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Background Vascular endothelial growth factor-A (VEGF-A) is known as the major skin angiogenesis factor and can be produced by various resident skin cells including keratinocytes. Objectives To identify and characterize the role of VEGF-A in the pathogenesis of prurigo. Methods Expression of VEGF, VEGFR2, CD-31, and D2-40 was analyzed in the skin of eleven prurigo patients and seven healthy controls by immunohistochemistry. Results VEGF immunoreactivity (IR) was markedly increased in the epidermis, dermis and subcutis of prurigo patients, whereas expression of the main receptor for VEGF-A in the skin, VEGFR2, was comparable to that of healthy controls. The increased VEGF expression in the skin was associated with a marked increase in the number (12.8 ± 2.1 vs 5.6 ± 0.5, P < 0.05) but not in the size of blood vessels, as assessed by staining of the endothelial cell marker CD31. This increase in small blood vessels correlated closely with increases in the epidermal thickness in prurigo lesions. The number of lymphatic vessels as assessed by D2-40 staining was found to be similar in prurigo patients and healthy controls. Conclusions Based on these findings, we speculate that the observed profound vascular remodelling in prurigo might contribute to the pathogenesis of prurigo and the corresponding clinical symptoms and that targeting of VEGF may present a novel therapeutic strategy in the treatment of prurigo patients. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Immune checkpoint inhibitors (ICI) are considered standard‐of‐care in the systemic treatment of melanoma. However, management of certain ICI‐associated adverse events (AE) can be challenging. Incidence, course and management of immune checkpoint inhibitor‐induced pancreatic injury (ICIPI) are not well‐documented and specific diagnostic and therapeutic algorithms are lacking. Current management includes serological monitoring of pancreatic enzymes, radiographic imaging and corticosteroid or further immunosuppressive treatment. Objectives: Based on previous data regarding adjuvant ICI treatment, we suspected that elevation of pancreatic enzymes may occur more frequently than reported while the clinical relevance of—particularly asymptomatic—ICIPI is still unclear.A collaboration of eight Austrian and Swiss dermato‐oncology centres was established to retrospectively analyse a large cohort of ICI‐treated patients regarding incidence and management of ICIPI. Additionally, a questionnaire‐based survey concerning ICIPI‐management was conducted.Among 1516 melanoma patients receiving ICI therapy, 204 patients exhibited ≥CTCAE II° lipase elevation. Of these patients, 41 (20.1%) had symptoms suggestive of pancreatitis. Immunotherapy was interrupted or discontinued due to pancreatic AE in almost half of the patients. Systemic corticosteroids were administered in 103 patients (50.5%), with higher doses reported in symptomatic cases. Six per cent of asymptomatic patients had radiographically proven pancreatitis. Maximum lipase elevation was >5xULN in all of these patients.Routine lipase monitoring was conducted in all participating centres, although not recommended in respective guidelines. Elevation of serum lipase was observed more frequently than recently reported. Although radiographic findings indicating pancreatitis were rare in asymptomatic patients, ICI treatment was frequently paused or discontinued and systemic steroids were administered. To reduce the existing uncertainty in routine clinical practice reflected by our findings, we provide an algorithm to guide the monitoring and management of potential pancreatic adverse events. Lipase measurement should be limited to symptomatic patients and/or those with radiographic findings indicative of pancreatic injury. [ABSTRACT FROM AUTHOR]

