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Background Blood usage and collections were impacted throughout 2020 both by the severity of the COVID‐19 pandemic as well as public health decisions affecting hospital operations. We sought to understand the longer‐term effects of the pandemic on blood usage via changes in case volume and clinical intensity as well as whether the blood needs of COVID‐19‐positive patients differed from other transfused patients. Study design and methods A single‐center retrospective study of blood use in 2020 as compared to 2014–2019 was conducted at a tertiary care center. Statistical analysis was performed in an R‐based workflow. p values are reported using two‐sided t‐tests for total hospital blood usage and using Mann–Whitney U tests for comparisons of patient blood usage. Results Mean monthly red cell usage in 2020 decreased by 11.2% (p = .003), plasma usage decreased by 23.8%, (p

AimsWhile the SARS-CoV-2 pandemic may be contained through vaccination, transfusion of convalescent plasma (CCP) from individuals who recovered from COVID-19 (CCP) is considered an alternative treatment. We investigate if CCP transfusion in patients with severe respiratory failure increases plasma titres of SARS-CoV-2 antibodies and improves clinical outcomes.MethodsPatients with COVID-19 (n=34) were consented for CCP transfusion and serial blood draws pretransfusion and post-transfusion. Plasma SARS-CoV-2 antireceptor binding domain (RBD) IgG and IgM titres were measured by ELISA serially, and compared with serial plasma titre levels from control patients (n=68). The primary outcome was survival at 30 days, and secondary outcomes were length of ventilator and/or extracorporeal membrane oxygenation (ECMO) support, length of stay (LOS) in the hospital and in the intensive care unit (ICU). Outcomes were compared with matched control patients (n=34). Kinetics of antibodies and clinical outcomes were compared using LOess regression and ORs, respectively.ResultsPrior to CCP transfusion, 74% of patients were anti-RBD seropositive for IgG (median 1:3200), and 81% were anti-RBD IgM seropositive (median 1:320), while 16% were seronegative. The kinetics of antibody titres in CCP recipients were similar to controls. CCP recipients presented with similar survival, duration on ventilatory and/or ECMO support, as well as ICU and hospital LOS compared with controls.ConclusionsCCP transfusion did not increase the kinetics of SARS-CoV2 antibodies and did not result in improved clinical outcomes in patients with COVID-19 with severe respiratory failure, suggesting that CCP may not be indicated in this category of patients.

The transfusion of blood products is a widely used practice but comes with the risk of transfusion-associated adverse events and fatalities. The primary aim of this study was to evaluate if strict adherence to transfusion guidelines would lead to a decrease in the rate of transfusion reactions that occurred when blood products were given outside of established indications. Hospital-wide educational programs and dedicated electronic transfusion order sets were used to encourage adherence to guidelines. A secondary aim of this study was to evaluate if a decrease in the incidence of transfusion reactions also lead to a decrease in associated healthcare costs.

Introduction Hypothermia at admission in trauma patients has been significantly associated with worse outcomes and increased blood usage. Previous studies have found variably significant associations between ambient temperatures and incidence of hypothermia in trauma patients. Methods The trauma quality improvement registry was queried for data on trauma patients admitted direct from the scene over a 5-year period. This database was matched to daily weather data taken from the nearest National Oceanic and Atmospheric Administration land-based climate monitoring center, and further combined with blood usage data from the laboratory information system. Results Multivariate logistic regression models predicted significant associations between ambient temperature and patient admission temperature for severely injured patients. No significant direct associations were predicted between ambient temperature and in-hospital mortality or blood usage. Models predicted a significant association between decreased admission temperature and increased likelihood of both blood transfusion and mortality for a severely injured subgroup. Conclusions Ambient temperature is a significant contributor to the rate of admission hypothermia in trauma patients. Most of the variability in admission temperatures for severely injured trauma patients remains unaccounted for by models using standard markers of anatomic and physiologic severity. Decreasing admission temperature is significantly associated with increased mortality and likelihood of blood transfusion for severely injured patients.

BACKGROUND Anemia is associated with poor outcome after major joint replacement surgery, but it is unclear whether sex and race modify its impact on outcome. We hypothesized that anemia would be associated with increased morbidity or mortality after knee arthroplasty surgery and that sex and race would be effect modifiers for this relationship. STUDY DESIGN AND METHODS We performed a retrospective cohort study of elective knee arthroplasty patients between 2013 and 2018 using data from the National Surgical Quality Improvement Program. Morbidity or mortality after surgery was compared between patients without anemia, with mild anemia, and with moderate to severe anemia. Multivariable logistic regression was used to determine adjusted odds for morbidity or mortality with anemia. Interaction terms were entered into the model to test for effect modification by sex and race. RESULTS 243 491 patients were included and 30 135 patients (12.4%) were anemic. Morbidity or mortality occurred in 3.7% of patients without anemia, 5.2% of patients with mild anemia, and 7.1% of patients with moderate to severe anemia (P

Background This study investigated the effect on mortality of transfusing ABO-incompatible plasma from all sources during trauma resuscitation. Methods Demographic, transfusion, and survival data were retrospectively extracted on civilian trauma patients. Patients were divided by receipt of any quantity of ABO-incompatible plasma from any blood product (incompatible group) or receipt of solely ABO-compatible plasma (compatible group). The primary outcome was 30-day mortality, while other outcomes included 6- and 24-hour mortality. Mixed-effects logistic regression was used to model the effect of various predictor variables, including receipt of incompatible plasma, on mortality outcomes. Results Nine hospitals contributed data on a total of 2618 trauma patients. There were 1282 patients in the incompatible group and 1336 patients in the compatible group. In both the unadjusted and adjusted models, the 6-hour, 24-hour, and 30-day mortality rates were not significantly different between these groups. The patients in the incompatible group were then divided into high volume (>342 mL) and low volume (≤342 mL) incompatible plasma recipients. In the adjusted model, the high-volume group had higher 24-hour mortality when the Trauma Injury Severity Score survival prediction was >50%. Mortality at 6 hours and 30 days was not higher in this model. The low-volume group did not have increased mortality at any of the time points in this adjusted model. Conclusion The transfusion of incompatible plasma in civilian trauma resuscitation does not lead to higher 30-day mortality. The finding of higher mortality in a select group of recipients in the secondary analysis warrants further study.

At the frontier of transfusion medicine and transplantation, the field of cellular therapy is emerging. Most novel cellular therapy products are produced under investigational protocols with no clear standardization across cell processing centers. Thus, the purpose of this study was to uncover any variations in manufacturing practices for similar cellular therapy products across different cell processing laboratories worldwide.An exploratory survey that was designed to identify variations in manufacturing practices in novel cellular therapy products was sent to cell processing laboratory directors worldwide. The questionnaire focused on the manufacturing life cycle of different cell therapies (i.e., collection, purification, in vitro expansion, freezing and storage, and thawing and washing), as well as the level of regulations followed to process each product type.The majority of the centers processed hematopoietic progenitor cells (HPCs) from peripheral blood (n = 18), bone marrow (n = 16) or cord blood (n = 19), making HPCs the most commonly processed cells. The next most commonly produced cellular therapies were lymphocytes (n = 19) followed by mesenchymal stromal cells (n = 14), dendritic cells (n = 9) and natural killer (NK) cells (n = 9). A minority of centers (5) processed pancreatic islet cells (n = 4), neural cells (n = 3) and induced-pluripotent stem cells (n = 3). Thirty-two laboratories processed products under an investigational status, for either phase I/II (n = 27) or phase III (n = 17) clinical trials. If purification methods were used, these varied for the type of product processed and by institution. Environmental monitoring methods also varied by product type and institution.This exploratory survey shows a wide variation in cellular therapy manufacturing practices across different cell processing laboratories. A better understanding of the effect of these variations on the quality of these cell-based therapies will be important to assess for further process evaluation and development.

