Dabrafenib plus trametinib in unselected advanced BRAF V600-mut melanoma: a non-interventional, multicenter, prospective trial.

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.

Evolution of characteristics and biologic treatment effectiveness in patients of the Austrian psoriasis registry from 2004-2022.

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).

Spectroscopic biofeedback on cutaneous carotenoids: A powerful tool for primary prevention in advanced age.

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.

Dithranol targets keratinocytes, their crosstalk with neutrophils and inhibits the IL-36 inflammatory loop in psoriasis.

Despite the introduction of biologics, topical dithranol (anthralin) has remained one of the most effective anti-psoriatic agents. Serial biopsies from human psoriatic lesions and both the c-Jun/JunB and imiquimod psoriasis mouse model allowed us to study the therapeutic mechanism of this drug. Top differentially expressed genes in the early response to dithranol belonged to keratinocyte and epidermal differentiation pathways and IL-1 family members (i.e. IL36RN) but not elements of the IL-17/IL-23 axis. In human psoriatic response to dithranol, rapid decrease in expression of keratinocyte differentiation regulators (e.g. involucrin, SERPINB7 and SERPINB13), antimicrobial peptides (e.g. ß-defensins like DEFB4A, DEFB4B, DEFB103A, S100 proteins like S100A7, S100A12), chemotactic factors for neutrophils (e.g. CXCL5, CXCL8) and neutrophilic infiltration was followed with much delay by reduction in T cell infiltration. Targeting keratinocytes rather than immune cells may be an alternative approach in particular for topical anti-psoriatic treatment, an area with high need for new drugs.

Consumption of fruits and vegetables: improved physical health, mental health, physical functioning and cognitive health in older adults from 11 European countries.

Objective: Regular consumption of fruits and vegetables has been found to contribute to physical health and physical functioning. However, health is not limited to the absence of physical diseases but also encompasses mental health and cognition. Thus, we wanted to examine how the consumption of fruit and vegetables is associated with overall health, including mental health and cognitive health of older European adults.Design: We used multilevel regression analysis (participants nested within countries) to examine the effects of nutrition on overall health. Participants were asked in 2011 about their health behaviour including nutritional habits. Several health outcomes were measured longitudinally in 2013: Self-rated health, grip strength, instrumental activities of daily living (IADL), activities of daily living (ADL), mobility, depression, quality of life, short-term memory, and long-term memory.Setting: We used the 2011 and 2013 waves of the Survey of Health, Ageing and Retirement in Europe (SHARE), a multi-national population survey of older adults.Subjects:N = 22,635 older adults were sampled from 11 European countries.Results: Frequent consumption of fruits and vegetables is associated with improved health outcomes, including cognitive and mental health.Conclusions: Frequent consumption of fruits and vegetables contributes to slower disablement processes and might be an easily implementable way to improve the overall health of older adults. Future studies should examine the cross-national differences in the observed effects.

Influence of Storage and Preservation Techniques on Egg-Derived Carotenoids: A Substantial Source for Cutaneous Antioxidants.

Antioxidants like carotenoids play a major role in the prevention of the destructive influence of free radicals in our skin. Carotenoids, as well as all other antioxidants, are substantial substances which must be supplied by nutrition. Resonance Raman spectroscopy (RRS) allows measurement of the carotenoid content of eggs, representing a rich carotenoid source in our nutrition. A previous study showed that eggs from organic production contain higher carotenoid levels in contrast to eggs from conventionally housed chicken. The uptake of these organically produced eggs led to an increased antioxidant concentration in the skin. In this study, the effects of different storage modalities, conservation techniques, and the effects of food processing on the carotenoid levels in eggs were investigated with RRS. Common storage modalities and preservation techniques showed only a limited influence on egg-derived carotenoid concentrations. However, a colder environment (at least for shell eggs) and high-pressure preservation had the best preservative influence on the carotenoid content. Surprisingly, food processing such as boiling increased the carotenoid concentration in eggs, whilst broiling destroyed the carotenoids almost completely. In conclusion, RRS is suitable for monitoring egg-derived carotenoid levels, and carotenoid levels in eggs are generally stable under common storage and preservation modalities. Boiling in contrast to broiling of eggs might be superior in terms of carotenoid preservation within food processing.

Knowledge and Influence of Predatory Journals in Dermatology: A Pan-Austrian Survey.

The aim of this study was to assess the knowledge and influence of predatory journals in the field of dermatology in Austria. A total of 286 physicians (50.5% men) completed a questionnaire. The vast majority of subjects read scientific articles (n = 281, 98.3%) and took them into consideration in their clinical decision-making (n = 271, 98.5% of participants that regularly read scientific literature). Open access was known by 161 (56.3%), predatory journals by 84 (29.4%), and the Beall's list by 19 physicians (6.7%). A total of 117 participants (40.9%) had been challenged by patients with results from the scientific literature, including 9 predatory papers. Participants who knew of predatory journals had a higher level of education as well as scientific experience, and were more familiar with the open-access system (p < 0.001). These results indicate that the majority of dermatologists are not familiar with predatory journals. This is particularly the case for physicians in training and in the early stages of their career.

