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BACKGROUND: While B-cells have historically been implicated in allergy development, a growing body of evidence supports their role in atopic dermatitis (AD). B-cell differentiation across ages in AD, and its relation to disease severity scores, has not been well defined. OBJECTIVE: To compare the frequency of B-cell subsets in blood of 0-5, 6-11, 12-17, and ≥18 years old patients with AD versus age-matched controls. METHODS: Flow cytometry was used to measure B-cell subset frequencies in the blood of 27 infants, 17 children, 11 adolescents, and 31 adults with moderate-to-severe AD and age-matched controls. IgD/CD27 and CD24/CD38 core gating systems and an 11-color flow cytometry panel were used to determine frequencies of circulating B-cell subsets. Serum total and allergen-specific IgE (sIgEs) levels were measured using ImmunoCAP®. RESULTS: Adolescents with AD had lower frequencies of major B-cells subsets (p < .03). CD23 expression increased with age and was higher in AD compared to controls across all age groups (p < .04). In AD patients, multiple positive correlations were observed between IL-17-producing T-cells and B-cell subsets, most significantly non-switched memory (NSM) B-cells (r = .41, p = .0005). AD severity positively correlated with a list of B-cell subsets (p < .05). IL-9 levels gradually increased during childhood, reaching a peak in adolescence, paralleling allergen sensitization, particularly in severe AD. Principal component analysis of the aggregated environmental sIgE data showed that while controls across all ages tightly clustered together, adolescents with AD demonstrated distinct clustering patterns relative to controls. CONCLUSIONS: Multiple correlations between B-cells and T-cells, as well as disease severity measures, suggest a complex interplay of immune pathways in AD. Unique B-cell signature during adolescence, with concurrent allergen sensitization and IL-9 surge, point to a potentially wider window of opportunity to implement interventions that may prevent the progression of the atopic march.
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There have been over 769 million cases of COVID-19, and up to 50% of infected individuals are asymptomatic. The purpose of this study aimed to assess the use of a clinical-grade physiological wearable monitoring system, ANNE One, to develop an artificial intelligence algorithm for (1) cough detection and (2) early detection of COVID-19, through the retrospective analysis of prospectively collected physiological data from longitudinal wear of ANNE sensors in a multicenter single arm study of subjects at high risk for COVID-19 due to occupational or home exposures. The study employed a two-fold approach: cough detection algorithm development and COVID-19 detection algorithm development. For cough detection, healthy individuals wore an ANNE One chest sensor during scripted activity. The final performance of the algorithm achieved an F-1 score of 83.3% in twenty-seven healthy subjects during biomarker validation. In the COVID-19 detection algorithm, individuals at high-risk for developing COVID-19 because of recent exposures received ANNE One sensors and completed daily symptom surveys. An algorithm analyzing vital parameters (heart rate, respiratory rate, cough count, etc.) for early COVID-19 detection was developed. The COVID-19 detection algorithm exhibited a sensitivity of 0.47 and specificity of 0.72 for detecting COVID-19 in 325 individuals with recent exposures. Participants demonstrated high adherence (≥ 4 days of wear per week). ANNE One shows promise for detection of COVID-19. Inclusion of respiratory biomarkers (e.g., cough count) enhanced the algorithm's predictive ability. These findings highlight the potential value of wearable devices in early disease detection and monitoring.
