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Objective This study aimed to provide an overview of the extent to which women with endometriosis are informed about, interested in, and make use of CAM, and to evaluate which of the methods are most often applied. Study Design A retrospective, two-center cohort study was conducted using a validated questionnaire among women with laparoscopically confirmed endometriosis at two urban teaching hospitals, certified as endometriosis centres. Results A total of 592 patients were included in the study and received the questionnaire; 114 (19.3 %) were included in the data analysis. Most of the women were not receiving hormone therapy at the time of the study (n = 60, 52.6 %). Most (n = 75, 65.8 %) were interested in CAM, but only a minority (n = 12, 10.5 %) had detailed knowledge about it. A total of 81 patients (71.1 %) had used at least one CAM method for disease management; the five most frequently used CAM methods were exercise (n = 55, 48.2 %), vitamins (n = 40, 35.1 %), yoga (n = 38, 33.3 %), homeopathy (n = 32, 28.1 %), and trace elements (n = 27, 23.7 %). Conclusions In our study population, women with endometriosis are strongly interested in using CAM, but have only limited information about it. Nevertheless, a majority of the patients had used at least one CAM method to relieve symptoms associated with the disease and the most often used was exercise.

Background More and more information about complementary and integrative medicine is becoming available, especially among cancer patients. However, little is known about the use of herbal medicine by patients with gynecologic cancers. This study aimed to assess the use of herbal products by gynecologic cancer patients compared with healthy controls. Methods This cross-sectional study was conducted at the Department for Gynecology and Obstetrics of Erlangen University Hospital and included 201 patients with gynecologic cancer and 212 healthy controls. Use of herbal medicines was evaluated using a standardized questionnaire. Medical information on cancer patients was collected from hospital records. Group comparisons were done using a logistic regression model. Risk ratios were assessed using a Poisson regression model. Results Gynecologic cancer patients used herbal medicine significantly less often than healthy persons. 69% of gynecologic cancer patients and 81% of healthy participants reported using herbal products. 40% of cancer patients and 56% of healthy persons reported using plants for medicinal purposes. Motives of cancer patients for using herbal medicine included treatment of cancer-related symptoms. The major source of information for both groups was family and friends. Conclusions Although herbal medicine was used less by patients with gynecologic cancer, herbal products were used by both cancer patients and healthy individuals. To provide cancer patients with optimal therapy, oncologists should be informed about the herbal products used by their patients as this will allow them to take their patientsʼ self-medication with herbal medicine into account. Counseling by oncologists on the use of herbal medicine should be encouraged.

Aims The aim of this official guideline published and coordinated by the German Society of Gynaecology and Obstetrics (DGGG) in cooperation with the Austrian Society for Gynaecology and Obstetrics (OEGGG) and the Swiss Society for Gynaecology and Obstetrics (SGGG) was to provide consensus-based recommendations for the diagnosis and treatment of endometriosis based on an evaluation of the relevant literature. Methods This S2k guideline represents the structured consensus of a representative panel of experts with different professional backgrounds commissioned by the Guideline Committee of the DGGG, OEGGG and SGGG. Recommendations Recommendations on the epidemiology, aetiology, classification, symptomatology, diagnosis and treatment of endometriosis are given and special situations are discussed.

Background/Aims: Macromastia can cause physical and psychological problems. Conservative treatments such as physiotherapy and painkillers lead to substantial long-term costs, without any proven medical benefit. In contrast, surgical treatment with reduction mammoplasty leads to improvements in nearly all respects. This study analyzed the costs of reduction mammoplasty and calculated an incremental cost-utility ratio for the treatment. Patients and Methods: The data on 76 patients who underwent reduction mammoplasty between 2008 and 2016 were collected using a two-part questionnaire (preoperative and postoperative) as well as the patients’ files. Topics examined besides demographic data included physician visits, medical imaging, integrative medical procedures, remedial procedures, rehabilitation and convalescent measures, drug intake, medical aids, exercise activity, and sick leave days before and after surgery. The data were used to calculate costs per year after surgical treatment for symptomatic macromastia. Costs of surgery, including the process of obtaining insurance reimbursement and postoperative complications, were taken into account to calculate the one-time costs of reduction mammoplasty. Results: The patients’ quality of life and satisfaction with the breasts improve after surgery. The one-time costs of reduction mammoplasty per patient amount to EUR 5,885, and the annual costs after surgery are EUR 200. The incremental cost-utility ratio for surgical treatments shows a saving of EUR 380 per quality-adjusted life-year (QALY) gained. Conclusions: These results show that reduction mammoplasty is a treatment that not only improves a patient’s quality of life but also saves money in the longer term in comparison with expensive and ineffective conservative treatment for macromastia.

Nahrungserganzungsmittel gewinnen immer mehr an Beliebtheit. Sowohl Patienten als auch gesunde Personen nehmen diese ein, um unter anderem eine Verbesserung der Lebensqualitat zu erreichen. Ob dies wirklich sinnhaftig ist, wird im Beitrag genauer untersucht. Ebenso wird eine genaue Ubersicht uber die Vitamine und die wichtigsten Spurenelemente gegeben. Mikronahrstoffe liefern dem Korper zwar keine Energie, mussen aber dennoch zugefuhrt werden. Am sinnvollsten ist es, alle notwendigen Vitamine und Spurenelemente uber die Nahrung aufzunehmen. Fur gesunde Personen mit einer ausgewogenen Ernahrung ist keine Supplementierung von Mikronahrstoffen notig. Allerdings ist bei Mangelzustanden, bei onkologischen Patienten, eine externe Zufuhr notwendig. Bei Krebspatienten sollte beispielsweise eine ausreichende Zufuhr an Vitamin C und D sichergestellt werden, falls notig auch uber Nahrungserganzungsmittel. Die aktuelle Datenlage zeigt, dass eine ubermasige Zufuhr aber teilweise sogar ins Gegenteil umschlagen kann. So wurde beispielsweise gezeigt, dass eine ubermasige Zufuhr von Vitamin B12 das Risiko fur ein Bronchialkarzinom erhohen kann. Ebenfalls kann aktuell aus onkologischer Sicht keine Empfehlung zur Supplementierung von Selen gegeben werden. Ein genauer Uberblick uber die aktuelle Datenlage wird im Artikel gegeben.

Purpose Second opinions in oncology are becoming increasingly important in an era of more complex treatments and a growing demand for information by patients. Therefore, we analyzed their effects and influencing factors like patients’ motives, subjective extent of information and satisfaction with communications. Methods This prospective study evaluated second opinions for patients with breast cancer or gynecological malignancy. The patients received a questionnaire before and two months after, which inquired expectations, reasons, and satisfaction with the second opinion and the attending physicians. Results A total of 164 patients were included and the majority had breast cancer (75.0%). Receiving the second opinion made 89.7% feel better informed, their need for information decreased (from 75.3% to 39.2%, P P = 0.0002). There were various reasons for requesting a second opinion, e.g., the extremely stressful situation of a cancer diagnosis, hope for change in the treatment recommendation or dissatisfaction with the initial physicians. Conclusions Second opinions can lead to significantly greater patient satisfaction, meeting the need for information and leading to better management of patients in the extremely stressful situation of a cancer diagnosis. Doctor–patient communications play a key role.

