Best practices for transfusion for patients with sickle cell disease

The β-globin gene mutation in sickle cell anemia results in anemia and repeated bouts of vascular occlusion. The cumulative effect of these vasocclusive events is progressive damage to many organs including the kidneys, lungs, and brain. The transfusion of red blood cells (RBC) can ameliorate many of these complications, but can be associated with both acute and chronic complications, including iron overload. The objective of the Best Practices in Transfusion Medicine for Patients with Sickle Cell Disease (SCD) Conference was to review the available published evidence and clinical experience surrounding the use of RBC transfusions for sickle cell disease by a panel of experts. The expert panel developed explicit clinical guidelines for the use of RBC in SCD patients. The panel also made recommendations for further research. A set of guidelines were produced for dissemination to pertinent stakeholders. If implemented, these clinical pathways have the potential to optimize the use of red blood cell transfusions in SCD

A single-blind, dose escalation, phase I study of high-fluence light-emitting diode-red light (LED-RL) on human skin: study protocol for a randomized controlled trial

SPIRIT checklist. (PDF 502 kb

Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS): a 24-year clinical experience with 178 patients

BACKGROUND: Thrombotic thrombocytopenic purpura and the hemolytic uremic syndrome (TTP-HUS) are related and uncommon disorders with a high fatality and complication rate if untreated. Plasma exchange therapy has been shown to produce high response rates and improve survival in patients with many forms of TTP-HUS. We performed a retrospective cohort study of 178 consecutively treated patients with TTP-HUS and analyzed whether clinical or laboratory characteristics could predict for important short- and long-term outcome measures. RESULTS: Overall 30-day mortality was 16% (n = 27). 171 patients (96%) received plasma exchange as the principal treatment, with a mean of 8 exchanges and a mean cumulative infused volume of 42 ± 71 L of fresh frozen plasma. The rate of complete response was 65% or 55% depending on whether this was defined by a platelet count of 100,000/μl or 150,000/μl, respectively. The rate of relapse was 18%. The Clinical Severity Score did not predict for 30-day mortality or relapse. The time to complete response did not predict for relapse. Renal insufficiency at presentation was associated with a decreased risk of relapse, with each unit increase in serum creatinine associated with a 40% decreased odds of relapse. 72% of our cohort had an idiopathic TTP-sporadic HUS, while 17% had an underlying cancer, received a solid organ transplant or were treated with a mitomycin-based therapy. The estimated overall 5-year survival was 55% and was significantly better in those without serious underlying conditions. CONCLUSION: Plasma exchange therapy produced both high response and survival rates in this large cohort of patients with TTP-HUS. The Clinical Severity Score did not predict for 30-day mortality or relapse, contrary to our previous findings. Interestingly, the presence of renal insufficiency was associated with a decreased risk of relapse. The most important predictor of mortality was the presence or absence of a serious underlying disorder

Multiplexed measurements of immunomodulator levels in peripheral blood of healthy subjects: Effects of analytical variables based on anticoagulants, age, and gender

Multiplex microbead immunoassay (MMIA) is a powerful technology for a wide range of biomedical and clinical applications. It is important to study the normal concentration ranges of immunomodulators under different sample preparation conditions and age groups of subjects in order to more precisely determine their reference values for use in assessing alterations of their levels in disease. The aim of this study was to determine the plasma concentrations of immunomodulators (cytokines, chemokines, and growth factors) in the peripheral blood from healthy subjects by the use of a large multiplex panel, and to determine the effects of different anticoagulants, age, and gender on the immunomodulator levels. In addition, the assay precision for these biomarker analytes was determined. Plasma samples from 107 healthy subjects, aged 18 to 85 years, were collected in three different anticoagulants (sodium citrate, EDTA, Heparin); corresponding serum samples were also obtained. Multiplex microbead immunoassays were performed for measuring a total of 23 analytes including chemokines, cytokines, and growth factors (IL-1β, IL-1ra, IL-2, IL-6, IL-7, IL-8, IL-12 p70, IL-17, IFN-γ, IP-10, MCP-1, PDGF-BB, RANTES, TNF-α, IL-1a, IL-16, HGF, MIG, TNF-β, PDGF-ABBB, EGF, Flt-3 Ligand, VEGF). For these analytes, our results showed that the anticoagulant affected the concentration measurements and the coefficients of variation. However, the relative levels of the analytes (profiles) of samples collected in a particular anticoagulant are consistent. The analytes IL-1β, IL-7, Flt-3 Ligand, and IL-12p70 show the largest variation (up to fourfold) between the age groups. In addition, no statistically significant differences in the level of the analytes were found between the sexes

Phase 1 Study of the E-Selectin Inhibitor GMI 1070 in Patients with Sickle Cell Anemia

