Decreased Antibiotic Exposure for Suspected Early-Onset Sepsis in the Neonatal Intensive Care Unit Through Implementation of an Antimicrobial Time-out.

Antimicrobials are among the most frequently prescribed drugs in the neonatal intensive care unit (NICU), although most neonates exposed lack a bacterial infection. Overuse of antimicrobials carries risk to the patient and fosters the development of resistant organisms. Strategic and systematic processes hold promise to limit the unnecessary use of these drugs in this population.

Survival outcomes in a prospective randomized multicenter Phase III trial comparing patients undergoing anatomical segmentectomy versus standard lobectomy for non-small cell lung cancer up to 2 cm.

Objectives: The oncological equivalence of anatomical segmentectomy for early stage non-small cell lung cancer (NSCLC) is still controversial. Primary aim of this study was survival outcomes in combination with improved quality of life after segmentectomy compared with lobectomy in patients with pathological stage Ia NSCLC (up to 2 cm, 7th edition) MATERIALS AND METHODS: We conducted a prospective, randomized, multicenter phase III trial to confirm the non-inferiority of segmentectomy to lobectomy in regard to prognosis (trial No. DRKS00004897).

Bronchoscopic Thermal Vapour Ablation for Localized Cancer Lesions of the Lung: A Clinical Feasibility Treat-and-Resect Study.

Background: Bronchoscopic thermal vapour ablation (BTVA) is an established and approved modality for minimally invasive lung volume reduction in severe emphysema. Preclinical data suggest potential for BTVA in minimally invasive ablation of lung cancer lesions.

Objectives: The objective of this study is to establish the safety, feasibility, and ablative efficacy of BTVA for minimally invasive ablation of lung cancers.

Perioperative course and quality of life in a prospective randomized multicenter phase III trial, comparing standard lobectomy versus anatomical segmentectomy in patients with non-small cell lung cancer up to 2 cm, stage IA (7th edition of TNM staging system).

Objectives: For early stage non-small cell lung cancer (NSCLC) retrospective data of functionally compromised patients undergoing segmentectomy showed equal outcomes for perioperative complications and quality of life (QoL) compared with lobectomy patients. However no prospectively randomized data comparing patients eligible for both procedures are available.

Materials And Methods: We conducted a prospective, randomized, multicenter phase III trial and investigated perioperative complications and QoL in patients with NSCLC stage IA (7th edition) undergoing segmentectomy versus lobectomy.

Endoscopic one-way valve implantation in patients with prolonged air leak and the use of digital air leak monitoring.

Background: Prolonged alveolar-pleural air leaks are associated with increased morbidity and mortality. Endoscopic valve therapy has been recently introduced as a potential less invasive treatment option. We aimed at quantifying the effects of valve therapy on air leak flow and clinical outcomes in patients with prolonged air leaks.

MADMAX - Management and analysis database for multiple ~omics experiments.

The rapid increase of ~omics datasets generated by microarray, mass spectrometry and next generation sequencing technologies requires an integrated platform that can combine results from different ~omics datasets to provide novel insights in the understanding of biological systems. MADMAX is designed to provide a solution for storage and analysis of complex ~omics datasets. In addition, analysis results (such as lists of genes) will be merged to reveal candidate genes supported by all datasets.

Detection of integrin-linked kinase in the serum of patients with malignant pleural mesothelioma.

Objective: Integrin-linked kinase, which is relevant to neoplastic transformation, is highly expressed in malignant pleural mesothelioma. Recently, detection of integrin-linked kinase in serum of patients with ovarian cancer has been reported. This study asks whether integrin-linked kinase can also be detected in serum of patients with malignant pleural mesothelioma and whether serum level has diagnostic or prognostic relevance for that disease.

Integrin-linked kinase, phosphorylated AKT and the prognosis of malignant pleural mesothelioma.

Objective: Integrin-linked kinase (ILK) is a cell membrane-bound molecule implicated in the metastatic progression of many tumour types. It phosphorylates the downstream target AKT (phosphorylated AKT, pAKT), and, by doing this, it activates anti-apoptotic pathways. We have recently shown ILK expression in malignant pleural mesothelioma (MPM).

Concordance between epidermal growth factor receptor status in primary non-small-cell lung cancer and metastases: a post-mortem study.

Objectives: Epidermal growth factor receptor (EGFR)-targeted therapies are a valid therapeutic option for advanced non-small-cell lung cancer (NSCLC), but unequivocally recognised predictive factors for therapeutic response are lacking. However, intrinsic resistance might occur due to loss of EGFR expression during the course of the disease or its treatment.

Methods: Paraffin-embedded tissue from cases with metastatic NSCLC obtained at autopsy was retrieved from our archive.

Immunoreactivity of integrin-linked kinase in primary non-small-cell lung cancer and survival after curative resection.

Objective: Increased immunoreactivity of integrin-linked kinase (ILK) in the primary tumour is an adverse prognostic factor in a variety of preclinical and clinical models of human cancer. Here, we investigate the relationship between ILK immunoreactivity in primary non-small-cell lung cancer (NSCLC) and the survival after curative lung resection.

Methods: Tumour specimens of 138 radically operated NSCLC patients have been retrieved from the pathology archive, mounted in tissue microarrays and immunostained against ILK.

