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Vor Einschluss in die Prostata (PCa)-Screeningstudie PROBASE hatten von 11.720 45-jährigen Männern 38,8% bereits eine digital-rektale Untersuchung, 17,4% eine PSA-Wert Messung erhalten. Diese Prozentsätze waren höher bei Männern mit positiver Krebs-Familienanamnese (FA) oder Krebs-Eigenanamnese (ohne PCa), mit Partner, höherem Schulabschluss bzw. privater Krankenversicherung. Probanden mit positiver erstgradiger PCa-FA (11,1%) hatten im Rahmen des Screenings tendenziell höhere PSA-Werte., Of 11.720 45-year-old men 38.8% had a digital rectal examination, 17.4% a PSA measurement prior to inclusion in the prostate cancer (PCa) screening trial PROBASE. Higher percentages were observed in men with a positive cancer history (without PCa) or cancer family history, a partner, higher school degree or a private health insurance. Men with a positive first-degree PCa family history (11.1%) had higher PSA levels.

Vor Einschluss in die Prostata (PCa)-Screeningstudie PROBASE hatten von 11.720 45-jährigen Männern 38,8% bereits eine digital-rektale Untersuchung, 17,4% eine PSA-Wert Messung erhalten. Diese Prozentsätze waren höher bei Männern mit positiver Krebs-Familienanamnese (FA) oder Krebs-Eigenanamnese (ohne PCa), mit Partner, höherem Schulabschluss bzw. privater Krankenversicherung. Probanden mit positiver erstgradiger PCa-FA (11,1%) hatten im Rahmen des Screenings tendenziell höhere PSA-Werte., Of 11.720 45-year-old men 38.8% had a digital rectal examination, 17.4% a PSA measurement prior to inclusion in the prostate cancer (PCa) screening trial PROBASE. Higher percentages were observed in men with a positive cancer history (without PCa) or cancer family history, a partner, higher school degree or a private health insurance. Men with a positive first-degree PCa family history (11.1%) had higher PSA levels.

Background: EGFR and its downstream signaling pathway are important targets for cancer therapy. Recently, the monoclonal anti-EGFR antibody Necitumumab in combination with gemcitabine and cisplatin was approved (EMA/14106/2016) for first-line treatment of squamous non-small cell carcinoma (SqNSCLC). Eligibility was restricted to cases with positive EGFR expression. In this context, a ring trial of the Quality Assurance Initiative for Pathology (QUIP (R)) was launched to prepare the German pathology community for a reliable and reproducible, immunohistochemically based biomarker test. Materials and methods: The trial was set up by a three-step approach. Two lead institutes were nominated to organize the trial process and to select appropriate cancer samples. These were first tested by the H-score (range 0-300) to identify positive and negative cases. Seven additional pathology institutes with experience in EGFR immunohistochemistry each tested the selected panel of identical cases (internal ring trial) to confirm the suitability of samples and scoring criteria. Then the open ring trial for all institutes of pathology in German speaking countries was announced. Results: For the internal trial 8 EGFR-positive and 2 negative lung sqNSCLC samples were selected. A cut-off value of cell membranous staining in >= 1% of tumor cells was introduced to define a case as EGFR negative or positive. Two points were attainable per correctly assessed sample leading to a maximum of 20 points, >= 18 points were required for a successful participation. All 7 panel institute passed this barrier, 5 with the maximum of 20 points and two with one error (18 points) being related to one case with incorrect interpretation of cytoplasmic versus membranous staining and one case with an H-score of 2 as being considered EGFR positive. A second cut-off value (H-score >= 3) was therefore introduced. In the open ring trial, 34 institutions participated of which 28 were successful according to the abo

Background: EGFR and its downstream signaling pathway are important targets for cancer therapy. Recently, the monoclonal anti-EGFR antibody Necitumumab in combination with gemcitabine and cisplatin was approved (EMA/14106/2016) for first-line treatment of squamous non-small cell carcinoma (SqNSCLC). Eligibility was restricted to cases with positive EGFR expression. In this context, a ring trial of the Quality Assurance Initiative for Pathology (QUIP (R)) was launched to prepare the German pathology community for a reliable and reproducible, immunohistochemically based biomarker test. Materials and methods: The trial was set up by a three-step approach. Two lead institutes were nominated to organize the trial process and to select appropriate cancer samples. These were first tested by the H-score (range 0-300) to identify positive and negative cases. Seven additional pathology institutes with experience in EGFR immunohistochemistry each tested the selected panel of identical cases (internal ring trial) to confirm the suitability of samples and scoring criteria. Then the open ring trial for all institutes of pathology in German speaking countries was announced. Results: For the internal trial 8 EGFR-positive and 2 negative lung sqNSCLC samples were selected. A cut-off value of cell membranous staining in >= 1% of tumor cells was introduced to define a case as EGFR negative or positive. Two points were attainable per correctly assessed sample leading to a maximum of 20 points, >= 18 points were required for a successful participation. All 7 panel institute passed this barrier, 5 with the maximum of 20 points and two with one error (18 points) being related to one case with incorrect interpretation of cytoplasmic versus membranous staining and one case with an H-score of 2 as being considered EGFR positive. A second cut-off value (H-score >= 3) was therefore introduced. In the open ring trial, 34 institutions participated of which 28 were successful according to the abo

