TY - JOUR A1 - Lux, Michael P. A1 - Schneeweiss, Andreas A1 - Hartkopf, Andreas D. A1 - Müller, Volkmar A1 - Janni, Wolfgang A1 - Belleville, Erik A1 - Stickeler, Elmar A1 - Thill, Marc A1 - Fasching, Peter A. A1 - Kolberg, Hans-Christian A1 - Untch, Michael A1 - Harbeck, Nadia A1 - Wöckel, Achim A1 - Thomssen, Christoph A1 - Schulmeyer, Carla E. A1 - Welslau, Manfred A1 - Overkamp, Friedrich A1 - Schütz, Florian A1 - Lüftner, Diana A1 - Ditsch, Nina T1 - Update Breast Cancer 2020 Part 5 – Moving Therapies From Advanced to Early Breast Cancer Patients JF - Geburtshilfe und Frauenheilkunde N2 - In recent years, significant progress has been made in new therapeutic approaches to breast cancer, particularly in patients with HER2-positive and HER2-negative/hormone receptor-positive (HR+) breast cancer. In the case of HER2-positive tumours, these approaches have included, in particular, treatment with pertuzumab, T-DM1, neratinib and, soon, also tucatinib and trastuzumab deruxtecan (neither of which has yet been authorised in Europe). In patients with HER2−/HR+ breast cancer, CDK4/6 inhibitors and the PIK3CA inhibitor alpelisib are of particular importance. Further novel therapies, such as Akt kinase inhibitors and oral SERDs (selective estrogen receptor down regulators), are already being investigated in ongoing clinical trials. These therapeutic agents are not only being introduced into curative, (neo-)adjuvant therapeutic settings for HER2-positive tumours; a first favourable study on abemaciclib as an adjuvant therapy has now also been published. In patients with triple-negative breast cancer, after many years of negative study results with the Trop-2 antibody drug conjugate (ADC) sacituzumab govitecan, a randomised study has been published that may represent a significant therapeutic advance. This review describes the latest developments in breast cancer subsequent to the ESMO Congress 2020. KW - early breast cancer KW - therapy KW - prognosis KW - immune therapy KW - digital medicine Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-369989 VL - 81 ER - TY - JOUR A1 - de Boer, Rudolf A. A1 - De Keulenaer, Gilles A1 - Bauersachs, Johann A1 - Brutsaert, Dirk A1 - Cleland, John G. A1 - Diez, Javier A1 - Du, Xiao-Jun A1 - Ford, Paul A1 - Heinzel, Frank R. A1 - Lipson, Kenneth E. A1 - McDonagh, Theresa A1 - Lopez-Andres, Natalia A1 - Lunde, Ida G. A1 - Lyon, Alexander R. A1 - Pollesello, Piero A1 - Prasad, Sanjay K. A1 - Tocchetti, Carlo G. A1 - Mayr, Manuel A1 - Sluijter, Joost P. G. A1 - Thum, Thomas A1 - Tschöpe, Carsten A1 - Zannad, Faiez A1 - Zimmermann, Wolfram-Hubertus A1 - Ruschitzka, Frank A1 - Filippatos, Gerasimos A1 - Lindsey, Merry L. A1 - Maack, Christoph A1 - Heymans, Stephane T1 - Towards better definition, quantification and treatment of fibrosis in heart failure. A scientific roadmap by the Committee of Translational Research of the Heart Failure Association (HFA) of the European Society of Cardiology JF - European Journal of Heart Failure N2 - Fibrosis is a pivotal player in heart failure development and progression. Measurements of (markers of) fibrosis in tissue and blood may help to diagnose and risk stratify patients with heart failure, and its treatment may be effective in preventing heart failure and its progression. A lack of pathophysiological insights and uniform definitions has hampered the research in fibrosis and heart failure. The Translational Research Committee of the Heart Failure Association discussed several aspects of fibrosis in their workshop. Early insidious perturbations such as subclinical hypertension or inflammation may trigger first fibrotic events, while more dramatic triggers such as myocardial infarction and myocarditis give rise to full blown scar formation and ongoing fibrosis in diseased hearts. Aging itself is also associated with a cardiac phenotype that includes fibrosis. Fibrosis is an extremely heterogeneous phenomenon, as several stages of the fibrotic process exist, each with different fibrosis subtypes and a different composition of various cells and proteins — resulting in a very complex pathophysiology. As a result, detection of fibrosis, e.g. using current cardiac imaging modalities or plasma biomarkers, will detect only specific subforms of fibrosis, but cannot capture all aspects of the complex fibrotic process. Furthermore, several anti-fibrotic therapies are under investigation, but such therapies