RESUMO
BACKGROUND: It is unknown whether skin biomarkers collected in infancy can predict the onset of atopic dermatitis (AD) and be used in future prevention trials to identify children at risk. OBJECTIVES: This study sought to examine whether skin biomarkers can predict AD during the first 2 years of life. METHODS: This study enrolled 300 term and 150 preterm children at birth and followed for AD until the age of 2 years. Skin tape strips were collected at 0 to 3 days and 2 months of age and analyzed for selected immune and barrier biomarkers. Hazard ratio (HR) with 95% confidence interval (CI) using Cox regression was calculated for the risk of AD. RESULTS: The 2-year prevalence of AD was 34.6% (99 of 286) and 21.2% (25 of 118) among term and preterm children, respectively. Skin biomarkers collected at birth did not predict AD. Elevated thymus- and activation-regulated chemokine/C-C motif chemokine ligand 17 -levels collected at 2 months of age increased the overall risk of AD (HR: 2.11; 95% CI: 1.36-3.26; P = .0008) and moderate-to-severe AD (HR: 4.97; 95% CI: 2.09-11.80; P = .0003). IL-8 and IL-18 predicted moderate-to-severe AD. Low filaggrin degradation product levels increased the risk of AD (HR: 2.04; 95% CI: 1.32-3.15; P = .001). Elevated biomarker levels at 2 months predicted AD at other skin sites and many months after collection. CONCLUSIONS: This study showed that noninvasively collected skin biomarkers of barrier and immune pathways can precede the onset of AD.
Assuntos
Dermatite Atópica , Criança , Recém-Nascido , Humanos , Pré-Escolar , Dermatite Atópica/epidemiologia , Pele , Quimiocina CCL17 , Biomarcadores , Quimiocinas , Interleucina-18 , Índice de Gravidade de DoençaRESUMO
BACKGROUND: There is currently no insight into biomarkers that can predict the onset of pediatric atopic dermatitis (AD). METHODS: Nested in a prospective birth cohort study that examined the occurrence of physician-diagnosed AD in 300 children, 44 random children with onset of AD in the first year of life were matched on sex and season of birth with 44 children who did not develop AD. Natural moisturizing factor (NMF), corneocyte surface protrusions, cytokines, free sphingoid bases (SBs) of different chain lengths and their ceramides were analyzed from tape strips collected at 2 months of age before onset of AD using liquid chromatography, atomic force microscopy, multiplex immunoassay, and liquid chromatography mass spectrometry, respectively. RESULTS: Significant alterations were observed for four lipid markers, with phytosphingosine ([P]) levels being significantly lower in children who developed AD compared with children who did not (median 240 pmol/mg vs. 540 pmol/mg, p < 0.001). The two groups of children differed in the relative amounts of SB of different chain lengths (C17, C18 and C20). Thymus- and activation-regulated chemokine (TARC/CCL17) was slightly higher in children who developed AD, whereas NMF and corneocyte surface texture were similar. AD severity assessed by the eczema area and severity index (EASI) at disease onset was 4.2 (2.0;7.2). [P] had the highest prediction accuracy among the biomarkers (75.6%), whereas the combination of 5 lipid ratios gave an accuracy of 89.4%. CONCLUSION: This study showed that levels and SB chain length were altered in infants who later developed AD, and that TARC/CCL17 levels were higher.
Assuntos
Dermatite Atópica , Criança , Lactente , Humanos , Dermatite Atópica/diagnóstico , Estudos de Coortes , Estudos Prospectivos , Quimiocina CCL17 , Biomarcadores , Índice de Gravidade de Doença , CeramidasRESUMO
BACKGROUND: Staphylococcus aureus may worsen already established atopic dermatitis (AD), but its primary role in the aetiopathogenesis and severity of AD is unclear. OBJECTIVES: To compare the prevalence of S. aureus colonization in early infancy in children who developed AD during the first 2â years of life with children who did not. METHODS: In this prospective birth cohort study, which included 450 infants, we analysed bacterial swabs collected from cheek skin at 0 and 2â months of age. The development of AD, and its severity, was diagnosed by a physician and monitored prospectively for 2â years. Information on parental atopy, filaggrin gene mutation status and use of antibiotics and emollients was included in the analyses. RESULTS: At birth, the occurrence of S. aureus colonization was similar in infants who developed subsequent AD and those who did not. At 2â months of age, S. aureus colonization was more common in children who later developed AD (adjusted hazard ratio 1.97, 95% confidence interval 1.21-3.19; P = 0.006). No association was found between S. aureus colonization and AD severity or age at onset. CONCLUSIONS: It remains unknown whether colonization with S. aureus may directly increase the risk of AD, or whether it should be considered as secondary to skin barrier impairment or a skewed immune activity, but according to our findings, S. aureus colonization is more commonly increased at 2â months of age in children who later developed AD.
Assuntos
Dermatite Atópica , Infecções Estafilocócicas , Lactente , Criança , Recém-Nascido , Humanos , Dermatite Atópica/complicações , Staphylococcus aureus , Estudos de Coortes , Estudos Prospectivos , Coorte de Nascimento , Bochecha , Infecções Estafilocócicas/complicações , Infecções Estafilocócicas/epidemiologiaRESUMO
In Denmark, around 4,500 people are diagnosed with colorectal cancer (CRC) annually. This review investigates that while the efficacy of immunotherapy in CRC is still being studied, immunotherapy is currently only indicated in the treatment of mismatch-repair deficient (dMMR) metastatic CRC, which accounts for 10-15% of patients. Recent studies indicate high rates of pathologic response in dMMR CRC treated with pre-operative immunotherapy while large-scale studies on novel immunotherapy combinations are ongoing.
Assuntos
Neoplasias do Colo , Neoplasias Colorretais , AVC Isquêmico , Arterite de Takayasu , Humanos , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/terapia , Neoplasias Colorretais/patologia , ImunoterapiaRESUMO
It is currently unknown whether alterations in the skin microbiome exist before development of atopic dermatitis (AD). In this prospective Danish birth cohort of 300 children, we examined whether skin microbiome alterations during the first 2 months of life were associated with an increased risk of AD in the first 2 years and its severity after adjustment for environmental factors and selected skin chemokine and natural moisturizing factor levels. We found no overall association between the skin microbiome at birth and age 2 months and AD during the first 2 years of life. However, when restricting the analysis to children with at least one parent with atopy, a lower alpha diversity at age 2 months was associated with an increased risk of AD (adjusted hazard ratio = 1.7, 95% confidence interval = 1.1-2.6). We observed a stronger association in children where both parents had atopy (adjusted hazard ratio = 4.4, 95% confidence interval = 1.1-18.2). The putative pathogenic role of changes in the skin microbiome on AD risk remains uncertain but may play a role in those with an atopic predisposition.