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Annals of Surgery Open : Perspectives... Sep 2023We aim to investigate the effects of genetically based HLA matching on patient and graft survival, and acute and chronic rejection after liver transplantation.
OBJECTIVE
We aim to investigate the effects of genetically based HLA matching on patient and graft survival, and acute and chronic rejection after liver transplantation.
BACKGROUND
Liver transplantation is a common treatment for patients with end-stage liver disease. In contrast to most other solid organ transplantations, there is no conclusive evidence supporting human leukocyte antigen (HLA) matching for liver transplantations. With emerging alternatives such as transplantation of bankable (stem) cells, HLA matching becomes feasible, which may decrease the need for immunosuppressive therapy and improve transplantation outcomes.
METHODS
We systematically searched the PubMed, Embase, and Cochrane databases and performed a meta-analysis investigating the effect of genetic HLA matching on liver transplantation outcomes (acute/chronic rejection, graft failure, and mortality).
RESULTS
We included 14 studies with 2682 patients. HLA-C mismatching significantly increased the risk of acute rejection (full mismatching: risk ratio = 1.90, 95% confidence interval = 1.08 to 3.33, = 0.03; partial mismatching: risk ratio = 1.33, 95% confidence interval = 1.07 to 1.66, = 0.01). We did not discern any significant effect of HLA mismatching per locus on acute rejection for HLA-A, -B, -DR, and -DQ, nor on chronic rejection, graft failure, or mortality for HLA-DR, and -DQ.
CONCLUSIONS
We found evidence that genetic HLA-C matching reduces the risk of acute rejection after liver transplantation while matching for other loci does not reduce the risk of acute rejection, chronic rejection, graft failure, or mortality.
PubMed: 37746594
DOI: 10.1097/AS9.0000000000000334 -
European Journal of Obstetrics,... May 2024Umbilical Artery Thrombosis (UAT) is an extremely rare complication of pregnancy strongly associated with severe fetal distress and death. The pathogenesis is still... (Review)
Review
Umbilical Artery Thrombosis (UAT) is an extremely rare complication of pregnancy strongly associated with severe fetal distress and death. The pathogenesis is still unclear but it is often associated with anatomical cord abnormalities that leads to blood stasis and thrombosis formation. Other possible risk factors are maternal thrombophilia, autoimmune disease, gestational diabetes, hypertension disorders of pregnancy and Rh-alloimmunization. The most common clinical symptom is the reduction of fetal movements. The diagnosis is histopathological, but it can be suspected by clinical and prenatal ultrasound findings. Generally, the first choice therapy is the immediate delivery with cesarean section. This study reported a case of a spontaneous intrauterine UAT in a low-risk pregnancy and a systematic review of the literature on clinical, ultrasound and histopathological findings of UAT, in order to help clinicians in the diagnostic process and management of this rare complication.
Topics: Pregnancy; Humans; Female; Umbilical Arteries; Cesarean Section; Pregnancy Complications; Prenatal Diagnosis; Thrombosis; Ultrasonography, Prenatal
PubMed: 38394717
DOI: 10.1016/j.ejogrb.2024.02.016 -
Influence of , , and genetic polymorphisms on disorders in transplant patients: a systematic review.Drug Metabolism and Personalized Therapy Dec 2021The glutathione-S-transferase (GST) enzymes are phase II isoenzymes responsible for protection against free radicals and xenobiotics. Since these proteins are described...
The glutathione-S-transferase (GST) enzymes are phase II isoenzymes responsible for protection against free radicals and xenobiotics. Since these proteins are described as polymorphic, polymorphisms in genes that encode them may alter enzymatic function and contribute to oxidative stress. In this context, such polymorphisms were already associated with several diseases and multiple therapeutic outcomes. A systematic review was performed to evaluate studies regarding the association between polymorphisms in three genes encoding enzymes of the GST family - , , and - and disorders in transplant patients. A total of 125 articles on which inclusion and exclusion criteria were applied were identified at PubMed database. Thirty-two studies met the target criteria and were included in the review. The mechanisms by which genotypes influence the development of disorders in transplant patients differ by disorder: they may participate in it by decreasing metabolism of drugs administered to patients undergoing transplantation, then exposing them to greater toxicity; by decreasing the repair ability against oxidative stress; or by encoding proteins that may be recognized as foreign, setting of an alloimmune reaction. Although some results are better established - such as null genotype's role in the development of toxicity events in transplant patients - others require further evidences, as influence on the development of pulmonary decline and posttransplant diabetes mellitus (PTDM). The importance of investigating these associations lies in a personalized medicine, in which the high-risk genotype patient has its treatment individualized and its care for prophylaxis and surveillance increased, potentially reducing this population's morbimortality.
