scholarly journals Correlates of gallbladder stones among patients with sickle cell disease: A meta‐analysis

JGH Open ◽  
2021 ◽  
Author(s):  
Sagad O O Mohamed ◽  
Omer A O Ibrahim ◽  
Dahlia A A Mohammad ◽  
Almigdad H M Ali
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Meta Analysis ◽  
Cell Disease ◽  
Gallbladder Stones

scholarly journals Antiphospholipid Antibodies in Sickle Cell Disease: A Systematic Review and Exploratory Meta-Analysis

2021 ◽  
Vol 27 ◽  
pp. 107602962110029
Author(s):  
Mira Merashli ◽  
Alessia Arcaro ◽  
Maria Graf ◽  
Matilde Caruso ◽  
Paul R. J. Ames ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Antiphospholipid Antibodies ◽  
Meta Analysis ◽  
Age Groups ◽  
Anticardiolipin Antibodies ◽  
Cell Disease ◽  
Pooled Prevalence ◽  
The Relationship

The relationship between antiphospholipid antibodies (aPL) and sickle cell disease (SCD) has never been systematically addressed. Our aim was to evaluate potential links between SCD and aPL in all age groups. EMBASE/PubMed was screened from inception to May 2020 and Peto odds ratios for rare events were calculated. The pooled prevalence (PP) of IgG anticardiolipin antibodies (aCL) was higher in individuals with SCD than in controls (27.9% vs 8.7%, P < 0.0001), that of IgM aCL was similar in the two groups (2.9% vs 2.7%); only individuals with SCD were positive for lupus anticoagulant (LA) (7.7% vs 0%, P < 0.0001). The PP of leg ulcers was similar between aPL positive and negative individuals (44% vs 53%) and between patients in acute crisis and stable patients (5.6% vs 7.3%). Reporting of aPL as a binary outcome and not as a titer precluded further interpretation. The results indicate that a prospective case-control study with serial measurements of a panel of aPL in SCD patients might be warranted, in order to understand further the possible pathogenic role of aPL in SCD.

scholarly journals Efficacy of Allogeneic Hematopoietic Cell Transplantation (HCT) in Sickle Cell Disease: Results of a Systematic Review/Meta-Analysis

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2106-2106
Author(s):  
Madiha Iqbal ◽  
Tea Reljic ◽  
Ernesto Ayala ◽  
Hemant S. Murthy ◽  
Ambuj Kumar ◽  
...  
Keyword(s):  
Systematic Review ◽  
Sickle Cell Disease ◽  
Clinical Outcomes ◽  
Sickle Cell ◽  
Pediatric Patients ◽  
Medical Literature ◽  
Meta Analysis ◽  
Adult Patients ◽  
Cell Disease ◽  
Allogeneic Hct

