ALK positively regulates MYCN activity through repression of HBP1 expression.

ALK mutations occur in 10% of primary neuroblastomas and represent a major target for precision treatment. In combination with MYCN amplification, ALK mutations infer an ultra-high-risk phenotype resulting in very poor patient prognosis. To open up opportunities for future precision drugging, a deeper understanding of the molecular consequences of constitutive ALK signaling and its relationship to MYCN activity in this aggressive pediatric tumor entity will be essential.

GPCR-specific autoantibody signatures are associated with physiological and pathological immune homeostasis.

Autoantibodies have been associated with autoimmune diseases. However, studies have identified autoantibodies in healthy donors (HD) who do not develop autoimmune disorders. Here we provide evidence of a network of immunoglobulin G (IgG) autoantibodies targeting G protein-coupled receptors (GPCR) in HD compared to patients with systemic sclerosis, Alzheimer's disease, and ovarian cancer.

Intense dose-dense epirubicin, paclitaxel, cyclophosphamide versus weekly paclitaxel, liposomal doxorubicin (plus carboplatin in triple-negative breast cancer) for neoadjuvant treatment of high-risk early breast cancer (GeparOcto-GBG 84): A randomised phase III trial.

Background: GeparOcto compared efficacy and safety of two chemotherapy regimens in high-risk early breast cancer (BC): sequential treatment with intense dose-dense epirubicin, paclitaxel, and cyclophosphamide (iddEPC) and weekly treatment with paclitaxel plus non-pegylated liposomal doxorubicin (M, Myocet®) with additional carboplatin (PM(Cb)) in triple-negative BC (TNBC).

Patients And Methods: Patients with cT1c-cT4a-d and centrally assessed human epidermal growth factor receptor (HER)2-positive BC or TNBC were eligible, irrespective of nodal status, luminal B-like tumours only if pN+. Patients were randomised (stratified by BC subtype, Ki67, lymphocyte-predominant BC) to receive 18 weeks of E (150 mg/m) followed by P (225 mg/m) followed by C (2000 mg/m), each q2w for 3 cycles or weekly P (80 mg/m) plus M (20 mg/m) plus, in TNBC, Cb (area under curve (AUC) 1.

Translational highlights in breast cancer research and treatment: recent developments with clinical impact.

Purpose Of Review: Over the last decades the time which is needed to translate a preclinical finding or idea in the clinic has reduced continuously. Especially but not only for breast cancer the number of tested drugs and targeted pathways have increased immensely. In addition, the introduction of immune-oncological treatments has further advanced the possibilities for future treatments.

Sjögren's syndrome: state of the art on clinical practice guidelines.

Sjögren's syndrome (SS) is a complex autoimmune rheumatic disease that specifically targets salivary and lachrymal glands. As such, patients typically had ocular and oral dryness and salivary gland swelling. Moreover, skin, nasal and vaginal dryness are frequently present.

Relapsing polychondritis: state of the art on clinical practice guidelines.

Due to the rarity of relapsing polychondritis (RP), many unmet needs remain in the management of RP. Here, we present a systematic review of clinical practice guidelines (CPGs) published for RP, as well as a list of the most striking unmet needs for this rare disease. We carried out a systematic search in PubMed and Embase based on controlled terms (medical subject headings and Emtree) and keywords of the disease and publication type (CPGs).

Antiphospholipid syndrome: state of the art on clinical practice guidelines.

Antiphospholipid syndrome (APS) is a rare disease characterised by venous and/or arterial thrombosis, pregnancy complications and the presence of specific autoantibodies called antiphospholipid antibodies. This review aims to identify existing clinical practice guidelines (CPG) as part of the ERN ReCONNET project, aimed at evaluating existing CPGs or recommendations in rare and complex diseases. Seventeen papers providing important data were identified; however, the literature search highlighted the scarceness of reliable clinical data to develop CPGs.

Mixed connective tissue disease: state of the art on clinical practice guidelines.

