Immunohistochemistry for c-myc and bcl-2 overexpression improves risk stratification in primary central nervous system lymphoma

Overexpression of bcl-2 and c-myc are defining features of double-expressor-lymphoma (DEL) but may also occur separately in patients with primary central nervous system lymphoma (PCNSL). Despite all progress in optimizing treatment regimen, there is lack of sufficient risk stratification models. Here, we first describe the relationship between DEL biology, the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI), treatment response, disease progression, and mortality in PCNSL. In this study, we determined c-myc and bcl-2 status immunohistochemically in samples of 48 patients with newly diagnosed PCNSL and followed these patients for a median interval of 6.2 years. Twelve, 18, and 17 patients harbored none, one, or both DEL features. Corresponding overall response rates after first-line therapy were strongly associated with DEL biology (100%, 42%, and 44% in patients with 0, 1, or 2 DEL features). Patients with one or both DEL features had a 5-fold and 13-fold higher 5-year risk of progression and/or death than patients without DEL features. These associations prevailed after adjusting for the NCCN-IPI. DEL improved the discriminatory capability of the NCCN-IPI (P = .0001). Furthermore, we could show that addition of DEL biology to the NCCN-IPI significantly improved the score's discriminatory potential both toward progression-free survival (increase in Harell's c = 0.15, P = .005) and overall survival (increase in Harell's c = 0.11, P = .029). In conclusion, DEL biology is a strong and simple-to-use predictor of adverse outcome in PCNSL. Addition of DEL to the NCCN-IPI improves its prognostic potential. Disease progression from PCNSL harboring both DEL features is invariably fatal. This defines a novel PCNSL patient subset with a great unmet need for improved therapy.     

Inpatient rehabilitation facilities’ hospital readmission rates for medicare beneficiaries treated following a stroke

ABSTRACT

Background

Stroke is the leading cause for admission to the nearly 1,200 Inpatient Rehabilitation Facilities (IRFs) nationally in the US. For many patients, post-acute care is an important component of their rehabilitation. Several quality measures have been publicly reported for post-acute care providers, including hospital readmissions. However, to date none have focused on specific medical conditions, limiting the usability for patients and quality improvement.     

Morphological measurements of anatomic landmarks in pulp chambers of human anterior teeth

This in vitro study measured key morphological features of pulp chambers in anterior teeth and tested the hypothesis that the distance from the lingual surface (midpoint from the cusp tip to the lingual CEJ) to the pulp chamber (the midpoint from the buccal to the lingual CEJ) was similar for different tooth types. Extracted human teeth were sorted and 100 samples of each of the following tooth types were chosen: maxillary central incisor (UCI), lateral incisor (ULI), and canine (UC), as well as mandibular central incisor (LCI), lateral incisor (LLI), and canine (LC). All teeth were digitally radiographed on a 1-mm X-ray grid. The mean values of measurement C, the distance from the lingual surface to the pulp chamber, varied significantly between tooth types (p<0.001). The mean values and SNK rankings were as follows: LC (5.9+/-0.5 mm)>UC (5.5+/-0.5)=UCI (5.4+/-0.4)>ULI (5.0+/-0.4)>LLI (4.8+/-0.5)>LCI (4.4+/-0.4).     

Chemically distinct stages in developing human fetal enamel

Chemical analyses and the appearance of developing enamel from maxillary first incisors of human fetuses aged 5–9 months distinguished two stages during this period of development. The first corresponded to the production of forming enamel, which was soft, translucent and partially mineralized, and the second to the maturation or secondary mineralization of enamel. The final stage in enamel development, i.e. the mature, hard enamel is, however, generally absent in the tooth of the 9 month old fetus. The concentrations of P and Ca of the forming enamel in the tooth axis did not change significantly, varying between 9–12 and 21–26 per cent by weight, respectively. However, the P and Ca concentrations rose steeply across the boundary between the forming and the maturing enamel to reach a maximum value of 17 and 35 per cent, respectively, in the second stage.     

Application of salivary noncoding microRNAs for the diagnosis of oral cancers

Oral cancer is on the rise globally and survival rates, despite improvements in clinical care, have not significantly improved. Early detection followed by immediate intervention is key to improving patient outcomes. The use of biomarkers has changed the diagnostic landscape for many cancers. For oral cancers, visual inspection followed by a tissue biopsy is standard practice. The discovery of microRNAs as potential biomarkers has attracted clinical interest but several challenges remain. These microRNAs can be found in bodily fluids such as blood and saliva which have been investigated as potential sources of biomarker discovery. As oral cancer is localized within the oral cavity, saliva may contain clinically relevant molecular markers for disease detection. Our review provides an outline of the current advances for the application of salivary microRNAs in oral cancer. We also provide a technical guide for the processing of salivary RNAs to ensure accurate clinical measurement and validation.