A Phase II Study to Assess the Safety and Efficacy of the Dual mTORC1/2 and PI3K Inhibitor Bimiralisib (PQR309) in Relapsed, Refractory Lymphoma.

Bimiralisib is an orally bioavailable pan-phosphatidylinositol 3-kinase and mammalian target of rapamycin inhibitor which has shown activity against lymphoma in preclinical models. This phase I/II study evaluated the response rate to bimiralisib at 2 continuous dose levels (60 mg and 80 mg) in patients with relapsed/refractory lymphoma. Fifty patients were enrolled and started treatment.

Comparative investigation of cell cycle and immunomodulatory genes in mucosal and cutaneous melanomas: Preliminary data suggest a potential promising clinical role for p16 and the PD-1/PD-L1 axis.

Mucosal melanomas arise from the mucosal lining of various organs. Their etiology is currently unknown and there are no tissue-based methods to differentiate it from cutaneous melanomas. Furthermore, prognostic and predictive markers (e.

Endoscopic vacuum therapy for the treatment of colorectal leaks - a systematic review and meta-analysis.

Background: During the last two decades, vacuum-assisted wound therapy has been successfully transferred to an endoscopic treatment approach of various upper and lower gastrointestinal leaks called endoscopic vacuum therapy (EVT). As mostly small case series are published in this field, the aim of our systematic review and meta-analysis was to evaluate the efficacy and safety of EVT in the treatment of colorectal leaks.

Methods: A systematic search of MEDLINE/PubMed and Cochrane databases was performed using search terms related to EVT and colorectal defects (anastomotic leakage, rectal stump insufficiency) according to the PRISMA guidelines.

The "Skewer Technique" for Stentgraft Delivery in the Aortic Arch: Advancing the Dilatator in The Innominate Artery Over a Right Femoro-Brachial Through-And-Through Wire.

Background: Thoracic endovascular aortic repair (TEVAR) is the preferred treatment for different aortic pathologies, because it has reduced mortality and morbidity rates. However, TEVAR is not feasible in all cases due to aortic angulations, the hemodynamics of the aortic arch and narrow or tortuous iliofemoral access. Therefore, different adjuvant techniques, such as iliac percutaneous transluminal angioplasty, iliathrough-and-through guidewires and external transapical guidewires have been previously reported.

Total health insurance costs in children with a migraine diagnosis compared to a control group.

Background: Health care costs of migraine constitute a major issue in health economics. Several publications analyzed health care costs for adult migraine patients, based on questionnaires or secondary (health insurance) data. Although migraine often starts already in primary school age, data on migraine related costs in children is scarce.

Different Prevalence of Alarm, Dyspeptic and Reflux Symptoms in Patients with Cardia and Non-cardia Gastric Cancer.

Background And Aims: Symptoms of patients with gastric cancer (GC) are often unspecific and differences in symptoms between patients with cardia and non-cardia GC have been poorly investigated. We aimed to characterize symptoms of patients with cardia and non-cardia GC.

Methods: Patients with cardia (Siewert type II and III) and non-cardia GC were recruited in the German multicenter cohort of the Gastric Cancer Research (staR) study between 2013 and 2017.

Identifying risk factors for early neurological outcomes following thoracic endovascular aortic repair using the SUMMIT database.

Objectives: The aim of this study was to assess risk factors for early neurological complications following thoracic endovascular aortic repair (TEVAR) for multiple thoracic aortic diseases using an aggregated dataset.

Methods: The Study to Assess Outcomes After Endovascular Repair for Multiple Throacic Aortic Disease dataset included data from 6 studies evaluating Zenith thoracic endografts. Post hoc analysis identified early (30-day) neurological complications by TEVAR indication and corresponding risk factors.

Feasibility and Preliminary Patency of Prophylactic Hypogastric Artery Stenting for Prevention of Spinal Cord Ischemia in Complex Endovascular Aortic Repair.

