Blood Group Compatibility Research Articles

Allele-specific long-range sequencing as a method for ABO haplotyping in clinical blood group diagnosis and immunohematology research.

Safe transfusion therapy requires accurate testing of blood donors and recipients to determine their ABO blood group compatibility. Genotyping does not always clarify serological blood typing discrepancies and conventional PCR methods are not suitable to identify ABO haplotypes. Therefore, an allele-specific long-range sequencing-based typing method was established. Study samples (n = 100) and six patient samples were ABO phenotyped and screened for specific single nucleotide polymorphisms (SNP) in the ABO gene. Based on identified heterozygous SNPs in intron 1 (12897G>A), 2 (437C>T) or 4 (102C>A, 1511G>T) both ABO alleles were investigated separately using a high-fidelity long-range PCR system and Sanger sequencing. The alleles were correlated to the ABO phenotypes determined. Direct sequencing of allelic PCR products up to 6743 bases has been successful in discriminating common combinations of the ABO*A1.01, ABO*A2.01, ABO*B.01, ABO*O.01.01, ABO*O.01.02 and ABO*O.02.01 alleles. 10 out of 64 haplotypes were found to be not previously described. The uncommon ABO*AW.31.01 and the unusual O alleles ABO*O.05 and ABO*O.02.03 alleles were detected in patient samples, resolving the initial inconclusive serologic ABO typing results. This method is an effective tool for analyzing ABO haplotypes. Applicable for ABO molecular diagnostics and immunohematology research it may help to improve pre-transfusion blood type testing.

A Multi-Step Precision Pathway for Predicting Allograft Survival in Heterogeneous Cohorts of Kidney Transplant Recipients.

Accurate prediction of allograft survival after kidney transplantation allows early identification of at-risk recipients for adverse outcomes and initiation of preventive interventions to optimize post-transplant care. Many prediction algorithms do not model cohort heterogeneity and may lead to inaccurate assessment of longer-term graft outcomes among minority groups. Using data from a national Australian kidney transplant cohort (2008-2017) as the derivation set, we developed P-Cube, a multi-step precision prediction pathway model for predicting overall graft survival in three ethnic subgroups: European Australians, Asian Australians and Aboriginal and Torres Strait Islander Peoples. The concordance index for the European Australians, Asian Australians, and Aboriginal and Torres Strait Islander Peoples subpopulations were 0.99 (0.98-0.99), 0.93 (0.92-0.94) and 0.92 (0.91-0.93), respectively. Similar findings were observed when validating P-cube using an external dataset [Scientific Registry of Transplant Recipient Registry (2006-2020)]. Six sub-categories of recipients with distinct risk factor profiles were identified. Some factors such as blood group compatibility were considered important across the entire transplant population. Other factors such as human leukocyte antigen (HLA)-DR mismatches were unique to older recipients. The P-cube model identifies allograft survival specific risk factors within a heterogenous population and offers personalized survival predictions in a diverse cohort.

Blood Group System: Clinical Insight and Relevance in Medical Practice

Purpose: Thirty three blood group systems have recently received recognition from the International Society of Blood Transfusion. Numerous types of antigens have been found on the red cell membranes in addition to the ABO and Rhesus systems. One of the few significant tests that the anesthesiologist orders during the perioperative period is blood grouping and cross matching. To avoid difficulties associated with transfusions, it is crucial to have a thorough awareness of the blood group system, their clinical importance, typing and cross-matching tests and current implications. To explore the various blood group systems, their clinical significance, and their relevance in medical practice, including transfusion medicine, prenatal care and genetic testing
 Methodology: Relevant databases such as PubMed, Google Scholar and Scopus to search for literature related to blood group system were used for this study. Search strategy including keywords related to barium studies, cross-sectional imaging and low resource economies. This may include terms such as blood group system, ABO blood group, clinical significance, medical practice. Search terms in combination with Boolean operators (AND, OR, NOT) are used to retrieve relevant articles.
 Findings: Undoubtedly blood group systems is highly relevant in medical practice so as to prevent haemolytic transfusion reaction and alloimmunization of individual blood which can result to death of infants and other individuals. As beneficial as blood transfusion is blood group system of the donor and recipient must be identified to make the blood transfusion process safe. Blood group systems also gives clinical insights in medical practice which make disease diagnosis and treatment easier to approach.
 Recommendations: Health care providers should be trained to properly identify and type blood samples and blood banks should have appropriate quality control measures in place to ensure the accuracy of blood typing and cross matching. Healthcare providers involved in organ transplantation should be familiar with the blood group compatibility guidelines and communicate effectively with blood banks to ensure the availability of compatible donor organs.

