Silencing of maternally expressed RNAs in Dlk1-Dio3 domain causes fatal vascular injury in the fetal liver.

The mammalian imprinted Dlk1-Dio3 domain contains multiple lncRNAs, mRNAs, the largest miRNA cluster in the genome and four differentially methylated regions (DMRs), and deletion of maternally expressed RNA within this locus results in embryonic lethality, but the mechanism by which this occurs is not clear. Here, we optimized the model of maternally expressed RNAs transcription termination in the domain and found that the cause of embryonic death was apoptosis in the embryo, particularly in the liver. We generated a mouse model of maternally expressed RNAs silencing in the Dlk1-Dio3 domain by inserting a 3 × polyA termination sequence into the Gtl2 locus. By analyzing RNA-seq data of mouse embryos combined with histological analysis, we found that silencing of maternally expressed RNAs in the domain activated apoptosis, causing vascular rupture of the fetal liver, resulting in hemorrhage and injury. Mechanistically, termination of Gtl2 transcription results in the silencing of maternally expressed RNAs and activation of paternally expressed genes in the interval, and it is the gene itself rather than the IG-DMR and Gtl2-DMR that causes the aforementioned phenotypes. In conclusion, these findings illuminate a novel mechanism by which the silencing of maternally expressed RNAs within Dlk1-Dio3 domain leads to hepatic hemorrhage and embryonic death through the activation of apoptosis.

The therapeutic effect of 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol on chemically induced atopic dermatitis.

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease worldwide. However, it is still urgent to develop innovative treatments that can effectively manage refractory patients with unpredictable chronic disease courses. In this study, we evaluated the therapeutic efficacy of 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) as a novel agent for AD treatment using a human-like mouse model of AD. PLAG significantly improved 2,4-dinitrochlorobenzene (DNCB)-induced AD skin lesions compared to those in mice treated with DNCB alone. PLAG substantially modulated the AD-induced infiltration of monocytes and eosinophils into skin lesions and humoral systemic responses involving immunoglobulin E (IgE), interleukin (IL)-4, and IL-13, restoring them to a normal state. Next, we compared the therapeutic efficacy of PLAG and abrocitinib for severe AD treatment. PLAG exhibited a significant therapeutic effect on AD skin lesions compared to abrocitinib. Unlike abrocitinib, PLAG significantly reduced AD-induced eosinophil infiltration to a level similar to that observed in untreated negative controls. Notably, both PLAG and abrocitinib downregulated IgE, IL-4, and IL-13 in a similar pattern, reaching levels similar to those in the untreated negative controls. Our findings strongly suggest that PLAG may serve as a therapeutic agent for AD with an efficacy comparable to that of abrocitinib.

Matching-Adjusted Indirect Comparison of the Efficacy and Safety of Difamilast 1% and Delgocitinib 0.5% in Patients with Moderate-to-Severe Atopic Dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a chronic condition with an increasing incidence in Japan. Difamilast and delgocitinib are both new topical drugs for AD proven to be efficacious and safe in phases 2 and 3 clinical trials in Japan. However, there are no head-to-head trials comparing their efficacy and safety. The aim of this study was to determine the proportion of patients by severity and compare the clinical efficacy and safety of difamilast with delgocitinib among patients with moderate-to-severe AD using a matching-adjusted indirect comparison (MAIC). METHODS: Phase 3 clinical trials of difamilast and delgocitinib for treating AD were included. The trials had similar designs but differed in baseline population characteristics. Anchored MAIC was used to align the baseline characteristics and calculate clinical outcomes. The primary outcome was to determine severity stages of the proportion of patients with AD through Eczema Area and Severity Index (EASI), while the secondary outcome included comparing other clinical efficacy and safety of difamilast with delgocitinib. RESULTS: A total of 340 patients were selected (170 each received difamilast and placebo) from the difamilast trial, with 158 (106 received delgocitinib; 52 received placebo) from the delgocitinib trial for the analysis. After matching patients from the difamilast trial with those from the delgocitinib trial, the effective sample sizes (ESS) reduced to 32.7-43.3% of the original difamilast (treatment/placebo) patients. At week 4, the ESS in the difamilast group demonstrated no statistically significant differences in the distribution of AD severity stages, as per EASI scores, compared with the delgocitinib group. In addition, no significant differences were found in modified EASI (mEASI) scores, mEASI 50 and 75 scores, and safety outcomes between the two treatments. CONCLUSIONS: The anchored MAIC analysis indicates that difamilast treatment, like delgocitinib, is a useful option for the treatment of patients with moderate-to-severe AD in Japan.

