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.

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.

Increased ATP synthesis might counteract hepatic lipid accumulation in acromegaly.

Patients with active acromegaly (ACRO) exhibit low hepatocellular lipids (HCL), despite pronounced insulin resistance (IR). This contrasts the strong association of IR with nonalcoholic fatty liver disease in the general population. Since low HCL levels in ACRO might be caused by changes in oxidative substrate metabolism, we investigated mitochondrial activity and plasma metabolomics/lipidomics in active ACRO. Fifteen subjects with ACRO and seventeen healthy controls, matched for age, BMI, sex, and body composition, underwent 31P/1H-7-T MR spectroscopy of the liver and skeletal muscle as well as plasma metabolomic profiling and an oral glucose tolerance test. Subjects with ACRO showed significantly lower HCL levels, but the ATP synthesis rate was significantly increased compared with that in controls. Furthermore, a decreased ratio of unsaturated-to-saturated intrahepatocellular fatty acids was found in subjects with ACRO. Within assessed plasma lipids, lipidomics, and metabolomics, decreased carnitine species also indicated increased mitochondrial activity. We therefore concluded that excess of growth hormone (GH) in humans counteracts HCL accumulation by increased hepatic ATP synthesis. This was accompanied by a decreased ratio of unsaturated-to-saturated lipids in hepatocytes and by a metabolomic profile, reflecting the increase in mitochondrial activity. Thus, these findings help to better understanding of GH-regulated antisteatotic pathways and provide a better insight into potentially novel therapeutic targets for treating NAFLD.

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.

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 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.

Motivating first-time, group O blood donors to return: Rationale and design of a randomized controlled trial of a post-donation telephone interview.

First-time blood donors are essential to the US donor pool, providing nearly a third of all donations. Unfortunately, there are a wide variety of obstacles to repeat donation and new donors are extremely difficult to retain. Because each donor experiences a unique set of deterrents, we developed a post-donation interview based on motivational interview principles in order to flexibly address individual barriers. The primary aim of this randomized clinical trial is to examine retention of first-time, group O blood donors who are randomly assigned to receive either a telephone-delivered interview with motivational and action planning components or a standard-of-care control call approximately six weeks after their donation. Measures of donation attitude, perceived behavioral control, intention, and motivational autonomy will be measured before and after the telephone contact using online surveys, and donation attempts will be tracked for one year using blood center donor databases. We hypothesize that, compared to controls, donors who receive the telephone interview will be more likely to make a donation attempt over the following year. In addition, we will examine possible mechanisms of action of the interview using key predictors of donation behavior as described by Self Determination Theory (i.e., motivational autonomy) and the Theory of Planned Behavior (i.e., attitude, perceived behavioral control, and intention). Results of this intervention may help to support a novel strategy to enhance retention of selected blood donors in an effort to better meet the nation's blood supply needs.

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.

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.

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.

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.

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.

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.

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.

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.

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.