Moderators of peak respiratory exchange ratio during exercise testing in children and adolescents with Fontan physiology.

OBJECTIVES: Many patients with Fontan physiology are unable to achieve the minimum criteria for peak effort during cardiopulmonary exercise testing. The purpose of this study is to determine the influence of physical activity and other clinical predictors related to achieving peak exercise criteria, signified by respiratory exchange ratio ≥ 1.1 in youth with Fontan physiology. METHODS: Secondary analysis of a cross-sectional study of 8-18-year-olds with single ventricle post-Fontan palliation who underwent cardiopulmonary exercise testing (James cycle protocol) and completed a past-year physical activity survey. Bivariate associations were assessed by Wilcoxon rank-sum test and simple regression. Conditional inference forest algorithm was used to classify participants achieving respiratory exchange ratio > 1.1 and to predict peak respiratory exchange ratio. RESULTS: Of the n = 43 participants, 65% were male, mean age was 14.0 ± 2.4 years, and 67.4% (n = 29) achieved respiratory exchange ratio ≥ 1.1. Despite some cardiopulmonary exercise stress test variables achieving statistical significance in bivariate associations with participants achieving respiratory exchange ratio > 1.1, the classification accuracy had area under the precision recall curve of 0.55. All variables together explained 21.4% of the variance in respiratory exchange ratio, with peak oxygen pulse being the most informative. CONCLUSION: Demographic, physical activity, and cardiopulmonary exercise test measures could not classify meeting peak exercise criteria (respiratory exchange ratio ≥ 1.1) at a satisfactory accuracy. Correlations between respiratory exchange ratio and oxygen pulse suggest the augmentation of stroke volume with exercise may affect the Fontan patient's ability to sustain high-intensity exercise.

Conversion of No-Show Patients to Telehealth in a Primary Medicine Clinic.

No-shows in primary care clinics prevent patients from receiving essential care and decrease clinic productivity. The COVID-19 pandemic forced physicians to adjust to telemedicine as a necessary method to provide care. In this study no-show patients were converted to telehealth visits thereby allowing physicians to care for their patients and maintain hospital revenue. The most common reasons for "no-shows" were found to be forgetting appointments and transportation issues.

Warm-reactive (immunoglobulin G) autoantibodies and laboratory testing best practices: review of the literature and survey of current practice.

BACKGROUND: Warm-reactive autoantibodies (WAAs) are the most common cause of autoimmune hemolytic anemia (AIHA) and can also be present without clinically significant hemolysis. WAAs complicate immunohematological testing, yet there is no commonly accepted approach to laboratory evaluation and red blood cell (RBC) selection. STUDY DESIGN AND METHODS: We searched PubMed/Cochrane Central for articles that described testing methodology and blood selection for patients with WAAs. We developed a 31-question survey regarding local practice for immunohematology testing and RBC selection in patients with WAAs (with or without AIHA). RESULTS: Eighty-six studies met the inclusion criteria and the aims of this review. Most of the literature was comprised of retrospective studies that often did not correlate laboratory results with clinical findings. Evidence-based protocols to guide testing and RBC selection for transfusion in patients with WAAs are lacking. Individuals representing 54 laboratories completed the survey. The responses indicated that numerous methodologies are used to identify underlying alloantibodies: 75% of respondents use autoadsorption; in patients who have a recent history of transfusion, 76% of respondents use alloadsorption; 58% of respondents perform direct antiglobulin testing (DAT) each time the indirect antiglobulin test is positive; and 48% perform eluate studies at the initial identification of WAAs. Responding laboratories may use phenotyping (98%) or genotyping (80%) at some point in the work-up. Seventy-five percent of respondents provide phenotype-matched or genotype-matched RBCs for transfusion. CONCLUSION: There is wide variability in immunohematology testing and RBC selection practices for patients who have WAAs (with or without AIHA). Future studies are needed to evaluate and compare the effectiveness of different testing algorithms and transfusion strategies.

A motivational interview promotes retention of blood donors with high internal motivation.

