eHealth-supported case management for patients with panic disorder or depression in primary care: Study protocol for a cRCT (PREMA).

Background: Panic disorder (PD), frequently occurring with agoraphobia (AG), and depression are common mental disorders in primary care and associated with considerable individual and societal costs. Early detection and effective treatment of depression and PD/AG are of major importance. Cognitive behavioural exposure exercises have been shown to be effective in reducing anxiety and depressive symptoms.

GEOFFREY HARRIS AWARD 2019: Translational research in pituitary tumours.

Although effective treatment regimens (surgical resection, drug treatment with dopamine agonists or somatostatin analogues, radiotherapy) have been established for the therapy of most pituitary tumours, a considerable proportion of affected patients cannot completely cured due to incomplete resection or drug resistance. Moreover, even if hormone levels have been normalized, patients with hormone-secreting tumours still show persistent pathophysiological alterations in metabolic, cardiovascular or neuropsychiatric parameters and have an impaired quality of life. In this review reasons for the discrepancy between biochemical cure and incomplete recovery from tumour-associated comorbidities are discussed and the clinical management is delineated exemplarily for patients with acromegaly and Cushing's disease.

Proteasome activator PA200 regulates myofibroblast differentiation.

The proteasome is essential for the selective degradation of most cellular proteins and is fine-tuned according to cellular needs. Proteasome activators serve as building blocks to adjust protein turnover in cell growth and differentiation. Understanding the cellular function of proteasome activation in more detail offers a new strategy for therapeutic targeting of proteasomal protein breakdown in disease.

Long-Term Courses of Sepsis Survivors: Effects of a Primary Care Management Intervention.

Background: Sepsis survivors face mental and physical sequelae even years after discharge from the intensive care unit. The aim of this study was to evaluate the long-term courses of sepsis survivors and the effects of a primary care management intervention in sepsis aftercare.

Methods: This study presents a 24-month follow-up of a randomized controlled trial that recruited 291 patients who survived sepsis (including septic shock) from nine German intensive care units.

Premedication with a cathepsin C inhibitor alleviates early primary graft dysfunction in mouse recipients after lung transplantation.

Neutrophil serine proteases (NSPs), like proteinase 3 (PR3) and neutrophil elastase (NE) are implicated in ischemia-reperfusion responses after lung transplantation (LTx). Cathepsin C (CatC) acts as the key regulator of NSP maturation during biosynthesis. We hypothesized that CatC inhibitors would reduce vascular breakdown and inflammation during reperfusion in pretreated lung transplant recipients by blocking NSP maturation in the bone marrow.

Panic Disorder in Primary Care.

Background: We evaluated a team-based program of exercises for patients with panic disorder with or without agoraphobia (PDA) in primary care.

Methods: 419 patients with PDA (mean age 46.2 years, standard deviation 14.

Low Prevalence of Isolated Growth Hormone Deficiency in Patients After Brain Injury: Results From a Phase II Pilot Study.

Growth hormone deficiency (GHD) results in an impaired health-related quality of life (HrQoL) and cognitive impairment in the attention and memory domain. GHD is assumed to be a frequent finding after brain injury due to traumatic brain injury (TBI), aneurysmal subarachnoid hemorrhage (SAH) or ischemic stroke. Hence, we set out to investigate the effects of growth hormone (GH) replacement therapy in patients with isolated GHD after brain injury on HrQoL, cognition, and abdominal fat composition.

Fiend and friend in the renin angiotensin system: An insight on acute kidney injury.

Besides assisting the maintenance of blood pressure and sodium homeostasis, the renin-angiotensin system (RAS) plays a pivotal role in pathogenesis of acute kidney injury (AKI). The RAS is equipped with two arms i) the pressor arm composed of Angiotensin II (Ang II)/Angiotensin converting enzyme (ACE)/Angiotensin II type 1 receptor (AT1R) also called conventional RAS, and ii) the depressor arm consisting of Angiotensin (1-7) (Ang 1-7)/Angiotensin converting enzyme 2 (ACE2)/MasR known as non-conventional RAS. Activation of conventional RAS triggers oxidative stress, inflammatory, hypertrophic, apoptotic, and pro-fibrotic signaling cascades which promote AKI.