Oncological second opinions are becoming increasingly important given more complex treatment strategies, simultaneously more patients use complementary and alternative medicine (CAM), and many comprehensive cancer centers initiate integrative medicine programs. The present study focuses on analyzing the effects of a second opinion in relation to attitudes toward CAM.In this prospective study patients (n = 97) with a diagnosis of breast cancer or gynecological malignancies who had requested a second opinion received a questionnaire before and after the second opinion concerning their attitudes toward CAM.The majority of patients had breast cancer (72.2%, n = 70). Only 6.2% (n = 6) stated that they had been informed about CAM by the doctors who treated them first, 21.6% (n = 21) had received information about it when seeking the second opinion. After the first opinion, 42.3% (n = 41) wanted to try CAM, the same proportion trusted orthodox medicine alone. After the second opinion, 24 patients (24.7%) wanted to try CAM, while 38.1% (n = 37) relied exclusively on orthodox medicine. There was a significant correlation between an increased patients' need for information and interest in CAM (p = 0.02).Today, aspects of CAM still are very often no part of oncological first and second opinions. This might hence lead to discouraging patients to try out CAM and therefore integrative medicine programs in comprehensive cancer centers might be problem-solving.Hintergrund und Ziele: Im Zeitalter der komplexeren Krebstherapien gewinnt zum einen die onkologische Zweitmeinung zunehmend an Bedeutung, zum anderen nutzen immer mehr Patientinnen komplementäre und alternativmedizinische Verfahren und in vielen zertifizierten Onkologischen Zentren entstehen Sprechstunden für Komplementär- und Alternativmedizin. Eine Ana­lyse der Effekte einer onkologischen Zweitmeinung in Bezug auf die Einstellung zur Komplementär- und Alternativmedizin war somit Fokus der vorliegenden Studie. Patientinnen und Methoden: In der prospektiven Untersuchung wurden onkologische Zweitmeinungen evalu­iert. Patientinnen (n = 97) mit der Diagnose eines Mammakarzinoms oder eines gynäkologischen Malignoms erhielten vor und zwei Monate nach der onkologischen Zweitmeinung einen Fragebogen zu ihrer Einstellung zur Komplementär- und Alternativmedizin. Ergebnisse und Beobachtungen: Die Mehrheit der Patientinnen wies ein Mammakarzinom auf (72,2%, n = 70). Nur 6,2% (n = 6) der Patientinnen gaben an von den erstbehandelnden Ärzten bzw. 21,6 % (n = 21) im Rahmen der Zweitmeinung zur Komplementär- und Alternativmedizin informiert worden zu sein. Nach der Erstmeinung wollten 42,3% (n = 41) Komplementär- und Alternativmedizin ausprobieren und genau der gleiche Anteil vertraute nur auf Schulmedizin (42,3%, n = 41). Nach der Zweitmeinung wollten 24 Patientinnen (24,7%) Komplementär- und Alternativme­dizin ausprobieren, und 38,1% (n = 37) vertrauten aus­schließlich auf Schulmedizin. Es zeigte sich eine signifikante Korrelation zwischen einem erhöhten Informations-bedürfnis der Patientinnen und dem Interesse an Komplementär- und Alternativmedizin (p = 0,02). Schlussfolgerung: Im Rahmen der onkologischen Erst- oder Zweitmeinung wird auch heute noch in vielen Fällen nicht auf Aspekte der Komplementär- und Alternativmedizin ein­gegangen, was dazu führen kann, dass Patientinnen von der Komplementär- und Alternativmedizin Abstand neh­men. Der Aufbau von Sprechstunden für Komplementär- und Alternativmedizin in zertifizierten Onkologischen Zentren könnte hier hilfreich sein.

Objective: The current study seeks to illustrate potential early and objective neurophysiological biomarkers of neurodegenerative cognitive decline by evaluating features of brain network physiological performance and structure utilizing different modalities.Methods: This study included 17 clinically healthy individuals with self-reported cognitive decline (Subjective Cognitive Decline group, SCD, no objective finding of cognitive decline), 12 individuals diagnosed with amnestic Mild Cognitive Impairment (aMCI), 11 individuals diagnosed with Dementia, and 15 healthy subjects. All subjects underwent computerized cognitive performance testing, MRI scans including T1 for gray matter (GM) volume quantification, DTI for quantification of white matter (WM) microstructure fractional anisotropy (FA) and mean diffusivity (MD), and brain network function evaluation using DELPHI (TMS-EEG) measures of connectivity, excitability, and plasticity.Results: Both DELPHI analysis of network function and DTI analysis detected a significant decrease in connectivity, excitability, and WM integrity in the SCD group compared to healthy control (HC) subjects; a significant decrease was also noted for aMCI and Dementia groups compared to HC. In contrast, no significant decrease was observed in GM volume in the SCD group compared to healthy norms, a significant GM volume decrease was observed only in objectively cognitively impaired aMCI subjects and in dementia subjects.Conclusions: This study results suggest that objective direct measures of brain network physiology and WM integrity may provide early-stage biomarkers of neurodegenerative-related changes in subjects that have not yet displayed any other objective measurable cognitive or GM volume deficits which may facilitate early preventive care for neurodegenerative decline and dementia.

Zusammenfassung Hintergrund Während einer Krebstherapie leiden viele Patienten an Mangelernährung oder Vitaminmangel. Die Behandlung nährstoffbezogener Mangelzustände sollte daher eine Ernährungstherapie und gegebenenfalls auch eine orale oder intravenöse Substitution von Mikronährstoffen beinhalten. Über Infusionstherapien mit mehreren Nährstoffen liegen nur wenige Informationen vor. Das Ziel dieser Studie bestand in der Entwicklung standardisierter Infusionsprotokolle für die Infusion von Mikronährstoffen im Rahmen der integrativen Medizin (IMed-Infusionen) und der Beschreibung von Nebenwirkungen der Behandlung und der Therapiezufriedenheit der Patientinnen. Methoden Für die IMed-Sprechstunde wurden in Zusammenarbeit mit der Apotheke des Universitätsklinikums Erlangen 4 spezielle Formulierungen für die intravenöse Anwendung entwickelt. Zwischen Oktober 2015 und Januar 2018 wurde eine retrospektive Querschnittsstudie durchgeführt, in der 45 Patientinnen mit gynäkologischen Krebserkrankungen oder Brustkrebs (BK) unter IMed-Infusionstherapie aufgenommen wurden. Von 20 Patientinnen wurden mithilfe eines standardisierten Fragebogens zu IMed-Infusionen Nachbeobachtungsdaten erhoben. Ergebnisse Während des Studienzeitraums wurden insgesamt 280 IMed-Infusionen verabreicht. Die meisten Patientinnen haben IMed-Regenerationsinfusionen erhalten (78 %). Die Patientinnen litten in der Mehrzahl der Fälle an BK und wurden mit Chemotherapie behandelt. Die meisten Patientinnen gaben ein hohes oder sehr hohes Maß an Zufriedenheit mit der Organisation (60 %), der allgemeinen Behandlung (65 %) und der Beratung (85 %) an. Über eine subjektive Besserung von krankheits- oder therapiebedingten Symptomen wie Fatigue, Polyneuropathie und Einschränkung der körperlichen Leistungsfähigkeit berichteten 70 % der Patientinnen, während 75 % eine subjektive Steigerung ihrer Lebensqualität angaben. Nebenwirkungen traten nur selten auf und waren leichter Natur. Schlussfolgerungen Die Therapie mit IMed-Infusionen bei Frauen mit BK oder gynäkologischen Krebserkrankungen muss denselben Standards genügen wie Arzneimitteltherapien. Obwohl es sich bei Vitaminen um Nahrungsergänzungsmittel handelt, sind eine gründliche Erhebung der Anamnese sowie eine angemessene Aufklärung der Patientinnen unerlässlich. Hierfür haben sich standardisierte Vorgehensweisen, wie im Rahmen der IMed-Sprechstunde der Fall, als hilfreich erwiesen.