Study objective The transfusion of older packed RBCs may be harmful in critically ill patients. We seek to determine the association between packed RBC age and mortality among trauma patients requiring massive packed RBC transfusion. Methods We analyzed data from the Pragmatic, Randomized Optimal Platelet and Plasma Ratios trial. Subjects in the parent trial included critically injured adult patients admitted to 1 of 12 North American Level I trauma centers who received at least 1 unit of packed RBCs and were predicted to require massive blood transfusion. The primary exposure was volume of packed RBC units transfused during the first 24 hours of hospitalization, stratified by packed RBC age category: 0 to 7 days, 8 to 14 days, 15 to 21 days, and greater than or equal to 22 days. The primary outcome was 24-hour mortality. We evaluated the association between transfused volume of each packed RBC age category and 24-hour survival, using random-effects logistic regression, adjusting for total packed RBC volume, patient age, sex, race, mechanism of injury, Injury Severity Score, Revised Trauma Score, clinical site, and trial treatment group. Results The 678 patients included in the analysis received a total of 8,830 packed RBC units. One hundred patients (14.8%) died within the first 24 hours. On multivariable analysis, the number of packed RBCs greater than or equal to 22 days old was independently associated with increased 24-hour mortality (adjusted odds ratio [OR] 1.05 per packed RBC unit; 95% confidence interval [CI] 1.01 to 1.08): OR 0.97 for 0 to 7 days old (95% CI 0.88 to 1.08), OR 1.04 for 8 to 14 days old (95% CI 0.99 to 1.09), and OR 1.02 for 15 to 21 days old (95% CI 0.98 to 1.06). Results of sensitivity analyses were similar only among patients who received greater than or equal to 10 packed RBC units. Conclusion Increasing quantities of older packed RBCs are associated with increased likelihood of 24-hour mortality in trauma patients receiving massive packed RBC transfusion (≥10 units), but not in those who receive fewer than 10 units.

Background Culturing residual blood components after suspected septic transfusion reactions guides management of patients and cocomponents. Current practice, accuracy of provider vital sign assessment, and performance of the AABB culture criteria are unknown. A multicenter international study was undertaken to investigate these issues and develop improved culture criteria. Study design and methods Retrospective data for all transfusion reactions resulting in residual blood component culture in 2016 were collected from participating hospitals. The performance of the AABB culture criteria were assessed for detection of positive culture results. Modifications to the AABB criteria including 1) recommending culturing in the setting of isolated high fevers, 2) defining hypotension and tachycardia using objective parameters, and 3) incorporating antipyretic use were tested to determine if modifications improved performance. Modifications associated with improvement were incorporate into the BEST criteria. The AABB and the BEST criteria were then tested against a data set enriched for positive culture results to determine which criteria were superior. Results Data were collected from 20 centers encompassing 779,143 transfusions, 3,187 reported transfusion reactions, and 1,104 cultured components. There was marked variation in reaction reporting and culturing rates (0.0%-100.0%). Of 35 total positive component cultures, only one of 35 (2.9%) had concordant patient cultures; 12 of 34 (35.3%) did not have patient cultures performed. The BEST criteria had better sensitivity for detection of a positive culture result compared to the AABB criteria (74% vs. 41%), although specificity decreased (45% vs. 65%). Conclusion Compared to the AABB criteria, the BEST criteria have improved sensitivity for positive culture detection.

Background Convalescent plasma is being used widely as a treatment for coronavirus disease 2019 (COVID-19). However, the clinical efficacy of COVID-19 convalescent plasma is unclear. Methods The Passive Immunity Trial for Our Nation (PassITON) is a multicenter, placebo-controlled, blinded, randomized clinical trial being conducted in the USA to provide high-quality evidence on the efficacy of COVID-19 convalescent plasma as a treatment for adults hospitalized with symptomatic disease. Adults hospitalized with COVID-19 with respiratory symptoms for less than 14 days are eligible. Enrolled patients are randomized in a 1:1 ratio to 1 unit (200–399 mL) of COVID-19 convalescent plasma that has demonstrated neutralizing function using a SARS-CoV-2 chimeric virus neutralization assay. Study treatments are administered in a blinded fashion and patients are followed for 28 days. The primary outcome is clinical status 14 days after study treatment as measured on a 7-category ordinal scale assessing mortality, respiratory support, and return to normal activities of daily living. Key secondary outcomes include mortality and oxygen-free days. The trial is projected to enroll 1000 patients and is designed to detect an odds ratio ≤ 0.73 for the primary outcome. Discussion This trial will provide the most robust data available to date on the efficacy of COVID-19 convalescent plasma for the treatment of adults hospitalized with acute moderate to severe COVID-19. These data will be useful to guide the treatment of COVID-19 patients in the current pandemic and for informing decisions about whether developing a standardized infrastructure for collecting and disseminating convalescent plasma to prepare for future viral pandemics is indicated. Trial registration ClinicalTrials.gov NCT04362176. Registered on 24 April 2020.

OBJECTIVESTo investigate if COVID-19 convalescent plasma (CCP) transfusion in patients with severe respiratory failure will increase plasma levels of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) antibody titers while improving survival and clinical outcomes.DESIGNObservational, retrospective, control study of anti-Receptor binding domain (RBD) of SARS-CoV-2 IgG and IgM titers from serial plasma samples drawn before and after CCP administration. Clinical improvement in CCP recipients is assessed and compared to COVID-19 control patients.SETTINGPatients hospitalized with severe COVID19, United States, between April 17 and July 19, 2020PARTICIPANTS34 patients hospitalized with severe or life threatening COVID-19 and who consented and received a CCP transfusion, 95 control patients with COVID-19 not transfused with CCP. 34 out the 95 control patients were matched for age, sex, and the level of respiratory support required. Patients less than 18 years old were excluded.MAIN OUTCOME MEASURESSerial trends of anti-RBD of SARS-CoV-2 IgG and IgM titers in CCP recipients are compared to those in control patients. The primary outcome is survival at 30 days, and the secondary outcomes are length of ventilatory and/or extracorporeal membrane oxygenation (ECMO) support, length of stay (LOS) in the hospital, and LOS in the ICU.RESULTSCCP transfusion occurred in 34 patients at a median of 12 days following COVID-19 symptom onset. Immediately prior to CCP transfusion, patients median anti-RBD SARS-CoV-2 IgG and IgM titers were 1:3200 (IQR, 1:50 to 1:9600) and 1:320 (IQR, 1:40 to 1:640) respectively. Following a Loess regression analysis, the kinetics and distribution of anti-RBD of SARS-CoV-2 IgG and IgM in plasma from CCP recipients were comparable to those from a control group of 68 patients who did not receive CCP. CCP recipients presented with similar survival, similar duration on ventilatory and/or ECMO support, as well as ICU and hospital LOS, compared to a matched control group of 34 patients.CONCLUSIONIn the present study, hospitalized COVID-19 patients with severe respiratory failure transfused with CCP presented with high titers of SARS-CoV-2 IgG antibodies before transfusion and did not show improved survival at 30 days.