generally target aspecific aspects of the fibrotic process and suffer from a lack of precision. This review discusses the mechanisms and the caveats and proposes a roadmap for future research. KW - fibrosis KW - heart failure KW - biomarkers KW - fibroblast KW - matrix KW - prognosis KW - imaging Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-223613 VL - 21 ER - TY - JOUR A1 - Altieri, Barbara A1 - Di Dato, Carla A1 - Martini, Chiara A1 - Sciammarella, Concetta A1 - Di Sarno, Antonella A1 - Colao, Annamaria A1 - Faggiano, Antongiulio T1 - Bone Metastases in Neuroendocrine Neoplasms: From Pathogenesis to Clinical Management JF - Cancers N2 - Bone represents a common site of metastases for several solid tumors. However, the ability of neuroendocrine neoplasms (NENs) to localize to bone has always been considered a rare and late event. Thanks to the improvement of therapeutic options, which results in longer survival, and of imaging techniques, particularly after the introduction of positron emission tomography (PET) with gallium peptides, the diagnosis of bone metastases (BMs) in NENs is increasing. The onset of BMs can be associated with severe skeletal complications that impair the patient's quality of life. Moreover, BMs negatively affect the prognosis of NEN patients, bringing out the lack of curative treatment options for advanced NENs. The current knowledge on BMs in gastro-entero-pancreatic (GEP) and bronchopulmonary (BP) NENs is still scant and is derived from a few retrospective studies and case reports. This review aims to perform a critical analysis of the evidence regarding the role of BMs in GEP- and BP-NENs, focusing on the molecular mechanisms underlining the development of BMs, as well as clinical presentation, diagnosis, and treatment of BMs, in an attempt to provide suggestions that can be used in clinical practice. KW - neuroendocrine neoplasms KW - bone metastases KW - bone microenvironment KW - skeletal-related events KW - epithelial-to-mesenchymal transition KW - microRNA KW - prognosis KW - treatment KW - denosumab Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-221079 VL - 11 ER - TY - JOUR A1 - Altieri, Barbara A1 - La Salvia, Anna A1 - Modica, Roberta A1 - Marciello, Francesca A1 - Mercier, Olaf A1 - Filosso, Pier Luigi A1 - de Latour, Bertrand Richard A1 - Giuffrida, Dario A1 - Campione, Severo A1 - Guggino, Gianluca A1 - Fadel, Elie A1 - Papotti, Mauro A1 - Colao, Annamaria A1 - Scoazec, Jean-Yves A1 - Baudin, Eric A1 - Faggiano, Antongiulio T1 - Recurrence-free survival in early and locally advanced large cell neuroendocrine carcinoma of the lung after complete tumor resection JF - Journal of Personalized Medicine N2 - Background: Large Cell Neuroendocrine Carcinoma (LCNEC) is a rare subtype of lung cancer with poor clinical outcomes. Data on recurrence-free survival (RFS) in early and locally advanced pure LCNEC after complete resection (R0) are lacking. This study aims to evaluate clinical outcomes in this subgroup of patients and to identify potential prognostic markers. Methods: Retrospective multicenter study including patients with pure LCNEC stage I-III and R0 resection. Clinicopathological characteristics, RFS, and disease-specific survival (DSS) were evaluated. Univariate and multivariate analyses were performed. Results: 39 patients (M:F = 26:13), with a median age of 64 years (44–83), were included. Lobectomy (69.2%), bilobectomy (5.1%), pneumonectomy (18%), and wedge resection (7.7%) were performed mostly associated with lymphadenectomy. Adjuvant therapy included platinum-based chemotherapy and/or radiotherapy in 58.9% of cases. After a median follow-up of 44 (4–169) months, the median RFS was 39 months with 1-, 2- and 5-year RFS rates of 60.0%, 54.6%, and 44.9%, respectively. Median DSS was 72 months with a 1-, 2- and 5-year rate of 86.8, 75.9, and 57.4%, respectively. At multivariate analysis, age (cut-off 65 years old) and pN status were independent prognostic factors for both RFS (HR = 4.19, 95%CI = 1.46–12.07, p = 0.008 and HR = 13.56, 95%CI 2.45–74.89, p = 0.003, respectively) and DSS (HR = 9.30, 95%CI 2.23–38.83, p = 0.002 and HR = 11.88, 95%CI 2.28–61.84, p = 0.003, respectively). Conclusion: After R0 resection of LCNEC, half of the patients recurred mostly within the first two years of follow-up. Age and lymph node metastasis could help to stratify patients for adjuvant therapy. KW - neuroendocrine tumor KW - LCNEC KW - pulmonary cancer KW - prognostic marker KW - prognosis KW - survival KW - lymph nodes KW - age KW - surgery KW - adjuvant therapy Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-304000 SN - 2075-4426 VL - 13 IS - 2 ER - TY - JOUR A1 - Schulmeyer, Carla E. A1 - Fasching, Peter A. A1 - Häberle, Lothar A1 - Meyer, Julia A1 - Schneider, Michael A1 - Wachter, David A1 - Ruebner, Matthias A1 - Pöschke, Patrik A1 - Beckmann, Matthias W. A1 - Hartmann, Arndt A1 - Erber, Ramona A1 - Gass, Paul T1 - Expression of the immunohistochemical markers CK5, CD117, and EGFR in molecular subtypes of breast cancer correlated with prognosis JF - Diagnostics N2 - Molecular-based subclassifications of breast cancer are important for identifying treatment options and stratifying the prognosis in breast cancer. This study aimed to assess the prognosis relative to disease-free survival (DFS) and overall survival (OS) in patients with triple-negative breast cancer (TNBC) and other subtypes, using a biomarker panel including cytokeratin 5 (CK5), cluster of differentiation 117 (CD117), and epidermal growth factor receptor (EGFR). This cohort–case study included histologically confirmed breast carcinomas as cohort arm. From a total of 894 patients, 572 patients with early breast cancer, sufficient clinical data, and archived tumor tissue were included. Using the immunohistochemical markers CK5, CD117, and EGFR, two subgroups were formed: one with all three biomarkers negative (TBN) and one with at least one of those three biomarkers positive (non-TBN). There were significant differences between the two biomarker subgroups (TBN versus non-TBN) in TNBC for DFS (p = 0.04) and OS (p = 0.02), with higher survival rates (DFS and OS) in the non-TBN subgroup. In this study, we found the non-TBN subgroup of TNBC lesions with at least one positive biomarker of CK5, CD117, and/or EGFR, to be associated with longer DFS and OS. KW - early breast cancer KW - therapy KW - prognosis KW - CK5 KW - CD117 KW - EGFR KW - triple-negative breast cancer Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-304987 SN - 2075-4418 VL - 13 IS - 3 ER - TY - JOUR A1 - Herbert, Saskia-Laureen A1 - Hirzle, Paula A1 - Bartmann, Catharina A1 - Schlaiß, Tanja A1 - Kiesel, Matthias A1 - Curtaz, Carolin A1 - Löb, Sanja A1 - Wöckel, Achim A1 - Diessner, Joachim T1 - Optimized process quality in certified breast centers through adherence to stringent diagnostic and therapeutic algorithms effects of structural as well as socio-demographic factors on start of therapy JF - Archives of Gynecology and Obstetrics N2 - Purpose An increasing incidence of breast cancer can be observed worldwide. Since a delay of therapy can have a negative impact on prognosis, timely cancer care is an important quality indicator. By receiving treatment at a certified breast cancer center, the patient has the best chance of treatment in accordance with guidelines and the best prognosis. The identification of risk factors for a delay of therapy is of central importance and should be the basis for a continuous optimization of treatment at breast cancer centers. Methods This retrospective study included women with breast cancer (primary diagnosis, relapse, or secondary malignancy) at the University Hospital Würzburg in 2019 and 2020. Data were retrieved from patients’ records. Correlations and regression analyses were performed to detect potential risk factors for treatment delay. Results Patients who received the histological confirmation of breast cancer at an external institution experienced a later therapy start than those patients who received the histological confirmation at the University Hospital Würzburg itself. (35.7 vs. 32.2 days). The interval between histological confirmation and the first consultation at the University Hospital Würzburg correlated statistically significant with age, distress and distance to the hospital. Conclusion Patients with an in-house diagnosis of breast cancer are treated more quickly than those whose diagnosis was confirmed in an external institution. We identified factors such as increased age, greater distance to the hospital as well as increased distress to prolong the time until start of oncological treatment. Intensified patient care should be offered to these subgroups. KW - breast cancer KW - delay of therapy KW - prognosis KW - quality of care Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324057 