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  • 1
    Language: English
    In: Clinical chemistry, October 2013, Vol.59(10), pp.1538-9
    Description: In a recent issue of Science , Lacetera, Macis, and Slonim summarize new information regarding the impact that economic rewards have on the blood supply and safety (1). For many years, the WHO has taken the stance that economic incentives decrease the safety of the blood supply. In support of the WHO position, the establishment of an all-volunteer blood supply led to a dramatic decrease in the incidence of posttransfusion hepatitis C. The authors submit, however, that the position of the WHO is based on studies that failed to control for several confounding variables (percentage of first-time donors, location of donation, and use of prisoners). Recent randomized field surveys reviewed by the authors found that economic incentives increase …
    Keywords: Guidelines As Topic ; Blood Donors -- Ethics ; Reimbursement, Incentive -- Ethics
    ISSN: 00099147
    E-ISSN: 1530-8561
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  • 2
    In: Transplantation, 2016, Vol.100(8), pp.1619-1628
    Description: ABSTRACT: The development of sensitive methods for alloantibody detection has been a significant advance in clinical transplantation. However, the complexity of the data from solid phase and crossmatch assays has led to potential confusion about how to use the results for clinical decision making. The goal of this review is to provide a practical guide for transplant physicians for the interpretation of antibody data to supplement consultation with local tissue typing experts. Sources of variability in both the solid phase and crossmatch assay are discussed as are recent data regarding C1q binding antibodies and IgG subclass testing. Although definitive approaches to alloantibody testing are not possible with our current knowledge, we outline a pragmatic approach that we hope will enhance clinical management in this area.
    Keywords: Medicine ; Anatomy & Physiology;
    ISSN: 0041-1337
    E-ISSN: 15346080
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  • 3
    Language: English
    In: Gastroenterology, April 2016, Vol.150(4), pp.S314-S314
    Description: To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/S0016-5085(16)31102-7 Byline: Rok Seon Choung, John R. Mills, Manish J. Gandhi, Joseph A. Murray, Melissa Snyder
    Keywords: Medicine
    ISSN: 0016-5085
    E-ISSN: 1528-0012
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  • 4
    In: Circulation, 2017, Vol.136(14), pp.1350-1352
    Keywords: Adult–Blood ; Allografts–Blood ; Biomarkers–Diagnosis ; Coronary Artery Disease–Immunology ; Female–Blood ; Graft Rejection–Diagnosis ; HLA Antigens–Immunology ; Heart Transplantation–Immunology ; Humans–Adverse Effects ; Isoantibodies–Blood ; Male–Immunology ; Middle Aged–Methods ; Minnesota–Methods ; Monitoring, Immunologic–Methods ; Predictive Value of Tests–Methods ; Risk Factors–Methods ; Time Factors–Methods ; Treatment Outcome–Methods ; Young Adult–Methods ; Abridged ; Biomarkers ; HLA Antigens ; Isoantibodies ; HLA Antigens ; Coronary Artery Disease ; Graft Rejection ; Heart Transplantation;
    ISSN: 0009-7322
    E-ISSN: 15244539
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  • 5
    In: Transplantation, 2014, Vol.98(2), pp.229-238
    Description: BACKGROUND: Acute allograft dysfunction (AAD) is an important cause of morbidity among heart transplant recipients. The role of donor-specific antibodies (DSAs) in AAD, with the increasing use of single antigen bead (SAB) assays that have improved the ability to detect DSA, remains unclear. METHODS: We retrospectively reviewed 329 heart transplant recipients followed up at our institution. AAD was defined as an acute decline in left ventricular ejection fraction to less than 50% and a decrement of 10% or higher compared to baseline in the absence of cellular rejection. Patients with AAD were compared with matched 30 heart transplant controls. RESULTS: There were 10 (3%) patients with AAD, 4 (40%) had DSA detectable by SAB assay compared to 16 (53%) controls (P=0.43). Peak DSA mean fluorescent intensity (MFI) levels were significantly higher at baseline (class I and class II) in AAD compared to controls. DSA MFI values increased at the time of AAD and returned to baseline values during follow-up for these patients with AAD (P〈0.05) but remained unchanged over time for controls. Six (60%) patients with AAD and 1 (3%) control had antibody-mediated rejection (AMR) by endomyocardial biopsy (P〈0.01). There were 4 (40%) patients with AAD with no DSA or AMR. CONCLUSIONS: AAD after heart transplant is a heterogeneous process characterized by 1) AMR and DSA, 2) AMR but no DSA, and 3) no AMR or DSA. The presence of DSA is not associated with AAD, but the quantity assessed by MFI levels may play a role.