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COVID-19 , Dispositivos Electrónicos Vestibles , Humanos , Algoritmos , Inteligencia Artificial , Tos/diagnóstico , COVID-19/diagnóstico , Prueba de COVID-19 , Reacción en Cadena de la Polimerasa , Estudios RetrospectivosRESUMEN
Importance: Chronic skin disorders in children frequently are visible and can cause stigmatization. However, the extent of stigmatization from chronic skin disease and association with mental health needs further study. Objective: To examine the extent of stigma, dependence on disease visibility and severity, and association with mental health and quality of life (QOL) in chronic pediatric skin disease. Design, Setting, and Participants: A cross-sectional, single-visit study was conducted at 32 pediatric dermatology centers in the US and Canada from November 14, 2018, to November 17, 2021. Participants included patients aged 8 to 17 years with chronic skin disease and 1 parent. Main Outcomes and Measures: Using the Patient-Reported Outcomes Measurement Instrumentation System (PROMIS) Stigma-Skin, the extent of stigma with child-, caregiver-, and physician-assessed disease visibility (primary outcome) and severity was compared, as well as reduced QOL (assessed by Skindex-Teen), depression, anxiety, and poor peer relationships (PROMIS child and proxy tools) (secondary outcomes). Results: The study included 1671 children (57.9% female; mean [SD] age, 13.7 [2.7] years). A total of 56.4% participants had self-reported high disease visibility and 50.5% had moderate disease severity. Stigma scores significantly differed by level of physician-assessed and child/proxy-assessed disease visibility and severity. Among children with chronic skin disorders, predominantly acne, atopic dermatitis, alopecia areata, and vitiligo, only 27.0% had T scores less than 40 (minimal or no stigma) and 43.8% had at least moderate stigma (T score ≥45) compared with children with a range of chronic diseases. Stigma scores correlated strongly with reduced QOL (Spearman ρ = 0.73), depression (ρ = 0.61), anxiety (ρ = 0.54), and poor peer relationships (ρ = -0.49). Overall, 29.4% of parents were aware of bullying of their child, which was strongly associated with stigma (Cohen d = -0.79, with children who were not bullied experiencing lower levels of stigma). Girls reported more stigma than boys (Cohen d = 0.26). Children with hyperhidrosis and hidradenitis suppurativa were most likely to have increased depression and anxiety. Conclusions and Relevance: The findings of this study suggest that physician assessment of disease severity and visibility is insufficient to evaluate the disease impact in the patient/caregiver. Identifying stigmatization, including bullying, and tracking improvement through medical and psychosocial interventions may be a key role for practitioners.
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Salud Mental , Calidad de Vida , Enfermedades de la Piel , Estigma Social , Humanos , Femenino , Masculino , Niño , Adolescente , Estudios Transversales , Enfermedades de la Piel/psicología , Enfermedad Crónica , Canadá , Estereotipo , Índice de Severidad de la Enfermedad , Depresión/epidemiología , Depresión/psicología , Depresión/etiología , Estados Unidos , Ansiedad/psicología , Ansiedad/epidemiología , Ansiedad/etiología , Medición de Resultados Informados por el PacienteRESUMEN
Internet platforms have become a common source of information for individuals with skin diseases such as vitiligo, and the vitiligo community frequently turns to online sources for diet modifications that may be beneficial for their disease. In this study, our objective was to summarize information from the most frequently visited websites providing diet suggestions that reportedly affected vitiligo symptoms. Notable diet categories for food components included vitamins, fruits, omega-3 fatty acids, grains, minerals, vegetables, and nuts. Evidence supporting online dietary recommendations for vitiligo is limited in the published scientific literature. Further controlled clinical trials are warranted to assess the relationship between diet and vitiligo and evaluate the accuracy of online diet recommendations for vitiligo.
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Vitíligo , Humanos , Dieta , Vitaminas , Frutas , VerdurasRESUMEN
PURPOSE: To develop the PROMIS Pediatric Stigma (PPS) and Skin (PPS-Skin) by constructing a common metric for measuring stigma in children with various conditions, while capturing the unique features of each condition. METHODS: Data from 860 children, ages 8-17, with a diagnosis of epilepsy, pNF (neurofibromatosis type 1 associated neurofibroma plexform), MD (muscular dystrophy), cancer, or skin conditions recruited from three projects were analyzed. Children with epilepsy, pNF and MD (sample-1) completed the original 18-item Neuro-QoL Stigma, while children with cancer and skin conditions (e.g., atopic dermatitis, psoriasis, and genetic skin disorders; sample-2) completed a 16-item version and 6 additional skin related items. Exploratory factor analysis (EFA) and confirmatory analysis (CFA) were used to evaluate unidimensionality of 24 stigma items. Differential item functioning (DIF) was used to evaluate measurement equivalence on group, gender, age, and conditions. Item response theory model (IRT) was used to construct the final measure. RESULTS: Sufficient unidimensionality was supported by both EFA and CFA. No items showed significant DIF indicating stable measurement properties across groups of comparison. All items fit the IRT model and were able to be calibrated together to form the PPS which consists of 18 core items. The PPS-Skin (18 cores items + 6 skin items) was developed by calibrating 6 skin items onto the common metric as the PPS. CONCLUSIONS: We used IRT techniques to successfully develop the PPS and the PPS-Skin, which share a common metric and account for unique and common concerns related to chronic conditions.