Item does not contain fulltext, The rationale of alpha1-antitrypsin (AAT) augmentation therapy to treat progressive emphysema in AAT-deficient patients is based on inhibition of neutrophil elastase; however, the benefit of this treatment remains unclear. Here we show that clinical grade AAT (with elastase inhibitory activity) and a recombinant form of AAT (rAAT) without anti-elastase activity reduces lung inflammatory responses to LPS in elastase-deficient mice. WT and elastase-deficient mice treated with either native AAT or rAAT exhibited significant reductions in infiltrating neutrophils (23% and 68%), lavage fluid levels of TNF-alpha (70% and 80%), and the neutrophil chemokine KC (CXCL1) (64% and 90%), respectively. Lung parenchyma TNF-alpha, DNA damage-inducible transcript 3 and X-box binding protein-1 mRNA levels were reduced in both mouse strains treated with AAT; significantly lower levels of these genes, as well as IL-1beta gene expression, were observed in lungs of AAT-deficient patients treated with AAT therapy compared with untreated patients. In vitro, LPS-induced cytokines from WT and elastase-deficient mouse neutrophils, as well as neutrophils of healthy humans, were similarly reduced by AAT or rAAT; human neutrophils adhering to endothelial cells were decreased by 60-80% (P < 0.001) with either AAT or rAAT. In mouse pancreatic islet macrophages, LPS-induced surface expression of MHC II, Toll-like receptor-2 and -4 were markedly lower (80%, P < 0.001) when exposed to either AAT or rAAT. Consistently, in vivo and in vitro, rAAT reduced inflammatory responses at concentrations 40- to 100-fold lower than native plasma-derived AAT. These data provide evidence that the anti-inflammatory and immunomodulatory properties of AAT can be independent of elastase inhibition.

Item does not contain fulltext, The rationale of alpha1-antitrypsin (AAT) augmentation therapy to treat progressive emphysema in AAT-deficient patients is based on inhibition of neutrophil elastase; however, the benefit of this treatment remains unclear. Here we show that clinical grade AAT (with elastase inhibitory activity) and a recombinant form of AAT (rAAT) without anti-elastase activity reduces lung inflammatory responses to LPS in elastase-deficient mice. WT and elastase-deficient mice treated with either native AAT or rAAT exhibited significant reductions in infiltrating neutrophils (23% and 68%), lavage fluid levels of TNF-alpha (70% and 80%), and the neutrophil chemokine KC (CXCL1) (64% and 90%), respectively. Lung parenchyma TNF-alpha, DNA damage-inducible transcript 3 and X-box binding protein-1 mRNA levels were reduced in both mouse strains treated with AAT; significantly lower levels of these genes, as well as IL-1beta gene expression, were observed in lungs of AAT-deficient patients treated with AAT therapy compared with untreated patients. In vitro, LPS-induced cytokines from WT and elastase-deficient mouse neutrophils, as well as neutrophils of healthy humans, were similarly reduced by AAT or rAAT; human neutrophils adhering to endothelial cells were decreased by 60-80% (P < 0.001) with either AAT or rAAT. In mouse pancreatic islet macrophages, LPS-induced surface expression of MHC II, Toll-like receptor-2 and -4 were markedly lower (80%, P < 0.001) when exposed to either AAT or rAAT. Consistently, in vivo and in vitro, rAAT reduced inflammatory responses at concentrations 40- to 100-fold lower than native plasma-derived AAT. These data provide evidence that the anti-inflammatory and immunomodulatory properties of AAT can be independent of elastase inhibition.