One of the most common adverse events (AEs) occurring during treatment with aromatase inhibitors (AIs) is musculoskeletal pain. The aim of our study was to analyze the influence of preexisting muscle/limb pain and joint pain on the development of AI-induced musculoskeletal AEs. Women eligible for upfront adjuvant endocrine therapy with letrozole were included in the PreFace study, a multicenter phase IV trial. During the first treatment year, they were asked to record musculoskeletal AEs monthly by answering questions regarding pain symptoms and rating the pain intensity on a numeric rating scale from 0 (no pain) to 10 (very strong pain). Pain values were compared using nonparametric statistical tests. Overall, 1,416 patients were evaluable. The average pain value over all time points in women with preexisting muscle/limb pain was 4.3 (median 4.3); in those without preexisting pain, it was 2.0 (median 1.7). In patients without preexisting muscle/limb pain, pain levels increased relatively strongly within the first 6 months (mean increase +0.9, p < 0.00001) in comparison with those with preexisting pain (mean increase +0.3, p < 0.001), resulting in a statistically significant difference (p < 0.00001) between the two groups. The development of joint pain was similar in the two groups. Women without preexisting muscle/limb pain or joint pain have the greatest increase in pain after the start of adjuvant AI therapy. Women with preexisting pain have significantly higher pain values. The main increase in pain values takes place during the first 6 months of treatment.

Background: The usefulness of clinical breast examination (CBE) in general and in breast cancer screening programs has been a matter of debate. This study investigated whether adding vision-impaired medical tactile examiners (MTEs) improves the predictiveness of CBE for suspicious lesions and analyzed the feasibility and acceptability of this approach. Methods: The prospective study included 104 patients. Physicians and MTEs performed CBEs, and mammography and ultrasound results were used as the gold standard. Sensitivity and specificity were calculated and logistic regression models were used to compare the predictive value of CBE by physicians alone, MTEs alone, and physicians and MTEs combined. Results: For CBEs by physicians alone, MTEs alone, and both combined, sensitivity was 71, 82, and 89% and specificity was 55, 45, and 35%, respectively. Using adjusted logistic regression models, the validated areas under the curve were 0.685, 0.692, and 0.710 (median bootstrapped p value (DeLong) = 0.381). Conclusion: The predictive value for a suspicious breast lesion in CBEs performed by MTEs in patients without prior surgery was similar to that of physician-conducted CBEs. Including MTEs in the CBE procedure in breast units thus appears feasible and could be a way of utilizing their skills.

This study is a retrospective chart review of 200 clients who participated in a non-verbal restorative cognitive remediation training (rCRT) program between 2012 and 2020. Each client participated in the program for about 16 weeks, and the study as a whole occurred over a five-year period. The program was applied to effect proper neural functional remodeling needed to support resilient, flexible, and adaptable behaviors after encountering a mild closed head traumatic brain injury (mTBI). The rCRT program focused on improving functional performance in executive cognitive control networks as defined by fMRI studies. All rCRT activities were delivered in a semi-game-like manner, incorporating a brain-computer interface (BCI) that provided in-the-moment neural network performance integrity metrics (nPIMs) used to adjust the level of play required to properly engage long-term potentiation (LTP) and long-term depression (LTD) network learning rules. This study reports on t-test and Reliable Change Index (RCI) changes found within individual cognitive abilities’ performance metrics derived from the Woodcock-Johnson Cognitive Abilities III Test. We compared pre- and post-scores from seven cognitive abilities considered dependent on executive cognitive control networks against seven non-executive control abilities. We observed significant improvements (p < 10-4) with large Cohen’s deffect sizes (0.78-1.20) across 13 of 14 cognitive ability domains with a medium effect size (0.49) on the remaining one. The mean percent change for the pooled trained domain was double that observed for the pooled untrained domain, at 17.2% versus 8.3%, respectively. To further adjust for practice effects, practice effect RCI values were computed and further supported the effectiveness of the rCRT (trained RCI 1.4-4.8; untrained RCI 0.­08-0.75).

Purpose Mammographic density (MD) is one of the strongest risk factors for breast cancer (BC). However, the influence of MD on the BC prognosis is unclear. The objective of this study was therefore to investigate whether percentage MD (PMD) is associated with a difference in disease-free or overall survival in primary BC patients. Methods A total of 2525 patients with primary, metastasis-free BC were followed up retrospectively for this analysis. For all patients, PMD was evaluated by two readers using a semi-automated method. The association between PMD and prognosis was evaluated using Cox regression models with disease-free survival (DFS) and overall survival (OS) as the outcome, and the following adjustments: age at diagnosis, year of diagnosis, body mass index, tumor stage, grading, lymph node status, hormone receptor and HER2 status. Results After median observation periods of 9.5 and 10.0 years, no influence of PMD on DFS (p = 0.46, likelihood ratio test (LRT)) or OS (p = 0.22, LRT), respectively, was found. In the initial unadjusted analysis higher PMD was associated with longer DFS and OS. The effect of PMD on DFS and OS disappeared after adjustment for age and was caused by the underlying age effect. Conclusions Although MD is one of the strongest independent risk factors for BC, in our collective PMD is not associated with disease-free and overall survival in patients with BC., Highlights • Mammographic density (MD) is one of the strongest risk factors for breast cancer (BC). • Results from a large BC cohort on the impact of percentage MD (PMD) on prognosis. • No association between PMD with disease-free and overall survival was found. • Risk stratification based on PMD seems not feasible for clinical routine.

