Antioxidant supplementation for sickle cell disease.

BACKGROUND: Sickle cell disease (SCD) refers to a group of genetic disorders characterized by the presence of an abnormal haemoglobin molecule called haemoglobin S (HbS). When subjected to oxidative stress from low oxygen concentrations, HbS molecules form rigid polymers, giving the red cell the typical sickle shape. Antioxidants have been shown to reduce oxidative stress and improve outcomes in other diseases associated with oxidative stress. Therefore, it is important to review and synthesize the available evidence on the effect of antioxidants on the clinical outcomes of people with SCD. OBJECTIVES: To assess the effectiveness and safety of antioxidant supplementation for improving health outcomes in people with SCD. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 15 August 2023. SELECTION CRITERIA: We included randomized and quasi-randomized controlled trials comparing antioxidant supplementation to placebo, other antioxidants, or different doses of antioxidants, in people with SCD. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data, assessed the risk of bias and certainty of the evidence, and reported according to Cochrane methodological procedures. MAIN RESULTS: The review included 1609 participants in 26 studies, with 17 comparisons. We rated 13 studies as having a high risk of bias overall, and 13 studies as having an unclear risk of bias overall due to study limitations. We used GRADE to rate the certainty of evidence. Only eight studies reported on our important outcomes at six months. Vitamin C (1400 mg) plus vitamin E (800 mg) versus placebo Based on evidence from one study in 83 participants, vitamin C (1400 mg) plus vitamin E (800 mg) may not be better than placebo at reducing the frequency of crisis (risk ratio (RR) 1.18, 95% confidence interval (CI) 0.64 to 2.18), the severity of pain (RR 1.33, 95% CI 0.40 to 4.37), or adverse effects (AE), of which the most common were headache, nausea, fatigue, diarrhoea, and epigastric pain (RR 0.56, 95% CI 0.31 to 1.00). Vitamin C plus vitamin E may increase the risk of SCD-related complications (acute chest syndrome: RR 2.66, 95% CI 0.77 to 9.13; 1 study, 83 participants), and increase haemoglobin level (median (interquartile range) 90 (81 to 96) g/L versus 93.5 (84 to 105) g/L) (1 study, 83 participants) compared to placebo. However, the evidence for all the above effects is very uncertain. The study did not report on quality of life (QoL) of participants and their caregivers, nor on frequency of hospitalization. Zinc versus placebo Zinc may not be better than placebo at reducing the frequency of crisis at six months (rate ratio 0.62, 95% CI 0.17 to 2.29; 1 study, 36 participants; low-certainty evidence). We are uncertain whether zinc is better than placebo at improving sickle cell-related complications (complete healing of leg ulcers at six months: RR 2.00, 95% CI 0.60 to 6.72; 1 study, 34 participants; very low-certainty evidence). Zinc may be better than placebo at increasing haemoglobin level (g/dL) (MD 1.26, 95% CI 0.44 to 1.26; 1 study, 36 participants; low-certainty evidence). The study did not report on severity of pain, QoL, AE, and frequency of hospitalization. N-acetylcysteine versus placebo N-acetylcysteine (NAC) 1200 mg may not be better than placebo at reducing the frequency of crisis in SCD, reported as pain days (rate ratio 0.99 days, 95% CI 0.53 to 1.84; 1 study, 96 participants; low-certainty evidence). Low-certainty evidence from one study (96 participants) suggests NAC (1200 mg) may not be better than placebo at reducing the severity of pain (MD 0.17, 95% CI -0.53 to 0.87). Compared to placebo, NAC (1200 mg) may not be better at improving physical QoL (MD -1.80, 95% CI -5.01 to 1.41) and mental QoL (MD 2.00, 95% CI -1.45 to 5.45; very low-certainty evidence), reducing the risk of adverse effects (gastrointestinal complaints, pruritus, or rash) (RR 0.92, 95% CI 0.75 to 1.14; low-certainty evidence), reducing the frequency of hospitalizations (rate ratio 0.98, 95% CI 0.41 to 2.38; low-certainty evidence), and sickle cell-related complications (RR 5.00, 95% CI 0.25 to 101.48; very low-certainty evidence), or increasing haemoglobin level (MD -0.18 g/dL, 95% CI -0.40 to 0.04; low-certainty evidence). L-arginine versus placebo L-arginine may not be better than placebo at reducing the frequency of crisis (monthly pain) (RR 0.71, 95% CI 0.26 to 1.95; 1 study, 50 participants; low-certainty evidence). However, L-arginine may be better than placebo at reducing the severity of pain (MD -1.41, 95% CI -1.65 to -1.18; 2 studies, 125 participants; low-certainty evidence). One participant allocated to L-arginine developed hives during infusion of L-arginine, another experienced acute clinical deterioration, and a participant in the placebo group had clinically relevant increases in liver function enzymes. The evidence is very uncertain whether L-arginine is better at reducing the mean number of days in hospital compared to placebo (MD -0.85 days, 95% CI -1.87 to 0.17; 2 studies, 125 participants; very low-certainty evidence). Also, L-arginine may not be better than placebo at increasing haemoglobin level (MD 0.4 g/dL, 95% CI -0.50 to 1.3; 2 studies, 106 participants; low-certainty evidence). No study in this comparison reported on QoL and sickle cell-related complications. Omega-3 versus placebo Very low-certainty evidence shows no evidence of a difference in the risk of adverse effects of omega-3 compared to placebo (RR 1.05, 95% CI 0.74 to 1.48; 1 study, 67 participants). Very low-certainty evidence suggests that omega-3 may not be better than placebo at increasing haemoglobin level (MD 0.36 g/L, 95% CI -0.21 to 0.93; 1 study, 67 participants). The study did not report on frequency of crisis, severity of pain, QoL, frequency of hospitalization, and sickle cell-related complications. AUTHORS' CONCLUSIONS: There was inconsistent evidence on all outcomes to draw conclusions on the beneficial and harmful effects of antioxidants. However, L-arginine may be better than placebo at reducing the severity of pain at six months, and zinc may be better than placebo at increasing haemoglobin level. We are uncertain whether other antioxidants are beneficial for SCD. Larger studies conducted on each comparison would reduce the current uncertainties.

