Donor Gender Research Articles

Cytomegalovirus infection in kidney transplant patients: Prevalence, risk factors, and impact on outcome – A local multicentre experience

BackgroundCMV infection prevalence in kidney transplant recipients (KTR) is reported to be high in the literature, reaching rates of over 80%. ObjectivesThe primary endpoints were the evaluation of the prevalence, the risks factors, and the effects of CMV infection on graft function and survival, as well as patient survival at three years after kidney transplantation. Material and methodsWe retrospectively reviewed the medical records of 288 kidney transplant patients operated in three Lebanese transplant centers between 1998 and 2017 with three years of follow-up. The patients were divided into two groups: those free of any CMV infection (271 patients (94%); Group I) and those who suffered from CMV infection (17 patients (6%); Group II). ResultsBaseline demographics of the two groups were similar, including recipient and donor gender and age, cause of renal disease, recipient body mass index, pre-transplant fasting blood sugar and dialysis duration, HLA matching between donor and recipient, degree of sensitization in the recipient, type of CMV prophylaxis, maintenance immunosuppression and immunological characteristics. The prevalence of CMV infection is 5.9% among KTR. There were significant differences between the two groups concerning the type of induction therapy and the duration of anti-CMV prophylaxis. The rate of infected patients and infectious episodes were significantly higher in Group II. At 3-years, graft function and survival, patient survival, and the rate of new-onset diabetes were similar between the two groups. ConclusionThe present study is the first to explore the incidence and risk factors of CMV in kidney transplant patients in Lebanon. Comprehensive nationwide studies are therefore necessary to determine the epidemiology and risk factors of CMV infection after kidney transplantation in Lebanon.

Assessing the performance of a plateletpheresis unit at a tertiary-care academic medical center in Mexico: A 6-year experience.

Optimization of platelet (PLT) apheresis collection is a priority to satisfy the increasing demand of hemato-oncology patients. We assessed the performance of a plateletpheresis unit supporting hematology patients. This descriptive retrospective study included 561 plateletpheresis collections from 2013 to 2018. For data analysis, descriptive statistics and receiver operating characteristic (ROC) curve were used. A 5-item satisfaction questionnaire was analyzed. Ninety percent of the donors were males. The median plateletpheresis time was 89 minutes; its success rate was 92.5%; median donor PLT count was 232 × 109 /L, women median PLT count was 247 × 109 /L vs 231x109 /L in men (P=.017). Seventy-seven percent donors were candidates for a double product and 24.5% were processed; 20.8% of these donors had a weight ≤75 and 79.2% >75 kg, P=.003, and 6.6% were women and 93.4% men, P=.161. Thirty-six of donors had ≥250 × 109 /L and 16.8% was processed as a triple product. ROC analysis showed that with donor PLT counts ≥200 × 109 /L the sensitivity for obtaining double products was 0.981 and specificity 0.714, with an area under the curve (AUC)=0.877. The adverse effect rate was 4.3%. Of the potential donors, 6.3% were rejected. The cost of processing single or double products was 430 USD. Comfort and time spent during plateletpheresis were areas for improvement. Platelet count and donor weight predicted PLT yield and obtaining double products. Women had higher PLT counts, but no significant difference was found between donor gender and processed products. Assessment of the apheresis unit can help to improve its performance.

A comparative analysis of factors influencing haemoglobin content in RBC units

Background and objectivesThe increment in a patient’s haemoglobin level is based upon the haemoglobin content of the transfused RBC units. The total haemoglobin present in the blood bags can vary because of the blood donor, processing method, volume and type of bag used. The study is done to analyse the factors causing variation of haemoglobin content in RBC units. Materials and MethodsA total of 260 RBC units were tested for the haemoglobin content and analysed with the donor variables (age, gender, weight & capillary haemoglobin). The blood bags were then separated into two groups based on the donor capillary haemoglobin (normal 12.5–15.0 g/dL vs high 15.1–18.0 g/dL), volume (350 vs 450 mL), processing method (Platelet rich plasma vs buffy coat) and further analysis was carried out. ResultsThe mean haemoglobin content was 54.7 g ranging from 34.2–80 g per unit. The factors which significantly influenced (p < 0.0001) were capillary haemoglobin, gender and weight of donor, volume of blood collected and the processing method. There was a significant difference (p < 0.0001) in haemoglobin content between the two groups in all the three categories (capillary haemoglobin, volume and processing method). Regression analysis showed all three of them contributed to 80 % variability of haemoglobin content in the RBC unit. ConclusionThe marked variation of haemoglobin content in our study revealed that there is a need for standardizing RBC unit. Labelling of units with haemoglobin content and transfusion based on it will result in better patient care.

Gambaran Hasil Pemeriksaan HIV pada Darah Donor

HIV cases in Jepara District in recent years have demanded the handling of several aspects simultaneously including the Blood Transfusion Unit (BTU). HIV can be transmitted through blood transfusion or other blood products. BTU of PMI Jepara Regency carries out recruitment of voluntary donor from Jepara society. The HIV examination as part of an IMLTD screening test is done for safety of donor blood. The HIV examination in all donor blood uses rapid and elisa method. Examination results are stated as reactive and non reactive. Research objective to find out the description of HIV examination results in donor blood at the BTU of PMI Kabupaten Jepara in 2019. Research method the research type was descriptive using records of donor data at BTU of PMI Kabupaten Jepara in 2019. The examination results of reactive HIV in 12 donor blood (0,08%). non-reactive blood donor of HIV in age groups 18 years, 18-24, 25-44, 45-59, and ≥ 60 years respectively 9,55%, 22,39%, 51,75%, 16,01% and 0,21%. Reactive HIV in age groups 18-24, 25-44, and 45-59 years were 0,034%, 0,034%, and 0,13%. Non-reactive HIV in men 68,22% and in women 31,70%. Reactive HIV in men 0,07%, and women 0,01%. Non-reactive HIV in voluntary donor blood was 99,779% and substitute donor was 0,127%. HIV of reactive voluntary donor blood was 0,074%, and substitute donor was 0,007%. HIV filter test is indispensable for blood safety because the age, gender and blood type of donors have the potential for reactive HIV.

Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia in Argentina: Results Comparing Matched Related, Unrelated or Haploidentical Donors. a Grupo Argentino De Trasplante De Medula Osea (GATMO) Experience

Allogeneic hematopoietic cell transplantation (HCT) is a curative therapy for many Acute Myeloid Leukemia (AML) patients. There are not direct comparisons of results of HCT according to donor type in our region.Objective: To evaluate the impact of donor type in different outcomes as overall survival (OS), non relapse mortality (NRM), relapse (Rel) and disease free survival (DFS) in HCT for AML patients. Secondary objective was to evaluate early variables like engraftment, Acute Graft versus Host Disease (aGVHD), CMV reactivations, fungal infections and bacteriemias.Materials and Methods: A retrospective analysis of 250 medical records was conducted, addressing all patients who received an HCT for AML in seven Argentinian centers performing all three types of transplants, between January 2012 and December 2016. Mean patient´s age was 37 years; mean donors age 34 years; forty one percent (41%) of patients and 51% of donors were male; 89 patients (36%) received a matched related Allo-SCT (Sib), 78 (31%) an unrelated Allo-SCT (UD) and 83 (33%) a haploidentical Allo-SCT (Haplo). Pretrasplant HCT-CI score was low risk in 51% of the patients, 48% of the population were in CR 1 A myeloablative-conditioning (MAC) was used in 81% of the general population, peripheral blood stem cells were used in 85%.OS and DFS were tested with Kaplan Meier and NRM and Rel with cumulative incidence. Dichotomic variables were tested with Chi2. We conducted a multivariate analysis (MVA) for time dependent variables with Cox Regression.Results: Median follow up were 1.59 years. Patient and donor gender, age, HCT-CI and MAC were similar between the three type of donors., Haplo and UD groups were more likely to be in late stage compared to Sib (64% and 62% vs. 36%; p<0.001). BM source was more frequently used in Haplo (27% vs. 8% Sib and 6% UD ; p=0.001). Engraftment was slower in the Haplo group than in Sib and UD (≥15 days) (85% vs. 35% vs. 40% respectively; p=0.001). Graft failure rates were higher in Haplo than Sib and UD (16% vs. 1% and 4%; p=0.001). CMV reactivation was also more frequent in the Haplo and UD setting (53% and 56% vs.34%; p=0.02). There was a trend to a higher aGVHD incidence in UD group (60% vs. 43% Sib vs 42% Haplo; p=0.06), with no differences in GII-IV (41% vs. 27% vs 33%; p=0.19) or cGVHD (27% vs. 22% vs. 25%; p=0.65).Early NRM (day 100) was lower in Sib (4% Sib vs 13% UD vs 12% Haplo) as well as NRM at 1-3 years, (12-15% vs 21-25% vs 27-29% respectively; p=0.04) (Figure 1). Relapse rates (1-3 years) were higher among Sib and Haplo (39-44% Sib vs 40-40% Haplo vs 21-29% UD; p=0.05) (Figure 2). DFS (1-3 years) was higher in Sib and UD compared to Haplo (50-42% vs 57-46% vs 32-31% respectively; p=0.03) (Figure 3) as was OS (1-3 years 61-51% Sib vs 65-51% UD vs 44-34% Haplo; p=0.01) (Figure 4). This difference remained significant in the early stage disease (p=0.04) but no for late stageMultivariate analysis (expressed as Hazard Ratios with 95% confidence interval) showed that pretrasplant intermediate or high risk HCT-CI score were associated with poorer OS (HR 2.40, 1.34 - 4.30) and (2.67, 1.20 - 5.95). No association was seen with the type of donor used. Late stage disease at diagnosis was associated with higher relapse rates, independent of the type of donor and type of conditioning regime used (HR 2.05, 1.16-3.64). No factor affected negatively NRM after adjustment in MVA.Conclusion: Although early toxicity was similar in both Haplo and UD when expressed as NRM (day 100), worse 1 y and 3 y NRM and higher rates of relapse were observed in Haplo, resulting in a negative impact in OS. This experience shows that Haplo HCT is a complex procedure in the real world. Larger number of patients and prospective trials are needed to establish firm conclusions regarding the best strategy for patients with AML requiring a HCT [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Bone Marrow Transplant Product Quality Has Decreased Over Time— a Retrospective Examination of NMDP Collected Bone Marrow Products from 1994-2016