Background The COVID-19 pandemic caused downtrends in both blood collections and blood usage. Rapidly visualizing the impact of the pandemic and newly implemented hospital policies on usage could potentially inform blood ordering practices to help avoid wastage. Study design and methods Blood usage data were obtained from the laboratory information system. An R-based workflow was written in R Markdown for analysis and visualization. Reports were generated daily and shared with blood bank leadership. Selected reports were shared with institutional leadership, other departments, and collaborating blood suppliers. Results Mean daily transfusions dropped 42% from 3/9-13 to 3/16-20, with a significant decrease in usage of red cells, plasma, and cryoprecipitate. The greatest decline in use was seen in the general operating rooms, whereas outpatient transfusions remained steady. Weekly total blood usage decreased through the end of March into April and returned to normal levels in May. Conclusion During two 5-weekday periods of changing hospital policies, overall blood usage decreased by almost half. Visualization of usage by hospital location showed a large decrease in general operating room usage after cancellation of elective procedures. This data visualization has informed decisions to modify standing product orders during an initial period of decreased usage as well as return to normal orders in later months.

Background Whole blood (WB) is rapidly emerging as the treatment modality of choice for the initial resuscitation of civilian trauma patients across the United States. The reemergence of WB has been rapid and driven in part by recognition of the importance of early plasma transfusion in the resuscitation process. Study design and methods The study was designed as a critical analysis of the available literature on WB transfusion in civilian trauma patients. Studies were included if they reported on transfusion of cold-stored WB used in a civilian setting and measured safety, feasibility, or a direct clinical outcome. Results Examination of the available literature supports the feasibility and safety of WB used in treatment of civilian trauma patients. The evidence regarding clinical outcomes, particularly with direct comparison to equivalent doses of component therapy, is more limited. The literature is predominantly descriptive and retrospective in nature and limited by the heterogeneity of clinical WB protocols being used. Based on this limited data set, there are limited conclusions that can be used to definitely support or refute the clinical superiority of WB to component therapy. Conclusion Current literature supports the safety and feasibility of WB, but prospective randomized trials comparing WB to component therapy are needed to provide the definitive evidence on this topic.

BACKGROUND Growth in size and complexity of clinical hematopoietic progenitor cell (HPC) transplant programs necessitates parallel increases in cellular therapy laboratory (CTL) workload. Typically individually developed, HPC product processing is labor and time intensive. Variation in procedure type and numbers across CTLs complicates direct comparisons, and benchmark data are not readily available. STUDY DESIGN AND METHODS Studies were undertaken at seven CTLs. Transplant volume and staff numbers were determined. Staff recorded time performing tasks broken down into steps: paperwork, product acceptance, transport/infusion, processing, and cryopreservation. Times were added to obtain total times for 15 common CTL procedures. RESULTS Annual transplant volume ranged from 53.4 to 463.2, with products processed by a range of 2 to 10 dedicated CTL staff. Paperwork time constituted 23.7% to 62.3% total time; product processing time accounted for 1.8 (for National Marrow Donor Program product receipt) to 62.6% (for red blood cell reduction of allogeneic HPC products from bone marrow) of total processing time. Mean time for 15 procedures ranged from 1.27 to 8.28 hours (standard deviation range, 0.35-2.71 hr). Mean time for products from bone marrow versus peripheral blood was 6.6 ± 2.0 versus 5.5 ± 1.1 hours (p = 0.02). Cryopreservation (6.5 ± 1.6 vs. 4.4 ± 0.85 hr; p

Background Viability testing is a common practice in laboratories. The goal of this study was to ascertain current laboratory practices internationally for performing viability testing for cryopreserved cord blood (CB) products and glean information about how to standardize the method to improve interlaboratory reproducibility. Study design and methods A survey to evaluate current laboratory practices for viability testing was designed and distributed internationally. The question topics included sampling and testing methods, responses to unexpected results, and the rating of the reliability of the CB quality tests, together with expectations for standardization. Results There were 32 respondents to the survey, of whom 28 responded to the more detailed questionnaire about viability methods. Overall, responses indicated that various stains were used among the laboratories, and when multiple sites used the same viability stain the methods differed. The majority of the respondents were in favor of standardizing the viability testing methods. A wide variety of preferences were communicated about how to standardize the method, but a majority did advocate the use of 7-aminoactinomycin D (7-AAD) with flow cytometry. Conclusions The survey results revealed a variety of tests and inconsistent interlaboratory practices for performing the viability assay. Flow cytometry with a 7-AAD dye was suggested as a first step toward standardization.

Kidney transplant patients are frequently anemic and at risk for red blood cell (RBC) transfusion. Previous studies suggest that pre-transplant RBC transfusion may improve kidney transplant outcomes; however, RBC transfusion is also associated with infection. The purpose of our study was to characterize the relationships between intraoperative RBC transfusion, delayed graft function (DGF), postoperative surgical site infection (SSI), and sepsis. Analysis was performed on a historical cohort of adult kidney transplant patients from a single medical center during a two-year period. Crude odds ratios for DGF, superficial and deep SSI, and sepsis were calculated for transfused patients and multivariate regression was used to control for potential confounders when significant relationships were identified. Four hundred forty-one patients had kidney transplant during the study period; 27.0% had RBC transfusion, 38.8% had DGF, 7.0% had superficial SSI, 7.9% had deep SSI, and 1.8% had sepsis. High dose RBC transfusion was associated with improved graft function, but this was negated after adjusting for confounders (OR = 0.86, 95% CI 0.26 to 2.88). There was no association between RBC transfusion and SSI. RBC transfusion was independently associated with sepsis (OR = 8.98, 95% CI 1.52 to 53.22), but the confidence interval was wide. Intraoperative RBC transfusion during kidney transplant is not associated with improved allograft function or incisional SSI, but is associated with postoperative sepsis. RBCs should not be liberally transfused during kidney transplant surgery to improve graft outcomes.

BACKGROUND Red blood cell (RBC) transfusion can be life-saving; however, the risks of RBC transfusion have been increasingly recognized, and current guidelines recommend restrictive transfusion in most patients. We hypothesized that RBC transfusions are decreasing in surgical patients. STUDY DESIGN AND METHODS A retrospective review of the National Surgical Quality Improvement Program database was performed from 2011 to 2015. Index cases in five surgical specialties were studied: neurosurgery, thoracic surgery, gynecologic surgery, orthopedic surgery, and vascular surgery. Patient characteristics, preoperative laboratory values, and surgery details were compared between years. The study's primary outcome was perioperative RBC transfusion, which was compared over the 5-year period for each specialty. Secondary outcomes were myocardial infarction and renal failure after surgery. In addition, trends in RBC transfusion between low-risk and high-risk patients and between emergency and elective surgery were examined. RESULTS RBC transfusion decreased in all surgical specialties except for thoracic and gynecologic surgery. RBC transfusion decreased substantially in orthopedic surgery, falling from 22.4% in 2011 to 6.3% in 2015 (p ≤ 0.0001). High-risk patients had greater reductions in the receipt of RBC transfusion than low-risk patients, and there were no increases in myocardial infarction or renal failure after surgery in any specialty. CONCLUSION RBC transfusion appears to be decreasing across multiple surgical specialties, with no apparent increase in myocardial infarctions or renal failure. This likely represents an important improvement in patient care. Continued efforts are needed to develop patient blood management programs and further reduce RBC transfusion.

