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  • 1
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    Daten des Frankfurter Netzwerks für Suizidprävention (FRANS): Suizidstatistik 2014–2017
    Georg Thieme Verlag KG ; 2020
    In:  Psychiatrische Praxis Vol. 47, No. 07 ( 2020-10), p. 376-382
    Details
    In: Psychiatrische Praxis, Georg Thieme Verlag KG, Vol. 47, No. 07 ( 2020-10), p. 376-382
    Abstract: Ziel Das Frankfurter Netzwerk für Suizidprävention (FRANS) dokumentiert die Entwicklung der Suizidzahlen in Frankfurt a. M., um gezielt Präventionsbedarfe zu erkennen. Methode Auswertung der Leichenschauscheine mit Todesursache „Selbsttötung“. Die Suizidstatistik erhebt Geschlecht, Alter, Suizidmethode, Wohn- und Geburtsort, die Meldeadresse sowie Ort und Datum des Suizides. Ergänzt werden die Daten durch Informationen aus dem Einwohnermelderegister. Ergebnisse Die Auswertung zeigt eine relativ konstante Zahl von ca. 90 Suiziden pro Jahr, die Gesamtsuizidrate reduzierte sich im Erhebungszeitraum 2014–2017 von 12,84 auf 12,68 pro 100 000 Einwohner. Die höchste Suizidrate zeigt sich in der Altersklasse der über 81-Jährigen. Die Anzahl der vollendeten Suizide lag bei Männern deutlich höher als bei Frauen, die häufigste Methode war Erhängen. Schlussfolgerung Die Analyse der Daten macht eine gezielte Präventionsarbeit und an den konkreten lokalen Bedarfen ausgerichtete Maßnahmen möglich.
    Type of Medium: Online Resource
    ISSN: 0303-4259 , 1439-0876
    URL: Article
    DOI: 10.1055/a-1142-0965
    RVK:
    XA 10000
    Language: German
    Publisher: Georg Thieme Verlag KG
    Publication Date: 2020
    detail.hit.zdb_id: 124981-2
    SSG: 5,2
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  • 2
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    Prediction of cerebral venous thrombosis with a new clinical score and D-dimer levels
    Ovid Technologies (Wolters Kluwer Health) ; 2020
    In:  Neurology Vol. 95, No. 7 ( 2020-08-18), p. e898-e909
    Details
    In: Neurology, Ovid Technologies (Wolters Kluwer Health), Vol. 95, No. 7 ( 2020-08-18), p. e898-e909
    Abstract: To investigate prediction of cerebral venous thrombosis (CVT) by clinical variables and D-dimer levels. Methods This prospective multicenter study included consecutive patients with clinically possible CVT. On admission, patients underwent clinical examination, blood sampling for D-dimers measuring (ELISA test), and magnetic resonance/CT venography. Predictive value of clinical variables and D-dimers for CVT was calculated. A clinical score to stratify patients into groups with low, moderate, or high CVT risk was established with multivariate logistic regression. Results CVT was confirmed in 26.2% (94 of 359) of patients by neuroimaging. The optimal estimate of clinical probability was based on 6 variables: seizure(s) at presentation (4 points), known thrombophilia (4 points), oral contraception (2 points), duration of symptoms 〉 6 days (2 points), worst headache ever (1 point), and focal neurologic deficit at presentation (1 point) (area under the curve [AUC] 0.889). We defined 0 to 2 points as low CVT probability (negative predictive value [NPV] 94.1%). Of the 186 (51.8%) patients who had a low probability score, 11 (5.9%) had CVT. The frequency of CVT was 28.3% (34 of 120) in patients with a moderate (3–5 points) and 92.5% (49 of 53) in patients with a high (6–12 points) probability score. All low CVT probability patients with CVT had D-dimers 〉 500 μg/L. Predictive value of D-dimers for CVT for 〉 675 μg/L (best cutoff) vs 〉 500 μg/L was as follows: sensitivity 77.7%, specificity, 77%, NPV 90.7%, and accuracy 77.2% vs sensitivity 89.4%, specificity 66.4%, NPV 94.6%, and accuracy 72.4%, respectively. Adding the clinical score to D-dimers 〉 500 μg/L resulted in the best CVT prediction score explored (at the cutoff ≥6 points: sensitivity 83%/specificity 86.8%/NPV 93.5%/accuracy 84.4%/AUC 0.937). Conclusion The proposed new clinical score in combination with D-dimers may be helpful for predicting CVT as a pretest score; none of the patients with CVT showed low clinical probability for CVT and D-dimers 〈 500 μg/L. ClinicalTrials.gov identifier NCT00924859.