Purpose Symptomatic macromastia causes physical and psychological problems that can lead to restrictions in the patients’ social and working lives and a reduced quality of life. Associated medical treatments also have a considerable impact on health-care costs. Several studies have assessed these costs, but the total disease costs of macromastia have never been evaluated on the basis of real-world data. Methods The data for 76 patients who underwent reduction mammoplasty between 2008 and 2016 were collected using a two-part questionnaire (preoperative and postoperative), as well as the patient files. Topics surveyed, besides demographic data, included physician visits, medical imaging, medical procedures, medical treatments, rehabilitation and convalescent measures, drug intake, medical aids, exercise activity, and sick leave days before surgery, to calculate the costs per year of conservative treatment of symptomatic macromastia. Results The mean time from start of symptoms to surgery was 11.82 years. The data for this group of patients with symptomatic macromastia show that costs per patient amount to €1677.55 per year. These costs include medical consultation, radiological imaging, medical treatments and procedures, physical therapy and rehabilitation, medication, special brassieres, exercise classes costs for sick leave due to problems with macromastia, and travel expenses. Conclusions These results show that considerable health-care costs arise due to macromastia with conservative treatment. Overall, macromastia costs €1677.55 per patient/year. In particular, lost productivity due to sick days and the costs of physiotherapy are factors driving the high costs.

Purpose Despite patients’ widespread use and acceptance of complementary and integrative medicine (IM), few data are available regarding health-care professionals’ current implementation of it in clinical routine. A national survey was conducted to assess gynecologists’ attitudes to and implementation of complementary and integrative treatment approaches. Methods The Working Group on Integrative Medicine of the German Society of Gynecological Oncology conducted an online survey in collaboration with the German Society of Gynecology and Obstetrics (DGGG) in July 2019. A 29-item survey was sent to all DGGG members by email. Results Questionnaires from 180 gynecologists were analyzed, of whom 61 were working office-based in private practice and 95 were employed in hospitals. Seventy percent stated that IM concepts are implemented in their routine clinical work. Most physicians reported using IM methods in gynecological oncology. The main indications for IM therapies were fatigue (n = 98), nausea and vomiting (n = 89), climacteric symptoms (n = 87), and sleep disturbances (n = 86). The most commonly recommended methods were exercise therapy (n = 86), mistletoe therapy (n = 78), and phytotherapy (n = 74). Gynecologists offering IM were more often female (P = 0.001), more often had qualifications in anthroposophic medicine (P = 0.005) or naturopathy (P = 0.019), and were more often based in large cities (P = 0.016). Conclusions There is strong interest in IM among gynecologists. The availability of evidence-based training in IM is increasing. Integrative therapy approaches are being implemented in clinical routine more and more, and integrative counseling services are present all over Germany. Efforts should focus on extending evidence-based knowledge of IM in both gynecology and gynecological oncology.

ObjectiveThe aim of this study was to evaluate brain white matter (WM) fibers connectivity damage in stroke and traumatic brain injury (TBI) subjects by direct electrophysiological imaging (DELPHI) that analyzes transcranial magnetic stimulation (TMS)-evoked potentials (TEPs).MethodsThe study included 123 participants, out of which 53 subjects with WM-related pathologies (39 stroke, 14 TBI) and 70 healthy age-related controls. All subjects underwent DELPHI brain network evaluations of TMS-electroencephalogram (EEG)-evoked potentials and diffusion tensor imaging (DTI) scans for quantification of WM microstructure fractional anisotropy (FA).ResultsDELPHI output measures show a significant difference between the healthy and stroke/TBI groups. A multidimensional approach was able to classify healthy from unhealthy with a balanced accuracy of 0.81 ± 0.02 and area under the curve (AUC) of 0.88 ± 0.01. Moreover, a multivariant regression model of DELPHI output measures achieved prediction of WM microstructure changes measured by FA with the highest correlations observed for fibers proximal to the stimulation area, such as frontal corpus callosum (r = 0.7 ± 0.02), anterior internal capsule (r = 0.7 ± 0.02), and fronto-occipital fasciculus (r = 0.65 ± 0.03).ConclusionThese results indicate that features of TMS-evoked response are correlated to WM microstructure changes observed in pathological conditions, such as stroke and TBI, and that a multidimensional approach combining these features in supervised learning methods serves as a strong indicator for abnormalities and changes in WM integrity.

Background: Risk factors for ipsilateral breast cancer tumor recurrence (IBTR) are well established and include grading, nodal status, and receptor status. Little is known about the influence of the local distance between the primary tumor and recurrences on changes in tumor characteristics and prognosis. Methods: In a retrospective setting, we analyzed primary breast cancers and their recurrences. Localizations of primary and recurrent breast cancer were recorded to calculate the relative distance in pixels. Analysis was performed regarding tumor characteristics, relative distance between both, and their impact on breast cancer prognosis. Results: In a cohort of 142 patients with ipsilateral recurrence, no statistically significant difference could be shown in the change in tumor characteristics depending on distance. Progesterone receptor (PR) and estrogene receptor (ER) status changed in 22.7% and 14.9% of cases, respectively. human epidermal growth factor receptor 2 (ERBB2, HER2) status changed in 18.3% of cases. Survival was in accordance with the literature, with luminal-A-like tumors as best and triple negative breast cancers (TNBC) as worst prognosis. With a threshold of 162 pixels, the survival was significantly better in the group with shorter distance. Conclusion: Change in tumor characteristics from primary breast cancer to recurrence occurs more often in PR than ER. In contrast to other work, in this dataset, recurrences with a larger distance to the primary tumor had a worse prognosis in univariate analysis. A Cox model might indicate the possibility that this influence is independent of other risk factors.

Purpose This is an official guideline, published and coordinated by the Gynecological Oncology Working Group (AGO) of the German Cancer Society (DKG) and the German Society for Gynecology and Obstetrics (DGGG). Vaginal cancers are rare tumors, which is why there is very little evidence on these tumors. Knowledge about the optimal clinical management is limited. This first German S2k guideline on vaginal cancer has aimed to compile the most current expert knowledge and offer new recommendations on the appropriate treatment as well as providing pointers about individually adapted therapies with lower morbidity rates than were previously generally available. The purpose of this guideline is also to set up a register to record data on treatment data and the course of disease as a means of obtaining evidence in future. Methods The present S2k guideline was developed by members of the Vulvar und Vaginal Tumors Commission of the AGO in an independently moderated, structured, formal consensus process and the contents were agreed with the mandate holders of the participating scientific societies and organizations. Recommendations To optimize the daily care of patients with vaginal cancer: 1. Monitor the spread pattern; 2. Follow the step-by-step diagnostic workup based on initial stage at detection; 3. As part of individualized clinical therapeutic management of vaginal cancer, follow the sentinel lymph node protocol described here, where possible; 4. Participate in the register study on vaginal cancer.