Background. Platelet transfusion is a critical therapy for hematology-oncology patients at risk of transfusion-transmitted infection (TTI) and pulmonary injury. Amotosalen-UVA pathogen reduction (PR) treatment of apheresis platelet components (PC) in plasma or additive solution (INTERCEPT Blood System for Platelets, Cerus, Concord, CA) is FDA approved to reduce risk of TTI and transfusion associated graft vs. host disease (TA-GVHD). PRPC meet the FDA bacteria risk reduction guidance, and approximately 50% of U.S. PC are PRPC. Amotosalen-UVA PR replaces bacteria screening, gamma irradiation, and CMV serology. PR is performed within 24 hours of collection enabling early release of PRPC with 5-day storage. We tested the hypothesis that PRPC were not inferior to conventional PC(CPC) for the incidence of pulmonary injury. Methods. An open-label sequential cohort study in platelet transfusion dependent hematology-oncology patients was conducted under routine practice conditions in 15 clinical centers. Each site enrolled a CPC cohort followed by a PRPC cohort using 4 primary therapy strata matched ± 10%: chemotherapy without hematopoietic cell transplant (HCT), HCT with myeloablation, HCT with non-myeloablative conditioning, and HCT with reduced intensity conditioning (RIC). Patients were supported with the assigned PC type for up to 21 days with 7 days of surveillance after the last PC exposure. Patients participated in only one cohort. The primary endpoint was treatment emergent assisted mechanical ventilation (TEAMV) by intubation or tight mask with positive end expiration pressure (5cm H 2O) after initiation of study PC. All endpoint patients were adjudicated by a blinded pulmonary expert panel (PEP) for diagnosis of acute respiratory distress syndrome (ARDS) by the Berlin Criteria. Secondary endpoints included: time to initiation of TEAMV, clinically significant pulmonary adverse events (CSPAE, CTCAE ≥ Grade 2), transfusion reactions, and mortality. The incidence of TEAMV by non-inferiority (margin = 2.3%), and secondary endpoints were analyzed by modified intention to treat (mITT) and per protocol (PP). Sensitivity analyses with propensity score matching for key variables were conducted for the primary endpoint. The associations between PC and categorical variables were tested by stratified Cochran-Mantel-Haenszel and continuous variables by ANOVA for two-sided significance p = 0.05. results. A total of 2291 pediatric and adult patients (1068 PRPC and 1223 CPC) were enrolled in the respective cohorts with transfusion of 5,277 PRPC and 5,491 CPC. PC assignment compliance and study completion were > 94%. For the mITT data set, the cumulative incidence of TEAMV was lower for the PRPC cohort (log rank p = 0.039) than the CPC cohort (2.9% versus 4.6%, HR = 0.633: 95% CI 0.408-0.982). PRPC by mITT were non-inferior to CPC for the incidence of TEAMV due to all indications, and for TEAMV with pulmonary dysfunction (PD) by PEP (Table). PP analyses were consistent with mITT. Relative risk (RR) of TEAMV showed significantly (p Figure 1 Figure 1. Disclosures Wheeler: Novo Nordisk A/S: Consultancy; Bayer: Consultancy; BioMarin: Consultancy; HEMA Biologics: Consultancy; Spark: Consultancy; Takeda: Consultancy; UniQure: Consultancy. Nooka: Janssen Oncology: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Sanofi: Consultancy; Oncopeptides: Consultancy; Amgen: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy; Adaptive technologies: Consultancy; GlaxoSmithKline: Consultancy, Other: Travel expenses; Karyopharm Therapeutics: Consultancy. Uhl: UpToDate: Patents & Royalties; Abbott: Consultancy, Speakers Bureau; Grifols: Consultancy, Speakers Bureau. Spinella: Secure Transfusion Services: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company; Cerus Corporation: Consultancy, Research Funding. Liu: Cerus Corporation: Current Employment, Current equity holder in publicly-traded company. Benjamin: Cerus Corporation: Current Employment, Current equity holder in publicly-traded company. Corash: Cerus Corporation: Current Employment, Current equity holder in publicly-traded company.

The clinical link between loss of β-cell mass and diabetes susceptibility provides a promising avenue of research for novel therapeutics targeting the proliferative axis. To identify potential new pathways involved we utilized two zebrafish genetic models Alström Syndrome (AS) and Bardet-Biedl Syndrome (BBS) that exhibit strikingly different diabetes rates, ∼75% in AS and ∼4% in BBS. We have previously shown β-cell loss in AS and increase in BBS, corresponding to their diabetes rates. RNA-Sequencing of these models identified several exocrine pancreas proteases that were differentially expressed between AS and BBS. Thus, we hypothesized that the exocrine pancreas proteases affect endocrine pancreas function. To test our hypothesis, we overexpressed each enzyme in transgenic zebrafish embryos in which β-cells can be visualized. In control animals, overexpression of exocrine pancreas proteases significantly increased the β-cell number. Overexpression rescued the loss of β-cells observed in animals depleted of alms1. We found ctrb1 overexpression led to increased β-cell proliferation in transgenic larvae and rescued the AS model reduction in proliferation. To test for endogenous protease uptake, we generated a transgenic GFP-tagged CTRB1 and found that 10% of β-cells were GFP+, suggesting a direct interaction between the exocrine and endocrine pancreas. We also found that the inactive, zymogen, form of these enzymes are taken up by β-cells in vitro and induce proliferation in cultured MIN6 β-cells and freshly isolated ex vivo islet cultures, suggesting this effect is conserved in mammalian systems. These data support an important role for exocrine pancreatic enzymes in the modulation of β-cells in diabetes. Disclosure T.L. Hostelley: None. J. Dunleavey: None. E.J. Larkin: None. A.J. Jones: None. D.L. Boyes: None. M.J. Fontaine: None. N.A. Zaghloul: None. Funding National Institutes of Health (F31DK115179-01A1, T32DK098107, R01DK102001, R25GM055036)

BACKGROUND Plasma volume reduction (PVR) may reduce the risk of hemolysis associated with transfusion of plateletpheresis blood products (PLTs) containing ABO-incompatible plasma. But PVR may delay PLT issue. In collaboration with our blood donor center we evaluated an automated screen of PLT for high-titer ABO antibody and to apply PVR to high-titer PLTs. STUDY DESIGN AND METHODS At the donor center, plasma from PLT donors was tested using an automated microplate system (PK7300, Beckman). PK settings were set for a detection cutoff equivalent to 1 in 256 using a manual tube method. The donors associated with high-titer PLTs were characterized by sex and age. In the transfusion service, the number of PVR procedures was evaluated before and after implementation of the high-titer screen. RESULTS During validation, 157 of 1008 PLT units (15%) were positive by the automated method versus 121 (12%) by manual method. After implementation, 2112 of 15,240 PLT units were high-titer, with higher frequency in donations from females versus males (18% vs. 12%, p

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.