Fruit and vegetable consumption is associated with improved mental and cognitive health in older adults from non-Western developing countries.

OBJECTIVES: Consumption of fruits and vegetables has been shown to contribute to mental and cognitive health in older adults from Western industrialized countries. However, it is unclear whether this effect replicates in older adults from non-Western developing countries. Thus, the present study examined the contribution of fruit and vegetable consumption to mental and cognitive health in older persons from China, India, Mexico, Russia, South Africa and Ghana. DESIGN: Representative cross-sectional and cross-national study.Setting/SubjectsWe used data from the WHO Study on Global Ageing and Adult Health (SAGE), sampled in 2007 to 2010. Our final sample size included 28 078 participants. RESULTS: Fruit and vegetable consumption predicted an increased cognitive performance in older adults including improved verbal recall, improved delayed verbal recall, improved digit span test performance and improved verbal fluency; the effect of fruit consumption was much stronger than the effect of vegetable consumption. Regarding mental health, fruit consumption was significantly associated with better subjective quality of life and less depressive symptoms; vegetable consumption, however, did not significantly relate to mental health. CONCLUSIONS: Consumption of fruits is associated with both improved cognitive and mental health in older adults from non-Western developing countries, and consumption of vegetables is associated with improved cognitive health only. Increasing fruit and vegetable consumption might be one easy and cost-effective way to improve the overall health and quality of life of older adults in non-Western developing countries.

Body mass index may predict the response to ipilimumab in metastatic melanoma: An observational multi-centre study.

INTRODUCTION: Immunotherapy is a well-established treatment option in patients with metastatic melanoma. However, biomarkers that can be used to predict a response in these patients have not yet been found, putting patients at risk of severe side effects. METHODS: In this retrospective analysis, we investigated the association between the body mass index and ipilimumab treatment response in patients with metastatic melanoma. Patients with metastatic melanoma who received a monotherapy of up to 4 doses of ipilimumab (3 mg/kg) every 3 weeks from 2011 to 2014 in three major hospitals in Austria were included. Patients were classified into two groups: normal group (BMI<25) and overweight group (BMI≥25). RESULTS: 40 patients had a normal BMI, and 36 had a BMI above normal. Patients with a BMI that was above normal showed significantly higher response rates (p = 0.024, χ2), and lower likelihood of brain metastases (p = 0.012, χ2). No differences were found between both groups with respect to gender (p = 0.324, χ2), T-stage (p = 0.197, χ2), or the occurrence of side effects (p = 0.646, χ2). Patients with a BMI above normal showed a trend towards longer overall survival (p = 0.056, Log-Rank), but no difference was found regarding progression-free survival (p = 0.924, Log-Rank). CONCLUSIONS: The BMI correlated with the response to ipilimumab treatment in a cohort of metastatic melanoma patients.

Lebensqualität und Behandlungsziele bei Psoriasis aus Patientensicht: Ergebnisse eines österreichweiten Querschnitt-Survey.

HINTERGRUND: Patienten mit Psoriasis sind mit einer krankheitsbedingten Einschränkung ihrer Lebensqualität konfrontiert, weshalb einer hochqualitativen dermatologischen Versorgung ein besonderer Stellenwert zukommt. PATIENTEN UND METHODIK: Wir führten einen bundesweiten Querschnitt-Survey in Österreich (BQSAustria Psoriasis 2014/2015) mit dem Schwerpunkt auf Lebensqualität und Therapiezufriedenheit bei Patienten mit Psoriasis in dermatologischer Behandlung vorwiegend an Zentren mit überwiegend tertiären Versorgungsaufgaben durch. ERGEBNISSE: 70,2 % der 1184 befragten Patienten berichtete über eine eingeschränkte Lebensqualität (DLQI 2-5: 29,4 %; 6-10: 19,3 %; 11-15: 11,5 %; 16-20: 5,2 % und > 20: 4,9 %) trotz Behandlung innerhalb der letzten vier Wochen (mit lokaler Therapie in 88,2 % und/oder systemischer Therapie in 38,7 % der Fälle). Mit den verabreichten Therapien konnte im Durchschnitt kein einziges von 25 definierten subjektiven Behandlungszielen im gewünschten Ausmaß erreicht werden. So litten 82,2 % der Patienten trotz Behandlung weiter unter Juckreiz, wobei statistisch hochsignifikante Assoziationen mit einem schlechten Gesundheitszustand in der letzten Woche (Spear-man-Rangkorrelation; p = 1.1e-45), dem Ausmaß des psoriatischen Körperoberflächenbefalls (p = 3.2e-11) und Kopfhautbefalls (p = 3.2e-11) sowie Schmerzen (p = 2.3e-22) vorlagen. Die Behandlung mit einem Biologikum war mit einer signifikant höheren Patientenzufriedenheit verbunden (Wilcoxon-Test, p = 2.0e-16). SCHLUSSFOLGERUNGEN: Die Lebensqualität der meisten österreichischen Patienten mit Psoriasis in dermatologischer Versorgung ist krankheitsbedingt beeinträchtigt, und es besteht ein Verbesserungspotenzial bei der Umsetzung von Behandlungszielen.

