RESUMEN
COVID-19 results in increased expression of inflammatory cytokines, but inflammation-targeting clinical trials have yielded poor to mixed results. Our studies of other disorders with an inflammatory component, including Alzheimer's disease, chemobrain, Down syndrome, normal aging, and West Nile Virus infection, showed that treatment with the 'pro-inflammatory' cytokine granulocyte-macrophage colony stimulating factor (GM-CSF) in humans or mouse models alleviated clinical, behavioral, and pathological features. We proposed that human recombinant GM-CSF (sargramostim) be repurposed to promote both the innate and adaptive immune responses in COVID-19 to reduce viral load and mortality1. Here, we report the results of a placebo-controlled study of GM-CSF in human ACE2 transgenic mice inoculated intranasally with SARS-CoV2 virus, a model of COVID-19. Infection resulted in high viral titers in lungs and brains and over 85% mortality. GM-CSF treatment beginning one day after infection increased anti-viral antibody titers, lowered mean lung viral titers proportionately (p=0.0020) and increased the odds of long-term survival by up to 5.8-fold (p=0.0358), compared to placebo. These findings suggest that, as an activator of both the innate and adaptive immune systems, GM-CSF/sargramostim may be an effective COVID-19 therapy with the potential to protect from re-infection more effectively than treatment with antiviral drugs or monoclonal antibodies.
RESUMEN
Pigmented villonodular synovitis affecting the hip is rare. Seven new patients are presented and 117 cases from the literature are reviewed. Among the new patients, two refused treatment; in one patient, severe bone loss was observed after a radiographic followup of 21 years; the second patient showed no radiographic changes 2 years after diagnosis. One patient underwent a synovectomy and had a recurrence 9 years later, requiring a total hip replacement. The remaining four patients underwent synovectomy and primary total hip replacement with no recurrences detected after an average followup of 13 years (range, 2-23 years). Among 117 cases published, 62 patients (53%) did not have enough information for analysis. A metaanalysis using the remaining 55 patients was done. In nine patients (16%; nine of 55) the diagnosis was made with a preoperative biopsy. Treatment consisted of synovectomy in 26 patients (47%; 26 of 55), arthroplasty in 24 (43%; 24 of 55), arthrodesis in two (4%; two of 55), and hindquarter amputation in a patient misdiagnosed as having synovial sarcoma (2%; one of 55). Two patients (4%; two of 55) were not treated. Ten patients had a recurrence (19%; 10 of 53); nine in the synovectomy group (35 %; nine of 26) and one in the joint replacement group (4%; one of 24). Synovectomy is recommended for patients with preserved articular cartilage and total hip replacement is recommended for patients with secondary osteoarthritis. Removal of all macroscopic tumors including careful curetting of the osteolytic lesions should be done as they may constitute a source of recurrence.