Blood group incompatibility remains a significant barrier to kidney transplantation. Approximately, one-third of donors are blood group incompatible with their intended recipient. Options for these donor-recipient pairs include blood group incompatible transplantation or kidney paired donation. However, the optimal protocol for blood group incompatible transplantation is unknown. Protocols differ in techniques to remove ABO antibodies, titer targets, and immunosuppression regimens. In addition, the mechanisms of graft accommodation to blood group antigens remain poorly understood. We describe a blood group incompatible protocol using pretransplant therapeutic plasma exchange (TPE), high-dose intravenous immunoglobulin, and rituximab in addition to prednisone, mycophenolate mofetil, and tacrolimus. In this protocol, we do not exclude patients based on a high initial titer and do not implement post-transplant TPE. All 16 patients who underwent this protocol received a living donor transplant with 100% patient and graft survival, and no reported episodes of antibody-mediated rejection to date with a median follow-up of 2.6 years (range 0.75-4.7 years). We conclude that blood group incompatible transplantation can be achieved without post-transplant TPE.

BACKGROUND Transfusion-transmitted babesiosis (TTB) has been rapidly increasing in incidence since the beginning of the 21st century. Asymptomatic individuals with Babesia infection are able to donate blood in the United States because of the lack of specific blood donation testing. Blood products collected in Babesia-endemic areas are distributed nationally; thus, clinicians in nonendemic states may fail to include babesiosis in the differential diagnosis of a patient who had a recent transfusion history and a fever of unknown origin. STUDY DESIGN AND METHODS We report the details of two cases of clinical transfusion-transmitted babesiosis and one asymptomatic infection identified in red blood cell recipients in two nonendemic states (South Carolina and Maryland), which, when combined with three recent additional cases in nonendemic states, totals six recipient infections in three nonendemic states. RESULTS Delayed diagnosis of transfusion-transmitted babesiosis places patients at risk for increased morbidity and mortality and may result in clinical mismanagement or unnecessary treatments. A peripheral blood smear should be reviewed in any patient with a recent transfusion and a fever of unknown origin. Prompt communication of the diagnosis among physicians is key to ensuring that patients with transfusion-transmitted babesiosis are treated expeditiously, and a transfusion service investigation is necessary to identify additional recipients from the same donor. CONCLUSION TTB is appearing in traditionally nonendemic states because of blood product distribution patterns. Clinicians should include TTB on the differential diagnosis in any patient presenting who had a recent transfusion history and a fever of unknown origin, regardless of where the transfusion took place.

Background Clinical studies have demonstrated that the early and empiric use of plasma improves survival after hemorrhagic shock. We have demonstrated in rodent models of hemorrhagic shock that resuscitation with plasma is protective to the lungs compared with lactated Ringer's solution. As our long-term objective is to determine the molecular mechanisms that modulate plasma's protective effects in injured bleeding patients, we have used human plasma in a mouse model of hemorrhagic shock. The goal of the current experiments is to determine if there are significant adverse effects on lung injury when using human versus mouse plasma in an established murine model of hemorrhagic shock and laparotomy. Methods Mice underwent laparotomy and 90 minutes of hemorrhagic shock to a mean arterial pressure (MAP) of 35 ± 5 mm Hg followed by resuscitation at 1× shed blood using either mouse fresh frozen plasma (FFP), human FFP, or human lyophilized plasma. Mean arterial pressure was recorded during shock and for the first 30 minutes of resuscitation. After 3 hours, animals were killed, and lungs collected for analysis. Results There was a significant increase in early MAP when mouse FFP was used to resuscitate animals compared with human FFP or human lyophilized plasma. However, despite these differences, analysis of the mouse lungs revealed no significant differences in pulmonary histopathology, lung permeability, or lung edema between all three plasma groups. Analysis of neutrophil infiltration in the lungs revealed that mouse FFP decreased neutrophil influx as measured by neutrophil staining; however, myeloperoxidase immunostaining revealed no significant differences in between groups. Conclusion The study of human plasma in a mouse model of hemorrhagic shock is feasible but does reveal some differences compared with mouse plasma-based resuscitation in physiologic measures such as MAP postresuscitation. Measures of end organ function such as lung injury appear to be comparable in this acute model of hemorrhagic shock and resuscitation.

BACKGROUND Red blood cell transfusion related to select surgical procedures accounts for approximately 2.8 million transfusions in the United States yearly and occurs commonly after hip fracture surgeries. Randomized controlled trials have demonstrated lack of clinical benefit with higher versus lower transfusion thresholds in postoperative hip fracture repair patients with cardiac disease or risk factors for cardiac disease. The economic implications of a higher versus lower hemoglobin (Hb) threshold have not yet been investigated. STUDY DESIGN AND METHODS A decision tree analysis was constructed to estimate differences in healthcare costs and charges between a Hb transfusion threshold strategy of 8 g/dL versus 10 g/dL from the perspective of both Centers for Medicare and Medicaid Services (CMS) as well as hospitals. Secondary outcome measures included differences in transfusion-related adverse events. RESULTS Among the 133,697 Medicare beneficiaries undergoing hip fracture repair in 2012, we estimated that 45,457 patients would be anemic and at risk for transfusion. CMS would save an estimated $11.3 million to $24.3 million in payments, while hospitals would reduce charges by an estimated $52.7 million to $93.6 million if the restrictive transfusion strategy were to be implemented nationally. Additionally, rates of transfusion-associated circulatory overload, transfusion-related acute lung injury, acute transfusion reactions, length of stay, and mortality would be reduced. CONCLUSIONS This model suggests that the uniform adoption of a restrictive transfusion strategy among patients with cardiac disease and risk factors for cardiac disease undergoing hip fracture repair would result in significant reductions in clinically important outcomes with significant cost savings.

BACKGROUND: Recent studies show that transfusing older blood may lead to increased mortality. This raises the issue of whether transfusing fresher blood can be achieved without jeopardizing blood availability. STUDY DESIGN AND METHODS: We propose a simple family of policies that is defined by a single threshold: rather than transfusing the oldest available blood that is younger than 42 days, we transfuse the oldest blood that is younger than the threshold, and if there is no blood younger than the threshold then we transfuse the youngest blood that is older than the threshold. To assess this policy, we build a simulation model using data from Stanford University Medical Center. We focus on the tradeoff between the mean age of transfused blood and the fraction of transfused blood that is imported. RESULTS: For hospitals in which the local supply is greater than demand, our policy with a threshold of 14 days leads to a decrease of 10 to 20 days in the mean age of transfused blood while increasing the fraction of imported blood to less than 0.005 (i.e., 0.5%). If the health benefits from transfusing fresher blood can be confirmed by randomized clinical trials, then conservative assumptions suggest that this policy could reduce the annual number of transfused patients who die within 1 year by 20,000. CONCLUSION: The proposed allocation policy with a threshold of 14 days could allow many US hospitals to significantly reduce the age of transfused blood, thereby possibly reducing morbidity and mortality, while having a negligible impact on supply chain operations. T he allocation of available red blood cells (RBCs) for transfusion to patients is a difficult problem: compatibility between donor and recipient must be maintained, and the age and quantity of available RBCs need to be accounted for. More specifically, while there is a tendency to use older available blood to prevent outdating, stored RBCs undergo biochemical changes that impact RBC function, and the age of transfused blood has been reported to be associated with an increased risk of infection, postoperative complications, and/or short-term and long-term mortality.

