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  • 1
    Electronic Resource
    Electronic Resource
    Oxford BSL : Blackwell Science Ltd
    British journal of dermatology 140 (1999), S. 0 
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    British journal of dermatology 143 (2000), S. 0 
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    British journal of dermatology 147 (2002), S. 0 
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    British journal of dermatology 149 (2003), S. 0 
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary Background Melanoma-associated retinopathy (MAR) is a paraneoplastic syndrome with symptoms of night blindness, light sensations, visual loss, defect in visual fields, and reduced b-waves in the electroretinogram. Patients with MAR often suffer from a sudden onset of ocular symptoms that are believed to result from antibody production against melanoma-associated antigens that cross-react with corresponding epitopes on retinal depolarizing bipolar cells. Objectives To correlate the frequency of subclinical symptoms suggestive of MAR in melanoma patients to different stages of disease, patient age, type and thickness of the primary tumour, form of therapy, S-100 level and tumour burden. Methods We analysed 28 patients with melanoma in stages I–IV (according to the American Joint Committee on Cancer tumour classification) for the presence of subclinical MAR symptoms using scotopic electroretinography, static and kinetic perimetry and nyctometry. Results Seven patients had clinical signs and symptoms consistent with MAR, 18 had some indications, while the remaining three had none. We found no correlation between clinical symptoms and stage of disease, tumour burden or S-100 level, but findings suggestive of MAR were observed more frequently in advanced stages of disease. Conclusions Subclinical retinal involvement characteristic of MAR appears to be more common than previously suspected in patients with cutaneous malignant melanoma. Our findings in this small cohort seem to indicate that the percentage of patients with symptoms suggestive of MAR is higher in advanced stages of disease. Further clinical studies are required to evaluate if the presence of subclinical symptoms suggestive of MAR is correlated with a worse prognosis and a shortened progression-free and overall survival.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1433-0474
    Keywords: SchlüsselwörterNeisseria meningitidis ; Septischer Schock ; Waterhouse-Friderichsen-Syndrom ; Mortalität im Kindesalter ; Erworbene Hämostasestörung ; Key wordsN. meningitidis ; Septic shock ; Waterhouse Friderichsen syndrome ; Childhood mortality ; Acquired coagulation deficiency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Background: N. meningitidis infections may present as severe fulminant sepsis with poor prognosis. We assessed the frequency, age distribution, hemostaseological skin findings, need for intensive care therapy and prognosis of this infection. Methods: The data were collected using an active monthly surveillance system, the „Erhebungseinheit für seltene pädiatrische Erkrankungen in Deutschland (ESPED)“ from July 1994 to June 1995 in 320 childrens hospitals in Germany. Patients over to the age of 16 were excluded. The answering rate was 91 %. Results: 291 infections according to the case definition (N. meningitidis in blood culture and/or cerebrospinal fluid) were reported. Frequency peaked in the first year of life (n = 87) and from age 13 to 16 (n = 53). Intensive care measures (mechanical ventilation, dialysis, catecholamines) were needed in 42 children; 29 of those survived. The overall mortality was 4.5 %, but was relatively higher in 5–6 year old children (15 %). Petechiae and small hematomas (〈 10 mm) were a frequent finding (112/291 [38 %] patients), all these children survived. Ecchymoses (〉 10 mm) and/or skin necroses were observed in 82 children; 12 (15 %) of those died. Four survivors required surgical interventions for correction of necroses (skin transplants and/or amputations). Conclusions: Petechiae and small subcutaneous bleedings (〈 10 mm) are not indicative for an unfavourable prognosis of N. meningitidis infections. The overall mortality was low (4.5 %), however, despite early antibiotic therapy relatively high in 5–6 year old children (15 %). The findings ecchymoses and/or skin necroses alone are not sufficient to evaluate the efficacy of innovative therapeutical measures.
