BCL11A +58/+55 enhancer-editing facilitates HSPC engraftment and HbF induction in rhesus macaques conditioned with a CD45 antibody-drug conjugate.

Editing the +58 region of the BCL11A erythroid enhancer has shown promise in treating β-globin disorders. To address variations in fetal hemoglobin (HbF) response, we investigated editing both +58 and +55 enhancers. Rhesus macaques transplanted with edited hematopoietic stem/progenitor cells (HSPCs) following busulfan conditioning exhibited durable, high-level (∼90%) editing frequencies post transplantation with sustained HbF reactivation over 4 years, without hematological perturbations.

PREVALENCE OF CHRONIC KIDNEY DISEASE AMONG STEADY STATE SICKLE CELL DISEASE ADULT PATIENTS ATTENDING AHMADU BELLO UNIVERSITY TEACHING HOSPITAL, ZARIA.

Background: Chronic kidney disease is a long-term complication of sickle cell disease (SCD) in adults because of persistent recurrent vaso-occlusive crises, and hyperfiltration. SCD patients are in a steady state, although may be from crises, but may have deranged kidney function.

Objectives: This research studied the prevalence of chronic kidney disease among steady-state SCD patients in ABUTH, Zaria.

ASSESSMENT OF SEVERITY OF CHRONIC KIDNEY DISEASE AMONG STEADY STATE HBSS AND HBSC HOMOZYGOUS PATIENTS ATTENDING A TERTIARY HEALTH CARE INSTITUTION IN NORTHERN NIGERIA.

Background: Chronic Kidney Disease (CKD) among patients with Sickle Cell Disease (SCD) notably HbSS and HbSC are increasingly being recognized due to improved health care a comparative severity of CKD among these subgroups is not known in ABUTH Zaria.

Objective: This study was to assess the severity of kidney function among stable patients with HbSS and HbSC in ABUTH, Zaria.

Method: A cross-sectional descriptive study involving steady state 188 HbSS and 22 HbSC attending Haematology Clinic in ABUTH Zaria.

Microalbuminuria in Children With Sickle Cell Disease in the Eastern Province of Saudi Arabia.

Background And Objective: Sickle cell disease (SCD) complications, such as sickle cell nephropathy (SCN), may begin in childhood and progress insidiously to chronic kidney disease in adulthood. In Saudi Arabia (SA), there is a lack of studies evaluating kidney function in children with SCD. This study aims to assess microalbuminuria (MA) as an early marker of renal dysfunction in SCD children living in the Eastern region of SA, to potentially institute appropriate early treatment.

SMARCB1-deficient renal medullary carcinoma with an EML4::ALK fusion gene in a Japanese woman.

Renal medullary carcinoma is a rare, high-grade carcinoma arising in the renal medulla, which is usually associated with sickle cell trait, and there are very few documented cases in the Japanese population. We report a case of renal medullary carcinoma, immunohistochemically defined as SMARCB1 deficient, in a 67-year-old Japanese woman without a history of sickle cell trait. Somatic mutation of SMARCB1 and an EML4::ALK fusion gene were identified by comprehensive genomic profiling.

8-Aminopurines: A Promising New Direction for Purine-Based Therapeutics.

Research in purinergic pharmacology has yielded major advances in cardiovascular therapeutics such as adenosine for terminating atrioventricular reentrant tachycardia, regadenoson for pharmacological ischemic stress testing, and selective P2Y receptor antagonists for prevention of stroke and myocardial infarction. Mechanistically, these FDA-approved purine-based therapeutics activate or antagonize receptors having endogenous ligands containing the purine nucleobase adenine. Recent discoveries suggest a novel direction for purine-based therapeutics.

Zinc finger nuclease-mediated gene editing in hematopoietic stem cells results in reactivation of fetal hemoglobin in sickle cell disease.

BIVV003 is a gene-edited autologous cell therapy in clinical development for the potential treatment of sickle cell disease (SCD). Hematopoietic stem cells (HSC) are genetically modified with mRNA encoding zinc finger nucleases (ZFN) that target and disrupt a specific regulatory GATAA motif in the BCL11A erythroid enhancer to reactivate fetal hemoglobin (HbF). We characterized ZFN-edited HSC from healthy donors and donors with SCD.

Inhibition of sodium-glucose cotransporter-2 improves anaemia in mice and humans with sickle cell disease, and reduces infarct size in a murine stroke model.

