Clinical and radiographic predictors for angiography in pelvic trauma: An analysis of 1703 patients.

INTRODUCTION: Patients who present with hemorrhage from pelvic fractures have an increased risk of mortality with prolonged time to intervention. Identifying risk factors associated with hemorrhage can expedite treatment. In this study we explore clinical and radiographic predictors for angiography in trauma patients with pelvic fractures. METHOD: Retrospective, single-center review between 2009 and 2019 at a level 1 trauma center of all trauma patients with pelvic fractures. We excluded patients who died prior to arrival or in the trauma bay who did not undergo computed tomography ("CT"). Finalized attending descriptions of CT findings were reviewed, including size of hematomas, and presence of extravasation. Chi-square, Mann-Whitney U and multi-variate regressions were performed. RESULTS: We analyzed 1,703 trauma patients with pelvic fractures. Most common mechanisms of injury included MVC (45 %), fall (27 %) and motorcycle accident (12 %). 48 % (819/1703) of patients had pelvic hematomas on CT scan. 17 %(138/819) of patients with a hematoma also had evidence of extravasation. Significant predictors for extravasation on CT included large hematoma on CT, AIS extremity ≥2, binder placement, increased ISS, HR, and decreased GCS and SBP (p < 0.005). Significant predictors for angiography were similar, including AIS extremity ≥2, binder placement, presence of moderate and large hematoma and active extravasation on CT (p < 0.01). Stepwise logistic regression model incorporated ISS, HR, AIS extremity score, binder placement, and contrast extravasation with an AUC = 0.9345. CONCLUSION: In this large retrospective review of traumatic pelvic fractures, specific clinical and radiographic factors were significantly associated with pelvic hematomas, extravasation and/or need for angiography. Future collaborative work with orthopedics and interventional radiology is planned to better triage pelvic fracture patients and identify those at risk for bleeding that require earlier intervention.

A value-based healthcare model for initiating and switching psoriasis therapies-Results from the prospective multicentre IMPROVE study.

BACKGROUND: Little is known about the therapeutic benefits of a value-based healthcare model compared to a traditional activity-based incentive model in psoriasis (PsO). OBJECTIVES: This prospective non-interventional study evaluated an outcome-based, patient-centred management model for patients with PsO. METHODS: In total, 49 patients with a Psoriasis Area and Severity Index (PASI) ≥3 who were starting or switching between treatments were included. Patients were assessed at baseline, 3 and 9 months. The patient benefit index (PBI) was calculated using predefined questionnaires. An expected PBI was calculated and adjusted for risk factors known to complicate treatment, that is overweight and smoking. The model remunerated the department on whether the observed PBI exceeded the expected PBI to incentivize over-performance. RESULTS: In total, 40 patients (80%) completed all three visits; 32.7% were smokers and 73.5% were overweight. Mean PASI at baseline was 11.5 (SD 9.1); PASI improved significantly from baseline through 3 months: mean reduction, 8.0 (SD 9.2), p < 0.001 and was maintained until 9 months: mean further reduction, 0.1 (SD 3.3), p = 0.893. The mean PBI was 2.5 (SD 1.3) and 2.8 (SD 1.1) at 3 and 9 months, respectively. A PBI ≥1 was achieved by 87.8% at 3 and 95.1% at 9 months. Overall, the department was remunerated a mean 2721.1 DKK (SD 4472.8) per patient. In subgroup analysis, the department was remunerated a mean of, respectively, 2428.6 (SD 5089.5), 2636.6 (SD 4471.3) and 3196.5 (SD 4497.1) DKK for patients with none, 1 or 2 risk factors, that is smoking or/and overweight. CONCLUSIONS: The model evaluated herein is the first value-based model to calculate remuneration from patient reported outcomes and showed to successfully predict the expected PBI and remunerate treatment based on whether the expected treatment goal was met or exceeded. This can be utilized in the patient-centred management of PsO.

ESMO Expert Consensus Statements on Cancer Survivorship: promoting high-quality survivorship care and research in Europe.