▪BackgroundBone marrow (BM) is an essential hematopoietic stem cell (HSC) source for many allogeneic transplants (HCT) and is the preferred cell source for specific disease indications in adults (e.g., Aplastic Anemia), the majority of pediatric transplants, and when the benefits of a decreased risk of chronic graft versus host disease (GVHD) outweigh other considerations. The advent of G-CSF mobilized peripheral blood stem cells (PBSC), with logistic benefits over the collection of BM, has resulted in a significant decrease in the utilization of BM. Since the advent of PBSC, BM has declined from 100% in the early 1990s to 15% in 2015, of unrelated donor products. This decreased utilization of BM has a number of potential consequences from a quality perspective. Many centers perform a limited number of BM collections per year and thus, the ability to ensure ongoing competency of staff in this technical procedure can be challenging. Proper assessment of BM harvest metrics is difficult in an individual collection facility when limited procedures are performed. Previous data from a single center noted that the total number of nucleated cells (TNC) received in BM products for individual patients decreased over the years. The aim of this study was to examine the trends in BM harvest quality in a large cohort of NMDP donors to see if this observation can be generalized.MethodsThe primary outcome of this study was examination of the total nucleated cells collected per milliliter (TNC/mL) of BM as an estimate of product quality. The population studied was BM donations from domestic unrelated donors reported to the NMDP/CIBMTR from 1994-2016 (analyzed over 5 time periods). The TNC/mL for each harvest was calculated based on the total number of nucleated cells (TNC) collected in harvest and the volume (mL) of final product including additives. Additional covariates, including time period of harvest, the number of harvests performed per year at the center, donor age, donor body mass index (BMI), donor weight, donor race/ethnicity, and donor gender were examined.ResultsExamination of >15,000 BM donations revealed a significant decline in the concentration of total nucleated cells from 21.8 TNC x 106/mL in the earliest era to 18.7 TNC x106/mL in the 2012-2016 era (p<0.001). (Table 1). The number of overall collections performed per center in the 2012-2016 era was similar to other eras (Table 2). The number of collections performed by a collection center did not appear to explain the decrease in BM quality as median TNC/mL decreased over time intervals regardless of collection centre size (Figure 1). Interestingly, the total product volume harvest increased over the eras (p<0.001), while the duration of the harvest decreased (p<0.001). Donor characteristics were examined across eras. In recent years, donors are significantly more likely to be male (p<0.001) and young (p<0.001). For example, in the 2012-2016 era, 54% of the donors were under the age of 30 as compared to the 1994-1996 and 1997-2001 eras where only 25% of the donors were under the age of 30. Similarly, 65% of the donors were male in the 2012-2016 era, compared to 53% in the 1994-1996 era.ConclusionIn conclusion, we showed a significant decrease in the TNC/mL in BM products over time. This did not appear to be related to the number of collections per center, suggesting that cell number collected is not directly related to the number of procedures performed but rather other factors in the collection process. Interestingly, the significant decrease in TNC concentration in BM observed in this study persisted despite the increased use of optimal donors. Further analysis will be required to elucidate the exact cause of decreased concentration of TNC collected in products. Factors such as technique, rate of collection, materials /equipment used, training, and collector experience may have profound influences on the quality of BM collected. For example, the number of personnel performing harvests, number of harvests performed per collector, or turn-over of personnel at each collection center maybe contributing factors. These further studies will help to better understand the entire process and help improve the quality of the products, an issue crucial to ensuring bone marrow remains a quality cell source for transplant. [Display omitted] DisclosuresPulsipher:Jazz Pharmaceuticals: Other: advisory board, education; CSL Behring: Other: advisory board Feb 2017; Adaptive: Other: Advisory board 6/17; Chimerix: Other: Advisory board Dec 2015; Novartis Pharmaceuticals Corporation: Consultancy, Other: Phase II steering committee.

Determinants of Long-Term Survival Following Allogeneic Stem Cell Transplantation for Multiple Myeloma: A Multi-Centre Analysis Across the United Kingdom and Australia

IntroductionDespite the accepted utility of autologous stem cell transplantation for multiple myeloma, the role of allogeneic stem cell transplantation (alloSCT) remains controversial (Dhakal et al., 2016). The differences in practices across centres in patient selection, conditioning regimens and post-transplant care clouds the comparison of available studies. Moreover, the high rates of non-relapse mortality despite disease eradication demand an understanding of pre-allograft determinants of long-term survival. Included within these determinants is the appropriate timing for alloSCT, an important variable given the growing list of available myeloma therapies. We sought to identify the variables, including the influence of transplant centre and timing that govern long term survival following alloSCT for myeloma within integrated data in a large group of patients across three centres.MethodsA retrospective analysis of 93 patients undergoing alloSCT for multiple myeloma between January 2000 and June 2017 at three tertiary transplant centres - the Royal Melbourne Hospital, Australia and The Christie and Central Manchester NHS Foundation Trusts, United Kingdom. We collected: demographic data; disease-specific data, including previous treatment, disease status prior to alloSCT, and time from autologous SCT to alloSCT; and peri-transplant data including donor source and gender, stem cell dose, conditioning regime, and donor and recipient cytomegalovirus serological status. We measured overall survival, cause of death, acute and chronic graft versus host disease and progression free survival. Log-rank testing and cox regression analysis was performed with a multivariate regression model established on the basis of significant univariate associations.ResultsMedian age for the 93 patients at transplant was 49 years old (range 28 to 66 years). 65% of patients were male (n=60). 51 patients underwent alloSCT at the Royal Melbourne Hospital, 18 and 24 patients at the Christie and Central Manchester NHS Foundation Trusts, respectively. Patients received a median number of 2 lines of treatments prior to alloSCT (range 0-6). 51% (n=47) patients received stem cells from voluntary unrelated donors (VUD), and 49% from siblings (n=46). 78% (n=72) received a reduced intensity conditioning consisting of either 25mg/m2 fludarabine, 60mg/kg cyclophosphamide or 30mg/m2 fludarabine with 2Gy total body irradiation; 20% (n=18) received non-myeloablative conditioning with 30mg/m2 fludarabine and 750mg/m2 cyclophosphamide, 2% (n=3) underwent myeloablative conditioning with 60mg/kg cyclophosphamide and 4Gy total body irradiation.Median overall survival (OS) for the whole group was 8.1 years (interquartile range = 1.3 to 12.7 years). No difference was observed in OS across the three centres (log rank p=0.84) or across country (log-rank p=0.56). Conditioning regimens containing total body irradiation showed no association with relapse post allo SCT (odds ratio 0.68, 95% CI 0.30-1.55) and did not affect OS (hazard ratio, HR =1.00, 95% CI = 0.51-2.00).In accordance with previous findings (Dhakal et al., 2016), age over 40 at alloSCT was associated with a poorer survival (HR = 2.47, 95%CI 1.20 to 5.09). Patients who had stable or progressive disease at allograft showed poorer OS, even when controlling for number of lines of therapy and previous relapse (HR = 3.03, 95% CI 1.31-6.97).Patients who underwent alloSCT over one year following autologous SCT showed 3.4 times increased risk of death (95% CI 1.52-7.09) and 2.16 times increased risk of relapse (95% CI 1.18-3.93) even when controlling for age, prior relapse history, number of lines of treatment, disease status prior to alloSCT and transplanting hospital (Figure 1).ConclusionThis large multi-centre multivariate analysis demonstrates that transplant centre and low dose total body irradiation does not influence OS following alloSCT for multiple myeloma. Importantly, the time between autologous SCT and alloSCT of greater than one year is a strong predictor of poor OS. This remains true when controlling for several established risk factors. Our results demonstrate the importance of patient selection and timing in order to maximise OS for patients undergoing alloSCT for multiple myeloma.ReferenceDhakal B, et al. 2016. Allogeneic stem cell transplantation for multiple myeloma: is there a future? Bone Marrow Transplant, 51, 492-500. [Display omitted] DisclosuresRoutledge:Gilead: Honoraria; Celgene: Honoraria; Bristol-Myers Squibb: Honoraria. Harrison:Celgene: Consultancy, Research Funding, Speakers Bureau. Cavet:Celgene: Membership on an entity's Board of Directors or advisory committees, Other: Speaker, Research Funding. Tholouli:Pfizer: Honoraria, Speakers Bureau; MSD: Honoraria, Speakers Bureau; Jazz Pharmaceuticals: Honoraria, Speakers Bureau. Ritchie:Amgen Inc.: Honoraria.