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Epilepsia , Neoplasias , Humanos , Niño , Calidad de Vida/psicología , Encuestas y Cuestionarios , Enfermedad Crónica , Psicometría/métodosRESUMEN
BACKGROUND: Race and socioeconomic status are thought to influence the severity of atopic dermatitis (AD), but findings differ between countries and measures used. The role of social determinants of health versus biologic factors in causing these differences is poorly understood. OBJECTIVE: We hypothesized that spatially-derived factors correlate with AD severity and patient-reported outcome (PRO) in a pediatric cohort from Chicago, USA. METHODS: Children with AD and caregivers were enrolled from February 2018 to April 2019 in this single-site cross-sectional study. Severity was self- and physician-assessed using validated measures. Patient addresses were geocoded and linked to census tract IDs. Deprivation index (DI) was calculated using variables of the 2018 American Community Survey. RESULTS: Among 216 children aged 5-17 years old, 111 (51.4%) lived in urban, 104 (48.1%) suburban, and one (0.5%) in rural areas. Race was self-classified as White in 31.0%, Black 24.5%, other or mixed 25.0%, and Asian 19.4%; 24.5% were Hispanic. Median DI was 0.32 (range 0.03-0.72), with higher scores indicating more deprivation. DI correlated with insurance type, family income, ethnicity, race, and parental education, and weakly with selected PRO T-scores. However, no correlations between any AD severity score and DI, race, ethnicity, income, education, or insurance type were found. CONCLUSION: The impact of socioeconomic factors on AD severity in our study population was less pronounced than expected. This could be because of regional differences, including access to high-quality care. The role of access as a deciding factor in the impact of socioeconomic status on AD outcome deserves further investigation.
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Dermatitis Atópica , Factores Socioeconómicos , Adolescente , Niño , Preescolar , Humanos , Estudios Transversales , Dermatitis Atópica/epidemiología , EtnicidadRESUMEN
Keloids are benign, fibroproliferative dermal tumors that typically form owing to abnormal wound healing. The current standard of care is generally ineffective and does not prevent recurrence. To characterize keloid scars and better understand the mechanism of their formation, we performed transcriptomic profiling of keloid biopsies from a total of 25 subjects of diverse racial and ethnic origins, 15 of whom provided a paired nonlesional sample, a longitudinal sample, or both. The transcriptomic signature of nonlesional skin biopsies from subjects with keloids resembled that of control skin at baseline but shifted to closely match that of keloid skin after dermal trauma. Peripheral keloid skin and rebiopsied surrounding normal skin both showed upregulation of epithelial-mesenchymal transition markers, extracellular matrix organization, and collagen genes. These keloid signatures strongly overlapped those from healthy wound healing studies, usually with greater perturbations, reinforcing our understanding of keloids as dysregulated and exuberant wound healing. In addition, 219 genes uniquely regulated in keloids but not in normal injured or uninjured skin were also identified. This study provides insights into mature and developing keloid signatures that can act as a basis for further validation and target identification in the search for transformative keloid treatments.