Quality of life and treatment goals in psoriasis from the patient perspective: results of an Austrian cross-sectional survey.

BACKGROUND: Patients with psoriasis experience impairment in quality of life. Thus, high-quality dermatological care is of particular importance. PATIENTS AND METHODS: We performed a nationwide cross-sectional survey in Austria (BQSAustria Psoriasis 2014/2015) with a special focus on quality of life and satisfaction with treatment among psoriasis patients predominantly treated at tertiary care centers. RESULTS: Overall, 70.2 % of 1,184 patients reported impaired quality of life (DLQI 2-5: 29.4 %; 6-10: 19.3 %; 11-15: 11.5 %; 16-20: 5.2 % and > 20: 4.9 %) despite treatment over the preceding four weeks (topical treatment in 88.2 % of cases and/or systemic treatment in 38.7 %). On average, none of the 25 defined subjective treatment goals was achieved to a sufficient degree. In particular, 82.2 % of patients continued to have pruritus despite treatment, which was highly significantly associated with a poor general health status over the preceding week (Spearman's rank correlation; p  =  1.1e-45), the extent of body surface area (p  =  3.2e-11) and scalp area (p  =  3.2e-11) affected, as well as pain (p  =  2.3e-22). Treatment with a biologic was significantly correlated with higher patient satisfaction (Wilcoxon-Test, p  =  2.0e-16). CONCLUSIONS: Despite dermatological care, the majority of Austrian psoriasis patients continues to experience impaired quality of life; there is potential for improvement in the achievement of treatment goals.

The Prevalence of Periodontitis Is Increased in Psoriasis and Linked to Its Inverse Subtype.

Periodontitis and psoriasis are suggested to be co-occurring, chronic inflammatory conditions with overlapping characteristics. However, respective evidence is rare and data on risk factors of periodontitis in psoriasis patients are minimal. The aim of this study was to expand the evidence of psoriasis-associated periodontitis and establish a potential risk profile for periodontitis. In total, data from 209 exacerbated psoriasis patients were retrospectively analyzed on recordings of periodontitis and compared with those of 91 patients with chronic spontaneous urticaria (CSU). Analysis showed a significantly increased prevalence of periodontitis in psoriasis compared to CSU patients with an odds ratio of 3.76 (95% CI = 1.60-10.27, p = 0.001). Within the psoriatic subtypes, the presence of the inverse type (affecting intertriginous body areas) was strongly linked to periodontitis with an odds ratio of 5.11 (95% CI = 1.36-20.38, p = 0.006). These results are enlarging the evidence for psoriasis-associated periodontitis and identify a link between the inverse type of psoriasis and periodontitis.

Prognostic value of the area and density of lymphatic vessels in cutaneous squamous cell carcinoma.

BACKGROUND AND OBJECTIVES: Cutaneous squamous cell carcinoma (SCC) is known for its capacity to metastasize via lymphatic vessels. In recent studies, the level of lymphangiogenesis has been reported as a potential prognostic factor for several skin tumors. The aim of this study was to quantify lymphangiogenesis in SCC using either computer-assisted image analysis or the Chalkley count technique. Vascular parameters were evaluated and compared with respect to their predictive power for tumor metastasis. PATIENT AND METHODS: In this case-control study, clinical and histological data of 15 metastatic and 15 nonmetastatic SCC patients were retrospectively analyzed. SCC samples were immunostained for the lymphatic endothelial marker D2-40 and the panvascular marker CD31, and analyzed using computer-assisted morphometric image analyses within hot spots as well as the digitalized Chalkley counting method. RESULTS: Lymphatic vessel density, relative lymphatic vessel area, and lymphatic Chalkley count were significantly elevated in metastatic SCC. Tumor thickness was significantly higher in metastatic SCC, and had the highest predictive power for metastatic disease. Tumor thickness was a significant predictor of lymphangiogenic parameters. CONCLUSIONS: Lymphangiogenesis is elevated in metastatic SCC but its extent is influenced by tumor thickness. Tumor thickness remains the most reliable predictive factor for metastatic disease.