Validation of the MCL35 gene expression proliferation assay in randomized trials of the European Mantle Cell Lymphoma Network.

Mantle cell lymphoma (MCL) is still considered incurable and the course of the disease is highly variable. Established risk factors include the Mantle Cell Lymphoma International Prognostic Index (MIPI) and the quantification of the proliferation rate of the tumour cells, e.g.

Cell-surface phenotyping identifies CD36 and CD97 as novel markers of fibroblast quiescence in lung fibrosis.

Fibroblasts play an important role in lung homeostasis and disease. In lung fibrosis, fibroblasts adopt a proliferative and migratory phenotype, with increased expression of α-smooth muscle actin (αSMA) and enhanced secretion of extracellular matrix components. Comprehensive profiling of fibroblast heterogeneity is limited because of a lack of specific cell-surface markers.

Preservation with α-antitrypsin improves primary graft function of murine lung transplants.

Background: Vascular damage and primary graft dysfunction increase with prolonged preservation times of transplanted donor lungs. Hence, storage and conservation of donated lungs in protein-free, dextran-containing electrolyte solutions, like Perfadex, is limited to about 6 hours. We hypothesized that transplanted lungs are protected against neutrophil-mediated proteolytic damage by adding α-anti-trypsin (AAT), a highly abundant human plasma proteinase inhibitor, to Perfadex.

DNA methylation-based reclassification of olfactory neuroblastoma.

Olfactory neuroblastoma/esthesioneuroblastoma (ONB) is an uncommon neuroectodermal neoplasm thought to arise from the olfactory epithelium. Little is known about its molecular pathogenesis. For this study, a retrospective cohort of n = 66 tumor samples with the institutional diagnosis of ONB was analyzed by immunohistochemistry, genome-wide DNA methylation profiling, copy number analysis, and in a subset, next-generation panel sequencing of 560 tumor-associated genes.

Autologous Stem Cell Transplantation for Patients with Early Progression of Follicular Lymphoma: A Follow-Up Study of 2 Randomized Trials from the German Low Grade Lymphoma Study Group.

Patients with follicular lymphoma (FL) and progression of disease (POD) within 24 months after frontline treatment (POD24) have poor overall survival (OS). The optimal salvage treatment for these patients is unknown. We assessed the role of high-dose therapy and autologous stem cell transplantation (ASCT) in transplant-eligible patients.

Intratumoural expression of deoxycytidylate deaminase or ribonuceotide reductase subunit M1 expression are not related to survival in patients with resected pancreatic cancer given adjuvant chemotherapy.

Background: Deoxycytidylate deaminase (DCTD) and ribonucleotide reductase subunit M1 (RRM1) are potential prognostic and predictive biomarkers for pyrimidine-based chemotherapy in pancreatic adenocarcinoma.

Methods: Immunohistochemical staining of DCTD and RRM1 was performed on tissue microarrays representing tumour samples from 303 patients in European Study Group for Pancreatic Cancer (ESPAC)-randomised adjuvant trials following pancreatic resection, 272 of whom had received gemcitabine or 5-fluorouracil with folinic acid in ESPAC-3(v2), and 31 patients from the combined ESPAC-3(v1) and ESPAC-1 post-operative pure observational groups.

Results: Neither log-rank testing on dichotomised strata or Cox proportional hazard regression showed any relationship of DCTD or RRM1 expression levels to survival overall or by treatment group.

Expression of dihydropyrimidine dehydrogenase (DPD) and hENT1 predicts survival in pancreatic cancer.