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BACKGROUND/OBJECTIVES: Healthcare transition (HCT) refers to movement from pediatric to adult healthcare models. Lack of HCT preparation contributes to poor health outcomes. This study measures readiness to transition in individuals with genetic skin conditions. METHODS: Participants signed IRB-approved consents/assents. Participants ages 14-22 years with genetic skin disorders were surveyed with measures of QoL (Children's Dermatology Life Quality Index/CDLQI or DLQI) and HCT readiness using the Transition Readiness Assessment Questionnaire (TRAQ) and adapted non-validated measures of Skin Knowledge and Psychosocial Factors (5 = highest readiness). Mean TRAQ was compared with historical data on controls and other chronic conditions (t-tests) and correlated (Pearson) with Skin Knowledge and Psychosocial. Multivariable regression compared demographics and QoL with transition readiness. RESULTS: A total of 45 participants were enrolled (mean age 17.8 years, 67% female, 71% White; disorders of cornification [n = 31], ectodermal dysplasias [n = 7], epidermolysis bullosa [n = 4], tuberous sclerosis [n = 3]). Mean TRAQ (3.3 ± 0.9) was lower than controls (3.9; p < .001) and some chronic disorders (sickle cell [3.7; p < .05], type 1 diabetes [3.7; p < .01]), but higher than with spina bifida (2.8; p < .001) and congenital heart disease (2.9; p < .01). Mean Skin Knowledge was 4.2 ± 1.0, and mean Psychosocial was 3.4 ± 0.8. TRAQ correlated strongly with Skin Knowledge (r = .61; p < .05), but not Psychosocial (r = .12; p = .6). Ages 14-17 years versus 18-22 years and public versus private insurance predicted lower TRAQ scores. Poor DLQI predicted higher TRAQ and Skin Knowledge, but poor DLQI and CDLQI predicted lower Psychosocial. CONCLUSIONS: Adolescents and young adults with genetic skin disorders demonstrated low transition readiness, especially among younger-aged and lower socioeconomic groups. We recommend a HCT intervention to improve health outcomes.
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Enfermedades de la Piel , Transición a la Atención de Adultos , Humanos , Adolescente , Femenino , Adulto Joven , Niño , Anciano , Masculino , Calidad de Vida , Encuestas y Cuestionarios , Enfermedades de la Piel/terapia , Enfermedad CrónicaRESUMEN
BACKGROUND: Patients with atopic dermatitis (AD) have systemic biomarker dysregulation that differs by age group; however, the proteomic characteristics of these age-based changes are unknown. OBJECTIVE: To profile blood proteins of patients with AD across different age groups versus age-appropriate controls. METHODS: Using the Olink high-throughput proteomic platform, we profiled 375 serum proteins of 20 infants (age, 0-5 years), 39 children (age, 6-11 years), 21 adolescents (age, 12-17 years), and 20 adults (age, ≥18 years) with moderate-to-severe AD and 83 age-appropriate controls. RESULTS: Each group presented a distinct systemic proteomic signature. Th2-related proteins were increased in infant AD and further intensified with age through adolescence and adulthood (interleukin 4/CCL13/CCL17). In contrast, Th1 axis down-regulation was detected in infants with AD and gradually reversed to increased Th1 products (interferon γ/CXCL9/CXCL10/CCL2) in patients with AD from childhood to adulthood. Despite their short disease duration, infants already had evidence of systemic inflammation, with significant upregulation of innate immunity (interleukin 17C/ interleukin-1RN), T-cell activation/migration (CCL19), Th2 (CCL13/CCL17), and Th17 (PI3) proteins. Adults with AD present unique upregulation of cardiovascular proteins related to coagulation and diabetes. LIMITATIONS: Cross-sectional observational study with a single time point. CONCLUSION: Systemic immune signatures of AD are age-specific beyond the shared Th2 immune activation. These data advocate for precision medicine approaches based on age-specific AD profiles.