Objective: The efficacy of combined BRAF and MEK inhibition for BRAF V600-mutant melanoma in a broad patient population, including subgroups excluded from phase 3 trials, remains unanswered. This noninterventional study (DATUM-NIS) assessed the real-world efficacy, safety and tolerability of dabrafenib plus trametinib in Austrian patients with unresectable/metastatic melanoma., Methods: This multicenter, open-label, non-interventional, post-approval, observational study investigated the effectiveness of dabrafenib plus trametinib prescribed in day-to-day clinical practice to patients ( N  = 79) with BRAF V600-mutant unresectable/metastatic melanoma with M1c disease (American Joint Committee on Cancer staging manual version 7), ECOG > 1, and elevated serum lactate dehydrogenase (LDH). The primary endpoint was 6-, 12- and 18-month progression-free survival (PFS) rates. Secondary endpoints were median PFS, disease control rate and overall survival (OS)., Results: The 6-, 12- and 18-month PFS rates were 76%, 30.6% and 16.2%, respectively. Subgroup analysis showed a significant PFS benefit in the absence of lung metastasis. The median PFS and OS were 9.1 (95% CI, 7.1-10.3) months and 17.9 (95% CI, 12.7-27.8) months, respectively. The 12- and 24-month OS rates were 62.7% and 26.8%, respectively. Subgroup analyses showed significant OS benefits in the absence of bone or lung metastasis and the presence of other metastases (excluding bone, lung, brain, liver and lymph nodes). Furthermore, S100 and Eastern Cooperative Oncology Group performance status (ECOG PS) showed a significant impact on survival. No new safety signals were observed., Conclusion: Despite an unselected population of melanoma patients with higher M1c disease, ECOG PS > 1 and elevated LDH, this real-world study demonstrated comparable efficacy and safety with the pivotal phase 3 clinical trials for dabrafenib-trametinib., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background and Objectives: This study analyzed the extent to which the recent introduction of more effective treatments has led to an improvement in real-world psoriasis patients., Patients and Methods: Patient characteristics and the first-year treatment effectiveness in biologic-naive patients have been analyzed since 2004 until now, irrespective of treatment switches., Results: Data from 2,729 patients were eligible for this analysis. The proportion of female patients increased significantly over the years from 29.9% to 36.2% (p < 0.028), while the number of patients with psoriatic arthritis declined from 36.6% to 30.0% (p < 0.001). Moreover, the duration of psoriatic disease and PASI at the start of the treatment significantly decreased. Last observation carrief forward (LOCF) analysis indicated that PASI 90 response increased from 18.9 to 44.6% at 3 months and from 32.9 to 66.8% at 12 months after treatment started. Similary, the PASI ≤ 3 rates increased from 33.2% to 66.0% at 3 months and from 41.9% to 78.9% at 12 months after the treatment started., Conclusions: The continuous introduction of more efficient biologics has led to significant improvements in patient care and clinical outcomes. Though one out of three to five patients, depending on the endpoint selected, nowadays still does not achieve an entirely satisfactory treatment response (i.e., PASI 90 or PASI ≤ 3)., (© 2023 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by John Wiley & Sons Ltd on behalf of Deutsche Dermatologische Gesellschaft.)

Background: Simple Congenital Heart Defects such as septal defects constitute a large proportion of Congenital Heart Defects. New research has demonstrated more co-morbidities than previously thought. In particular, co-morbidities involving neurocognitive, psychiatric, and social difficulties have been described. Neurocognitive and psychiatric morbidities affect social interaction. Social interaction is important in everyday social life (education, work life, family life). In this study, we investigated social interaction through self- and proxy-answered Social Responsiveness Scale 2 (SRS-2) in young adults with simple Congenital Heart Defects and compared their social interaction profile to healthy matched controls., Methods: We included a total of 80 patients with either atrial or ventricular septal defect (age 26.6 years) and 38 heart-healthy, age, sex, and ISCED educational matched controls (age: 25.3 years). A close relative proxy from each participant took part in the study as well. All participants answered the Social Responsiveness Scale 2 (SRS-2) ( n  = 225). Our primary and secondary outcomes were the SRS-2 Total score and the SRS-2 sub-scores., Results: In the Congenital Heart Defects group, 31.3% had a Total score above 60 compared to 7.9% in the control group ( p  = 0.005, RR = 3.96). The participants with a septal defect had a higher Total score (52.5 vs. 45.5, p  = 0.004), a higher Social Cognition sub-score (55.0 vs. 47.0, p  = 0.0004), and a higher Social Motivation sub-score (50.0 vs. 45.0, p  = 0.003) than the heart-healthy participants. We found no difference between the two groups regarding the sub-scores of Social Awareness and Social Communication. A multiple linear regression model showed that the variable that explained most of the variation in Total Score was having a previously diagnosed psychiatric disorder., Conclusion: We found that young adults with atrial or ventricular septal defects have a fourfold increased risk of social interaction difficulties compared to heart-healthy peers. They have a social interaction profile, with difficulties in social cognition and social motivation, and preserved social awareness and social communication. Psychiatric morbidity explained most of the variation in social interaction problems. As social difficulties and psychiatric morbidities are intertwined, social interaction difficulties could be an indication of already underlying psychiatric morbidities or a risk factor for future psychiatric morbidity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Lau-Jensen, Asschenfeldt, Evald and Hjortdal.)

