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American Family Physician Aug 2023Well-coordinated prenatal care that follows an evidence-based, informed process results in fewer hospital admissions, improved education, greater satisfaction, and lower...
Well-coordinated prenatal care that follows an evidence-based, informed process results in fewer hospital admissions, improved education, greater satisfaction, and lower pregnancy-associated morbidity and mortality. Care initiated at 10 weeks or earlier improves outcomes. Identification and treatment of periodontal disease decreases preterm delivery risk. A prepregnancy body mass index greater than 25 kg per m2 is associated with gestational diabetes mellitus, hypertension, miscarriage, and stillbirth. Advanced maternal and paternal age (35 years or older) is associated with gestational diabetes, hypertension, miscarriage, intrauterine growth restriction, aneuploidy, birth defects, and stillbirth. Rho(D) immune globulin decreases alloimmunization risk in a patient who is RhD-negative carrying a fetus who is RhD-positive. Treatment of iron deficiency anemia decreases the risk of preterm delivery, intrauterine growth restriction, and perinatal depression. Ancestry-based genetic risk stratification using family history can inform genetic screening. Folic acid supplementation (400 to 800 mcg daily) decreases the risk of neural tube defects. All pregnant patients should be screened for asymptomatic bacteriuria, sexually transmitted infections, and immunity against rubella and varicella and should receive tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap), influenza, and COVID-19 vaccines. Testing for group B Streptococcus should be performed between 36 and 37 weeks, and intrapartum antibiotic prophylaxis should be initiated to decrease the risk of neonatal infection. Because of the impact of social determinants of health on outcomes, universal screening for depression, anxiety, intimate partner violence, substance use, and food insecurity is recommended early in pregnancy. Screening for gestational diabetes between 24 and 28 weeks is recommended for all patients. People at risk of preeclampsia, including those diagnosed with COVID-19 in pregnancy, should be offered 81 mg of aspirin daily starting at 12 weeks. Chronic hypertension should be treated to a blood pressure of less than 140/90 mm Hg.
Topics: Infant, Newborn; Female; Pregnancy; Humans; Adult; Prenatal Care; Abortion, Spontaneous; Fetal Growth Retardation; Stillbirth; COVID-19 Vaccines; Diabetes, Gestational; Premature Birth; COVID-19
PubMed: 37590852
DOI: No ID Found -
Science Translational Medicine Oct 2023Immune cell-based therapies are promising strategies to facilitate immunosuppression withdrawal after organ transplantation. Regulatory dendritic cells (DCreg) are...
Immune cell-based therapies are promising strategies to facilitate immunosuppression withdrawal after organ transplantation. Regulatory dendritic cells (DCreg) are innate immune cells that down-regulate alloimmune responses in preclinical models. Here, we performed clinical monitoring and comprehensive assessment of peripheral and allograft tissue immune cell populations in DCreg-infused live-donor liver transplant (LDLT) recipients up to 12 months (M) after transplant. Thirteen patients were given a single infusion of donor-derived DCreg 1 week before transplant (STUDY) and were compared with 40 propensity-matched standard-of-care (SOC) patients. Donor-derived DCreg infusion was well tolerated in all STUDY patients. There were no differences in postoperative complications or biopsy-confirmed acute rejection compared with SOC patients up to 12M. DCreg administration was associated with lower frequencies of effector T-betEomesCD8 T cells and CD16 natural killer (NK) cells and an increase in putative tolerogenic CD141CD163 DCs compared with SOC at 12M. Antidonor proliferative capacity of interferon-γ (IFN-γ) CD4 and CD8 T cells was lower compared with antithird party responses in STUDY participants, but not in SOC patients, at 12M. In addition, lower circulating concentrations of interleukin-12p40 (IL-12p40), IFN-γ, and CXCL10 were detected in STUDY participants compared with SOC patients at 12M. Analysis of 12M allograft biopsies revealed lower frequencies of graft-infiltrating CD8 T cells, as well as attenuation of cytolytic T1 effector genes and pathways among intragraft CD8 T cells and NK cells, in DCreg-infused patients. These reductions may be conducive to reduced dependence on immunosuppressive drug therapy or immunosuppression withdrawal.
Topics: Humans; CD8-Positive T-Lymphocytes; Liver Transplantation; Dendritic Cells; Living Donors; Killer Cells, Natural; Interferon-gamma; Graft Rejection
PubMed: 37820009
DOI: 10.1126/scitranslmed.adf4287 -
Journal of Clinical Pharmacology Dec 2023Janus kinase (JAK) inhibitors are a novel group of immunosuppressive drugs approved to treat certain rheumatic and allergic disorders; however, their efficacy in the... (Review)
Review
Janus kinase (JAK) inhibitors are a novel group of immunosuppressive drugs approved to treat certain rheumatic and allergic disorders; however, their efficacy in the regulation of alloimmune responses after solid organ transplantation has not yet been elucidated. In the present review, we have summarized the results of in vitro, in vivo, experimental, and clinical trial studies about the efficacy and safety of JAK inhibitors in improving allograft survival in solid organ transplantations, including kidney, heart, lung, and liver transplants. Moreover, reports on administering JAK inhibitors to steroid-resistant patients with graft versus host disease (GvHD) after solid organ transplantation have been reviewed. Overall findings are suggestive of a beneficial role for JAK inhibitors in organ transplantation: for example, they have been shown to improve allograft function, reduce the rate and score of acute rejection, downregulate the expression of proinflammatory cytokines and adhesion molecules, and decrease oxidative stress. However, the adverse effects of these drugs, in particular bone marrow suppression and infection, remain an obstacle.
