholders of Novartis Pharma AG, Switzerland. S.R. is an employee and stockholder of Novartis Pharmaceuticals Corp., USA. P.M.-B. has received honoraria for acting as a consultant and/or as a speaker for Regeneron, Pfizer, Eli Lilly, AbbVie, Janssen, Novartis, LEO Pharma, Almirall, Sanofi, Viatris, L’Oréal, Organon, Cantabria Labs, Evelo Biosciences and CSL; and has been principal investigator in clinical trials supported by Pfizer, Biogen, Janssen, Amgen, AbbVie, Sanofi, and Novartis., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Management of prostate cancer (PC) might be improved by combining external beam radiotherapy (EBRT) and prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) with lutetium-177 ( 177 Lu)-labeled PSMA inhibitors. We hypothesized a higher efficacy of the combination due to augmentation of the radiation dose to the tumor and interactions of EBRT with PSMA expression potentially increasing radiopharmaceutical uptake. Therefore, this study analyzed the influence of radiation on PSMA expression levels in vitro . The results were translated to evaluate the efficacy of the combination of photon EBRT and [ 177 Lu]Lu-PSMA-617 in a murine PC xenograft model. Finally, a clinical case report on a combined elective field EBRT with RLT dose escalation illustrates a proof-of-concept. Methods: PSMA gene and protein expression were assessed in human PSMA-overexpressing LNCaP cells after irradiation using reverse transcription quantitative polymerase chain reaction (RT-qPCR), flow cytometry and On-Cell Western assays. In the in vivo therapy study, LNCaP tumor-bearing BALB/c nu/nu mice were irradiated once with 2 Gy X-ray EBRT and injected with 40 MBq [ 177 Lu]Lu-PSMA-617 after 4 h or received single or no treatment (n = 10 each). Tumor-absorbed doses by [ 177 Lu]Lu-PSMA-617 were calculated according to the Medical Internal Radiation Dosimetry (MIRD) formalism after deriving time-activity curves using a gamma probe. An exemplified patient case is demonstrated where fractionated EBRT (54 Gy to prostate; 45 Gy to pelvic lymphatics) and three cycles of [ 177 Lu]Lu-PSMA-617 (3.4-6.0 GBq per cycle) were sequentially combined under concurrent androgen deprivation for treating locally advanced PC. Results: At 4 h following irradiation with 2-8 Gy, LNCaP cells displayed a PSMA protein upregulation by around 18% relative to non-irradiated cells, and a stronger upregulation on mRNA level (up to 2.6-fold). This effect was reversed by 24 h when PSMA protein levels were downregulated by up to 22%. Mice treated with the combination therapy showed significantly improved outcomes regarding tumor control and median survival (p < 0.0001) as compared to single or no treatment. Relative to monotherapy with PSMA-RLT or EBRT, the tumor doubling time was prolonged 1.7- or 2.7-fold and the median survival was extended by 24% or 60% with the combination, respectively. Additionally, tumors treated with EBRT exhibited a 14% higher uptake of the radiopharmaceutical as evident from the calculated tumor-absorbed dose, albeit with high variability in the data. Concerning the patient case, the tri-modality treatment was well tolerated and the patient responded with a long-lasting complete biochemical remission for five years following end of PSMA-RLT. The patient then developed a biochemical relapse with oligo-recurrent disease on follow-up imaging. Conclusion: The present preclinical and clinical data demonstrate that the combination of EBRT with dose escalation by PSMA-RLT improves tumor control and potentially prolongs survival. This may pave the way for further clinical investigations of this approach to explore the curative potential of the combination therapy., Competing Interests: Competing Interests: This work was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) - grant BA 6696/2-1 and DFG - grant 423813989/GRK2606. ME and ACE hold patent rights on PSMA-targeting inhibitors., (© The author(s).)

Competing Interests: Conflicts of interest Xiaoling Wei is an employee of Novartis. Anna Passera, Elisa Muscianisi, Lorenz Uhlmann, Li Chen, Santiago G Moreno, Ruvie Martin, Marc Vandemeulebroecke, Deborah Keefe, Shoba Ravichandran, Magdalena B. Wozniak are employees of Novartis and hold company stock.