Predictive Factors for Long-Term High Responders to Upadacitinib Treatment in Patients with Atopic Dermatitis.

Background: Upadacitinib, a Janus kinase 1 inhibitor, is an effective medicine for moderate-to-severe atopic dermatitis (AD). Identifying long-term responders to upadacitinib is crucial for optimal treatment strategies in real-world clinical practice. To identify predictive factors for long-term high responders to upadacitinib 15 mg or 30 mg, defined as achievers of investigator's global assessment (IGA) 0/1 with ≥2-point improvement from baseline IGA at week 48. Methods: A retrospective study was conducted from August 2021 to September 2023 on 63 AD patients treated with upadacitinib 15 mg and 31 patients with 30 mg. Patients of each group were categorized into long-term high responders (achievers of IGA 0/1 at week 48) and low responders (non-achievers). We compared baseline values of clinical indexes and laboratory parameters between long-term responders and nonresponders. Results: In 15 mg group, long-term high responders showed lower rate of bronchial asthma (BA), lower values of baseline eczema area and severity index (EASI) of head and neck, IgE, and systemic inflammatory response index (SIRI) compared with low responders. In 30 mg group, long-term high responders showed lower baseline levels of IgE compared with low responders. Conclusion: Patients with lower baseline EASI of head and neck, IgE, or SIRI or without BA and those with lower baseline IgE may have a higher potential to become long-term high responders to upadacitinib 15 mg and 30 mg treatment, respectively.

Influence of Leaders' Emotional Labor and Its Perceived Appropriateness on Employees' Emotional Labor.

Emotional labor is a crucial yet often overlooked aspect of effective leadership. To address this, the current study adopts the Emotion as Social Information (EASI) model as a theoretical framework to investigate the influence of leaders' emotional labor and perceived appropriateness on employees' emotional labor. A two (leaders' emotional labor strategies: surface acting vs. deep acting) by two (perceived appropriateness: appropriate vs. inappropriate) between-subjects experiment was designed with a sample of 120 front-line service employees from hotels in Shanghai. The results showed that regardless of whether the perception of a leader's surface acting was deemed appropriate or not, employees tended to perform surface acting, while the impact of the perceived appropriateness regarding the leader's deep acting was different, wherein an appropriate display of deep acting by the leader significantly influenced employees to engage in deep acting themselves. The managerial implications and limitations of the findings are also discussed.

Defining and Measuring the Scope of Atopic Dermatitis.

Atopic dermatitis (AD) has no definitive diagnostic test and has a large range of phenotypes, making it a difficult disease to assess and define. However, an agreed-upon definition of AD is important for clinical trials, population-based studies, and clinical practice. Several diagnostic criteria systems have been proposed to fill these needs, with none considered the gold standard. To further aid in standardized assessment of AD patients, numerous disease severity and quality-of-life measurement tools have been proposed. There is similarly no gold standard and efforts are ongoing to develop a single consensus scale. Finally, assessment of AD-associated comorbidities, including allergic/immunologic conditions, psychiatric disorders, and metabolic/cardiac conditions, is important when evaluating this patient population.

Real-World Clinical, Psychosocial and Financial Burden of Atopic Dermatitis: Results from the Spanish Cohort of the MEASURE-AD Trial. / Carga clínica, psicosocial y económica de la dermatitis atópica en vida real: resultados de la cohorte española del estudio MEASURE-AD.