    Type of Medium: Online Resource
    ISSN: 0028-3878 , 1526-632X
    URL: Article
    DOI: 10.1212/WNL.0000000000009998
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
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  • 3
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    SOX2 Expression Associates with Stem Cell State in Human Ovarian Carcinoma
    American Association for Cancer Research (AACR) ; 2013
    In:  Cancer Research Vol. 73, No. 17 ( 2013-09-01), p. 5544-5555
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 73, No. 17 ( 2013-09-01), p. 5544-5555
    Abstract: The SRY-related HMG-box family of transcription factors member SOX2 regulates stemness and pluripotency in embryonic stem cells and plays important roles during early embryogenesis. More recently, SOX2 expression was documented in several tumor types including ovarian carcinoma, suggesting an involvement of SOX2 in regulation of cancer stem cells (CSC). Intriguingly, however, studies exploring the predictive value of SOX2 protein expression with respect to histopathologic and clinical parameters report contradictory results in individual tumors, indicating that SOX2 may play tumor-specific roles. In this report, we analyze the functional relevance of SOX2 expression in human ovarian carcinoma. We report that in human serous ovarian carcinoma (SOC) cells, SOX2 expression increases the expression of CSC markers, the potential to form tumor spheres, and the in vivo tumor-initiating capacity, while leaving cellular proliferation unaltered. Moreover, SOX2-expressing cells display enhanced apoptosis resistance in response to conventional chemotherapies and TRAIL. Hence, our data show that SOX2 associates with stem cell state in ovarian carcinoma and induction of SOX2 imposes CSC properties on SOC cells. We propose the existence of SOX2-expressing ovarian CSCs as a mechanism of tumor aggressiveness and therapy resistance in human SOC. Cancer Res; 73(17); 5544–55. ©2013 AACR.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/0008-5472.CAN-12-4177
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2013
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 4
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    A novel biomarker-based prognostic score in acute ischemic stroke : The CoRisk score
    Ovid Technologies (Wolters Kluwer Health) ; 2019
    In:  Neurology Vol. 92, No. 13 ( 2019-03-26), p. e1517-e1525
    Details
    In: Neurology, Ovid Technologies (Wolters Kluwer Health), Vol. 92, No. 13 ( 2019-03-26), p. e1517-e1525
    Abstract: To derive and externally validate a copeptin-based parsimonious score to predict unfavorable outcome 3 months after an acute ischemic stroke (AIS). Methods The derivation cohort consisted of patients with AIS enrolled prospectively at the University Hospital Basel, Switzerland. The validation cohort was prospectively enrolled after the derivation cohort at the University Hospital of Bern and University Hospital Basel, Switzerland, as well as Frankfurt a.M., Germany. The score components were copeptin levels, age, NIH Stroke Scale, and recanalization therapy (CoRisk score). Copeptin levels were measured in plasma drawn within 24 hours of AIS and before any recanalization therapy. The primary outcome of disability and death at 3 months was defined as modified Rankin Scale score of 3 to 6. Results Overall, 1,102 patients were included in the analysis; the derivation cohort contributed 319 patients, and the validation cohort contributed 783. An unfavorable outcome was observed among 436 patients (40%). For the 3-month prediction of disability and death, the CoRisk score was well calibrated in the validation cohort, for which the area under the receiver operating characteristic curve was 0.819 (95% confidence interval [CI] 0.787–0.849). The calibrated CoRisk score correctly classified 75% of patients (95% CI 72–78). The net reclassification index between the calibrated CoRisk scores with and without copeptin was 46% (95% CI 32–60). Conclusions The biomarker-based CoRisk score for the prediction of disability and death was externally validated, was well calibrated, and performed better than the same score without copeptin. ClinicalTrials.gov identifier NCT00390962 (derivation cohort) and NCT00878813 (validation cohort).