Mixed connective tissue disease (MCTD) is a complex overlap disease with features of different autoimmune connective tissue diseases (CTDs) namely systemic sclerosis, poly/dermatomyositis and systemic lupus erythematous in patients with antibodies targeting the U1 small nuclear ribonucleoprotein particle. In this narrative review, we summarise the results of a systematic literature research which was performed as part of the European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases project, aimed at evaluating existing clinical practice guidelines (CPGs) or recommendations. Since no specific CPGs on MCTD were found, other CPGs developed for other CTDs were taken into consideration in order to discuss what can be applied to MCTD even if designed for other diseases.

Systemic sclerosis: state of the art on clinical practice guidelines.

Systemic sclerosis (SSc) is an orphan disease characterised by autoimmunity, fibrosis of the skin and internal organs, and vasculopathy. SSc may be associated with high morbidity and mortality. In this narrative review we summarise the results of a systematic literature research, which was performed as part of the European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases project, aimed at evaluating existing clinical practice guidelines or recommendations.

Machine learning provides novel neurophysiological features that predict performance to inhibit automated responses.

Neurophysiological features like event-related potentials (ERPs) have long been used to identify different cognitive sub-processes that may contribute to task performance. It has however remained unclear whether "classical" ERPs are truly the best reflection or even causal to observable variations in behavior. Here, we used a data-driven strategy to extract features from neurophysiological data of n = 240 healthy young individuals who performed a Go/Nogo task and used machine learning methods in combination with source localization to identify the best predictors of inter-individual performance variations.

Do adolescents with extreme obesity differ according to previous treatment seeking behavior? The Youth with Extreme obesity Study (YES) cohort.

Objectives: Adolescent extreme obesity is associated with somatic and psychiatric comorbidity, low quality of life, and social dysfunction. Nevertheless, few adolescents seek obesity treatment, thus many may elope appropriate care. We examine whether previous treatment seeking relates to disease burden, and whether previously non-treatment seeking adolescents accept diagnostic and therapeutic offers.

Systematic analysis of parameters predicting pathological axillary status (ypN0 vs. ypN+) in patients with breast cancer converting from cN+ to ycN0 through primary systemic therapy (PST).

Optimization of axillary staging among patients converting from clinically node-positive disease to clinically node-negative disease through primary systemic therapy is needed. We aimed at developing a nomogram predicting the probability of positive axillary status after chemotherapy based on clinical/pathological parameters. Patients from study arm C of the SENTINA trial were included.

Is whole-brain radiotherapy still a standard treatment for primary central nervous system lymphomas?

Purpose Of Review: In primary central nervous system lymphomas (PCNSL), optimal therapy remains to be established, and the role of whole-brain radiotherapy (WBRT) is a matter of debate. With radiation alone, transient responses and clinical improvement are frequent, but long-term disease control is exceptional. WBRT has been considered possible consolidation therapy after high-dose methotrexate (HDMTX)-based initial chemotherapy.

Evaluation of supportive and barrier-protective skin care products in the daily prevention and treatment of cutaneous toxicity during systemic chemotherapy.

Introduction: The purpose of this multicenter, prospective, observational, open-label study was to evaluate the use and tolerability of dermo-cosmetic products in preventing skin reactions associated with cancer treatments.

Patients And Methods: A 12-product kit was supplied to patients before chemotherapy began and was to be used throughout the treatment phase. Cutaneous adverse events were evaluated at each treatment session.

Generalization after ocular onset in myasthenia gravis: a case series in Germany.

Background And Purpose: Approximately, 50% of myasthenia gravis (MG) patients initially present with purely ocular symptoms. Of these, about 60% will develop secondary generalized MG, typically within 2 years. Risk factors for secondary generalization are still controversial.

Heart-brain Interactions in Heart Failure.

Heart failure (HF) is a complex disease with a growing incidence worldwide. HF is accompanied by a wide range of conditions which affect disease progression, functional performance and contribute to growing healthcare costs. The interactions between a failing myocardium and altered cerebral functions contribute to the symptoms experienced by patients with HF, affecting many comorbidities and causing a poor prognosis.