Topics: Humans; Janus Kinase Inhibitors; Organ Transplantation; Immunosuppressive Agents; Graft vs Host Disease; Transplantation, Homologous; Graft Rejection
PubMed: 37500063
DOI: 10.1002/jcph.2325 -
Trends in Immunology Jan 2024In the quest for more precise and effective organ transplantation therapies, chimeric antigen receptor (CAR) regulatory T cell (T) therapies represent a potential... (Review)
Review
In the quest for more precise and effective organ transplantation therapies, chimeric antigen receptor (CAR) regulatory T cell (T) therapies represent a potential cutting-edge advance. This review comprehensively analyses CAR T and how they may address important drawbacks of polyclonal T and conventional immunosuppressants. We examine a growing body of preclinical findings of CAR T therapy in transplantation, discuss CAR T design specifics, and explore established and attractive new targets in transplantation. In addition, we explore present impediments where future studies will be necessary to determine the efficacy of CAR T in reshaping alloimmune responses and transplant microenvironments to reduce reliance on chemical immunosuppressants. Overall, ongoing studies and trials are crucial for understanding the full scope of CAR T therapy in transplantation.
Topics: Humans; Receptors, Chimeric Antigen; Immunotherapy, Adoptive; Organ Transplantation; Immunosuppressive Agents; T-Lymphocytes, Regulatory; Receptors, Antigen, T-Cell
PubMed: 38123369
DOI: 10.1016/j.it.2023.11.005 -
Current Opinion in Organ Transplantation Oct 2023De novo HLA-DQ antibodies are the most frequently observed after solid-organ allotransplantation; and are associated with the worse adverse graft outcomes compared with... (Review)
Review
PURPOSE OF REVIEW
De novo HLA-DQ antibodies are the most frequently observed after solid-organ allotransplantation; and are associated with the worse adverse graft outcomes compared with all other HLA antibodies. However, the biological explanation for this observation is not yet known. Herein, we examine unique characteristics of alloimmunity directed specifically against HLA-DQ molecules.
RECENT FINDINGS
While investigators attempted to decipher functional properties of HLA class II antigens that may explain their immunogenicity and pathogenicity, most early studies focused on the more expressed molecule - HLA-DR. We here summarize up-to-date literature documenting specific features of HLA-DQ, as compared to other class II HLA antigens. Structural and cell-surface expression differences have been noted on various cell types. Some evidence suggests variations in antigen-presenting function and intracellular activation pathways after antigen/antibody interaction.
SUMMARY
The clinical effects of donor-recipient incompatibility at HLA-DQ, the risk of generating de novo antibodies leading to rejection, and the inferior graft outcomes indicate increased immunogenicity and pathogenicity that is unique to this HLA antigen. Clearly, knowledge generated for HLA-DR cannot be applied interchangeably. Deeper understanding of features unique to HLA-DQ may support the generation of targeted preventive-therapeutic strategies and ultimately improve solid-organ transplant outcomes.
Topics: Humans; Kidney Transplantation; Isoantibodies; HLA-DQ Antigens; Histocompatibility Testing; HLA-DR Antigens; Graft Rejection
PubMed: 37219535
DOI: 10.1097/MOT.0000000000001079 -
Clinics in Laboratory Medicine Dec 2023Patients with MDS often suffer from anemia, and less often thrombocytopenia, and thus are a frequently transfused population. Red blood cell (RBC) transfusion may be... (Review)
Review
Patients with MDS often suffer from anemia, and less often thrombocytopenia, and thus are a frequently transfused population. Red blood cell (RBC) transfusion may be used to improve functional capacity and quality of life in this population, while platelet transfusion is typically used to decrease bleeding risk. Despite the frequency of transfusion in patients with MDS, there are few well-defined guidelines for RBC and platelet transfusion support in this patient population. Transfusion is not without risk-patients with MDS who are frequently transfused may develop alloantibodies to RBC antigens, which can lead to hemolytic transfusion reactions and delays in obtaining compatible RBCs. Regular communication between clinicians and blood bank physicians is crucial to ensure that patients with MDS receive the most appropriate blood products.