Background: To report early results of feasibility and patency of prophylactic hypogastric artery (HA) stenting during complex endovascular aortic repair.

Methods: This is a single centre retrospective non comparative cohort study of all consecutive patients undergoing prophylactic HA stenting during fenestrated and/or branched EVAR (F/B EVAR) in order to prevent spinal cord ischemia (SCI). Endpoints included technical success and early outcomes in terms of morbidity, mortality and patency of the implanted stents.

Pre-Loaded Fenestrated Thoracic Endografts for Distal Aortic Arch Pathologies: Multicentre Retrospective Analysis of Short and Mid Term Outcomes.

Objective: To determine short and midterm outcomes of a pre-loaded fenestrated thoracic endograft (f-TEVAR) for exclusion of distal aortic arch pathologies.

Methods: This was a multicentre, retrospective study including consecutive patients from six experienced European vascular centres undergoing f-TEVAR for distal arch pathologies. Primary endpoints included peri-operative mortality and peri-operative stroke and/or spinal cord ischaemia rates.

Effects of Acetyl-DL-Leucine on Ataxia and Downbeat-Nystagmus in Six Patients With Ataxia Telangiectasia.

Background: There is no authorized treatment for ataxia telangiectasia (AT). As cerebellar symptoms of storage diseases were improved by acetyl-DL-leucine (ADLL), the authors hypothesized a symptomatic and disease-modifying effect in AT upon supplementation with ADLL.

Methods: Six patients were treated with ADLL 3 g/day for 1 week followed by 5g/day for 3 weeks to 1 year.

Validation of POD24 as a robust early clinical end point of poor survival in FL from 5225 patients on 13 clinical trials.

Observational studies and stand-alone trials indicate that patients with follicular lymphoma (FL) who experience disease progression within 24 months of front-line chemoimmunotherapy (POD24), have poor outcomes. We performed a pooled analysis of 13 randomized clinical trials of patients with FL in the pre- and postrituximab eras to identify clinical factors that predict POD24. Logistic regression models evaluated the association between clinical factors and POD24.

DNA methylation profiling identifies two distinct subgroups in breast cancers with low hormone receptor expression, mainly associated with HER2 amplification status.

Background: Current clinical guidelines suggest that breast cancers with low hormone receptor expression (LowHR) in 1-10% of tumor cells should be regarded as hormone receptor positive. However, clinical data show that these patients have worse outcome compared to patients with hormone receptor expression above 10%. We performed DNA methylation profiling on 23 LowHR breast cancer specimens, including 13 samples with HER2 amplification and compared our results with a reference breast cancer cohort from The Cancer Genome Atlas to clarify the status for this infrequent but important patient subgroup.

Mucosal melanomas of different anatomic sites share a common global DNA methylation profile with cutaneous melanoma but show location-dependent patterns of genetic and epigenetic alterations.

Cutaneous, ocular, and mucosal melanomas are histologically indistinguishable tumors that are driven by a different spectrum of genetic alterations. With current methods, identification of the site of origin of a melanoma metastasis is challenging. DNA methylation profiling has shown promise for the identification of the site of tumor origin in various settings.

Subclinical cardiac impairment relates to traditional pulmonary function test parameters and lung volume as derived from whole-body MRI in a population-based cohort study.

To evaluate the relationship of cardiac function, including time-volume-curves, with lung volumes derived from pulmonary function tests (PFT) and MRI in subjects without cardiovascular diseases. 216 subjects underwent whole-body MRI and spirometry as part of the KORA-FF4 cohort study. Lung volumes derived semi-automatically using an in-house algorithm.

Availability of interventional-radiological revascularization procedures in Germany - an analysis of the DeGIR Registry Data 2018/19.

Purpose: Peripheral artery disease (PAD) is a common condition with high socio-economic relevance. Therefore, qualified nationwide provision of interventional treatments of PAD is important for maintaining a high quality medical service in Germany.