VL - 307 IS - 4 ER - TY - JOUR A1 - Dietl, Alexander A1 - Prieschenk, Christine A1 - Eckert, Franziska A1 - Birner, Christoph A1 - Luchner, Andreas A1 - Maier, Lars S. A1 - Buchner, Stefan T1 - 3D vena contracta area after MitraClip© procedure: precise quantification of residual mitral regurgitation and identification of prognostic information JF - Cardiovascular Ultrasound N2 - Background Percutaneous mitral valve repair (PMVR) is increasingly performed in patients with severe mitral regurgitation (MR). Post-procedural MR grading is challenging and an unsettled issue. We hypothesised that the direct planimetry of vena contracta area (VCA) by 3D–transoesophageal echocardiography allows quantifying post-procedural MR and implies further prognostic relevance missed by the usual ordinal scale (grade I-IV). Methods Based on a single-centre PMVR registry containing 102 patients, the association of VCA reduction and patients’ functional capacity measured as six-minute walk distance (6 MW) was evaluated. 3D–colour-Doppler datasets were available before, during and 4 weeks after PMVR. Results Twenty nine patients (age 77.0 ± 5.8 years) with advanced heart failure (75.9% NYHA III/IV) and severe degenerative (34%) or functional (66%) MR were eligible. VCA was reduced in all patients by PMVR (0.99 ± 0.46 cm\(^2\) vs. 0.22 ± 0.15 cm\(^2\), p < 0.0001). It remained stable after median time of 33 days (p = 0.999). 6 MW improved after the procedure (257.5 ± 82.5 m vs. 295.7 ± 96.3 m, p < 0.01). Patients with a decrease in VCA less than the median VCA reduction showed a more distinct improvement in 6 MW than patients with better technical result (p < 0.05). This paradoxical finding was driven by inferior results in very large functional MR. Conclusions VCA improves the evaluation of small residual MR. Its post-procedural values remain stable during a short-term follow-up and imply prognostic information for the patients’ physical improvement. VCA might contribute to a more substantiated estimation of treatment success in the heterogeneous functional MR group. KW - percutaneous mitral valve repair KW - MitraClip KW - 3D echocardiography KW - vena contracta area KW - six-minute walk test KW - NT-proBNP KW - prognosis KW - functional mitral regurgitation Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-225318 VL - 16 ER - TY - JOUR A1 - Tütüncü, Serdar A1 - Olma, Manuel C. A1 - Kunze, Claudia A1 - Krämer, Michael A1 - Dietzel, Joanna A1 - Schurig, Johannes A1 - Filser, Paula A1 - Pfeilschifter, Waltraud A1 - Hamann, Gerhard F. A1 - Büttner, Thomas A1 - Heuschmann, Peter U. A1 - Kirchhof, Paulus A1 - Laufs, Ulrich A1 - Nabavi, Darius G. A1 - Röther, Joachim A1 - Thomalla, Götz A1 - Veltkamp, Roland A1 - Eckardt, Kai‐Uwe A1 - Haeusler, Karl Georg A1 - Endres, Matthias T1 - Levels and dynamics of estimated glomerular filtration rate and recurrent vascular events and death in patients with minor stroke or transient ischemic attack JF - European Journal of Neurology N2 - Background and purpose Impaired kidney function is associated with an increased risk of vascular events in acute stroke patients, when assessed by single measurements of estimated glomerular filtration rate (eGFR). It is unknown whether repeated measurements provide additional information for risk prediction. Methods The MonDAFIS (Systematic Monitoring for Detection of Atrial Fibrillation in Patients with Acute Ischemic Stroke) study randomly assigned 3465 acute ischemic stroke patients to either standard procedures or an additive Holter electrocardiogram. Baseline eGFR (CKD‐EPI formula) were dichotomized into values of < versus ≥60 ml/min/1.73 m\(^{2}\). eGFR dynamics were classified based on two in‐hospital values as “stable normal” (≥60 ml/min/1.73 m\(^{2}\)), “increasing” (by at least 15% from baseline, second value ≥ 60 ml/min/1.73 m\(^{2}\)), “decreasing” (by at least 15% from baseline of ≥60 ml/min/1.73 m\(^{2}\)), and “stable decreased” (<60 ml/min/1.73 m\(^{2}\)). The composite endpoint (stroke, major bleeding, myocardial infarction, all‐cause death) was assessed after 24 months. We estimated hazard ratios in confounder‐adjusted models. Results Estimated glomerular filtration rate at baseline was available in 2947 and a second value in 1623 patients. After adjusting for age, stroke severity, cardiovascular risk factors, and randomization, eGFR < 60 ml/min/1.73 m\(^{2}\) at baseline (hazard ratio [HR] = 2.2, 