Loss of heterozygosity leading to incorrect HLA typing for platelet-transfusion refractory patient.

BACKGROUND: Management of platelet-transfusion refractory (PR) patients due to anti-HLA antibodies includes the provision of HLA-matched (HLAm) platelets (PLT) or PLTs that are negative for HLA antigens corresponding to the recipient antibodies. Obtaining HLAm PLTs is predicated on accurate HLA antigen typing of the recipient and donor. Here, we present the clinical implications of a case involving loss of heterozygosity (LOH) in a patient presented for PR workup. STUDY DESIGN AND METHODS: HLA typing was performed by three methods: (1) Real-time PCR; (2) Sequence-specific oligonucleotide (SSO) typing test; and (3) Next-Generation Sequencing (NGS). Cytogenomic SNP microarray was utilized to assess LOH. RESULTS: A 30-year-old female with newly diagnosed acute myelogenous leukemia was found to be PR secondary to HLA sensitization. A peripheral blood (PB) sample, containing 93% myeloid blast cells, was sent for HLA typing for the provision of HLAm PLTs. HLA typing revealed homozygosity at the HLA-A locus but was heterozygous at the -B and -C loci. After chemotherapy, HLA typing on a new PB sample, devoid of blast cells, identified HLA-A locus heterozygosity, which was subsequently confirmed by real-time PCR and NGS. Cytogenomic SNP microarray analysis demonstrated LOH of the HLA-A locus on chromosome 6p in the pretreatment sample but not in the posttreatment sample. CONCLUSION: In hematologic patients with high tumor burden, HLA homozygosity should be viewed with suspicion for potential LOH. Therefore, HLA testing should be repeated, preferably with a non-hematological source (e.g., buccal swab) or following successful reduction of the tumor burden.

Employment status at transplant influences ethnic disparities in outcomes after deceased donor kidney transplantation.

BACKGROUND: African American (AA) recipients of deceased-donor (DD) kidney transplants (KT) have shorter allograft survival than recipients of other ethnic groups. Reasons for this disparity encompass complex interactions between donors and recipients characteristics. METHODS: Outcomes from 3872 AA and 19,719 European American (EA) DDs who had one kidney transplanted in an AA recipient and one in an EA recipient were analyzed. Four donor/recipient pair groups (DRP) were studied, AA/AA, AA/EA, EA/AA, and EA/EA. Survival random forests and Cox proportional hazard models were fitted to rank and evaluate modifying effects of DRP on variables associated with allograft survival. These analyses sought to identify factors contributing to the observed disparities in transplant outcomes among AA and EA DDKT recipients. RESULTS: Transplant era, discharge serum creatinine, delayed graft function, and DRP were among the top predictors of allograft survival and mortality among DDKT recipients. Interaction effects between DRP with the kidney donor risk index and transplant era showed significant improvement in allograft survival over time in EA recipients. However, AA recipients appeared to have similar or poorer outcomes for DDKT performed after 2010 versus before 2001; allograft survival hazard ratios (95% CI) were 1.15 (0.74, 1.76) and 1.07 (0.8, 1.45) for AA/AA and EA/AA, compared to 0.62 (0.54, 0.71) and 0.5 (0.41, 0.62) for EA/EA and AA/EA DRP, respectively. Recipient mortality improved over time among all DRP, except unemployed AA/AAs. Relative to DDKT performed pre-2001, employed AA/AAs had HR = 0.37 (0.2, 0.69) versus 0.59 (0.31, 1.11) for unemployed AA/AA after 2010. CONCLUSION: Relative to DDKT performed before 2001, similar or worse overall DCAS was observed among AA/AAs, while EA/EAs experienced considerable improvement regardless of employment status, KDRI, and EPTS. AA recipients of an AA DDKT, especially if unemployed, had worse allograft survival and mortality and did not appear to benefit from advances in care over the past 20 years.

Stem cell donor HLA typing improves CPRA in kidney allocation.

