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Obstetrics and Gynecology Jul 2024To evaluate maternal and neonatal outcomes by type of antihypertensive used in participants of the CHAP (Chronic Hypertension in Pregnancy) trial. (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
OBJECTIVE
To evaluate maternal and neonatal outcomes by type of antihypertensive used in participants of the CHAP (Chronic Hypertension in Pregnancy) trial.
METHODS
We conducted a planned secondary analysis of CHAP, an open-label, multicenter, randomized trial of antihypertensive treatment compared with standard care (no treatment unless severe hypertension developed) in pregnant patients with mild chronic hypertension (blood pressure 140-159/90-104 mm Hg before 20 weeks of gestation) and singleton pregnancies. We performed three comparisons based on medications prescribed at enrollment: labetalol compared with standard care, nifedipine compared with standard care, and labetalol compared with nifedipine. Although active compared with standard care groups were randomized, medication assignment within the active treatment group was not random but based on clinician or patient preference. The primary outcome was the occurrence of superimposed preeclampsia with severe features, preterm birth before 35 weeks of gestation, placental abruption, or fetal or neonatal death. The key secondary outcome was small for gestational age (SGA) neonates. We also compared medication adverse effects between groups. Relative risks (RRs) and 95% CIs were estimated with log binomial regression to adjust for confounding.
RESULTS
Of 2,292 participants analyzed, 720 (31.4%) received labetalol, 417 (18.2%) received nifedipine, and 1,155 (50.4%) received no treatment. The mean gestational age at enrollment was 10.5±3.7 weeks; nearly half of participants (47.5%) identified as non-Hispanic Black; and 44.5% used aspirin. The primary outcome occurred in 217 (30.1%), 130 (31.2%), and 427 (37.0%) in the labetalol, nifedipine, and standard care groups, respectively. Risk of the primary outcome was lower among those receiving treatment (labetalol use vs standard adjusted RR 0.82, 95% CI, 0.72-0.94; nifedipine use vs standard adjusted RR 0.84, 95% CI, 0.71-0.99), but there was no significant difference in risk when labetalol was compared with nifedipine (adjusted RR 0.98, 95% CI, 0.82-1.18). There were no significant differences in SGA or serious adverse events between participants receiving labetalol and those receiving nifedipine.
CONCLUSION
No significant differences in predetermined maternal or neonatal outcomes were detected on the basis of the use of labetalol or nifedipine for treatment of chronic hypertension in pregnancy.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov, NCT02299414.
Topics: Humans; Pregnancy; Female; Labetalol; Nifedipine; Antihypertensive Agents; Adult; Pregnancy Outcome; Hypertension; Infant, Newborn; Pregnancy Complications, Cardiovascular; Hypertension, Pregnancy-Induced; Administration, Oral; Infant, Small for Gestational Age; Pre-Eclampsia; Chronic Disease
PubMed: 38949541
DOI: 10.1097/AOG.0000000000005613 -
World Journal of Clinical Pediatrics Jun 2024Acute fulminant liver failure rarely occurs in the neonatal period. The etiologies include viral infection (15%), metabolic/genetic disease (10%), hematologic disorders...
BACKGROUND
Acute fulminant liver failure rarely occurs in the neonatal period. The etiologies include viral infection (15%), metabolic/genetic disease (10%), hematologic disorders (15%), and ischemic injury (5%). Gestational alloimmune liver disease usually manifests as severe neonatal liver failure, with extensive hepatic and extrahepatic iron overload, sparing the reticuloendothelial system. Empty liver failure is a rare cause of liver failure where a patient presents with liver failure in the neonatal period with no hepatocytes in liver biopsy.
CASE SUMMARY
A 5-week-old male presented with jaundice. Physical examination revealed an alert but deeply icteric infant. Laboratory data demonstrated direct hyperbilirubinemia, a severely deranged coagulation profile, normal transaminase, and normal ammonia. Magnetic resonance imaging of the abdomen was suggestive of perinatal hemochromatosis. Liver biopsy showed histiocytic infiltration with an absence of hepatocytes. No hemosiderin deposition was identified in a buccal mucosa biopsy.
CONCLUSION
Neonatal liver failure in the absence of hepatocellular regeneration potentially reflects an acquired or inborn defect in the regulation of hepatic regeneration.
PubMed: 38947999
DOI: 10.5409/wjcp.v13.i2.92263 -
International Journal of General... 2024Alloimmunisation remains a major consequence of blood transfusion among sickle cell disease (SCD) and thalassemia patients due to the exposure to non-self-red blood cell...
