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Cytomegalovirus (CMV) is the most common cause of congenital infection worldwide. We report on a fatal fetal manifestation of primary maternal CMV infection including cerebellar hemorrhage and hydrops. The diagnosis was established by maternal serological tests, culture and polymerase chain reaction testing of amniotic fluid and fetal blood. The pregnancy was terminated. Postmortem examination confirmed the diagnosis. [ABSTRACT FROM AUTHOR]

The article presents a case study of 66-year-old male patient who was HIV positive for more than 10 years and he was detected under therapy with tenofovir disaproxil fumarate, emtricitabine and norvir-boosted atazanavir. It mentions his histological examination revealed dense cell infiltrate of immunoblast-like cells with pale basophil cytoplasm and bulked chromatin nuclei with prominent-centred nucleoli. He was diagnosis with plasmoblastic lymphoma.

Hypomethylating agents (HMAs) are widely used in patients with higher-risk myelodysplastic syndromes (MDS) not eligible for stem cell transplantation; however, the response rate is <50%. Reliable predictors of response are still missing, and it is a major challenge to develop new treatment strategies. One current approach is the combination of azacytidine (AZA) with checkpoint inhibitors; however, the potential benefit of targeting the immunomodulator indoleamine-2,3-dioxygenase (IDO-1) has not yet been evaluated. We observed moderate to strong IDO-1 expression in 37% of patients with high-risk MDS. IDO-1 positivity was predictive of treatment failure and shorter overall survival. Moreover, IDO-1 positivity correlated inversely with the number of infiltrating CD8 + T cells, and IDO-1+ patients failed to show an increase in CD8 + T cells under AZA treatment. In vitro experiments confirmed tryptophan catabolism and depletion of CD8 + T cells in IDO-1+ MDS, suggesting that IDO-1 expression induces an immunosuppressive microenvironment in MDS, thereby leading to treatment failure under AZA treatment. In conclusion, IDO-1 is expressed in more than one-third of patients with higher-risk MDS, and is predictive of treatment failure and shorter overall survival. Therefore, IDO-1 is emerging as a promising predictor and therapeutic target, especially for combination therapies with HMAs or checkpoint inhibitors., (© 2020 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

The mitotic spindle assembly checkpoint (SAC) maintains genome stability and marks an important target for antineoplastic therapies. However, it has remained unclear how cells execute cell fate decisions under conditions of SAC-induced mitotic arrest. Here, we identify USP9X as the mitotic deubiquitinase of the X-linked inhibitor of apoptosis protein (XIAP) and demonstrate that deubiquitylation and stabilization of XIAP by USP9X lead to increased resistance toward mitotic spindle poisons. We find that primary human aggressive B-cell lymphoma samples exhibit high USP9X expression that correlate with XIAP overexpression. We show that high USP9X/XIAP expression is associated with shorter event-free survival in patients treated with spindle poison-containing chemotherapy. Accordingly, aggressive B-cell lymphoma lines with USP9X and associated XIAP overexpression exhibit increased chemoresistance, reversed by specific inhibition of either USP9X or XIAP. Moreover, knockdown of USP9X or XIAP significantly delays lymphoma development and increases sensitivity to spindle poisons in a murine Eμ-Myc lymphoma model. Together, we specify the USP9X-XIAP axis as a regulator of the mitotic cell fate decision and propose that USP9X and XIAP are potential prognostic biomarkers and therapeutic targets in aggressive B-cell lymphoma., (© 2016 The Authors. Published under the terms of the CC BY 4.0 license.)

Although targeting the Bruton tyrosine kinase (BTK) with ibrutinib has changed lymphoma treatment, patients with mantle cell lymphoma (MCL) remain incurable. In this study, we characterized a broad range of MCL cell lines and primary MCL cells with respect to the response to the BTK inhibitor, ibrutinib, and compared it with the response to the protein kinase C (PKC) inhibitor, sotrastaurin. At clinically relevant concentrations, each drug induced potent cell death only in the REC-1 cell line, which was accompanied by robust inhibition of AKT and ERK1/ERK2 (ERK1/2, also termed MAPK3/MAPK1) phosphorylation. In sensitive REC-1 cells, the drug-mediated impaired phosphorylation was obvious on the levels of B-cell receptor-induced and basal phosphorylation. Similar results were obtained in primary MCL cells with ibrutinib and in a subset with sotrastaurin. The various drug-resistant MCL cell lines showed very distinct responses in terms of basal AKT and ERK1/2 phosphorylation. Interestingly, targeting PKC and BTK at the same time led to ibrutinib-mediated rescue of a weak sotrastaurin-induced apoptosis in MINO cells. Additional targeting of AKT sensitized MINO cells to inhibitor-mediated cytotoxicity. In summary, MCL cells are heterogeneous in their response to BTK or PKC inhibition, indicating the need for even more individualized targeted treatment approaches in subsets of MCL patients., (© 2016 John Wiley & Sons Ltd.)

CXCR4 is a G-protein-coupled receptor that mediates recruitment of blood cells toward its ligand SDF-1. In cancer, high CXCR4 expression is frequently associated with tumor dissemination and poor prognosis. We evaluated the novel CXCR4 probe [(68)Ga]Pentixafor for in vivo mapping of CXCR4 expression density in mice xenografted with human CXCR4-positive MM cell lines and patients with advanced MM by means of positron emission tomography (PET). [(68)Ga]Pentixafor PET provided images with excellent specificity and contrast. In 10 of 14 patients with advanced MM [(68)Ga]Pentixafor PET/CT scans revealed MM manifestations, whereas only nine of 14 standard [(18)F]fluorodeoxyglucose PET/CT scans were rated visually positive. Assessment of blood counts and standard CD34(+) flow cytometry did not reveal significant blood count changes associated with tracer application. Based on these highly encouraging data on clinical PET imaging of CXCR4 expression in a cohort of MM patients, we conclude that [(68)Ga]Pentixafor PET opens a broad field for clinical investigations on CXCR4 expression and for CXCR4-directed therapeutic approaches in MM and other diseases., (© 2015 The Authors. Published under the terms of the CC BY 4.0 license.)

Objective: To evaluate a combined indocyanine green-enhanced optical imaging/radiography system for the detection of arthritic joints in a rat model of antigen-induced arthritis., Methods: Arthritis of the knee and ankle joints was induced in 6 Harlan rats, using peptidoglycan-polysaccharide polymers. Three rats served as untreated controls. Optical imaging of the knee and ankle joints was done with an integrated optical imaging/radiography system before and up to 24 hours following intravenous injection of 10 mg/kg indocyanine green. The fluorescence signal intensities of arthritic and normal joints were compared for significant differences, using generalized estimating equation models. Specimens of knee and ankle joints were further processed and evaluated by histology., Results: Immediately after administration, indocyanine green provided a significant increase in the fluorescence signal of arthritic joints compared with baseline values (P < 0.05). The fluorescence signal of arthritic joints was significantly higher compared with that of nonarthritic control joints at 1-720 minutes after intravenous injection (P < 0.05). Fusion of indocyanine green-enhanced optical imaging and radiography allowed for anatomic coregistration of the inflamed tissue with the associated joint. Hematoxylin and eosin staining confirmed marked synovial inflammation of arthritic joints and the absence of inflammation in control joints., Conclusion: Indocyanine green-enhanced optical imaging is a clinically applicable tool for detection of arthritic tissue. Using relatively high doses of indocyanine green, long-term enhanced fluorescence of arthritic joints can be achieved. This may facilitate simultaneous evaluations of multiple joints in a clinical setting. Fusion of indocyanine green-enhanced optical imaging scans with radiography increases anatomic resolution.