Background\ud \ud Sickle cell anemia is an inherited disorder of hemoglobin that leads to a variety of acute and chronic complications. Abnormal cellular adhesion, mediated in part by selectins, has been implicated in the pathophysiology of the vaso-occlusion seen in sickle cell anemia, and selectin inhibition was able to restore blood flow in a mouse model of sickle cell disease.\ud \ud Methods\ud \ud We performed a Phase 1 study of the selectin inhibitor GMI 1070 in patients with sickle cell anemia. Fifteen patients who were clinically stable received GMI 1070 in two infusions.\ud \ud Results\ud \ud The drug was well tolerated without significant adverse events. There was a modest increase in total peripheral white blood cell count without clinical symptoms. Plasma concentrations were well-described by a two-compartment model with an elimination T1/2 of 7.7 hours and CLr of 19.6 mL/hour/kg. Computer-assisted intravital microscopy showed transient increases in red blood cell velocity in 3 of the 4 patients studied.\ud \ud Conclusions\ud \ud GMI 1070 was safe in stable patients with sickle cell anemia, and there was suggestion of increased blood flow in a subset of patients. At some time points between 4 and 48 hours after treatment with GMI 1070, there were significant decreases in biomarkers of endothelial activation (sE-selectin, sP-selectin, sICAM), leukocyte activation (MAC-1, LFA-1, PM aggregates) and the coagulation cascade (tissue factor, thrombin-antithrombin complexes). Development of GMI 1070 for the treatment of acute vaso-occlusive crisis is ongoing

Cancer Health Empowerment for Living without Pain (Ca-HELP): study design and rationale for a tailored education and coaching intervention to enhance care of cancer-related pain

Abstract Background Cancer-related pain is common and under-treated. This article describes a study designed to test the effectiveness of a theory-driven, patient-centered coaching intervention to improve cancer pain processes and outcomes. Methods/Design The Cancer Health Empowerment for Living without Pain (Ca-HELP) Study is an American Cancer Society sponsored randomized trial conducted in Sacramento, California. A total of 265 cancer patients with at least moderate pain severity (Worst Pain Numerical Analog Score >=4 out of 10) or pain-related impairment (Likert score >= 3 out of 5) were randomly assigned to receive tailored education and coaching (TEC) or educationally-enhanced usual care (EUC); 258 received at least one follow-up assessment. The TEC intervention is based on social-cognitive theory and consists of 6 components (assess, correct, teach, prepare, rehearse, portray). Both interventions were delivered over approximately 30 minutes just prior to a scheduled oncology visit. The majority of visits (56%) were audio-recorded for later communication coding. Follow-up data including outcomes related to pain severity and impairment, self-efficacy for pain control and for patient-physician communication, functional status and well-being, and anxiety were collected at 2, 6, and 12 weeks. Discussion Building on social cognitive theory and pilot work, this study aims to test the hypothesis that a brief, tailored patient activation intervention will promote better cancer pain care and outcomes. Analyses will focus on the effects of the experimental intervention on pain severity and impairment (primary outcomes); self-efficacy and quality of life (secondary outcomes); and relationships among processes and outcomes of cancer pain care. If this model of coaching by lay health educators proves successful, it could potentially be implemented widely at modest cost. Trial Registration [Clinical Trials Identifier: NCT00283166

Predictors of survival for younger patients less than 50 years of age with non-small cell lung cancer (NSCLC): A California Cancer Registry analysis

BackgroundNon-small cell lung cancer (NSCLC) is uncommonly diagnosed in patients younger than 50 years of age. We analyzed the California Cancer Registry (CCR) to describe epidemiologic characteristics and outcomes in this patient subset and to identify factors prognostic for cause-specific survival (CSS).MethodsPatients diagnosed with NSCLC between 1/1/98 through 12/31/09 and reported to the (CCR) as of October 2011 were included. The primary outcome measure was CSS. Cox regression models were used to evaluate predictors of CSS in young patients with NSCLC, adjusted for potential confounders. Interaction analysis was performed between age groups (<50 vs. ≥50) and specific demographic and tumor covariates.ResultsWe identified 132,671 lung cancer cases, of which 114,451 (86.3%) had NSCLC. Of these, 6389 (5.6%) were<50 years of age (median, 46 years). The most common histology was adenocarcinoma (3697, 57.9%). Most patients had stage III (1522, 23.8%) or IV (3655, 57.2%) disease. Fewer young patients were diagnosed in recent years (n, % of total NSCLC population of that era): 1998-2001 (2355, 6.0), 2002-2005 (2182, 5.7), and 2006-2009 (1852, 5.0), P<0.001. Multivariate analysis showed that age <50 years was an independent predictor of improved CSS (HR 0.827, P<0.001). Significant predictors of better CSS in patients <50 years included female sex, Asian or Hispanic ethnicity, lower stage, later year of diagnosis, and higher socioeconomic status, among others. Adenocarcinoma histology was not associated with improved CSS in this patient subset (HR 0.987, P=0.78). Interaction analysis revealed that Hispanic race and bronchioloalveolar histology had differential CSS outcomes dependent on age group.ConclusionsThis large registry study found that age <50 years is an independent predictor of improved CSS. Variables prognostic for CSS differed somewhat from those in older patients

Sickle cell disease: an inherited thrombophilia.

Activation of the hemostatic system occurs in patients with sickle cell disease. The extent to which this activation contributes to sickle cell pathophysiology is uncertain. Clinical trials of anticoagulants or platelet inhibitors have demonstrated the ability to decrease biomarkers of hemostatic activation, but this has generally not resulted in improvement in clinically relevant outcomes. Venous thromboembolism (VTE: deep venous thrombosis and pulmonary embolism) has been until recently an underappreciated complication of sickle cell disease, with incident event and recurrence rates consistent with a strong thrombophilia. There is no strong evidence that management should differ than for other patients with VTE, with the possible exception that secondary prophylaxis be extended regardless of provocation, given the persistent strong thrombophilic state