The Measurable Residual Disease Status of Acute Myeloid Leukemia in First Complete Remission at Allogeneic Hematopoietic Cell Transplantation Interacts with Conditioning Intensity to Predict Outcome

BACKGROUND: Allogeneic hematopoietic cell transplant (allo-HCT) is offered to selected patients with acute myeloid leukemia (AML) in first complete remission (CR1). Despite overall survival (OS) benefits compared to non-HCT therapy, transplant related mortality (TRM) & relapse incidence (RI) remain obstacles. Reduced intensity (RIC) & non-myeloablative (NMA) conditioning regimens have reduced early toxicity & permit extension of allo-HCT to older or infirm patients but RI offsets this benefit. Disease status at allo-HCT predicts subsequent relapse. Patients with AML CR1 & measurable residual disease (MRD POS) have a higher RI than those who are MRD NEG. We hypothesised that in AML CR1, MRD status would interact with conditioning intensity to predict survival & toxicity in patients <50y & ≥50y. METHODS: This was a multicentre, retrospective registry study by the Acute Leukemia Working Party of the European Society for Blood & Bone Marrow Transplantation. Eligibility: Age ≥18y, first allo-HCT 2000-15, diagnosis of AML with a molecular marker, CR1 & availability of MRD status (polymerase chain reaction / immunophenotyping as per center policy), peripheral blood stem cells (PBSC) or bone marrow (BM) from a matched related (MRD), volunteer unrelated (VUD) or haplo-identical donor.Univariate & Cox Regression multivariate analyses (MVA) were applied to data. Measured outcomes included 2y OS, leukemia free survival (LFS), non-relapse mortality (NRM), graft vs host disease (GVHD) & GVHD-free/relapse-free survival (GRFS).RESULTS: A total of 2292 patients, 1192 male, were eligible. Conditioning intensity was high intensity “myeloablative” (MAC) in 1254 (55%), RIC in 867 (38%) & NMA in 171 (7%). Patients were defined by age, MRD status & conditioning. This yielded 4 paired groups of patients: <50y MRD POS MAC (N=240) vs RIC/NMA (N=58); <50y MRD NEG MAC (N=665) vs RIC/NMA (N=195); ≥50y MRD POS MAC (N=126) vs RIC/NMA (N=230) & ≥50y MRD NEG MAC (N=223) vs RIC/NMA (N=555). Groups were comparable for the following parameters: Cytogenetic risk groups (intermediate in 71% & high risk in 29%); FLT3 or NPM1 mutation status (reported in 55% & 45%); CR rate with first induction (69% & reported in 1706 [74%]). While donor source & gender were also comparable, there was significantly greater use of PBSC than BM within all groups. In vivo T-cell depletion (TCD) was used in 46% & 59% of MAC & RIC allo-HCT overall & retained significance within all paired groups.Univariate analysis of all patients confirmed the predictive effect of MRD status on allo-HCT outcomes. Patients <50y & MRD POS benefited from MAC vs NMA/RIC allo-HCT with RI 36.6% vs 50.7% (P=0.013), LFS 49% vs 36.5% (P=0.004), OS 59.4% vs 43.7% (P=0.008) & GRFS 35.3% vs 28.2% (P=0.025). In contrast, patients who were <50y MRD NEG, ≥50y MRD POS or ≥50y MRD NEG derived no survival benefits from MAC compared to RIC/NMA allo-HCT.Next, Cox regression analysis was performed, adjusting for age by decade, cytogenetic risk, stem cell source, donor & TCD. In <50y MRD POS, RIC/NMAwas inferior to MAC for RI (HR 1.7 CI 1.05-2.79) & LFS (HR 1.6 CI 1.01-2.40) with a trend to lower OS. Use of TCD reduced acute GVHD grades III-IV (HR 0.32 CI 0.12-0.843).In <50y MRD NEG, RIC/NMA & MAC allo-HCT had equivalent RI, NRM, LFS & OS but less chronic GVHD following RIC/NMA regimens (HR 0.7 CI 0.52- 0.99). Adverse factors in this group were poor risk cytogenetics (impacting RI, LFS & OS) & use of VUD vs MRD, associated with higher aGVHD & cGVHD rates. TCD conferred reduced GVHD & LFS without significant effect on OS. Use of PBSC increased NRM & GVHD toxicity without significant effect on LFS or OS.In ≥50y MRD POS patients, RI, NRM, LFS & OS were unaffected by conditioning intensity. Poor risk cytogenetics exerted adverse effects on RI (HR 1.8 CI 1.26-2.57), LFS (HR 1.7 CI 1.28-2.31) & OS (HR 1.8 CI 1.32-2.47). Increasing recipient age associated with increased risk of aGVHD (III-IV) (HR 3.2 CI 1.36 - 7.61) but no other parameter altered outcome.In ≥50y MRD NEG patients, no benefits accrued to MAC for RI, NRM, LFS & OS & there was a trend to lower NRM in RIC/NMA (HR 0.7 CI 0.48-1.03). TCD increased RI & reduced NRM & GRFS without effect on LFS or OS.CONCLUSION: MAC allo-HCT benefits <50y MRD POS patients. RIC allo-HCT may be sufficient for other groups. Procedural toxicity may be reduced further by in vivo TCD. MRD impact on allo-HCT needs prospective evaluation & standardization of molecular & immunophenotyping assays. DisclosuresMohty:Sanofi: Honoraria, Speakers Bureau. Savani:Jazz Pharmaceuticals: Speakers Bureau.