Delayed identification of coagulopathy and bleeding increases the risk of organ failure and death in hospitalized patients. Timely and accurate identification of impaired coagulation at the point-of-care can proactively identify bleeding risk and guide resuscitation, resulting in improved outcomes for patients. We test the accuracy of a novel optical coagulation sensing approach, termed iCoagLab, for comprehensive whole blood coagulation profiling and investigate its diagnostic accuracy in identifying patients at elevated bleeding risk. Whole blood samples from patients (N = 270) undergoing conventional coagulation testing were measured using the iCoagLab device. Recalcified and kaolin-activated blood samples were loaded in disposable cartridges and time-varying intensity fluctuation of laser speckle patterns were measured to quantify the clot viscoelastic modulus during coagulation. Coagulation parameters including the reaction time (R), clot progression time (K), clot progression rate (α), and maximum clot strength (MA) were derived from clot viscoelasticity traces and compared with mechanical thromboelastography (TEG). In all patients, a good correlation between iCoagLab- and TEG-derived parameters was observed (p

We describe a method for quantifying the contractile forces that tumor spheroids collectively exert on highly nonlinear three-dimensional collagen networks. While three-dimensional traction force microscopy for single cells in a nonlinear matrix is computationally complex due to the variable cell shape, here we exploit the spherical symmetry of tumor spheroids to derive a scale-invariant relationship between spheroid contractility and the surrounding matrix deformations. This relationship allows us to directly translate the magnitude of matrix deformations to the total contractility of arbitrarily sized spheroids. We show that our method is accurate up to strains of 50% and remains valid even for irregularly shaped tissue samples when considering only the deformations in the far field. Finally, we demonstrate that collective forces of tumor spheroids reflect the contractility of individual cells for up to 1 hr after seeding, while collective forces on longer timescales are guided by mechanical feedback from the extracellular matrix.

We describe a method for quantifying the contractile forces that tumor spheroids collectively exert on highly nonlinear three-dimensional collagen networks. While three-dimensional traction force microscopy for single cells in a nonlinear matrix is computationally complex due to the variable cell shape, here we exploit the spherical symmetry of tumor spheroids to derive a scale-invariant relationship between spheroid contractility and the surrounding matrix deformations. This relationship allows us to directly translate the magnitude of matrix deformations to the total contractility of arbitrarily sized spheroids. We show that our method is accurate up to strains of 50% and remains valid even for irregularly shaped tissue samples when considering only the deformations in the far field. Finally, we demonstrate that collective forces of tumor spheroids reflect the contractility of individual cells for up to 1 hr after seeding, while collective forces on longer timescales are guided by mechanical feedback from the extracellular matrix.

Introduction: Oncological second opinions are becoming increasingly important in the era of complex treatments and established certified cancer centers. Oncological guidelines with the highest levels of evidence are available, but these can only be effective to the extent that they are implemented. Therefore, we analyzed the effects of second opinions with regard to their agreement with first opinions and conformity with guidelines. Methods: In 164 patients with a diagnosis of breast cancer or gynecological malignancy who requested a second opinion, the first and second opinions, established at the interdisciplinary tumor conference, and conformity with the guidelines were evaluated. Results: The first opinion was not in agreement with the guidelines in 34.8% (15.2% diagnosis, 12.8% surgical therapy, 13.4% systemic therapy, and 5.5% radiotherapy), and the recommendations were optimized in the second opinion in 56.7% (28.7% diagnosis, 15.9% surgical therapy, 30.5% systemic therapy, and 8.5% radiotherapy). Conclusions: Oncological second opinions showed significant effects and one-third of first opinions were not in conformity with the guidelines. In a significant proportion of cases, the existing treatment plan was changed or supplemented to allow modern and individualized treatment approaches.

Context.— Paget disease of the breast, in most cases, represents intraepidermal spread of ductal carcinoma in situ. Molecular subtypes of invasive carcinoma of the breast have prognostic and therapeutic significance and show characteristic distribution. Little is known about the distribution of molecular subtypes in Paget disease of the breast. Objectives.— To examine the distribution of molecular subtypes in Paget disease of the breast and to compare them to concurrent invasive carcinoma of the breast, if present. Design.— We examined 48 cases of Paget disease of the breast with immunohistochemistry and antibodies against estrogen and progesterone receptors, human epidermal growth factor receptor 2 (HER2), and Ki-67, as well as HER2 chromogenic in situ hybridization, to classify the cases into molecular subtypes. Then, we compared the results to the molecular subtypes of associated invasive carcinoma of the breast, if present. Results.— The HER2 subtype was the most common found in Paget disease of the breast, followed by the luminal B subtype and 2 cases of the triple-negative subtype. The associated invasive carcinoma cases were most often of the luminal B subtype, followed by the HER2 subtype and the triple-negative subtype. The molecular subtype of Paget disease and invasive carcinoma was congruent in most of the cases. Conclusions.— Molecular subtypes of invasive carcinoma of the breast can already be detected in Paget disease. The distribution of molecular subtypes of Paget disease and of Paget disease–associated invasive carcinoma differs from invasive carcinoma without associated Paget disease, with the HER2 subtype overrepresented in Paget disease and associated invasive carcinoma and the luminal and triple-negative subtypes underrepresented.

Background In women with early breast cancer, a pathological complete response (pCR) after neoadjuvant chemotherapy is reported to be associated with an improvement of the survival. The aim of this survey among physicians was to investigate whether the probability of achieving pCR in patients with a hormone receptor-positive, HER2-negative disease encourages physicians to recommend neoadjuvant chemotherapy. Methods The study was conducted via an online survey that was sent to 493 physicians, who were either known as members of national guideline committees, heads of breast cancer centers, being high recruiters in clinical trials or leading a private practice. Participants were asked about a specific case that should resemble patients for whom it is unclear, whether they should be treated with chemotherapy. Results 113 (24.5%) physicians participated at the survey, out of which 96.5% had a work experience of more than 10 years and 94.7% were board certified in their specialty. A total of 84.1% would consider pCR for a decision concerning neoadjuvant chemotherapy. With regard to the pCR probability, 2.7 and 10.6% of the participants demanded at least a pCR rate of 5 and 10%, respectively, while 25.7% were satisfied with 20% probability, and another 25.7% with a pCR rate of 30%. Conclusions The vast majority of the long-term experienced physicians would embrace the implementation of a further method such as the prediction of pCR probability in clinical routine to support decision making regarding the necessity of neoadjuvant chemotherapy. The cut-off of around 30% pCR probability seems to be a realizable rate to distinguish patient groups.