Materials And Methods: All data on revascularization procedures from the quality management system of the German interventional radiological society (DeGIR) for the years 2018 and 2019 were retrospectively analysed.

Single-nucleotide Fcγ receptor polymorphisms do not impact obinutuzumab/rituximab outcome in patients with lymphoma.

Single-nucleotide polymorphisms (SNPs) have been shown to influence Fcγ receptor (FcγR) affinity and activity, but their effect on treatment response is unclear. We assessed their importance in the efficacy of obinutuzumab or rituximab combined with chemotherapy in untreated advanced follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) in the GALLIUM (www.clinicaltrials.

Platelet-Cancer Interplay: Molecular Mechanisms and New Therapeutic Avenues.

Although platelets are critically involved in thrombosis and hemostasis, experimental and clinical evidence indicate that platelets promote tumor progression and metastasis through a wide range of physical and functional interactions between platelets and cancer cells. Thrombotic and thromboembolic events are frequent complications in patients with solid tumors. Hence, cancer modulates platelet function by directly inducing platelet-tumor aggregates and triggering platelet granule release and altering platelet turnover.

DNA methylation-based prediction of response to immune checkpoint inhibition in metastatic melanoma.

Background: Therapies based on targeting immune checkpoints have revolutionized the treatment of metastatic melanoma in recent years. Still, biomarkers predicting long-term therapy responses are lacking.

Methods: A novel approach of reference-free deconvolution of large-scale DNA methylation data enabled us to develop a machine learning classifier based on CpG sites, specific for latent methylation components (LMC), that allowed for patient allocation to prognostic clusters.

We Have a Lot to Do: Lack of Sexual Protection and Information-Results of the German-Language Online Survey "Let's Talk About Chemsex".

The prevalence of chemsex and sexualized substance use is increasing in several European countries, particularly among men who have sex with men. In this subgroup, illegal substance use is associated with increased sexual risk behavior, which can result in severe physical and psychological impairments. The present study examined the incidence and prevalence of chemsex in German-speaking countries.

Efficacy and Tolerability of Quinacrine Monotherapy and Albendazole Plus Chloroquine Combination Therapy in Nitroimidazole-Refractory Giardiasis: A TropNet Study.

Background: Giardiasis failing nitroimidazole first-line treatment is an emerging problem in returning European travelers. We present data on the efficacy and tolerability of 2 second-line treatment regimens.

Methods: This prospective, open-label, multicenter study assessed the efficacy and tolerability of quinacrine monotherapy (100 mg 3 times per day for 5 days) and albendazole plus chloroquine combination therapy (400 mg twice daily plus 155 mg twice daily for 5 days) in nitroimidazole-refractory giardiasis.

Automated Analysis of Cerebrospinal Fluid Cells Using Commercially Available Blood Cell Analysis Devices-A Critical Appraisal.

The analysis of cells in the cerebrospinal fluid (CSF) is a routine procedure that is usually performed manually using the Fuchs-Rosenthal chamber and cell microscopy for cell counting and differentiation. In order to reduce the requirement for manual assessment, automated analyses by devices mainly used for blood cell analysis have been also used for CSF samples. Here, we summarize the current state of investigations using these automated devices and critically review their limitations.

Sources of systematic error in DCE-MRI estimation of low-level blood-brain barrier leakage.

Purpose: Dynamic contrast-enhanced (DCE) -MRI with Patlak model analysis is increasingly used to quantify low-level blood-brain barrier (BBB) leakage in studies of pathophysiology. We aimed to investigate systematic errors due to physiological, experimental, and modeling factors influencing quantification of the permeability-surface area product PS and blood plasma volume v , and to propose modifications to reduce the errors so that subtle differences in BBB permeability can be accurately measured.

Methods: Simulations were performed to predict the effects of potential sources of systematic error on conventional PS and v quantification: restricted BBB water exchange, reduced cerebral blood flow, arterial input function (AIF) delay and error.