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Higher levels of daily physical activity are associated with better skin microvascular function in type 2 diabetes-The Maastricht Study.
Sörensen, BM, van der Heide, FCT, Houben, AJHM, Koster, A, T J M Berendschot, T, S A G Schouten, J, Kroon, AA, van der Kallen, CJH, Henry, RMA, van Dongen, MCJM, et al
Microcirculation (New York, N.Y. : 1994). 2020;(4):e12611
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Abstract
OBJECTIVE Physical activity may provide a means for the prevention of cardiovascular disease via improving microvascular function. Therefore, this study investigated whether physical activity is associated with skin and retinal microvascular function. METHODS In The Maastricht Study, a population-based cohort study enriched with type 2 diabetes (n = 1298, 47.3% women, aged 60.2 ± 8.1 years, 29.5% type 2 diabetes), we studied whether accelerometer-assessed physical activity and sedentary time associate with skin and retinal microvascular function. Associations were studied by linear regression and adjusted for major cardiovascular risk factors. In addition, we investigated whether associations were stronger in type 2 diabetes. RESULTS In individuals with type 2 diabetes, total physical activity and higher-intensity physical activity were independently associated with greater heat-induced skin hyperemia (regression coefficients per hour), respectively, 10 (95% CI: 1; 18) and 36 perfusion units (14; 58). In individuals without type 2 diabetes, total physical activity and higher-intensity physical activity were not associated with heat-induced skin hyperemia. No associations with retinal arteriolar %-dilation were identified. CONCLUSION Higher levels of total and higher-intensity physical activity were associated with greater skin microvascular vasodilation in individuals with, but not in those without, type 2 diabetes.
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Effects of Long-Versus Short-Term Exposure to the Mediterranean Diet on Skin Microvascular Function and Quality of Life of Healthy Adults in Greece and the UK.
Klonizakis, M, Grammatikopoulou, MG, Theodoridis, X, Milner, M, Liu, Y, Chourdakis, M
Nutrients. 2019;(10)
Abstract
The beneficial effects of the Mediterranean diet (MD) adherence in reducing cardiovascular disease (CVD) risk and improving CVD-related physiological indices have been well-documented. However, the exact MD adherence duration needed for these effects to occur is under-researched. The aim of the present, two-arm, two-site study clinical trial was to assess the effects of long- vs. short-term MD adherence on the skin microvascular circulation, and quality of life. Two groups were recruited, one being long-term MD adherers (>5 years; from Greece; control group), and one of the non-adherers (from the UK), with the latter participating in a four-week MD intervention (intervention group). Our main outcome was skin microvascular function assessed by cutaneous vascular conductance (CVC). Secondary outcomes included quality of life, dietary intake, blood pressure and lipidemic profile. At the end of the intervention, both groups had high MD adherence. For the intervention group, significantly improved post-intervention CVC values were noted concerning the initial peak phase (2.0 ± 0.6 vs. 2.8 ± 0.8; p < 0.05). CVC values of the control group, were however higher at the plateau phase in comparison to the intervention group (intervention end; 3.8 ± 0.8 vs. 3.1 ± 1.2; p < 0.05). As per QoL, the physical domain was improved post-intervention (13.7 ± 1.2 vs. 15.9 ± 1.2; p < 0.05). No differences were observed in the lipidemic profile between groups, or between the baseline and final intervention phases. The findings indicate that although short-term MD adherence is effective in improving certain microvascular physiological properties and QoL domains, there is room for additional improvement, observed in long-term adherers. Our findings are important in the design of future, MD-based, lifestyle interventions, with the advisable durations differing between target groups.
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Complete response under sorafenib in patients with hepatocellular carcinoma: Relationship with dermatologic adverse events.