This paper outlines the development and psychometric evaluation of the Manifestations and Vulnerabilities of Behavioural Insomnia in Childhood Scale (MAVBICS), an instrument intended to assess the manifestations of, and factors underpinning, child behavioural insomnia. The MAVBICS comprises two sections: a more general sleep and bedtime information section (Section 1), and a psychometric measure of six theoretically derived factors that underlie, contribute to, and are manifestations of, child sleep problems (Section 2), that is the focus of this research. Study 1 comprised an exploratory factor analysis of Section 2 items (EFA; n = 328 parents of children aged 3-12 years), with a final 25 items found to load highly onto 6 factors; Sleep Maintenance Problems (4 items, α = 0.88), Co-Sleeping Behaviours (4 items, α = 0.93), Bedtime Routines (5 items, α = 0.82), Bedtime Resistance (5 items, α = 0.88), Bedtime Worries (3 items, α = 0.85) and Bedtime Fears (4 items, α = 0.86). Study 2 comprised a confirmatory factor analysis (CFA) of Section 2 items and tests of convergent validity (n = 313), with results confirming the factor structure and providing evidence for convergent validity through correlations in expected directions between MAVBICS scores and other sleep, anxiety and behaviour measures. Study 3 tested the test-retest reliability of Section 2 items (n = 53), and found support for the temporal stability of the MAVBICS over a 2-week period. Overall, the results provide strong preliminary evidence for the validity of the MAVBICS total score and its subscales, although the Bedtime Routines subscale may be less useful., (© 2023. The Author(s).)

We consider the statistical analysis of clinical trial designs with multiple simultaneous treatments per subject and multiple raters. The work is motivated by a clinical research project in dermatology where different hair removal techniques were assessed based on a within-subject comparison. We assume that clinical outcomes are assessed by multiple raters as continuous or categorical scores, e.g. based on images, comparing two treatments on the subject-level in a pairwise manner. In this setting, a network of evidence on relative treatment effects is generated, which bears strong similarities to the data underlying a network meta-analysis of clinical trials. We therefore build on established methodology for complex evidence synthesis and propose a Bayesian approach to estimate relative treatment effects and to rank the treatments. The approach is, in principle, applicable to situations with any number of treatment arms and/or raters. As a major advantage, all available data is brought into a network and analyzed in one single model, which ensures consistent results among the treatment comparisons. We obtain operating characteristics via simulation and illustrate the method with a real clinical trial example., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: Breast cancer (BC) is the most common malignancy among women and prognosis is strongly influenced by tumor subtype. Neoadjuvant chemotherapy (NAC) is the standard treatment for both locally advanced- and early-stage triple-negative and Her2-positive BC. Pathologic complete response (pCR) to NAC is an important predictor of patient outcomes. Neutrophil-to-lymphocyte-ratio (NLR) in peripheral blood is associated with prognosis in various malignancies. Here, we investigated the value of the pretreatment NLR as a response predictor in neoadjuvant-treated patients with BC., Methods: A retrospective chart analysis of 862 patients with invasive BC treated with NAC at the Heidelberg University Hospital during 2003-2015 was conducted. NLR was calculated as the ratio of the absolute neutrophil and lymphocyte counts in peripheral blood, and pCR was defined as absence of invasive or in situ carcinoma in breast and axillary lymph nodes., Results: A total of 151 patients with invasive BC who underwent NAC were included in this study. NLR tended to be higher in the pCR group than the non-pCR group (p < 0.1). Analyses of BC subtypes demonstrated that NLR was significantly higher in the pCR- compared with the non-pCR group (3.304 vs. 2.379, respectively; p = 0.048) in patients with luminal B/Her2-negative tumors. Further, we found a significant difference in NLR according to remission status in postmenopausal patients (2.861 vs. 2.313, respectively; p = 0.043)., Conclusion: NLR was significantly higher only for patients achieving pCR in the Luminal B/Her2-negative and postmenopausal subgroups. Hence, NLR is a candidate additional predictive factor in patients with Luminal B/Her2-negative BC., (© 2022. The Author(s).)