    Type of Medium: Online Resource
    ISSN: 0028-3878 , 1526-632X
    URL: Article
    DOI: 10.1212/WNL.0000000000007177
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2019
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  • 5
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    Update on the diagnosis and treatment of neuromyelitis optica spectrum disorders (NMOSD) – revised recommendations of the Neuromyelitis Optica Study Group (NEMOS). Part II: Attack therapy and long-term management
    Springer Science and Business Media LLC ; 2023
    In:  Journal of Neurology
    Details
    In: Journal of Neurology, Springer Science and Business Media LLC
    Abstract: This manuscript presents practical recommendations for managing acute attacks and implementing preventive immunotherapies for neuromyelitis optica spectrum disorders (NMOSD), a rare autoimmune disease that causes severe inflammation in the central nervous system (CNS), primarily affecting the optic nerves, spinal cord, and brainstem. The pillars of NMOSD therapy are attack treatment and attack prevention to minimize the accrual of neurological disability. Aquaporin-4 immunoglobulin G antibodies (AQP4-IgG) are a diagnostic marker of the disease and play a significant role in its pathogenicity. Recent advances in understanding NMOSD have led to the development of new therapies and the completion of randomized controlled trials. Four preventive immunotherapies have now been approved for AQP4-IgG-positive NMOSD in many regions of the world: eculizumab, ravulizumab - most recently-, inebilizumab, and satralizumab. These new drugs may potentially substitute rituximab and classical immunosuppressive therapies, which were as yet the mainstay of treatment for both, AQP4-IgG-positive and -negative NMOSD. Here, the Neuromyelitis Optica Study Group (NEMOS) provides an overview of the current state of knowledge on NMOSD treatments and offers statements and practical recommendations on the therapy management and use of all available immunotherapies for this disease. Unmet needs and AQP4-IgG-negative NMOSD are also discussed. The recommendations were developed using a Delphi-based consensus method among the core author group and at expert discussions at NEMOS meetings.
    Type of Medium: Online Resource
    ISSN: 0340-5354 , 1432-1459
    URL: Article
    DOI: 10.1007/s00415-023-11910-z
    RVK:
    XA 10000
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 1421299-7
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  • 6
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    Cardiac Hyaluronan Synthesis Is Critically Involved in the Cardiac Macrophage Response and Promotes Healing After Ischemia Reperfusion Injury
    Ovid Technologies (Wolters Kluwer Health) ; 2019
    In:  Circulation Research Vol. 124, No. 10 ( 2019-05-10), p. 1433-1447
    Details
    In: Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 124, No. 10 ( 2019-05-10), p. 1433-1447
    Abstract: Immediate changes in the ECM (extracellular matrix) microenvironment occur after myocardial ischemia and reperfusion (I/R) injury. Objective: Aim of this study was to unravel the role of the early hyaluronan (HA)-rich ECM after I/R. Methods and Results: Genetic deletion of Has2 and Has1 was used in a murine model of cardiac I/R. Chemical exchange saturation transfer imaging was adapted to image cardiac ECM post-I/R. Of note, the cardiac chemical exchange saturation transfer signal was severely suppressed by Has2 deletion and pharmacological inhibition of HA synthesis 24 hours after I/R. Has2 KO ( Has2 deficient) mice showed impaired hemodynamic function suggesting a protective role for endogenous HA synthesis. In contrast to Has2 deficiency, Has1 -deficient mice developed no specific phenotype compared with control post-I/R. Importantly, in Has2 KO mice, cardiac macrophages were diminished after I/R as detected by 19 F MRI (magnetic resonance imaging) of perfluorcarbon-labeled immune cells, Mac-2/Galectin-3 immunostaining, and FACS (fluorescence-activated cell sorting) analysis (CD45 + CD11b + Ly6G − CD64 + F4/80 + cells). In contrast to macrophages, cardiac Ly6C high and Ly6C low monocytes were unaffected post-I/R compared with control mice. Mechanistically, inhibition of HA synthesis led to increased macrophage apoptosis in vivo and in vitro. In addition, α-SMA (α-smooth muscle actin)–positive cells were reduced in the infarcted myocardium and in the border zone. In vitro, the myofibroblast response as measured by Acta2 mRNA expression was reduced by inhibition of HA synthesis and of CD44 signaling. Furthermore, Has2 KO fibroblasts were less able to contract collagen gels in vitro. The effects of HA/CD44 on fibroblasts and macrophages post-I/R might also affect intercellular cross talk because cardiac fibroblasts were activated by monocyte/macrophages and, in turn, protected macrophages from apoptosis. Conclusions: Increased HA synthesis contributes to postinfarct healing by supporting macrophage survival and by promoting the myofibroblast response. Additionally, imaging of cardiac HA by chemical exchange saturation transfer post-I/R might have translational value.