Background: Dihydropyrimidine dehydrogenase (DPD) tumour expression may provide added value to human equilibrative nucleoside transporter-1 (hENT1) tumour expression in predicting survival following pyrimidine-based adjuvant chemotherapy.

Methods: DPD and hENT1 immunohistochemistry and scoring was completed on tumour cores from 238 patients with pancreatic cancer in the ESPAC-3(v2) trial, randomised to either postoperative gemcitabine or 5-fluorouracil/folinic acid (5FU/FA).

Results: DPD tumour expression was associated with reduced overall survival (hazard ratio, HR = 1.

Cub domain-containing protein 1 negatively regulates TGF-β signaling and myofibroblast differentiation.

Fibroblasts are thought to be the prime cell type for producing and secreting extracellular matrix (ECM) proteins in the connective tissue. The profibrotic cytokine transforming growth factor-β1 (TGF-β1) activates and transdifferentiates fibroblasts into α-smooth muscle actin (α-SMA)-expressing myofibroblasts, which exhibit increased ECM secretion, in particular collagens. Little information, however, exists about cell-surface molecules on fibroblasts that mediate this transdifferentiation process.

Distinct niches within the extracellular matrix dictate fibroblast function in (cell free) 3D lung tissue cultures.

Cues from the extracellular matrix (ECM) and their functional interplay with cells play pivotal roles for development, tissue repair, and disease. However, the precise nature of this interplay remains elusive. We used an innovative 3D cell culture ECM model by decellularizing 300-µm-thick ex vivo lung tissue scaffolds (d3D-LTCs) derived from diseased and healthy mouse lungs, which widely mimics the native (patho)physiological in vivo ECM microenvironment.

MiRIAD update: using alternative polyadenylation, protein interaction network analysis and additional species to enhance exploration of the role of intragenic miRNAs and their host genes.

http://www.miriad-database.org.

Lung ageing and COPD: is there a role for ageing in abnormal tissue repair?

Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death worldwide, with increasing prevalence, in particular in the elderly. COPD is characterised by abnormal tissue repair resulting in (small) airways disease and emphysema. There is accumulating evidence that ageing hallmarks are prominent features of COPD.

Incorporation of brentuximab vedotin into first-line treatment of advanced classical Hodgkin's lymphoma: final analysis of a phase 2 randomised trial by the German Hodgkin Study Group.

Background: A high proportion of patients with relapsed classical Hodgkin's lymphoma achieve a response with the antibody-drug conjugate brentuximab vedotin, and the drug is well tolerated. We modified the escalated BEACOPP regimen (eBEACOPP; bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) and implemented brentuximab vedotin with the aim to reduce toxic effects while maintaining the protocol's efficacy.

Methods: We did an open-label, multicentre, randomised phase 2 study at 20 study sites in Germany.

The instructive extracellular matrix of the lung: basic composition and alterations in chronic lung disease.

The pulmonary extracellular matrix (ECM) determines the tissue architecture of the lung, and provides mechanical stability and elastic recoil, which are essential for physiological lung function. Biochemical and biomechanical signals initiated by the ECM direct cellular function and differentiation, and thus play a decisive role in lung development, tissue remodelling processes and maintenance of adult homeostasis. Recent proteomic studies have demonstrated that at least 150 different ECM proteins, glycosaminoglycans and modifying enzymes are expressed in the lung, and these assemble into intricate composite biomaterials.

microRNA cluster 106a~363 is involved in T helper 17 cell differentiation.

T-helper cell type 17 (Th17) mediated inflammation is associated with various diseases including autoimmune encephalitis, inflammatory bowel disease and lung diseases such as chronic obstructive pulmonary disease and asthma. Differentiation into distinct T helper subtypes needs to be tightly regulated to ensure an immunological balance. As microRNAs (miRNAs) are critical regulators of signalling pathways, we aimed to identify specific miRNAs implicated in controlling Th17 differentiation.