Background: Few therapeutic options are available for patients with moderate-to-severe hidradenitis suppurativa. We aimed to assess the efficacy of secukinumab in patients with moderate-to-severe hidradenitis suppurativa in two randomised trials., Methods: SUNSHINE and SUNRISE were identical, multicentre, randomised, placebo-controlled, double-blind phase 3 trials done in 219 primary sites in 40 countries. Patients aged 18 years old or older with the capacity to provide written informed consent and with moderate-to-severe hidradenitis suppurativa (defined as a total of ≥5 inflammatory lesions affecting ≥2 distinct anatomical areas) for at least 1 year were eligible for inclusion. Included patients also agreed to daily use of topical over-the-counter antiseptics on the areas affected by hidradenitis suppurativa lesions while on study treatment. Patients were excluded if they had 20 or more fistulae at baseline, had ongoing active conditions requiring treatment with prohibited medication (eg, systemic biological immunomodulating treatment, live vaccines, or other investigational treatments), or met other exclusion criteria. In both trials, patients were randomly assigned (1:1:1) by means of interactive response technology to receive subcutaneous secukinumab 300 mg every 2 weeks, subcutaneous secukinumab 300 mg every 4 weeks, or subcutaneous placebo all via a 2 mL prefilled syringe in a double-dummy method as per treatment assignment. The primary endpoint was the proportion of patients with a hidradenitis suppurativa clinical response, defined as a decrease in abscess and inflammatory nodule count by 50% or more with no increase in the number of abscesses or in the number of draining fistulae compared with baseline, at week 16, assessed in the overall population. Hidradenitis suppurativa clinical response was calculated based on the number of abscesses, inflammatory nodules, draining fistulae, total fistulae, and other lesions in the hidradenitis suppurativa affected areas. Safety was assessed by evaluating the presence of adverse events and serious adverse events according to common terminology criteria for adverse events, which were coded using Medical Dictionary for Regulatory Activities terminology. Both the SUNSHINE, NCT03713619, and SUNRISE, NCT03713632, trials are registered with ClinicalTrials.gov., Findings: Between Jan 31, 2019, and June 7, 2021, 676 patients were screened for inclusion in the SUNSHINE trial, of whom 541 (80%; 304 [56%] women and 237 [44%] men; mean age 36·1 years [SD 11·7]) were included in the analysis (181 [33%] in the secukinumab every 2 weeks group, 180 [33%] in the secukinumab every 4 weeks group, and 180 [33%] in the placebo group). Between the same recruitment dates, 687 patients were screened for inclusion in the SUNRISE trial, of whom 543 (79%; 306 [56%] women and 237 [44%] men; mean age 36·3 [11·4] years) were included in the analysis (180 [33%] in the secukinumab every 2 weeks group, 180 [33%] in the secukinumab every 4 weeks group, and 183 [34%] in the placebo group). In the SUNSHINE trial, significantly more patients in the secukinumab every 2 weeks group had a hidradenitis suppurativa clinical response (rounded average number of patients with response in 100 imputations, 81·5 [45%] of 181 patients) compared with the placebo group (60·7 [34%] of 180 patients; odds ratio 1·8 [95% CI 1·1-2·7]; p=0·0070). However, there was no significant difference between the number of patients in the secukinumab every 4 weeks group (75·2 [42%] of 180 patients) and the placebo group (1·5 [1·0-2·3]; p=0·042). Compared with the placebo group (57·1 [31%] of 183 patients), significantly more patients in the secukinumab every 2 weeks group (76·2 [42%] of 180 patients; 1·6 [1·1-2·6]; p=0·015) and the secukinumab every 4 weeks group (83·1 [46%] of 180 patients; 1·9 [1·2-3·0]; p=0·0022) had a hidradenitis suppurativa clinical response in the SUNRISE trial. Patient responses were sustained up to the end of the trials at week 52. The most common adverse event by preferred term up to week 16 was headache in both the SUNSHINE (17 [9%] patients in the secukinumab every 2 weeks group, 20 [11%] in the secukinumab every 4 weeks group, and 14 [8%] in the placebo group) and SUNRISE (21 [12%] patients in the secukinumab every 2 weeks group, 17 [9%] in the secukinumab every 4 weeks group, and 15 [8%] in the placebo group) trials. No study-related