BACKGROUND: Based on the hypothesis that self-determined motivation is associated with an increased likelihood of future behavior, the present study examined the ability of a motivational interview to promote internal motivation for giving blood and future donation attempts. STUDY DESIGN AND METHODS: A sample of 484 recent whole-blood and double red blood cell donors (62.4% female; age = 30.2 ± 11.8 years) were randomly assigned to either a telephone-delivered motivational interview or a control call approximately 6 weeks after donating. Several weeks before the call and again 1 week after the call, participants completed the Blood Donor Identity Survey, a multidimensional measure of donor motivation, to derive indices of amotivation, external motivation, and internal motivation to give blood. Repeat donation attempts were tracked using blood center records. RESULTS: Relative to controls, participants in the motivational interview group showed a shift toward more self-determined motivation, as indicated by significant decreases in amotivation (p = 0.01) and significant increases in external (p = 0.009) and internal (p = 0.002) motivation. Furthermore, those with initially high levels of autonomous motivation were more likely to make a donation attempt in the subsequent year if they completed the motivational interview (71.1%) versus the control call (55.1%). CONCLUSION: Motivational interviewing is a potentially useful strategy to enhance retention of existing blood donors, particularly among those who express a greater sense of internal motivation for giving.

A brief motivational interview with action and coping planning components enhances motivational autonomy among volunteer blood donors.

BACKGROUND: In contrast to standard donor retention strategies (e.g., mailings, phone calls, text messages), we developed a brief telephone interview, based on motivational interviewing principles, that encourages blood donors to reflect upon their unique motivators and barriers for giving. This study examined the effect of this motivational interview, combined with action and coping plan components, on blood donor motivations. STUDY DESIGN AND METHODS: The design was to randomly assign blood donors to receive either a telephone-delivered motivational interview with action and coping plan components or a control call approximately 6 weeks after their most recent donation. Participants completed a series of surveys related to donation motivation approximately 3 weeks before telephone contact (precall baseline) and then repeated these surveys approximately 1 week after telephone contact (postcall). RESULTS: The sample was 63% female, included a majority (52.6%) of first-time blood donors, and had a mean age of 30.0 years (SD, 11.7 years). A series of analyses of variance revealed that, relative to controls (n = 244), donors in the motivational interview group (n = 254) had significantly larger increases in motivational autonomy (p = 0.001), affective attitude (p = 0.004), self-efficacy (p = 0.03), anticipated regret (p = 0.001), and intention (p = < 0.001), as well as larger decreases in donation anxiety (p = 0.01), from precall baseline to postcall assessment. CONCLUSION: This study supports motivational interviewing with action and coping planning as a novel strategy to promote key contributors to donor motivation.

Making thawed universal donor plasma available rapidly for massively bleeding trauma patients: experience from the Pragmatic, Randomized Optimal Platelets and Plasma Ratios (PROPPR) trial.

BACKGROUND: The Pragmatic, Randomized Optimal Platelets and Plasma Ratios (PROPPR) trial was a randomized clinical trial comparing survival after transfusion of two different blood component ratios for emergency resuscitation of traumatic massive hemorrhage. Transfusion services supporting the study were expected to provide thawed plasma, platelets, and red blood cells within 10 minutes of request. STUDY DESIGN AND METHODS: At the 12 Level 1 trauma centers participating in PROPPR, blood components transfused and delivery times were tabulated, with a focus on universal donor (UD) plasma management. The adequacy of site plans was assessed by comparing the bedside blood availability times to study goals and the new American College of Surgeons guidelines. RESULTS: Eleven of 12 sites were able to consistently deliver 6 units of thawed UD plasma to their trauma-receiving unit within 10 minutes and 12 units in 20 minutes. Three sites used blood group A plasma instead of AB for massive transfusion without complications. Approximately 4700 units of plasma were given to the 680 patients enrolled in the trial. No site experienced shortages of AB plasma that limited enrollment. Two of 12 sites reported wastage of thawed AB plasma approaching 25% of AB plasma prepared. CONCLUSION: Delivering UD plasma to massively hemorrhaging patients was accomplished consistently and rapidly and without excessive wastage in high-volume trauma centers. The American College of Surgeons Trauma Quality Improvement Program guidelines for massive transfusion protocol UD plasma availability are practicable in large academic trauma centers. Use of group A plasma in trauma resuscitation needs further study.

