Deficiency of Plasminogen Activator Inhibitor Type 2 Limits Brain Edema Formation after Traumatic Brain Injury.

Plasminogen activator inhibitor-2 (PAI-2/SerpinB2) inhibits extracellular urokinase plasminogen activator (uPA). Under physiological conditions, PAI-2 is expressed at low levels but is rapidly induced by inflammatory triggers. It is a negative regulator of fibrinolysis and serves to stabilize clots.

Child maltreatment is mediating long-term consequences of household dysfunction in a population representative sample.

Background: Adverse childhood experiences (ACE) exhibit long-lasting consequences on later life and are considered as a major public health problem. ACEs can be divided into household dysfunctions, which affect the child indirectly, and direct maltreatment. As a high correlation between ACEs in general is known, we assessed the risk for child maltreatment associated with the occurrence of household dysfunctions.

Paradigm shift in geriatric fracture treatment.

The number of geriatric patients is increasing. These patients exhibit specific characteristics, which influence the type of fracture care. Many patients have comorbidities, which make them more vulnerable to surgical procedures.

A non-functional neoepitope specific CD8 T-cell response induced by tumor derived antigen exposure .

Cancer-associated mutations, mostly single nucleotide variations, can act as neoepitopes and prime targets for effective anti-cancer T-cell immunity. T cells recognizing cancer mutations are critical for the clinical activity of immune checkpoint blockade (ICB) and they are potent vaccine antigens. High frequencies of mutation-specific T cells are rarely spontaneously induced.

Harnessing Tumor Mutations for Truly Individualized Cancer Vaccines.

T cells are key effectors of anticancer immunity. They are capable of distinguishing tumor cells from normal ones by recognizing major histocompatibility complex-bound cancer-specific peptides. Accumulating evidence suggests that peptides associated with T cell-mediated tumor rejection arise predominantly from somatically mutated proteins and are unique to every patient's tumor.

Assessing quality of care for the dying from the bereaved relatives' perspective: Using pre-testing survey methods across seven countries to develop an international outcome measure.

Background:: The provision of care for dying cancer patients varies on a global basis. In order to improve care, we need to be able to evaluate the current level of care. One method of assessment is to use the views from the bereaved relatives.

Translating Science into Survival: Report on the Fourth International Cancer Immunotherapy Conference.

On September 30 to October 3, 2018, in New York City, the Fourth International Cancer Immunotherapy Conference (CICON) was hosted jointly by the Cancer Research Institute (CRI), the Association for Cancer Immunotherapy (CIMT), the European Academy of Tumor Immunology, and the American Association for Cancer Research (AACR). For the fourth straight year, more than 1,400 people attended the 4-day event, which covered the latest advances in cancer immunology and immunotherapy. This year's meeting also coincided with the announcement that the 2018 Nobel Prize in Medicine or Physiology would be awarded to one of CICON's attendees, James P.

Actively personalized vaccination trial for newly diagnosed glioblastoma.

Patients with glioblastoma currently do not sufficiently benefit from recent breakthroughs in cancer treatment that use checkpoint inhibitors. For treatments using checkpoint inhibitors to be successful, a high mutational load and responses to neoepitopes are thought to be essential. There is limited intratumoural infiltration of immune cells in glioblastoma and these tumours contain only 30-50 non-synonymous mutations.

Fully robotic Ivor-Lewis esophagectomy (RAMIE4) for esophageal cancer after emergency surgery and ligation of the gastroduodenal artery.

We report a case of a 69-year-old patient with esophageal cancer and severe upper gastrointestinal bleeding during neoadjuvant radiochemotherapy who required mass transfusion followed by complex emergency procedures. Despite endoscopic stenting, the bleeding recurred, and thus emergency open surgery was required. Gastric wedge resection of the minor curvature necessitated by perforation caused by the endoscopic stent maneuver and duodenotomy with ligation of the gastroduodenal artery, as the cause of persistent intraluminal bleeding, were performed.

IL-10 signaling prevents gluten-dependent intraepithelial CD4 cytotoxic T lymphocyte infiltration and epithelial damage in the small intestine.

Breach of tolerance to gluten leads to the chronic small intestinal enteropathy celiac disease. A key event in celiac disease development is gluten-dependent infiltration of activated cytotoxic intraepithelial lymphocytes (IELs), which cytolyze epithelial cells causing crypt hyperplasia and villous atrophy. The mechanisms leading to gluten-dependent small intestinal IEL infiltration and activation remain elusive.

Responsiveness to anti-PD-1 and anti-CTLA-4 immune checkpoint blockade in SB28 and GL261 mouse glioma models.

Immune checkpoint blockade (ICB) is currently evaluated in patients with glioblastoma (GBM), based on encouraging clinical data in other cancers, and results from studies with the methylcholanthrene-induced GL261 mouse glioma. In this paper, we describe a novel model faithfully recapitulating some key human GBM characteristics, including low mutational load, a factor reported as a prognostic indicator of ICB response. Consistent with this observation, SB28 is completely resistant to ICB, contrasting with treatment sensitivity of the more highly mutated GL261.

