Podoplanin discriminates distinct stromal cell populations and a novel progenitor subset in the liver.

Podoplanin/gp38(+) stromal cells present in lymphoid organs play a central role in the formation and reorganization of the extracellular matrix and in the functional regulation of immune responses. Gp38(+) cells are present during embryogenesis and in human livers of primary biliary cirrhosis. Since little is known about their function, we studied gp38(+) cells during chronic liver inflammation in models of biliary and parenchymal liver fibrosis and steatohepatitis. Gp38(+) cells were analyzed using flow cytometry and confocal microscopy, and the expression of their steady state and inflammation-associated genes was evaluated from healthy and inflamed livers. Gp38(+) cells significantly expanded in all three models of liver injury and returned to baseline levels during regression of inflammation. Based on CD133 and gp38 expression in the CD45(-)CD31(-)Asgpr1(-) liver cell fraction, numerous subsets could be identified that were negative for CD133 (gp38(hi)CD133(-), gp38(low)CD133(-), and gp38(-)CD133(-)). Moreover, among the CD133(+) cells, previously identified as progenitor population in injured liver, two subpopulations could be distinguished based on their gp38 expression (gp38(-)CD133(+) and CD133(+)gp38(+)). Importantly, the distribution of the identified subsets in inflammation illustrated injury-specific changes. Moreover, the gp38(+)CD133(+) cells exhibited liver progenitor cell characteristics similar to the gp38(-)CD133(+) population, thus representing a novel subset within the classical progenitor cell niche. Additionally, these cells expressed distinct sets of inflammatory genes during liver injury. Our study illuminates a novel classification of the stromal/progenitor cell compartment in the liver and pinpoints a hitherto unrecognized injury-related alteration in progenitor subset composition in chronic liver inflammation and fibrosis.

A Case of Pseudomonas straminea Blood Stream Infection in an Elderly Woman with Cellulitis.

Here, we report the simultaneous isolation of Pseudomonas straminea from blood cultures and from a skin ulcer in an elderly woman who suffered from atopic dermatitis and psoriasis and developed acute cellulitis of both arms requiring hospital treatment. To the best of our knowledge, P. straminea has not been previously reported to cause invasive infections in humans. This case highlights how chronic diseases and older age increase the susceptibility to bacterial infections with environmental bacteria of low virulence. Our study describes the microbiological identification of the blood culture isolate, including morpho-molecular characterization and virulence demonstration in a Galleria mellonella model.

Case report: Disseminated gonococcal infection, a story of camouflage and deceit.

We report on a 38-year-old male patient with disseminated gonococcal infection. Preceding the discharge diagnosis, the patient was treated regarding rheumatoid arthritis, which resulted in the deterioration of the patient's medical condition due to the immunomodulatory nature of the applied medication. The causative agent was identified by culturing joint puncture fluid inoculated into blood culture vials. Primary infection with the pathogen could not be pinpointed in terms of time, but on further questioning, the patient reported intimate contacts with a number of different male partners, which may be assumed to have included the infection source. The case hereby demonstrates the impact that an early misdiagnosis and a limited anamnesis can have on the progress of a patient's disease. Furthermore, this case has helped us to propose possible improvements in both clinical and microbiological diagnostic approaches.

Hospital sanitary facilities on wards with high antibiotic exposure play an important role in maintaining a reservoir of resistant pathogens, even over many years.

BACKGROUND: Hospitals with their high antimicrobial selection pressure represent the presumably most important reservoir of multidrug-resistant human pathogens. Antibiotics administered in the course of treatment are excreted and discharged into the wastewater system. Not only in patients, but also in the sewers, antimicrobial substances exert selection pressure on existing bacteria and promote the emergence and dissemination of multidrug-resistant clones. In previous studies, two main clusters were identified in all sections of the hospital wastewater network that was investigated, one K. pneumoniae ST147 cluster encoding NDM- and OXA-48 carbapenemases and one VIM-encoding P. aeruginosa ST823 cluster. In the current study, we investigated if NDM- and OXA-48-encoding K. pneumoniae and VIM-encoding P. aeruginosa isolates recovered between 2014 and 2021 from oncological patients belonged to those same clusters. METHODS: The 32 isolates were re-cultured, whole-genome sequenced, phenotypically tested for their antimicrobial susceptibility, and analyzed for clonality and resistance genes in silico. RESULTS: Among these strains, 25 belonged to the two clusters that had been predominant in the wastewater, while two others belonged to a sequence-type less prominently detected in the drains of the patient rooms. CONCLUSION: Patients constantly exposed to antibiotics can, in interaction with their persistently antibiotic-exposed sanitary facilities, form a niche that might be supportive for the emergence, the development, the dissemination, and the maintenance of certain nosocomial pathogen populations in the hospital, due to antibiotic-induced selection pressure. Technical and infection control solutions might help preventing transmission of microorganisms from the wastewater system to the patient and vice versa, particularly concerning the shower and toilet drainage. However, a major driving force might also be antibiotic induced selection pressure and parallel antimicrobial stewardship efforts could be essential.

Tumour-associated circulating microparticles: A novel liquid biopsy tool for screening and therapy monitoring of colorectal carcinoma and other epithelial neoplasia.

Up to date, novel tools for low-cost, minimal invasive cancer surveillance, cancer screening and treatment monitoring are in urgent need. Physicians consider the so-called liquid biopsy as a possible future tool successfully achieving these ultimate goals. Here, we aimed to identify circulating tumour-associated MPs (taMPs) that could aid in diagnosing minimal-invasively the presence and follow up treatment in non-small cell lung carcinoma (NSCLC), colorectal carcinoma (CRC) and pancreas carcinoma (PaCa). Tumour-associated MPs (taMPs) were quantified after isolation by centrifugation followed by flow cytometry analysis from the serum of cancer patients with CRC (n = 52), NSCLC (n = 40) and PaCa (n = 11). Healthy subjects (n = 55) or patients with struma nodosa (thyroid nodules) (n = 43) served as negative controls. In all three types of tumour entities, the presence of tumour was associated with an increase of circulating EpCAM+ and EpCAM+CD147+ taMPs. The presence of CD147+EpCAM+ taMPs were specific to tumour-bearing patients thus allowing the specific distinction of malignancies from patients with thyroid nodules. Increased level of EpCAM single positive MPs were, in turn, also detected in patients with thyroid nodules. Importantly, EpCAM+CD147+ taMPs correlated with the measured tumour-volume in CRC patients. EpCAM+ taMPs decreased at 7 days after curative R0 tumour resection suggesting a close dependence with tumour presence. AUROC values (up to 0.85 and 0.90), sensitivity/specificity scores, and positive/negative predictive values indicated a high diagnostic accuracy of EpCAM+CD147+ taMPs. Taken together, EpCAM+CD147+ double positive taMPs could potentially serve as novel promising clinical parameter for cancer screening, diagnosis, surveillance and therapy monitoring.

The complex myeloid network of the liver with diverse functional capacity at steady state and in inflammation.

In recent years, it has been an explosion of information regarding the role of various myeloid cells in liver pathology. Macrophages and dendritic cell (DC) play crucial roles in multiple chronic liver diseases such as fibrosis and non-alcoholic fatty liver disease (NAFLD). The complexity of myeloid cell populations and the missing exclusive marker combination make the interpretation of the data often extremely difficult. The current review aims to summarize the multiple roles of macrophages and DCs in chronic liver diseases, especially pointing out how these cells influence liver immune and parenchymal cells thereby altering liver function and pathology. Moreover, the review outlines the currently known marker combinations for the identification of these cell populations for the study of their role in liver immunology.