Obedient Men and Obsessive Women: Donor Insemination, Gender and Psychology in Belgium

AbstractDrawing on contemporary studies and oral history interviews, this article analyses psychiatric evaluations of heterosexual couples requesting donor insemination in Belgium in the 1970s. It contains two interrelated arguments. First, it reassesses the reason why mental health professionals were incorporated into fertility clinics. In response to negative assumptions about the mental stability of candidates seeking donor insemination, they had to act as gatekeepers. This finding contradicts earlier research, which linked the integration of mental health professionals in reproductive medicine to the growing awareness of the emotional consequences of infertility and to the exclusivity of in vitro fertilisation. Second, this article shows that psychiatric evaluations were influenced by both traditional gender roles and newer models of equality. As the mirror of a society that was changing at different speeds, they reflected both the transformation of traditional ideals of family, sex and marriage and the discomfort sparked by these changes.

MO931PRETRANSPLANT ANGIOTENSIN II TYPE 1 RECEPTOR ANTIBODIES INFLUENCE GRAFT FUNCTION BUT NOT GRAFT SURVIVAL AT 1 YEAR AFTER KIDNEY TRANSPLANTATION IN A LOW IMMUNOLOGICAL RISK COHORT

Abstract Background and Aims Angiotensin II type 1 receptor antibodies (AT1R-Ab) are associated with graft rejection and poor graft outcomes in kidney transplantation (KT). It has been shown that AT1R-Ab have a negative impact on both short-term and long-term graft function, even in the absence of rejection, but this has not been confirmed by other studies. Our aim was to assess the frequency of pretransplant AT1R-Ab and to determine their influence on graft function and survival at 1 year after KT. Method We performed a prospective, observational cohort study in 67 adult KT recipients, transplanted between October 2018 and October 2019. Clinical, biological and immunological data of the recipients, age, gender and type of donor, transplant and immunosuppression parameters were collected at the moment of transplantation. A cut-off &amp;gt; 10 U/mL was used for AT1R-Ab detection. Results Among the 67 recipients mean age was 41.3 ± 10.3 years, male gender was predominant (59.7%) and the main known cause of end-stage renal disease was glomerular disease. Six patients out of 67 (9%) had a previous kidney transplant. The donor mean age was 50 ± 15.5 years and 65.7% of patients received the kidney graft from a cadaveric donor. Pretransplant AT1R-Ab were detected in 7 out of 67 patients (10.4%) and none of the patients had specific antibodies against human leucocyte antigen. After 1 year of follow-up, median estimated glomerular filtration rate (eGFR) of the recipients was 54 ml/min/1.73 m2 (40.6 – 65.9), 10.4% of patients developed delayed graft function, 7.5% had graft failure and no cases of biopsy proven graft rejection or death was reported. Patients with pretransplant AT1R-Ab had a significant reduced graft function at 1 year after KT compared to those without antibodies [35 (29.8- 55.2) vs 56.1 (41.3 – 66.5) ml/min, p=0.02]. After multivariate linear regression analysis, pretransplant AT1R-Ab were an independent determinant of eGFR at 1 year after KT (β: -14.066; 95% CI: -27.44 - -0.68; p=0.04). Cox regression analysis was used to assess the association of AT1R-Ab along with other clinical, biological and immunological parameters with graft failure. Neither the univariate (HR= 2.07, 95% CI: 0.23-18.52, p=0.51) nor the multivariate (HR= 1.36, 95% CI: 0.10-14.09, p=0.80) Cox regression models showed that pretransplant AT1R-Ab were an independent predictor for graft loss. Conclusion We showed that pretransplant AT1R-Ab are an independent determinant of graft function but do not influence the graft survival at 1 year after transplantation in a prospective low immunological risk cohort of kidney transplant recipients.

Fecal Microbiota Transplantation is a Promising Switch Therapy for Patients with Prior Failure of Infliximab in Crohn's Disease.