BACKGROUND: The increased number of cancer survivors and the recognition of physical and psychosocial challenges, present from cancer diagnosis through active treatment and beyond, led to the discipline of cancer survivorship. DESIGN AND METHODS: Herein, we reflected on the different components of survivorship care, existing models and priorities, in order to facilitate the promotion of high-quality European survivorship care and research. RESULTS: We identified five main components of survivorship care: (i) physical effects of cancer and chronic medical conditions; (ii) psychological effects of cancer; (iii) social, work and financial effects of cancer; (iv) surveillance for recurrences and second cancers; and (v) cancer prevention and overall health and well-being promotion. Survivorship care can be delivered by structured care models including but not limited to shared models integrating primary care and oncology services. The choice of the care model to be implemented has to be adapted to local realities. High-quality care should be expedited by the generation of: (i) focused and shared European recommendations, (ii) creation of tools to facilitate implementation of coordinated care and (iii) survivorship educational programs for health care teams and patients. The research agenda should be defined with the participation of health care providers, researchers, policy makers, patients and caregivers. The following patient-centered survivorship research areas were highlighted: (i) generation of a big data platform to collect long-term real-world data in survivors and healthy controls to (a) understand the resources, needs and preferences of patients with cancer, and (b) understand biological determinants of survivorship issues, and (ii) develop innovative effective interventions focused on the main components of survivorship care. CONCLUSIONS: The European Society for Medical Oncology (ESMO) can actively contribute in the efforts of the oncology community toward (a) promoting the development of high-quality survivorship care programs, (b) providing educational material and (c) aiding groundbreaking research by reflecting on priorities and by supporting research networking.

Fit for Surgery-feasibility of short-course multimodal individualized prehabilitation in high-risk frail colon cancer patients prior to surgery.

BACKGROUND: Prehabilitation is a promising modality for improving patient-related outcomes after major surgery; however, very little research has been done for those who may need it the most: the elderly and the frail. This study aimed to investigate the feasibility of a short course multimodal prehabilitation prior to primary surgery in high-risk, frail patients with colorectal cancer and WHO performance status I and II. METHODS: The study was conducted as a single-center, prospective one-arm feasibility study of eight patients with colon cancer between October 4, 2018, and January 14, 2019. The intervention consisted of a physical training program tailored to the patients with both high-intensity interval training and resistance training three times a week in sessions of approximately 1 h in length, for a duration of at least 4 weeks, nutritional support with protein and vitamins, a consultation with a dietician, and medical optimization prior to surgery. Feasibility was evaluated regarding recruitment, retention, compliance and adherence, acceptability, and safety. Retention was evaluated as the number of patients that completed the intervention, with a feasibility goal of 75% completing the intervention. Compliance with the high-intensity training was evaluated as the number of sessions in which the patient achieved a minimum of 4 min > 90% of their maximum heart rate and adherence as the attended out of the offered training sessions. RESULTS: During the study period, 64 patients were screened for eligibility, and out of nine eligible patients, eight patients were included and seven completed the intervention (mean age 80, range 66-88). Compliance to the high-intensity interval training using 90% of maximum heart rate as the monitor of intensity was difficult to measure in several patients; however, adherence to the training sessions was 87%. Compliance with nutritional support was 57%. Half the patients felt somewhat overwhelmed by the multiple appointments and six out of seven reported difficulties with the dosage of protein. CONCLUSIONS: This one-arm feasibility study indicates that multimodal prehabilitation including high-intensity interval training can be performed by patients with colorectal cancer and WHO performance status I and II. TRIAL REGISTRATION: Clinicaltrials.gov : the study current feasibility study was conducted prior to the initiation of a full ongoing randomized trial registered by NCT04167436; date of registration: November 18, 2019. Retrospectively registered. No separate prospectively registration of the feasibility trial was conducted but outlined by the approved study protocol (Danish Scientific Ethical Committee SJ-607).

The mitochondrial DNA constitution shaping T-cell immunity in patients with rectal cancer at high risk of metastatic progression.