BACKGROUND: Laboratory-based quality improvement (QI) initiatives can improve clinical outcomes and patient safety. STUDY DESIGN AND METHODS: We present three cases of QI that impact processes from the transfusion service (TS) laboratory to the patient's bedside. RESULTS: Case 1 was event discovery reporting (EDR). We were able to reduce our biologic product deviation reports from 41 (17%) of 238 EDRs to only 19 (7%) of 272 (p

BACKGROUND: Evolving concerns about storage lesions for red blood cells (RBCs) have led to ongoing trials evaluating the benefits of transfusing fresher blood to acutely ill patients. STUDY DESIGN AND METHODS: We evaluated several RBC maximum shelf lives (MSLs) and their impact on RBC availability and outdate rate. First, we determined the mean age of the RBC units in our inventory by analyzing the data set of 18,987 nonirradiated RBC units transfused at our institution from April 2008 to March 2009. Second, we determined the feasibility of issuing RBC units of a designated age to patients using the same data set. We defined six scenarios where RBC units have different MSLs: Scenarios 1, 2, 3, 4, and 5 used a MSL of 7, 14, 21, 28, and 35 days, respectively. Scenario 6 used a combination of different MSLs depending on the category of patients. RESULTS: RBC units spent on average 8.6 days on the shelf with a mean age of 10.2 days at delivery and 18.8 days at issue for transfusion. Using the original 18,987 data points, we observed a shortfall in the availability of RBC units, decreased by 51, 20, 10, 4, 1, and 0% and an increase in the outdate rate to 3.2, 2.2, 1.0, 0.6, 0.4, and 4.5% for Scenarios 1, 2, 3, 4, 5, and 6, respectively, compared to baseline. CONCLUSION: Changing the MSL for RBC units would require novel approaches to RBC inventory management to meet hospital demands with acceptable outdate rates.

Background The decision to use red blood cell transfusion and/or blood products (fresh frozen plasma, platelets, cryoprecipitate) to manage obstetric hemorrhage or treat postpartum anemia is often made empirically by physicians. We performed a retrospective study to review transfusion outcomes in pregnant and postpartum patients at a large obstetric center. Methods A retrospective, observational study was performed of obstetric in-patients who received red blood cell transfusion and/or blood products over a one-year period. Data abstracted included transfusion data, pre-transfusion hemoglobin (Hb) and lowest recorded (nadir) Hb, and maternal and neonatal outcomes. Results During the study period, 74 patients received transfusion therapy (1.4%). Pre-transfusion and nadir Hb values were 7.6g/dL and 7.0g/dL respectively. Median [IQR] total red blood cells transfused were 2 units [2-3], with 41 (55%) patients receiving 1-2 units. Based on chart review, no specific indications for transfusion were identified in 25 patients (34%), and 13 patients (18%) had undetected postpartum anemia (Hb values Conclusion More formal assessment and documentation of the etiologic factors associated with transfusion management in pregnant patients is advised. In addition, the identification and management of undetected postpartum anemia is underappreciated.

BACKGROUND: Blood centers and hospital transfusion services are challenged with maintaining an adequate platelet (PLT) inventory to minimize the number of outdated units without risking a major shortage. A novel approach to inventory management was established at our institution through a collaboration between the Stanford University Medical Center (SUMC) Transfusion Service, the Stanford Blood Center (SBC), and the Department of Management Science and Engineering. STUDY DESIGN AND METHODS: An analysis of the supply chain performance between SBC and SUMC Transfusion Service was performed. First, the interaction between processes, such as blood collection, rotation, and inventory management, was studied. Second, changes were implemented based on the recommendations from the analysis team. Finally, a postanalysis was performed reflecting on the improvement of the operations between SUMC and SBC. RESULTS: A comprehensive data analysis of the PLT supply chain allowed the identification of three series of improvements to be implemented: 1) on SBC's PLT collection, 2) on SBC's rotation process, and 3) on the PLT inventory management policy at SUMC. A postimplementation analysis showed a reduction in the overall PLT outdate rate from 19% in the first quarter of 2006, down to 9% in the third quarter of 2008. CONCLUSION: A multidisciplinary effort among SUMC Transfusion Service, SBC, and experts in supply chain management resulted in a process improvement, which reduced the rate of PLT outdate at both SBC and SUMC Transfusion Service down to 9%, with a significant cost reduction of more than half a million dollars per year.

The histologic hallmark of the development of type 1 diabetes (T1D) is insulitis, characterized by leukocytic infiltration of the pancreatic islets. The molecules controlling the early influx of leukocytes into the islets are poorly understood. Tumor necrosis factor alpha (TNFalpha)-stimulated gene 6 (TSG-6) is involved in inflammation, extracellular matrix formation, cell migration, and development. In the present study, we examined the expression and cellular localization of TSG-6 protein in islets of female non-obese diabetic (NOD) mice using frozen section immunofluorescence staining. Pancreata from nondiabetic (8 and 25 weeks old), prediabetic (230-280 mg/dl blood glucose) and diabetic (300 mg/dl blood glucose) NOD mice were stained for TSG-6, insulin, CD3, CD11c, Mac3 and CD31. TSG-6 protein was detected in 67% of islets of prediabetic mice, 27% of islets of 25-week old nondiabetic mice, and less than 7% of islets of diabetic mice and 8-week old nondiabetic mice. Lastly, islet-derived TSG-6 protein was localized to the infiltrating CD3 and CD11c positive leukocytes.

Strategies inhibiting cell death signaling pathways may enhance the availability of islet transplantation for patients with type 1 diabetes mellitus. The epsilon isoform of protein kinase C (PKC epsilon) has been shown to have an anti-apoptotic effect in many cell types. The present study investigated whether activation of PKC epsilon may improve the yield of functional islet cells for transplantation. Islet cells were isolated from wild-type BALB/c mice preconditioned with either a PKC epsilon activator (psi epsilon RACK) or a TAT carrier control peptide and further treated with the same agents during isolation and in vitro for either 0, 1, 16, or 40 hours. Islet cells were assessed at each time point for viability, apoptosis, and function. psi epsilon RACK-treated islets showed significantly decreased islet cell death up to 40 hours after isolation compared with TAT-treated control islets. Beta-cell function in response to high glucose challenge remained unchanged.

Transfusion therapy of liver transplant patients remains a challenge. High volumes of intraoperative blood transfusion have been shown to increase the risk of poor graft or patient survival. We conducted a retrospective study of 209 consecutive liver transplant cases at our institution. Only patients receiving their first liver transplant, with no other simultaneous organ transplants, were included. Cox proportional hazard modeling was used to identify clinical variables correlated with postoperative patient mortality. Statistically significant variables for poor patient survival were the number of red blood cell and plasma units transfused, a history of red blood cell alloantibodies, and the immunosuppressive regimen used. History of pregnancy also approached statistical significance but was less robust than the other 3 variables. Our findings suggest that blood transfusion and immune modulation greatly affect the survival of patients after liver transplantation.