Red Cell Alloimmunisation Among Sickle Cell Disease and Thalassemia Patients Following Rh- and K-Matched Red Cell Transfusion in Southwestern Saudi Arabia: A Multicenter Study.
BACKGROUND
Alloimmunisation remains a major consequence of blood transfusion among sickle cell disease (SCD) and thalassemia patients due to the exposure to non-self-red blood cell (RBC) antigen. The complication is associated with transfusion reactions and delayed transfusion procedure because of the difficulty of finding compatible blood. This study aims to determine the prevalence of alloimmunisation to RBC and alloantibody specificities among SCD and thalassemia patients in, an endemic area of SCD and thalassemia, Jazan province of Saudi Arabia, from three major hospitals.
METHODS
This is a retrospective, multicenter cross-sectional study conducted on 1027 patients with SCD and thalassemia, which received Rh/K matched transfusions in 2019 in the three centers. Demographic data and medical records of participants from three transfusion institutions were collected and analysed.
RESULTS
A total of 1027 were enrolled in the cohort; 906 (88.2%) and 121 (11.8%) patients with SCD and thalassemia, respectively. There were 483 (47%) males and 544 (53%) females with median age of 15 (range 1-48). Among the studied population, 78 were alloimmunised with an overall alloimmunisation rate of 7.6%. These patients developed a total of 108 alloantibodies, and anti-E was the most detected antibody (25.9%) followed by anti-K (24.1%).
CONCLUSION
The overall rate of alloimmunisation to RBC antigen among the studied population in Jazan was low compared to other areas in the country. Most alloantibodies detected were against E and K antigens. The knowledge of most encountered alloantibodies in our population will aid in selecting the most appropriate antigen-negative red cells. Further research, however, is needed to explore factors associated with residual risk of alloimmunisation in these patients.
PubMed: 38947563
DOI: 10.2147/IJGM.S444949 -
Frontiers in Immunology 2024CD39 plays an important role in the immunoregulation and inhibition of effector cells. It is expressed on immune cells, including Tregs, and on extracellular vesicles...
INTRODUCTION
CD39 plays an important role in the immunoregulation and inhibition of effector cells. It is expressed on immune cells, including Tregs, and on extracellular vesicles (EVs) budding from the plasma membrane. Platelet transfusion may induce alloimmunization against HLA-I antigens, leading to refractoriness to platelet transfusion with severe consequences for patients. Tregs may play a key role in determining whether alloimmunization occurs in patients with hematologic disorders. We hypothesized that CD39 EVs might play an immunoregulatory role, particularly in the context of platelet transfusions in patients with hematologic disorders. Such alloimmunization leads to the production of alloantibodies and is sensitive to the regulatory action of CD39.
METHODS
We characterized CD39 EVs in platelet concentrates by flow cytometry. The absolute numbers and cellular origins of CD39 EVs were evaluated. We also performed functional tests to evaluate interactions with immune cells and their functions.
RESULTS
We found that CD39 EVs from platelet concentrates had an inhibitory phenotype that could be transferred to the immune cells with which they interacted: CD4 and CD8 T lymphocytes (TLs), dendritic cells, monocytes, and B lymphocytes (BLs). Moreover, the concentration of CD39 EVs in platelet concentrates varied and was very high in 10% of concentrates. The number of these EVs present was determinant for EV-cell interactions. Finally, functional interactions were observed with BLs, CD4 TLs and CD39 EVs for immunoglobulin production and lymphoproliferation, with potential implications for the immunological management of patients.
Topics: Humans; Extracellular Vesicles; Blood Platelets; Tetraspanin 29; Cell Communication; Platelet Transfusion; Female; B-Lymphocytes; Male; Apyrase; T-Lymphocytes, Regulatory; Antigens, CD
PubMed: 38947317
DOI: 10.3389/fimmu.2024.1397967 -
MedRxiv : the Preprint Server For... Jun 2024Prioritization of HLA antigen-level matching in the US kidney allocation system intends to improve post-transplant survival but causes racial disparities and thus has...
BACKGROUND
Prioritization of HLA antigen-level matching in the US kidney allocation system intends to improve post-transplant survival but causes racial disparities and thus has been substantially de-emphasized. Recently, molecular matching based on eplets has been found to improve risk stratification compared to antigen matching.