The Organ Procurement and Transplantation Network (OPTN) Kidney Allocation System provides a priority to sensitized candidates based on the calculated panel reactive antibody (CPRA) value. The human leukocyte antigen (HLA) haplotype reference panel used for calculation of the CPRA by the United Network for Organ Sharing (UNOS), the OPTN contractor, has limitations. We derived a novel panel from the National Marrow Donor Program HLA haplotype data set and compared the accuracy of CPRA values generated with this panel (NMDP-CPRA) to those generated from the UNOS panel (UNOS-CPRA), using predicted and actual deceased donor kidney offers for a cohort of 24 282 candidates. The overall accuracy for kidney offers was similar using NMDP-CPRA and UNOS-CPRA. Accuracy was slightly higher for NMDP-CPRA than UNOS-CPRA for candidates in several highly sensitized CPRA categories, with deviations in linkage disequilibrium for Caucasians and the smaller size of the UNOS panel as contributing factors. HLA data derived from stem cell donors yields CPRA values that are comparable to those derived from deceased kidney donors while improving upon several problems with the current reference panel. Consideration should be given to using stem cell donors as the reference panel for calculation of CPRA to improve equity in kidney transplant allocation.

The impact of belatacept on third-party HLA alloantibodies in highly sensitized kidney transplant recipients.

Recent evidence suggests that belatacept reduces the durability of preexisting antibodies to class I and class II human leukocyte antigens (HLAs). In this case series of 163 highly sensitized kidney transplant candidates whose calculated panel-reactive antibody (cPRA) activity was ≥98% to 100%, the impact of belatacept on preexisting HLA antibodies was assessed. Of the 163 candidates, 72 underwent transplantation between December 4, 2014 and April 15, 2017; 60 of these transplanted patients remained on belatacept consecutively for at least 6 months. We observed a decrease in the breadth and/or strength of HLA class I antibodies as assessed by FlowPRA in belatacept-treated patients compared to controls who did not receive belatacept. Specifically, significant HLA antibody reduction was evident for class I (P < .0009). Posttransplant belatacept-treated patients also had a clinically significant reduction in their cPRA compared to controls (P < .01). Collectively, these findings suggest belatacept can reduce HLA class I antibodies in a significant proportion of highly sensitized recipients and could be an option to improve pretransplant compatibility with organ donors.

Evidence of Chronic Allograft Injury in Liver Biopsies From Long-term Pediatric Recipients of Liver Transplants.

BACKGROUND & AIMS: A substantial proportion of pediatric liver transplant recipients develop subclinical chronic allograft injury. We studied whether there are distinct patterns of injury based on histopathologic features and identified associated immunologic profiles. METHODS: We conducted a cross-sectional study of 157 stable, long-term pediatric recipients of transplanted livers (70 boys; > 6 years old at time of transplantation; mean, 8.9 ± 3.46 years after liver transplantation) who underwent liver biopsy analysis from August 13, 2012, through May 1, 2014. Participants had received livers from a living or deceased donor and had consistently normal results from liver tests. Liver biopsy specimens were scored by a central pathologist; an unsupervised hierarchical cluster analysis of histologic features was used to sort biopsy samples into 3 clusters. We conducted transcriptional and cytometric analyses of liver tissue samples and performed a systems biology analysis that incorporated clinical, serologic, histologic, and transcriptional data. RESULTS: The mean level of alanine aminotransferase in participants was 27.6 ± 14.57 U/L, and the mean level of γ-glutamyl transferase was 17.4 ± 7.93 U/L. Cluster 1 was characterized by interface activity (n = 34), cluster 2 was characterized by periportal or perivenular fibrosis without interface activity (n = 45), and cluster 3 had neither feature (n = 78). We identified a module of genes whose expression correlated with levels of alanine aminotransferase, class II donor-specific antibody, portal inflammation, interface activity, perivenular inflammation, portal and perivenular fibrosis, and cluster assignment. The module was enriched in genes that regulate T-cell-mediated rejection (TCMR) of liver and other transplanted organs. Functional pathway analysis showed overrepresentation of TCMR gene sets for cluster 1 but not clusters 2 or 3. CONCLUSION: In an analysis of biopsies from an apparently homogeneous group of stable, long-term pediatric liver transplant recipients with consistently normal liver test results, we found evidence of chronic graft injury (inflammation and/or fibrosis). Biopsy samples with interface activity had a gene expression pattern associated with TCMR.