PURPOSE: A significant percentage of colorectal cancer patients proceeds to metastatic disease. We hypothesised that mitochondrial DNA (mtDNA) polymorphisms, generated by the high mtDNA mutation rate of energy-demanding clonal immune cell expansions and assessable in peripheral blood, reflect how efficiently systemic immunity impedes metastasis. PATIENTS AND METHODS: We studied 44 rectal cancer patients from a population-based prospective biomarker study, given curative-intent neoadjuvant radiation and radical surgery for high-risk tumour stage and followed for metastatic failure. Blood specimens were sampled at the time of diagnosis and analysed for the full-length mtDNA sequence, composition of immune cell subpopulations and damaged serum mtDNA. RESULTS: Whole blood total mtDNA variant number above the median value for the study cohort, coexisting with an mtDNA non-H haplogroup, was representative for the mtDNA of circulating immune cells and associated with low risk of a metastatic event. Abundant mtDNA variants correlated with proliferating helper T cells and cytotoxic effector T cells in the circulation. Patients without metastatic progression had high relative levels of circulating tumour-targeting effector T cells and, of note, the naïve (LAG-3+) helper T-cell population, with the proportion of LAG-3+ cells inversely correlating with cell-free damaged mtDNA in serum known to cause antagonising inflammation. CONCLUSION: Numerous mtDNA polymorphisms in peripheral blood reflected clonal expansion of circulating helper and cytotoxic T-cell populations in patients without metastatic failure. The statistical associations suggested that patient's constitutional mtDNA manifests the helper T-cell capacity to mount immunity that controls metastatic susceptibility. TRIAL REGISTRATION: ClinicalTrials.gov NCT01816607; registration date: 22 March 2013.

HSP90 inhibitor RGRN-305 for oral treatment of plaque-type psoriasis: efficacy, safety and biomarker results in an open-label proof-of-concept study.

BACKGROUND: HSP90 is a downstream regulator of tumour necrosis factor (TNF)-α and interleukin (IL)-17A signalling and may therefore serve as a novel target in the treatment of psoriasis. OBJECTIVES: This phase Ib proof-of-concept study was undertaken to evaluate the safety and efficacy of a novel HSP90 inhibitor (RGRN-305) in the treatment of plaque psoriasis. METHODS: We conducted an open-label, single-arm, dose-selection, single-centre proof-of-concept study. Patients with plaque psoriasis were treated with 250 mg or 500 mg RGRN-305 daily for 12 weeks. Efficacy was evaluated clinically using the Psoriasis Area and Severity Index (PASI), body surface area (BSA), Physician's Global Assessment (PGA) scores and the Dermatology Life Quality Index (DLQI). Skin biopsies collected at baseline and at 4, 8 and 12 weeks after initiation of treatment were used for immunohistochemical staining and for gene expression analysis. Safety was monitored via laboratory tests, vital signs, electrocardiogram and physical examinations. RESULTS: Six of the 11 patients who completed the study responded to RGRN-305 with a PASI improvement between 71% and 94%, whereas five patients were considered nonresponders with a PASI response < 50%. No severe adverse events were reported. Four of seven patients treated with 500 mg RGRN-305 daily experienced a mild-to-moderate exanthematous drug-induced eruption owing to the study treatment. Two patients chose to discontinue the study because of this exanthematous eruption. RGRN-305 treatment resulted in pronounced inhibition of the IL-23, TNF-α and IL-17A signalling pathways and normalization of both histological changes and psoriatic lesion gene expression profiles in patients who responded to treatment. CONCLUSIONS: Treatment with RGRN-305 showed acceptable safety, especially in the low-dose group, and was associated with clinically meaningful improvement in a subset of patients with plaque psoriasis, indicating that HSP90 may serve as a novel future target in psoriasis treatment.

The potential of iodinated contrast reduction in dual-energy CT thoracic angiography; an evaluation of image quality.