    Type of Medium: Online Resource
    ISSN: 0009-7330 , 1524-4571
    URL: Article
    DOI: 10.1161/CIRCRESAHA.118.313285
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2019
    detail.hit.zdb_id: 1467838-X
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  • 7
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    Identification of a novel type of ITD mutations located in nonjuxtamembrane domains of the FLT3 tyrosine kinase receptor
    American Society of Hematology ; 2009
    In:  Blood Vol. 113, No. 17 ( 2009-04-23), p. 4074-4077
    Details
    In: Blood, American Society of Hematology, Vol. 113, No. 17 ( 2009-04-23), p. 4074-4077
    Abstract: In acute myeloid leukemia (AML), internal tandem duplications (ITDs) of the juxtamembrane (JM) of FLT3 have been shown to play a crucial role in driving proliferation and survival of the leukemic clone. Here, we report the identification of FLT3_ITD mutations located in non-JM domains of the FLT3-receptor. This novel type of FLT3_ITD mutation was found in 216 of 753 (28.7%) of unselected FLT3_ITD-positive AML cases. An FLT3 receptor harbouring a prototypic non-JM ITD (FLT3_ITD627E) mediated constitutive phosphorylation of FLT3 and of STAT5, suggesting that non-JM ITDs confer constitutive activation of the receptor. FLT3_ITD627E induced transformation of hematopoietic 32D cells and led to a lethal myeloproliferative disease in a syngeneic mouse model. Our results indicate that a significant proportion of activating FLT3_ITD mutations is not confined to the JM domain of FLT3. Further studies are warranted to define the biologic and clinical characteristics of non-JM ITDs.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood-2007-11-125476
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 8
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    Differences in Demographic Characteristics and Risk Factors in Patients With Spontaneous Vertebral Artery Dissections With and Without Ischemic Events
    Ovid Technologies (Wolters Kluwer Health) ; 2010
    In:  Stroke Vol. 41, No. 4 ( 2010-04), p. 802-804
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 41, No. 4 ( 2010-04), p. 802-804
    Abstract: Background and Purpose— Spontaneous vertebral artery dissection (sVADs) mainly cause cerebral ischemia, with or without associated local symptoms and signs (headache, neck pain, or cervical radiculopathy), or with local symptoms and signs only. Methods— We compared the presenting characteristics of consecutive patients with single sVADs and ischemic events and those with local symptoms and signs only. Results— Of the 186 patients with first-ever unilateral sVAD, 165 (89%) presented with cerebral ischemia, and 21 (11%) presented with local symptoms and signs only. Patients with sVAD and ischemia were more often male (63% vs 29%; P =0.002), older (mean±SD age, 43.6±9.9 vs 38.6±9.0 years; P =0.027), and smokers (14% vs 3%; P =0.010), but less often, they had a history of migraine without aura (17% vs 38%; P =0.025) than did patients without ischemia. The multivariate analysis confirmed independent associations between male sex ( P =0.024), increasing age (0.027), and smoking ( P =0.012) and sVADs causing cerebral ischemia. Conclusions— These results suggest that men, older patients, and smokers with sVADs may be at increased risk for ischemic events.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.109.570655
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2010
    detail.hit.zdb_id: 1467823-8
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  • 9
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    Gene-Expression Profiling of Mucinous Ovarian Tumors and Comparison with Upper and Lower Gastrointestinal Tumors Identifies Markers Associated with Adverse Outcomes
    American Association for Cancer Research (AACR) ; 2022
    In:  Clinical Cancer Research Vol. 28, No. 24 ( 2022-12-15), p. 5383-5395
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 28, No. 24 ( 2022-12-15), p. 5383-5395