Background: How to handle patients with anti-tumor necrosis factor (anti-TNF) failure was a common challenge to clinicians in Crohn’s disease (CD). The present study is dedicated to clarifying whether fecal microbiota transplantation (FMT) could be a switch therapy for patients with prior failure of infiiximab (IFX) in CD in a long-term observation. Methods: Thirty-six patients with CD who had prior failure of IFX were recruited from January 2013 to December 2019. The “one-hour FMT protocol” was followed in all patients. All patients received the first course of FMT through gastroscopy or mid-gut transendoscopic enteral tubing. After April 2014, the methodology of FMT was coined as washed microbiota transplantation (WMT), substituting for the manual methods, which is dependent on the automatic microbiota purification system and the washing process. The primary endpoint of this study was the clinical remission at one month and one year after FMT. The secondary endpoint was the safety of FMT in the short and long term, and clinical factors as predictors for long-term efficacy of FMT. Clinical factors as independent predictors of efficacy from FMT were isolated using univariable and multivariable logistic regression analysis. Results: There was no significant difference in the rates of clinical response and remission between IFX treatment stage and FMT treatment stage (at one month, three months and six months after administration) (p > 0.05). Compared with those of 19 patients who achieved clinical remission at one month after FMT, the rates of clinical relapse were significantly higher in 18 patients who achieved clinical remission at one month after IFX [log-rank test p = 0.0009 HR = 3.081 (95% CI 1.43–6.639)]. Multivariate analysis revealed that the gender of donor (95% CI: 0.001–0.72; p = 0.031) was an independent predictor of efficacy at one year after FMT. No serious adverse events (AEs) associated with FMT were observed during and after FMT. The rate of AEs was significantly lower in group FMT than that in group IFX (p = 0.002). Conclusion: The present findings first time provided the evidence for clinicians to consider FMT into practice as an alternative switch therapy for patients with prior loss of response or intolerance to IFX in CD. Clinical Trial Registration: https://clinicaltrials.gov, identifier NCT01793831

Seroepidemiology of Hepatitis B and C Virus Infections: A Five-Year Retrospective Study among Blood Donors in Saboba District in the Northern Region of Ghana.

Methods A five-year hospital-based retrospective study was carried out among 8605 blood donors comprising 8517 males and 88 females using data on blood donors from Saboba Assemblies of God Hospital located in the Saboba District in the Northern Region of Ghana from 2013 to 2017. Blood bank records on HBV and HCV potential blood donors who visited the hospital to donate blood were retrieved. Donor demographic details, i.e., age and gender, were also recovered. Donors who were registered to the hospital but were not residents of the Northern Region were excluded from the study. Donors with incomplete records were also excluded from the study. The data was managed using Microsoft Excel spreadsheet 2016 and analysed using GraphPad Prism statistical software. Results The overall prevalence of asymptomatic viral hepatitis B and C infections in the general adult population was 9.59% (95% CI: 9.00-10.20) and 12.71% (95% CI: 12.00-13.40), respectively, with an HBV/HCV coinfection rate of 2.23% (95% CI: 1.90-2.60). The number of donors generally declined with advancement in years from 2038 (23.68%) since 2013 to as low as 1169 (13.59%) in 2016, except for 2017 where a sharp increase of 1926 (22.38%) was observed. The first and second highest proportions of donors fell within the age categories of 20-29 (51.53% (4434)) and 30-39 (32.90% (2831)) respectively. The seroprevalence rate of HBV, HCV, and HBV/HCV coinfection rates were generally higher among the female group than those observed among the male category. The year-to-year variation in HBV, HCV, and HBV/HCV infections was statistically significant. The highest year-to-year HBV seropositivity rate was 11.48% in the year 2013, while that for HCV and HBV/HCV coinfection was 16.24% and 5.85%, respectively, both documented in the year 2014. HBV and HBV/HCV coinfection rates were highest among donors aged <20 years old, while HCV seroprevalence was highest among donors aged 50-59 years old. Significantly higher odds of HBV/HCV coinfection (OR = 5.2; 95% CI:3.3-8.1) was observed in the 2014 compared to the year 2013. Donors aged <20years were at higher risks of HBV and HBV/HCV coinfection rates compared to the other age groups. Conclusion The seroprevalence of HBV and HCV among donors in the Saboba District of the Northern Region of Ghana is endemic. The HBV/HCV coinfection rate also raises serious concern owing to its high prevalence rate among the younger age. Intensive public health education coupled with mobile screening and mass vaccination of seronegative individuals is advised so as to help curb further spread of the infection and in effect help safeguard the health status of potential donors in the district.

Extracorporeal Membrane Oxygenation-Induced Hemolysis: An In Vitro Study to Appraise Causative Factors

In vitro hemolysis testing is commonly used to determine hemocompatibility of ExtraCorporeal Membrane Oxygenation (ECMO). However, poor reproducibility remains a challenging problem, due to several unidentified influencing factors. The present study investigated potential factors, such as flow rates, the use of anticoagulants, and gender of blood donors, which could play a role in hemolysis. Fresh human whole blood was anticoagulated with either citrate (n = 6) or heparin (n = 12; 6 female and 6 male blood donors). Blood was then circulated for 360 min at 4 L/min or 1.5 L/min. Regardless of flow rate conditions, hemolysis remained unchanged over time in citrated blood, but significantly increased after 240 min circulation in heparinized blood (p ≤ 0.01). The ratio of the normalized index of hemolysis (NIH) of heparinized blood to citrated blood was 11.7-fold higher at 4 L/min and 16.5–fold higher at 1.5 L/min. The difference in hemolysis between 1.5 L/min and 4 L/min concurred with findings of previous literature. In addition, the ratio of NIH of male heparinized blood to female was 1.7-fold higher at 4 L/min and 2.2-fold higher at 1.5 L/min. Our preliminary results suggested that the choice of anticoagulant and blood donor gender could be critical factors in hemolysis studies, and should be taken into account to improve testing reliability during ECMO.

