The Association between Educational Attainment and Patterns of Emergency Department Utilization among Adults with Sickle Cell Disease.

PURPOSE: Patients with low educational attainment may be at increased risk for unplanned health care utilization. This study aimed to determine what factors are related to emergency department (ED) visits in hopes of guiding treatments and early interventions. METHODS: At two medical centers in the Mid-Atlantic United States, 258 adults with sickle cell disease aged 19-70 years participated in a retrospective study where we examined whether education level is independently associated with ED visits after accounting for other socioeconomic status (SES) variables, such as pain and disease severity and psychosocial functioning. RESULTS: The data showed that patients without a high school education visited the ED three times as frequently as patients with post secondary education. Controlling for poverty and employment status decreased the effect of education on ED visits by 33.24 %. Further controlling for disease severity and/or psychosocial functioning could not account for the remaining association between education and ED visits, suggesting that education is independently associated with potentially avoidable emergency care. CONCLUSIONS: Early interventions addressing disparities in academic performance, especially for those children most at risk, may lead to improved long-term health outcomes in this population.

Venous thromboembolism incidence in the Cooperative Study of Sickle Cell Disease.

BACKGROUND: Venous thromboembolism (VTE) has been recently recognized as a complication of sickle cell disease (SCD); however, the incidence of VTE in SCD is unknown. OBJECTIVES: The primary objective of this study was to determine the incidence of first VTE, including pulmonary embolism (PE) and deep vein thrombosis (DVT), among SCD patients age ≥ 15 years. We also evaluated genotypic differences in VTE risk and determined the relationship between VTE and mortality. PATIENTS/METHODS: In this retrospective cohort study, we used data from the Cooperative Study of Sickle Cell Disease (CSSCD) to calculate incidence rates for first VTE. We used Cox proportional hazard models to estimate hazard ratios (HRs) for time to VTE by genotype and time to death by VTE status. RESULTS: We included 1523 SCD patients aged ≥ 15 years with 8862 years of follow-up in this analysis. The incidence rate for first VTE was 5.2 events/1000 person-years (95% confidence interval [CI] 3.8-6.9) with a cumulative incidence of 11.3% (95% CI 8.3-15.3) by age 40 years. Individuals with the SS/Sß(0) -thalassemia genotype had the highest rate of VTE (7.6 events/1000 person-years [95% CI 5.3-10.6]). The incidence of PE exceeded that of isolated DVT (3.6 [95% CI 2.5-5.1] events/1000 person-years vs. 1.6 [95% CI 0.9-2.7] events/1000 person-years), although this difference was not statistically significant. SCD patients with VTE had a higher mortality rate (adjusted HR 2.32 [95% CI 1.20-4.46]) than those without VTE. CONCLUSIONS: Patients with SCD are at substantial risk for VTE, and individuals with VTE are at higher risk of death than those without VTE.

Dental infections increase the likelihood of hospital admissions among adult patients with sickle cell disease.

THE OBJECTIVE: To determine if dental infections increase the likelihood of hospital admission among adult patients with sickle cell disease (SCD). BASIC RESEARCH DESIGN: Cross-sectional analysis of data from the Nationwide Emergency Department Sample (NEDS) pooled for the years 2006 through 2008. Prevalence ratios (PR) for the effects of interest were estimated using Poisson regression with robust estimates of the variance. PARTICIPANTS: Adults, aged 18 and over, diagnosed with SCD using ICD-9-CM codes excluding participants discharged with a code for sickle cell trait. MAIN OUTCOME MEASURE: Emergency department (ED) visit disposition, dichotomised to represent whether or not the ED visit ended in admission versus being treated and released. RESULTS: Among patients having a sickle cell crisis, those with dental infections were 72% more likely to be admitted compared to those not having dental infections (PR = 1.72, 95% CI 1.58-1.87). No association was observed among adult SCD patients not having a sickle crisis event. Based on preliminary data from this analysis, prevention of dental infection among patients with SCD could result in an estimated cost saving of $2.5 million dollars per year. CONCLUSIONS: Having a dental infection complicated by a sickle cell crisis significantly increases the likelihood of hospital admission among adult SCD patients presenting to the ED.

Graft failure in a patient with systemic lupus erythematosus (SLE) treated with high-dose immunosuppression and autologous stem cell rescue.

A 32-year-old female with WHO grade IV, dialysis dependent, lupus nephritis was treated with high-dose immunosuppression and autologous stem cell rescue. Stem cells were mobilized with cyclophosphamide (CY) and G-CSF, and 4.07 x 10(6) CD34+ cells/kg were obtained after CD34+ cell selection using the CellPro column. The preparative regimen consisted of CY, and antithymocyte globulin (ATG), with methylprednisolone. After apparent primary engraftment of neutrophils on day 9, the patient developed recurrent neutropenia on day 19. She showed no evidence of engraftment by day 35, and back-up unmanipulated stem cells were given without effect. Subsequently, she received unmanipulated peripheral stem cells (2 x 10(6) CD34+ cells/kg) from an HLA-identical sibling. The patient remained pancytopenic and expired on day 62 from disseminated fungal infection. An autopsy revealed no evidence of hematopoietic recovery. Progenitor cell assays were performed with the patient's stem cells, which were collected prior to transplantation, and serum collected day 27. Morphologic examination of the patient's cell colonies grown in the presence of her serum revealed abnormal shapes and non-adherent cells. There were significantly fewer BFU-e colonies and a trend toward fewer CFU-GM colonies with the patient's cells and serum compared to normal donor cells. We concluded that a substance present in her serum mediated graft failure and prevented engraftment after additional stem cell infusions.