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Dermatitis Atópica , Adulto , Niño , Adolescente , Humanos , Lactante , Adulto Joven , Recién Nacido , Preescolar , Proteómica , Estudios Transversales , Inflamación , Proteínas , Células Th2RESUMEN
STUDY OBJECTIVES: We assessed the real-world performance of the ANNE Sleep system against 2 Food and Drug Administration-cleared home sleep testing platforms and the intraindividual night-to-night variability of respiratory event index measured by ANNE Sleep. METHODS: We evaluated the home performance of the ANNE Sleep system compared with 2 Food and Drug Administration-cleared home sleep testing platforms (WatchPAT: n = 29 and Alice NightOne: n = 46) during a synchronous night with unsupervised patient application. Additionally, we evaluated night-to-night variability of respiratory event index and total sleep time using the ANNE Sleep system (n = 30). RESULTS: For the diagnosis of moderate and severe obstructive sleep apnea, the ANNE Sleep system had a positive percent agreement of 58% (95% confidence interval, 28-85%) and a negative percent agreement of 100% (95% confidence interval, 80-100%) compared to WatchPAT. The positive and negative percent agreement for ANNE Sleep vs Alice NightOne was 85% (95% confidence interval, 66-96%) and 95% (95% confidence interval, 74-100%). There were no differences in mean total sleep time or respiratory event index across multiple nights of monitoring with ANNE. There were no differences consistent with a first-night effect but testing multiple nights reclassified obstructive sleep apnea severity in 5 (17%) individuals and detected 3 additional cases of moderate disease, with only a 12% (standard deviation, 28%) mean fluctuation in respiratory event index from the first night of testing compared to a mean of multiple nights. Overall, 80% of users found ANNE comfortable and easy to use. CONCLUSIONS: ANNE Sleep exhibited stronger concordance with Alice NightOne compared to WatchPAT. While we illustrated low night-to-night variability for ANNE Sleep, the results suggest multiple nights increased detection of moderate or severe obstructive sleep apnea. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: ANNE Diagnostic Agreement With Home Sleep Testing; URL: https://clinicaltrials.gov/ct2/show/NCT05421754; Identifier: NCT05421754. CITATION: Walter J, Lee JY, Blake S, et al. A new wearable diagnostic home sleep testing platform: comparison with available systems and benefits of multinight assessments. J Clin Sleep Med. 2023;19(5):865-872.
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Apnea Obstructiva del Sueño , Dispositivos Electrónicos Vestibles , Humanos , Polisomnografía/métodos , Sueño , Apnea Obstructiva del Sueño/diagnóstico , Duración del SueñoRESUMEN
IMPORTANCE: Treatment of congenital ichthyoses primarily focuses on reversing skin scaling and is not pathogenesis based. Recent studies showed Th17 immune skewing, as in psoriasis, across the spectrum of ichthyosis, suggesting that targeting this pathway might broadly reduce disease severity. OBJECTIVE: To determine whether secukinumab, an IL-17A inhibitor, can improve ichthyosis across several congenital ichthyosis subtypes. DESIGN: Exploratory 16-week double-blind, randomized, placebo-controlled trial comparing secukinumab 300 mg every 4wks to placebo (1:1 randomization) in adults with the four major congenital ichthyosis subtypes (NCT03041038), followed by a 16-week open-label phase to evaluate response of the placebo-first group and a 20-week extension for safety. Significant differences in secukinumab- vs. placebo-treated subjects at Wk16 in the Ichthyosis Area Severity Index (IASI) score and lack of increased mucocutaneous bacterial and/or fungal infections were the co-primary efficacy and safety endpoints, respectively. SETTING: Two tertiary referral centers: Northwestern University Feinberg School of Medicine, Chicago, and Mount Sinai Icahn School of Medicine, New York. PARTICIPANTS: Twenty subjects ≥ 18 yo with genotype-confirmed epidermolytic ichthyosis, Netherton syndrome, lamellar ichthyosis, or congenital ichthyosiform erythroderma with at least moderate erythroderma. RESULTS: IL-17A inhibition did not significantly reduce severity or increase mucocutaneous infections among the 18 who completed the 16-week double-blind phase. Five patients with 29-50% clinical improvement at Wk32 requested drug continuation. Th17-related biomarkers were not significantly reduced vs. baseline or placebo-treated levels. LIMITATIONS: Small sample size; heterogeneous ichthyosis subsets. CONCLUSION: IL-17 inhibition with secukinumab is safe, but not efficacious across the spectrum of adult ichthyoses. GOV REGISTRATION NUMBER: NCT03041038; first posted on 02/02/2017.
