Evolutionary trajectories of small cell lung cancer under therapy.

The evolutionary processes that underlie the marked sensitivity of small cell lung cancer (SCLC) to chemotherapy and rapid relapse are unknown. Here we determined tumour phylogenies at diagnosis and throughout chemotherapy and immunotherapy by multiregion sequencing of 160 tumours from 65 patients. Treatment-naive SCLC exhibited clonal homogeneity at distinct tumour sites, whereas first-line platinum-based chemotherapy led to a burst in genomic intratumour heterogeneity and spatial clonal diversity.

Sublesional fat grafting leads to a temporary improvement of wound healing in chronic leg ulcers: A prospective, randomised clinical trial.

Chronic wounds remain a therapeutic and financial challenge for physicians and the health care systems. Innovative, inexpensive and effective treatment methods would be of immense value. The sublesional fat grafting could be such treatment, although effectiveness and safety have only been assessed in a few randomised clinical trials.

Sarcoidosis involvement of the diaphragm leading to right diaphragmatic elevation: a case report.

A 69-year-old male Caucasian presenting with dyspnea on exertion related to unilateral diaphragmatic dysfunction as caused by sarcoidosis is described. First, right diaphragmatic elevation was unexplained, while the patient presented with a restrictive pattern in lung function testing using bodyplethysmography and with reduced global and diaphragmatic respiratory muscle strength as evidenced by respiratory pressures. Subsequently, surgical diaphragm plication was performed, unfortunately, without any clinical improvement.

Comparison of Biocartis IDYLLA ™ cartridge assay with Qiagen GeneReader NGS for detection of targetable mutations in EGFR, KRAS/NRAS, and BRAF genes.

Lung and colorectal cancers (CRC) have two of the highest mortality rates among all cancer types, and their occurrence and the need for personalized diagnostics and subsequent therapy were not influenced by the COVID-19 pandemics. However, due to the disruption of established delivery chains, standard assays for in vitro diagnostics of those cancers were temporarily not available, forcing us to implement alternative testing methods that enabled at least basic therapy decision making. For this reason, we evaluated rapid testing on the Biocartis Idylla™ platform (Biocartis, Mechelen, Belgium) for four important genes commonly mutated in lung and colorectal cancers, namely EGFR, NRAS, KRAS, and BRAF.

Differential cytology profiles in bronchoalveolar lavage (BAL) in COVID-19 patients: A descriptive observation and comparison with other corona viruses, Influenza virus, Haemophilus influenzae, and Pneumocystis jirovecii.

Brochoalvelolar lavages (BALs) from patients suffering from hospitalized infections with SARS-CoV-2, other corona viruses (human coronavirus (HCoV)-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU1), Influenza virus type A and B, Haemophilus influenzae and Pneumocystis jirovecii were compared cytopathologically.The aim of the study was to evaluate if the cellular profile detectable in BAL may be specific for the respective pathogens and could lead to diagnosis of COVID-19 even in the absence of PCR results.Differential cytology and flow cytometry datasets of 62 patients were observed and compared.

Oncotype DX Breast Cancer recurrence score resists inter-assay reproducibility with RT-Profiler Multiplex RT-PCR.

The Oncotype Dx assay is frequently used to test if breast cancer patients can be spared from chemotherapy without negative effects for their future clinical course. However, due to conflicting data on the assay utility, in the recent past its reimbursement situation in Germany was revised; due to continued requests by clinicians for predictive values, our group decided to implement an Oncotype Dx like alternative assay with the objective of obtaining quality and cost optimization. Customized RT-Profiler assays covering the 21 gene panel of the Oncotype Dx assay were applied to a pilot cohort of breast cancer patients with known Oncotype Dx Recurrence Score (RS).

Association of the Human Bocavirus With Tonsil Squamous Cell Carcinomas.