A diagnostic 'C' saw: the ups and downs of C1q testing.

PURPOSE OF REVIEW: The present review will focus on recently published data of solid organ allograft recipients reporting that patients with de-novo donor-specific HLA antibodies (DSA) that fix complement in vitro have a significantly higher risk for antibody-mediated rejection (AMR) and/or graft loss compared to patients whose de-novo DSA do not fix complement or patients who present with preexisting complement fixing DSA. RECENT FINDINGS: HLA DSAs that fix complement in vitro appear to be a key indicator for rejection and failure of kidney, heart, and lung allografts from studies performed around the world. The majority of these studies are population based and retrospective in nature. Although these studies seemingly indicate that in-vitro complement activating DSAs represent a higher clinical risk than noncomplement fixing DSAs, the majority have not accounted for false-negative reactions attributable to the so-called prozone/interference phenomenon. In the limited number of published studies addressing that concern, high mean fluorescence intensity (MFI) value noncomplement fixing DSAs correlate as well as complement fixing DSAs with AMR and graft loss. Combined with the cost of additional testing, these observations bring into question whether there is sufficient clinical applicability to warrant routine testing for complement fixing antibodies. SUMMARY: Complement fixing DSAs are clearly associated with AMR and/or loss of transplanted allografts. However, under appropriate testing conditions, complement fixing capability typically correlates with MFI values of the DSAs. As such, the routine implementation of in-vitro assays to determine whether DSAs fix complement is of questionable value especially when considering additional issues such as cost of testing, logistics, and whether the test results factor into individualized patient care.

Comparison of de novo IgM and IgG anti-HLA DSAs between belatacept- and calcineurin-treated patients: An analysis of the BENEFIT and BENEFIT-EXT trial cohorts.

Preventing conversion of donor-specific anti-HLA antibodies (DSAs) from an IgM-to-IgG could a way to prevent chronic rejection. We evaluated whether belatacept-treated patients (belatacept less-intensive [LI] or more-intensive [MI] regimens) have a lower rate of conversion than do cyclosporine A (CsA)-treated patients. We included 330 HLA-mismatched patients from 2 phase 3 trials with either (a) complete donor/recipient HLA-A, -B, -DR, and -DQ loci typing or (b) incomplete HLA typing with IgG DSAs detected pretransplant or posttransplant. IgM and IgG DSAs were tested with single antigen beads at 0, 6, 12, 24, and 36 months posttransplant. The overall (preexisting or de novo) rates of IgM- and IgG-positive DSAs were 29% and 34%, respectively. The pretransplant IgM and IgG DSA-positive frequencies were similar between treatment groups. The IgG-positive dnDSA rate was significantly higher in the CsA-treated group (34%) compared with the belatacept-LI (8%) and belatacept-MI (11%) (P < .001) groups. In IgM-positive dnDSA patients, the IgG-positive dnDSA rate of conversion was 2.8 times higher in the CsA group than in the combined belatacept groups (P = .006). However, the observed association between belatacept treatment and more limited conversion of IgM-to-IgG dnDSAs was based on a limited number of patients and requires further validation.

Stability of anti-A blood group titers among blood group B renal transplant candidates.

BACKGROUND: As deceased donor kidney allocation is based in part on blood type compatibility, group B candidates are disadvantaged due to their disproportionate representation on the wait list compared to the group B donor pool. To mitigate this discrepancy, group B candidates can receive group A2 or A2 B donor kidneys if their anti-A titers are below a predetermined cutoff. Currently, eligibility is reverified quarterly to UNet based on individual center protocols, which can vary due to a lack of set guidelines for monitoring ABO titers in these patients. Our goal was to assess the stability of anti-A titers in blood group B renal transplant candidates over time to provide data that could aid in the development of standardized ABO titer protocols. STUDY DESIGN AND METHODS: Titers performed between January 2011 and December 2015 were assessed for 191 group B patients with two or more documented titers. RESULTS: Fifty patients (26%) were ineligible, as the first titer exceeded the cutoff of 8. Of the remaining 141 patients, 19 (13%) became ineligible as the second titer exceeded 8. Thirty-nine patients (28%) had no change in titer between samples, while 71 (50%) had a titer change that never exceeded 8. Only 12 patients (8.5% of total) experienced a titer change that affected eligibility after the second test. CONCLUSION: Although patients experience some variability in anti-A titers over time, in most cases, stability did not affect candidate eligibility. Our results indicate that regular testing beyond the second titer may be unnecessary and represent test overutilization.