Rimola, J, Díaz-González, Á, Darnell, A, Varela, M, Pons, F, Hernandez-Guerra, M, Delgado, M, Castroagudin, J, Matilla, A, Sangro, B, et al
Hepatology (Baltimore, Md.). 2018;(2):612-622
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Abstract
The clinical benefit of sorafenib in patients with hepatocellular carcinoma (HCC) has been undervalued due to the absence of complete responses, even though patients who develop early dermatologic reactions have shown to have a positive outcome. In addition, sorafenib is described as an antiangiogenic drug, but it also acts on immunological cells. Thus, the goal of this study was to assess the complete response rate in a retrospective cohort of HCC patients treated with sorafenib and to describe the profile of the patients who achieve complete response for identifying factors related to this event and their connection with the immunological profile of sorafenib. Ten Spanish centers submitted cases of complete response under sorafenib. The baseline characteristics, development of early dermatologic reactions, and cause of treatment discontinuation were annotated. Radiological images taken before starting sorafenib, at first control, after starting sorafenib, at the time of complete response, and at least 1 month after treatment were centrally reviewed. Of the 1119 patients studied, 20 had been classified as complete responders by the centers, but eight of these patients were excluded after central review. Ten patients had complete disappearance of all tumor sites, and two had just a small residual fibrotic scar. Thus, 12 patients were classified as complete responders (58% HCV, median age 59.7 years, 83.4% Child-Pugh class A, Eastern Cooperative Oncology Group performance status 0 91.7%, and Barcelona Clinic Liver Cancer stage C 83.3%). The median overall survival and treatment duration were 85.8 and 40.1 months, respectively. All but one patient developed early dermatologic reactions, and seven patients discontinued sorafenib after achieving complete response due to adverse events, patient decision, or liver decompensation. Conclusion: Complete response affects 1% of patients with HCC who are treated with sorafenib. The association of complete response with early dermatologic reactions supports the role of a specific immune/inflammatory patient profile in the improved response to sorafenib. (Hepatology 2018;67:612-622).
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Significant disparities in allergy prevalence and microbiota between the young people in Finnish and Russian Karelia.
Ruokolainen, L, Paalanen, L, Karkman, A, Laatikainen, T, von Hertzen, L, Vlasoff, T, Markelova, O, Masyuk, V, Auvinen, P, Paulin, L, et al
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. 2017;(5):665-674
Abstract
BACKGROUND Atopic allergy has been more common among schoolchildren in Finland, as compared to Russian Karelia. These adjacent regions show one of the most contrasting socio-economical differences in the world. OBJECTIVE We explored changes in allergy from school age to young adulthood from 2003 to 2010/2012 in these two areas. The skin and nasal microbiota were also compared. METHODS Randomly selected children from Finnish (n = 98) and Russian Karelia (n = 82) were examined in 2003, when the children were 7-11 years of age, and again in 2010 (Finnish Karelia) and 2012 (Russian Karelia). We analysed self-reported allergy symptoms and sensitization to common allergens by serum sIgE values. The skin (volar forearm) and nasal mucosa microbiota, collected in 2012 (aged 15-20 years), identified from DNA samples, were compared with multivariate methods. RESULTS Asthma, hay fever, atopic eczema, self-reported rhinitis, as well as atopic sensitization, were threefold to 10-fold more common in Finland, as compared to Russian Karelia. Hay fever and peanut sensitization were almost non-existent in Russia. These patterns remained throughout the 10-year follow-up. Skin microbiota, as well as bacterial and fungal communities in nasal mucosa, was contrastingly different between the populations, best characterized by the diversity and abundance of genus Acinetobacter; more abundant and diverse in Russia. Overall, diversity was significantly higher among Russian subjects (Pskin < 0.0001, Pnasal-bacteria < 0.0001 and Pnasal-fungi < 0.01). Allergic diseases were not associated with microbial diversity in Finnish subjects. CONCLUSIONS AND CLINICAL RELEVANCE Differences in allergic phenotype, developed in early life, remain between populations. A parallel difference in the composition of skin and nasal microbiota suggests a potential underlying mechanism. Our results also suggest that high abundance and diversity of Acinetobacter might contribute to the low allergy prevalence in Russia. Implications of early-life exposure to Acinetobacter should be further investigated.
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N-Acetylcysteine in the Treatment of Excoriation Disorder: A Randomized Clinical Trial.