INTRODUCTION: The purpose of this study was to compare a dual energy CT (DECT) protocol with 50% reduction of iodinated contrast to a single energy CT (SECT) protocol using standard contrast dose in imaging of the thoracic aorta. METHODS: DECT with a 50% reduction in iodinated contrast was compared with SECT. For DECT, monoenergetic images at 50, 55, 60, 65, 68, 70, and 74 keV were reconstructed with adaptive statistical iterative reconstruction (ASiR-V) of 50% and 80%. Objective image quality parameters included intravascular attenuation (HU), image noise (SD), contrast-to-noise ratio (CNR), and signal-to-noise ratio (SNR). Two independent radiologists subjectively assessed the image quality for the 55 and 68 keV DECT reconstructions and SECT on a five-point Likert scale. RESULTS: Across 14 patients, the intravascular attenuation at 50-55 keV was comparable to SECT (p > 0.05). The CNRs were significantly lower for DECT with ASIR-V 50% compared to SECT for all keV-values (p < 0.05 for all). For ASIR-V 80%, CNR was comparable to SECT at energies below 60 keV (p > 0.05). The subjective image quality was comparable between DECT and SECT independent of keV level. CONCLUSION: This study indicates that a 50% reduction in iodinated contrast may result in adequate image quality using DECT with monoenergetic reconstructions at lower energy levels for the imaging of the thoracic aorta. The best image quality was obtained for ASiR-V 80% image reconstructions at 55 keV. IMPLICATIONS OF PRACTICE: Dual energy CT with a reduction in iodinated contrast may result in adequate image quality in imaging of the thoracic aorta. However, increased radiation dose may limit the use to patients in which a reduction in fluid and iodinated contrast volume may outweigh this risk.

Early indicators of primary brain tumours: a population-based study with 10 years' follow-up.

BACKGROUND AND PURPOSE: To improve diagnoses of primary brain tumours, knowledge about early indicators is needed. Nationwide Danish health registries were used to conduct a population-based case-control study including all persons diagnosed with a primary brain tumour between 2005 and 2014 in Denmark. METHODS: All 5135 adults diagnosed with a primary brain tumour in the Danish Cancer Registry were matched to 19 572 general population comparisons from the Danish Civil Registration System. Conditional logistic regression analyses were applied to estimate age- and multivariable-adjusted odds ratios (ORs) for the occurrence of a primary brain tumour up to 10 years after hospital diagnoses or prescription of medications related to nervous system diseases and mental and behavioural disorders. RESULTS: Increased odds for primary brain tumour after nervous system diseases and mental and behavioural disorders manifested up to 10 years before tumour diagnosis were found. Increased odds were seen especially for hospital contacts for inflammatory nervous system diseases [OR 11.3; 95% confidence interval (CI) 6.5-19.7], epilepsy (OR 9.0; 95% CI 7.6-10.7) and antiepileptic medications (OR 3.6; 95% CI 3.2-4.0), whilst antidementia medications provided a strong, protective association for primary brain tumours (OR 0.5; 95% CI 0.3-0.8). CONCLUSIONS: Sub-groups of patients diagnosed with or being prescribed certain medications targeting nervous system diseases and mental and behavioural disorders may be at increased risk of being diagnosed with a primary brain tumour. Further studies should disentangle the potential underlying common pathogenetic pathways. The results are important for the development of systematic clinical approaches to ensure early diagnosis of primary brain tumours.

Feasibility and estimated efficacy of blood flow restricted training in female patients with rheumatoid arthritis: a randomized controlled pilot study.

Objectives: The study aimed to evaluate the feasibility of a blood flow restriction (BFR) training regimen in patients with rheumatoid arthritis (RA); and to compare the effects of 4 weeks of BFR training with low-intensity strength training on muscle strength, muscle endurance, and joint pain in patients with RA.Method: In this non-blinded pilot randomized controlled trial, 18 women with RA aged 18-65 years performed low-intensity strength training for the lower limbs three times a week for 4 weeks, and were randomized to train with or without occlusion bands. The primary outcomes were registration of the recruitment process, compliance with training sessions, side effects, perceived pain, and a satisfaction survey. The secondary outcomes were changes in muscle strength, muscle endurance, and joint pain.Results: The findings of this pilot study included a challenging recruitment process, well tolerated training and test protocols, overall good patient satisfaction, no serious side effects, and high compliance. Both groups achieved significant improvements in knee extensor strength from baseline to follow-up, with a change of 11.5 kg [interquartile range (IQR) 9.8;13.0] in the intervention group and 8.4 kg (IQR 5.5;12.4) in the control group, and a significant between-group difference in favour of the intervention group (p = 0.0342).Conclusions: The feasibility results of this study indicated a challenging recruitment process, general satisfaction with the BFR and exercises, good compliance, and only expected non-serious side effects. BFR training may improve knee extensor strength in women with RA, compared low-intensity strength training without BFR.

