CECR2 drives breast cancer metastasis by promoting NF-κB signaling and macrophage-mediated immune suppression.

Metastasis is the major cause of cancer-related deaths due to the lack of effective therapies. Emerging evidence suggests that certain epigenetic and transcriptional regulators drive cancer metastasis and could be targeted for metastasis treatment. To identify epigenetic regulators of breast cancer metastasis, we profiled the transcriptomes of matched pairs of primary breast tumors and metastases from human patients. We found that distant metastases are more immune inert with increased M2 macrophages compared to their matched primary tumors. The acetyl-lysine reader, cat eye syndrome chromosome region candidate 2 (CECR2), was the top up-regulated epigenetic regulator in metastases associated with an increased abundance of M2 macrophages and worse metastasis-free survival. CECR2 was required for breast cancer metastasis in multiple mouse models, with more profound effect in the immunocompetent setting. Mechanistically, the nuclear factor κB (NF-κB) family member v-rel avian reticuloendotheliosis viral oncogene homolog A (RELA) recruits CECR2 to increase chromatin accessibility and activate the expression of their target genes. These target genes include multiple metastasis-promoting genes, such as TNC, MMP2, and VEGFA, and cytokine genes CSF1 and CXCL1, which are critical for immunosuppression at metastatic sites. Consistent with these results, pharmacological inhibition of CECR2 bromodomain impeded NF-κB-mediated immune suppression by macrophages and inhibited breast cancer metastasis. These results reveal that targeting CECR2 may be a strategy to treat metastatic breast cancer.

Pathogen Reduction: The State of the Science in 2019.

In the past 30 years, transfusion safety has increased substantially and blood transfusion is now a safer procedure than at any time in the past. Herein, we provide a comprehensive review of pathogen reduction, which is the new paradigm in transfusion safety. Specifically, we describe the various processes and technologies that are capable of diminishing or neutralizing infectious threats, including those that are not addressed or may not be detected by standard screening techniques. A special emphasis is placed on recent developments that are likely to impact patient care in 2019 and beyond.

How do we integrate pathogen reduced platelets into our hospital blood bank inventory?

For more than 50 years there has been an ongoing effort to combat transfusion-transmitted infections and provide patients with the safest possible blood. This initiative has driven much of the research within the transfusion community. Initial methods included screening donors for travel histories to banned areas and for high-risk behaviors, but pathogen-specific assays performed at the collection and manufacturing sites also have become key factors in assuring blood safety. Many of these have focused on donor and laboratory-based screening for transfusion-transmitted diseases, as evidenced by the hepatitis and human immunodeficiency virus screening in the 1970s, 1980s, and 1990s. More recently, this effort has expanded to develop donor screening assays to identify other blood-borne pathogens, such as Zika and West Nile viruses and Babesia. Bacterial contamination of units of platelets (PLTs), however, remains a significant concern. In recent years, the Food and Drug Administration has approved rapid tests to identify bacterially contaminated PLT units in the blood bank before transfusion. Other supplemental methods have been developed, however, that aim to inactivate blood-borne pathogen(s) present in the blood product, rather than to rely on our ability to identify and interdict contaminated and infected components. Pathogen reduction technology, as this is referred to, provides a proactive way to further reduce the risk posed by transfusion-transmitted infections.

The malleus cap: Anatomic description of cartilage of the lateral process of the malleus.

PURPOSE: To anatomically describe a cartilaginous cap attached to the lateral process of the malleus. STUDY DESIGN: Histologic and gross anatomic review. METHODS: Twenty temporal bones were histologically reviewed. The anatomical relationship between the tympanic membrane and malleus was then defined at the level of the lateral process of the malleus and the long process of the malleus. Separately, gross evaluation of these levels at the macroscopic level was undertaken through endoscopic imaging in five subjects. RESULTS: All temporal bones reviewed revealed the presence of a cartilaginous cap articulating between the tympanic membrane and the lateral process of the malleus. The cartilaginous cap was also readily identifiable in gross evaluation of the tympanic membrane from views lateral and medial to the tympanic membrane during endoscopic evaluation. CONCLUSION: The cartilaginous cap of the lateral process of the malleus is an important and reliable anatomical structure of the middle ear that has not previously been described. Through knowledge of the structure surgeons may exploit its presence by creating a cleavage plane between the cartilaginous cap and the malleus during tympanoplasty, possibly allowing for safer and more efficient surgery.

Hepatic Malignancy in an Infant with Wolf-Hirschhorn Syndrome.

INTRODUCTION: Wolf-Hirschhorn syndrome (WHS) is a contiguous gene syndrome involving deletions of the chromosome 4p16 region associated with growth failure, characteristic craniofacial abnormalities, cardiac defects, and seizures. CASE REPORT: This report describes a six-month-old girl with WHS with growth failure and typical craniofacial features who died of complex congenital heart disease. Genetic studies revealed a 9.8 Mb chromosome 4p-terminal deletion. At autopsy, the liver was grossly unremarkable. Routine sampling and histologic examination revealed two hepatocellular nodular lesions with expanded cell plates and mild cytologic atypia. Immunohistochemical staining revealed these nodules were positive for glutamine synthetase and glypican 3, with increased Ki-67 signaling and diffuse CD34 expression in sinusoidal endothelium. These findings are consistent with hepatoblastoma or hepatocellular carcinoma. CONCLUSIONS: A possible association between WHS and hepatic malignancy may be an important consideration in the care and management of WHS patients.