METHODS
To assign eplets unambiguously, we utilized a cohort of 5193 individuals with high resolution allele-level HLA genotypes from the National Kidney Registry. Using repeated random sampling to simulate donor-recipient genotype pairings based on the ethnic composition of the historical US deceased donor pool, we profiled the percentage of well-matched donors for candidates by ethnicity.
RESULTS
The percentage of well-matched donors with zero-DR/DQ eplet mismatch was 3-fold less racially disparate for Black and Asian candidates than percentage of donors with zero-ABDR antigen mismatches, and 2-fold less racially disparate for Latino candidates. For other HLA antigen and eplet mismatch thresholds, the percentage of well-matched donors was more similar across candidate ethnic groups.
CONCLUSIONS
Compared to the current zero-ABDR antigen mismatch, prioritizing a zero-DR/DQ eplet mismatch in allocation would decrease racial disparities and increase the percentage of well-matched donors. High resolution HLA deceased donor genotyping would enable unambiguous assignment of eplets to operationalize molecular mismatch metrics in allocation.
KEY POINTS
What is the impact of prioritizing low molecular mismatch transplants on racial and ethnic disparities in US deceased-donor kidney allocation, compared to the current prioritization of antigen-level matching? The lowest-risk eplet mismatch approach decreases racial disparities up to 3-fold compared to lowest-risk antigen mismatch and identifies a larger number of the lowest allo-immune risk donors. Prioritizing eplet matching in kidney transplant allocation could both improve outcomes and reduce racial disparities compared to the current antigen matching.
PubMed: 38947023
DOI: 10.1101/2024.06.13.23290644 -
Biomedicines Jun 2024Dendritic cells (DCs) are a heterogeneous group of antigen-presenting cells crucial for fostering allograft tolerance while simultaneously supporting host defense... (Review)
Review
Dendritic cells (DCs) are a heterogeneous group of antigen-presenting cells crucial for fostering allograft tolerance while simultaneously supporting host defense against infections and cancer. Within the tumor microenvironment, DCs can either mount an immune response against cancer cells or foster immunotolerance, presenting a dual role. In immunocompromised individuals, posttransplant malignancies pose a significant health concern, with DCs serving as vital players in immune responses against cancer cells. Both recipient- and donor-derived DCs play a critical role in the rejection process, infiltrating the transplanted organ and sustaining T-cell responses. The use of immunosuppressive drugs represents the predominant approach to control this immunological barrier in transplanted organs. Evidence has shed light on the immunopharmacology of these drugs and novel strategies for manipulating DCs to promote allograft survival. Therefore, comprehending the mechanisms underlying this intricate microenvironment and the effects of immunosuppressive therapy on DCs is crucial for developing targeted therapies to reduce graft failure rates. This review will delve into the fundamental immunobiology of DCs and provide a detailed exploration of their clinical significance concerning alloimmune responses and posttransplant malignancies.
PubMed: 38927447
DOI: 10.3390/biomedicines12061240 -
Transfusion Jun 2024
PubMed: 38924565
DOI: 10.1111/trf.17933 -
Journal of Cardiothoracic Surgery Jun 2024We previously demonstrated that the hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitor (statins) play an important role in the regulation of alloimmune responses....
Graft protective effects and donor-specific antibody suppression by CD4CD25Foxp3 regulatory T cell induced by HMG-CoA reductase inhibitor rosuvastatin in a murine heart transplant model.
BACKGROUND
We previously demonstrated that the hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitor (statins) play an important role in the regulation of alloimmune responses. However, little is known regarding the effects of statin on allograft protection or donor-specific antibodies (DSA). In this study, we investigated the graft-protective and immunomodulatory effects of rosuvastatin in a model of fully major histocompatibility complex-mismatched murine cardiac allograft transplantation.
METHODS
CBA mice underwent transplantation of C57BL/6 (B6) hearts and received 50 and 500 μg/kg/day of rosuvastatin from the day of transplantation until seven days after the completion of transplantation. To confirm the requirement for regulatory T cells (Tregs), we administered an anti-interleukin-2 receptor alpha antibody (PC-61) to rosuvastatin-treated CBA recipients. Additionally, histological and fluorescent staining, cell proliferation analysis, flow cytometry, and DSA measurements were performed.