POS-702 IMPACT OF DONOR-RECIPIENT GENDER ON GRAFT SURVIVAL

A number of donor and recipient factors have been identified that increase the risk of both early and late adverse outcomes after kidney transplantation. Most literature has emphasized the importance of immunologic mismatches; however, earlier studies have also demonstrated that nonimmunologic factors may influence graft and patient outcome.The aim of this study was to analyze whether sex mismatch between donor and recipient influence survival results of kidney transplant grafts. We performed a cohort-retrospective study using data on kidney transplantation ,done between January 1995 to December 2014 in our department. All patients achieved a minimum follow-up of 5-years.The patients were subdivided into four groups according to recipient and donor gender. Graft survival was calculated by the Kaplan–Meier method and compared using the log rank test. The study cohort included 133 kidney transplant recipients with a mean age of 31,58±9.8 years. Of these, 63.2% of kidneys were from female donors and 71.4% of recipients were male.The proportion of female donor–male recipient;male donor–male recipient;male donor–female recipient and female donor–female recipient were 54.1%,24.1%,12.8%,9% respectively. Female donor to male recipient had the inferior long-term graft survival (70.8% have graft estimated Glomerular Filtration RateGFR <60 ml/min at 5 years) compared to the other groups male donor–male recipient (62.5%);male donor–female recipient (52.9%)and female donor–female recipient (33.3%)(P < 0.01). Previous studies have shown inferior outcome when female kidneys are transplanted into male patients. A finding that might be explained by nephron-underdosing theory. The results presented confirm this hypothesis and suggest that the sex matching between donors and recipients should be considered as a criterion for choice of donor and recipient pairs.

Extracorporeal Life Support Registry: Analysis of Ex Vivo Lung Perfusion Utilization in Donor after Cardiac Death and Donor after Brain Death

<h3>Purpose</h3> Ex vivo lung perfusion (EVLP) improves organ quality and makes the lungs safe that were previously unsuitable for bilateral lung transplant (BLT). We investigated EVLP utilization in BLT from our ECLS registry and compared the outcome in DCD and DBD. <h3>Methods</h3> Patient data involving BLT were collected from the National ECLS Registry and stratified by EVLP in DCD and DBD. ECLS usage information was obtained and analyzed with Chi-square testing or Fisher's exact test to determine a relationship with donor groupings in EVLP. Lung transplant procedure details, patient and donor demographics and post-operative survival were analyzed using Wilcoxon rank sum test or Chi-square testing to determine distribution. Kaplan-Meier survival curves with log-rank testing to assess mortality between donor groups with EVLP use. P-values <0.05 were considered statistically significant. <h3>Results</h3> Out of 932 BLT, there were total 66 EVLP: 20 DCD and 46 DBD cases. Demographics data showed age:54±14 years, BMI 25 ± 5 kg/m², 34M, LAS - 44±14, PHTN - 51 patients, prior ECMO - 2, donor age 38 ± 14, donor gender - 38M, total ischemic time - 578±149 min, Use of ECLS - CPB:7, ECMO:26, Modified bypass:8, Off-pump:25, PGD at 48h-72h - 18, Post-op ECMO: VA - 3, VV - 12, VVA - 1. Death before discharge - 9, before 90d - 5, before 1yr - 9. Tracheostomy - 15 patients, post-op pneumonia - 10 patients, median length of stay - 22 days. Unadjusted comparison reveals significant differences in 1yr survival with EVLP vs DBD vs DCD utilization (HR:2.16; CI- 1.00-4.66; p=0.05), but when adjusted, there were no significant differences (HR:0.93; CI- 0.33-2.60; p=0.883). Kaplan-Meier curve showed no statistical significance in DCD and DBD groups when used for EVLP. <h3>Conclusion</h3> EVLP utilization did not have any significant effect in survival when used in DCD and DBD transplantation. It suggests EVLP can be safely utilized in both groups thereby increasing the donor pool.

Impact of Gender Matching in Heart Transplantation: Does Sex Matter?

Purpose Appropriate allocation of suitable donor organs has a major impact on outcome after Heart transplantation (HTx). In contrast to body weight and height matching of respective donor and recipient, gender mismatch remains a matter of discussion. Particularly, gender-related differences in sex hormones and immunological processes that may impact the outcome after HTx are still not fully understood. Methods Between 2010 and 2020 a total of 178 patients underwent HTx in our department. The patients could be divided into four groups according to gender matching (male donor for male recipient: MDMR group, n=92; male for female: MDFR group, n=9; female for male: FDMR group, n=42; female for female: FDFR group, n=35). Results The groups were comparable regarding, age, underlying disease, graft function and allograft ischemia, but recipients of male donor organs were significantly more often listed with high urgency (HU) status. In addition, height (p 1R). Hospitalization time, stay on intensive care unit and duration of mechanical ventilation did not differ either. However, there was a slight trend towards impaired 30-day survival (MDMR group: 91.0%, MDFRgroup: 100%, FDMR group: 92.9%, FDFR group: 76.5%, p=0.09) and one-year (MDMR group: 83.3%, MDFR group: 62.5%, FDMRgroup: 74.4%, FDFR group: 77.1%, p=0.22) survival of female recipients compared to male ones. Conclusion We did not find any significant differences in outcome after HTx related to gender matching of donors and recipients. However, there was a trend towards impaired early survival for female recipients. This effect was irrespective of the donor's gender. Our results indicate that sex does not matter for the outcome after HTx. Therefore, we suggest mainly to focus on our parameters such as size and weight matching instead of gender in order to achieve the best results for all patients undergoing HTx.