Predictors of Posttraumatic Stress Disorder, Anxiety Disorders, Depressive Disorders, and Any Mental Health Condition Among U.S. Soldiers and Marines, 2001-2011.

Understanding mental health disorder diagnosis and treatment seeking among active-duty military personnel is a topic with both clinical and policy implications. It has been well documented in military populations that individual-level military experience, including deployment history and combat exposure, influences mental health outcomes, but the impact of unit-level factors is less well understood. In the current study, we used administrative longitudinal data to examine a comprehensive set of unit- and individual-level predictors of posttraumatic stress disorder (PTSD), non-PTSD anxiety disorders, depressive disorders, and overall mental health diagnoses among Army and Marines Corps personnel. Using Cox survival models for time-dependent variables, we analyzed time from military accession (between January 1, 2001 and December 31, 2011) until first mental health diagnosis for 773,359 soldiers and 332,093 Marines. Prior diagnosis of a substance abuse disorder during one's military career, hazard ratios (HRs) = 1.68-3.10, and cumulative time spent deployed, HRs = 1.11-2.04, were the most predictive risk factors for all outcomes. Male sex, HRs = 0.35-0.57, and officer rank, HRs = 0.13-0.23, were the most protective factors. Unit-level rate of high deployment stress was a small but significant predictor of all outcomes after controlling for individual-level deployment history and other predictors, HRs = 1.01-1.05. Findings suggest both unit- and individual-level risk and protective factors of mental health diagnoses associated with treatment seeking. Clinical, including mental health assessment and management, and policy implications related to the military environment and the individual as it relates to mental health disorders are discussed.

De novo DQ donor-specific antibodies are associated with worse outcomes compared to non-DQ de novo donor-specific antibodies following heart transplantation.

BACKGROUND: Antibody-mediated rejection (AMR) resulting from de novo donor-specific antibodies (dnDSA) leads to adverse outcomes following heart transplantation (HTx). It remains unclear what role dnDSA to specific HLA antigens play in adverse outcomes. This study compares outcomes in patients developing dnDSA to DQ antigens with those developing non-DQ dnDSA and those free from dnDSA. METHODS: The present study was a single-center, retrospective analysis of 122 consecutive HTx recipients. The primary outcome was a composite of death or graft dysfunction. RESULTS: After 3.3 years of follow-up, 31 (28%) patients developed dnDSA. Mean time to dnDSA was 539 days. Of 31 patients, 19 developed DQ antibodies and 12 developed non-DQ antibodies. Compared to non-DQ dnDSA, DQ antibodies presented with higher MFI values (P=.001) were more likely persistent (P=.001) and appeared later post-HTx (654 vs 359 days, P=.035). In a multivariable analysis, DQ dnDSA was associated with increased risk of the primary endpoint (HR 6.15, 95% CI 2.57-14.75, P=.001), whereas no increased risk was seen with non-DQ dnDSA (P=.749). CONCLUSIONS: dnDSA to DQ antigens following HTx are associated with increased risk of death and graft dysfunction.

Becoming a chef in the human leukocyte antigen kitchen: interpretation and modification of human leukocyte antigen-antibody assays.