Correction to: Quality of life in bladder cancer patients receiving medical oncological treatment; a systematic review of the literature.

The original article contains a major error whereby a main Table is omitted. Thus, the following corrections to the original article should be considered.

Quality of life in bladder cancer patients receiving medical oncological treatment; a systematic review of the literature.

BACKGROUND: Previous quality of life (QoL) literature in bladder cancer (BC) patients has focused on finding the preferred urinary diversion while little is known about the QoL of patients in medical oncological treatment (MOT). We performed a systematic review to assess the existing literature on QoL in patients with muscle-invasive BC (MIBC) undergoing MOT. METHODS: A systematic search of Pubmed and Embase was performed. Inclusion criteria were studies containing QoL data for patients undergoing chemo- and/or radiotherapy. We extracted all QoL scorings at different time intervals and on the six most prevalent domains: overall QoL, urinary, bowel sexual symptoms, pain and fatigue. The study was carried out according to PRISMA guidelines for systematic reviews and GRADE was used to rate the quality of evidence from the included studies. RESULTS: Of 208 papers reviewed, 21 papers were included. Twenty-one different QoL instruments were applied. The only data on QoL during chemotherapy was from patients in clinical trials investigating new treatments. No studies were found for patients in neoadjuvant treatment. The level of evidence at each time point was graded as very low to moderate. From the studies included the overall QoL seemed inversely related to the organ-specific impairment from sexual and urinary symptoms and increased with decreasing organ-specific symptoms for long term survivors > 6 months after treatment. CONCLUSIONS: Collection of data on QoL from patients with MIBC disease undergoing MOT has been sparse and diverse. The present data can act as a summary but prompts for more prospective collection of QoL data from BC patients.

Does losing a parent early influence the education you obtain? A nationwide cohort study in Denmark.

BACKGROUND: Health inequalities are rooted in education and we investigate the association between early parental death and attainment across the educational spectrum. METHODS: Using total population data on Danes born between 1982 and 2000 (n = 1 043 813), we assess incidence rate ratios (RRs) by gender for attainment of each educational level (basic school, high school or vocational training, bachelor degree or professional programme, and university graduate degree) according to loss of a parent before the age of 18 years. We adjust for family income, education and psychiatric illness and examine parent's gender, cause of death and child's age at time of death as potential moderators. RESULTS: Bereaved people had significantly lower attainment rates than non-bereaved people: basic school (RR = 0.95; 95% CI: 0.93-0.97 for men and 0.96; 0.94-0.98 for women), high school or vocational training (0.78; 0.76-0.80 for men and 0.82; 0.80-0.84 for women), bachelor degree or professional programme (0.74; 0.70-0.79 for men and 0.83; 0.79-0.86 for women) and university graduate degree (0.77; 0.68-0.86 for men and 0.77; 0.69-0.86 for women). Parent's gender, cause of death and child's age at the death did not modify the associations. CONCLUSIONS: As education impacts population health, support for bereaved school children may be more important than realized.

The effect of an attachment-oriented couple intervention for breast cancer patients and partners in the early treatment phase: A randomised controlled trial.

OBJECTIVE: Patients and partners both cope individually and as a dyad with challenges related to a breast cancer diagnosis. The objective of this study was to evaluate the effect of a psychological attachment-oriented couple intervention for breast cancer patients and partners in the early treatment phase. METHODS: A randomised controlled trial including 198 recently diagnosed breast cancer patients and their partners. Couples were randomised to the Hand in Hand (HiH) intervention in addition to usual care or to usual care only. Self-report assessments were conducted for both patients and partners at baseline, postintervention (5 months), and follow-up (10 months), assessing cancer-related distress, symptoms of anxiety and depression, and dyadic adjustment. Patients' cancer-related distress was the primary outcome. RESULTS: Cancer-related distress decreased over time in both patients and partners, but the intervention did not significantly affect this decrease at postintervention (P = .08) or follow-up (P = .71). A significant positive effect was found on dyadic adjustment at follow-up for both patients (P = .04) and partners (P = .02). CONCLUSIONS: There was no significant effect of the HiH intervention cancer-related distress. The results suggest that most couples can cope with cancer-related distress in the context of usual care. However, the positive effect on dyadic adjustment implies that the HiH intervention benefitted both patients and partners. Future studies should investigate how to integrate a couple focus in usual cancer care to improve dyadic coping in the early treatment phase.