Until recently, the division of pulmonary carcinomas into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) was adequate for therapy selection. Due to the emergence of new treatment options subtyping of NSCLC and predictive testing have become mandatory. A practical approach to the new requirements involving interaction between pulmonologist, oncologist and molecular pathology to optimize patient care is described. The diagnosis of lung cancer involves (i) the identification and complete classification of malignancy, (ii) immunohistochemistry is used to predict the likely NSCLC subtype (squamous cell vs. adenocarcinoma), as in small diagnostic samples specific subtyping is frequently on morphological grounds alone not feasible (NSCLC-NOS), (iii) molecular testing. To allow the extended diagnostic and predictive examination (i) tissue sampling should be maximized whenever feasible and deemed clinically safe, reducing the need for re-biopsy for additional studies and (ii) tissue handling, processing and sectioning should be optimized.Complex diagnostic algorithms are emerging, which will require close dialogue and understanding between pulmonologists and others who are closely involved in tissue acquisition, pathologists and oncologists who will ultimately, with the patient, make treatment decisions. Personalized medicine not only means the choice of treatment tailored to the individual patient, but also reflects the need to consider how investigative and diagnostic strategies must also be planned according to individual tumour characteristics. © 2011 Elsevier Ireland Ltd., SCOPUS: re.j, info:eu-repo/semantics/published

Until recently, the division of pulmonary carcinomas into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) was adequate for therapy selection. Due to the emergence of new treatment options subtyping of NSCLC and predictive testing have become mandatory. A practical approach to the new requirements involving interaction between pulmonologist, oncologist and molecular pathology to optimize patient care is described. The diagnosis of lung cancer involves (i) the identification and complete classification of malignancy, (ii) immunohistochemistry is used to predict the likely NSCLC subtype (squamous cell vs. adenocarcinoma), as in small diagnostic samples specific subtyping is frequently on morphological grounds alone not feasible (NSCLC-NOS), (iii) molecular testing. To allow the extended diagnostic and predictive examination (i) tissue sampling should be maximized whenever feasible and deemed clinically safe, reducing the need for re-biopsy for additional studies and (ii) tissue handling, processing and sectioning should be optimized.Complex diagnostic algorithms are emerging, which will require close dialogue and understanding between pulmonologists and others who are closely involved in tissue acquisition, pathologists and oncologists who will ultimately, with the patient, make treatment decisions. Personalized medicine not only means the choice of treatment tailored to the individual patient, but also reflects the need to consider how investigative and diagnostic strategies must also be planned according to individual tumour characteristics. © 2011 Elsevier Ireland Ltd., SCOPUS: re.j, info:eu-repo/semantics/published

Until recently, the division of pulmonary carcinomas into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) was adequate for therapy selection. Due to the emergence of new treatment options subtyping of NSCLC and predictive testing have become mandatory. A practical approach to the new requirements involving interaction between pulmonologist, oncologist and molecular pathology to optimize patient care is described. The diagnosis of lung cancer involves (i) the identification and complete classification of malignancy, (ii) immunohistochemistry is used to predict the likely NSCLC subtype (squamous cell vs. adenocarcinoma), as in small diagnostic samples specific subtyping is frequently on morphological grounds alone not feasible (NSCLC-NOS), (iii) molecular testing. To allow the extended diagnostic and predictive examination (i) tissue sampling should be maximized whenever feasible and deemed clinically safe, reducing the need for re-biopsy for additional studies and (ii) tissue handling, processing and sectioning should be optimized. Complex diagnostic algorithms are emerging, which will require close dialogue and understanding between pulmonologists and others who are closely involved in tissue acquisition, pathologists and oncologists who will ultimately, with the patient, make treatment decisions. Personalized medicine not only means the choice of treatment tailored to the individual patient, but also reflects the need to consider how investigative and diagnostic strategies must also be planned according to individual tumour characteristics.

Until recently, the division of pulmonary carcinomas into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) was adequate for therapy selection. Due to the emergence of new treatment options subtyping of NSCLC and predictive testing have become mandatory. A practical approach to the new requirements involving interaction between pulmonologist, oncologist and molecular pathology to optimize patient care is described. The diagnosis of lung cancer involves (i) the identification and complete classification of malignancy, (ii) immunohistochemistry is used to predict the likely NSCLC subtype (squamous cell vs. adenocarcinoma), as in small diagnostic samples specific subtyping is frequently on morphological grounds alone not feasible (NSCLC-NOS), (iii) molecular testing. To allow the extended diagnostic and predictive examination (i) tissue sampling should be maximized whenever feasible and deemed clinically safe, reducing the need for re-biopsy for additional studies and (ii) tissue handling, processing and sectioning should be optimized. Complex diagnostic algorithms are emerging, which will require close dialogue and understanding between pulmonologists and others who are closely involved in tissue acquisition, pathologists and oncologists who will ultimately, with the patient, make treatment decisions. Personalized medicine not only means the choice of treatment tailored to the individual patient, but also reflects the need to consider how investigative and diagnostic strategies must also be planned according to individual tumour characteristics.