Grant, JE, Chamberlain, SR, Redden, SA, Leppink, EW, Odlaug, BL, Kim, SW
JAMA psychiatry. 2016;(5):490-6
Abstract
IMPORTANCE Excoriation (skin-picking) disorder (SPD) is a disabling, underrecognized condition in which individuals repeatedly pick at their skin, leading to noticeable tissue damage. To date, there has been no clearly effective pharmacologic or psychological treatment for SPD. OBJECTIVE To determine whether N-acetylcysteine, an amino acid that appears to restore extracellular glutamate concentration in the nucleus accumbens, will be more effective than placebo in reducing compulsive picking behavior. DESIGN, SETTING, AND PARTICIPANTS A randomized, double-blind trial was conducted at ambulatory care centers at the University of Minnesota (September 12, 2011, to June 15, 2012) and the University of Chicago (December 17, 2012, to June 26, 2015) and included 66 adults with SPD. Data analysis was performed from July 16 to September 9, 2015. INTERVENTIONS N-acetylcysteine (dosing range, 1200-3000 mg/d) or placebo was administered for 12 weeks. MAIN OUTCOMES AND MEASURES Participants were assessed using measures of skin-picking severity, including the modified Yale-Brown Obsessive Compulsive Scale (NE-YBOCS); total scores range from 0 to 40, with higher scores reflective of greater symptom severity. Another measure of skin-picking severity was the Clinical Global Impression-Severity Scale; total scores range from 1 (normal) to 7 (among the most extremely ill patients), and improvement ratings range from 7 (very much worse) to 1 (very much improved). Selected cognitive tasks included the Intra-dimensional/Extra-dimensional Shift Task to examine cognitive flexibility, with the key outcome measures being the number of errors, and Stop-Signal Reaction Time task, which evaluates motor inhibition. Outcomes were examined using a linear mixed-effects model. RESULTS Of the 66 participants (31 randomized to placebo and 35 to N-acetylcysteine) included in the analysis, 59 (89%) were women; mean (SD) age was 34.8 (11.0) years. Compared with placebo, N-acetylcysteine treatment was associated with significant improvements in the NE-YBOCS. At baseline, NE-YBOCS scores were 18.9 and 17.9 for the treatment and placebo groups, respectively, and at 12 weeks, the scores were 11.5 and 14.1 for the treatment and placebo groups, respectively (P = .048). For the Clinical Global Impression-Severity scale, baseline scores were 3.5 and 4.0 and 12-week scores were 3.0 and 4.2, respectively (P = .003). These effects were significant both in terms of treatment by time interactions and post hoc tests at 1 or more individual time points. At the study's end point, of the 53 participants who completed the study, 15 of the 32 participants (47%) receiving N-acetylcysteine were much or very much improved compared with 4 of the 21 participants (19%) receiving placebo (P = .03). There were no significant differences between the active and placebo arms in terms of psychosocial functioning. CONCLUSIONS AND RELEVANCE N-acetylcysteine treatment resulted in significant reductions in skin-picking symptoms and was well tolerated. The glutamate system may prove a beneficial target in treating SPD and other compulsive behaviors. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01063348.
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A phase 2a randomized, double-blind, placebo-controlled, sequential dose-escalation study to evaluate the efficacy and safety of ASP015K, a novel Janus kinase inhibitor, in patients with moderate-to-severe psoriasis.