BACKGROUND: Atopic dermatitis (AD) is one of the most prevalent skin diseases, but there are numerous knowledge gaps surrounding the impact this disease has on quality of life (QoL), mental health, and out-of-pocket expenses involved in the management of AD. The available scientific evidence on the multidimensional burden of AD is usually based on studies with measures reported by patients themselves. METHODS: In this context, the MEASURE-AD trial was developed as a cross-sectional, multicenter, multinational trial using patient- and physician-reported measures to characterize the multidimensional burden of AD in adults with moderate-to-severe AD. RESULTS: This paper presents the results of the Spanish cohort. We found that Spanish adults with moderate-to-severe AD and high EASI score (21.1-72) had a significantly increased disease burden, high severity of symptoms such as itch and sleep disturbances, impaired mental health and QoL, higher use of health care resources, and more out-of-pocket expenses than patients with low EASI scores (0-7 or 7.1-21). CONCLUSIONS: This study provides information to better understand disease burden, and identify aspects to be improved in the management of AD.

Wearable 12-Lead ECG Acquisition Using a Novel Deep Learning Approach from Frank or EASI Leads with Clinical Validation.

The 12-lead electrocardiogram (ECG) is crucial in assessing patient decisions. However, portable ECG devices capable of acquiring a complete 12-lead ECG are scarce. For the first time, a deep learning-based method is proposed to reconstruct the 12-lead ECG from Frank leads (VX, VY, and VZ) or EASI leads (VES, VAS, and VAI). The innovative ECG reconstruction network called M2Eformer is composed of a 2D-ECGblock and a ProbDecoder module. The 2D-ECGblock module adaptively segments EASI leads into multi-periods based on frequency energy, transforming the 1D time series into a 2D tensor representing within-cycle and between-cycle variations. The ProbDecoder module aims to extract Probsparse self-attention and achieve one-step output for the target leads. Experimental results from comparing recorded and reconstructed 12-lead ECG using Frank leads indicate that M2Eformer outperforms traditional ECG reconstruction methods on a public database. In this study, a self-constructed database (10 healthy individuals + 15 patients) was utilized for the clinical diagnostic validation of ECG reconstructed from EASI leads. Subsequently, both the ECG reconstructed using EASI and the recorded 12-lead ECG were subjected to a double-blind diagnostic experiment conducted by three cardiologists. The overall diagnostic consensus among three cardiology experts, reaching a rate of 96%, indicates the significant utility of EASI-reconstructed 12-lead ECG in facilitating the diagnosis of cardiac conditions.

Safety and efficacy of eblasakimab, an interleukin 13 receptor α1 monoclonal antibody, in adults with moderate-to-severe atopic dermatitis: A phase 1b, multiple-ascending dose study.

BACKGROUND: Eblasakimab, an interleukin (IL)-13 receptor α1 antagonist, blocks IL-4 and IL-13 signaling through the type 2 receptor. OBJECTIVE: The safety and efficacy of eblasakimab was evaluated in adults with moderate-to-severe atopic dermatitis (AD). METHODS: In this phase 1b randomized, double-blinded study, 52 patients with moderate-to-severe AD received weekly subcutaneous injections of eblasakimab 200, 400, or 600 mg, or placebo for 8 weeks. Primary outcome was the incidence of treatment-emergent adverse events. Secondary outcomes included percentage change in the Eczema Area and Severity Index from baseline; Eczema Area and Severity Index improvement of at least 50%, 75%, or 90% from baseline; and percentage change in the peak-pruritus numeric rating scale score from baseline. RESULTS: Treatment-emergent adverse events were reported in 47% placebo and 71% eblasakimab patients; most were considered mild or moderate and did not lead to study discontinuation. At week 8 eblasakimab 600 mg showed statistically significant improvement in mean percentage change in Eczema Area and Severity Index versus placebo (-65% vs -27%, P = .014). Other key secondary physician- and patient-reported end points were met. LIMITATIONS: Longer studies are required to confirm eblasakimab safety and efficacy in AD patients. CONCLUSIONS: Treatment of adults with moderate-to-severe AD with eblasakimab was well-tolerated and associated with significant clinical improvements versus placebo.

Feasibility of His bundle pacing facilitated by EASI derived 12­lead ECG.