Retrospective Review of Transfusion Practices in Neonatal Intensive Care Unit (NICU) of Benghazi Children Hospital (2021-2022)

This research aims to study the incidence of blood transfusion in relation to totally admitted cases at Neonatal department of Benghazi Libya children hospital, and to estimate most common causes that need blood transfusion, weight, sex, and age at transfusion. Out of 3036 were admitted to Neonatal word from January 2021 to December 2022, 54 cases were received blood transfusion (1.7%), male to female ratio (1.3:1), mean weight was 2.4kg, mean age at transfusion was 24days, 51.9% had compatible blood group of mother and baby blood group, and in 48.1% were non-compatible blood.

Is ABO Compatibility Important in Islet Transplantation?

One of the current criteria for clinical islet allotransplantation is ABO blood group compatibility between donor and recipient.1 The distribution of ABH antigens in human pancreata was first examined >40 y ago, revealing expression in acinar and vascular cells but not in islets.2 This underlined the importance of ABO matching in whole pancreas transplantation, but the situation in islet transplantation is more complicated. Although islets in situ appear to be ABH-negative,2 islets prepared for transplant are invariably contaminated with exocrine tissue including acinar cells. Furthermore, it is not known whether the islet isolation and transplantation process itself influence ABH expression. It is therefore somewhat surprising that ABH expression in islet preparations before and after transplant has not been characterized until now. In this issue of Transplantation, Verhoeff et al3 present a detailed immunohistochemical and flow cytometric survey of ABH antigen levels in human pancreatic tissue, isolated human clinical-grade islets, and islets derived from human embryonic stem cells (hESCs). After confirming that ABH antigens are present on acinar cells but not on endocrine and ductal cells in the pancreas, the authors demonstrate that islet preparations consist primarily of ABH-negative endocrine cells but are significantly contaminated with ABH-positive acinar cells. When islets were transplanted into immunodeficient rats, the endocrine component was ABH-negative at 24 wk, whereas remnant acinar tissue stained positive. Pancreatic endocrine progenitors derived from hESCs were ABH-negative and remained so after in vivo maturation following transplantation into rats, although this was not unexpected given that the hESC donor was blood group O. The human-to-immunodeficient rat islet xenograft model used in the latter part of the study does have some limitations. First, the kidney subcapsular site does not accurately reflect the clinical scenario, in which islets are transplanted intraportally.1 Subcapsular delivery co-localizes the islets with acinar tissue fragments and potentially exposes the islets to “bystander” injury and inflammation when anti-ABH antibodies attack the acinar cells. In contrast, intraportal delivery disperses islets and acinar fragments widely throughout the liver microvasculature, which probably minimizes co-localization and thus reduces the likelihood of bystander effects. Furthermore, subcapsular but not intraportal delivery shields the graft from exposure to anti-ABH IgM antibodies. Although these differences are not relevant in the immunodeficient rat model, they may well be relevant in the clinical setting. Second, the immunodeficient rat model does not allow investigation of the importance of the in vivo anti-ABH immune response to islet grafts. I have worked with one of the authors (L.J.W.) to develop a mouse model of anti-A antibody-mediated rejection of transgenic blood group A-expressing cardiac grafts.4 However, these A-transgenic donor mice are unsuitable for examining anti-A–mediated islet graft rejection because expression of the antigen is endothelial cell-restricted and absent on islets. Humanized mouse models may be more appropriate, as suggested by the authors. The take-home message of this interesting paper is that ABO matching is indeed likely to be important in islet allotransplantation—as is the case for HLA matching5—but may become less so if islet purification efficiency improves sufficiently or if hESC-derived islets are used. On the former point, the authors speculate that the restriction of surface expression of ABH antigens to acinar tissue (starkly illustrated by Figure 6A in the paper) provides an opportunity to enrich the purity of A, B, or AB islets by some form of negative selection. Although practicality at scale may be an issue, this is an intriguing proposition that is worthy of further consideration.