Depression and anxiety following hematopoietic stem cell transplantation: a prospective population-based study in Germany.

In this prospective multicenter study, we investigated the course of depression and anxiety during hematopoietic stem cell transplantation (HSCT) until 5 years after transplantation adjusting for medical information. Patients were consulted before HSCT (n=239), at 3 months (n=150), 12 months (n=102) and 5 years (n=45) after HSCT. Depression and anxiety were assessed with the Hospital Anxiety and Depression Scale (HADS). Detailed medical and demographic information was collected. Prevalence rates were compared with an age- and gender-matched control group drawn from a large representative sample (n=4110). The risk of depression before HSCT was lower for patients than for the control group (risk ratio (RR), 0.56; 95% confidence interval (CI), 0.39/0.81). Prevalence rates of depression increased from 12 to 30% until 5 years post HSCT. Anxiety rates were most frequently increased before HSCT (29%, RR, 1.31; 95% CI, 1.02/1.68) and then reached a stable level comparable to the background population (RR 0.83, 95% CI, 0.56/1.22). This study confirms the low levels of depression in the short term after HSCT and identifies depression as a long-term effect. Furthermore, it confirms previous results of heightened anxiety before HSCT. Surveillance of symptoms of anxiety during the short-term phase of HSCT and of depression during the following years is crucial.

The risk of being depressed is significantly higher in cancer patients than in the general population: Prevalence and severity of depressive symptoms across major cancer types.

BACKGROUND: Depression is a common co-morbidity of cancer that has a detrimental effect on quality of life, treatment adherence and potentially survival. We conducted an epidemiological multi-center study including a population-based random comparison sample and estimated the prevalence of depressive symptoms by cancer site, thereby identifying cancer patients with the highest prevalence of depression. PATIENTS AND METHODS: We included 4020 adult cancer inpatients and outpatients from five distinct regions across Germany in a proportional stratified random sample based on the nationwide cancer incidence and a comparison group consisting of 5018 participants. Both groups reported depressive symptoms by filling in the Patient Health Questionnaire (PHQ-9). In multivariate analyses adjusted for age and sex, we calculated the odds of being depressed. RESULTS: Out of 5818 eligible patients, 69% participated (51% women, mean age = 58 years). We estimated that one in four cancer patients (24%) is depressed (PHQ-9 ≥ 10). The odds of being depressed among cancer patients were more than five times higher than in the general population (OR, 5.4; 95% CI, 4.6-6.2). Patients with pancreatic (M = 8.0, SD = 5.0), thyroid (M = 7.8, SD = 6.3) and brain tumours (M = 7.6, SD = 4.9) showed the highest prevalence, whereas patients with prostate cancer (M = 4.3, SD = 3.8) and malignant melanoma (M = 5.3, SD = 4.3) had the lowest levels of depressive symptoms. CONCLUSION: Our results help clinicians identify cancer patients in need of psychosocial support when navigating in the growing survivor population.

Danish guidelines on management of otitis media in preschool children.

INTRODUCTION: Otitis media is one of the most common diseases in small children. This underlines the importance of optimizing diagnostics and treatment of the condition. Recent literature points toward a stricter approach to diagnosing acute otitis media (AOM). Moreover, ventilating tube treatment for recurrent AOM (RAOM) and chronic otitis media with effusion (COME) has become the most frequently performed surgical procedure in pre-school children. Therefore, the Danish Health and Medicines Authority and the Danish Society of Otorhinolaryngology, Head and Neck Surgery deemed it necessary to update the Danish guidelines regarding the diagnostic criteria for acute otitis media and surgical treatment of RAOM and COME. METHODS: The GRADE system (The Grading of Recommendations Assessment, Development and Evaluation) was used in order to comply with current standards of evidence assessment in formulation of recommendations. An extensive literature search was conducted between July and December 2014. The quality of the existing literature was assessed using AGREE II (Appraisal of Guidelines for Research & Evaluation), AMSTAR (assessing the Methodological Quality of Systematic Reviews), QUADAS-2 (Quality of Diagnostic Accuracy Studies), Cochrane Risk of Bias Tool for randomized trials and ACROBAT-NRSI (A Cochrane Risk of Bias Assessment Tool for Non-Randomized Studies). The working group consisted of otolaryngologists, general practitioners, pediatricians, microbiologists and epidemiologists. CONCLUSION: Recommendations for AOM diagnosis, surgical management for RAOM and COME, including the role of adenoidectomy and treatment of ventilating tube otorrhea, are proposed in the guideline.