Background Endocrine treatment (ET) with an aromatase inhibitor (AI) is the treatment of choice in post-menopausal patients with hormone receptor–positive early breast cancer (EBC). However, adverse events (AEs) often lead to treatment discontinuation. This analysis aimed to identify side-effects that lead to patients failing to persist with letrozole treatment. Patients and methods Post-menopausal hormone receptor–positive EBC patients starting ET with letrozole were enroled in EvAluate-TM, a non-interventional study. Information regarding treatment compliance and persistence was gathered in months 6 and 12. Persistence was defined as the time from 30 d after the start to the end of treatment. The influence on persistence of musculoskeletal syndrome, menopausal disorder, sleep disorder and other AEs within the first 30 d was analysed using Cox regression analyses. Results Among 3887 patients analysed, the persistence rate after 12 months was >85%. In all, 568 patients (14.6%) discontinued the treatment, 358 of whom (63.0%) did so only because of side-effects. The main AEs influencing persistence were musculoskeletal symptoms (hazard ratio [HR] 2.55; 95% confidence interval [CI], 1.90–3.42), sleep disorders (HR 1.95; 95% CI, 1.41–2.70) and other AEs (HR 2.03; 95% CI, 1.51–2.73). Menopausal disorder was not associated with non-persistence (HR 1.17; 95% CI, 0.74–1.84). Conclusions These results suggest that side-effects of AIs such as musculoskeletal syndrome and sleep disorder lead to ET discontinuation within the first treatment year in significant numbers of EBC patients. Compliance programmes adapted for subgroups that are at risk for early non-persistence might help to ensure the recommended therapy duration. Clinical Trials Number CFEM345DDE19.

Complementary medicine services are nowadays usually quite heterogeneous, and little information is available on standards for running an integrative medicine consultancy service. This study aimed to assess patients' satisfaction with a standardized treatment service on integrative medicine.Using a cross-sectional design, 75 breast cancer patients from the integrative medicine consultancy service at the University Breast Center for Franconia were evaluated between January 2016 and March 2017. At primary consultation, patients answered a standardized questionnaire on their medical history and treatment goals regarding integrative medicine. In a subsequent interview, patients evaluated their satisfaction with the treatment service and individual treatment goals.72% of the patients (n = 54) reported high satisfaction with the overall approach of the treatment service. 76% of the patients (n = 57) were very satisfied or satisfied with their individual treatment plans. The most frequently reported goals were to slow tumor progression (n = 64, 85.3%), reducing the side effects of conventional cancer treatments (n = 60, 80%), and a desire to participate actively in the treatment of breast cancer (n = 64, 85.3%).Using a standardized procedure in integrative medicine allows a high quality level to be offered to patients. Overall, breast cancer patients report very high satisfaction with the integrative medicine consultancy service and state long-term treatment goals. Hence, long-term treatment with integrative medicine methods should be taken into consideration.

The 2017 Berlin Concussion in Sport Group Consensus Statement provides a global summary of best practice in concussion prevention, diagnosis and management, underpinned by systematic reviews and expert consensus. Due to their different settings and rules, individual sports need to adapt concussion guidelines according to their specific regulatory environment. At the same time, consistent application of the Berlin Consensus Statement’s themes across sporting codes is likely to facilitate superior and uniform diagnosis and management, improve concussion education and highlight collaborative research opportunities. This document summarises the approaches discussed by medical representatives from the governing bodies of 10 different contact and collision sports in Dublin, Ireland in July 2017. Those sports are: American football, Australian football, basketball, cricket, equestrian sports, football/soccer, ice hockey, rugby league, rugby union and skiing. This document had been endorsed by 11 sport governing bodies/national federations at the time of being published.

Introduction The care of patients with breast cancer is extremely complex and requires interdisciplinary care in certified facilities. These specialized facilities provide numerous services without being correspondingly remunerated. The question whether breast cancer surgery should be performed in an outpatient setting to reduce costs is increasingly being debated. This study compares inpatient surgical treatment with a model of the same surgery performed on an outpatient basis to examine the potential financial impact. Material and Methods A theoretical model was developed and the DRG fees for surgical interventions to treat primary breast cancer were calculated. A theoretical 1-day DRG was then calculated to permit comparisons with outpatient procedures. The costs of outpatient surgery were calculated based on the remuneration rates of the AOP (Outpatient Surgery) Contract and the EBM (Uniform Assessment Scale) and compared to the costs of the 1-day DRG. Results The DRG fee for both breast-conserving surgery and mastectomy is higher than the fee paid in the context of the EBM system, although the same procedures were carried out in both systems. If a hospital were to carry out breast-conserving surgery as an outpatient procedure, the fee would be € 1313.81; depending on the type of surgery, the hospital would therefore only receive between 39.20% and 52.82% of the DRG fee. This was the case even for a 1-day treatment. Compared to the real DRG fees the difference would be even more striking. Conclusion Carrying out breast cancer surgery as an outpatient procedure would result in a significant shortfall of revenues. Additional services from certified centers, such as the interdisciplinary planning of treatment, psycho-oncological and social-medical care with the involvement of relatives, detailed documentation, etc., which are currently provided without surcharge or adequate remuneration, could no longer be maintained. The quality of processes and excellent results which have been achieved and ultimately the care given by certified facilities would be significantly at risk.

Purpose: The growing popularity and acceptance of integrative medicine is evident both among patients and among the oncologists treating them. As little data are available regarding health-care professionals’ knowledge, attitudes, and practices relating to the topic, a nationwide online survey was designed. Methods: Over a period of 11 weeks (from July 15 to September 30, 2014) a self-administered, 17-item online survey was sent to all 676 members of the Research Group on Gynecological Oncology (Arbeitsgemeinschaft Gynäkologische Onkologie) in the German Cancer Society. The questionnaire items addressed the use of integrative therapy methods, fields of indications for them, advice services provided, level of specific qualifications, and other topics. Results: Of the 104 respondents (15.4%) using integrative medicine, 93% reported that integrative therapy was offered to breast cancer patients. The second most frequent type of tumor in connection with which integrative therapy methods were recommended was ovarian cancer, at 80% of the participants using integrative medicine. Exercise, nutritional therapy, dietary supplements, herbal medicines, and acupuncture were the methods the patients were most commonly advised to use. Conclusion: There is considerable interest in integrative medicine among gynecological oncologists, but integrative therapy approaches are at present poorly implemented in routine clinical work. Furthermore there is a lack of specific training. Whether future efforts should focus on extending counseling services on integrative medicine approaches in gynecologic oncology or not, have to be discussed. Evidence-based training on integrative medicine should be implemented in order to safely guide patients in their wish to do something by themselves.

Background: GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic t...

Fibrosis is a condition shared by numerous inflammatory diseases. Our incomplete understanding of the molecular mechanisms underlying fibrosis has severely hampered effective drug development. CXCL4 is associated with the onset and extent of fibrosis development in systemic sclerosis, a prototypic inflammatory and fibrotic disease. Here, we integrated 65 paired longitudinal transcriptional and methylation profiles from monocyte-derived cells with/without CXCL4 exposure. Using data-driven gene regulatory network analyses, we demonstrate that CXCL4 dramatically alters the trajectory of monocyte differentiation, inducing a novel pro-inflammatory and pro-fibrotic phenotype mediated via key transcriptional regulators including CIITA. CXCL4 exposed monocyte-derived cells directly trigger a fibrotic cascade by producing ECM molecules and inducing myofibroblast differentiation. Inhibition of CIITA mimicked CXCL4 in inducing a pro-inflammatory and pro-fibrotic phenotype, validating the relevance of the gene regulatory network. Our study unveils CXCL4 as a key secreted factor driving innate immune training and forming the long-sought link between inflammation and fibrosis.