    Keywords: Medicine ; Anatomy & Physiology;
    ISSN: 0041-1337
    E-ISSN: 15346080
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  • 6
    In: Transplantation, 2017, Vol.101(6), pp.1222-1227
    Description: BACKGROUND: We previously showed that bortezomib (BTZ) partially depletes plasma cells, yet has limited efficacy for desensitization in kidney transplant candidates when up to 16 doses is given. METHODS: This study aimed to determine the safety and efficacy of 32 doses of BTZ (1.3 mg/m of body surface area) in 10 highly sensitized kidney transplant candidates with alloantibodies against their intended living donor. RESULTS: Dose reduction was needed in 2 patients and 2 others completely discontinued therapy for adverse events. Anti-HLA antibodies mean fluorescence intensity (MFI) values were stable prior to BTZ (P = 0.96) but decreased after therapy (mean decrease of 1916 [SE, 425] MFI, P 〈 0.01). No patient developed a negative crossmatch against their original intended donor, and the calculated panel-reactive antibodies based on MFI of 2000, 4000, and 8000 was unchanged in all patients. CONCLUSIONS: These data suggest that 32 doses of BTZ monotherapy was not well tolerated and resulted in only a modest reduction in anti-HLA antibodies.
    ISSN: 0041-1337
    Source: Copyright © 2013 Lippincott Williams & Wilkins. All rights reserved.〈img src=http://exlibris-pub.s3.amazonaws.com/LWW%20logo.png style="vertical-align:middle;margin-left:7px"〉
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  • 7
    Language: English
    In: Transfusion, Sept, 2012, Vol.52, p.1880(9)
    Description: To purchase or authenticate to the full-text of this article, please visit this link: http://onlinelibrary.wiley.com/doi/10.1111/j.1537-2995.2011.03533.x/abstract Byline: Manish J. Gandhi(1), Kimberly Duffy(1), Mary Benike(1), Sarah Jenkins(1), James R. Stubbs(1) BACKGROUND: The NHANES-III survey found hemoglobin (Hb) concentrations of more than 13.5 g/dL and more than 12.0 g/dL in normal Caucasian males and females. In the United States, a Hb of least 12.5 g/dL is required for blood donation, which allows aanemica males to donate while excluding anormala females. Low Hb is the major cause of deferral in donors and deferrals are associated with decreased donor return rates. Additionally, frequent blood donations are associated with depletion of body iron stores. Analysis of the effect of various Hb cutoffs and interdonation intervals on our center's blood supply is presented. STUDY DESIGN AND METHODS: Whole blood donor data for a 12-month period were studied. Potential effects on the blood supply by increasing male Hb eligibility levels and/or increasing the interdonation interval were analyzed. RESULTS: A total of 13,519 individuals (females, 56%) donated 30,678 units (mean frequency, male 2.7 and females 2.1) with the majority (42%) donating once. Increasing the male Hb eligibility to at least 13.5 g/dL will decrease collections by 1457 (5%) units. In addition, decreasing the female Hb eligibility to at least 12.0 g/dL will result in total gain of 307 (1%) units. Considering 12-week interdonation interval and Hb eligibility of at least 13.5 g/dL (male) and at least 12.5 g/dL (female) results in decrease of 11% (3352) units. CONCLUSIONS: Increasing the Hb cutoff for male donors and/or interdonation interval for all donors will decrease available blood, some of which may be reduced by decreasing the Hb cutoff for females to at least 12.0 g/dL. As a majority of the donors donate only once with mean donation frequency being 2.4, it may be possible to overcome this shortfall by targeted recruitment of donors donating once. Author Affiliation: (1)From the Division of Transfusion Medicine, Mayo Clinic, Rochester, Minnesota. Correspondence: (*) Manish J. Gandhi, MD, Division of Transfusion Medicine, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905; e-mail: Gandhi.manish@mayo.edu; mjgandhi@hotmail.com. Received for publication October 13, 2011; revision received November 25, 2011, and accepted November 25, 2011.