Barriers to the use of hydroxyurea in the management of sickle cell disease in Nigeria.

Hydroxyurea (HU) is a well-known Hb F-inducing agent with proven clinical and laboratory efficacy for patients with sickle cell disease. However, concerns about its long-term safety and toxicity have limited its prescription by physicians and acceptability by patients. Thus, this study aims to evaluate clinician's barriers to the use of HU in the management of patients with sickle cell disease in Nigeria. An online survey targeted physicians in pediatrics, hematology, medicine, family medicine and general medical practice managing sickle cell disease in Nigeria. The survey was in four sections: demographic, knowledge and experience with HU, and barriers to the use of HU. Ninety-one (73.0%) of 123 contacts completed the survey. Seventy-three percent and 74.0% of the respondents noted that HU reduced transfusion rates and improved overall quality of life (QOL) of patients, respectively. While the majority of the practitioners (55.6%) see between 10-50 patients per month, most (66.7%) write <5 prescriptions for HU per month. Lack of a national guideline for use of HU, especially in children (52.0%), concern for infertility (52.0%), and safety profile of HU in pregnancy and lactation (48.2%), top the factors considered by the respondents as major barriers to the use of HU. Hydroxyurea is grossly under prescribed in Nigeria, despite that the vast majority of physicians who attend patients with sickle cell disease know about its clinical efficacy. Evidence-based clinical practice guidelines could be explored as a way to standardize practices and improve confidence of practitioners to improve physicians' prescription of HU in the management of sickle cell disease.

Clinical features associated with poor response and early relapse following BCMA-directed therapies in multiple myeloma.