The human bocavirus (HBoV) is known to persist latently in the infected host cells and seems to replicate its DNA via the DNA damage response system, which is frequently defect in tumors and correlates with microsatellite instability (MSI). Because HBoV is able to persist in the infected tissues, induces pro-fibrotic and pro- cancerogenic cytokines and , and is detected in colorectal and lung tumors, the virus may be involved in cancerogenesis at least as a cofactor. Recently it was shown that the adenotonsillar tissue is an important site of HBoV1 persistence and replication.

Human bocavirus is detected in human placenta and aborted tissues.

Background: To date, four human bocaviruses (HBoV) have been described. The most closely related viruses (bovine and canine parvoviruses) are associated with miscarriage in their hosts. The objective of this retrospective study was to determine the frequency of HBoV DNA in miscarriage.

NGS-dataset of putative driver mutations associated with benign peritoneal strumosis.

A rare case of benign peritoneal strumosis was screened for driver mutations in genes relevant to currently approved cancer therapies. Therefore, three formalin fixed paraffin embedded issue sections were screened with the GeneReader Actionable Insights NGS panel (Qiagen, Hilden, Germany) for the occurrence of driver mutations. Several mutations were identified in drug-targetable genes, such as ALK, EGFR, and BRAF.

Detailed overview on the mutations detected by and the sensitivity of the GeneReader NGS sequencing platform.

This article presents additional next generation data from our pre-clinical validation study. In total 121 samples (clinical specimen and interlaboratory test samples) were tested successfully with next generation sequencing. 38 different mutations in six different genes were detected.

Microsatellite instability testing in colorectal cancer using the QiaXcel advanced platform.

Background: Microsatellite instability (MSI) is a major predictive and diagnostic marker in several cancers including colorectal carcinomas. Diagnostic testing for microsatellites is generally performed using capillary sequencers, which requires expensive high-end equipment including expensive chemistry using fluorescent dyes labelling the PCR products of interest. In this study we have modified such a diagnostic protocol and established the microsatellite testing on the QiaXcel Advanced platform.

Pre-clinical validation of a next generation sequencing testing panel.

Objective: Next Generation Sequencing (NGS) has become a useful tool for gene mutation testing which is required for targeted therapies. The aim of this study was to validate the GeneRead QIAact Actionable Insights Tumor Panel (Qiagen) on the GeneReader System in a diagnostic laboratory setting.

Methods: The GeneRead QIAact Actionable Insights Tumor Panel allows the analysis of 773 variant positions in 12 genes (ALK, BRAF, EGFR, ERBB2, ERBB3, ESR1, KIT, KRAS, NRAS, PDGFRA, PIK3CA and RAF1).

Cost Saving Opportunities in NSCLC Therapy by Optimized Diagnostics.

With an incidence of 68 new cases per 100,000 people per year, an estimated total number of up to 350,000 new non-small-cell lung cancer (NSCLC) cases are diagnosed each year in the European Union. Up to 10% of NSCLC patients are eligible for therapy with novel ALK (anaplastic lymphoma kinase) inhibitors, as they have been diagnosed with a mutation in the gene coding for ALK. The ALK inhibitor therapy costs add up to approx.

Latent infection of human bocavirus accompanied by flare of chronic cough, fatigue and episodes of viral replication in an immunocompetent adult patient, Cologne, Germany.

Introduction: The human bocavirus (HBoV) is a parvovirus and is associated with mild to life-threatening acute or persisting respiratory infections, frequently accompanied by further pathogens. So far, there is limited knowledge on the mechanisms of persistence, and no reports on chronic infections or latency have been published so far.

Case Presentation: An immunocompetent male patient suffers from a chronic HBoV1 infection, i.

Pneumocystis jirovecii-induced chronic interstitial lung disease in Waldenström's macroglobulinemia.

Infections with Pneumocystis jirovecii can result in asymptomatic colonization or induce life threatening clinical symptoms. However, there appears to be a 'gray area' between colonization and severe pneumonia that remains underestimated so far. We describe a case with chronic interstitial lung disease and chronic cough that was attributed to P.