Primary synovial sarcoma of the lung as an incidental finding.

Synovial sarcoma of the lung (SSL) is a very rare but aggressive primary lung tumor. Due to its unusual histological features, it can easily be misdiagnosed, if only small biopsies of the tumor are investigated. Here, we review two recent cases of SSL diagnosed and treated in our institution.

Growing clinical evidence for the interaction of the p53 genotype and response to induction chemotherapy in advanced non-small cell lung cancer.

Objective: The objective of this study is to establish clinical evidence that the p53 genotype can serve as a predictive marker for response to cisplatin-based induction therapy.

Methods: Patients with advanced non-small cell lung cancer who had received neoadjuvant chemotherapy in the context of a prospective phase II trial were analyzed for the p53 genotype of their tumors. Response to induction therapy was then correlated to the p53 genotype as assessed by complete direct DNA sequencing.

Reactivity of integrin-linked kinase in human mesothelial cell proliferation.

Integrin-linked kinase (ILK) is a protein kinase that links integrins and growth factors to a range of signalling pathways. ILK expression and activity are increased in a variety of human cancers. However, little is known regarding the role of ILK in malignant pleural mesothelioma (MPM).

A pilot study testing whether concentrations of levofloxacin in interstitial space fluid of soft tissues may serve as a surrogate for predicting its pharmacokinetics in lung.

Recent observations indicate that pharmacokinetics of beta-lactam antibiotics in the lung can be predicted by the use of concentration versus time profiles in peripheral soft tissues. If this observation is transferred to other classes of antimicrobials, measurement of antimicrobial concentrations in peripheral tissues would enable prediction of the pharmacokinetics of antimicrobials at the site of the respiratory tract infection. We set out to test the hypothesis that concentrations of the fluoroquinolone levofloxacin in the respiratory tract can be predicted on the basis of knowledge of its pharmacokinetics in peripheral soft tissues.

Conformational change of membrane proteins leads to shape changes of red blood cells.

High-resolution atomic force microscopy (AFM) allows a new insight into the surface of mammalian cells. Using the human red blood cell (RBC) as a model, we have demonstrated an important correlation between the conformation of membrane proteins measured from the external face of the cell and the cell shape.

Evaluation of normal and neoplastic human mast cells for expression of CD172a (SIRPalpha), CD47, and SHP-1.

Signal regulatory proteins (SIRPs) and tyrosine phosphatases have recently been implicated in the control of receptor tyrosine kinase (RTK)-dependent cell growth. In systemic mastocytosis (SM), neoplastic cells are driven by the RTK KIT, which is mutated at codon 816 in most patients. We examined expression of SIRPalpha, SIRPalpha ligand CD47, and Src homology 2 domain-containing protein tyrosine phosphatase-1 (SHP-1), a tyrosine phosphatase-type, negative regulator of KIT-dependent signaling, in normal human lung mast cells (HLMC) and neoplastic MC obtained from nine patients with SM.

Using a dedicated lung-marker system for localization of pulmonary nodules before thoracoscopic surgery.

Objective: Our aim was to evaluate the effectiveness of a commercially available dedicated lung-marker system for localization of pulmonary nodules before video-assisted thoracoscopic surgery.

Subjects And Methods: Guidewires were positioned under CT fluoroscopy guidance in 16 patients (11 men, five women; age range, 39-79 years; mean age, 60.4 years).

Activation of human mast cells through stem cell factor receptor (KIT) is associated with expression of bcl-2.

Background: Mast cells (MCs) are multifunctional effector cells of the immune system. These cells originate from pluripotent hemopoietic progenitors. In contrast to basophils and other leukocytes, MCs exhibit a remarkably long life span (years) in vivo.

Simvastatin reduces expression of cytokines interleukin-6, interleukin-8, and monocyte chemoattractant protein-1 in circulating monocytes from hypercholesterolemic patients.

Objective: A number of studies have shown that statins decrease morbidity and mortality in patients with cardiovascular diseases. The anti-inflammatory effects of statins have recently been implicated in the clinical benefit that can be obtained in the treatment of atherosclerosis. Little is known about the mechanisms by which statins counteract inflammation.

Detection of novel CD antigens on the surface of human mast cells and basophils.

Background: Mast cells (MC) and basophils are effector cells of allergic reactions. Growth and function of these cells are regulated by a network of cytokines, other ligands, and respective cell surface membrane receptors.

Methods: In the present study, we examined the expression of novel CD antigens on human lung MC, skin MC, blood basophils, the MC line HMC-1, and the basophil cell line KU-812.

Closed-chest microdialysis to measure antibiotic penetration into human lung tissue.

The majority of bacterial lung infections are localized to the interstitial space fluid, which is therefore an important target site for antimicrobial chemotherapy. Direct measurement of interstitial concentrations of antimicrobial agents in human lung tissue would allow for a more informed approach to appropriate dosing of antimicrobial agents, but until now this was beyond technical reach. In this exploratory pharmacokinetic study, we measured the time versus concentration profile of cefpirome after a single intravenous dose administration of 2 g in the lung interstitial fluid by flexible microdialysis catheters, which were implanted during lung surgery for pulmonary tumors in five patients.