Topics: Case-Control Studies; Genetic Predisposition to Disease; Genotype; Glutathione S-Transferase pi; Glutathione Transferase; Humans; Polymorphism, Genetic; Risk Factors
PubMed: 34856092
DOI: 10.1515/dmpt-2021-0165 -
American Journal of Reproductive... Oct 2022The efficacy of lymphocyte immunotherapy (LIT) in the treatment of recurrent pregnancy loss (RPL) from alloimmunity has been debated for years. There is conflicting... (Meta-Analysis)
Meta-Analysis
PROBLEM
The efficacy of lymphocyte immunotherapy (LIT) in the treatment of recurrent pregnancy loss (RPL) from alloimmunity has been debated for years. There is conflicting evidence on the therapeutic role of LIT, since the etiology of most cases of RPL is previously classified as idiopathic.
METHOD OF STUDY
A systematic search of PubMed and Cochrane databases was done for randomized controlled trials that assessed the efficacy of paternal lymphocyte or third donor LIT among patients with primary or secondary RPL. The primary outcome was live birth rate after LIT. Random-effect meta-analysis was conducted using the software RevMan 5.4. Pre-planned subgroup analyses of source of lymphocytes, timing and frequency of administration, and concentration per immunization dose were conducted.
RESULTS
Data from eight trials showed a statistically significant benefit of LIT (RR = 1.45, 95% CI 1.05-2.01). The overall live birth rate is higher in the treatment group (65.6%) compared to placebo or no treatment (45.2%). Subgroup analysis based on source of lymphocytes revealed a trend towards benefit with paternal LIT but with wide confidence interval (RR = 1.34, 95% CI = .84-2.14). Multiple doses of immunotherapy before pregnancy and low dose (5×10 cells) LIT showed significant benefit. Sensitivity analysis involving studies with a low risk of bias demonstrated significant benefit of increased live birth rate among patients treated with LIT compared to those who received placebo or no treatment (RR = 1.97, 95% CI = 1.53-2.53).
CONCLUSION
LIT demonstrate benefit in improving pregnancy outcome of patients with RPL from alloimmunity.
Topics: Abortion, Habitual; Birth Rate; Female; Humans; Immunotherapy; Lymphocytes; Pregnancy; Pregnancy Outcome
PubMed: 35894648
DOI: 10.1111/aji.13605 -
The Cochrane Database of Systematic... Jul 2020Sickle cell disease is one of the commonest severe monogenic disorders in the world, due to the inheritance of two abnormal haemoglobin (beta globin) genes. Sickle cell... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Sickle cell disease is one of the commonest severe monogenic disorders in the world, due to the inheritance of two abnormal haemoglobin (beta globin) genes. Sickle cell disease can cause severe pain, significant end-organ damage, pulmonary complications, and premature death. Stroke affects around 10% of children with sickle cell anaemia (HbSS). Chronic blood transfusions may reduce the risk of vaso-occlusion and stroke by diluting the proportion of sickled cells in the circulation. This is an update of a Cochrane Review first published in 2002, and last updated in 2017.
OBJECTIVES
To assess risks and benefits of chronic blood transfusion regimens in people with sickle cell disease for primary and secondary stroke prevention (excluding silent cerebral infarcts).
SEARCH METHODS
We searched for relevant trials in the Cochrane Library, MEDLINE (from 1946), Embase (from 1974), the Transfusion Evidence Library (from 1980), and ongoing trial databases; all searches current to 8 October 2019. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register: 19 September 2019.
SELECTION CRITERIA
Randomised controlled trials comparing red blood cell transfusions as prophylaxis for stroke in people with sickle cell disease to alternative or standard treatment. There were no restrictions by outcomes examined, language or publication status.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed trial eligibility and the risk of bias and extracted data.
MAIN RESULTS
We included five trials (660 participants) published between 1998 and 2016. Four of these trials were terminated early. The vast majority of participants had the haemoglobin (Hb)SS form of sickle cell disease. Three trials compared regular red cell transfusions to standard care in primary prevention of stroke: two in children with no previous long-term transfusions; and one in children and adolescents on long-term transfusion. Two trials compared the drug hydroxyurea (hydroxycarbamide) and phlebotomy to long-term transfusions and iron chelation therapy: one in primary prevention (children); and one in secondary prevention (children and adolescents). The quality of the evidence was very low to moderate across different outcomes according to GRADE methodology. This was due to the trials being at a high risk of bias due to lack of blinding, indirectness and imprecise outcome estimates. Red cell transfusions versus standard care Children with no previous long-term transfusions Long-term transfusions probably reduce the incidence of clinical stroke in children with a higher risk of stroke (abnormal transcranial doppler velocities or previous history of silent cerebral infarct), risk ratio 0.12 (95% confidence interval 0.03 to 0.49) (two trials, 326 participants), moderate quality evidence. Long-term transfusions may: reduce the incidence of other sickle cell disease-related complications (acute chest syndrome, risk ratio 0.24 (95% confidence interval 0.12 to 0.48)) (two trials, 326 