bims-sicedi 2024-12-22 papers

Hemasphere. 2024 Dec;8(12): e70032

Inflammatory pathways and anti-inflammatory therapies in sickle cell disease.

Karina Tozatto-Maio, Felipe A Rós, Ricardo Weinlich, Vanderson Rocha.

Sickle cell disease (SCD) is a monogenic disease, resulting from a single-point mutation, that presents a complex pathophysiology and high clinical heterogeneity. Inflammation stands as a prominent characteristic of SCD. Over the past few decades, the role of different cells and molecules in the regulation of the inflammatory process has been elucidated. In conjunction with the polymerization of hemoglobin S (HbS), intravascular hemolysis, which releases free heme, HbS, and hemoglobin-related damage-associated molecular patterns, initiates multiple inflammatory pathways that are not yet fully comprehended. These complex phenomena lead to a vicious cycle that perpetuates vaso-occlusion, hemolysis, and inflammation. To date, few inflammatory biomarkers can predict disease complications; conversely, there is a plethora of therapies that reduce inflammation in SCD, although clinical outcomes vary widely. Importantly, whether the clinical heterogeneity and complications are related to the degree of inflammation is not known. This review aims to further our understanding of the roles of main immune cells, and other inflammatory factors, as potential prognostic biomarkers for predicting clinical outcomes or identifying novel treatments for SCD.

DOI: https://doi.org/10.1002/hem3.70032

Transplant Cell Ther. 2024 Dec 17. pii: S2666-6367(24)00808-X. [Epub ahead of print]

Lipid levels increase to the normal range after nonmyeloablative hematopoietic cell transplantation for sickle cell disease.

Jackie Queen, Emily Limerick, Neal Jeffries, Matthew M Hsieh, Robert D Shamburek, Courtney D Fitzhugh.

BACKGROUND: Individuals with sickle cell disease (SCD) have a unique type of dyslipidemia characterized by low total cholesterol (TC), low low-density lipoprotein cholesterol (LDL-c), low high-density lipoprotein cholesterol (HDL-c), and normal triglycerides (TG). This lipid state is theorized to be cardioprotective against atherosclerosis. In SCD, hematopoietic cell transplant (HCT) offers a potentially curative therapy. Long-term survivors of HCT for hematologic malignancies are at increased risk for dyslipidemia and atherosclerosis long-term. The effects of HCT on SCD dyslipidemia are unknown.
OBJECTIVE: This retrospective cohort study characterizes lipid profiles at baseline and after nonmyeloablative allogeneic HCT for SCD.
STUDY DESIGN: We analyzed data from 116 patients after nonmyeloablative HLA-matched sibling or haploidentical HCT for SCD at the NIH from 2009 to 2021. Total cholesterol, HDL-c, LDL-c, and TG were collected pre-HCT, one year post-HCT, and annually thereafter. Data were analyzed using linear generalized estimating equation regression modeling.
RESULTS: Successful HCT was associated with a rise in TC, LDL-c, and HDL-c and a decline in TG post-HCT. After HCT, previously low lipid levels increased to the normal range. These changes occurred within the first year of HCT and were maintained thereafter. In patients with graft failure, TC and LDL-c levels remain unchanged from their pre-HCT baseline. Sirolimus use for graft versus host disease prophylaxis was associated with higher TG levels.
CONCLUSIONS: These findings suggest that SCD dyslipidemia resolves with reversal of the SCD phenotype. The normalization of lipid parameters suggests SCD patients are not at increased risk for atherosclerosis after successful HCT compared to their peers; further studies with longer follow-up are required.

DOI: https://doi.org/10.1016/j.jtct.2024.12.008

J Assoc Physicians India. 2024 Dec;72(12): e12-e16

Association of Copper, Zinc, Copper-to-zinc ratio and Disease Severity Scores in Sickle Cell Anemia: An Observational Analytical Study.

Preetam N Wasnik, Suparva Patel, Pankaj K Kannauje, Pranita, Vinay R Pandit, Eli Mohapatra, Tarun Sahu, Jyoti Sahu.

OBJECTIVE: The purpose of the study was to assess the amount of serum copper, zinc, and copper-to-zinc ratio in sickle cell anemia patients and healthy subjects and to relate the parameters with an objective disease severity score. Further, to see the correlation between copper and zinc levels with fetal hemoglobin level in sickle cell anemia (SCA) subjects in both stable state and during the crisis.
MATERIALS AND METHODS: Copper and zinc levels in serum of 100 SCA and 100 healthy subjects were measured using commercially available kits. The copper-to-zinc ratio was then obtained by dividing the copper and zinc levels. High-performance liquid chromatography (HPLC) was used to determine the fetal hemoglobin level of every participant. The data were compared between SCA subjects in a stable state, crisis state, and control subjects using the Student's t-test, and the variables were linked with disease severity levels using the Pearson's correlation coefficient.
RESULTS: The levels of copper and the ratio of copper-to-zinc were notably elevated in SCA patients compared to controls, whereas zinc levels were lower in the SCA patients. Zinc level was associated negatively (r = -0.350; p < 0.001), while the ratio of copper to zinc was associated positively (r = 0.246; p = 0.014) with objective disease severity scores.
CONCLUSION: Copper levels were elevated, while zinc levels were reduced in sickle cell anemia patients, and the ratio of copper-zinc in these patients may predict the severity of the disease.

DOI: https://doi.org/10.59556/japi.72.0762

Rev Bras Enferm. 2024 ;pii: S0034-71672024001000168. [Epub ahead of print]77(6): e20230545

Respectful care for postpartum women with sickle cell disease: a netnographic study.

Zannety Conceição Silva do Nascimento Souza, Luana Gabriella Pinheiro Barrêto, Paulo Roberto Lima Falcão do Vale, Elysangela Dittz Duarte, Cristiane Dos Santos Silva, Evanilda Souza de Santana Carvalho.

OBJECTIVES: to analyze principles of respectful maternity care in narratives of postpartum women with sickle cell disease, relating them to Sustainable Development Goals.
METHODS: netnographic study, with two videos published in 2020. Deductive iconographic and thematic analysis by Respectful Maternity Care Charter, organized in MAXQDA.
RESULTS: principles identified were the right to: freedom from harm and ill-treatment; information, informed consent, refusal of medical procedures, and respect for their choices and preferences including companion; be considered a person from birth, with dignified and respectful treatment; health at the highest possible level; newborns being with their parents or guardians. The Sustainable Development Goals for women by 2030 were not positively contemplated in postpartum women's experience.
FINAL CONSIDERATIONS: it is appropriate that health workers qualify themselves to provide respectful maternity care, with qualified listening, understanding, and resolution of unique demands of postpartum women with sickle cell disease, seeking equality in care for women.

DOI: https://doi.org/10.1590/0034-7167-2023-0545