Die Anwendung von integrativer Medizin erfreut sich bei Anwendern und Arzten zunehmender Beliebtheit. Aktuell nutzen 38–60 % aller Krebspatienten in den westlichen Industrielandern komplementare und alternative Medizin (CAM) im Krankheitsverlauf zur Therapieunterstutzung. Beim Mammakarzinom sind es stadiumabhangig sogar bis zu 90 %. Definition, Historie, Zahlen und Fakten zur integrativen Medizin werden prasentiert und Systeme und Hauptmethoden dargestellt. Die aktuelle Literatur und Publikationen werden ausgewertet und Expertenforen analysiert. Die integrative Medizin ist als ein ganzheitliches Konzept zu verstehen, bei dem die wissenschaftliche evidenzbegrundete Medizin mit der komplementaren, zumeist erfahrungsbegrundeten Medizin vereint wird. Komplementare Methoden, deren Erkenntnisgewinne haufig durch Erfahrungen und andere Wissensgewinnmethoden begrundet sind, werden in Erganzung zur konventionellen Medizin eingesetzt. Sinnvolle und geeignete komplementare Methoden mussen unbedingt von den umstrittenen alternativen Methoden und Ausenseitermethoden abgegrenzt werden. Je nach Indikation und Behandlungskonzept konnen mit integrativer Medizin gute Erfolge erzielt werden. Wenn bestimmte Grenzen, insbesondere wenn es um die Sicherheit der Patientin geht, eingehalten werden, zweifelhafte Methoden kritisch hinterfragt werden und geeignete Methoden den ublichen medizinischen Regeln folgend angewandt werden, bieten sich im Rahmen der integrativen Medizin erganzende Moglichkeiten, den Genesungsprozess bzw. Gesundheitszustand der Patientinnen zu verbessern sowie den Menschen mit seiner Erkrankung ganzheitlich und individuell zu behandeln.

Although mammography screening programs do not include ultrasound examinations, some diagnostic units do provide women with both mammography and ultrasonography. This article is concerned with estimating the risk of a breast cancer patient diagnosed in a hospital-based mammography unit having a tumor that is visible on ultrasound but not on mammography. A total of 1,399 women with invasive breast cancer from a hospital-based diagnostic mammography unit were included in this retrospective study. For inclusion, mammograms from the time of the primary diagnosis had to be available for computer-assisted assessment of percentage mammographic density (PMD), as well as Breast Imaging Reporting and Data System (BIRADS) assessment of mammography. In addition, ultrasound findings were available for the complete cohort as part of routine diagnostic procedures, regardless of any patient or imaging characteristics. Logistic regression analyses were conducted to identify predictors of mammography failure, defined as BIRADS assessment 1 or 2. The probability that the visibility of a tumor might be masked at diagnosis was estimated using a regression model with the identified predictors. Tumors were only visible on ultrasound in 107 cases (7.6%). PMD was the strongest predictor for mammography failure, but age, body mass index and previous breast surgery also influenced the risk, independently of the PMD. Risk probabilities ranged from 1% for a defined low-risk group up to 40% for a high-risk group. These findings might help identify women who should be offered ultrasound examinations in addition to mammography.

Several clinical trials have investigated the prognostic and predictive usefulness of molecular markers. With limited predictive value, molecular markers have mainly been used to identify prognostic subgroups in which the indication for chemotherapy is doubtful and the prognosis is favorable enough for chemotherapy to be avoided. However, limited information is available about which groups of patients may benefit from additional therapy. This study aimed to describe the prognostic effects of Ki-67 in several common subgroups of patients with early breast cancer. This retrospective study analyzed a single-center cohort of 3140 patients with HER2−, hormone receptor-positive breast cancer. Five-year disease-free survival (DFS) rates were calculated for low (

Background Physical exercise and nutritional treatment are promising measures to prevent muscle wasting that is frequently observed in advanced-stage cancer patients. However, conventional exercise is not always suitable for these patients due to physical weakness and therapeutic side effects. In this pilot study, we examined the effect of a combined approach of the novel training method whole-body electromyostimulation (WB-EMS) and individualized nutritional support on body composition with primary focus on skeletal muscle mass in advanced cancer patients under oncological treatment. Methods In a non-randomized controlled trial design patients (56.5% male; 59.9 ± 12.7 years) with advanced solid tumors (UICC III/IV, N = 131) undergoing anti-cancer therapy were allocated to a usual care control group (n = 35) receiving individualized nutritional support or to an intervention group (n = 96) that additionally performed a supervised physical exercise program in form of 20 min WB-EMS sessions (bipolar, 85 Hz) 2×/week for 12 weeks. The primary outcome of skeletal muscle mass and secondary outcomes of body composition, body weight and hand grip strength were measured at baseline, in weeks 4, 8 and 12 by bioelectrical impedance analysis and hand dynamometer. Effects of WB-EMS were estimated by linear mixed models. Secondary outcomes of physical function, hematological and blood chemistry parameters, quality of life and fatigue were assessed at baseline and week 12. Changes were analyzed by t-tests, Wilcoxon signed-rank or Mann-Whitney-U-tests. Results Twenty-four patients of the control and 58 of the WB-EMS group completed the 12-week trial. Patients of the WB-EMS group had a significantly higher skeletal muscle mass (0.53 kg [0.08, 0.98]; p = 0.022) and body weight (1.02 kg [0.05, 1.98]; p = 0.039) compared to controls at the end of intervention. WB-EMS also significantly improved physical function and performance status (p

Background During cancer therapy, many patients suffer from malnutrition or vitamin deficiency. Treatment for nutrition-related deficiencies should therefore include nutritional therapy and possibly oral or intravenous substitution of micronutrients. Little information exists on multinutrient infusion therapies. The aim of this study was to develop standardized infusion protocols for integrative medicine infusions with micronutrients (IMed infusions) and to report on side effects of the treatment and patientsʼ satisfaction with it. Methods For the IMed consultancy service, four special formulas for intravenous use were developed in cooperation with the pharmacy at Erlangen University Hospital. A retrospective cross-sectional study was conducted between October 2015 and January 2018 in which 45 patients with gynecological or breast cancer (BC) and IMed infusion therapy were included. Follow-up data were obtained from 20 patients using a standardized questionnaire on IMed infusions. Results A total of 280 IMed infusions were administered in the study period. The majority of the patients received an IMed regeneration infusion (78%). The majority of the patients had BC and were receiving chemotherapy. Most patients reported a high or very high level of satisfaction with the organization (60%), general treatment (65%) and counseling (85%). Subjective improvement in their disease-related and therapy-induced symptoms, such as fatigue, polyneuropathy and physical efficiency, was reported by 70% of the patients, while 75% reported a subjective increase in quality of life. Side effects were rare and minor. Conclusions Therapy with IMed infusions in women with BC or gynecological cancer requires the same standards set for drug therapy. Although vitamins represent dietary supplements, appropriate assessment of the patientʼs medical history is needed and patients must receive appropriate information. For this purpose, standardized processes, as in the context of an IMed consultancy service, are helpful.