    Notes: Zusammenfassung Hintergrund: Neisseria meningitidis-Infektionen sind beim Auftreten einer Sepsis mit einer hohen Mortalität behaftet. Ziel der Untersuchung war die Evaluierung von Inzidenz, Klinik, Therapie und Prognose dieser Infektionskrankheiten. Methode:Über die „Erhebungseinheit für seltene pädiatrische Erkrankungen in Deutschland“ (ESPED) wurden von Juli 1994 bis Juni 1995 monatlich die oben genannten Parameter in 320 Kinderkliniken bei Kindern und Jugendlichen (≤ 16 Jahre) erfragt. Die Rückantwortquote war 91 %. Ergebnisse: Es wurden 291 Infektionen gemäß der Falldefinition gemeldet. Infektionen traten am häufigsten im 1. Lebensjahr (n = 87) und vom 13. bis 16. Lebensjahr (n = 53) auf. Intensivtherapie erhielten 42 Patienten, von denen 29 überlebten. Die Gesamtmortalität betrug 4,5 % war jedoch bei den 5- bis 6jährigen Kindern mit 15 % hoch. Petechien und kleine Hämatome waren mit 112 von 291 (38 %) ein häufiger Befund; diese Kinder überlebten alle. Flächenhafte Hautblutungen (mit oder ohne Petechien) und/oder Hautnekrosen traten bei 82 Kindern auf, von denen 12 (15 %) verstarben. Schlußfolgerungen: Petechien und kleine Hautblutungen als einzige klinische Zeichen der Hämostasestörung sind per se nicht mit einer ungünstigen Prognose verbunden. Diese bundesweite Erhebung zu Neisseria-meningitidis-Infektionen zeigt, daß bei insgesamt hoher Fallzahl die Gesamtmortalität gering war, jedoch trotz frühzeitiger Antibiotikabehandlung eine überraschend hohe Sterblichkeit im Vorschulalter vorlag. Großflächige Blutungen und/oder Hautnekrosen als einzige Kriterien haben eine zu geringe prognostische Aussagekraft, um die Effektivität zusätzlicher Therapiemaßnahmen in vertretbarer Zeit und Zahl evaluieren zu können.
    Type of Medium: Electronic Resource
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  • 7
    Publication Date: 2015-02-28
    Description: Background Kinase inhibitors targeting the BRAF V600 mutation have become standard in the treatment of metastatic melanoma. Albeit in wide clinical use, the patterns associated with therapy outcome are not fully elucidated. The present study was aimed to identify predictive factors of therapy response and survival under the BRAF inhibitor vemurafenib. Patients and methods This multicenter retrospective study analyzed patient, tumor, and pretreatment characteristics collected in BRAF V600-mutated stage IV melanoma patients before single-agent therapy with the BRAF inhibitor vemurafenib. Results A total of 300 patients from 14 centers were included into this study with a median follow-up time of 13.0 months. Median progression-free survival (PFS) was 5.1 months; median overall survival (OS) was 7.6 months. Best response under vemurafenib was associated with serum lactate dehydrogenase (LDH; ≤ versus 〉upper normal limit; P = 0.0000001), Eastern Cooperative Oncology Group (ECOG) overall performance status (OPS) (0 versus ≥1; P = 0.00089), and BRAF mutation subtype (V600E versus V600K; P = 0.016). Multivariate analysis identified ECOG OPS ≥1 [hazard ratio (HR) = 1.88; P = 0.00005], immunotherapy pretreatment (HR = 0.53; P = 0.0067), elevated serum LDH (HR = 1.45; P = 0.012), age 〉55 years (HR = 0.72; P = 0.019), and chemotherapy pretreatment (HR = 1.39; P = 0.036) as independent predictors of PFS. For OS, elevated serum LDH (HR = 1.99; P = 0.00012), ECOG OPS ≥1 (HR = 1.90; P = 0.00063), age 〉55 years (HR = 0.65; P = 0.011), kinase inhibitor pretreatment (HR = 1.86; P = 0.014), immunotherapy pretreatment (HR = 0.57; P = 0.025), chemotherapy pretreatment (HR = 2.17; P = 0.039), and male gender (HR = 0.70; 95% confidence interval 0.50–0.98; P = 0.039) were found as predictors. Conclusion Our data demonstrate that the type of pretreatment strongly influences the outcome of vemurafenib therapy, with a precedent immunotherapy showing a positive, and a prior chemotherapy and kinase inhibitors showing a negative impact on survival, respectively. Moreover, we show that the patient's OPS, serum LDH, age, and gender independently impact vemurafenib therapy outcome. These findings should be taken into account for the future design of therapy sequencing in BRAF V600 mutation-positive melanoma patients.