Antioxidants exhibit a powerful defense mechanism against aging and chronic disease. The human skin reflects the overall antioxidant status of the body. The cutaneous carotenoid concentration is a biomarker for individual nutritional intake of antioxidants, as it correlates with the overall antioxidant status. The cutaneous carotenoid concentrations of 44 adults were measured using a multiple spatially resolved reflection spectroscopy. During the first phase of the study, measurements of carotenoid concentrations were performed without revealing the antioxidant status, followed by an intervention phase during which the volunteers were informed about their individual values by biofeedback. During the third phase, biofeedback was combined with an additional intake of fruit juices. Across time points, participants showed increasing levels of carotenoid status. Thus, biofeedback leads to an improvement of the carotenoid value of the skin. Providing a biofeedback measurement to monitor the individual antioxidative status may be an easy and cost-effective way of primary prevention., (© 2023 The Authors. Journal of Biophotonics published by Wiley-VCH GmbH.)

Background: Adults with simple congenital heart defects (CHD) have increased risk of neurodevelopmental challenges including executive dysfunction. It is unknown if the executive dysfunction is universal or if it is driven by dysfunction in specific clinical subscales and how it might affect psychosocial aspects of everyday life., Methods: The self-reported and informant-reported executive function of adults with an average age of 26 ± 5 (range 18-41) who underwent childhood surgery for atrial septal defects (n = 34) or ventricular septal defects (n = 32) and matched controls (n = 40) were evaluated using the Behavior Rating Inventory of Executive Functions - Adult version (BRIEF-A)., Results: The CHD group reported having more executive dysfunction than controls in all BRIEF-A clinical subscales (p < 0.020) and more than their informants reported on their behalf (p < 0.006). The CHD group had received three times more special teaching (44% compared to 16%) and pedagogical psychological counselling (14% compared to none) and had a three times higher occurrence of psychiatric disorders than controls (33% compared to 11%). Lower educational levels and psychiatric disorders were associated with higher BRIEF-A scores (p < 0.03)., Conclusions: Adults operated for septal defects in childhood report more challenges with all aspects of the executive functions than controls and more than relatives are aware of.

Background Delayed brain development, brain injury, and neurodevelopmental disabilities are commonly observed in infants operated for complex congenital heart defect. Our previous findings of poorer neurodevelopmental outcomes in individuals operated for simple congenital heart defects calls for further etiological clarification. Hence, we examined the microstructural tissue composition in cerebral cortex and subcortical structures in comparison to healthy controls and whether differences were associated with neurodevelopmental outcomes. Methods and Results Adults (n=62) who underwent surgical closure of an atrial septal defect (n=33) or a ventricular septal defect (n=29) in childhood and a group of healthy, matched controls (n=38) were enrolled. Brain diffusional kurtosis imaging and neuropsychological assessment were performed. Cortical and subcortical tissue microstructure were assessed using mean kurtosis tensor and mean diffusivity and compared between groups and tested for associations with neuropsychological outcomes. Alterations in microstructural tissue composition were found in the parietal, temporal, and occipital lobes in the congenital heart defects, with distinct mean kurtosis tensor cluster-specific changes in the right visual cortex (pericalcarine gyrus, P =0.002; occipital part of fusiform and lingual gyri, P =0.019). Altered microstructural tissue composition in the subcortical structures was uncovered in atrial septal defects but not in ventricular septal defects. Associations were found between altered cerebral microstructure and social recognition and executive function. Conclusions Children operated for simple congenital heart defects demonstrated altered microstructural tissue composition in the cerebral cortex and subcortical structures during adulthood when compared with healthy peers. Alterations in cerebral microstructural tissue composition were associated with poorer neuropsychological performance. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03871881.