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1.
J Invest Dermatol ; 143(2): 273-283.e12, 2023 02.
Article in English | MEDLINE | ID: mdl-36116506

ABSTRACT

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by recurring suppurating lesions of the intertriginous areas, resulting in a substantial impact on patients' QOL. HS pathogenesis remains poorly understood. An autoimmune component has been proposed, but disease-specific autoantibodies, autoantigens, or autoreactive T cells have yet to be described. In this study, we identify a high prevalence of IgM, IgG, and IgA antibodies directed against Nε-carboxyethyl lysine (CEL), a methylglyoxal-induced advanced glycation end-product, in the sera of patients with HS. Titers of anti-CEL IgG and IgA antibodies were highly elevated in HS compared with those in healthy controls and individuals with other inflammatory skin diseases. Strikingly, the majority of anti-CEL IgG was of the IgG2 subclass and correlated independently with both disease severity and duration. Both CEL and anti-CEL‒producing plasmablasts could be isolated directly from HS skin lesions, further confirming the disease relevance of this autoimmune response. Our data point to an aberration of the methylglyoxal pathway in HS and support an autoimmune axis in the pathogenesis of this debilitating disease.


Subject(s)
Hidradenitis Suppurativa , Humans , Autoantibodies , Lysine , Quality of Life , Pyruvaldehyde , Immunoglobulin G
2.
J Invest Dermatol ; 140(12): 2421-2432.e10, 2020 12.
Article in English | MEDLINE | ID: mdl-32387270

ABSTRACT

Hidradenitis suppurativa (HS) is a chronic, recurring inflammatory dermatosis characterized by abscesses, deep-seated nodules, sinus tracts, and fibrosis in skin lesions around hair follicles of the axillary, inguinal, and anogenital regions. Whereas the exact pathogenesis remains poorly defined, clear evidence suggests that HS is a multifactorial inflammatory disease characterized by innate and adaptive immune components. Bioactive lipids are important regulators of cutaneous homeostasis, inflammation, and resolution of inflammation. Alterations in the lipid mediator profile can lead to malfunction and cutaneous inflammation. We used targeted lipidomics to analyze selected omega-3 and omega-6 polyunsaturated fatty acids in skin of patients with HS and of healthy volunteers. Lesional HS skin displayed enrichment of 5-lipoxygenase (LO)‒derived metabolites, especially leukotriene B4. In addition, 15-LO‒derived metabolites were underrepresented in HS lesions. Changes in the lipid mediator profile were accompanied by transcriptomic dysregulation of the 5-LO and 15-LO pathways. Hyperactivation of the 5-LO pathway in lesional macrophages identified these cells as potential sources of leukotriene B4, which may cause neutrophil influx and activation. Furthermore, leukotriene B4-induced mediators and pathways were elevated in HS lesions, suggesting a contribution of this proinflammatory lipid meditator to the pathophysiology of HS.


Subject(s)
Arachidonate 15-Lipoxygenase/metabolism , Arachidonate 5-Lipoxygenase/metabolism , Hidradenitis Suppurativa/immunology , Leukotriene B4/metabolism , Skin/pathology , Adult , Aged , Biopsy , Cells, Cultured , Fatty Acids, Omega-3/analysis , Fatty Acids, Omega-3/metabolism , Fatty Acids, Omega-6/analysis , Fatty Acids, Omega-6/metabolism , Female , Gene Expression Profiling , Hidradenitis Suppurativa/pathology , Hidradenitis Suppurativa/surgery , Humans , Inflammation/immunology , Inflammation/pathology , Leukotriene B4/immunology , Lipid Metabolism/genetics , Lipid Metabolism/immunology , Lipidomics , Male , Middle Aged , Primary Cell Culture , Signal Transduction/genetics , Signal Transduction/immunology , Skin/chemistry , Skin/immunology , Up-Regulation , Young Adult
3.
Neurourol Urodyn ; 38(6): 1657-1662, 2019 08.
Article in English | MEDLINE | ID: mdl-31134684