Case report of transfusion-related acute lung injury in a pediatric spine surgery patient transfused leukoreduced red blood cells.

Despite leukoreduced red blood cells (LR-RBCs) reducing the risk of transfusion-related acute lung injury (TRALI), we present a case of a 16-year-old female with kyphosis who received a transfusion of one unit of LR-RBCs, which lead to life-threatening, intraoperative TRALI. The clinical presentation included pulmonary edema, severe postoperative lactic acidosis, left ventricular dysfunction, increased creatine phosphokinase, fatty infiltration of the liver, and hemodynamic instability requiring inotropic support. This presentation is not the classic description of TRALI. Our patient improved with supportive treatment and was successfully extubated on postoperative day 4. TRALI work-up revealed antibody formation to HLA A2, A68, B44, and DQA 5 for the LR-RBCs unit administered.

Does early initiation of therapeutic plasma exchange improve outcome in pediatric stem cell transplant-associated thrombotic microangiopathy?

BACKGROUND: The use of therapeutic plasma exchange (TPE) in hematopoietic stem cell transplant-associated thrombotic microangiopathy (TA-TMA) is controversial because the exact mechanism of injury in TA-TMA is not yet understood. STUDY DESIGN AND METHODS: The study objective was to retrospectively review the outcome of children receiving TPE for TA-TMA at our institution. We hypothesized that patients initiating TPE earlier in their disease course would receive a greater benefit than those starting later, regardless of the therapeutic mechanism. RESULTS: We identified 10 consecutive pediatric patients with TA-TMA treated with TPE. Nine of these patients showed normalization of the laboratory variables associated with microangiopathy during their TPE course, but only five patients recovered renal function and survived TA-TMA. The five survivors started TPE a median of 17 days (range, 4-25 days) after TA-TMA diagnosis while the five patients who died started TPE a median of 32 days (range, 17-73 days) after TA-TMA was diagnosed. Three of the five survivors had multiorgan failure at TA-TMA diagnosis and completely recovered with early institution of TPE. These three survivors were able to discontinue renal replacement therapy, and all achieved a normal posttreatment creatinine. The five patients with later institution of TPE progressed to end-stage renal disease and all died. There were no serious TPE-related complications in either group. CONCLUSION: This is the first report evaluating TPE response in regard to procedure initiation time after TA-TMA diagnosis. Our data suggests that early initiation of TPE might be beneficial even in patients with multiorgan failure due to TA-TMA.

Laboratory variables for assessing iron deficiency in REDS-II Iron Status Evaluation (RISE) blood donors.

BACKGROUND: Iron deficiency is common in regular blood donors. We evaluated the diagnostic sensitivity and specificity of red blood cell (RBC) hematology analyzer indices to assess iron status as a part of donor management. STUDY DESIGN AND METHODS: A total of 1659 male and female donors from the Retrovirus Epidemiology Donor Study-II (REDS-II) Donor Iron Status Evaluation (RISE) study who were either first-time/reactivated (FT/RA; no donations for 2 years) or frequent donors were recruited into a longitudinal study of regular donation of RBCs. Of these, 1002 donors returned 15 to 24 months later for a final assessment. Absent iron stores (AIS) was defined as plasma ferritin level of less than 12 µg/L. Logarithm of the ratio of soluble transferrin receptor to ferritin of at least 2.07 (≥97.5% in FT/RA males) was used to define iron-deficient erythropoiesis (IDE). Receiver operating characteristics analysis was performed to assess selected RBC indices (e.g., percentage of hypochromic mature RBCs, proportion of hypochromic mature RBCs [HYPOm], and hemoglobin [Hb] content of reticulocytes [CHr]) in identifying AIS and IDE. RESULTS: HYPOm and CHr detected IDE with comparable sensitivity, 72% versus 69%, but differed in specificity: HYPOm 68% and CHr 53%. For detecting AIS, sensitivity was improved to 85% for HYPOm and 81% for CHr but specificity was reduced for both. Venous Hb had high specificity but poor sensitivity for IDE and AIS. A plasma ferritin level of less than 26.7 µg/L was a good surrogate for assessing IDE. CONCLUSION: RBC indices correlate with AIS and IDE and are more informative than Hb measurement, but lack sufficient sensitivity and specificity to be used as diagnostic tools in blood donors at risk for iron deficiency.