TSLP, IL-31, IL-33 and sST2 are new biomarkers in endophenotypic profiling of adult and childhood atopic dermatitis.

BACKGROUND: Recent years have seen growing interest in identifying new biomarkers in atopic dermatitis (AD) that could serve as indicators of disease severity and predictors of treatment response. OBJECTIVES: We compared serum levels of thymic stromal lymphopoietin (TSLP), interleukin(IL)-31, IL-33 and soluble(s)ST2 in AD patients and healthy controls, investigated the possible correlation with disease severity, investigated if other atopic comorbidities could play a role, and assessed their potential as biomarkers in AD. METHODS: Using standard enzyme-linked immunosorbent assay techniques, we measured target serum levels in 71 adults and 61 children with AD, and 31 adult controls. We characterized our cohort by disease severity, radioallergosorbent test status concerning both dietary and inhalant allergens, and anamnestic reports of food allergy, concomitant allergic asthma and/or allergic rhinitis. RESULTS: Serum levels of TSLP, IL-31 and IL-33, but not sST2, were significantly elevated in AD patients compared with controls. In AD patients, both IL-31 and IL-33 serum levels were higher in children than in adults, while the opposite was the case for sST2. We observed no correlation between disease severity and any of the investigated targets. While serum TSLP levels were unaffected by concomitant allergies and atopic comorbidities, serum levels of IL-31, IL-33 and sST2 were affected to a small extent. We found a positive correlation between TSLP, IL-31 and IL-33, and an inverse relationship between IL-33 and sST2. CONCLUSIONS: The studied targets hold little potential as indicators of disease severity. The serum values of our targets show robustness against atopic comorbidities, allergies and changes in disease severity. This robustness strengthens their potential use in biomarker-based stratification and could be instrumental in identifying subgroups and predicting the possible benefit of therapeutic and prevention approaches.

Tumour necrosis factor-α plays a significant role in the Aldara-induced skin inflammation in mice.

BACKGROUND: Recently, the Aldara-induced psoriasis-like skin inflammation model in mice has attracted increased attention, due to its dependence on the same immunological pathways and cell types as in human psoriasis. OBJECTIVES: To study the impact of constitutive deficiency of tumour necrosis factor (TNF)-α and its upstream regulator mitogen-activated protein kinase-activated protein kinase 2 (MAPKAPK-2, herein MK2) in the Aldara-induced psoriasis-like skin inflammation model. METHODS: TNF-α knockout (KO), MK2 KO and wild-type (WT) mice divided into separate groups received either 45-mg Aldara cream or control cream for 5 consecutive days. The skin inflammation was evaluated clinically, histologically, and by quantitative reverse transcription-polymerase chain reaction. RESULTS: We found that TNF-α KO mice developed significantly less skin inflammation compared with WT mice, as evaluated clinically and histologically. At the molecular level, we demonstrated that the Aldara-induced mRNA expression of the psoriasis-related inflammatory markers interleukin (IL)-17C, IL-23p19, IL-12p40, IL-17A, IL-22 and S100A8 was significantly decreased in TNF-α KO mice compared with WT mice. No significant difference in the mRNA expression of these inflammatory markers between MK2 KO mice and WT mice was found, although Aldara-treated MK2 KO mice showed a tendency towards a lower mRNA expression of IL-17A and IL-22 compared with WT mice. CONCLUSIONS: We were able to demonstrate significantly lower levels of inflammation in TNF-α KO mice compared with WT mice, supporting the use of this model in future studies characterizing the role of TNF-α in psoriasis.