Fatal HBoV-1 infection in adult female cystic fibrosis patient.

A clinical case of fatal HBoV infection in an adult cystic-fibrosis patient awaiting lung transplantation is reported. The case is important as the genetic background of the underlying disease is congruent with the background of the sole permissive permanent cell culture CuFi-8 which originates also from a CF patient donor.

Presurgical mapping of basal cell carcinoma or squamous cell carcinoma by confocal laser endomicroscopy compared to traditional micrographic surgery: a single-centre prospective feasibility study.

Background: At present, no ideal diagnostic tools exist in the market to excise cancer tissue with the required safety margins and to achieve optimal aesthetic results using tissue-conserving techniques.

Objectives: In this prospective study, confocal laser endomicroscopy (CLE) and the traditional gold standard of magnifying glasses (MG) were compared regarding the boundaries of in vivo basal cell carcinoma and squamous cell carcinoma.

Materials & Methods: Tumour diameters defined by both methods were measured and compared with those determined by histopathological examination.

PD-L1 expression in non-small cell lung cancer: Correlations with genetic alterations.

Inhibition of the PD-1/PD-L1 pathway may induce anticancer immune responses in non-small cell lung cancer (NSCLC). Two PD-L1 immunohistochemistry (IHC) assays have been approved as companion diagnostic tests for therapeutic anti-PD-1 antibodies. However, many aspects of PD-L1 prevalence and association with genetically defined subtypes have not been addressed systematically.

Epidemiology of driver mutations in lung cancer in a German tertiary hospital in patients with testing indication.

Background: KRAS, BRAF, EGFR and ALK-mutation testing is a prerequisite for non-small-cell lung cancer treatments, but there remains limited epidemiological information about such mutations in German cohorts.

Materials & Methods: Between February 2010 and June 2015, a total of 1080 tumor samples from 1019 non-small-cell lung cancer patients were analyzed for KRAS, BRAF, EGFR and ALK-mutations by Therascreen-pyrosequencing and FISH.

Results: Mutation patterns differed dependent on the histological subtype and sex.

Low Titer Pneumocystis jirovecii Infections: More than Just Colonization?

Non-pneumonia colonization is thought to occur frequently in immunocompetent individuals. The aim was to analyze if low-titer detections have more impact than just colonization. From our total cohort of patients for which testing by qPCR was requested, we selected exclusively those that were fully immunocompetent.

Lung Infection by Human Bocavirus Induces the Release of Profibrotic Mediator Cytokines In Vivo and In Vitro.

Human Bocavirus subtype 1 (HBoV1) is associated with respiratory diseases and may contribute to chronic lung diseases by persisting in the infected host. Here the question was addressed if HBoV infections could contribute to fibrogenesis processes as suggested by previously published clinical observations. Cytokine profiles induced by HBoV infection in CuFi-8 air-liquid interphase cell cultures and in bronchoalveolar lavage fluid (BALF) of 20 HBoV-positive and 12 HBoV-negative patients were analysed by semi-quantitative Western spot blot analyses.

Case Report: Human Bocavirus Associated Pneumonia as Cause of Acute Injury, Cologne, Germany.

Although the human bocavirus (HBoV) is known since a decade, limited information about its pathogenesis is available due to the lack of an animal model. Thus, clinical cases and studies are the major source of novel information about the course of infection and the related pathophysiology.In this context, a clinical case of an adult patient suffering from severe HBoV-pneumonia is described that was associated with loss of consciousness followed by acute rib fracture and subsequent neurological disorder.

Spontaneous regression of non-small cell lung cancer after biopsy of a mediastinal lymph node metastasis: a case report.

Introduction: Spontaneous regression of cancer is defined as a complete or partial, temporary or permanent disappearance of tumor in the absence of specific therapy. With only a few cases reported, spontaneous regression is extremely rare in primary lung cancer. Regarding spontaneous regression in lung cancer, recent investigations revealed the role of immunological mechanisms, thus indicating potential treatment options by specific immunotherapy in the future.