PURPOSE OF REVIEW: Fluorescence-based human leukocyte antigen (HLA) antibody detection methods, including flow cytometric crossmatch and single antigen bead assays revolutionized HLA antibody identification and assessment of immunological risk in transplant candidates and patients. Nevertheless, these assays are not flawless and their interpretation can be complex. This review highlights the limitations of the single antigen bead and flow cytometric crossmatch assays and discusses protocol modifications and interpretive approaches to address these issues. RECENT FINDINGS: Several limitations of HLA antibody detection methods have been identified in recent years. Protocol variability, denatured epitopes, and interfering factors can all significantly impact the identification of clinically relevant HLA antibodies. A number of solutions to address these challenges have been developed. These include pretreatment of sera, method standardization, and protocol modifications. In addition, HLA epitope-based analysis approaches to improve interpretation of antibody test results have been introduced. SUMMARY: In the 50 years, since Patel and Terasaki first developed the crossmatch assay there have been remarkable advances in HLA antibody testing methodology. However, with these advances, new problems emerged and solutions had to be developed. As the technology continues to evolve, our methods and ability to interpret results must keep pace to provide transplant patients with the best possible care.

Mental Health Utilization Patterns During a Stepped, Collaborative Care Effectiveness Trial for PTSD and Depression in the Military Health System.

BACKGROUND: Integrated health care models aim to improve access and continuity of mental health services in general medical settings. STEPS-UP is a stepped, centrally assisted collaborative care model designed to improve posttraumatic stress disorder (PTSD) and depression care by providing the appropriate intensity and type of care based on patient characteristics and clinical complexity. STEPS-UP demonstrated improved PTSD and depression outcomes in a large effectiveness trial conducted in the Military Health System. The objective of this study was to examine differences in mental health utilization patterns between patients in the stepped, centrally assisted collaborative care model relative to patients in the collaborative care as usual-treatment arm. METHODS: Patients with probable PTSD and/or depression were recruited at 6 large military treatment facilities, and 666 patients were enrolled and randomized to STEPS-UP or usual collaborative care. Utilization data acquired from Military Health System administrative datasets were analyzed to determine mental health service use and patterns. Clinical complexity and patient characteristics were based on self-report questionnaires collected at baseline. RESULTS: Compared with the treatment as usual arm, STEPS-UP participants received significantly more mental health services and psychiatric medications across primary and specialty care settings during the year of their participation. Patterns of service use indicated that greater clinical complexity was associated with increased service use in the STEPS-UP group, but not in the usual-care group. CONCLUSIONS: Results suggest that stepped, centrally assisted collaborative care models may increase the quantity of mental health services patients receive, while efficiently matching care on the basis of the clinical complexity of patients.

Class I and II HLA antibodies in pediatric patients with thalassemia major.

BACKGROUND: HLA alloimmunization is a potential complication of red blood cell (RBC) transfusion with detrimental consequences for future organ or hematopoietic stem cell transplantation. STUDY DESIGN AND METHODS: The study aimed to determine the prevalence and specificity of HLA antibodies among pediatric patients with thalassemia major (TM) and antibody changes over time while on leukoreduced chronic transfusion therapy. HLA antibodies were measured at two or more time points in children and young adults ages 3 to 21 years with TM. HLA Class I and II antibodies were measured by FlowPRA screening. Positive screening assays were confirmed with LabScreen single-antigen bead assays for antibody specificity. RESULTS: HLA antibodies were detected in 10 of 19 (53%) subjects: seven of 19 (37%) with HLA Class I and II antibodies, two of 19 (11%) with only HLA Class I antibodies, and one of 19 (5%) with only HLA Class II antibodies. Subjects with HLA antibodies were older (14.6 years vs. 7.1 years, p = 0.05), predominantly male (80%), and more likely to have a remote history of nonleukoreduced transfusions (p = 0.057). Median time between testing was 3.7 years. De novo HLA antibodies were detected in two of 11 patients who initially had negative panel-reactive antibody screens, while one subject lost detection of Class II antibody. Two of seven patients with HLA antibodies had antibodies to self-HLA. CONCLUSION: HLA antibodies have a high prevalence in TM patients and may be associated with nonleukoreduced transfusions and older age. For such patients, antibody identification will be useful if subsequent organ or stem cell transplantation is needed.

Combat-Acquired Traumatic Brain Injury, Posttraumatic Stress Disorder, and Their Relative Associations With Postdeployment Binge Drinking.