Wider perspectives: It's a changing world-The use of ABO-incompatible plasma for resuscitating massively bleeding patients.

Wider perspectives: It's a changing world-The use of ABO-incompatible plasma for resuscitating massively bleeding patients.

Robust possibilistic programming to design a closed-loop blood supply chain network considering service-level maximization and lateral resupply.

Reconfiguring the structure of the supply chain network is one of the most strategic and vital decisions in designing a supply chain network. In this study, a Closed-Loop Blood Supply Chain Network (CLBSCN) considering blood group compatibility, ABO-Rh(D), and blood product shelf life has been studied to determine the best strategic and tactical decisions simultaneously considering lateral resupply/transshipment and service-level maximization. Several vital parameters, including supply and demand, are considered fuzzy numbers to approximate reality due to the nature of the world. Furthermore, two crucial factors include ABO-Rh(D) and blood product shelf life considered, while the concept of lateral resupply governs the interconnections of hospitals’ excess blood units. We propose a fuzzy multi-objective Mixed-Integer Non-Linear Programming (MINLP) model to consider two critical objective functions: minimizing the total costs of the network and maximizing the minimum service level to the patients at each Hospital. The fuzzy multi-objective MINLP model is converted to a deterministic multi-objective model using the equivalent auxiliary crisp model to deal with uncertainty. Then, by utilizing two interactive fuzzy solution approaches, the results have been compared based on a real case study to suggest the best solution for the proposed model. Also, we conduct sensitivity analysis on essential parameters such as demand, supply, and capacity to understand how these parameter variations impact two proposed objective functions. Then, the proposed model is tested on a real case study for model validation. The results confirmed that considering the lateral resupply could significantly save the costs of the designed network by a total of $343,000. Interestingly, maximizing the minimum service level at hospitals increased the service level from 58% to 68%.

Enzymatic blood group conversion of human kidneys during ex vivo normothermic machine perfusion.

A major restriction to transplantation is the requirement for ABO blood group compatibility between donor and recipient. In this study, an α-galactosidase enzyme from Bacteroides fragilis was used successfully to remove type B blood group antigens enzymatically from human kidneys using ex vivo normothermic machine perfusion. This provides the first step for a strategy to overcome the ABO barrier in kidney transplantation.

Aetiology of neonatal jaundice in apparently well late-preterm and term neonates at a mission hospital, Southwestern Nigeria

Background: The knowledge of the aetiology for neonatal jaundice is important in the early detection and effective management of infants with or at risk of severe jaundice before hospital discharge. This study assessed the aetiological factors of neonatal jaundice among apparently well late preterm and termnewborns to ensure timely intervention where these risk factors exist.Method: This was a cross sectional study involving 174 apparently well neonates at a tertiary mission hospital. Detailed history, physical examination, relevant haematological and biochemical tests were undertaken. Significant jaundice was defined as serum bilirubin greater than 2 standard deviations above the postnatal age and weight dependent treatment concentration.Results: Of the 844 neonates admitted into the neonatal care unit, 174 (20.6%) had significant jaundice. Median age at presentation was 3 days (95% CI of median 3-4days). The mean ±SD gestation age and birth weight of the neonates at recruitment were 38.1±1.6 weeks and 3.1± 0.5kg respectively. Males were 108 (62.4%; M: F.1.6.1). The mean ±SD total serum bilirubin was 13.9±4.7mg/dl. Significant jaundice was more common with maternal-baby concordant paired blood group of AA, O-O compared with discordant materno-baby group pairs. Of the known causes of significant neonatal jaundice, G6PD deficiency (57-38.5%) ranked topmost. Half (87-50.0%) of the causes of significant jaundice were unidentified.Conclusion : G6PD deficiency remains the leading aetiology for significant neonatal jaundice. G6PD screening should be mandated before hospital discharge, compatible mother-baby blood group pairs do not rule the risk for significant jaundice; further research is required to elucidate other inherent unidentified aetiologies.