Ticlopidine-, clopidogrel-, and prasugrel-associated thrombotic thrombocytopenic purpura: a 20-year review from the Southern Network on Adverse Reactions (SONAR).

Thienopyridine-derivatives (ticlopidine, clopidogrel, and prasugrel) are the primary antiplatelet agents. Thrombotic thrombocytopenic purpura (TTP) is a rare drug-associated syndrome, with the thienopyridines being the most common drugs implicated in this syndrome. We reviewed 20 years of information on clinical, epidemiologic, and laboratory findings for thienopyridine-associated TTP. Four, 11, and 11 cases of thienopyridine-associated TTP were reported in the first year of marketing of ticlopidine (1989), clopidogrel (1998), and prasugrel (2010), respectively. As of 2011, the FDA received reports of 97 ticlopidine-, 197 clopidogrel-, and 14 prasugrel-associated TTP cases. Severe deficiency of ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) was present in 80% and antibodies to 100% of these TTP patients on ticlopidine, 0% of the patients with clopidogrel-associated TTP (p < 0.05), and an unknown percentage of patients with prasugrel-associated TTP. TTP is associated with use of each of the three thienopyridines, although the mechanistic pathways may differ.

Donation return time at fixed and mobile donation sites.

BACKGROUND: This study investigated the effect of blood donation environment, fixed or mobile with differing sponsor types, on donation return time. STUDY DESIGN AND METHODS: Data from 2006 through 2009 at six US blood centers participating in the Retrovirus Epidemiology Donor Study-II (REDS-II) were used for analysis. Descriptive statistics stratified by whole blood (WB), plateletpheresis (PP), and double red blood cell (R2) donations were obtained for fixed and mobile locations, including median number of donations and median interdonation interval. A survival analysis estimated median return time at fixed and mobile sites, while controlling for censored return times, demographics, blood center, and mandatory recovery times. RESULTS: Two-thirds (67.9%) of WB donations were made at mobile sites, 97.4% of PP donations were made at fixed sites, and R2 donations were equally distributed between fixed and mobile locations. For donations at fixed sites only or alternating between fixed and mobile sites, the highest median numbers of donations were nine and eight, respectively, and the shortest model-adjusted median return times (controlling for mandatory eligibility times of 56 and 112 days) were 36 and 30 days for WB and R2 donations, respectively. For PP donations, the shortest model-adjusted median return time was 23 days at a fixed location and the longest was 693 days at community locations. CONCLUSION: WB, PP, and R2 donors with the shortest time between donations were associated with fixed locations and those alternating between fixed and mobile locations, even after controlling for differing mandatory recovery times for the different blood donation procedures.

The difference between fingerstick and venous hemoglobin and hematocrit varies by sex and iron stores.

BACKGROUND: Fingerstick blood samples are used to estimate donor venous hemoglobin (Hb). STUDY DESIGN AND METHODS: Fingerstick Hb or hematocrit (Hct) was determined routinely for 2425 selected donors at six blood centers, along with venous Hb. Using sex and measures of iron status including absent iron stores (AIS; ferritin < 12 ng/mL), linear regression models were developed to predict venous Hb from fingerstick. RESULTS: Across all subjects, fingerstick Hb was higher than venous Hb in the higher part of the clinical range, but lower in the lower part of the range. The relationship varied by sex and iron status. Across centers, a female donor had on average a venous Hb result 0.5 to 0.8 g/dL lower than a male donor with the same fingerstick Hb and iron status. Similarly, a donor with AIS had on average a venous Hb result 0.3 to 1.1 g/dL lower than an iron-replete donor with the same fingerstick value and sex. An iron-replete male donor with a fingerstick result at the cutoff (Hb 12.5 g/dL) had an acceptable expected venous Hb (12.8 to 13.8 g/dL). A female donor with AIS with a fingerstick result at the cutoff had an expected venous Hb below 12.5 g/dL (11.7 to 12.4 g/dL). Of females with AIS, 40.2% donated blood when their venous Hb was less than 12.5 g/dL. CONCLUSIONS: Fingerstick is considered a useful estimator of venous Hb. However, in some donor groups, particularly female donors with AIS, fingerstick overestimates venous Hb at the donation cutoff. This significant limitation should be considered in setting donor fingerstick Hb or Hct requirements.