OBJECTIVE: To examine whether experiencing a traumatic brain injury (TBI) on a recent combat deployment was associated with postdeployment binge drinking, independent of posttraumatic stress disorder (PTSD). METHODS: Using the 2008 Department of Defense Survey of Health Related Behaviors among Active Duty Military Personnel, an anonymous survey completed by 28 546 personnel, the study sample included 6824 personnel who had a combat deployment in the past year. Path analysis was used to examine whether PTSD accounted for the total association between TBI and binge drinking. MAIN MEASURES: The dependent variable, binge drinking days, was an ordinal measure capturing the number of times personnel drank 5+ drinks on one occasion (4+ for women) in the past month. Traumatic brain injury level captured the severity of TBI after a combat injury event exposure: TBI-AC (altered consciousness only), TBI-LOC of 20 or less (loss of consciousness up to 20 minutes), and TBI-LOC of more than 20 (loss of consciousness >20 minutes). A PTSD-positive screen relied on the standard diagnostic cutoff of 50+ on the PTSD Checklist-Civilian. RESULTS: The final path model found that while the direct effect of TBI (0.097) on binge drinking was smaller than that of PTSD (0.156), both were significant. Almost 70% of the total effect of TBI on binge drinking was from the direct effect; only 30% represented the indirect effect through PTSD. CONCLUSION: Further research is needed to replicate these findings and to understand the underlying mechanisms that explain the relationship between TBI and increased postdeployment drinking.

Posttraumatic Stress Disorder in U.S. Military Primary Care: Trajectories and Predictors of One-Year Prognosis.

We examined the longitudinal course of primary care patients in the active duty Army with posttraumatic stress disorder (PTSD) and identified prognostic indicators of PTSD severity. Data were drawn from a 6-site randomized trial of collaborative primary care for PTSD and dpression in the military. Subjects were 474 soldiers with PTSD (scores ≥ 50 on the PTSD Checklist -Civilian Version). Four assessments were completed at U.S. Army installations: baseline, and follow-ups at 3 months (92.8% response rate [RR]), 6 months (90.1% RR), and 12 months (87.1% RR). Combat exposure and 7 validated indicators of baseline clinical status (alcohol misuse, depression, pain, somatic symptoms, low mental health functioning, low physical health functioning, mild traumatic brain injury) were used to predict PTSD symptom severity on the Posttraumatic Diagnostic Scale (Cronbach's α = .87, .92, .95, .95, at assessments 1-4, respectively). Growth mixture modeling identified 2 PTSD symptom trajectories: subjects reporting persistent symptoms (Persisters, 81.9%, n = 388), and subjects reporting improved symptoms (Improvers 18.1%, n = 86). Logistic regression modeling examined baseline predictors of symptom trajectories, adjusting for demographics, installation, and treatment condition. Subjects who reported moderate combat exposure, adjusted odds ratio (OR) = 0.44, 95% CI [0.20, 0.98], or who reported high exposure, OR = 0.39, 95% CI [0.17, 0.87], were less likely to be Improvers. Other baseline clinical problems were not related to symptom trajectories. Findings suggested that most military primary care patients with PTSD experience persistent symptoms, highlighting the importance of improving the effectiveness of their care. Most indicators of clinical status offered little prognostic information beyond the brief assessment of combat exposure.

Deceased donor multidrug resistance protein 1 and caveolin 1 gene variants may influence allograft survival in kidney transplantation.