Induction of immunosuppressive functions and NF-κB by FLIP in monocytes.

Immunosuppression is a hallmark of tumor progression, and treatments that inhibit or deplete monocytic myeloid-derived suppressive cells could promote anti-tumor immunity. c-FLIP is a central regulator of caspase-8-mediated apoptosis and necroptosis. Here we show that low-dose cytotoxic chemotherapy agents cause apoptosis linked to c-FLIP down-regulation selectively in monocytes.

Do we get the message through? Difficulties in the prevention of abusive head trauma.

Many programs aim to prevent abusive head trauma throughout the USA, Europe, and in many other regions of the world. Most of these programs inform mothers shortly after delivery about the dangers of abusive head trauma. Effectiveness of these programs usually is measured by the increase of knowledge on abusive head trauma.

A prospective multicenter evaluation of immediately functionalized tapered conical connection implants for single restorations in maxillary anterior and premolar sites: 3-year results.

Objectives: This multicenter prospective clinical trial investigated immediately provisionalized, anodized, conical connection, tapered implants with platform shifting in maxillary anterior and premolar sites.

Materials And Methods: Patients requiring single-tooth implant-supported restorations in maxillary anterior and premolar sites were enrolled. Implants were immediately provisionalized and evaluated at insertion, 6 months, and annually thereafter.

Association of child maltreatment subtypes and long-term physical health in a German representative sample.

: Child maltreatment is a major public problem, associated with enormous consequences on the individual and socioeconomic level. Studies show a clear impact of child maltreatment on long-term physical health. However, there is a lack of analyses comprising a wide variety of subtypes of maltreatment and addressing cumulative effects of different maltreatment subtypes experienced during childhood on physical health.

Design and rationale of a randomised controlled trial comparing apixaban to phenprocoumon in patients with atrial fibrillation on chronic haemodialysis: the AXADIA-AFNET 8 study.

Introduction: Patients with end-stage kidney disease requiring maintenance haemodialysis treatment experience a dramatic cardiovascular morbidity and mortality. Due to the high atherosclerotic and arteriosclerotic burden and profound alterations in haemostasis, they frequently suffer and die from both thromboembolic and bleeding events. This is a particular concern in patients on haemodialysis with atrial fibrillation (AF).

Studying Tumor-ReacTive T Cells: A Personalized Organoid Model.

Recently in Cell, Dijkstra et al. (2018) introduced a tumor organoid/lymphocyte co-culture-based approach to expand and analyze tumor-specific T cell responses in a patient-specific manner. The platform is applicable for epithelial cancers and may have significant value for clinical translation of novel personalized immunotherapies.

An RNA toolbox for cancer immunotherapy.

Cancer immunotherapy has revolutionized oncology practice. However, current protein and cell therapy tools used in cancer immunotherapy are far from perfect, and there is room for improvement regarding their efficacy and safety. RNA-based structures have diverse functions, ranging from gene expression and gene regulation to pro-inflammatory effects and the ability to specifically bind different molecules.

In vivo imaging of the immune response upon systemic RNA cancer vaccination by FDG-PET.

Background: [F]Fluoro-2-deoxy-2-D-glucose positron emission tomography (FDG-PET) is commonly used in the clinic for diagnosis of cancer and for follow-up of therapy outcome. Additional to the well-established value in tumor imaging, it bears potential to depict immune processes in modern immunotherapies. T cells enhance their glucose consumption upon activation and are crucial effectors for the success of such novel therapies.

Ice water test in multiple sclerosis: A pilot trial.

Objectives: To investigate the significance of the ice water test in patients with multiple sclerosis and to evaluate a novel ice water test nomogram in a large patient cohort.

Methods: A total of 201 ice water tests of patients with multiple sclerosis were retrospectively evaluated. Incontinence episodes in 24 h and sex were correlated with the ice water test.

Ramadan Observance during Pregnancy in Germany: a Challenge for Prenatal Care.

Introduction: Fasting during Ramadan while pregnant has been shown to have long-term negative effects on the offspring's physical and cognitive health. Even though most Muslims do not believe pregnant women are obligated to fast during Ramadan, fasting rates of up to 87% have been reported for pregnant women. No data exists to date about Ramadan adherence and behavior in Germany.

Brain Delivery of Multifunctional Dendrimer Protein Bioconjugates.

Neurological disorders are undoubtedly among the most alarming diseases humans might face. In treatment of neurological disorders, the blood-brain barrier (BBB) is a challenging obstacle preventing drug penetration into the brain. Advances in dendrimer chemistry for central nervous system (CNS) treatments are presented here.

Trends in child maltreatment in Germany: comparison of two representative population-based studies.

Background: Child maltreatment of all types is a serious concern for society, and it is important to monitor trends in incidence in order to inform child welfare agencies and policy-makers about emerging issues. In Germany, however, information on such trends is limited: apart from official sources, the only published study is a comparison of surveys conducted in 1992 and 2011 that had focused primarily on sexual abuse. The present study is the first to look at more recent trends and to examine other types of maltreatment as well.