deaths were reported up to week 16. The safety profile of secukinumab in both trials was consistent with that previously reported, with no new or unexpected safety findings detected., Interpretation: When given every 2 weeks, secukinumab was clinically effective at rapidly improving signs and symptoms of hidradenitis suppurativa with a favourable safety profile and with sustained response up to 52 weeks of treatment., Funding: Novartis Pharma., Competing Interests: Declaration of interests ABK reports grants from AbbVie, Anapyts Bio, Aristea, Bristol Myers Squibb, ChemoCentryx, Eli Lilly, Incyte, Janssen, Moonlake, Novartis, Pfizer, UCB, and Sonoma Bio and fellowship funding from AbbVie and Janssen paid to her institution; royalties from BIDMC; consulting fees from AbbVie, Alumis, Bayer, Bristol Myers Squibb, Boehringer-Ingelheim, Eli Lilly, FIDE, Novartis, Moonlake, Janssen, Pfizer, Priovant, Sonoma Bio, Sanofi, Target RWE, UCB, and Ventyx; stock in Ventyx; serving on advisory boards for Target RWE; serving as an advisory council member to the National Institute of Health Director; and serves on the board of directors of Almirall. GBEJ reports grants from AbbVie, Boehringer-Ingelheim, CSL Behring, Regeneron, InflaRx, Novartis, LEO Foundation, and UCB, paid to their institution, and honoraria for advisory board meetings from Coloplast, Union Therapeutics, Toosonix, Boehringer-Ingelheim, Kymera, Sanofi, Viela Bio, ChemoCentryx, LEO Pharma, Afyx, Incyte, InflaRx, Janssen Cilag, Novartis, and UCB. AA reports consulting fees from AbbVie, Boehringer-Ingelheim, InflaRx, and UCB, paid to their institution, and consulting fees from Novartis, AbbVie, and Boehringer-Ingelheim. ZR reports consulting fees and honoraria from AbbVie, Amgen, Janssen-Cilag, Novartis, UCB, Sanofi; consulting fees from Celltrion; personal fees for attending meetings or for travel from AbbVie, Janssen-Cilag, Novartis, UCB, and Sanofi; and payment for expert testimony from AbbVie, Amgen, Celltrion, Janssen-Cilag, Novartis, and UCB. ABG reports research and educational grants from AnaptysBio, Janssen, Novartis, Ortho Dermatologics, Sun Pharma, BMS, and UCB Pharma, paid to their institution; consulting fees from Amgen, AnaptysBio, Avotres Therapeutics, Boehringer-Ingelheim, Bristol Myers Squibb, Dermavant, Eli Lilly, Janssen, Novartis, Pfizer, Sanofi, Sun Pharma, UCB Pharma, and DiCE Therapeutics; honoraria as an advisory board member, or non-promotional speaker from Amgen, AnaptysBio, Avotres Therapeutics, Boehringer-Ingelheim, Bristol Myers Squibb, Dermavant, Eli Lilly, Janssen, Novartis, Pfizer, Sanofi, Sun Pharma, and UCB Pharma; is a president of International Dermatology Outcome Measures; and holds stock options in XBiotech, for work on a rheumatoid arthritis project. FGB reports consulting fees from AbbVie, Novartis, and UCB; honoraria and support for attending meetings or travel from AbbVie, Janssen Cilag, Novartis, and UCB; and served on a Data Safety Monitoring Board or Advisory Board for AbbVie, Boehringer-Ingelheim, Janssen Cilag, Novartis, UCB, Incyte, and Moonlake. CP reports consulting fees from Almirall, AbbVie, Amgen, BMS, Boehringer-Ingelheim, Celgene, GSK, Janssen, LEO Pharma, Eli Lilly, Merck, Novartis, Pfizer, Sanofi, and UCB and served on a Data Safety Monitoring Board or Advisory Board for IQVIA. EJGB reports grants from Horizon 2020 ImmunoSep and RISKinCOVID, Horizon Health EPIC-CROWN-2, Sobi, bioMérieux, MSD, Abbott, Novartis, UCB, and AbbVie, paid to their institution, and consulting fees from Sobi, Pfizer, Abbott, ThermoFisher, and Menarini. APV reports consulting fees from Janssen-Cilag; payment or honoraria from AbbVie, Almirall, BMS, Janssen-Cilag, Leo Pharma, Eli Lilly, MSD, Novartis, and UCB; and support for attending meetings or travel from Janssen-Cilag and UCB. AS reports consulting fees from Regeneron, Novartis, and AbbVie, paid to their institution; payment or honoraria from AbbVie, Novartis, Regeneron, Sanofi; support for attending meetings or travel from AbbVie, Janssen-Cilag, Novartis, and Sanofi; and fees for participation on a Data Safety Monitoring Board or Advisory Board from AbbVie, Novartis, and Sanofi. FR reports grants from ALK-Abelló, Allergopharma, Blueprint Medicines, Mylan, Novartis, and ThermoFisher; served on a Data Safety Monitoring Board or Advisory Board for ALK-Abelló, Boehringer-Ingelheim, Blueprint Medicines, Leo Pharma, and