Population-based screening for anemia using first-time blood donors.

Anemia is an important public health concern. Data from population-based surveys such as the National Health and Nutrition Examination Survey (NHANES) are the gold standard, but are obtained infrequently and include only small samples from certain minority groups. We assessed whether readily available databases of blood donor hemoglobin values could be used as a surrogate for population hemoglobin values from NHANES. Blood donor venous and fingerstick hemoglobin values were compared to 10,254 NHANES 2005-2008 venous hemoglobin values using demographically stratified analyses and ANOVA. Fingerstick hemoglobins or hematocrits were converted to venous hemoglobin estimates using regression analysis. Venous hemoglobin values from 1,609 first time donors correlated extremely well with NHANES data across different ages, genders, and demographic groups. Cigarette smoking increased hemoglobin by 0.26-0.59 g/dL depending on the intensity. Converted fingerstick hemoglobin from 36,793 first time donors agreed well with NHANES hemoglobin (weighted mean hemoglobin of 15.53 g/dL for donors and 15.73 g/dL for NHANES) with similar variation in mean hemoglobin by age. However, compared to NHANES, the larger donor data set showed reduced differences in mean hemoglobin between Blacks and other races/ethnicities. Overall, first-time donor fingerstick hemoglobins approximate US population data and represent a readily available public health resource for ongoing anemia surveillance.

Impact of a transfusion-related acute lung injury reduction strategy on apheresis platelet collections.

BACKGROUND: Most blood centers in the US have implemented transfusion-related acute lung injury (TRALI) mitigation strategies for apheresis platelet (AP) donations based on theoretical impact of donor loss. The aim of this study is to determine the actual impact of a TRALI mitigation strategy in a US blood center. STUDY DESIGN AND METHODS: Daily collection events and resulting products were retrospectively obtained before and after implementation of a TRALI reduction strategy (HLA antibody testing female AP donors four or more pregnancies) for comparison. The retention rate of reassigned donors was determined by reviewing whole blood (WB) and/or apheresis red blood cell (AR) donations post reassignment. Data were obtained to compare donor frequency and split rate from reassigned (historical data) and new AP donors. RESULTS: Mean daily collections (27.7 vs. 30.0) and total products (12,211 vs. 12,957) were significantly higher after implementation, but the number of products/collection event was lower (1.49 vs. 1.40). Mean collections/donor/year (4.0 vs. 1.8) and split rate (36% vs. 27%) were historically higher for reassigned (n = 45) versus new AP donors (n = 1,090). Seventy-three of 112 donors (65%) testing positive for HLA antibodies returned for WB or AR donations, 31 of 45 (69%) active AP donors returned. CONCLUSIONS: Donor loss may not be adequate to estimate impact on AP inventory, as donation characteristics may differ between new donors and those reassigned. We show successful implementation of a TRALI mitigation strategy by increasing collection goals and AP donor recruitment efforts beyond donor loss. Retaining the majority of reassigned donors is feasible.

Milestones for Apheresis education.

Milestones represent the essential knowledge, skills, and attitudes required for the practice of a medical discipline. Defining these milestones for each medical specialty has become a focus for the American Council of Graduate Medical Education (ACGME). Practitioners of Apheresis Medicine come from a variety of medical specialties making it challenging to establish the essential educational milestones for all. The American Society for Apheresis (ASFA) has an interest in promoting standards of excellence for Apheresis Medicine. ASFA's Physician's Curriculum Content Committee is a group of physician educators in the field of Apheresis Medicine, both donor and therapeutic, from across the United States, who have met regularly for several years to discuss the appropriate educational milestones in Apheresis training. The committee members teach residents and fellows from Pathology, Transfusion Medicine, Hematology/Oncology, Nephrology and other specialties. In this document, we have outlined the basic set of Apheresis milestones required in the ACGME defined competency areas of Patient Care and Medical Knowledge. We have also recommended methods of evaluation and estimated the time necessary for the acquisition of these cognitive and behavioral elements.