    Keywords: Hemoglobins -- Analysis
    ISSN: 0041-1132
    Source: Cengage Learning, Inc.
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  • 8
    Language: English
    In: Transfusion, Sept, 2012, Vol.52, p.1880(9)
    Keywords: Hemoglobins -- Analysis
    ISSN: 0041-1132
    Source: Cengage Learning, Inc.
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  • 9
    Language: English
    In: Transplant Immunology, 2011, Vol.25(1), pp.77-81
    Description: Pre-transplant (Tx) presence of HLA antibodies (HLA-Ab) especially donor specific antibodies (DSA) has been correlated with post-Tx rejection. While crossmatch (XM) is the specific method to identify DSA, logistical reasons prevent performing a prospective XM in all transplants. In such cases DSA as identified by solid-phase assay (SPA) are being used to perform a virtual crossmatch (VXM). We present two cases, a heart-lung transplant and a kidney transplant, for which testing detected a presumptive DSA with discordant results: a negative flow cytometric crossmatch (FXM) and a positive VXM using SPA. The subsequent investigation determined the antibody, in both cases, was presumably directed against an epitope of a HLA-B*44 antigen found on the single antigen beads (SAB) used in the SPA but not against the native form on the donor lymphocytes used in the FXM. Manufacturing of SAB beads results in denaturation of epitopes, majority of which are removed from the final product, but residual amount is present on the final product. Denaturation of majority of antigen epitopes on single antigen beads did not remove the activity of the recipient's antibodies but it did diminish the activity of positive control serum. This indicates denaturation of some of the HLA-B*44 antigen during manufacturing of the SAB may have lead to the reactivity. Antibody mediated rejection does not appear to be associated with the titer of this antibody to denatured antigen in the first case and so clinical relevance of such antibodies is unclear. Subsequently a second case of discordant FXM and VXM was identified in a potential kidney transplant patient who went on to an uneventful transplant. In this case, lymphocytes from the donor were positively shown to express HLA-B*44:02 using known anti- HLA-B*44:02 control serum. Platelets identified as HLA-B*44:02 could adsorb the anti-HLA-B*44:02 from the control serum activity but not from that of the recipient's anti- HLA-B 44 antibody adding evidence that this antibody should best be classified as a false positive finding. The presence of such an antibody if misidentified may result in unnecessary therapy being instituted or the inappropriate denial of an organ for transplantation. ► Anti-HLA specificities detected by solid phase assays are used to perform virtual crossmatch (VXM) ► VXM is used as a substitute for actual crossmatch. ► We present two cases with positive VXM and negative flow cytometric crossmatch. ► Denatured antigens may explain discordant results. ► Antibodies to denatured antigens may be clinically irrelevant.
    Keywords: HLA Antibody ; Donor Specific Antibody ; Virtual Crossmatch ; Antibody to Denatured HLA Antigen ; Solid Phase HLA Antibody Testing ; False Positive Virtual Crossmatch ; Medicine ; Biology
    ISSN: 0966-3274
    E-ISSN: 1878-5492
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  • 10
    Language: English
    In: Human Immunology, Oct, 2014, Vol.75, p.73
    Description: To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.humimm.2014.08.098 Byline: Manish J. Gandhi, Steven DeGoey, Nicole Henderson, Laurie Voit, Justin Kreuter Abstract: Detection of donor-specific anti-HLA antibodies (DSA) by solid phase assay (SpA) helps donor selection by predicting the actual crossmatch (xM), a process referred as a virtual crossmatch (VxM). At our center we find good correlation (R.sup.2 =0.85) between flow xM (FxM) and VxM using single antigen bead (SAB) assay to identify DSA. The SAB assay is considered a sensitive SpA; however, a concern is that clinically insignificant anti-HLA antibodies (HLA-Ab) may be detected and preclude the recipient from receiving a transplant. The complement fixing (C1q) SAB assay has been proposed as a way to minimize the detection of clinically insignificant HLA-Ab. We present a summary of our evaluation of this assay.
    ISSN: 0198-8859
    Source: Cengage Learning, Inc.
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