The role of donor-recipient gender matching in lung transplantation: a systematic review.

Donor to recipient (D-R) matching in lung transplantation (LTx) is firstly directed by blood group (identity or compatibility), immunological status and morphological criteria. Sex matching is ignored and impact on outcome less investigated. Systematic review of English literature using PubMed (1990-2019) was performed to evaluate the potential role of D-R matching in determining long-term outcome in patients after LTx. Search terms included (LTx) AND (sex) OR (gender) OR (matching) OR (mismatch) OR (donor characteristics) and were restricted to articles' title. Only articles directly reporting LTx survival outcome according to gender match/mismatch and D-R gender combination in LTx were included. Two authors independently extracted articles using predefined data fields, including study quality indicators. MOOSE Guidelines for Meta-Analyses and Systematic Reviews of Observational Studies applied. Nine articles were analyzed and included into this study. All studies analyzed the effect of the different D-R gender combinations on survival while seven of them investigated exclusively the role of sex matching on LTx outcome. In this latter group two out of seven showed a trend towards an overall survival advantage for sex matching LTx combination. The worst survival results were reported for F to M gender combination in 3 studies and for M to F gender combination by 1 study. No differences were reported in remaining 4 studies. This systematic review suggests that sex matching and several gender combinations could play a role in determining overall survival rate after LTx. Data deriving from unbiased studies supported that matching female-female (F-F) and male-male (M-M) could improve LTx outcome while FD-MR combination should be avoided. Unfortunately, a good part of the analyzed data are affected by bias due to confounding factors. Up-to-date immunological, hormonal and morphological factors could explain the gender-based difference in LTx outcome. Further investigations should clarify their role and importance to define the effects of gender combinations on survival.

Effects of Blood Group and ABO Compatibility on Lung Transplant Waitlist and Post-Transplant Outcomes

PurposeBlood group O individuals are universal donors, but O recipients are limited to O donors. This constraint combined with the current lung allocation system places O recipients at a hypothetical disadvantage. This study evaluates waitlist outcomes, post-transplant outcomes, and overall survival from time of listing by blood group.MethodsLung transplant candidates from 2/2015 - 2/2019 were identified from the Scientific Registry of Transplant Recipients. A Fine and Gray model adjusted for OPO region, height, sex, and LAS was used to determine the competing risk for waitlist mortality or transplant by blood group and a model adjusted for LAS at transplant used to determine the competing risk for post-transplant mortality. A Cox proportional hazards regression model utilizing a time-varying covariate of transplant and adjusted for the above was used to determine the adjusted risk from listing to death by blood group. Unadjusted outcomes were visualized using Kaplan-Meir curves.ResultsA total of 9,846 candidates were identified, with 8,181 (83%) receiving a lung transplant and 964 (10%) experiencing waitlist death. Blood group A candidates had higher adjusted access to transplant (sHR 1.23, 1.17-1.29) and lower waitlist mortality (sHR 0.77, CI 0.66-0.89) (Fig 1a). AB candidates had a higher adjusted access to transplant (sHR 1.24, CI 1.1-1.4). There was no difference in the adjusted risk for post-transplant death by blood type (Fig 1b). There was no significant difference in mortality from time of listing across blood groups (Fig 1c) and in graft failure or post-transplant mortality by ABO compatibility.ConclusionTransplant equity varies across blood groups with significant differences in adjusted access to transplant and waitlist mortality by blood group. Despite this, post-transplant survival and survival from the time of listing are similar across blood groups. These results support the need to reconsider allocation schemas to mitigate blood group waitlist inequalities. Blood group O individuals are universal donors, but O recipients are limited to O donors. This constraint combined with the current lung allocation system places O recipients at a hypothetical disadvantage. This study evaluates waitlist outcomes, post-transplant outcomes, and overall survival from time of listing by blood group. Lung transplant candidates from 2/2015 - 2/2019 were identified from the Scientific Registry of Transplant Recipients. A Fine and Gray model adjusted for OPO region, height, sex, and LAS was used to determine the competing risk for waitlist mortality or transplant by blood group and a model adjusted for LAS at transplant used to determine the competing risk for post-transplant mortality. A Cox proportional hazards regression model utilizing a time-varying covariate of transplant and adjusted for the above was used to determine the adjusted risk from listing to death by blood group. Unadjusted outcomes were visualized using Kaplan-Meir curves. A total of 9,846 candidates were identified, with 8,181 (83%) receiving a lung transplant and 964 (10%) experiencing waitlist death. Blood group A candidates had higher adjusted access to transplant (sHR 1.23, 1.17-1.29) and lower waitlist mortality (sHR 0.77, CI 0.66-0.89) (Fig 1a). AB candidates had a higher adjusted access to transplant (sHR 1.24, CI 1.1-1.4). There was no difference in the adjusted risk for post-transplant death by blood type (Fig 1b). There was no significant difference in mortality from time of listing across blood groups (Fig 1c) and in graft failure or post-transplant mortality by ABO compatibility. Transplant equity varies across blood groups with significant differences in adjusted access to transplant and waitlist mortality by blood group. Despite this, post-transplant survival and survival from the time of listing are similar across blood groups. These results support the need to reconsider allocation schemas to mitigate blood group waitlist inequalities.

