Variability in intraosseous flush practices of emergency physicians.

OBJECTIVE: Intramedullary pressure changes during intraosseous (IO) procedures have been implicated in the intravasation of bone marrow fat and with pain in conscious patients. The objective of this study was to demonstrate inter-provider variability in pressures generated during initial flush procedures. METHODS: IO cannulas were inserted into the proximal tibiae and humeri by study personnel. A second cannula was placed in the mid diaphysis of each bone to record intramedullary pressures. Fifteen emergency physicians performed 60 flushes in random order in two cadavers while flush duration and IO pressure were continuously recorded. Providers were blinded to the flush pressures they generated and the flush techniques of others. RESULTS: The median IO pressure (IOP) generated by providers was 903 mm Hg (range, 83-2941 mm Hg) and the median flush duration was 5.2 seconds (range, 1.0-13.4 seconds). Significant differences were noted among providers in peak IOP generated (analysis of variance P<.001). Providers were consistent in the forces they generated relative to each other. An inverse, nonlinear relationship was observed between flush duration and the peak IOP generated. Significant differences were noted in intramedullary flush pressures at flush sites within cadavers (analysis of variance P: cadaver #1 P<.001; cadaver #2 P=.012). CONCLUSIONS: The IO compartment pressures generated by physicians demonstrated significant interoperator variability with greater than 35-fold difference in flush forces, and an inverse relationship between intraosseous pressure and flush duration. It may be prudent practice for providers to extend the flush over several seconds, thus limiting maximal pressures.

Endometriosis presenting with hemorrhagic ascites, severe anemia, and shock.

Hemorrhagic ascites due to endometriosis is an exceedingly uncommon diagnosis rarely reported in the medical literature. We present a case of a 27-year-old woman who presented to the emergency department for flank and neck pain and was found to be hypotensive with massive hemorrhagic ascites and severe anemia. After emergency department resuscitation and hospitalization, her condition was found to be due to complications of endometriosis. A paracentesis of more than 4000 mL of bloody ascitic fluid revealed no evidence of cancer, and she was discharged on hospital day 3 with hormone therapy and no recurrence of symptoms upon outpatient follow-up. This case illustrates the clinical management, diagnostic approach, and underlying etiology of an infrequent but life-threatening complication of endometriosis.

Overwhelming post-splenectomy infection (OPSI): a case report and review of the literature.

BACKGROUND: Overwhelming post-splenectomy infection (OPSI) is a serious disease that can progress from a mild flu-like illness to fulminant sepsis in a short time period. Although relatively rare, it has a high mortality rate with delayed or inadequate treatment, and therefore, it is important for Emergency Physicians to be familiar with it. Patients who are asplenic or hyposplenic are at an increased risk for infection and death from encapsulated organisms and other dangerous pathogens. OBJECTIVES: There is an abundance of literature discussing OPSI from the perspective of hematologists and infectious disease specialists, but an Emergency Medicine perspective is necessary to truly understand the acute nature of the disease. The objective of this article is to present a careful examination of the literature with a focus on early diagnosis and management to provide Emergency Physicians with the ability to positively affect outcomes of this deadly disease. CASE REPORT: We present the case of a well-appearing 5-month-old girl with congenital asplenia who presented to the Emergency Department with fever, and rapidly progressed to septic shock as a result of OPSI. Aggressive resuscitation was initiated, including empiric antibiotics, and after a prolonged hospital course in the pediatric intensive care unit, the child recovered. CONCLUSION: Rapid identification of patients at risk for OPSI, followed by administration of intravenous antibiotics, usually vancomycin and ceftriaxone, combined with early goal-directed therapy, are the keys to successful treatment. If initiated early in the patient's course, the 70% mortality rate can be reduced to the 10-40% range.

Hyperactivation of p21ras and PI3K cooperate to alter murine and human neurofibromatosis type 1-haploinsufficient osteoclast functions.

Individuals with neurofibromatosis type 1 (NF1) have a high incidence of osteoporosis and osteopenia. However, understanding of the cellular and molecular basis of these sequelae is incomplete. Osteoclasts are specialized myeloid cells that are the principal bone-resorbing cells of the skeleton. We found that Nf1(+/-) mice contain elevated numbers of multinucleated osteoclasts. Both osteoclasts and osteoclast progenitors from Nf1(+/-) mice were hyperresponsive to limiting concentrations of M-CSF and receptor activator of NF-kappaB ligand (RANKL) levels. M-CSF-stimulated p21(ras)-GTP and Akt phosphorylation was elevated in Nf1(+/-) osteoclasts associated with gains of function in survival, proliferation, migration, adhesion, and lytic activity. These gains of function are associated with more severe bone loss following ovariectomy as compared with that in syngeneic WT mice. Intercrossing Nf1(+/-) mice and mice deficient in class 1(A) PI3K (p85alpha) restored elevated PI3K activity and Nf1(+/-) osteoclast functions to WT levels. Furthermore, in vitro-differentiated osteoclasts from NF1 patients also displayed elevated Ras/PI3K activity and increased lytic activity analogous to those in murine Nf1(+/-) osteoclasts. Collectively, our results identify a what we believe to be a novel cellular and biochemical NF1-haploinsufficient phenotype in osteoclasts that has potential implications for the pathogenesis of NF1 bone disease.

Nf1+/- mast cells induce neurofibroma like phenotypes through secreted TGF-beta signaling.

Neurofibromas are common tumors found in neurofibromatosis type 1 (NF1) patients. These complex tumors are composed of Schwann cells, mast cells, fibroblasts and perineurial cells embedded in collagen that provide a lattice for tumor invasion. Genetic studies demonstrate that in neurofibromas, nullizygous loss of Nf1 in Schwann cells and haploinsufficiency of Nf1 in non-neuronal cells are required for tumorigenesis. Fibroblasts are a major cellular constituent in neurofibromas and are a source of collagen that constitutes approximately 50% of the dry weight of the tumor. Here, we show that two of the prevalent heterozygous cells found in neurofibromas, mast cells and fibroblasts interact directly to contribute to tumor phenotype. Nf1+/- mast cells secrete elevated concentrations of the profibrotic transforming growth factor-beta (TGF-beta). In response to TGF-beta, both murine Nf1+/- fibroblasts and fibroblasts from human neurofibromas proliferate and synthesize excessive collagen, a hallmark of neurofibromas. We also establish that the TGF-beta response occurs via hyperactivation of a novel Ras-c-abl signaling pathway. Genetic or pharmacological inhibition of c-abl reverses fibroblast proliferation and collagen synthesis to wild-type levels. These studies identify a novel molecular target to inhibit neurofibroma formation.