Artery of Percheron Infarction: A Case Report of Bilateral Thalamic Stroke Presenting with Acute Encephalopathy.

The artery of Percheron (AOP) is a relatively rare anatomic variant in which a solitary arterial trunk branches from the proximal segment of the posterior cerebral artery and provides arterial supply to the paramedian region of the thalami bilaterally and often to the rostral part of the midbrain. Occlusion of the artery of Percheron results in bilateral paramedian thalamic infarcts with and without midbrain involvement. Recognition of this condition as an acute stroke may be challenging due to various nonlocalized clinical presentations, given the wide range of neurological functions subserved by the thalamus. Prompt neuroimaging, preferably with magnetic resonance imaging (MRI), in conjunction with familiarity with this relatively rare vascular variation can facilitate initiation of appropriate time contingent thrombolytic treatment and improved long-term prognosis. We present a case of a 56-year-old African American female with a bilateral thalamic infarct secondary to the artery of Percheron thromboembolism. This patient presented unresponsive without focal neurologic findings but with an initial Glasgow Coma Score (GCS) of 7, and subsequent computed tomographic (CT) head revealed bilateral thalamic hypodensities. Confirmatory MRI exhibited bilateral subacute thalamic infarcts, which were thought to be embolic with the source from the left ventricular thrombus as the patient had at least three distinct clots. Unfortunately, the patient's mental status did not improve significantly, and she was discharged to a nursing facility for extended care. AOP infarction may be missed on vascular imaging utilizing CT, MRI, and even catheter angiography. Clinical recognition that the AOP is one of the only single artery occlusions that can affect bilateral structures and frequently present solely as altered mental status without focal neurologic deficits is crucial to the diagnosis.

Adjudicating bleeding events in a platelet dose study: impact on outcome results and challenges.

BACKGROUND: In the SToP platelet dose study, the World Health Organization (WHO) bleeding grade was assigned using adjudication. This study describes the challenges associated with adjudicating bleeding events and compares the adjudicated and bedside results for bleeding grade. STUDY DESIGN AND METHODS: To categorize bleeding, the following information was provided to adjudicators: daily bleeding assessments, interventions to stop or control bleeding, daily blood counts, and transfused blood components. Each daily assessment was sent to two adjudicators who independently assigned a grade and anatomic site of bleeding. Discordant cases where disagreement occurred were sent to a third adjudicator and subsequently to a fourth or fifth adjudicator in an attempt to reach agreement. Disagreement after five adjudicators was resolved by consensus. The final adjudicated grade was compared with the grade of bleeding assigned at the bedside by study personnel. RESULTS: A total of 1150 case report forms were adjudicated. Disagreement on grade of bleeding was common: 31.2% after the first two adjudicators, 4.0% after the third adjudicator, 0.7% after four, and 0.05% after five. Disagreement on anatomic site was less but still occurred in 17% of cases after two adjudicators. The frequency of bleeding (≥ Grade 2) based on adjudication was higher than bedside grading (standard-dose arm, 47.5% vs. 34.4%; low-dose arm, 50.0% vs. 43.1%). CONCLUSION: The frequency of WHO bleeding varies depending on the method used to assign grade. Adjudication to assign bleeding grade resulted in significant disagreement when two adjudicators were used.

Blood donations from previously transfused or pregnant donors: a multicenter study to determine the frequency of alloexposure.