Background: Sickle cell disease (SCD) is an inherited hemoglobinopathy which affects over 300,000 children born each year worldwide. In spite of improvement in supportive care in recent years, there is still a lack of effective treatment options. SCD leads to debilitating and cyclic episodes of erythrocyte sickling with progressive organ injury, contributing to lifetime morbidity and shortened life expectancy. Allogeneic HCT (allo-HCT) is a potentially curative therapy for SCD because engraftment is associated with resolution of the clinical phenotype of the disease and abrogation of its complications. Medical literature on allo-HCT for SCD is largely limited to children. Recent studies have evaluated the efficacy of allo-HCT in the adult population. Here, we conduct a systematic review/meta-analysis to assess the totality of evidence pertaining to the efficacy (or lack thereof) of allo-HCT in children and adults. Materials and methods: We performed a comprehensive search of the medical literature using PubMed/Medline, EMBASE and Cochrane library on July 3rd, 2019. We extracted data on clinical outcomes related to benefits (overall [OS] and disease free/event free survival [EFS/DFS]) and harms (non-relapse mortality [NRM] and graft failure [GF]), independently by two authors. Our search strategy identified 1001 references but only 30 studies (n= 1995 patients) were included in this systematic review/meta-analysis. We also performed a sub analysis on clinical outcomes for studies that included only pediatric patients (defined as <18 years) and those in patients ≥18 years of age. Results: Median age for patients enrolled in all the studies was at 10 years. Recurrent veno-occlusive crises represented the most common indication for allo-HCT followed by acute chest syndrome and stroke; nevertheless, most patients had more than one indication. Matched related donors (MRD) were the most common donor source (93%). Bone marrow was the most common source of hematopoietic stem cells (77%). Majority of patients underwent conditioning with myeloablative regimens (77%). Pooled OS rates (n=29 studies, 1681 patients) after allogeneic HCT was 95% (95%CI=93-96%) with low heterogeneity (I2=6.4%) among included studies (Figure 1). Pooled EFS/DFS rates (n=29 studies, 1894 patients) post-allografting was 90% (95%CI=87-93%) with moderate heterogeneity (I2=54%). Pooled NRM rates from 30 studies (1995 patients) was 4% (95%CI=2-6%) with low heterogeneity (I2=29.4%). Pooled GF rates from 28 studies (1851 patients) was 4% (95%CI=2-6%) with moderate heterogeneity (I2=55%). A subset analysis specifically for pediatric patients (n= 11 studies, 1009 patients, median age at 9.7 years) showed a pooled OS rate of 96% (95%CI=94-97%) with low heterogeneity (I2=0%); and for adult patients (n=3 studies, 51 patients, median age at 33.4 years) the pooled OS was 94% (95%CI=80-100%) with moderate heterogeneity (I2=52%). Pooled EFS/DFS for pediatric patients (n= 11 studies, 1009 patients) was at 89 %( 95%CI=84-93%) with moderate heterogeneity (I2=55.1%); and for adult patients (n=2 studies, 30 patients) was at 95% (95%CI=83-100%) with high heterogeneity (I2=96.5%). Pooled NRM from 10 studies with pediatric patients (281 patients) was at 6 % (95%CI=3-10%) with low heterogeneity (I2=0%); and from 3 studies with adult patients (51 patients) was at 1% (95%CI=0-7%) with low heterogeneity (I2=15.1%). Pooled GF from 10 studies with pediatric patients (281 patients) was at 3 % (95%CI=1-7%) with moderate heterogeneity (I2=40%); and from 2 studies with adult patients (30 patients) was at 5% (95%CI=0-17%) with high heterogeneity (I2=95.4%). Conclusions: The results of our systematic review/meta-analysis show excellent OS, EFS/DFS in children and adults undergoing allo-HCT with pooled OS rates exceeding 90%. The main limitation to offering an allo-HCT in SCD remains the availability of a suitable donor as 85% of patients meeting criteria do not have a MRD. We anticipate that with emergence of haploidentical transplantation the number of allo-HCT will increase in the future. GF remains a significant concern in this population and future studies should focus on novel immune suppression strategies to help reduce GF. Disclosures Kharfan-Dabaja: Pharmacyclics: Consultancy; Daiichi Sankyo: Consultancy.

scholarly journals Identifying Potential Drug Targets for Sickle Cell Disease through Gene Expression and Pathway Analysis of GEO Data

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 15-16
Author(s):  
Sharjeel Syed ◽  
Jihad Aljabban ◽  
Jonathan Trujillo ◽  
Saad Syed ◽  
Robert Cameron ◽  
...  
Keyword(s):  
Gene Expression ◽  
Amino Acid ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Drug Targets ◽  
Meta Analysis ◽  
Cell Disease ◽  
Blood Samples ◽  
Disease Modifying Therapies ◽  
Disease Modifying