INTRODUCTION: His bundle pacing (HBP) has become popular in recent years as a more physiological alternative to conventional right ventricular pacing. Implantation requires 12­lead ECG during surgery, which is not readily available in a standard operating room. Often but not always HBP is performed in an electrophysiology lab. EASI is a reduced lead system which enables derived 12­lead ECG. EASI derived 12­lead ECGs on modern tablet computers offer a more mobile and lightweight ECG solution which does not obstruct fluoroscopy during implantation. This case series aims to compare standard 12­lead ECG to EASI derived 12­lead ECG in patients undergoing HBP implantation. METHODS AND RESULTS: A total of 11 patients received permanent HBP guided only by fluoroscopy, a pacing system analyzer (Medtronic CareLink SmartSync Device Manager) and EASI derived 12­lead ECG (CardioSecur Pro). During the first postoperative device interrogation HBP criteria, as defined in the EHRA consensus paper on conduction system pacing, were evaluated with the EASI derived system as well as a standard 12­lead ECG and compared to each other. There was perfect agreement with regards to these criteria which lead to identical conclusions in all cases. CONCLUSION: HBP implantation can be performed with EASI derived 12­lead ECG instead of conventional 12­lead ECG. Criteria for discriminating between selective His bundle, non-selective His bundle or myocardial capture alone are clearly visible in the EASI derived ECG leading to the same conclusion when compared to standard 12­lead ECG. Compared to a conventional 12­lead ECG the EASI system offers a leaner setup with less visual obstruction on fluoroscopy.

Electroporation-based Easi-CRISPR yields biallelic insertions of EGFP-HiBiT cassette in immortalized chicken oviduct epithelial cells.

Laying hens are an excellent experimental oviduct model for studying reproduction biology. Because chicken oviduct epithelial cells (cOECs) have a crucial role in synthesizing and secreting ovalbumin, laying hens have been regarded an ideal bioreactor for producing pharmaceuticals in egg white through transgene or gene editing of the ovalbumin (OVA) gene. However, related studies in cOECs are largely limited because of the lack of immortalized model cells. In addition, the editing efficiency of conventional CRISPR-HDR knock-in in chicken cells is suboptimal (ranging from 1 to 10%) and remains elevated. Here, primary cOECs were isolated from young laying hens, then infected with a retrovirus vector of human telomerase reverse transcriptase (hTERT), and immortalized cOECs were established. Subsequently, an electroporation-based Easi-CRISPR (Efficient additions with ssDNA inserts-CRISPR) method was adopted to integrate an EGFP-HiBiT cassette into the chicken OVA locus (immediately upstream of the stop codon). The immortalized cOECs reflected the self-renewal capability and phenotype of oviduct epithelial cells. This is because these cells not only maintained stable proliferation and normal karyotype and had no potential for malignant transformation, but also expressed oviduct markers and an epithelial marker and had a morphology similar to that of primary cOECs. EGFP expression was detected in the edited cells through microscopy, flow cytometry, and HiBiT/Western blotting. The EGFP-HiBiT knock-in efficiency reached 27.9% after a single round of electroporation, which was determined through genotyping and DNA sequencing. Two single cell clones contained biallelic insertions of EGFP-HiBiT donor cassettes. In conclusion, our established immortalized cOECs could act as an in vitro cell model for gene editing in chicken, and this electroporation-based Easi-CRISPR strategy will contribute to the generation of avian bioreactors and other gene-edited (GE) birds.

Comparative Efficacy of Targeted Systemic Therapies for Moderate-to-Severe Atopic Dermatitis without Topical Corticosteroids: An Updated Network Meta-analysis.