Clinical Safety of Combined Targeted and L. Therapy in Oncological Patients.

: Despite improvement of tumor response rates, targeted therapy may induce toxicities in cancer patients. Recent studies indicate amelioration of adverse events (AEs) by add-on mistletoe ( L., VA) in standard oncological treatment.

CCR5del32 genotype in human enteroviral cardiomyopathy leads to spontaneous virus clearance and improved outcome compared to wildtype CCR5.

Background: Enteroviral cardiomyopathy is a life-threatening disease, and detection of enterovirus (EV) RNA in the initial endomyocardial biopsy is associated with adverse prognosis and increased mortality. Some patients with EV infection may spontaneously eliminate the virus and recover, whereas those with virus persistence deteriorate and progress to heart failure. Interferon-beta (IFN-β) therapy eliminates the virus, resulting in increased survival of treated patients.

A Five-MicroRNA Signature Predicts Survival and Disease Control of Patients with Head and Neck Cancer Negative for HPV Infection.

Purpose: Human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) is associated with unfavorable prognosis, while independent prognostic markers remain to be defined.

Experimental Design: We retrospectively performed miRNA expression profiling. Patients were operated for locally advanced HPV-negative HNSCC and had received radiochemotherapy in eight different hospitals (DKTK-ROG; = 85).

A common classification framework for neuroendocrine neoplasms: an International Agency for Research on Cancer (IARC) and World Health Organization (WHO) expert consensus proposal.

The classification of neuroendocrine neoplasms (NENs) differs between organ systems and currently causes considerable confusion. A uniform classification framework for NENs at any anatomical location may reduce inconsistencies and contradictions among the various systems currently in use. The classification suggested here is intended to allow pathologists and clinicians to manage their patients with NENs consistently, while acknowledging organ-specific differences in classification criteria, tumor biology, and prognostic factors.

Urine neutrophil gelatinase-associated lipocalin predicts outcome and renal failure in open and endovascular thoracic abdominal aortic aneurysm surgery.

Urine neutrophil gelatinase-associated lipocalin (uNGAL) has been evaluated as a biomarker for AKI detection and adverse outcome in open and endovascular thoracoabdominal aortic aneurysm surgery. This observational, retrospective study included 52 patients. UNGAL was measured peri-operatively (48 h) and correlated with AKI requiring dialysis, tracheotomy and adverse outcome.

Contingency Contracts for Weight Gain of Patients with Anorexia Nervosa in Inpatient Therapy: Practice Styles of Specialized Centers.

The treatment of patients with anorexia nervosa (AN) is often challenging, due to a high degree of ambivalence towards recovery and weight gain these patients often express. One part of the multimodal treatment is the utilization of treatment contracts (i.e.

Morphology and tumour-infiltrating lymphocytes in high-stage, high-grade serous ovarian carcinoma correlated with long-term survival.

Aims: Advanced-stage ovarian high-grade serous carcinoma (HGSC) is a poor-prognosis cancer; however, a small and poorly characterised subset of patients shows long-term survival. We aimed to establish a cohort of HGSC long-term survivors for histopathological and molecular analysis.

Methods And Results: Paraffin blocks from 151 patients with primary FIGO III/IV HGSC and progression-free survival (PFS) >5 years were collected within the Tumorbank Ovarian Cancer (TOC) Network; 77 HGSC with a PFS <3 years were used as a control group.

Closed Incision Negative Pressure Therapy Reduces Surgical Site Infections in Vascular Surgery: A Prospective Randomised Trial (AIMS Trial).

Background: Surgical site infections (SSIs) of the groin remain a crucial problem in vascular surgery, prompting great interest in preventative techniques, such as closed incision negative pressure therapy (ciNPT). This prospective randomised study aimed to assess the potential benefits of ciNPT application after groin incisions for vascular surgery.

Method: The study included 204 patients who underwent vascular surgery for peripheral artery disease (PAD) at two sites between July 2015 and May 2017.