RESULTS
CBA recipients with no treatment rejected B6 cardiac graft acutely (median survival time [MST], 7 days). CBA mice treated with 500 μg/kg/day of rosuvastatin prolonged allograft survival (MSTs, 77 days). Fluorescent staining studies showed that rosuvastatin-treated recipients had strong aggregation of CD4Foxp3 cells in the myocardium and around the coronary arteries of cardiac allografts two weeks after grafting. Flow cytometry studies performed two weeks after transplantation showed an increased number of splenic CD4CD25Foxp3 T cells in rosuvastatin-treated recipients. The addition of rosuvastatin to mixed leukocyte cultures suppressed cell proliferation by increasing the number of CD4CD25Foxp3 Tregs. Additionally, Tregs suppressed DSA production in rosuvastatin-treated recipients.
CONCLUSION
Rosuvastatin treatment may be a complementary graft-protective strategy for suppressing DSA production in the acute phase, driven by the promotion of splenic and graft-infiltrating CD4CD25Foxp3 Tregs.
Topics: Animals; Rosuvastatin Calcium; Heart Transplantation; T-Lymphocytes, Regulatory; Mice; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Mice, Inbred C57BL; Mice, Inbred CBA; Graft Rejection; Graft Survival; Interleukin-2 Receptor alpha Subunit; Male; Forkhead Transcription Factors; Disease Models, Animal; Flow Cytometry
PubMed: 38918849
DOI: 10.1186/s13019-024-02888-4 -
Transplantation Direct Jul 2024Biomarkers that predict posttransplant alloimmunity could lead to improved long-term graft survival. Evaluation of the number of mismatched epitopes between donor and...
BACKGROUND
Biomarkers that predict posttransplant alloimmunity could lead to improved long-term graft survival. Evaluation of the number of mismatched epitopes between donor and recipient HLA proteins, termed molecular mismatch analysis, has emerged as an approach to classify transplant recipients as having high, intermediate, or low risk of graft rejection. When high-resolution genotypes are unavailable, molecular mismatch analysis requires algorithmic assignment, or imputation, of a high-resolution genotyping. Although imputation introduces inaccuracies in molecular mismatch analyses, it is unclear whether these inaccuracies would impact the clinical risk assessment for graft rejection.
METHODS
Using renal transplant patients and donors from our center, we constructed cohorts of surrogate donor-recipient pairs with high-resolution and low-resolution HLA genotyping that were racially concordant or discordant. We systemically assessed the impact of imputation on molecular mismatch analysis for cohorts of 180-200 donor-recipient pairs for each of 4 major racial groups. We also evaluated the effect of imputation for a racially diverse validation cohort of 35 real-world renal transplant pairs.
RESULTS
In the surrogate donor-recipient cohorts, imputation preserved the molecular mismatch risk category for 90.5%-99.6% of racially concordant donor-recipient pairs and 92.5%-100% of racially discordant pairs. In the validation cohort, which comprised 72% racially discordant pairs, we found that imputation preserved the molecular mismatch risk category for 97.1% of pairs.
CONCLUSIONS
Overall, these data demonstrate that imputation preserves the molecular mismatch risk assessment in the vast majority of cases and provides evidence supporting imputation in the performance of molecular mismatch analysis for clinical assessment.
PubMed: 38911277
DOI: 10.1097/TXD.0000000000001639 -
Cureus May 2024Fy3 is a high-prevalence red blood cell antigen of the Duffy (Fy) blood group system. Anti-Fy3 antibodies are rare and solely arise in individuals with a Duffy null...
Fy3 is a high-prevalence red blood cell antigen of the Duffy (Fy) blood group system. Anti-Fy3 antibodies are rare and solely arise in individuals with a Duffy null phenotype (Fy(a-b-)), which is a phenotype that mainly occurs in people of African descent. Clinically, anti-Fy3 antibodies can cause both acute and delayed hemolytic transfusion reactions in adults as well as hemolytic disease in fetuses and newborns. Here, we report the case of a 26-year-old male with sickle cell disease (SCD) and a history of anti-E alloantibodies, who was admitted to the hospital with a vaso-occlusive crisis (VOC) and associated low hemoglobin (Hb) level. For the latter he received one unit of antigen-matched and crossmatch-compatible packed red blood cells (pRBCs) without complications. Ten days later the patient was readmitted with a further VOC and associated low Hb level, again requiring a red cell transfusion. However, no crossmatch-compatible pRBCs could be identified. Laboratory testing demonstrated pan-reactivity with additional reference testing demonstrating the presence of anti-E, anti-Fy3 and anti-Jk alloantibodies. This case highlights the diagnostic and therapeutic challenges associated with blood transfusion in SCD patients with rare alloimmunization profiles.
PubMed: 38910632
DOI: 10.7759/cureus.60939