Background: The pathogenesis of sickle cell disease (SCD) and its complications have been well characterized down to the molecular level. However, there remains a relative dearth of disease modifying therapies that reduce the frequency and number of vas-occlusive crises, hospitalizations, and deaths. Recent advancements in utilizing hydroxyurea and L-glutamine, which both impact unique disease pathways, should pave way for the identification of other molecular pathways as ideal drug targets. In this regard, our meta-analysis serves to identify key genes and associated pathways that are differentially expressed in SC patients. Methods: We employed our STARGEO platform to tag samples from the NCBI Gene Expression Omnibus and performed meta-analysis to compare SC and healthy control transcriptomes. For the meta-analysis, we tagged 285 peripheral blood samples from SC patients and 86 samples from healthy subjects as a control. We then analyzed the signature in Ingenuity Pathway Analysis to elucidate top disease functions from our analysis. Results: From our meta-analysis, we identified iron homeostasis signaling, NRF2-mediated oxidative stress response, cell senescence, and pyrimidine interconversion/biosynthesis as top canonical pathways that were upregulated in the peripheral blood samples from SC patients. Top upstream regulators included membrane associated protein and transporter ABCB6, non-coding RNY3, and erythroid maturation transcription factors GATA1, KLF1, and HIPK2 (with predicted activation). The most upregulated genes included inflammatory modulators RNF182 and IFI27, the latter of which has been shown to inhibit vascular endothelial growth and repair. Several membrane-associated protein coding genes such as GYPA, RAP1GAP, and PAQR9 were also upregulated in the SC samples. RAP1GAP is known to modulate neutrophil cell adhesion and homing while PAQR9 has roles in regulating protein quality control: a role also seen in similarly upregulated YOD1, a deubiquitinating enzyme involved in trafficking of misfolded proteins. Expectedly, also upregulated were HBBP1 and SOX6, which regulate globin genes and have been shown to silence γ-globin expression. Lastly, SLC6A19, the neutral amino acid transporter mutated in Hartnup disease, was also upregulated. Of the downregulated genes, WASF3, a member of the Wiskott-Aldrich syndrome protein family, has been linked to poor survival in many malignancies, including AML and CMML, but has not previously been linked to SCD pathogenesis. ENKUR was also downregulated and has been annotated as a tethering protein to cation channels as well as linked to pathways involving vascular leakage. SIGLEC10, which binds to vascular adhesion proteins, is a key suppressor of inflammatory responses to damage; it's downregulation along with ELAPOR1, a transmembrane protein involved in cellular response to stress, was also observed. Finally, based off the focus genes in our analysis we identified several networks with most being involved in amino acid metabolism, cellular assembly, function, and maintenance, hematological disease, and organismal injury. The top pathway is illustrated in Figure 1. Conclusions: Our study illustrates differentially expressed gene activity in SCD consistent with known pathophysiology such as immune response, endothelial damage and adherence, heme metabolism, and globin regulation. We also showed evidence of genes not previously studied in SCD, which may have novel roles such as those part of the ubiquitin-proteasome system like YOD1 and RNF182. Additionally, while some genes in our analysis like EKLF and GAT1 have been shown to enhance δ-globin expression, paving way for possible drug therapies for B-hemoglobinopathies, others like IFI27, PAQR9, RAP1GAP, ENKUR, SIGLEC10, WASF3, and SOX9 have yet to be studied as mediators of disease pathogenesis in SCD. A target to SOX9, a known suppressor of γ-globin, or ABCB6, a known modulator of erythroid cell shape and hydration, have particularly promising potential as disease modifying therapies. Finally, HIPK2, HBBP1, and SLC6A19 have previously been shown to have intriguing effects on hydroxyurea dosing and responsivity in SC patients and may also be candidate target molecules to enhance existing therapies. These data identify potential candidate pathways for mechanistic studies seeking to confirm a causative role in the pathogenesis of sickle cell disease. Disclosures No relevant conflicts of interest to declare.

Hydroxyurea can be used in children with sickle cell disease and cerebral vasculopathy for the prevention of chronic complications? A meta-analysis

2019 ◽  
Vol 24 (1) ◽  
pp. 64-77
Author(s):  
Ramiro Manzano Núñez ◽  
Carlos Andrés Portilla Figueroa ◽  
Herney Andrés García-Perdomo
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Lower Risk ◽  
Meta Analysis ◽  
Risk Difference ◽  
Cell Disease ◽  
High Quality Research ◽  
Abnormal Hemoglobin ◽  
High Concentrations ◽  
The Impact

We conducted a systematic review for evaluating the impact of hydroxyurea and chronic blood transfusion in children with sickle cell disease (SCD). A search was done in four databases from inception to 2017. Trials enrolling pediatric patients with SCD and cerebral vasculopathy with or without previous episode of stroke and that reported outcomes of occurrence of stroke and other events were included. Trained reviewers determined eligibility, risk of bias, and abstracted data. Random-effects meta-analysis was conducted. We found that the primary outcome was the occurrence of stroke. We found two trials that recruited 254 patients. No difference was found for confirmed stroke occurrence (risk difference 0.04 [95% CI: −0.03 to 0.03]) and for new-onset neurological deficit (risk difference 0.11 [95% CI: −0.00 to 0.21]). Transfusions provided a significant lower risk of vaso-occlussive crisis (risk difference 0.10 [95% CI: 0.001 to 0.20]). Finally, transfusions provided a lower risk of having high concentrations of abnormal hemoglobin S (mean difference 37.94 [95% CI: 27.55 to 48.32]). As a conclusion, transfusions plus chelation therapy might be used instead of hydroxyurea in children with SCD. There is a lack of high-quality research in the care of children with SCD, and therefore a call for action is needed.

scholarly journals Sickle cell disease, sickle trait and the risk for venous thromboembolism: a systematic review and meta-analysis

2018 ◽  
Vol 16 (1) ◽  
Author(s):  
Jean Jacques Noubiap ◽  
Mazou N. Temgoua ◽  
Ronni Tankeu ◽  
Joel Noutakdie Tochie ◽  
Ambroise Wonkam ◽  
...  
Keyword(s):  
Systematic Review ◽  
Venous Thromboembolism ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Meta Analysis ◽  
Cell Disease

scholarly journals Iron stores in pregnant women with sickle cell disease: a protocol for a systematic review and meta-analysis