    Abstract: Advanced-stage mucinous ovarian carcinoma (MOC) has poor chemotherapy response and prognosis and lacks biomarkers to aid stage I adjuvant treatment. Differentiating primary MOC from gastrointestinal (GI) metastases to the ovary is also challenging due to phenotypic similarities. Clinicopathologic and gene-expression data were analyzed to identify prognostic and diagnostic features. Experimental Design: Discovery analyses selected 19 genes with prognostic/diagnostic potential. Validation was performed through the Ovarian Tumor Tissue Analysis consortium and GI cancer biobanks comprising 604 patients with MOC (n = 333), mucinous borderline ovarian tumors (MBOT, n = 151), and upper GI (n = 65) and lower GI tumors (n = 55). Results: Infiltrative pattern of invasion was associated with decreased overall survival (OS) within 2 years from diagnosis, compared with expansile pattern in stage I MOC [hazard ratio (HR), 2.77; 95% confidence interval (CI), 1.04–7.41, P = 0.042]. Increased expression of THBS2 and TAGLN was associated with shorter OS in MOC patients (HR, 1.25; 95% CI, 1.04–1.51, P = 0.016) and (HR, 1.21; 95% CI, 1.01–1.45, P = 0.043), respectively. ERBB2 (HER2) amplification or high mRNA expression was evident in 64 of 243 (26%) of MOCs, but only 8 of 243 (3%) were also infiltrative (4/39, 10%) or stage III/IV (4/31, 13%). Conclusions: An infiltrative growth pattern infers poor prognosis within 2 years from diagnosis and may help select stage I patients for adjuvant therapy. High expression of THBS2 and TAGLN in MOC confers an adverse prognosis and is upregulated in the infiltrative subtype, which warrants further investigation. Anti-HER2 therapy should be investigated in a subset of patients. MOC samples clustered with upper GI, yet markers to differentiate these entities remain elusive, suggesting similar underlying biology and shared treatment strategies.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1078-0432.CCR-22-1206
    RVK:
    XA 36791
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
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  • 10
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    Bis(1 H ‐indol‐2‐yl)methanones are effective inhibitors of FLT3‐ITD tyrosine kinase and partially overcome resistance to PKC412A in vitro
    Wiley ; 2009
    In:  British Journal of Haematology Vol. 144, No. 6 ( 2009-03), p. 865-874
    Details
    In: British Journal of Haematology, Wiley, Vol. 144, No. 6 ( 2009-03), p. 865-874
    Abstract: Inhibition of the mutated fms‐like tyrosine kinase 3 (FLT3) receptor tyrosine kinase is a promising therapeutic strategy in acute myeloid leukaemia (AML). However, development of resistance to FLT3 tyrosine kinase inhibitors (TKI), such as PKC412A, has been described recently. This observation may have an increasing impact on the duration of response and relapse rates in upcoming clinical trials employing FLT3‐TKI. Herein we investigated two representatives of a novel class of FLT3‐TKI: Bis(1 H ‐indol‐2‐yl)methanones. Both compounds effectively induced apoptosis in FLT3‐internal tandem duplicate (ITD)‐transfected murine myeloid cells and in primary FLT3‐ITD positive blasts. Combination of both compounds with chemotherapy revealed synergistic effects in apoptosis assays. The compounds did not show significant toxicity in human bone marrow cells derived from healthy donors. Compound102 overcame resistance to PKC412 within a non‐myelotoxic dose‐range. Western Blotting experiments of 32D‐FLT3‐ITD cells showed dose‐dependent dephosphorylation of FLT3‐ITD and of its downstream targets STAT5, AKT and ERK upon incubation with either compound. In conclusion, bis(1 H ‐indol‐2‐yl)methanones overcome resistance mediated by FLT3‐ITD mutations at position N676 and show strong efficacy in FLT3‐ITD‐positive cells alone as well as in combination with chemotherapy. We propose that further development of methanone compounds overcoming resistance to currently established FLT3‐TKIs is an important step forward to an anticipated need within our future therapeutic algorithm in FLT3‐ITD‐positive AML.
    Type of Medium: Online Resource
    ISSN: 0007-1048 , 1365-2141
    URL: Issue
    URL: Article
    DOI: 10.1111/bjh.2009.144.issue-6
    DOI: 10.1111/j.1365-2141.2008.07567.x
    RVK:
    XA 34100
    Language: English
    Publisher: Wiley
    Publication Date: 2009
    detail.hit.zdb_id: 1475751-5
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