BACKGROUND: Transfusion-related acute lung injury (TRALI) mitigation strategies include the deferral of female donors from apheresis platelet (PLT) donations and the distribution of plasma for transfusion from male donors only. We studied the implications of these policies in terms of component loss at six blood centers in the United States. STUDY DESIGN AND METHODS: We collected data from allogeneic blood donors making whole blood and blood component donations during calendar years 2006 through 2008. We analyzed the distribution of donations in terms of the sex, transfusion and pregnancy histories, and blood type. RESULTS: A TRALI mitigation policy that would not allow plasma from female whole blood donors to be prepared into transfusable plasma components would result in nearly a 50% reduction in the units of whole blood available for plasma manufacturing and would decrease the number of type AB plasma units that could be made from whole blood donations by the same amount. Deferral of all female apheresis PLT donors, all female apheresis PLT donors with histories of prior pregnancies, or all female apheresis PLT donors with histories of prior pregnancies and positive screening test results for antibodies to human leukocyte antigens (HLAs) will result in a loss of 37.1, 22.5, and 5.4% of all apheresis PLT donations, respectively. CONCLUSION: A TRALI mitigation policy that only defers female apheresis PLT donors with previous pregnancies and HLAs would result in an approximately 5% decrease in the inventory of apheresis PLTs, but would eliminate a large proportion of components that are associated with TRALI.

The Leukocyte Antibody Prevalence Study-II (LAPS-II): a retrospective cohort study of transfusion-related acute lung injury in recipients of high-plasma-volume human leukocyte antigen antibody-positive or -negative components.

BACKGROUND: We used a multicenter retrospective cohort study design to evaluate whether human leukocyte antigen (HLA) antibody donor screening would reduce the risk of transfusion-related acute lung injury (TRALI) or possible TRALI. STUDY DESIGN AND METHODS: In the Leukocyte Antibody Prevalence Study-II (LAPS-II), we evaluated pulmonary outcomes in recipients of 2596 plasma-rich blood components (transfusable plasma and plateletpheresis) sent to participating hospitals; half of the components were collected from anti-HLA-positive donors (study arm) and half from anti-HLA-negative donors (control arm) matched by sex, parity, and blood center. A staged medical record review process was used. Final recipient diagnosis was based on case review by a blinded expert panel of pulmonary or critical care physicians. RESULTS: TRALI incidence was 0.59% (seven cases) in study arm recipients versus 0.16% (two cases) in control arm recipients for an odds ratio (OR) of 3.6 (95% confidence interval [CI], 0.7-17.4; p = 0.10). For possible TRALI cases (nine study arm, eight control arm), the OR was 1.2 (95% CI, 0.4-3.0; p = 0.81), and for TRALI and possible TRALI aggregated together, it was 1.7 (95% CI, 0.7-3.7; p = 0.24). Transfusion-associated circulatory overload incidence was identical in the two arms (1.17 and 1.22%, respectively; OR, 1.0; p = 1.0). CONCLUSIONS: TRALI incidence in recipients of anti-HLA-positive components was relatively low for a lookback study (1 in 170) and was higher than in the control arm, but did not reach significance. Based on this trend, the data are consistent with the likelihood that TRALI risk is decreased by selecting high-volume plasma components for transfusion from donors at low risk of having HLA antibodies.

A high-throughput de novo sequencing approach for shotgun proteomics using high-resolution tandem mass spectrometry.

BACKGROUND: High-resolution tandem mass spectra can now be readily acquired with hybrid instruments, such as LTQ-Orbitrap and LTQ-FT, in high-throughput shotgun proteomics workflows. The improved spectral quality enables more accurate de novo sequencing for identification of post-translational modifications and amino acid polymorphisms. RESULTS: In this study, a new de novo sequencing algorithm, called Vonode, has been developed specifically for analysis of such high-resolution tandem mass spectra. To fully exploit the high mass accuracy of these spectra, a unique scoring system is proposed to evaluate sequence tags based primarily on mass accuracy information of fragment ions. Consensus sequence tags were inferred for 11,422 spectra with an average peptide length of 5.5 residues from a total of 40,297 input spectra acquired in a 24-hour proteomics measurement of Rhodopseudomonas palustris. The accuracy of inferred consensus sequence tags was 84%. According to our comparison, the performance of Vonode was shown to be superior to the PepNovo v2.0 algorithm, in terms of the number of de novo sequenced spectra and the sequencing accuracy. CONCLUSIONS: Here, we improved de novo sequencing performance by developing a new algorithm specifically for high-resolution tandem mass spectral data. The Vonode algorithm is freely available for download at http://compbio.ornl.gov/Vonode.