Time from Start of Agonal Phase to Pulmonary Artery Cross Clamp in Donor Cardiac Death Donors Does Not Correlate with Diminished Recipient Lung Function or Survival

Purpose Donor cardiac death (DCD) donors could expand the field of lung donors, but the acceptably safe time interval between the onset of agonal phase and application of the pulmonary artery clamp is controversial. The purpose of this study was to determine if the time from the beginning of the agonal phase to placement of the pulmonary artery cross clamp in DCD donors is associated with worse recipient lung function or long-term survival. Methods The Scientific Registry for Transplant Research database (2008-2019) was queried for lung transplants performed from DCD donors (N=227) excluding pediatric, multi-organ, and redo lung transplants. Time from the beginning of agonal phase to the time of pulmonary artery cross clamp placement was determined, and donor and recipient characteristics and outcomes were examined for 3 groups: 0-30 minutes (N=178), 30-45 minutes (N=25), and over 45 minutes (N=21). Eight DCD donor lungs had an agonal phase to pulmonary artery cross clamp time between 75 and 120 minutes. The primary endpoints were forced expiratory volume in 1 second (FEV1) at 1 and 2 years and overall survival using Kaplan Meier analysis. Results There were no significant differences in donor age, gender or body mass index between the three groups. Recipient characteristics were comparable between the three groups, and there was no difference in recipient FEV1 at 1 (80.47+/-22.45%, 79.81+/-16.60%, and 76.67+/-13.30%, p=0.840) and 2 years (76.23+/-27.13%, 76.11+/-24.31%, 82.17+/-17.58%, p=0.868) for the three groups (0-30 minutes, 30-45 minutes, and over 45 minutes, respectively) . There was no difference in long term survival out to 10 years between the three groups using Kaplan Meier analysis. Conclusion Lung transplant recipient lung function and survival is similar for recipients of DCD donor lungs regardless of the time from start of the agonal phase to application of the pulmonary artery transplant out to and beyond 45 minutes.

Sex-Based Outcomes of Heart Re-Transplantation: Analysis from UNOS Database

<h3>Purpose</h3> Heart re-transplantation (re-HTx) outcomes are thought to more challenging than primary transplants. There is limited information about the impact of sex matching on prognosis in re-HTx. In this study, we aim to elucidate sex-based outcomes of re-HTx using United Network for Organ Sharing (UNOS) database. <h3>Methods</h3> Adult (≧ 18 years) patients undergoing re-HTx from January 2007 and March 2016 were identified from the UNOS database. Demographic data and outcomes were compared on the recipient sex differences. <h3>Results</h3> There were 463 patients and 179 (38.7%) were female. Compared with male, female recipients were younger (p<.0001), smaller body mass index (p=0.013), lower total bilirubin (p<0.001), fewer smokers (p<0.001), more likely to have renal dysfunction (p=0.002), donor gender female (p<.0001) and larger predicted heart mass ratio (p<0.001). The 30-day and one-year mortality was significantly higher in female recipients compared to male (11.3% vs. 5.0%, p=0.012 and 21.3% vs. 16.9 %, p=0.042, respectively). Kaplan-Meier curve showed significantly worse outcome in female donor-female recipients' cohort (Figure). On multivariable cox regression analysis, female donor-female recipients (HR 1.693, 95% CI 1.035-2.768, p=0.036) was a significant factor of 1-year mortality. <h3>Conclusion</h3> The outcome of female recipients for re-HTx is worse than that of male recipients. Female recipients who receive a female donor had a worst outcome.

Risk indices predicting graft use, graft and patient survival in solid pancreas transplantation: a systematic review

BackgroundRisk indices such as the pancreas donor risk index (PDRI) and pre-procurement pancreas allocation suitability score (P-PASS) are utilised in solid pancreas transplantation however no review has compared all derived and validated indices in this field. We systematically reviewed all risk indices in solid pancreas transplantation to compare their predictive ability for transplant outcomes.MethodsMedline Plus, Embase and the Cochrane Library were searched for studies deriving and externally validating risk indices in solid pancreas transplantation for the outcomes of pancreas and patient survival and donor pancreas acceptance for transplantation. Results were analysed descriptively due to limited reporting of discrimination and calibration metrics required to assess model performance.ResultsFrom 25 included studies, discrimination and calibration metrics were only reported in 88% and 38% of derivation studies (n = 8) and in 25% and 25% of external validation studies (n = 12) respectively. 21 risk indices were derived with mild to moderate ability to predict risk (C-statistics 0.52–0.78). Donor age, donor body mass index (BMI) and donor gender were the commonest covariates within derived risk indices. Only PDRI and P-PASS were subsequently externally validated, with variable association with post-transplant outcomes. P-PASS was not associated with pancreas graft survival.ConclusionMost of the risk indices derived for use in solid pancreas transplantation were not externally validated (90%). PDRI and P-PASS are the only risk indices externally validated for solid pancreas transplantation, and when validated without reclassification measures, are associated with 1-year pancreas graft survival and donor pancreas acceptance respectively. Future risk indices incorporating recipient and other covariates alongside donor risk factors may have improved predictive ability for solid pancreas transplant outcomes.

Who Controls the Purse Strings? A Longitudinal Study of Gender and Donations in Canadian Politics

AbstractGender gaps in voter turnout and electoral representation have narrowed, but other forms of gender inequality remain. We examine gendered differences in donations: who donates and to whom? Donations furnish campaigns with necessary resources, provide voters with cues about candidate viability, and influence which issues politicians prioritize. We exploit an administrative data set to analyze donations to Canadian parties and candidates over a 25-year period. We use an automated classifier to estimate donor gender and then link these data to candidate and party characteristics. Importantly, and in contrast to null effects from research on gender affinity voting, we find women are more likely to donate to women candidates, but women donate less often and in smaller amounts than men. The lack of formal gendered donor networks and the reliance on more informal, male-dominated local connections may influence women donors’ behavior. Change over a quarter century has been modest, and large gender gaps persist.