Natural course of total mismatch and predictors for tissue infarction.

Objective: We longitudinally assessed patients presenting with total mismatch and hypothesized that hypoperfusion intensity ratio (HIR), severity of stroke, and occlusion of blood vessel are predictors of tissue fate.

Methods: Patients with suspected stroke or TIA admitted to our emergency department between September 2008 and October 2012 with suspected stroke or TIA were eligible to participate in the ongoing stroke imaging study 1000Plus. Patients received acute and follow-up stroke MRI, basic demographics were collected, and stroke severity was rated according to the NIH Stroke Scale (NIHSS).

CD8+ tumour-infiltrating lymphocytes in relation to HPV status and clinical outcome in patients with head and neck cancer after postoperative chemoradiotherapy: A multicentre study of the German cancer consortium radiation oncology group (DKTK-ROG).

We examined the prognostic value of tumour-infiltrating lymphocytes (TILs) in patients with squamous cell carcinoma of the head and neck (SCCHN) after surgery and postoperative cisplatin-based chemoradiotherapy. FFPE-tissue originating from the surgery of 161 patients treated in 8 DKTK partner sites was immunohistochemically stained for CD3 and CD8. Their expression was correlated with clinicopathological characteristics as well as overall survival (OS), local progression-free survival (LPFS) and distant metastases free-survival (DMFS), also in the context of the HPV16-DNA/p16 status.

Topotecan plus cyclophosphamide in adults with relapsed or refractory pediatric-type sarcoma: a retrospective analysis from the German Sarcoma Medical Oncology Group (AIO).

Background: To assess the efficacy and safety of topotecan and cyclophosphamide (TC) in adult patients with pediatric-type sarcoma subtypes who failed induction chemotherapy.

Patients And Methods: Patients with pediatric sarcoma subtypes, refractory to or relapsed after at least one prior induction chemotherapy, inoperable, ECOG PS 0-2, with measurable, progressive disease (PD), adequate organ functions, who have been treated with TC combination were retrospectively analysed within the AIO and SAREZ/BMBF network.

Results: Thirty-nine patients, median age 28 years (18-58), 14 females, 25 males, have been identified.

Long-term safety, efficacy, and quality of life in patients with juvenile idiopathic arthritis treated with intravenous abatacept for up to seven years.

Objective: The efficacy and safety of abatacept in patients with juvenile idiopathic arthritis (JIA) who experienced an inadequate response to disease-modifying antirheumatic drugs were previously established in a phase III study that included a 4-month open-label lead-in period, a 6-month double-blind withdrawal period, and a long-term extension (LTE) phase. The aim of this study was to present the safety, efficacy, and patient-reported outcomes of abatacept treatment (10 mg/kg every 4 weeks) during the LTE phase, for up to 7 years of followup.

Methods: Patients enrolled in the phase III trial could enter the open-label LTE phase if they had not achieved a response to treatment at month 4 or if they had received abatacept or placebo during the double-blind period.

Self-adjuvanted mRNA vaccination in advanced prostate cancer patients: a first-in-man phase I/IIa study.

Background: CV9103 is a prostate-cancer vaccine containing self-adjuvanted mRNA (RNActive®) encoding the antigens PSA, PSCA, PSMA, and STEAP1. This phase I/IIa study evaluated safety and immunogenicity of CV9103 in patients with advanced castration-resistant prostate-cancer.

Methods: 44 Patients received up to 5 intra-dermal vaccinations.

Outlook on PI3K/AKT/mTOR inhibition in acute leukemia.

Technological advances allowing high throughput analyses across numerous cancer tissues have allowed much progress in understanding complex cellular signaling. In the future, the genetic landscape in cancer may have more clinical relevance than diagnosis based on tumor origin. This progress has emphasized PI3K/AKT/mTOR, among others, as a central signaling center of cancer development due to its governing control in cellular growth, survival, and metabolism.

Tshz1 Regulates Pancreatic β-Cell Maturation.

The homeodomain transcription factor Pdx1 controls pancreas organogenesis, specification of endocrine pancreas progenitors, and the postnatal growth and function of pancreatic β-cells. Pdx1 expression in human-derived stem cells is used as a marker for induced pancreatic precursor cells. Unfortunately, the differentiation efficiency of human pancreatic progenitors into functional β-cells is poor.

No relevant pharmacokinetic interaction between pantoprazole and mycophenolate in renal transplant patients: a randomized crossover study.

Aims: Mycophenolic acid (MPA) suppresses lymphocyte proliferation through inosine monophosphate dehydrogenase (IMPDH) inhibition. Two formulations have been approved: mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS). Pantoprazole (PAN) inhibits gastric acid secretion, which may alter MPA exposure.

Efficacy and safety of etanercept in patients with the enthesitis-related arthritis category of juvenile idiopathic arthritis: results from a phase III randomized, double-blind study.

Objective: To evaluate the efficacy and safety of etanercept in patients with enthesitis-related arthritis (ERA) in juvenile idiopathic arthritis (JIA).

Methods: This was a 2-phase study in JIA patients with active, refractory ERA. Phase I was an open-label, uncontrolled 24-week study period in which all patients were administered etanercept.

Long-lived plasma cells are early and constantly generated in New Zealand Black/New Zealand White F1 mice and their therapeutic depletion requires a combined targeting of autoreactive plasma cells and their precursors.

Introduction: Autoantibodies contribute significantly to the pathogenesis of systemic lupus erythematosus (SLE). Unfortunately, the long-lived plasma cells (LLPCs) secreting such autoantibodies are refractory to conventional immunosuppressive treatments. Although generated long before the disease becomes clinically apparent, it remains rather unclear whether LLPC generation continues in the established disease.