INTRODUCTION: The treatment landscape for moderate-to-severe atopic dermatitis (AD) continues to expand. This network meta-analysis (NMA) updates a previously conducted NMA to include data from the most recent phase 3 trials to assess the comparative efficacy of targeted systemic therapies without the addition of topical corticosteroids (TCS) and/or topical calcineurin inhibitors (TCI) in adults with moderate-to-severe AD. METHODS: Data from recent phase 3 monotherapy trials of lebrikizumab, ADvocate1 (NCT04146363) and ADvocate2 (NCT04178967), were included in the analyses, along with other eligible phase 3/4 randomized placebo-controlled trials for abrocitinib, baricitinib, dupilumab, tralokinumab, and upadacitinib identified through a systemic literature review in Silverberg et al. (Dermatol Ther (Heidelb) 12(5):1181-1196, 2022). The proportion of patients achieving Eczema Area and Severity Index (EASI) improvement ≥ 90% from baseline (EASI-90), EASI improvement ≥ 75% from baseline (EASI-75), ≥ 4-point improvement on Pruritus Numerical Rating Scale from baseline (ΔNRS ≥ 4), and Investigator Global Assessment (IGA) score of 0 or 1 (clear or almost clear) and reduction of ≥ 2 points from baseline (IGA 0/1) were evaluated using a Bayesian network meta-analysis. RESULTS: The updated NMA analyzed 13 unique placebo-controlled trials involving 7105 patients in 32 arms across 6 targeted therapies. Upadacitinib 30 mg was the most efficacious therapy across all endpoints at the primary timepoint (week 12 or 16) and at earlier timepoints, generally followed by abrocitinib 200 mg, upadacitinib 15 mg, dupilumab 300 mg, and lebrikizumab 250 mg or abrocitinib 100 mg. Baricitinib 2 mg and tralokinumab were generally ranked lower across outcomes. CONCLUSIONS: Many factors need to be considered for treatment selection for AD, especially as new treatments continue to emerge. After incorporating recent placebo-controlled phase 3 data of lebrikizumab, upadacitinib 30 mg, upadacitinib 15 mg, and abrocitinib 200 mg remain the most efficacious targeted systemic therapies over 12-16 weeks of therapy in AD. These updated findings can help healthcare providers when creating a patient's personalized treatment plan.

Assessing Response in Atopic Dermatitis: A Systematic Review of the Psychometric Performance of Measures Used in HTAs and Clinical Trials.

INTRODUCTION: Assessing treatment response is key to determining treatment value in atopic dermatitis (AD). Currently, response is assessed using various clinician- or patient-reported measures and response criteria. This variation creates a mismatch of evidence across trials, hindering the ability of clinicians, regulators, and payers to compare the efficacy of treatments. This review identifies which measures and criteria are used to determine response in clinical trials and health technology assessments (HTAs). Moreover, it systematically reviews the psychometric performance of those measures and criteria to understand which perform best in capturing patient-relevant symptoms and treatment benefits. METHODS: A scoping review of clinical trials and HTAs in AD identified the following measures for inclusion: the Eczema Area and Severity Index (EASI), the Investigator's Global Assessment (IGA), the Dermatology Life Quality Index (DLQI) and the Peak Pruritus Numerical Rating Scale (PP-NRS). A systematic search was performed in MEDLINE and Embase to identify studies testing the psychometric performance of these measures in adults or adolescents with AD. RESULTS: A lack of consistency in the assessment of response was observed across clinical trials and HTAs. Important gaps in psychometric evidence were identified. No content validations of the EASI and IGA in AD were found, while some quantitative studies suggested that these measures fail to capture itch, a core symptom. The PP-NRS and DLQI performed well. No studies compared the performance of different response criteria. CONCLUSION: Content validation of the PP-NRS confirmed the importance of itch as a core symptom and treatment priority in AD; however, itch is not well covered in the EASI or IGA. Including the PP-NRS in clinical trials and HTAs will better capture patient-relevant benefit and response. Although various response criteria were used, no studies compared the performance of different criteria to inform which were most appropriate to compare treatments in clinical trials and HTAs.

The assessment of treatment response is important in determining treatment value in atopic dermatitis (AD). This study aimed to identify which outcome measures and criteria are used to determine treatment response in clinical trials and health technology assessments (HTAs). The psychometric performance of identified outcome measures and criteria was then systematically reviewed to understand which perform best in capturing patient-relevant symptoms and treatment benefits in AD. The review identified and included the Eczema Area and Severity Index (EASI), Investigator's Global Assessment (IGA), Dermatology Life Quality Index (DLQI) and Peak Pruritus Numerical Rating Scale (PP-NRS) as response measures. Lack of consistency in how response is assessed across clinical trials and HTAs makes it difficult for clinicians and payers to compare the efficacies and cost-effectivenesses of different treatments and to make optimal treatment decisions. The review found that content validity (the extent to which a measure covers those symptoms and treatment benefits which are important to patients) was not assessed for EASI and IGA. EASI and IGA are often used to assess response in clinical trials and HTAs, but they miss key elements of the patient-relevant disease impact and treatment benefit, including itch. Treatments leading to improvements in missed symptoms (e.g. itch) will be undervalued using EASI and IGA, decreasing the chances of regulatory approval and reimbursement. Moreover, response criteria used in clinical trials and HTAs are sometimes adopted in prescriber settings. Here, if response assessment does not capture patient-relevant benefit, patients' access to tailored treatment may be restricted due to the perceived non-response.

