RESUMO
Bacterial spinal epidural abscess (SEA) is a rare suppurative infection that commonly presents with nonspecific symptoms along with the infrequent triad of fever, back pain, and neurological deficits. Risk factors include diabetes mellitus, intravenous drug use, degenerative disc disease, infection with human immunodeficiency virus, and recent trauma or surgery. Patients with SEA often experience poor outcomes such as permanent neurological deficits, residual motor weakness, and even death. Staphylococcus aureus is the most predominant organism known to cause SEA; however, gram-negative bacteria are isolated in a small percentage of cases. Here we report three cases of SEA caused by gram-negative organisms. Each patient had identifiable risk factors known to increase the risk for SEA, and upon presentation had symptoms of SEA. Upon work up, the patients had positive cultures for gram-negative organisms and MRI imaging confirmed the presence of SEA. One patient made a full recovery while the other two cases resulted in permanent paraplegia. These cases stress the importance of considering SEA even in the presence of gram-negative infections, despite them being a rare cause. Furthermore, these cases emphasize the importance of broad-spectrum antibiotics that cover gram-negative bacteria in patients found to have risk factors along with symptoms of SEA.
RESUMO
Osteoporosis leads to reduced bone mass and disrupted bone architecture. Bisphosphonates are used to treat osteoporosis by inhibiting bone resorption. Chronic bisphosphonate use has been associated with adverse effects including atypical femoral fractures (AFF). We report the case of a 63-year-old woman with a history of osteoporosis treated with alendronate, who presented with bilateral hip and groin pain. Radiography detected a chronic-appearing callus in the left hip concerning for a chronic stress fracture versus malignancy. Initial imaging could not rule out malignancy, prompting positron emission tomography (PET) and bone biopsy. PET scan was negative for malignancy and biopsy found changes consistent with chronic bisphosphonate use. This prompted prophylactic intramedullary nailing of the femur. This case highlights the importance of considering AFF in patients with a history of hip pain in the setting of chronic BPs use and reviews criteria within the literature to manage patients with AFFs.
RESUMO
The epithelial-mesenchymal transition (EMT) endows carcinoma cells with phenotypic plasticity that can facilitate the formation of cancer stem cells (CSCs) and contribute to the metastatic cascade. While there is substantial support for the role of EMT in driving cancer cell dissemination, less is known about the intracellular molecular mechanisms that govern formation of CSCs via EMT. Here we show that ß2 and ß5 proteasome subunit activity is downregulated during EMT in immortalized human mammary epithelial cells. Moreover, selective proteasome inhibition enabled mammary epithelial cells to acquire certain morphologic and functional characteristics reminiscent of cancer stem cells, including CD44 expression, self-renewal, and tumor formation. Transcriptomic analyses suggested that proteasome-inhibited cells share gene expression signatures with cells that have undergone EMT, in part, through modulation of the TGF-ß signaling pathway. These findings suggest that selective downregulation of proteasome activity in mammary epithelial cells can initiate the EMT program and acquisition of a cancer stem cell-like phenotype. As proteasome inhibitors become increasingly used in cancer treatment, our findings highlight a potential risk of these therapeutic strategies and suggest a possible mechanism by which carcinoma cells may escape from proteasome inhibitor-based therapy.