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Eritrodermia Ictiosiforme Congénita , Ictiosis Lamelar , Ictiosis , Psoriasis , Adulto , Humanos , Ictiosis Lamelar/tratamiento farmacológico , Anticuerpos Monoclonales/uso terapéutico , Interleucina-17 , Ictiosis/tratamiento farmacológico , Psoriasis/tratamiento farmacológico , Eritrodermia Ictiosiforme Congénita/tratamiento farmacológico , Índice de Severidad de la Enfermedad , Método Doble Ciego , Resultado del TratamientoRESUMEN
Alopecia areata/AA is an autoimmune cause of nonscarring hair loss. The pathogenesis of AA involves many immune axes, including Th1/Th2 pathways. Delgocitinib is a pan-Janus kinase/JAK inhibitor that broadly blocks pro-inflammatory cytokines and has been effective in other inflammatory skin conditions. Recent human studies/reports have shown that use of some systemic JAK inhibitors led to hair regrowth, suggesting this medication class as a potential therapy for AA. However, topical treatment is desirable due to potential systemic side effects. To assess the efficacy and safety of topical delgocitinib in AA, we conducted a double-blind, randomized, vehicle-controlled clinical trial in 31 moderate-to-severe AA patients that were randomized 2:1 to receive delgocitinib ointment 30 mg/g (n = 20) or ointment vehicle (n = 11) for 12 weeks. The primary endpoint was change in severity of Alopecia Tool/SALT score from baseline to week 12. The secondary endpoint included safety profile by reported adverse events. Twenty-three subjects completed the trial, with eight discontinuing mostly due to voluntary withdrawal. Ten patients receiving delgocitinib ointment and three patients receiving vehicle showed SALT score improvements after 12 weeks, but the mean percent SALT improvement at week 12 compared to baseline between the two arms was not significant (p = 0.92). Our study suggests that delgocitinib ointment is not effective in moderate-to-severe AA, likely due to its inability to penetrate sufficiently deeply into the dermis of the scalp, but larger studies are necessary to assess whether a different formulation of topical JAK inhibitors may be suitable to treat mild or more localized forms of AA.
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Alopecia Areata , Inhibidores de las Cinasas Janus , Humanos , Alopecia Areata/tratamiento farmacológico , Inhibidores de las Cinasas Janus/efectos adversos , Pomadas/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND: Fatigue is a symptom that can negatively impact patients' quality of life. However, the relationship of AD with fatigue has not been fully studied, especially in children. OBJECTIVE: To determine the prevalence of fatigue in AD patients, and whether AD severity, demographics and comorbidities are associated with increased fatigue in children. METHODS: A cross-sectional observational study was performed among 248 children with AD. Paediatric patients (ages 8-17 years) and parents (of children ages 0-17 years) completed a questionnaire, including demographics, history of atopic comorbidities and validated severity measures of AD, itch, pain, sleep disturbance, sleep-related impairment and fatigue. AD severity was also assessed by clinician-reported Eczema Area and Severity Index (EASI), Scoring AD (SCORAD) and Investigator's Global Assessment (IGA). Fatigue was assessed using Patient Reported Outcome Measurement Information System (PROMIS) Pediatric Fatigue T-score. RESULTS: Most children with AD had no (38.6%) or mild (32.1%) fatigue, with fewer having moderate (27.2%) or severe (2%) fatigue. Moderate/severe PROMIS Pediatric fatigue T-scores were increased with moderate (25.7%/1.4%) and severe (39.3%/5.4%) IGA vs. mild IGA (18.0%/0.0%) and those with 5-6 (44.4%/0.0%) and 7 (44.2%/5.2%) nights of SD from eczema. Moderate-severe PROMIS Pediatric Fatigue T-scores were associated with history of hay fever (adjusted OR [95% Cl]: 2.803 [1.395-5.632]) and family income (<$100,000: 3.049 [1.294-7.181]), but inversely with Black (0.40 [0.168-0.969]) and AAPI (0.285 [0.094-0.859]) race. In multivariable regression models controlling for demographic factors, PROMIS Pediatric Fatigue T-score was significant with more severe scores for IGA, POEM, EASI, SCORAD, NRS-itch, SCORAD-itch, average itch in the past 7 days, PROMIS Pediatric Pain severity, PROMIS Pediatric SD, PROMIS Pediatric SRI, SCORAD-sleep and more frequent SD from AD. CONCLUSIONS: Fatigue is a common yet underappreciated symptom in children with AD, particularly those with moderate-severe AD, and warrants more attention in clinical practice and trials.