Papp, K, Pariser, D, Catlin, M, Wierz, G, Ball, G, Akinlade, B, Zeiher, B, Krueger, JG
The British journal of dermatology. 2015;(3):767-76
Abstract
BACKGROUND Many immune-mediated disorders, including psoriasis, involve cytokine signalling via Janus kinase (JAK) enzymes. ASP015K (also designated JNJ-54781532), a novel oral JAK inhibitor, has shown moderate selectivity for JAK3 over JAK1 and JAK2 in enzyme assays. OBJECTIVES The objective of this study was to evaluate the efficacy and safety of escalating, sequentially grouped, doses of ASP015K vs. placebo in patients with moderate-to-severe psoriasis. METHODS This phase 2a multicentre, double-blind, randomized, placebo-controlled study (NCT01096862) enrolled 124 patients with moderate-to-severe plaque psoriasis. Five sequential ASP015K cohorts were enrolled, consisting of four twice-daily dosing groups (10, 25, 60, 100 mg) and one once-daily dosing group (50 mg) for 6 weeks. RESULTS The primary efficacy end point [mean change in Psoriasis Area and Severity Index score from baseline to end of treatment (EOT; day 42)] significantly favoured ASP015K (overall treatment effect; P < 0.001) vs. placebo, with greater improvements at higher doses. By EOT, the secondary end points [Physician Static Global Assessment (PSGA) score, percentage of patients achieving PSGA success, and change in percentage, body surface area (BSA)] also improved with ASP015K vs. placebo (P < 0.001 for PSGA score and BSA; P < 0.01 for PSGA success). Epidermal thickness and proliferation decreased from baseline with ASP015K vs. placebo. ASP015K was generally well tolerated, with no serious adverse events (AEs) reported. CONCLUSIONS In patients with moderate-to-severe psoriasis, ASP015K demonstrated dose-dependent improvements in clinical and histological measures of severity over 6 weeks of treatment. At all doses, ASP015K was well tolerated, with no reported serious AEs.
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A prospective observational study to examine the relationship between quality of life and adverse events of first-line chemotherapy plus cetuximab in patients with KRAS wild-type unresectable metastatic colorectal cancer: QUACK Trial.
Ooki, A, Ando, M, Sakamoto, J, Sato, A, Fujii, H, Yamaguchi, K
Japanese journal of clinical oncology. 2014;(4):383-7
Abstract
We have planned a multicentre prospective study to examine the relative impact of the efficacy and adverse events of cetuximab plus first-line chemotherapy on the quality of life in Japanese patients with KRAS wild-type unresectable colorectal cancer. The Dermatology Life Quality Index and the European Organization for Research Treatment of Cancer Quality of Life Questionnaire Core 30 will be used to assess dermatology-specific and health-related quality of life. The severity of adverse events will be assessed by using the National Cancer Institute Common Terminology Criteria for adverse Events ver. 4.0. The endpoints will be the following associations: adverse events, including skin toxicity and quality of life; efficacy and skin toxicity; efficacy and quality of life; and skin-related quality of life and health-related quality of life. A total of 140 patients are considered to be appropriate for inclusion in this study. The results of this study will provide more information to both patients and physicians regarding the practical use of cetuximab and its impact on quality of life in patients with unresectable colorectal cancer in Japan. This study was registered at the University Hospital Medical Information Network Clinical Trial Registry as UMIN000010985.
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Noninvasive skin fluorescence spectroscopy is comparable to hemoglobin A1c and fasting plasma glucose for detection of abnormal glucose tolerance.
Olson, BP, Matter, NI, Ediger, MN, Hull, EL, Maynard, JD
Journal of diabetes science and technology. 2013;(4):990-1000
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AIM: We compare performance of noninvasive skin fluorescence spectroscopy (SFS), fasting plasma glucose (FPG), and hemoglobin A1c (A1C) for detection of abnormal glucose tolerance (AGT). METHODS The NSEEDS trial evaluated SFS, FPG, and A1C in an at-risk population of 479 previously undiagnosed subjects from nine US centers, each of whom received a 75 g, 2 h oral glucose tolerance test (OGTT). Skin fluorescence spectra were collected and analyzed with SCOUT DS® devices. Disease truth was AGT, defined as OGTT ≥140 mg/dl. Abnormal glucose tolerance sensitivity, false positive rate (FPR), and receiver operating characteristic (ROC) curves were computed for each measurement technique. Skin fluorescence spectroscopy reproducibility was also assessed. RESULTS The AGT sensitivity of SFS was 68.2%, higher than that of FPG (thresholds of 100 and 110 mg/dl) and A1C (thresholds of 5.7% and 6.0%). The FPR of SFS was 37.7%, comparable to A1C at the 5.7% threshold (30.7%). Partial ROC areas of SFS, FPG, and A1C were similar for FPRs of 20-50% (average sensitivities of 64.0%, 59.0%, and 68.6%, respectively). The interday coefficient of variation for SFS was 7.6%. CONCLUSIONS Skin fluorescence spectroscopy has similar screening performance to FPG and A1C and is a viable approach for detection of AGT.