Management of massive, life-threatening primary postpartum hemorrhage in the labor and delivery service is a challenge for the clinical team and hospital transfusion service. Because severe postpartum obstetrical hemorrhage is uncommon, its occurrence can result in emergent but variable and nonstandard requests for blood products. The implementation of a standardized massive transfusion protocol for the labor and delivery department at our institution after a maternal death caused by amniotic fluid embolism is described. This guideline was modeled on a existing protocol used by the trauma service mandating emergency release of 6 units of group O D- red cells (RBCs), 4 units of fresh frozen or liquid plasma, and 1 apheresis unit of platelets (PLTs). The 6:4:1 fixed ratio of uncrossmatched RBCs, plasma, and PLTs allows the transfusion service to quickly provide blood products during the acute phase of resuscitation and allows the clinical team to anticipate and prevent dilutional coagulopathy. The successful management of three cases of massive primary postpartum hemorrhage after the implementation of our new massive transfusion protocol in the maternal and fetal medicine service is described.

After completing this article, readers should be able to: 1. Describe acute immune-mediated transfusion reactions seen in neonates, their treatment, and their prevention. 2. Describe acute nonimmune-mediated transfusion reactions seen in neonates, their treatment, and their prevention. 3. Describe delayed transfusion complications. 4. Delineate the steps involved in the blood donor screening process in the United States. The safest blood transfusion is the one not administered. When a transfusion is needed, it is important for both physicians and nursing staff to be aware of its potential acute and delayed adverse effects. Adverse consequences may be minimized through early recognition and prompt therapeutic intervention. Noninfectious complications may be either acute (occurring within hours of transfusion) or delayed. Acute reactions may be categorized further according to their pathogenesis: immunologic versus nonimmunologic. Patients should be monitored closely during the transfusion. For all suspected transfusion reactions, the ordering physician and the nursing staff should be trained to stop the transfusion immediately, keep the intravenous line open, check that the blood component was given to the correct patient, and assess and treat symptoms. A posttransfusion blood specimen and the blood bags should be sent to the Transfusion Service (TS) along with a transfusion reaction report form that includes patient diagnosis, history of previous reactions, date and time of reaction with associated symptoms, and vital signs before and after the transfusion. The TS technologist performs a clerical check, inspects posttransfusion blood samples for hemolysis, and repeats ABO/Rh testing on both the transfused unit and the patient’s sample along with a direct antiglobulin (Coombs) test. Further testing is guided by the nature of the patient’s symptoms. Suspected delayed complications of transfusion also should be reported to the TS so the appropriate investigation may be initiated. ### Acute Immune-mediated Transfusion Reactions Acute hemolytic transfusion reactions are the second most common cause of transfusion-related fatality in adult patients, …

Transplantation of islets isolated from deceased donor pancreata is an attractive method of β-cell replacement therapy for patients with type 1 diabetes (T1D). However, the loss of islet cell viability and function during the peritransplant period is a limiting factor to long-term islet engraftment. Activation of the isoenzyme PKCe may improve islet survival and function. The current study assesses the effects of PKCe activation on islet graft function in a syngeneic streptozotocin-induced diabetic mouse model. Islets were isolated from wild-type BALB/c mice preconditioned with either a PKCe activator (ψεRACK) or a TAT carrier control peptide. Islets were further treated with the same agents during isolation, purification, and incubation prior to transplantation. Two hundred seventy-five islet equivalents were transplanted under the kidney capsule of streptozotocin-induced diabetic BALB/c mice. Islet function was assessed by measurement of blood glucose levels every 3 days for 42 days after transplant and through an intraperitoneal glucose tolerance test (IPGTT). The time for return to euglycemia in mice transplanted with islets treated with ψεRACK was improved at 14 ± 6 days versus 21 ± 6 days with TAT-treated islets. The IPGTT showed a 50% reduction in the area under the curve associated with an improved insulin response in mice transplanted with ψεRACK-treated islets compared to TAT-treated islets. A preconditioning regimen using PKCe agonist before pancreatic recovery and during islet isolation improves islet graft function and resistance to high glucose stress after transplantation.

Preservation of the ileocecal valve improves absorptive function and decreases the amount of small bowel needed for survival in patients with short gut syndrome. We compared the results of small and large bowel transplant (SLBTx), small bowel transplant only (SBTx), and SBTx with the ileocecal valve (ICVTx) in a porcine model. Total enterectomy was performed on 18 Yorkshire-Landrace pigs followed by orthotopic SBLTx (n = 6), SBTx (n = 6), and ICVTx (n = 6). A jejunostomy and an ileostomy were constructed for biopsies. Overall mean survival was 17 d with no statistically significant difference between groups. Rejection was seen in 6/6 SLBTx, 4/6 SBTx, and 4/6 ICVTx recipients. Acute rejection was seen in 84.3% of SLBTx, 52.3% of SBTx, and 42.5% of the ICVTx mucosal biopsy samples. Two cases of intra-abdominal infection were in the ICVTx group only. Weight loss was 147 g/d in the SLBTx group, 643 g/d in the SBTx group, and 393 g/d in the ICVTx group. While the functional outcome after SLBTx and ICVTx was noticeably better than the SBTx group, the increased rejection and intra-abdominal infection rates make transplanting the large bowel or the ileocecal valve a less attractive clinical option.

Background. The optimal biopsy site of bowel allografts for rejection surveillance remains controversial. We compared the results of jejunal (JBx) and ileal (IBx) biopsies after bowel transplantation in a porcine model. Methods. Eighteen Yorkshire-Landrace pigs served as donors. Eighteen recipient pigs underwent total enterectomy followed by orthotopic small bowel transplantation with or without the colon. A jejunostomy and a Bishop-Koop ileostomy were constructed for biopsies. Immunosuppression consisted of FK506 (target level 10-15 ng/ml by enzyme immunoparticle assay) and prednisone administered via the jejunostomy. Simultaneous JBx and IBx were performed twice weekly. Acute rejection was graded as mild, moderate, or severe based on previously published criteria. Results. Mean overall survival after the transplant was 17.4 days. A total of 162 specimens were collected and evaluated for rejection (JBx, 81; IBx, 81). Acute rejection was detected in 41 JBx cases (50.7%) and 40 IBx cases (49.4%). The presence or absence of rejection was concordant between JBx and IBx in 70 of 81 case pairs (86.4%). Of the 11 discordant case pairs, 6 were JBx positive/IBx negative, whereas 5 were JBx negative/IBx positive. A total of 35 case pairs were synchronously positive, 24 (68.8%) of which demonstrated the same degree of rejection. Conclusions. The correlation between JBx and IBx of bowel allografts in diagnosing the presence of acute rejection is quite good. However, performing IBx alone would have missed about 7.5% of the rejection episodes. Because the early treatment of rejection in bowel transplantation is of paramount importance, in selected cases, biopsies from both the ileum and jejunum should be considered if technically feasible.

Hepatocyte allotransplantation has been performed successfully in several small animal models for the amelioration of inborn metabolic errors. Before a human clinical trial of hepatocyte allotransplantation can be attempted, preliminary experience in a large animal model is needed. We transplanted isolated mongrel hepatocytes into the spleen of dalmatians in the attempt to cure their inborn error of uric acid metabolism. Of 10 dalmatian recipients, two that received 9-10 x 10(9) mongrel hepatocytes died early after surgery of acute portal hypertension and hemorrhage. The eight long-term survivors received 5-6 x 10(9) hepatocytes and were randomized either to no treatment or to oral cyclosporine (CsA). Levels of CsA were adjusted to maintain trough levels between 400 and 800 ng/ml. In the four nonimmunosuppressed dalmatians, a reproducible average reduction in urinary uric acid excretion (UUAEx) of 23.7% was achieved; values returned to baseline within 14 days. In the CsA-immunosuppressed dalmatians, the average decline in UUAEx was 30%. The partial correction of the metabolic defect persisted for an average of 25 days in three immunosuppressed dogs, whereas in one dog, the partial correction lasted for over 90 days. No change in UUAEx was observed in two dalmatians that underwent sham laparotomy and intrasplenic injection of saline solution; CsA given alone to dalmatians did not modify UUAEx. We conclude that the dalmatian dog is a valuable large animal model for studies of the role of hepatocyte transplantation in the cure of inborn hepatic metabolic errors.