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Dermatitis Atópica , Eccema , Humanos , Niño , Adolescente , Recién Nacido , Lactante , Preescolar , Dermatitis Atópica/complicaciones , Dermatitis Atópica/epidemiología , Dermatitis Atópica/diagnóstico , Estudios Transversales , Calidad de Vida , Prevalencia , Índice de Severidad de la Enfermedad , Eccema/complicaciones , Prurito/etiología , Prurito/complicaciones , Fatiga/epidemiología , Fatiga/etiología , Inmunoglobulina ARESUMEN
STUDY OBJECTIVES: Evaluate per-patient diagnostic performance of a wireless dual-sensor system (ANNE sleep) compared with reference standard polysomnography (PSG) for the diagnosis of moderate and severe obstructive sleep apnea (OSA) with a minimum prespecified threshold of 80% for both sensitivity and specificity. METHODS: A multicenter clinical trial was conducted to evaluate ANNE sleep vs PSG to diagnose moderate and severe OSA in individuals 22 years or older. For each testing approach, apnea-hypopnea index (AHI) was manually scored and averaged by 3 registered sleep technologists blinded to the other system. Average variations > 15% were adjudicated by a sleep medicine physician. RESULTS: In a total of n = 225 participants (mean age 53 years, range 22-88 years), PSG diagnosed 30% (n = 68) of participants with moderate or severe OSA (AHI ≥ 15 events/h) compared to 29% (n = 65) diagnosed by ANNE sleep (P = .55). The sensitivity and specificity for ANNE sleep were 90% (95% confidence interval: 80-96%) and 98% (95% confidence interval: 94-99%), respectively. Strong correlation was shown in terms of final AHI (r = .93), with an average AHI bias of 0.5 (95% limits of agreement: -12.8 to 11.8). The majority of users noted comfort with using the ANNE sleep in the home setting. No adverse events were noted. CONCLUSIONS: Using PSG as the gold standard, ANNE sleep demonstrated high sensitivity and specificity for the diagnosis of moderate or severe OSA. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Comparative Study of the ANNE™ One System to Diagnose Obstructive Sleep Apnea; URL: https://clinicaltrials.gov/ct2/show/NCT04643782; Identifier: NCT04643782. CITATION: Davies C, Lee JY, Walter J et al. A single-arm, open-label, multicenter, and comparative study of the ANNE sleep system vs polysomnography to diagnose obstructive sleep apnea. J Clin Sleep Med. 2022;18(12):2703-2712.