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StrataGraft skin substitute is well-tolerated and is not acutely immunogenic in patients with traumatic wounds: results from a prospective, randomized, controlled dose escalation trial.
Centanni, JM, Straseski, JA, Wicks, A, Hank, JA, Rasmussen, CA, Lokuta, MA, Schurr, MJ, Foster, KN, Faucher, LD, Caruso, DM, et al
Annals of surgery. 2011;(4):672-83
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OBJECTIVE The goal of this study was to assess the immunogenicity and antigenicity of StrataGraft skin tissue in a randomized phase I/II clinical trial for the temporary management of full-thickness skin loss. BACKGROUND StrataGraft skin tissue consists of a dermal equivalent containing human dermal fibroblasts and a fully stratified, biologically active epidermis derived from Near-diploid Immortalized Keratinocyte S (NIKS) cells, a pathogen-free, long-lived, consistent, human keratinocyte progenitor. METHODS Traumatic skin wounds often require temporary allograft coverage to stabilize the wound bed until autografting is possible. StrataGraft and cadaveric allograft were placed side by side on 15 patients with full-thickness skin defects for 1 week before autografting. Allografts were removed from the wound bed and examined for allogeneic immune responses. Immunohistochemistry and indirect immunofluorescence were used to assess tissue structure and cellular composition of allografts. In vitro lymphocyte proliferation assays, chromium-release assays, and development of antibodies were used to examine allogeneic responses. RESULTS One week after patient exposure to allografts, there were no differences in the numbers of T or B lymphocytes or Langerhans cells present in StrataGraft skin substitute compared to cadaver allograft, the standard of care. Importantly, exposure to StrataGraft skin substitute did not induce the proliferation of patient peripheral blood mononuclear cells to NIKS keratinocytes or enhance cell-mediated lysis of NIKS keratinocytes in vitro. Similarly, no evidence of antibody generation targeted to the NIKS keratinocytes was seen. CONCLUSIONS These findings indicate that StrataGraft tissue is well-tolerated and not acutely immunogenic in patients with traumatic skin wounds. Notably, exposure to StrataGraft did not increase patient sensitivity toward or elicit immune responses against the NIKS keratinocytes. We envision that this novel skin tissue technology will be widely used to facilitate the healing of traumatic cutaneous wounds.This study was registered at www.clinicaltrials.gov (NCT00618839).
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Skin toxicity as a risk factor for major infections in breast cancer patients treated with docetaxel.
Poikonen, P, Sjöström, J, Klaar, S, Nittby, LT, Sigurdsson, H, Madsen, EL, Joensuu, H, Blomqvist, C
Acta oncologica (Stockholm, Sweden). 2004;(2):190-5
Abstract
Docetaxel-related skin toxicity, oral and gastrointestinal mucosal toxicity, and changes in blood cell counts were investigated as predictive factors for major infections in 143 women treated with 3-weekly docetaxel (100 mg/m2) as second-line therapy for metastatic breast cancer in a randomized trial. Each patient with a major infection (n = 37) was compared with two controls. Skin toxicity (odds ratio 2.97, 95% CI 1.37-6.47), oral mucositis (1.98, CI 1.30-3.04), and the leukocyte nadir (0.12, CI 0.02-0.51) were significantly associated with a major infection in a univariate logistic regression analysis. In a multivariate analysis, skin toxicity was the only independent factor predictive for grade 3 to 4 infection (2.75, CI 1.00-7.58). A major infection was diagnosed in 62% (8 out of 13) of the docetaxel cycles in severely (grade 4) leukopenic patients who had grade 2 to 4 skin toxicity. Major infections are common in leukopenic patients who develop docetaxel-associated skin toxicity, and leukopenic patients presenting with docetaxel-induced skin toxicity may be candidates for prophylactic anti-infection measures such as prophylactic therapy with hematopoietic growth factors.