The 2007 Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists Clinical Practice Guideline for Perioperative Blood Transfusion and Blood Conservation in Cardiac Surgery was ...recently promulgated and has received much attention. Using a survey of cardiac anesthesiologists and perfusionists' clinical practice, we aimed to assess the current practices of perfusion, anesthesia, and surgery, as recommended by the Guidelines, and to also determine the role the Guidelines had in changing these practices.
Nontrainee members of the Society of Cardiovascular Anesthesiologists, the American Academy of Cardiovascular Perfusion, the Canadian Society of Clinical Perfusion, and the American Society of ExtraCorporeal Technology were surveyed using a standardized survey instrument that examined clinical practices and responses to the Guidelines.
A total of 1402 surveys from 1061 institutions principally in the United States (677 institutions) and Canada (34 institutions) were returned, a 32% response rate. There was wide distribution of the Guidelines with 78% of anesthesiologists and 67% of perfusionists reporting having read all, part, or a summary of the Guidelines. However, only 20% of respondents reported that an institutional discussion had taken place as a result of the Guidelines, and only 14% of respondents reported that an institutional monitoring group had been formed. There was wide variability in current preoperative testing, perfusion, surgical, and pharmacological practices reported by respondents. Twenty-six percent of respondents reported 1 or more practice changes in response to the Guidelines. The changes made were reported to be highly (9%) or somewhat (31%) effective in reducing overall transfusion rates. Only 4 of 38 Guideline recommendations were reported by >5% of respondents to have been changed in response to the Guidelines.
Wide variation in clinical practices of cardiac surgery was reported. Little change in clinical practices was attributed to the Society of Thoracic Surgeons/Society of Cardiovascular Anesthesiologists Guidelines.
Our laboratory has demonstrated previously that human tonsillar B lymphocytes express IL-13 mRNA
We sought to investigate IL-13 production by human B cells and the association between B cell–derived ...IL-13 and IgE secretion.
Human B lymphocytes were isolated from tonsils and purified by means of rosetting with sheep RBCs or positive or negative selection with magnetic beads. They were stimulated with anti-CD40 antibodies with or without recombinant IL-4. Total mRNA was extracted, and IL-13 mRNA was measured by means of standard RT-PCR or by means of real-time PCR with commercially available primers. B cells were cultured with or without IL-13 neutralizing antibodies, and Cε transcripts and supernatant IgE levels were measured.
IL-13 mRNA was detected in human B lymphocytes stimulated with anti-CD40 antibodies and IL-4 or IL-2 but not in unstimulated B cells. Real-time PCR demonstrated a 10- to 15-fold increase in IL-13 mRNA, maximizing at 36 hours. IL-13 protein was detected from B lymphocytes on day 3 and accumulated through day 7. The synthesis of IL-13 required both CD40 and IL-4 stimulation. The presence of IL-13 was confirmed by means of intracellular staining of cultured B lymphocytes and antigen-stimulated nasal biopsy specimens from atopic individuals. Addition of IL-13 neutralizing antibodies to purified B-cell cultures inhibited IgE production by up to 80% and diminished IgE (Cε) transcripts by 50%.
Human B lymphocytes express IL-13 mRNA after ligation of CD40 and the addition of cytokines. Human B lymphocytes produce significant IL-13, and neutralization of IL-13 impairs IgE synthesis. IL-13 might be an important autocrine growth factor for IgE-producing B lymphocytes.
Food desensitization via oral immunotherapy (OIT) is gaining acceptance in clinical practice. Owing to adverse reactions, the duration of the buildup phase until a maintenance dose is achieved may be ...prolonged, and in a minority of cases, OIT is stopped.
We aimed to assess factors associated with the probability of reaching the maintenance dose in cow's milk (CM) OIT.
We collected data from patients undergoing CM OIT at the Montreal Children's Hospital, BC Children's Hospital, and Hospital for Sick Children. We compared univariable and multivariable Cox regressions to evaluate sociodemographic factors, comorbidities, clinical characteristics, and biomarkers at study entry associated with the likelihood of reaching a maintenance dose of 200 mL of CM.
Among 69 children who reached 4 mL of milk, the median age was 12 years (interquartile range, 9-15 years); 59% were male. Median duration of buildup phase from 4 to 200 mL was 24.0 weeks (interquartile range, 17.7-33.4 weeks). After adjusting for age and sex, higher baseline levels of specific IgE antibodies for α-lactalbumin (hazard ratio HR = 0.80; 95% confidence interval CI, 0.67-0.95), β-lactoglobulin (HR = 0.86; 95% CI, 0.76-0.98), casein (HR = 0.82; 95% CI, 0.72-0.94), and total CM (HR = 0.79; 95% CI, 0.65-0.97) were associated with a decreased probability of reaching maintenance. In addition, for every 10-mL increase in CM tolerated at entry challenge, the probability of reaching maintenance increased by 10%.
The data suggest that higher levels of CM-specific IgE decreased the likelihood of reaching maintenance, whereas an increased cumulative CM dose at entry challenge increased the likelihood. Assessing these factors before therapy may assist in predicting the success of CM OIT.
Purpose
Common variable immunodeficiency (CVID) is characterized by hypogammaglobulinemia and clinical manifestations such as infections, autoimmunity, and malignancy. We sought to determine if ...responsiveness to interleukin-21 (IL-21), a key cytokine for B cell differentiation, correlates with distinct clinical phenotypes in CVID.
Methods
CVID subjects were recruited through the Canadian Primary Immunodeficiency Evaluative Survey registry. Peripheral blood mononuclear cells were cultured with anti-CD40 ± interferon-gamma, interleukin-4 (IL-4), IL-21, and/or IL-4+IL-21. B cell subpopulations and IgG production were determined at baseline and day 7 by flow cytometry and ELISA. Clinical complications were compared using contingency tables.
Results
CVID subjects exhibited decreased CD27
+
B cells and IgG production after 7 days of stimulation with anti-CD40+IL-21 (
p
< 0.05). In a subset of subjects CVID responders (R), the addition of IL-4 led to significant increases in CD27
+
B cells and IgG (
p
< 0.05). In CVID non-responders (NR), CD27
+
B cells and IgG remained lower despite the addition of IL-4. CVID NR experienced significantly more non-infectious clinical complications of CVID than R OR 8.8, 95% confidence interval (CI) 1.6 to 48.13. Previous studies reported that CVID subjects with ≤ 2% class-switched memory B cells were more at risk of these complications, but no significant association was found among this cohort of subjects OR 3.5, CI 0.9 to 13.3. In fact, 34.6% of CVID NR had > 2% class-switched memory B cells at baseline.
Conclusions
The IL-4 and IL-21 in vitro assays distinguish two groups of CVID subjects and can be used with baseline B cell subpopulation phenotyping to better identify patients experiencing more vs. fewer clinical non-infectious complications and potentially to modulate therapy.
Human immunoglobulin preparations for intravenous or subcutaneous administration are the cornerstone of treatment in patients with primary immunodeficiency diseases affecting the humoral immune ...system. Intravenous preparations have a number of important uses in the treatment of other diseases in humans as well, some for which acceptable treatment alternatives do not exist. We provide an update of the evidence-based guideline on immunoglobulin therapy, last published in 2006. Given the potential risks and inherent scarcity of human immunoglobulin, careful consideration of its indications and administration is warranted.
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