ABO Blood Group Incompatibility Protects Against SARS-CoV-2 Transmission.

ABO blood groups appear to be associated with the risk of SARS-CoV-2 infection, but the underlying mechanisms and their real importance remain unclear. Two hypotheses have been proposed: ABO compatibility-dependence (neutralization by anti-ABO antibodies) and ABO-dependent intrinsic susceptibility (spike protein attachment to histo-blood group glycans). We tested the first hypothesis through an anonymous questionnaire addressed to hospital staff members. We estimated symptomatic secondary attack rates (SAR) for 333 index cases according to spouse ABO blood group compatibility. Incompatibility was associated with a lower SAR (28% vs. 47%; OR 0.43, 95% CI 0.27–0.69), but no ABO dependence was detected in compatible situations. For the second hypothesis, we detected no binding of recombinant SARS-CoV-2 RBD to blood group-containing glycans. Thus, although no intrinsic differences in susceptibility according to ABO blood type were detected, ABO incompatibility strongly decreased the risk of COVID-19 transmission, suggesting that anti-ABO antibodies contribute to virus neutralization.

Plasma Isoagglutinin Depletion for Blood Group Independent Plasma Transfusion

<b><i>Background:</i></b> Plasma transfusion is one of the basic treatments in patients with major blood loss. The anti-A and anti-B antibodies contained in the plasma demand ABO blood group compatibility. This is limiting the use of plasma in emergency situations and can cause a shortage in the supply of plasma of certain blood groups. We developed a method for anti-A and anti-B depletion by adsorbing plasma isoagglutinins using red blood cells. <b><i>Materials and Methods:</i></b> Three units of fresh frozen plasma were thawed after quarantine storage, pooled, and an aliquot of red cell concentrate was added. After 2 h of incubation at room temperature antibody-red-cell complexes were removed by centrifugation, the isoagglutinin-depleted plasma was split into three units and deep frozen. Isoagglutinin titers, free hemoglobin, residual red cells, clotting factor activity, and sterility of plasma units were determined after isoagglutinin depletion and a double freeze-thawing procedure. <b><i>Results:</i></b> Anti-B titers in group A plasma were reduced from values of 1:64 to 1:1 or lower, anti-A titers in group B plasma decreased from values of 1:128 to at least 1:16. Postprocedure clotting factor activities were preserved with 88.0 ± 7.3% (factor V), 106.9 ± 11.4% (factor VIII), and 84.0 ± 7.5% (factor XI) fulfilling the quality control requirements. No residual red cells were found, but free hemoglobin slightly increased to 53.7 ± 5.2 μmol/L. All units were sterile. <b><i>Discussion:</i></b> We described a method for the production of anti-A- and anti-B-depleted plasma in a closed system that uses standard equipment. The resulting isoagglutinin-depleted plasma may allow for blood group independent plasma transfusion.