Sodium-glucose cotransporter-2 (SGLT-2) is expressed in the kidney and may contribute to anaemia and cardiovascular diseases. The effect of SGLT-2 inhibition on anaemia and vascular endpoints in sickle cell disease (SCD) is unknown. A murine model of SCD was studied to determine the effects of the SGLT-2 inhibitor, empagliflozin, on anaemia and stroke size.

Characterizing left ventricular systolic dysfunction in sickle cell disease: three contrasting case reports.

Background: Left ventricular systolic dysfunction (LVSD) is an uncommon but life-threatening complication of sickle cell disease (SCD), with poorly characterized aetiology. We present three SCD patients with LVSD due to different underlying mechanisms.

Case Summary: The first case describes rapid deterioration in LV function secondary to severe cardiac iron overload in a 37-year-old female with poor chelation compliance after 10 years of top-up transfusions for SCD.

Could oxygen gradient ektacytometry help to detect sickle cell trait carriers at risk for kidney disorders or exercise-related complications?

The study of Ellsworth et al. (Br J Haematol, 2024) demonstrated the usefulness of oxygen gradient ektacytometry technique to better identify the physiological parameters that could increase the risk of sickling of red blood cells (RBCs) from sickle cell trait (SCT) carriers. Oxygen gradient ektacytometry combined with pH and osmolality modulations could help in identifying SCT carriers at risk for kidney disorders or exercise-related complications.

Early Detection of Renal Complication in Children With Sickle Cell Disease: A Single Center Prospective Study.

Introduction: This observational cross-sectional study aimed to identify predictors of renal complications in pediatric patients with sickle cell disease (SCD) at King Salman Armed Forces Hospital, Tabuk, Saudi Arabia, over six months from February 2023 to July 2023. The study evaluated microalbuminuria as an early indicator of renal injury and explored its correlations with clinical and laboratory parameters and abdominal ultrasound (US) findings.

Methods: Included were pediatric patients aged 1 to 14 years with confirmed SCD, excluding those with acute infections or pre-existing renal diseases.

Development and IND-enabling studies of a novel Cas9 genome-edited autologous CD34 cell therapy to induce fetal hemoglobin for sickle cell disease.

Sickle cell disease (SCD) is a common, severe genetic blood disorder. Current pharmacotherapies are partially effective and allogeneic hematopoietic stem cell transplantation is associated with immune toxicities. Genome editing of patient hematopoietic stem cells (HSCs) to reactivate fetal hemoglobin (HbF) in erythroid progeny offers an alternative potentially curative approach to treat SCD.

Double Trouble: COVID-19 Infection Exacerbates Sickle Cell Crisis Outcomes in Hospitalized Patients-Insights from National Inpatient Sample 2020.

This study investigated the impact of COVID-19 on patients with sickle cell crisis (SCC) using National Inpatient Sample (NIS) data for the year 2020. A retrospective cohort analysis was conducted utilizing International Classification of Diseases (ICD-10) codes to identify adults who were admitted with a principal diagnosis of sickle cell crisis. The primary outcomes examined were inpatient mortality, while the secondary outcomes assessed included morbidity, hospital length of stay, and resource utilization.

The Not-So-Benign Sickle Cell Trait: A Case of Renal Medullary Carcinoma.

Sickle cell trait (SCT) has long been considered a benign carrier state with malarial protection, but carriers can be affected by increased venous thromboembolism, exercise-related injury, renal complications and very rarely a fatal renal malignancy. Renal medullary carcinoma is a very rare and aggressive renal tumor described almost exclusively in sickle cell trait. A review of the current literature provides clues to this link and describes trends expected in these cases.

Unexpected Death of a Sickle Cell Disease Patient: A Case Report and Literature Review.

Sickle cell disease (SCD) is an autosomal recessive genetic disorder characterized by the abnormal formation of sickle hemoglobin (HbS). Under conditions of deoxygenation, HbS undergoes polymerization, resulting in microvascular occlusion, tissue hypoxia, and infarction. The elevated mortality rate associated with SCD is primarily attributed to complications such as sepsis, acute chest syndrome, stroke, acute multiorgan failure, and pulmonary hypertension.

Prevalence, Mortality, and Access to Care for Chronic Kidney Disease in Medicaid-Enrolled Adults With Sickle Cell Disease in California: Retrospective Cohort Study.

Background: Chronic kidney disease (CKD) is a significant complication in patients with sickle cell disease (SCD), leading to increased mortality.

Objective: This study aims to investigate the burden of CKD in Medicaid-enrolled adults with SCD in California, examine differences in disease burden between male and female individuals, and assess mortality rates and access to specialized care.

Methods: This retrospective cohort study used the California Sickle Cell Data Collection program to identify and monitor individuals with SCD.