Prognostischer Wert der Fläche und Dichte von Lymphgefäßen bei kutanem Plattenepithelkarzinom.

HINTERGRUND UND ZIELE: Kutane Plattenepithelkarzinome (SCC) sind bekannt für ihre Fähigkeit, über Lymphgefäße zu metastasieren. In neueren Studien wird das Ausmaß der Lymphangiogenese als möglicher prognostischer Faktor bei einigen Hauttumoren genannt. Ziel dieser Studie war die Quantifizierung der Lymphangiogenese bei SCC entweder durch computergestützte Bildanalyse oder mithilfe der Zählmethode nach Chalkley. Gefäßparameter wurden im Hinblick auf ihre Vorhersagekraft für die Bildung von Tumormetastasen beurteilt und verglichen. PATIENTEN UND METHODEN: In dieser Fallkontrollstudie wurden die klinischen und histologischen Daten von jeweils 15 SCC-Patienten mit bzw. ohne Metastasen retrospektiv analysiert. In den SCC-Proben wurde der für das Lymphendothel spezifische Marker D2-40 und der pan-vaskuläre Marker CD31 immunhistochemisch angefärbt und durch computergestützte morphometrische Bildanalyse in Hotspots sowie mithilfe der digitalisierten Zählmethode nach Chalkley analysiert. ERGEBNISSE: Die Dichte von Lymphgefäßen, die relative Lymphgefäßfläche und die mit der Chalkley-Methode ermittelte Zahl an Lymphgefäßen (Chalkley-Count) waren bei metastasierten SCC signifikant erhöht. Die Tumordicke war bei metastasierten SCC signifikant höher und besaß die höchste Vorhersagekraft für eine Metastasierung. Die Tumordicke war ein signifikanter Prädiktor für Lymphangiogeneseparameter. SCHLUSSFOLGERUNGEN: Die Lymphangiogenese ist bei metastasierten SCC erhöht, doch ihr Ausmaß wird von der Tumordicke beeinflusst. Die Tumordicke bildet weiterhin den zuverlässigsten prädiktiven Faktor für die Metastasierung.

Serum levels of hepatocyte growth factor as a potential tumor marker in patients with malignant melanoma.

Serum markers can be important tools for prognostic classification and treatment monitoring in cancer patients. The MAP-kinase pathway, which is upregulated in the majority of melanoma patients, can be activated by hepatocyte-growth factor (HGF) through the proto-oncogene c-MET. The aim of this study was to evaluate the predictive and prognostic value of circulating HGF in terms of treatment outcome and survival compared with a widely established serum marker, protein S-100B, in patients with advanced metastatic melanoma. HGF and S-100B were measured in serum samples of 101 patients with metastatic melanoma (American Joint Committee on Cancer stage IV) before and after treatment and 50 patients with stage I/II melanoma. HGF and S-100B correlated significantly with the stage of disease (P=0.032 and P<0.001, respectively). In stage IV melanoma patients, baseline serum levels of HGF and S-100B were significantly associated with treatment response (P=0.012 and 0.006, respectively). Furthermore, the Cox regression analysis confirmed that serum levels of HGF and S-100B proved to have a significant prognostic impact on progression-free survival (hazard ratio=1.39 and 1.29, respectively) and overall survival (hazard ratio=1.27 and 1.29, respectively) in advanced metastatic melanoma patients. In melanoma patients, serum levels of HGF and S-100B correlate significantly with the stage of disease. In stage IV melanoma, both markers are prognostic factors and correlate significantly with progression-free survival and overall survival. Measurement of serum HGF levels might be a useful additional tool in the management of melanoma patients.

Survival and Effectiveness of Tumour Necrosis Factor-alpha Inhibitors in the Treatment of Plaque Psoriasis under Daily Life Conditions: Report from the Psoriasis Registry Austria.

This retrospective multicentre analysis from the Psoriasis Registry Austria (PsoRA) was conducted to determine drug effectiveness and survival of anti-tumour necrosis factor alpha (anti-TNF-α) agents in patients with moderate-to-severe chronic plaque psoriasis over a 9-year period. Data on 1,019 treatment cycles with adalimumab (n = 460), etanercept (n = 501), and/or infliximab (n = 58) administered to 827 patients (272 women, 555 men) were available for analysis. Compared with etanercept, adalimumab and infliximab showed superior short-term effectiveness. Intention-to-treat-calculated median drug survivals for adalimumab (1,264 days) and etanercept (1,438 days) were similar to each other (p = 0.74), but significantly superior to that of infliximab (477 days) (p = 7.0e-07 vs. adalimumab and p=2.2e-07 vs. etanercept, respectively). Their drug survival rates at 36 months were 51.6%, 56.0%, and 22.6%, respectively. Survival rates correlated significantly with effectiveness for adalimumab and etanercept, but not for infliximab.