Topics: Humans; Erythrocytes; Quality of Life; Myelodysplastic Syndromes; Blood Transfusion; Erythrocyte Transfusion
PubMed: 37865510
DOI: 10.1016/j.cll.2023.07.002 -
Blood Reviews Nov 2023Platelet transfusion refractoriness due to HLA alloimmunization presents a significant medical problem, particularly among multiply transfused patients with hematologic... (Review)
Review
Platelet transfusion refractoriness due to HLA alloimmunization presents a significant medical problem, particularly among multiply transfused patients with hematologic malignancies and those undergoing hematopoietic stem cell transplants. HLA compatible platelet transfusions also impose significant financial burden on these patients. Recently, several novel mechanisms have been described in the development of HLA alloimmunization and platelet transfusion refractoriness. We review the history of platelet transfusions and mechanisms of HLA-sensitization and transfusion refractoriness. We also summarize advances in the diagnosis and treatment of platelet transfusion refractoriness due to HLA alloimmunization.
Topics: Humans; Platelet Transfusion; Isoantibodies; Thrombocytopenia; Blood Transfusion; Hematologic Neoplasms; Anemia, Hemolytic, Autoimmune; HLA Antigens; Blood Platelets
PubMed: 37805287
DOI: 10.1016/j.blre.2023.101135 -
Transfusion and Apheresis Science :... Oct 2023Sickle cell disease (SCD) is the most common hereditary hemoglobinopathy. The underlying pathophysiology of the red blood cell (RBC) leads to pan-systemic complications... (Review)
Review
Sickle cell disease (SCD) is the most common hereditary hemoglobinopathy. The underlying pathophysiology of the red blood cell (RBC) leads to pan-systemic complications which manifest at an early age. While curative and disease-modifying treatments exist for SCD, a key intervention in the management and treatment of SCD is RBC transfusion, which can alleviate or prevent many complications. SCD patients often require chronic RBC transfusion therapy which can result in complications, such as iron overload, alloimmunization and infection. In low- and middle-income countries (LMICs), SCD patients lack appropriate access to healthcare such as newborn screening, health education, prophylaxis for infection, and treatments to reduce both mortality and SCD-related adverse effects. Poor access to RBCs for transfusion, coupled with donated blood not meeting safety standards set by the World Health Organization, presents a significant barrier for patients requiring chronic transfusions in LMICs. Unmet needs associated with blood collection, blood component processing and recipient matching all pose a serious problem in many LMICs, although this varies depending on geographic location, political organizations and economy. This review aims to provide an overview of the global burden of SCD, focusing on the availability of current treatments and the burden of chronic RBC transfusions in patients with SCD.
Topics: Infant, Newborn; Humans; Anemia, Sickle Cell; Blood Transfusion; Erythrocytes; Erythrocyte Transfusion; Blood Group Incompatibility
PubMed: 37541800
DOI: 10.1016/j.transci.2023.103764 -
Frontiers in Immunology 2023Allogeneic hematopoietic cell transplantation (HCT) is a curative therapy for various hematologic malignancies. However, alloimmune response is a double-edged sword that... (Review)
Review
Allogeneic hematopoietic cell transplantation (HCT) is a curative therapy for various hematologic malignancies. However, alloimmune response is a double-edged sword that mediates both beneficial graft-versus-leukemia (GVL) effects and harmful graft-versus-host disease (GVHD). Separation of GVL effects from GVHD has been a topic of intense research to improve transplant outcomes, but reliable clinical strategies have not yet been established. Target tissues of acute GVHD are the skin, liver, and intestine, while leukemic stem cells reside in the bone marrow. Tissue specific effector T-cell migration is determined by a combination of inflammatory and chemotactic signals that interact with specific receptors on T cells. Specific inhibition of donor T cell migration to GVHD target tissues while preserving migration to the bone marrow may represent a novel strategy to separate GVL from GVHD. Furthermore, tissue specific GVHD therapy, promoting tissue tolerance, and targeting of the tumor immune microenvironment may also help to separate GVHD and GVL.
Topics: Humans; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; T-Lymphocytes; Hematologic Neoplasms; Immune Tolerance; Tumor Microenvironment
PubMed: 38116007
DOI: 10.3389/fimmu.2023.1296663 -
American Journal of Transplantation :... Nov 2023Biological sex affects immunity broadly, with recognized effects on the incidence and severity of autoimmune diseases, infections, and malignancies. Consequences of sex... (Review)
Review
Biological sex affects immunity broadly, with recognized effects on the incidence and severity of autoimmune diseases, infections, and malignancies. Consequences of sex on alloimmunity and outcomes in solid organ transplantation are less well defined. Clinical studies have shown that donor and recipient sex independently impact transplant outcomes, which are further modified by aging. Potential mechanisms have thus far not been detailed and may include hormonal, genetic, and epigenetic components. Here, we summarize relevant findings in immunity in addition to studies in clinical and experimental organ transplantation detailing the effects of biological sex on alloimmunity. Understanding both clinical impact and mechanisms is expected to provide critical insights on the complexity of alloimmune responses, with the potential to fine-tune treatment and allocation while providing a rationale to include both sexes in transplant research.
Topics: Male; Female; Humans; Clinical Relevance; Graft Rejection; Organ Transplantation; Tissue Donors
PubMed: 37543092
DOI: 10.1016/j.ajt.2023.07.022