Contextualizing the tone of the operating room in practice: drawing on the literature to connect the dots.

The study of teamwork in the operating room has made significant strides in uncovering key constructs which shape safe and effective intraoperative care. However, in recent years, there have been calls to understand teamwork in the operating room more fully by embracing the complexity of the intraoperative environment. We propose the construct of tone as a useful lens through which to understand intraoperative teamwork. In this article, we review the literature on culture, shared mental models, and psychological safety, linking each to the construct of tone. By identifying tone as a theoretical orientation to demonstrate the overlap between these concepts, we aim to provide a starting point for new ways to understand intraoperative team dynamics.

Baricitinib provides rapid and sustained improvements in absolute EASI and SCORAD outcomes in adults with moderate-to-severe atopic dermatitis.

BACKGROUND: Baricitinib is an oral selective Janus kinase 1/2 inhibitor approved for moderate-to-severe atopic dermatitis (AD) in adults. OBJECTIVES: To evaluate absolute Eczema Area and Severity Index (EASI) and SCORing of Atopic Dermatitis (SCORAD) outcomes over 16 weeks and to link disease severity categories to quality of life (QoL) improvements. METHODS: This post-hoc analysis included patients enrolled in Phase3 monotherapy (BREEZE-AD1/AD2) and topical corticosteroid (TCS) combination therapy (BREEZE-AD7) trials and analyzed baricitinib 2 and 4 mg vs. placebo. Categorical outcomes were analyzed using Fisher's exact test. RESULTS: Significantly more baricitinib-treated patients reached EASI ≤ 7 and SCORAD < 25 as early as week 1 in monotherapy and week 2 in TCS combination therapy, compared to placebo. Significant response vs. placebo was sustained until week 16 for EASI ≤ 7 (AD1/2 [p-value vs. placebo]: 2 mg = 19.9%, 4 mg = 25.4% [p = 0.001] and AD7: 2 mg = 40.4% [p = 0.087], 4 mg = 48.6% [p = 0.003]) and SCORAD < 25 (AD1/2: 2 mg = 12.2%, 4 mg = 19.4% [p = 0.001] and AD7: 2 mg = 30.3% [p = 0.025], 4 mg = 34.2% [p = 0.004]) severity categories. These effects were accompanied by rapid improvements in QoL. CONCLUSION: Baricitinib-treated patients rapidly achieved recommended absolute EASI and SCORAD treatment outcomes which were sustained until week 16. Improvements in QoL were greater than EASI severity categories reflected, indicating that physician-assessed scores do not necessarily correlate with patients' impression of AD severity.

The risk factors for food allergy in infants with atopic dermatitis.

BACKGROUND: There is a lack of information about which risk factors accompany food allergy (FA) in infants with atopic dermatitis (AD). We hypothesized that we would be able to predict FA through risk factors in infants with AD. METHODS: This prospective descriptive cross-sectional study was performed with infants aged 1-12 months with newly diagnosed AD. The SCORing Atopic Dermatitis (SCORAD) and Eczema Area and Severity Index (EASI), Infants` Dermatitis Quality Of Life (IDQOL), and Family Dermatological Life Quality (FDLQ) index scores were calculated at first admission. We developed a new tool, Sites of Eczema (SoE), to score sites of eczema on the body. RESULTS: A total of 279 infants with AD were included. FA was found in 166 (59.5%) infants with AD, of whom 112 had single and 54 had multiple FAs. The SCORAD index, EASI scores, IDQOL1, IDQOL2, and FDQL, and SoE scores were higher in the subgroup with FA compared to that without FA (p < 0.001). In the multivariate regression model, eosinophil count (odds ratio [OR]=1.00, 95% confidence interval: [CI, 1.00-1.00]; p=0.008), serum total IgE level (OR=1.02, 95% CI: [1.00-1.03]; p=0.002), pruritus score (OR=0.87, 95% CI: [0.77-0.97]; p=0.019), SCORAD index (OR=1.04, 95% CI: [1.01-1.08]; p=0.008), FDQL index (OR=1.09, 95% CI: [1.01-1.18]; p=0.014), and SoE score (OR=1.48, 95% CI: [1.00-2.19]; p=0.046) were identified as the highest risk factors for FA in infants with AD. CONCLUSIONS: Serum total IgE levels, eosinophil counts and ratio, SCORAD index and EASI scores, IDQOL and FDLQ index, pruritus and sleep disturbance scores, and SoE scores were identified as risk factors for FA in infants with AD in this study. The SoE score is an important risk factor for FA in infants with AD. We recommend that the risk factors for FA in patients with AD guide the management of these patients.

