Unbiased screen for pathogens in human paraffin-embedded tissue samples by whole genome sequencing and metagenomics.

Identification of bacterial pathogens in formalin fixed, paraffin embedded (FFPE) tissue samples is limited to targeted and resource-intensive methods such as sequential PCR analyses. To enable unbiased screening for pathogens in FFPE tissue samples, we established a whole genome sequencing (WGS) method that combines shotgun sequencing and metagenomics for taxonomic identification of bacterial pathogens after subtraction of human genomic reads. To validate the assay, we analyzed more than 100 samples of known composition as well as FFPE lung autopsy tissues with and without histological signs of infections.

COVID-19 Autopsies Reveal Underreporting of SARS-CoV-2 Infection and Scarcity of Co-infections.

Coronavirus disease 2019 (COVID-19) mortality can be estimated based on reliable mortality data. Variable testing procedures and heterogeneous disease course suggest that a substantial number of COVID-19 deaths is undetected. To address this question, we screened an unselected autopsy cohort for the presence of SARS-CoV-2 and a panel of common respiratory pathogens.

High throughput sequencing reveals high specificity of TNFAIP3 mutations in ocular adnexal marginal zone B-cell lymphomas.

The majority of ocular adnexal (OA) lymphomas (OAL) are extranodal marginal zone lymphomas (MZL). First high throughput sequencing (HTS) studies on OA-MZL showed inconsistent results and the distribution of mutations in reactive lymphoid lesions of this anatomic region has not yet been sufficiently addressed. We characterized OAL and lymphoid lesions of the OA by targeted HTS.

[Pathology of infectious diseases].

Pathology of infectious diseases The pathology of infectious diseases is an exciting interdisciplinary field, despite its niche existence that is somewhat overshadowed by tumor diagnostics. However, the strength of pathology lies in the correlation of the inflammatory patterns and pathogen detection. Moreover, corresponding tissue investigations often allow a rapid diagnosis of the disease, and additional investigations, such as immunohistochemistry or molecular pathology, enable a rapid pathogen characterization with a high sensitivity and specificity.

Multi-fungal sepsis and mucormycosis of the central nervous system in a patient treated with ibrutinib, a case report and review of the literature.

We report the case of a 71 years old patient with chronic lymphocytic leukemia (CLL), who developed a rapidly progressing multi-fungal infection including mucormycosis of the central nervous system (CNS) during treatment with ibrutinib. On autopsy mucorales species were demonstrated intravascularly by histomorphology of several organs and lymph nodes and were characterized as by polymerase-chain reaction (PCR) - analysis. In addition, invasive pulmonary was found and also confirmed by PCR.

Brain abscess caused by Cladophialophora bantiana: Total remission after full resection and short-course Voriconazole treatment.

We report on a brain abscess in an immunocompetent man caused by , a black mold known to prefer the brain for abscess-formations with a mortality rate up to 65%. The published cases so far show different therapeutical approaches and outcomes, whereby a standardized treatment could not yet be established. We report on a case of brain abscess with total remission of the abscess after full resection and a short antifungal treatment.

Reconstitution of mammalian cleavage factor II involved in 3' processing of mRNA precursors.

Cleavage factor II (CF II) is a poorly characterized component of the multiprotein complex catalyzing 3' cleavage and polyadenylation of mammalian mRNA precursors. We have reconstituted CF II as a heterodimer of hPcf11 and hClp1. The heterodimer is active in partially reconstituted cleavage reactions, whereas hClp1 by itself is not.

Single-Center Experience with a Targeted Next Generation Sequencing Assay for Assessment of Relevant Somatic Alterations in Solid Tumors.

Companion diagnostics rely on genomic testing of molecular alterations to enable effective cancer treatment. Here we report the clinical application and validation of the Oncomine Focus Assay (OFA), an integrated, commercially available next-generation sequencing (NGS) assay for the rapid and simultaneous detection of single nucleotide variants, short insertions and deletions, copy number variations, and gene rearrangements in 52 cancer genes with therapeutic relevance. Two independent patient cohorts were investigated to define the workflow, turnaround times, feasibility, and reliability of OFA targeted sequencing in clinical application and using archival material.