Atypical femur fracture during bisphosphonate drug holiday: a case series.

Recent studies have noted an increased risk of low energy subtrochanteric and femoral shaft fractures termed "atypical femur fractures" (AFFs) associated with long-term bisphosphonate use. As such, many clinicians have begun recommending a "drug holiday" to reduce the risks associated with long-term bisphosphonate use. We present two cases of AFFs occurring during a 4-year or greater drug holiday following long-term bisphosphonate use. These findings highlight the need to reevaluate optimal bisphosphonate therapy duration, dosage, as well as initiation and duration of a drug holiday with continued monitoring in the prevention of AFFs.

Differential expression of interleukin-32 in chronic rhinosinusitis with and without nasal polyps.

BACKGROUND: Chronic rhinosinusitis (CRS) is a heterogeneous disease characterized by local inflammation of the upper airways and sinuses and is frequently divided into polypoid CRS (CRSwNP) and nonpolypoid CRS (CRSsNP). However, the mechanism of inflammation in CRS has still not been fully elucidated. The aim of the study was to investigate the role of interleukin-32 (IL-32), a recently discovered proinflammatory cytokine, in CRS. METHODS: We collected nasal epithelial cells and nasal tissue from patients with CRS and control subjects. We assayed mRNA for IL-32 by real-time PCR and measured IL-32 protein using ELISA, Western blot, and immunohistochemistry. RESULTS: The expression of mRNA for IL-32 was elevated in epithelial cells from uncinate tissue from patients with CRSsNP compared with patients with CRSwNP (P < 0.05), control subjects (P=0.06), and epithelial cells from nasal polyp (NP) tissue (P < 0.05). Production of IL-32 was induced by IFN-γ, TNF, and dsRNA in primary airway epithelial cells. In whole-tissue extracts, the expression of IL-32 protein was significantly elevated in patients with CRSwNP compared with patients with CRSsNP and control subjects. Immunohistochemistry data showed that IL-32 was detected in mucosal epithelial cells and inflammatory cells in the lamina propria. Levels of IL-32 were correlated with the levels of CD3 and macrophage mannose receptor in NP tissue. Immunofluorescence data showed IL-32 co-localization with CD3-positive T cells and CD68-positive macrophages in NPs. CONCLUSION: Overproduction of IL-32 may be involved in the pathogenesis of CRS, although the role of IL-32 in the inflammation in CRSsNP and CRSwNP may be different.

Local administration of carbon monoxide inhibits neointima formation in balloon injured rat carotid arteries.

Recent studies indicate that systemic induction of heme oxygenase-1 (HO-1), which oxidatively degrades heme into iron, biliverdin, and carbon monoxide (CO), or adenoviral-mediated gene transfer of HO-1 inhibits neointima formation after experimental vascular injury. In the present study, we investigated whether the acute, local administration of the HO-1 product, CO, regulates the arterial remodeling response following injury. Immediately after balloon injury of rat carotid arteries, a saturated solution of CO or nitrogen (N2), or phosphate buffered saline (PBS) was incubated luminally within the injured vessels for 30 min. Two weeks after injury, arteries exposed to CO exhibited significantly reduced neointimal area, neointimal area/medial wall area ratio, neointimal thickness, and medial wall area compared to arteries exposed to N2 or PBS. Arteries exposed to CO also demonstrated significantly reduced DNA synthesis in the medial wall two days after injury as suggested by proliferating cell nuclear antigen immunostaining, and this was associated with a decrease in the protein expression of the G1 cyclins, cyclin E and A, and transforming growth factor-beta1. These results indicate that the acute, local delivery of CO blocks the pathophysiological remodeling response to vascular injury, and identifies CO as a potentially important therapeutic agent in the treatment of vasculoproliferative disease.