Pancreatic islet encapsulation within biosynthetic materials has had limited clinical success due to loss of islet function and cell death. As an alternative encapsulation material, a silk-based scaffold was developed to reestablish the islet microenvironment lost during cell isolation. Islets were encapsulated with ECM proteins (laminin and collagen IV) and mesenchymal stromal cells (MSCs), known to have immunomodulatory properties or to enhance islet cell graft survival and function. After a 7 day in vitro encapsulation, islets remained viable and maintained insulin secretion in response to glucose stimulation. Islets encapsulated with collagen IV, or laminin had increased insulin secretion at day 2 and day 7, respectively. A 3.2-fold synergistic improvement in islet insulin secretion was observed when islets were co-encapsulated with MSCs and ECM proteins. Furthermore, encapsulated islets had increased gene expression of functional genes; insulin I, insulin II, glucagon, somatostatin, and PDX-1, and lower expression of the de-differentiation genes cytokeratin 19 and vimentin compared to non-encapsulated cells. This work demonstrates that encapsulation in silk with both MSCs and ECM proteins enhances islet function and with further development may have potential as a suitable platform for islet delivery in vivo.

BACKGROUND: This study presents our implementation of a two-specimen requirement with no prior record of ABO/Rh to verify patients' blood type before transfusion. MATERIALS AND METHODS: Blood type verification was introduced, discussed, approved, and implemented over a 12-month period (May 2007 to May 2008). Potential barriers and impact on benchmark indicators were identified and tracked. RESULTS: Inpatient identification and/or specimen labeling for nursing and laboratory phlebotomists baseline corrected error rates were 1:467 and 1:5555, respectively. This study therefore sought and obtained approval to initiate a new policy of blood type verification before blood transfusion. Compliance in turnaround time (TAT) before and after implementation for completion of STAT type and screen/crossmatch within 60 minutes worsened marginally, from 90% to 80%. The impact on use of O–, uncrossmatched blood was found to be manageable. Seven (of 25 total) recorded electronic complaints were received after implementation. The corrected error rate for nurse phlebotomy draws after implementation was 1:630. CONCLUSION: Despite the lack of an instigating event, verification of blood type before blood transfusion was successfully implemented. An impact on resources and benchmark indicators such as TAT can be anticipated and managed. Further process improvement efforts will be needed to ensure safety (e.g., at time of blood transfusion) for patients receiving blood transfusions. ABO/Rh verification may be necessary even after future implementation of bar coding and/or RFID chips, because human errors continue to occur even with systems improvements.

Anemia is common in cancer patients and is often considered merely secondary to the underlying malignancy. Anemia associated with cancer varies widely with stage of disease and/or treatment and in general will develop slowly with hemoglobin values ranging from 8 to 10 g/dL (Mercuriali and Inghilleri 2002). But because anemia has an independent impact on length and quality of life (QOL) (Nissenson et al. 2003), anemia in cancer patients has been more closely scrutinized in order to improve its evaluation and treatment. Blood transfusion appears to overcome the negative prognostic effects of low presenting hemoglobin levels (Grogan et al. 1999), but is often associated with a higher risk of infection. Blood transfusions remain particularly helpful in the context of either severe anemia (Hb < 8.0 g/dL) or life-threatening anemia (Hb < 6.5 g/dL), particularly when the condition is aggravated by bleeding as a result of a surgical intervention. This chapter, focused on the use of human recombinant erythropoietin (rhEPO) in surgical cancer patients, will first attempt to review the transfusion requirements of cancer patients undergoing surgery and review the risks associated with allogeneic blood transfusion in these patients. Secondly, we will discuss the alternative use of rhEPO to treat perioperative anemia in cancer patients.

During pregnancy, maternal pancreatic islets grow to match dynamic physiological demands, but the mechanisms regulating adaptive islet growth in this setting are poorly understood. Here we show that menin, a protein previously characterized as an endocrine tumor suppressor and transcriptional regulator, controls islet growth in pregnant mice. Pregnancy stimulated proliferation of maternal pancreatic islet β-cells that was accompanied by reduced islet levels of menin and its targets. Transgenic expression of menin in maternal β-cells prevented islet expansion and led to hyperglycemia and impaired glucose tolerance, hallmark features of gestational diabetes. Prolactin, a hormonal regulator of pregnancy, repressed islet menin levels and stimulated β-cell proliferation. These results expand our understanding of mechanisms underlying diabetes pathogenesis and reveal potential targets for therapy in diabetes.

During the past decade, numerous studies in both humans and animals have demonstrated that C-peptide, although not influencing blood sugar control, might play a role in preventing and potentially reversing some of the chronic complications of type 1 diabetes. The aim of this paper is to present an up-to-date review of C-peptide, focusing on its role in insulin biosynthesis and in the classification of diabetes mellitus, as well as its potential clinical applications.The relevant literature cited in the MEDLINE database shows that the measurement of C-peptide production combined with screening for the presence of islet-cell and other autoantibodies seems to exert an important role in the accurate differentiation between patients with type 1 and type 2 diabetes. Also, both experimental and clinical data provide evidence suggesting that combined replacement of insulin and C-peptide has potential therapeutic value in patients with type 1 diabetes.Further study in this area is warranted, but the findings that pancreas transplants promote the reversal of diabetic neuropathy and stabilization of diabetic retinopathy and that both pancreas and islet transplants lead to the reversal of diabetic nephropathy lend credence to the concept that combined replacement of insulin and C-peptide may more effectively mitigate the inexorable progression of diabetes-related complications.

BACKGROUND: Preoperative autologous blood donation (PABD) has been used to reduce the need for allogeneic RBC transfusion, decreasing risk and conserving supply. A frozen PABD program for heart transplant patients was instituted at the Mayo Clinic in 1988, but participation has steadily declined. The aims of this study were to determine how the availability of PABD influenced the transfusion RBC components, whether the availability of PABD reduced exposure to allogeneic RBC components, and the costs of providing PABD units. STUDY DESIGN AND METHODS: A retrospective review of all heart transplant cases from 1988 to 1999 was performed (n = 141). Data on collection and transfusion practices were compared for patients with (n = 88, 62%) and without PABD (n = 53, 38%). RESULTS: Total RBC transfusion requirements did not differ between the groups. Patients with frozen PABD received fewer allogeneic units, but they also had less blood salvaged and reinfused. Twenty patients (23%) completely avoided exposure to allogeneic RBCs in the PABD group versus three patients (6%) in the group without PABD. Although patients in the PABD group successfully donated a total of 423 units, 41 percent were discarded. Over 11 years, the need for 251 units of allogeneic RBCs was avoided ($27,610), but $283,500 was spent to have the frozen PABD units available. CONCLUSION: PABD can be performed for heart transplantation, but it is expensive.