The Synthesis of Blood Group Antigenic A Trisaccharide and Its Biotinylated Derivative.

Blood group antigenic A trisaccharide represents the terminal residue of all A blood group antigens and plays a key role in blood cell recognition and blood group compatibility. Herein, we describe the synthesis of the spacered A trisaccharide by means of an assembly scheme that employs in its most complex step the recently proposed glycosyl donor of the 2-azido-2-deoxy-selenogalactoside type, bearing stereocontrolling 3-O-benzoyl and 4,6-O-(di-tert-butylsilylene)-protecting groups. Its application provided efficient and stereoselective formation of the required α-glycosylation product, which was then deprotected and subjected to spacer biotinylation to give both target products, which are in demand for biochemical studies.

Blood supply planning during natural disasters under uncertainty: a novel bi-objective model and an application for red crescent

In natural disasters, having a capable network of collecting and distributing crucial items such as blood is one of the major concerns. However, due to damage to the infrastructure after disasters, mobile blood collecting facilities (blood mobiles) are usually required. This paper aims to decide the locations of mobile facilities in each period for collecting donated blood, plan the blood distribution from the fixed and mobile facilities to the main blood centers, as well as from blood centers to the hospitals and field-hospitals, under uncertain conditions. To do so, a multi-period, bi-objective mixed-integer mathematical model is developed under a multiple-scenario, aiming to minimize the unsatisfied blood demand as well as the total cost of the network. In the proposed model, the blood group compatibility matrix, failure rate of the facilities, and patients’ urgency levels are considered. An augmented e-constraint method is applied to solve this bi-objective model. Due to the complex nature of the proposed blood supply chain model, the Lagrangian relaxation approach is used to solve the proposed model. An expected Istanbul earthquake is considered, and the blood supply planning through the Red Crescent’s European branch is performed utilizing the proposed model to examine its validity. According to the numerical results, the mobile facilities' locations in each period under each scenario are determined, the unsatisfied demand in each hospital and field-hospital for each blood type are reported, and the tradeoff between the supply chain costs and unsatisfied demand are discussed in detail. Finally, to illustrate the robustness of the proposed model, a detailed sensitivity analysis is performed. According to the study results, opening new blood centers near the high-demand sub-districts for faster testing and supply, increasing the hospitals' capacities, and usage of drones and helicopters for blood distribution are suggested can be considered as managerial insights.

Regional Report on Organ Transplantation in Trinidad and Tobago.

Regional Report on Organ Transplantation in Trinidad and Tobago.

ABO-incompatible kidney transplantation in Chhattisgarh – Challenges and outcome

Patients with chronic kidney disease stage 5 are usually excluded from renal transplantation if they do not have a compatible blood group donor. Paired kidney donation and ABO-incompatible kidney transplantation are the only options for such patients. We describe the case of a 49-year-old male patient who had blood Group B positive and potential donor; his wife had blood Group nagative. The patients had an initial anti-A antibody titer of 1:32 and underwent antibody depletion with plasmapheresis (two sessions). He also received rituximab 200 mg on minus 14th days and was induced with basiliximab. At the time of transplant, his anti-A titer was 1:8. Postoperatively, the patient had delayed graft function and received one session of hemodialysis but no plasmapheresis. Postoperatively, anti-A titer was 1:8. He was discharged on the 14th postoperative day with normal renal function.

Deceased donor liver transplantation under the Korean model for end-stage liver disease score-based liver allocation system: 2-year allocation results at a high-volume transplantation center.