Variants in donor multidrug resistance protein 1 (ABCB1) and caveolin 1 (CAV1) genes are associated with renal allograft failure after transplantation in Europeans. Here we assessed transplantation outcomes of kidneys from 368 African American (AA) and 314 European American (EA) deceased donors based on 38 single-nucleotide polymorphisms (SNPs) spanning ABCB1 and 16 SNPs spanning CAV1, including previously associated index and haplotype-tagging SNPs. Tests for association with time to allograft failure were performed for the 1233 resultant kidney transplantations, adjusting for recipient age, sex, ethnicity, cold ischemia time, panel reactive antibody, human leukocyte antigen match, expanded-criteria donation, and APOL1-nephropathy variants in AA donors. Interaction analyses between APOL1 with ABCB1 and CAV1 were performed. In a meta-analysis of all transplantations, ABCB1 index SNP rs1045642 was associated with time to allograft failure and other ABCB1 SNPs were nominally associated, but not CAV1 SNPs. ABCB1 SNP rs1045642 showed consistent effects with the 558 transplantations from EA donors, but not with the 675 transplantations from AA donors. ABCB1 SNP rs956825 and CAV1 SNP rs6466583 interacted with APOL1 in transplants from AA donors. Thus, the T allele at ABCB1 rs1045642 is associated with shorter renal allograft survival for kidneys from American donors. Interactions between ABCB1 and CAV1 with APOL1 may influence allograft failure for transplanted kidneys from AA donors.

Red blood cell transfusions are associated with HLA class I but not H-Y alloantibodies in children with sickle cell disease.

Blood transfusions can induce alloantibodies to antigens on red blood cells (RBCs), white blood cells and platelets, with these alloantibodies affecting transfusion and transplantation. While transfusion-related alloimmunization against RBC antigens and human leucocyte antigens (HLA) have been studied, transfusion-related alloimmunization to minor histocompatibility antigens (mHA), such as H-Y antigens, has not been clinically characterized. We conducted a cross-sectional study of 114 children with sickle cell disease (SCD) and tested for antibodies to 5 H-Y antigens and to HLA class I and class II. Few patients had H-Y antibodies, with no significant differences in the prevalence of any H-Y antibody observed among transfused females (7%), transfused males (6%) and never transfused females (4%). In contrast, HLA class I, but not HLA class II, antibodies were more prevalent among transfused than never transfused patients (class I: 33% vs. 13%, P = 0·046; class II: 7% vs. 8%, P = 0·67). Among transfused patients, RBC alloantibody history but not amount of transfusion exposure was associated with a high (>25%) HLA class I panel reactive antibody (Odds ratio 6·8, 95% confidence interval 2·1-22·3). These results are consistent with immunological responder and non-responder phenotypes, wherein a subset of patients with SCD may be at higher risk for transfusion-related alloimmunization.

Efficacy of Hip Strengthening Exercises Compared With Leg Strengthening Exercises on Knee Pain, Function, and Quality of Life in Patients With Knee Osteoarthritis.

OBJECTIVE: The purpose of this study was to compare the efficacy of hip and leg strengthening exercise programs on knee pain, function, and quality of life (QOL) of patients with knee osteoarthritis (KOA). DESIGN: Single-Blinded Randomized Clinical Trial. SETTING: Patients with KOA. PARTICIPANTS: Male and female subjects were recruited from patients referred to the University of Calgary Sport Medicine Center and from newspaper advertisements. INTERVENTIONS: Thirty-seven and 35 patients with KOA were randomly assigned to either a 12-week hip or leg strengthening exercise program, respectively. Both exercise programs consisted of strengthening and flexibility exercises, which were completed 3 to 5 days a week. The first 3 weeks of exercise were supervised and the remaining 9 weeks consisted of at-home exercise. MAIN OUTCOME MEASURES: Knee Injury and Osteoarthritis Score (KOOS) and Western Ontario McMaster Arthritis Index (WOMAC) questionnaires, 6-minute walk test, hip and knee range of motion (ROM), and hip and leg muscle strength. RESULTS: Statistically and clinically significant improvements in the KOOS and WOMAC pain subscale scores were observed in both the hip and leg strengthening programs. There was no statistical difference in the change in scores observed between the 2 groups. Equal improvements in the KOOS and WOMAC function and QOL subscales were observed for both programs. There was no change in hip and knee ROM or hip and leg strength in either group. CONCLUSIONS: Isolated hip and leg strengthening exercise programs seem to similarly improve knee pain, function, and QOL in patients with KOA. CLINICAL RELEVANCE: The results of this study show that both hip and leg strengthening exercises improve pain and QOL in patients with KOA and should be incorporated into the exercise prescription of patients with KOA.