Isolated hepatic sarcoidosis: A case series.

Sarcoidosis is a multi-organ inflammatory disease that can have hepatic involvement in up to 80% of cases. Rarely, sarcoidosis can manifest with only confined disease to the liver. While most patients with hepatic sarcoidosis are clinically silent, certain cases can have insidious onset leading to cirrhosis and secondary complications. Here, we describe three cases of isolated hepatic sarcoidosis to illustrate the range of presentations that may be associated with this condition. Clinicians should be vigilant in consideration of hepatic sarcoidosis as a culprit when investigating patients with undifferentiated liver disease.

The Hydroxypyridinone Iron Chelator DIBI Reduces Bacterial Load and Inflammation in Experimental Lung Infection.

Iron plays a critical role in lung infections due to its function in the inflammatory immune response but also as an important factor for bacterial growth. Iron chelation represents a potential therapeutic approach to inhibit bacterial growth and pathologically increased pro-inflammatory mediator production. The present study was designed to investigate the impact of the iron chelator DIBI in murine lung infection induced by intratracheal Pseudomonas aeruginosa (strain PA14) administration. DIBI is a polymer with a polyvinylpyrrolidone backbone containing nine 3-hydroxy-1-(methacrylamidoethyl)-2-methyl-4(1H) pyridinone (MAHMP) residues per molecule and was given by intraperitoneal injection either as a single dose (80 mg/kg) immediately after PA14 administration or a double dose (second dose 4 h after PA14 administration). The results showed that lung NF-κBp65 levels, as well as levels of various inflammatory cytokines (TNFα, IL-1ß, IL-6) both in lung tissue and bronchoalveolar lavage fluid (BALF), were significantly increased 24 h after PA14 administration. Single-dose DIBI did not affect the bacterial load or inflammatory response in the lungs or BALF. However, two doses of DIBI significantly decreased bacterial load, attenuated NF-κBp65 upregulation, reduced inflammatory cytokines production, and relieved lung tissue damage. Our findings support the conclusion that the iron chelator, DIBI, can reduce lung injury induced by P. aeruginosa, via its anti-bacterial and anti-inflammatory effects.

The 1000 Mitoses Project: A Consensus-Based International Collaborative Study on Mitotic Figures Classification.

Introduction. The identification of mitotic figures is essential for the diagnosis, grading, and classification of various different tumors. Despite its importance, there is a paucity of literature reporting the consistency in interpreting mitotic figures among pathologists. This study leverages publicly accessible datasets and social media to recruit an international group of pathologists to score an image database of more than 1000 mitotic figures collectively. Materials and Methods. Pathologists were instructed to randomly select a digital slide from The Cancer Genome Atlas (TCGA) datasets and annotate 10-20 mitotic figures within a 2 mm2 area. The first 1010 submitted mitotic figures were used to create an image dataset, with each figure transformed into an individual tile at 40x magnification. The dataset was redistributed to all pathologists to review and determine whether each tile constituted a mitotic figure. Results. Overall pathologists had a median agreement rate of 80.2% (range 42.0%-95.7%). Individual mitotic figure tiles had a median agreement rate of 87.1% and a fair inter-rater agreement across all tiles (kappa = 0.284). Mitotic figures in prometaphase had lower percentage agreement rates compared to other phases of mitosis. Conclusion. This dataset stands as the largest international consensus study for mitotic figures to date and can be utilized as a training set for future studies. The agreement range reflects a spectrum of criteria that pathologists use to decide what constitutes a mitotic figure, which may have potential implications in tumor diagnostics and clinical management.