participants); increase quality of life (difference estimate -0.54, 95% confidence interval -0.92 to -0.17) (one trial, 166 participants); but make little or no difference to IQ scores (least square mean: 1.7, standard error 95% confidence interval -1.1 to 4.4) (one trial, 166 participants), low quality evidence. We are very uncertain whether long-term transfusions: reduce the risk of transient ischaemic attacks, Peto odds ratio 0.13 (95% confidence interval 0.01 to 2.11) (two trials, 323 participants); have any effect on all-cause mortality, no deaths reported (two trials, 326 participants); or increase the risk of alloimmunisation, risk ratio 3.16 (95% confidence interval 0.18 to 57.17) (one trial, 121 participants), very low quality evidence. Children and adolescents with previous long-term transfusions (one trial, 79 participants) We are very uncertain whether continuing long-term transfusions reduces the incidence of: stroke, risk ratio 0.22 (95% confidence interval 0.01 to 4.35); or all-cause mortality, Peto odds ratio 8.00 (95% confidence interval 0.16 to 404.12), very low quality evidence. Several review outcomes were only reported in one trial arm (sickle cell disease-related complications, alloimmunisation, transient ischaemic attacks). The trial did not report neurological impairment, or quality of life. Hydroxyurea and phlebotomy versus red cell transfusions and chelation Neither trial reported on neurological impairment, alloimmunisation, or quality of life. Primary prevention, children (one trial, 121 participants) Switching to hydroxyurea and phlebotomy may have little or no effect on liver iron concentrations, mean difference -1.80 mg Fe/g dry-weight liver (95% confidence interval -5.16 to 1.56), low quality evidence. We are very uncertain whether switching to hydroxyurea and phlebotomy has any effect on: risk of stroke (no strokes); all-cause mortality (no deaths); transient ischaemic attacks, risk ratio 1.02 (95% confidence interval 0.21 to 4.84); or other sickle cell disease-related complications (acute chest syndrome, risk ratio 2.03 (95% confidence interval 0.39 to 10.69)), very low quality evidence. Secondary prevention, children and adolescents (one trial, 133 participants) Switching to hydroxyurea and phlebotomy may: increase the risk of sickle cell disease-related serious adverse events, risk ratio 3.10 (95% confidence interval 1.42 to 6.75); but have little or no effect on median liver iron concentrations (hydroxyurea, 17.3 mg Fe/g dry-weight liver (interquartile range 10.0 to 30.6)); transfusion 17.3 mg Fe/g dry-weight liver (interquartile range 8.8 to 30.7), low quality evidence. We are very uncertain whether switching to hydroxyurea and phlebotomy: increases the risk of stroke, risk ratio 14.78 (95% confidence interval 0.86 to 253.66); or has any effect on all-cause mortality, Peto odds ratio 0.98 (95% confidence interval 0.06 to 15.92); or transient ischaemic attacks, risk ratio 0.66 (95% confidence interval 0.25 to 1.74), very low quality evidence.
AUTHORS' CONCLUSIONS
There is no evidence for managing adults, or children who do not have HbSS sickle cell disease. In children who are at higher risk of stroke and have not had previous long-term transfusions, there is moderate quality evidence that long-term red cell transfusions reduce the risk of stroke, and low quality evidence they also reduce the risk of other sickle cell disease-related complications. In primary and secondary prevention of stroke there is low quality evidence that switching to hydroxyurea with phlebotomy has little or no effect on the liver iron concentration. In secondary prevention of stroke there is low-quality evidence that switching to hydroxyurea with phlebotomy increases the risk of sickle cell disease-related events. All other evidence in this review is of very low quality.
Topics: Adolescent; Anemia, Sickle Cell; Antisickling Agents; Blood Transfusion; Child; Child, Preschool; Early Termination of Clinical Trials; Erythrocyte Transfusion; Hemoglobin, Sickle; Humans; Hydroxyurea; Iron Chelating Agents; Phlebotomy; Primary Prevention; Secondary Prevention; Stroke; Young Adult
PubMed: 32716555
DOI: 10.1002/14651858.CD003146.pub4 -
American Journal of Obstetrics and... Mar 2024
Topics: Pregnancy; Female; Humans; Blood Transfusion, Intrauterine; Erythroblastosis, Fetal; Hydrops Fetalis; Parturition
PubMed: 37839589
DOI: 10.1016/j.ajog.2023.10.016 -
British Journal of Haematology May 2020The International Collaboration for Transfusion Medicine Guidelines (ICTMG) has published guidance on transfusion for haemoglobinopathies. To give a UK perspective on...
Position paper on International Collaboration for Transfusion Medicine (ICTM) Guideline 'Red blood cell specifications for patients with hemoglobinopathies: a systematic review and guideline'.
The International Collaboration for Transfusion Medicine Guidelines (ICTMG) has published guidance on transfusion for haemoglobinopathies. To give a UK perspective on this guidance, each of the recommendations in the ICTMG guideline were reviewed and the applicability for transfusion practice in the UK considered with reference to relevant published British Society for Haematology (BSH) guidelines and national standards . There was much consensus; however, there was disparity surrounding the recommendations for routinely extended matching in those with alloimmunisation.
Topics: Erythrocytes; Hemoglobinopathies; Humans; Transfusion Medicine
PubMed: 31961946
DOI: 10.1111/bjh.16405