In contemporary cryptographic systems, secret keys are usually exchanged by means of methods, which suffer from mathematical and technology inherent drawbacks. That could lead to unnoticed complete compromise of cryptographic systems, without a chance of control by its legitimate owners. Therefore a need for innovative solutions exists when truly and reliably secure transmission of secrets is required for dealing with critical data and applications. Quantum Cryptography (QC), in particular Quantum Key Distribution (QKD) can answer that need. The business white paper (BWP) summarizes how secret key establishment and distribution problems can be solved by quantum cryptography. It deals with several considerations related to how the quantum cryptography innovation could contribute to provide business effectiveness. It addresses advantages and also limitations of quantum cryptography, proposes a scenario case study, and invokes standardization related issues. In addition, it answers most frequently asked questions about quantum cryptography.

The report summarizes work done toward development and evaluation of an ultrasonic Doppler method for indirect measurement of arterial blood pressure in the aerospace environment. The systems developed were evaluated by observing the onset and disappearance of derived Doppler signals coincident with arterial opening motion, comparing systolic and diastolic pressures thus obtained to those acquired by auscultation and recording Korotkoff sounds, and by arterial catheterization. System tests were made with humans in laboratory, clinical, high airborne noise, high acceleration, and combat environments. Systolic and diastolic blood pressure values acquired from resting subjects in quiet environments with the ultrasonic Doppler system were 5 to 8 percent higher than those acquired by the conventional auscultatory method. Good data were acquired with the ultrasonic Doppler system in high level airborne noise environments where auscultation techniques were not usable. Tests made with patients in shock showed performance of the ultrasonic system to be superior to that of a Korotkoff sound system. The final ultrasonic Doppler blood pressure system consisted of a transducer-cuff assembly and a 2.25-pound electronics package, complete with rechargeable batteries. (Author)

This report summarizes work done in the development and evaluation of a recording incremental microflowmeter which will be applicable in studies of renal physiology, salivary gland physiology and rheologic study of lymph. The laboratory model has a stroke volume of 10 microliters and a maximum pumping rate of about 5700 microliters per minute with a demonstrated accuracy of 98 percent. Accumulated data are displayed on paper tape; both time and volume are recorded. Printout of accumulated volume occurs at 6-second intervals, and clearing occurs each minute. Elapsed time is recorded cumulatively on a minute basis. Pumping occurs when liquid level in the reservoir exceeds a critical level. Pumping rate is electronically controlled. The system requires about 175 watts of electrical power at 120 volts and 60 hertz. The laboratory model incremental microflowmeter was mounted in a 11 x 13 x 22-inch cabinet and weighs about 35 pounds. (Author)

NTRK gene fusions are sporadic genetic alterations that can occur across tumor entities. Whereas they are quite rare in most solid tumors they are present at much higher frequencies in certain rare tumors such as infantile fibrosarcoma, congenital mesoblastic nephroma, secretory breast, or salivary gland carcinoma. NTRK gene fusions or TRK fusion proteins are considered strong oncogenic drivers. If NTRK gene fusions are detected, TRK inhibitors such as entrectinib and larotrectinib can be used regardless of the tumor entity. So far only larotrectinib is approved in the European Union. Both drugs have been shown to be effective and well tolerated in phase I and phase II studies. The low prevalence of TRK fusion-positive cancers poses challenges for diagnostic and clinical work-flows. On one hand, patients with NTRK gene fusions should be identified; on the other hand, epidemiological, histological, and resource-related aspects have to be taken into account. Based on these premises, we suggest a diagnostic algorithm for TRK fusion cancers and present current data on TRK inhibitors.

NTRK gene fusions are sporadic genetic alterations that can occur across tumor entities. Whereas they are quite rare in most solid tumors they are present at much higher frequencies in certain rare tumors such as infantile fibrosarcoma, congenital mesoblastic nephroma, secretory breast, or salivary gland carcinoma. NTRK gene fusions or TRK fusion proteins are considered strong oncogenic drivers. If NTRK gene fusions are detected, TRK inhibitors such as entrectinib and larotrectinib can be used regardless of the tumor entity. So far only larotrectinib is approved in the European Union. Both drugs have been shown to be effective and well tolerated in phase I and phase II studies. The low prevalence of TRK fusion-positive cancers poses challenges for diagnostic and clinical work-flows. On one hand, patients with NTRK gene fusions should be identified; on the other hand, epidemiological, histological, and resource-related aspects have to be taken into account. Based on these premises, we suggest a diagnostic algorithm for TRK fusion cancers and present current data on TRK inhibitors.