95% confidence interval [CI] = 1.40–3.54) as well as decreasing (HR = 1.79, 95% CI = 1.07–2.99) and stable decreased eGFR (HR = 1.64, 95% CI = 1.20–2.24) were independently associated with the composite endpoint. In addition, eGFR < 60 ml/min/1.732 at baseline (HR = 3.02, 95% CI = 1.51–6.10) and decreasing eGFR were associated with all‐cause death (HR = 3.12, 95% CI = 1.63–5.98). Conclusions In addition to patients with low eGFR levels at baseline, also those with decreasing eGFR have increased risk for vascular events and death; hence, repeated estimates of eGFR might add relevant information to risk prediction. KW - kidney function KW - prognosis KW - stroke Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-287271 VL - 29 IS - 9 SP - 2716 EP - 2724 ER - TY - JOUR A1 - Lippert, Juliane A1 - Fassnacht, Martin A1 - Ronchi, Cristina L. T1 - The role of molecular profiling in adrenocortical carcinoma JF - Clinical Endocrinology N2 - Adrenocortical carcinoma (ACC) is a rare, aggressive cancer with still partially unknown pathogenesis, heterogenous clinical behaviour and no effective treatment for advanced stages. Therefore, there is an urgent clinical unmet need for better prognostication strategies, innovative therapies and significant improvement of the management of the individual patients. In this review, we summarize available studies on molecular prognostic markers and markers predictive of response to standard therapies as well as newly proposed drug targets in sporadic ACC. We include in vitro studies and available clinical trials, focusing on alterations at the DNA, RNA and epigenetic levels. We also discuss the potential of biomarkers to be implemented in a clinical routine workflow for improved ACC patient care. KW - adrenocortical cancer KW - biomarkers KW - precision medicine KW - prognosis KW - targeted treatment Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-258382 VL - 97 IS - 4 ER - TY - JOUR A1 - Schmidbauer, Moritz L. A1 - Ferse, Caroline A1 - Salih, Farid A1 - Klingner, Carsten A1 - Musleh, Rita A1 - Kunst, Stefan A1 - Wittstock, Matthias A1 - Neumann, Bernhard A1 - Schebesch, Karl-Michael A1 - Bösel, Julian A1 - Godau, Jana A1 - Lochner, Piergiorgio A1 - Adam, Elisabeth H. A1 - Jahnke, Kolja A1 - Knier, Benjamin A1 - Schirotzek, Ingo A1 - Müllges, Wolfgang A1 - Notz, Quirin A1 - Dengl, Markus A1 - Güldner, Andreas A1 - Onur, Oezguer A. A1 - Garcia Borrega, Jorge A1 - Dimitriadis, Konstantinos A1 - Günther, Albrecht T1 - COVID-19 and intracranial hemorrhage: a multicenter case series, systematic review and pooled analysis JF - Journal of Clinical Medicine N2 - Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) profoundly impacts hemostasis and microvasculature. In the light of the dilemma between thromboembolic and hemorrhagic complications, in the present paper, we systematically investigate the prevalence, mortality, radiological subtypes, and clinical characteristics of intracranial hemorrhage (ICH) in coronavirus disease (COVID-19) patients. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we performed a systematic review of the literature by screening the PubMed database and included patients diagnosed with COVID-19 and concomitant ICH. We performed a pooled analysis, including a prospectively collected cohort of critically ill COVID-19 patients with ICH, as part of the PANDEMIC registry (Pooled Analysis of Neurologic Disorders Manifesting in Intensive Care of COVID-19). Results: Our literature review revealed a total of 217 citations. After the selection process, 79 studies and a total of 477 patients were included. The median age was 58.8 years. A total of 23.3% of patients experienced the critical stage of COVID-19, 62.7% of patients were on anticoagulation and 27.5% of the patients received ECMO. The prevalence of ICH was at 0.85% and the mortality at 52.18%, respectively. Conclusion: ICH in COVID-19 patients is rare, but it has a very poor prognosis. Different subtypes of ICH seen in COVID-19, support the assumption of heterogeneous and multifaceted pathomechanisms contributing to ICH in COVID-19. Further clinical and pathophysiological investigations are warranted to resolve the conflict between thromboembolic and hemorrhagic complications in the future. KW - COVID-19 KW - intracranial hemorrhage KW - prognosis KW - anticoagulation Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-255236 SN - 2077-0383 VL - 11 IS - 3 ER -