ABSTRACT

AIMS: The aim of this study was to identify the problems and resources of women with urinary or fecal incontinence based on the International Classification of Function and Health (ICF) framework and detecting the impact on the personal environment and quality of life. This study forms part of a project with an overall goal to enable standardized planning and evaluation of interventions in multi-professional settings. METHODS: To answer the study question a mixed-method sequential design with a priority to the quantitative approach was considered appropriate. Regarding methods, focus groups were chosen to collect data. Transcripts were analyzed with content analysis and identified concepts linked to the corresponding ICF categories by two different raters. Cohen's kappa was calculated for interrater reliability. RESULTS: Thirteen women with a mean age of 69.9 years were recruited. Four focus groups were conducted, whereas saturation was reached after two focus groups. Overall transcripts 99 defined ICF categories at second level could be linked (body functions = 31, body structures = 5, activities and participation = 33, and environmental factors = 30) whereas 4 categories were not sufficiently covered by the ICF (3 = personal factors, 1 = not covered). CONCLUSIONS: This study has determined 103 resources and problems based on the ICF model of women with urinary and/or fecal incontinence. In spite of these results, it was shown that four concepts are not fully covered by the ICF framework. The current data highlight the importance of an extension of the ICF model, especially towards the personal factors of patients.


Subject(s)
Activities of Daily Living/psychology , Fecal Incontinence/psychology , Quality of Life/psychology , Surveys and Questionnaires , Urinary Incontinence/psychology , Aged , Aged, 80 and over , Disability Evaluation , Female , Focus Groups , Humans , Male , Middle Aged , Reproducibility of Results
4.
Neurourol Urodyn ; 38(6): 1663-1668, 2019 08.
Article in English | MEDLINE | ID: mdl-31129925

ABSTRACT

AIMS: This study seeks to explore barriers faced by and resources available to male patients with urinary (UI) and/or fecal incontinence (FI) based on the ICF framework. As a result, this study contributes to the development of the ICF-Incontinence Assessment Form (ICF-IAF), which is designed to be a standardized planning and evaluation tool for interventions in a multidisciplinary setting. METHODS: A mixed-method sequential design that places emphasis on the quantitative approach was considered appropriate for this study. Focus group interviews (FG) were chosen to collect data. Data were analysed with deductive content analysis and themes identified during FG were linked to the most corresponding ICF categories by two raters. Cohen's κ was calculated to determine interrater reliability. RESULTS: Four FG were conducted with a total of 13 male participants. The mean age of the participants was 74.7 years. A total of 73 barriers and resources on the second ICF level (body functions 26, body structures five, activities and participation 26 and environmental factors 16), whereby four categories were not sufficiently covered by the ICF, could be identified. The κ score for the two raters was 0.82. CONCLUSIONS: While barriers are fundamental factors affecting patients, this study found that resources are as important and should not be overlooked in the conventional treatment in both UI and FI-specific assessments.


Subject(s)
Activities of Daily Living/psychology , Fecal Incontinence/psychology , Quality of Life/psychology , Surveys and Questionnaires , Urinary Incontinence/psychology , Aged , Aged, 80 and over , Disability Evaluation , Focus Groups , Humans , Male , Middle Aged , Reproducibility of Results
5.
J Nurs Adm ; 46(5): 284-90, 2016 May.
Article in English | MEDLINE | ID: mdl-27093185

ABSTRACT

OBJECTIVE: The aim of this study is to compare rates and reasons for registered nurse (RN) turnover by Magnet® status. BACKGROUND: Although lower RN turnover rates in Magnet hospitals have been documented well in the literature, little is known about specific separation reasons for RN turnover and whether the reasons differ between Magnet and non-Magnet hospitals. METHODS: This descriptive, correlational study analyzed unit-level 2013 National Database of Nursing Quality Indicators® turnover data (2,958 units; 497 hospitals). Poisson regression and Wilcoxon-Mann-Whitney test were used. RESULTS: Registered nurse turnover due to environment-related reasons was higher on units in non-Magnet hospitals than units in Magnet hospitals. Units in non-Magnet hospitals had 4.684 times higher turnover rates due to staffing/workload and 1.439 times higher rates due to work schedules than did units in Magnet hospitals. CONCLUSIONS: Nursing administrators in both Magnet and non-Magnet hospitals need to continually strive to improve unit work environments, particularly staffing and workload conditions and work scheduling.


Subject(s)
Hospitals/classification , Nursing Staff, Hospital/psychology , Personnel Turnover/statistics & numerical data , Career Mobility , Databases, Factual , Family , Hospitals/standards , Humans , Multilevel Analysis , Nursing Staff, Hospital/economics , Nursing Staff, Hospital/organization & administration , Organizational Culture , Personnel Staffing and Scheduling , Personnel Turnover/economics , Poisson Distribution , Retirement , Social Environment , Workforce , Workload
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