Homing of long-term and short-term engrafting cells in vivo.

Long-term repopulating hematopoietic stem cells can be separated from cells which provided radioprotection (short-term repopulating cells) on the basis of size. This might be a result of the quiescent nature of long-term repopulating cells. To define the activity of these populations we utilized a dye, PKH26, which incorporates into the membrane of cells and is equally distributed to daughter cells when they divide. We were able to retrieve PKH26(+)-labeled cells posttransplant in the hematopoietic tissues of the recipients. We could also assess their cell cycle status and their ability, short- and long-term, to reconstitute secondary lethally irradiated hosts in limiting dilution. The results suggest that long-term repopulating cells remain quiescent in the bone marrow shortly after engraftment, whereas cells which radioprotect are more rapidly dividing. We could not detect labeled cells in the peripheral blood posttransplant, and even though cells homed to both the spleen and bone marrow the cells in the bone marrow were significantly more competent at reconstituting lethally irradiated secondary hosts.

Ex-vivo expansion of bone marrow progenitor cells for hematopoietic reconstitution following high-dose chemotherapy for breast cancer.

The use of hematopoietic growth factors, stromal monolayers, and frequent medium exchange allows the expansion of hematopoietic progenitors ex-vivo. We evaluated the use of ex-vivo expanded progenitor cells for hematopoietic reconstitution following high dose chemotherapy (HDC) in breast cancer patients. Patients with high-risk Stage II or metastatic breast carcinoma underwent bone marrow aspirations using general anesthesia. A total of 675-1125 x 10(6) mononuclear cells (MNC) were seeded for ex-vivo expansion for 12 days in controlled perfusion bioreactors (Aastrom Biosciences, Inc.). The bone marrow cultures, which included the stromal cells collected with the aspirate, were supplemented with erythropoietin, granulocyte-macrophage-colony stimulating factor (GM-CSF)/IL-3 fusion protein (PIXY 321), and flt3 ligand. Stem cell transplant was performed with expanded cells after HDC. A median bone marrow volume of 52.9 mL (range 42-187 mL) was needed to inoculate the bioreactors. Median fold expansion of nucleated cells (NC) and colony forming unit granulocyte-macrophage (CFU-GM) was 4.9 and 9.5, respectively. The median fold expansion of CD34+lin- and long-term culture-initiating culture (LTC-IC) was 0.42 and 0.32, respectively. Five patients were transplanted with ex-vivo expanded NC. Median days to an absolute neutrophil count > 500/microL was 18 (range 15-22). Median days to a platelet count > 20,000/microl was 23 (range 19-39). All patients had sustained engraftment of both neutrophils and platelets. Immune reconstitution was similar to that seen after HDC and conventional stem cell transplantation. We conclude that ex-vivo expansion of progenitor cells from perfusion cultures of small volume bone marrow aspirates, allows hematopoietic reconstitution after HDC.

Hematopoietic stem cell tracking in vivo: a comparison of short-term and long-term repopulating cells.

We have previously demonstrated that we could separate long-term repopulating stem cells from cells that provided radioprotection (short-term repopulating cells) on the basis of size and suggested that this might be due to the quiescent nature of long-term repopulating cells. To further define the activity of these populations, we used a dye (PKH26), which incorporates into the membrane of cells and is equally distributed to daughter cells when they divide. We developed an assay, which allowed us to retrieve PKH26(+) long-term and short-term repopulating cells in the hematopoietic tissues of the recipients posttransplant. We were able to recover the labeled cells and determine their cell cycle activity, as well as their ability to reconstitute secondary lethally irradiated hosts in limiting dilution. The results of our assay suggest that long-term repopulating cells are quiescent in the bone marrow (BM) 48 hours after transplant. We were able to detect only a few labeled cells in the peripheral blood posttransplant and even though cells homed to both the spleen and BM, more long-term repopulating cells homed to the marrow and only these cells, which homed to the marrow, were capable of reconstituting lethally irradiated secondary hosts long-term.

Cytokine induction of platelet activation.

Recent studies have focused on the accumulation of cytokines in stored platelet concentrates and the role that these cytokines play in mediating transfusion reactions. To elucidate any additional adverse effects that may be associated with cytokine accumulation, the authors examined whether cytokines, which normally accumulate during routine platelet storage, can cause platelet activation in vitro. Concentrations of IL-6 and IL-8 were first determined for random donor platelet concentrates on days 1 through 4 of storage. Fresh platelets were then incubated with these levels of exogenous cytokines, and activation measured by flow cytometry using a monoclonal antibody directed against p-Selectin. Significant platelet activation was observed with concentrations of cytokines which are normally present in days 3 and 4 of shelf life. The study data demonstrate that levels of cytokines that routinely accumulate in stored platelet products can affect platelet biology. Strategies to reduce cytokine generation during platelet storage may be a method to improve the function and viability of stored platelets used for transfusion.

Regulation of pml messenger-RNA expression in human breast-carcinoma cells.

We examined the mRNA expression profile of PML, a novel nuclear protein recently characterized from acute promyelocytic leukemia (APL) blast cells, in a number of breast carcinoma cell lines. PML mRNA was found to be differentially expressed among the cell lines examined. A correlation of borderline significance between PML mRNA expression and the proliferative capacity of the cell Lines was noted. Serum stimulation significantly elevated the PML mRNA levels in the T47D and MDA-MB-231 cells. These results would suggest that PML may function as a positive regulator of cellular proliferation in breast carcinoma cells.