Electrocortical Activity at 7 Days of Life is Affected in Extremely Premature Infants with Patent Ductus Arteriosus.

Background: The aim of this study was to determine whether the aEEG at 7 days of life is influenced by the presence of a PDA in non-sedated extremely low gestational age preterm infants.

Patients: We prospectively recruited infants born at less than 28 weeks of gestation between 11/2007 and 12/2009.

Method: aEEGs were recorded at seven days of life and assessed by using the Burdjalov score and the electronically assessed lower border (eLBA).

Corrigendum: Valenced action/inhibition learning in humans is modulated by a genetic variant linked to dopamine D2 receptor expression.

[This corrects the article on p. 140 in vol. 8, PMID: 25147510.

Downregulation of the Wnt inhibitor CXXC5 predicts a better prognosis in acute myeloid leukemia.

The gene CXXC5 on 5q31 is frequently deleted in acute myeloid leukemia (AML) with del(5q), suggesting that inactivation of CXXC5 might play a role in leukemogenesis. Here, we investigated the functional and prognostic implications of CXXC5 expression in AML. CXXC5 mRNA was downregulated in AML with MLL rearrangements, t(8;21) and GATA2 mutations.

Dose-dependent induction of signaling pathways by the flavonoid quercetin in human primary hepatocytes: A transcriptomic study.

Scope: Quercetin is widespread in plant kingdom and consumed regularly with human diet (16 mg/day). Due to reported positive effects on health, quercetin supplements with recommended doses up to 2 g/day are offered. However, molecular effects of such high doses on human liver have not been assessed yet.

Interrelated aldosterone and parathyroid hormone mutually modify cardiovascular mortality risk.

Background: Inappropriate aldosterone and parathyroid hormone (PTH) secretion is associated with increased cardiovascular risk. Accumulating evidence suggests bidirectional interplay between aldosterone and PTH.

Methods: We evaluated the cross-sectional relationship between plasma aldosterone concentration (PAC), aldosterone to renin ratio (ARR) and PTH and subsequently tested whether the interaction between PAC and PTH modified the risk of cardiovascular death.

Infarct volume-based subgroup selection in acute ischemic stroke trials.

Background And Purpose: We investigated whether hyperintensities with a diameter of at least 3, 3.5, and 4 cm and visible on at least 3 slices on diffusion-weighted imaging enables patient selection with an infarct volume of ≥15 mL.

Methods: Consecutive acute stroke patients were screened for the AXIS2 trial and examined according to a standardized magnetic resonance imaging protocol in 65 sites.

Reverse epidemiology in different stages of heart failure.

Background: In heart failure (HF), traditional cardiovascular risk factors (RF) as body mass index (BMI), total cholesterol (TC) and systolic blood pressure (SBP) are associated with better survival. It is unknown at which time point along the disease continuum the adverse impact of these RF ceases and may 'start to reverse'. We analyzed the distribution of RF and their association with survival across HF stages.

Evidence-based provisional clinical classification criteria for autoinflammatory periodic fevers.

The objective of this work was to develop and validate a set of clinical criteria for the classification of patients affected by periodic fevers. Patients with inherited periodic fevers (familial Mediterranean fever (FMF); mevalonate kinase deficiency (MKD); tumour necrosis factor receptor-associated periodic fever syndrome (TRAPS); cryopyrin-associated periodic syndromes (CAPS)) enrolled in the Eurofever Registry up until March 2013 were evaluated. Patients with periodic fever, aphthosis, pharyngitis and adenitis (PFAPA) syndrome were used as negative controls.

The combinatorial complexity of cancer precision medicine.

Precision medicine approaches have recently been developed that offer therapies targeting mainly single genetic alterations in malignant tumors. However, next generation sequencing studies have shown that tumors normally harbor multiple genetic alterations, which could explain the so far limited successes of personalized medicine, despite considerable benefits in certain cases. Combination therapies may contribute to a solution, but will pose a major challenge for clinical trials evaluating those therapies.

Automation of ALK gene rearrangement testing with fluorescence in situ hybridization (FISH): a feasibility study.

In the past several years we have observed a significant increase in our understanding of molecular mechanisms that drive lung cancer. Specifically in the non-small cell lung cancer sub-types, ALK gene rearrangements represent a sub-group of tumors that are targetable by the tyrosine kinase inhibitor Crizotinib, resulting in significant reductions in tumor burden. Phase II and III clinical trials were performed using an ALK break-apart FISH probe kit, making FISH the gold standard for identifying ALK rearrangements in patients.

READING and FEELING: the effects of a literature-based intervention designed to increase emotional competence in second and third graders.

Emotional competence has an important influence on development in school. We hypothesized that reading and discussing children's books with emotional content increases children's emotional competence. To examine this assumption, we developed a literature-based intervention, named READING and FEELING, and tested it on 104 second and third graders in their after-school care center.

Standardized Ki67 Diagnostics Using Automated Scoring--Clinical Validation in the GeparTrio Breast Cancer Study.

Purpose: Scoring proliferation through Ki67 immunohistochemistry is an important component in predicting therapy response to chemotherapy in patients with breast cancer. However, recent studies have cast doubt on the reliability of "visual" Ki67 scoring in the multicenter setting, particularly in the lower, yet clinically important, proliferation range. Therefore, an accurate and standardized Ki67 scoring is pivotal both in routine diagnostics and larger multicenter studies.