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Apnea Obstructiva del Sueño , Humanos , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Polisomnografía , Apnea Obstructiva del Sueño/diagnóstico , Sueño , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: The ichthyoses are rare genetic keratinizing disorders that share the characteristics of an impaired epidermal barrier and increased risk of microbial infections. Although ichthyotic diseases share a T helper (Th) 17 cell immune signature, including increased expression of antimicrobial peptides, the skin microbiota of ichthyoses is virtually unexplored. OBJECTIVES: To analyse the metagenome profile of skin microbiome for major congenital ichthyosis subtypes. METHODS: Body site-matched skin surface samples were collected from the scalp, upper arm and upper buttocks of 16 healthy control participants and 22 adult patients with congenital forms of ichthyosis for whole metagenomics sequencing analysis. RESULTS: Taxonomic profiling showed significant shifts in bacteria and fungi abundance and sporadic viral increases across ichthyosis subtypes. Cutibacterium acnes and Malassezia were significantly reduced across body sites, consistent with skin barrier disruption and depletion of lipids. Microbial richness was reduced, with specific increases in Staphylococcus and Corynebacterium genera, as well as shifts in fungal species, including Malassezia. Malassezia globosa was reduced at all body sites, whereas M. sympodialis was reduced in the ichthyotic upper arm and upper buttocks. Malassezia slooffiae, by contrast, was strikingly increased at all body sites in participants with congenital ichthyosiform erythroderma (CIE) and lamellar ichthyosis (LI). A previously undescribed Trichophyton species was also detected as sporadically colonizing the skin of patients with CIE, LI and epidermolytic ichthyosis subtypes. CONCLUSIONS: The ichthyosis skin microbiome is significantly altered from healthy skin with specific changes predominating among ichthyosis subtypes. Skewing towards the Th17 pathway may represent a response to the altered microbial colonization in ichthyosis. What is already known about this topic? The skin microbiome of congenital ichthyoses is largely unexplored. Microbes play an important role in pathogenesis, as infections are common. The relative abundances of staphylococci and corynebacteria is increased in the cutaneous microbiome of patients with Netherton syndrome, but extension of these abundances to all congenital ichthyoses is unexplored. What does this study add? A common skin microbiome signature was observed across congenital ichthyoses. Distinct microbiome features were associated with ichthyosis subtypes. Changes in microbiome may contribute to T helper 17 cell immune polarization. What is the translational message? These data provide the basis for comparison of the microbiome with lipidomic and transcriptomic alterations in these forms of ichthyosis and consideration of correcting the dysbiosis as a therapeutic intervention.
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Eritrodermia Ictiosiforme Congénita , Ictiosis Lamelar , Ictiosis , Microbiota , Adulto , Humanos , Ictiosis/genética , Ictiosis Lamelar/genética , Lípidos , Microbiota/genética , Piel/patologíaRESUMEN
Preliminary work suggested upregulation of inflammatory pathways in patients with common forms of ichthyosis. However, a comprehensive characterization of skin from various ichthyosis subtypes is unavailable, precluding the development of targeted treatments. Thus, we sought to characterize the immune and barrier profiles of common and subtype-specific skin transcriptomes in a large group of patients with ichthyosis. We performed a global RNA-sequencing analysis in 54 patients with ichthyosis (7 with Netherton syndrome, 13 with epidermolytic ichthyosis, 16 with lamellar ichthyosis, and 18 with congenital ichthyosiform erythroderma) and 40 healthy controls. Differentially expressed genes were defined on the basis of fold changes > 2 and false discovery rate < 0.05 criteria. We found robust and significant T helper (Th) 22/Th17 skewing in all subtypes (e.g., IL-17A/C/F, S100A7/8/9/12; P < 0.001) with modest changes in Th2 pathway, primarily in Netherton syndrome, and Th1 skewing in congenital ichthyosiform erythroderma. Across all subtypes (less evident in epidermolytic ichthyosis), lipid metabolism and barrier junction markers were downregulated (e.g., FA2H, CDH10/11/12/2; P < 0.05), whereas epidermal cornification and proliferation measures were upregulated (e.g., SPRR1A/1B/2C/2G, EREG; P < 0.05). Our findings suggest that the common ichthyosis variants share aberrations in Th17/Th22 and barrier function, with minimal Th2 modulation. This may help to elucidate the pathogeneses of these subtypes and inform the development of subtype-specific treatments.