BackgroundThe Korean model for end-stage liver disease (MELD) score-based liver allocation system was started in June 2016 in Korea.MethodsThis study analyzed the detailed allocation results of deceased donor liver transplantation (DDLT) during the first 2 years after the MELD score-based liver allocation system implementation at a high-volume liver transplantation (LT) center in Korea.ResultsThis study included 174 patients with age above 12 years. The patient ABO blood groups were A (n=65, 37.4%), B (n=51, 29.3%), O (n=28, 16.1%), and AB (n=30, 17.2%). The LT types were primary LT in 141 patients (81.0%) and retransplantation in 33 (19.0%). The Korean Network for Organ Sharing status categories at LT were as follows: status 1 (n=11, 6.3%), status 2 (n=82, 47.1%), status 3 (n=63, 36.2%), and status 4 (n=18, 10.3%). The mean MELD score at LT and waiting period were 36.6±4.6 and 62.1±98.2 days in blood group A; 37.6±3.6 and 25.7±38.1 days in blood group B; 38.8±2.7 and 26.0±30.5 days in blood group O; and 34.8±5.5 and 68.4±110.5 days in blood group AB (P<0.001 and P=0.012), respectively. Patients with blood group O and AB had the highest and lowest mean MELD scores at LT allocation, respectively.ConclusionsSerious deceased organ donor shortage resulted in very high MELD score cutoffs for DDLT allocation. Additionally, a significant inequality was observed in the possibility for DDLT according to blood group compatibility. Nationwide follow-up studies are necessary to precisely determine the allocation status of DDLT.

Spironolactone reduces oxidative stress in living donor kidney transplantation: a randomized controlled trial.

Mineralocorticoid receptor antagonism prevents acute kidney injury induced by ischemia-reperfusion in rodent and pig preclinical models. In a pilot study, we showed that spironolactone (25 mg) reduced oxidative stress after 5 days of kidney transplant (KT). In the present study, we investigated the effects of higher doses (50 and 100 mg) of spironolactone on kidney function, tubular injury markers, and oxidative stress in living donor KT recipients. We included KT recipients aged 18 yr or older who received immunosuppression therapy with IL-2 receptor antagonist, mycophenolate mofetil, corticosteroids, and tacrolimus with negative cross-match, and compatible blood group. Patients were randomized to receive placebo (n = 27), spironolactone (50 mg, n = 25), or spironolactone (100 mg, n = 25). Treatment was given from 3 days before and up to 5 days after KT. Serum creatinine, K+, urine neutrophil gelatinase-associated lipocalin-2, heat shock protein 72, and 8-hydroxy-2-deoxyguanosine levels were assessed. As expected, kidney function was improved after KT. Serum K+ remained in the normal range along the study. There was no significant effect of spironolactone on urinary neutrophil gelatinase-associated lipocalin-2 levels, whereas the increase in urinary heat shock protein 72 levels tended to be less intense in the 100 mg spironolactone-treated group (P = 0.054). In the placebo-treated group, urinary 8-hydroxylated-guanosine levels increased on days 3 and 5 after transplantation. This effect was prevented in patients that received spironolactone. In conclusion, spironolactone reduces the acute increase in urinary oxidative stress in living donor KT recipients.

Blood supply chain management: robust optimization, disruption risk, and blood group compatibility (a real-life case)

Based on the uncertain conditions such as uncertainty in blood demand and facility disruptions, and also, due to the uncertain nature of blood products such as perishable lifetime, distinct blood groups, and ABO-Rh(D) compatibility and priority rules among these groups, this paper aims to contribute blood supply chains under uncertainty. In this respect, this paper develops a bi-objective two-stage stochastic programming model for managing a red blood cells supply chain that observes above-mentioned issues. This model determines the optimum location-allocation and inventory management decisions and aims to minimize the total cost of the supply chain includes fixed costs, operating costs, inventory holding costs, wastage costs, and transportation costs along with minimizing the substitution levels to provide safer blood transfusion services. To handle the uncertainty of the blood supply chain environment, a robust optimization approach is devised to tackle the uncertainty of parameters, and the TH method is utilized to make the bi-objective model solvable. Then, a real case study of Mashhad city, in Iran, is implemented to demonstrate the model practicality as well as its solution approaches, and finally, the computational results are presented and discussed. Further, the impacts of the different parameters on the results are analyzed which help the decision makers to select the value of the parameters more accurately.