Association between short-term exposure to environmental air pollution and atopic dermatitis flare in patients treated with dupilumab.

Background: The magnitude of short/medium-term air pollution exposure on atopic dermatitis (AD) flare has not been fully investigated. The aim of the study was to investigate the association of short/medium-term exposure to airborne pollution on AD flares in patients treated with dupilumab. Methods: Observational case-crossover study. Patients with moderate-to-severe AD under treatment with dupilumab were included. The exposure of interest was the mean concentrations of coarse and fine particulate matter (PM10, PM2.5), nitrogen dioxide, and oxides (NO2, NOx). Different intervals were considered at 1 to 60 days before the AD flare and control visit, defined as the visit with the highest Eczema Area and Severity Index scores >8 and ≤7, respectively. A conditional logistic regression analysis adjusted for systemic treatments was employed to estimate the incremental odds (%) of flare every 10 µg/m3 pollutant concentration. Results: Data on 169 of 528 patients with AD having 1130 follow-up visits and 5840 air pollutant concentration measurements were retrieved. The mean age was 41.4 ± 20.3 years; 94 (55%) men. The incremental odds curve indicated a significant positive trend of AD flare for all pollutants in all time windows. At 60 days, every 10 µg/m3 PM10, PM2.5, NOx, and NO2 increase concentration was associated with 82%, 67%, 28%, and 113% odds of flare, respectively. Conclusions: In patients treated with dupilumab, acute air pollution exposure is associated with an increased risk for AD flare with a dose-response relationship.

Comparison of real-world treatment outcomes of systemic immunomodulating therapy in atopic dermatitis patients with dark and light skin types.

Background: Few data exist on differences in treatment effectiveness and safety in atopic dermatitis patients of different skin types. Objective: To investigate treatment outcomes of dupilumab, methotrexate, and ciclosporin, and morphological phenotypes in atopic dermatitis patients, stratified by Fitzpatrick skin type. Methods: In an observational prospective cohort study, pooling data from the Dutch TREAT (TREatment of ATopic eczema) NL (treatregister.nl) and UK-Irish A-STAR (Atopic eczema Systemic TherApy Register; astar-register.org) registries, data on morphological phenotypes and treatment outcomes were investigated. Results: A total of 235 patients were included (light skin types [LST]: Fitzpatrick skin type 1-3, n = 156 [Ethnicity, White: 94.2%]; dark skin types [DST]: skin type 4-6, n = 68 [Black African/Afro-Caribbean: 25%, South-Asian: 26.5%, and Hispanics: 0%]). DST were younger (19.5 vs 29.0 years; P < .001), more often had follicular eczema (22.1% vs 2.6%; P < .001), higher baseline Eczema Area and Severity Index (EASI) scores (20.1 vs 14.9; P = .009), less allergic contact dermatitis (30.9% vs 47.4%; P = .03), and less previous phototherapy use (39.7% vs 59.0%; P = .008). When comparing DST and LST corrected for covariates including baseline EASI, DST showed greater mean EASI reduction between baseline and 6 months with only dupilumab (16.7 vs 9.7; adjusted P = .032). No differences were found for adverse events for any treatments (P > .05). Limitations: Unblinded, non-randomized. Conclusion: Atopic dermatitis differs in several characteristics between LST and DST. Skin type may influence treatment effectiveness of dupilumab.