UCB; and is an active member of the German Association of Allergy and Clinical Immunology. AR and his institution received grants from AbbVie, Alvotech, Amgen, AnaptysBio, Argenx, Biothera, Bristol Myers Squibb, Celgene, Celltrion, Dermira, Galderma, Inflarx, Janssen, Kiniksa, Kymab, Leo Pharma, Novartis, Pfizer, Trevi Therapeutics, and UCB; payment or honoraria from Chema Rzeszow, Eli Lilly, Leo Pharma, Novartis, Sandoz, and Takeda; and served on a Data Safety Monitoring Board or Advisory Board for AbbVie, Galderma, Sandoz, and Sanofi Aventis. IL reports payment or honoraria from Novartis and support for attending meetings or travel from Sanofi. TP reporfts grants from Almirall, Incyte, and Pfizer, paid to their institution, and consulting fees from AbbVie, Almirall, Bristol Myers Squibb, Eli Lilly, Galderma, Incyte, Janssen, LEO Pharma, Novartis, and UCB. AM reports consulting fees from AbbVie, Boehringer-Ingelheim, Jansen, Eli Lilly, Novartis, Novo Nordisk, Sandoz, and UCB; payment for expert testimony or honoraria from AbbVie, Boehringer-Ingelheim, Jansen, Eli Lilly, Novartis, Novo Nordisk, Sandoz, and UCB; and support for attending meetings or travel from AbbVie, Novartis, Jansen, and UCB. PM-B reports consulting fees from AbbVie, Almirall, Eli Lilly, Janssen, LEO Pharma, Novartis, Pfizer, and Sanofi; payment or honoraria from AbbVie, Almirall, Janssen, LEO Pharma, Eli Lilly, Novartis, Organon, Pfizer, Sanofi, and Viatris; support for attending meetings or travel from AbbVie, Almirall, Janssen, LEO Pharma, Eli Lilly, Novartis, and Sanofi; and served on a Data Safety Monitoring Board or Advisory Board for AbbVie, Janssen, LEO Pharma, Eli Lilly, Novartis, Pfizer, and Sanofi. GK reports consulting fees from Bayer; payment or honoraria from AbbVie, Abbott, Actelion Pharmaceuticals, Amgen, Basilea Pharmaceutica, Biogen IDEC, Boehringer-Ingelheim, Bristol Myers Squibb, Celgene, Hexal, Janssen-Cilag, LEO Pharma, Eli Lilly, MSD, Mylan, Novartis, Parexel, Pfizer, and UCB; support for attending meetings or travel from AbbVie, Abbott, Amgen, Basilea Pharmaceutica, Celgene, Janssen-Cilag, LEO Pharma, MSD, Novartis, Pfizer, Sanofi, and UCB; and served on a Data Safety Monitoring Board or Advisory Board for AbbVie, Abbott, Amgen, Basilea, Bayer, Boehringer-Ingelheim, Bristol Myers Squibb, Celgene, Janssen-Cilag, LEO Pharma, Eli Lilly, Novartis, and UCB. P-AB reports consulting fees from Novartis, AbbVie, Pfizer, and UCB pharma; payment or honoraria from Novartis and AbbVie; support for attending meetings or travel from Novartis; and served on a Data Safety Monitoring Board or Advisory Board for Novartis. MBW, ALM, XW, LU, AP, DK, RM, CF, LC, MV, SR, and EM are employees of Novartis and hold company stock. RS is Director and Founder of Samson Medical, has participated in pharmaceutical advisory boards for Eli Lilly and Company, Pfizer, and Leo Pharmaceutical, has participated in speaker bureaus for AbbVie, Novartis, and Pfizer, and has acted as a principal investigator in clinical trials for AbbVie, Aerotech, Akesobio, Amgen, Arcutis, Arena, Ascend AstraZeneca, Bayer, Biotherapeutics Boehringer-Ingelheim, Bristol-Myer Squibb, Celgene, Coherus BioSciences, Connect, Demira, Eli Lilly, Galderma, GlaxoSmithKline, F Hoffman–La Roche, Janssen, MedImmune, Merck, Merck Sharpe & Dohme, Novartis, Oncobiologics, Pfizer, Principia, Regeneron, Roche, Reistone Biopharma, Samson Clinical, Sanofi-Genzyme, Sun Pharma UCB, Valeant, and Zai Labs. RS is President of the Australasian Hair and Wool Research Society, and Vice President of the International Society of Dermatology and The International Academy of Dermatology. LPR declares no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: COVID-19 has led to disruptions to the lives of Australian families through social distancing, school closures, a temporary move to home-based online learning, and effective lockdown. Understanding the effects on child and adolescent mental health is important to inform policies to support communities as they continue to face the pandemic and future crises. This paper sought to report on mental health symptoms in Australian children and adolescents during the initial stages of the pandemic (May to November 2020) and to examine their association with child/family characteristics and exposure to the broad COVID-19 environment., Methods: An online baseline survey was completed by 1327 parents and