Background Aberrant accumulation of extracellular matrix (ECM) in multiple organs or fibrosis is one of the three hallmarks that characterises the pathogenesis of systemic sclerosis (SSc), together with immune dysregulation and small vessel vasculopathy. Recent studies have shown that CXCL4 (Chemokine CXC motif ligand 4) levels are increased in patients with SSc and correlated with skin and lung fibrosis.1 CXCL4 plays key role in physiological processes, although it has been also implicated in several pathological conditions such as autoimmune diseases and cancer. We and others have shown that CXCL4 modulates the phenotype and function of immune cells 2, suggesting a critical role of this chemokine in innate and adaptive immune responses. However, how CXCL4 exactly modulates immune cell responses remains unclear. Objectives Here we investigated the impact of CXCL4 exposure on the transcriptome and DNA methylation of monocyte-derived dendritic cells (moDCs), and the consequence on their function. Methods We differentiated human moDCs in the presence of CXCL4. After 6 days differentiation, cells were stimulated with a TLR3 ligand (polyI:C) as described in our previous study.2 RNA sequencing and DNA methylation profiling was performed at various time points during differentiation and stimulation. Results Integration of high-throughput analyses of RNA sequencing and DNA methylation reveals that CXCL4 drives to dramatic changes on the transcriptome and epigenome levels. This is reflected in the dysregulation of critical innate and adaptive immune pathways, like antigen presentation, and cytokine signalling. For the first time, we show that CXCL4 potentiates a novel function to dendritic cells, namely, the production of ECM molecules, such as fibronectin (FN1) and osteopontin (OPN). Furthermore, we also found that CXCL4 exposure results in epigenetic imprinting during moDC differentiation. Using novel bioinformatic methods, we have found that CXCL4 mediates the altered cell function via key transcriptional regulators. Conclusions This study provides better understanding how CXCL4 affects moDCs through several immune and non-immune pathways and shows for the first time the direct implication of CXCL4 on the production of ECM by inflammatory cells, thereby underscoring the pivotal role of CXCL4 in inflammatory and fibrotic conditions such as SSc. References [1] L. van Bon, Affandi AJ, et al. Proteome-wide analysis and CXCL4 as a biomarker in systemic sclerosis. N. Engl. J. Med2014. doi:10.1056/NEJMoa1114576 [2] Silva-Cardoso SC, Affandi AJ, et al. CXCL4 Exposure Potentiates TLR-Driven Polarization of Human Monocyte-Derived Dendritic Cells and Increases Stimulation of T Cells. J. Immunol2017. doi:10.4049/jimmunol.1602020 Acknowledgements This study was supported by the: PhD fellowship SFRH/BD/89643/2012 from the Portuguese Fundaxxo para a Cixncia e a Tecnologia (FCT) to Sandra C. Silva-Cardoso; China Scholarship Council (CSC) fellowship No. 201606300050 to Weiyang Tao; ERC starting grant (CIRCUMVENT) and Arthritis foundation grant to Timothy R.D.J. Radstake. Disclosure of Interest None declared

Over the last two decades genetic testing for mutations in BRCA1 and BRCA2 has become standard of care for women and men who are at familial risk for breast or ovarian cancer. Currently, genetic testing more often also includes so-called panel genes, which are assumed to be moderate-risk genes for breast cancer. Recently, new large-scale studies provided more information about the risk estimation of those genes. The utilization of information on panel genes with regard to their association with the individual breast cancer risk might become part of future clinical practice. Furthermore, large efforts have been made to understand the influence of common genetic variants with a low impact on breast cancer risk. For this purpose, almost 450 000 individuals have been genotyped for almost 500 000 genetic variants in the OncoArray project. Based on first results it can be assumed that – together with previously identified common variants – more than 170 breast cancer risk single nucleotide polymorphisms can explain up to 18% of familial breast cancer risk. The knowledge about genetic and non-genetic risk factors and its implementation in clinical practice could especially be of use for individualized prevention. This includes an individualized risk prediction as well as the individualized selection of screening methods regarding imaging and possible lifestyle interventions. The aim of this review is to summarize the most recent developments in this area and to provide an overview on breast cancer risk genes, risk prediction models and their utilization for the individual patient.

Introduction: Recently, complementary and alternative medicine (CAM) has moved more into the focus, and cancer societies such as the German Cancer Society (Deutsche Krebsgesellschaft, DKG) have established working groups to develop aguideline for CAM. The present work aims to evaluate the acceptance of CAM in the whole radiation oncology community. Methods: We conducted an online survey on CAM and sent the modified questionnaire that was successfully distributed to all members of the Research Group on Gynecological Oncology (Arbeitsgemeinschaft Gynakologische Onkologie, AGO) of the DKG in 2014 to the members of the German Society of Radiation Oncology (Deutsche Gesellschaft für Radioonkologie und Strahlentherapie, DEGRO). The survey consisted of 17questions regarding personal information and current CAM guidelines within the workplace/clinic. Results: Atotal of 143 members participated. Of these, 12% had some CAM qualification. For hematological cancer in 35% and in up to 76% for breast cancer, CAM treatment is offered in German radiation oncology facilities, mainly due to fatigue symptoms. CAM is part of routine treatment in 32.2%, 22.0% are planning to incorporate it. Most physicians advise patients to partake in sports activities and recommend dietary supplements and nutritional counseling. The cost of CAM treatment is fully covered in 9.8% of all participating facilities. Conclusion: Today, CAM is integrated into cancer care; however, skepticism regarding its effect still exists. Evidence-based results must be generated to convince physicians of the effectiveness of CAM methods. CAM qualifications must be included in physicians’ training to improve their understanding and counseling regarding CAM options in cancer care.

The study of contact and collision sport athletes at risk for concussion began approximately three decades ago. Since then, sport-related concussion (SRC) research across several medical specialties has helped to develop consensus guidelines for clinical management through interdisciplinary efforts. The modern landscape of SRC research includes large-scale investigations to define the natural history of concussion and identify factors that should guide prevention, diagnosis, and treatment specific to the individual patient. We now know that the clinical and physiologic effects of concussion are related but independent constructs deserving further scientific exploration. This has sparked research that incorporates advanced neuroimaging, fluid biomarkers, biomechanics, and genomics, in addition to standard clinical outcomes. Additionally, translational research has informed our understanding of optimal rehabilitation strategies and led to a shift from the "complete rest" approach to earlier, active management interventions after concussion. Collectively, these advancements are likely to substantially improve patient outcomes after SRC and, ultimately, may prove beneficial for identifying and appropriately managing those at risk for longer-term difficulties associated with repetitive head impact exposure. The broader public health implications of improving sports safety and encouraging developmentally appropriate participation among youth and adolescents are a particularly important byproduct of continued research into SRC.