    Print ISSN: 0923-7534
    Electronic ISSN: 1569-8041
    Topics: Medicine
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  • 8
    Publication Date: 2015-04-11
    Description: Malignant melanoma is the most deadly form of skin cancer. There is a critical need to identify the patients that could be successfully treated by surgery alone and those that require adjuvant treatment. In this study, we demonstrate that the expression of tribbles2 ( TRIB2 ) strongly correlates with both the presence and progression of melanocyte-derived malignancies. We examined the expression of TRIB2 in addition to 12 previously described melanoma biomarkers across three independent full genome microarray studies. TRIB2 expression was consistently and significantly increased in benign nevi and melanoma, and was highest in samples from patients with metastatic melanoma. The expression profiles for the 12 biomarkers were poorly conserved throughout these studies with only TYR , S100B and SPP1 showing consistently elevated expression in metastatic melanoma versus normal skin. Strikingly we confirmed these findings in 20 freshly obtained primary melanoma tissue samples from metastatic lesions where the expression of these biomarkers were evaluated revealing that TRIB2 expression correlated with disease stage and clinical prognosis. Our results suggest that TRIB2 is a meaningful biomarker reflecting diagnosis and progression of melanoma, as well as predicting clinical response to chemotherapy.
    Print ISSN: 0143-3334
    Electronic ISSN: 1460-2180
    Topics: Medicine
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  • 9
    Publication Date: 2014-01-18
    Description: Purpose: Dermatofibrosarcoma protuberans (DFSP) is a rare cutaneous tumor. COL1A1–PDGFB gene fusion is frequent in DFSP, rendering tumor cell proliferation and survival dependent on PDGFRβ (platelet-derived growth factor receptor β) signaling. This trial investigated imatinib as neoadjuvant treatment of DFSP, including long-term follow-up. Experimental Design: The primary endpoint of this multicenter phase II trial was response; secondary endpoints were safety, tumor relapse, and response biomarkers. Patients with advanced primary or locally recurrent DFSP and measurable disease by RECIST (response evaluation criteria in solid tumors) were eligible and received imatinib 600 mg/d until definitive surgery with histopathologic proof of tumor-free margins. Results: Sixteen patients received imatinib, and 14 patients were evaluable for all endpoints. Median treatment duration was 3.1 months; median tumor shrinkage was 31.5%. Best overall response was 7.1% complete response (CR), 50.0% partial response (PR), 35.7% stable disease, and 7.1% progressive disease (PD). Toxicity was moderate with 25.0% grade 3 and 4 events. During a median follow-up of 6.4 years, one patient developed secondary resistance to imatinib but responded to second-line sunitinib. This patient also presented local recurrence, distant metastasis, and death from DFSP. Exploratory analysis showed that response to imatinib was associated with decreased tumor cellularity and formation of strong hyalinic fibrosis. Weak PDGFRB phosphorylation and pigmented-type DFSP were associated with nonresponse. Additional to PDGFRB, the kinases EGFR and insulin receptor were found activated in a high percentage of DFSPs. Conclusion: The neoadjuvant use of imatinib 600 mg/d in DFSP is efficacious and well tolerated. Long-term follow-up results do not definitely support smaller surgical margins after successful imatinib pretreatment, and presume that secondary resistance to imatinib might promote accelerated disease progression. Clin Cancer Res; 20(2); 499–510. ©2013 AACR .
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
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  • 10
    Publication Date: 2018-12-04
    Description: Purpose: Merkel cell carcinoma (MCC) is an aggressive skin cancer with neuroendocrine differentiation. There is an unmet need for MCC-specific blood-based surrogate biomarkers of tumor burden; circulating cell-free miRNA may serve this purpose. Experimental Design: Expression of miR-375 was quantified in 24 MCC and 23 non-MCC cell lines, 67 MCC and 58 non-MCC tumor tissues, sera of 2 preclinical MCC models, and sera of 109 patients with MCC and 30 healthy controls by nCounter human-v2-miRNA expression or miR-375–specific real-time PCR assays. The patients’ sera consisted of two retrospective (discovery and training) and two prospective (validation) cohorts. Results: miR-375 expression was high in MCC cell lines and tissues compared with non-MCCs. It was readily detected in MCC-conditioned medium and sera of preclinical models bearing MCC xenografts. miR-375 levels were higher in sera from tumor-bearing patients with MCC than in tumor-free patients or healthy controls ( P 〈 0.0005). Moreover, miR-375 serum levels correlated with tumor stage in tumor-bearing ( P = 0.037) but not in tumor-free ( P = 0.372) patients with MCC. miR-375 serum level showed high diagnostic accuracy to discriminate tumor-bearing and tumor-free patients with MCC as demonstrated by ROC curve analysis in the retrospective cohorts (AUC = 0.954 and 0.800) as well as in the prospective cohorts (AUC = 0.929 and 0.959). miR-375 serum level reflected dynamic changes in tumor burden of patients with MCC during therapeutic interventions. Conclusions: Circulating cell-free miR-375 proved as a surrogate marker for tumor burden in MCC without restriction to polyomavirus positivity; it thus appears to be useful for therapy monitoring and the follow-up of patients with MCC.
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
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