BMJ Open ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. e026497 ◽  
Author(s):  
Desmond Aroke ◽  
Benjamin Momo Kadia ◽  
Tsi Njim
Keyword(s):  
Systematic Review ◽  
Sickle Cell Disease ◽  
Iron Deficiency ◽  
Pregnant Women ◽  
Sickle Cell ◽  
Iron Deficiency Anaemia ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Cell Disease ◽  
Deficiency Anaemia

IntroductionSickle cell disease (SCD) is the most common inherited disease worldwide. The greatest disease burden is seen in sub-Saharan Africa. Early diagnosis and improved care of people living with SCD have led to an increase in the number of women with SCD reaching the reproductive age. Iron deficiency anaemia remains the most common cause of anaemia in pregnancy, affecting 51%–63% of pregnancies in Africa. However, the unavailability of guidelines on supplementation of iron in this pregnant subpopulation often leaves clinicians in a fix. We propose to conduct the first systematic review and possibly a meta-analysis on the prevalence, associated factors and maternal/fetal outcomes of iron deficiency anaemia among pregnant women with SCD.Methods and analysisWe will search the following electronic databases for studies on the iron status of pregnant women with SCD: PubMed, MEDLINE, EMBASE, Google Scholar, African Journals Online, African Index Medicus, Popline and the Cochrane Library. After the selection of eligible studies from the search output, review of full text, data extraction and data synthesis will be performed. Studies obtained from the review shall be evaluated for quality, risk of bias and heterogeneity. Appropriate statistical methods shall be used to pool prevalence estimates for matching studies globally and in subpopulations. This protocol has been reported as per the 2015 guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols.Ethics and disseminationThere is no requirement for ethical approval as the proposed study will use published data. The findings of this study will be published in a peer-reviewed journal and will be presented at conferences.Trial registration numberCRD42018109803.

Adjuvant interventions with opioids for vaso-occlusive crisis in sickle cell disease: A mixed treatment network meta-analysis of randomized controlled clinical trials

2020 ◽  
Vol 16 (4) ◽  
pp. 267-275
Author(s):  
Kannan Sridharan, MD, DM ◽  
Gowri Sivaramakrishnan, MDS
Keyword(s):  
Nitric Oxide ◽  
Sickle Cell Disease ◽  
Adverse Events ◽  
Magnesium Sulfate ◽  
Sickle Cell ◽  
Meta Analysis ◽  
Favorable Effect ◽  
Secondary Outcome ◽  
Cell Disease ◽  
Number Of Patients

Objective: Vaso-occlusive crisis is the most common clinical feature requiring opioid analgesics in patients with sickle cell disease. We conducted a network meta-analysis to compare the drugs that can be used as add-on with opioids for vaso-occlusive crisis.Design: Network meta-analysis of randomized clinical trials.Patients: Sickle cell disease patients with vaso-occlusive crisis receiving adjuvants to opioids for pain management.Main outcome measures: A number of patients with complete pain relief and pain scores assessed either by visual analog or by a numerical rating scale were the primary outcomes. Adverse events and dose of opioids (in morphine equivalents) for pain alleviation between the treatment arms were the secondary outcome measures.Results: Eleven studies evaluating the addition of ketorolac, magnesium sulfate, ketoprofen, ibuprofen, methadone, inhalational nitric oxide, methylprednisolone, and arginine with morphine were obtained. The pooled analysis showed a favorable effect in the pain reduction for the additions of arginine {–2 [–3.39, –0.61]} and ibuprofen {–1.7 [–3.26, –0.14]} with morphine. Arginine has high probability of being the “best” in the pool followed by ibuprofen. No significant differences were observed in the risk of adverse events {ketoprofen—0.84 [0.42, 1.65]; magnesium sulfate—1.81 [0.64, 5.81]; and arginine—2.08 [0.18, 24.31]}. A significant lower dose of opioid was required when given adjunctive to arginine, inhalational nitric oxide, and methylprednisolone.Conclusion: We observed that arginine and ibuprofen could produce additional analgesic effects when combined with morphine in vaso-occlusive crisis.

scholarly journals Role of innate immunity-triggered pathways in the pathogenesis of Sickle Cell Disease: a meta-analysis of gene expression studies

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Bidossessi Wilfried Hounkpe ◽  
Maiara Marx Luz Fiusa ◽  
Marina Pereira Colella ◽  
Loredana Nilkenes Gomes da Costa ◽  
Rafaela de Oliveira Benatti ◽  
...  
Keyword(s):  
Gene Expression ◽  
Innate Immunity ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Meta Analysis ◽  
Cell Disease ◽  
Expression Studies ◽  
Gene Expression Studies
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