carers of Australian children aged 4 to 17 years. Parents/carers reported on their child's mental health using five measures, including emotional symptoms, conduct problems, hyperactivity/inattention, anxiety symptoms and depressive symptoms. Child/family characteristics and COVID-related variables were measured., Results: Overall, 30.5%, 26.3% and 9.5% of our sample scored in the high to very high range for emotional symptoms, conduct problems and hyperactivity/inattention, respectively. Similarly, 20.2% and 20.4% of our sample scored in the clinical range for anxiety symptoms and depressive symptoms, respectively. A child's pre-existing mental health diagnosis, neurodevelopmental condition and chronic illness significantly predicted parent-reported child and adolescent mental health symptoms. Parental mental health symptoms, having a close contact with COVID-19 and applying for government financial assistance during COVID-19, were significantly associated with child and adolescent mental health symptoms., Conclusion: Our findings show that Australian children and adolescents experienced considerable levels of mental health symptoms during the initial phase of COVID-19. This highlights the need for targeted and effective support for affected youth, particularly for those with pre-existing vulnerabilities.

Understanding the mechanisms through which internalisation of societal body standards lead to negative outcomes for women is important to inform prevention and treatment strategies targeting female body image issues and problematic eating and exercise behaviours. This study investigated the mediating roles of body surveillance and social comparison on the relationship between fit-ideal internalisation and a range of negative eating and body image related outcomes. Participants were 448 females, aged 16-25 years who completed self-report measures of fit-ideal internalisation, body surveillance, social comparison, body dissatisfaction, dieting, bulimic behaviours and compulsive exercise. Consistent with hypotheses, the results of parallel mediation analyses suggested that both body surveillance and social comparison mediated the relationship between fit-ideal internalisation and body dissatisfaction, dieting and bulimic behaviours. However, only social comparison was found to mediate the relationship between fit-ideal internalisation and compulsive exercise. The results suggest both body surveillance and social comparison are mechanisms by which fit internalisation detriments women's body image, making them potentially useful treatment targets for future research., Competing Interests: Declaration of competing interest The authors have no conflict of interest or competing interests. The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Edible flowers have been widely consumed fresh in drinks, salads, desserts and salty dishes. This study evaluated the color parameters, chemical composition (phenolics, sugars, organic acids), volatiles compounds and microbiota (bacterial and fungal communities) in edible purple flowers (Torenia fournieri F. Lind.) cultivated in biocompost and traditional organic systems. Torenia flowers cultivated in biocompost had high (p < 0.05) contents of anthocyanins (cyanidin 3,5-diglucoside, delphinidin 3-glucoside), flavonols (quercitin 3-glycoside, myricetin and rutin), sugars (rhamnose and glucose), organic acids (citric and succinic), aldehydes (hexanal, cis-2-hexenal and trans-2-hexenal), and alcohols (trans-2-hexenol and 3-ethyl-4-methylpentan-1-ol). Flowers cultivated in biocompost showed higher (p < 0.05) abundance Cyanobacteria and Basidiomycota bacterial and fungal phyla, respectively, than flowers cultivated in traditional system. The high abundance of Oxyphotobacteria and Dothideomycetes classes, Acetobacterales and Cladosporiales orders, Oxyphotobacteriaceae and Cladosporiaceae families, and Raoultella and Cladosporium genera characterized torenia flowers cultivated in biocompost. The cultivation system influenced the torenia flowers microbiota and composition, primarily due to environmental response and enhanced uptake of nutrients. Our findings indicate that cultivation of torenia using the agroindustrial based-biocompost improves bioactive and volatiles contents in more purple and fruity flavored flowers, rendering flowers more attractive for consumption., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)