Three classes of BCMA-directed therapy (BDT) exist: antibody drug-conjugates (ADCs), CAR-T, and T-cell engagers (TCEs), each with distinct strengths and weaknesses. To aid clinicians in selecting between BDTs, we reviewed myeloma patients treated at Mayo Clinic with commercial or investigational BDT between 2018-2023. We identified 339 individuals (1-exposure = 297, 2-exposures = 38, 3-exposures = 4) who received 385 BDTs (ADC = 59, TCE = 134, CAR-T = 192), with median follow-up of 21-months. ADC recipients were older, with more lines of therapy (LOT), and penta-refractory disease. Compared to ADCs, CAR-T (aHR = 0.29, 95%CI = 0.20-0.43) and TCEs (aHR = 0.62, 95%CI = 0.43-0.91) had better progression-free survival (PFS) on analysis adjusted for age, the presence of extramedullary (EMD), penta-refractory disease, multi-hit high-risk cytogenetics, prior BDT, and the number of LOT in the preceding 1-year. Likewise, compared to ADCs, CAR-T (aHR = 0.28, 95%CI = 0.18-0.44) and TCEs (aHR = 0.60, 95%CI = 0.39-0.93) had superior overall survival. Prior BDT exposure negatively impacted all classes but was most striking in CAR-T, ORR 86% vs. 50% and median PFS 13-months vs. 3-months. Of relapses, 54% were extramedullary in nature, and a quarter of these cases had no history of EMD. CAR-T demonstrates superior efficacy and where feasible, should be the initial BDT. However, for patients with prior BDT or rapidly progressive disease, an alternative approach may be preferable.

Haematological indices and coagulation profile as predictors of disease severity and associations with clinical outcome among COVID-19 patients in Lagos, Nigeria.

Background: This study aims to evaluate the use of haematological indices and coagulation profiles as possible low-cost predictors of disease severity and their associations with clinical outcomes in COVID-19-hospitalized patients in Nigeria. Materials and Methods: We carried out a hospital-based descriptive 3-month observational longitudinal study of 58 COVID-19-positive adult patients admitted at the Lagos University Teaching Hospital, Lagos, Nigeria. We used a structured questionnaire to obtain the participants' relevant sociodemographic and clinical data, including disease severity. Basic haematologic indices, their derivatives, and coagulation profile were obtained from patients' blood samples. Receiver Operating Characteristic (ROC) analysis was used to compare these laboratory-based values with disease severity. A P < 0.05 was considered statistically significant. Results: The mean age of the patients was 54.4 ± 14.8 years. More than half of the participants were males (55.2%, n = 32) and most had at least one comorbidity (79.3%, n = 46). Significantly higher absolute neutrophil count (ANC), neutrophil-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), lower absolute lymphocyte count (ALC) and lymphocyte-monocyte ratio (LMR) were associated with severe disease (P < 0.05). Patients' hemoglobin concentration (P = 0.04), packed cell volume (P < 0.001), and mean cell hemoglobin concentration (P = 0.03) were also significantly associated with outcome. Receiver operating characteristic (ROC) analysis of disease severity was significant for the ANC, ALC, NLR, LMR, and SII. The coagulation profile did not show any significant associations with disease severity and outcomes in this study. Conclusion: Our findings identified haematological indices as possible low-cost predictors of disease severity in COVID-19 in Nigeria.

Résumé Contexte: Cette étude avait pour objectif d'évaluer l'utilité des indices hématologiques et profils de coagulation comme prédicteurs à faible coût de la sévérité de la maladie et leurs associations avec les résultats cliniques chez les patients hospitalisés pour COVID-19 au Nigéria. Méthodes: Nous avons mené une étude longitudinale observationnelle descriptive pendant 3 mois portant sur 58 patients adultes positifs au COVID-19, admis à Lagos University Teaching Hospital, Lagos, Nigéria. Un questionnaire structuré a été établit pour obtenir les données sociodémographiques et cliniques pertinentes des participants, y compris les données sur la sévérité de la maladie. Les indices hématologiques de base, leurs dérivés, et le profil de coagulation ont été obtenus à partir d'échantillons de sang de patients. La courbe caractéristique opérante du récepteur (ROC) a été utilisée pour comparer ces indices biologiques avec la sévérité de la maladie. Une valeur de P < 0.05 a été considéré statistiquement significatif. Résultats: L'âge moyen des patients était 54.4 ± 14.8 ans. Plus de la moitié des participants étaient des hommes (55.2 %, n = 32), et la majorité des participants présentaient au moins une comorbidité (79.3 %, n = 46). Un nombre absolu de neutrophiles (CNA), un rapport neutrophiles-lymphocytes (NLR), et une indice d'inflammation immunitaire systémique (SII) significativement élevé, et un nombre absolu de lymphocytes (ALC) et un rapport lymphocyte-monocytes (LMR) bas étaient associés à un maladie sévère (P < 0.05). La taux d'hémoglobine des patients (P = 0.04), l'hématocrite (P < 0.001), et concentration moyenne d'hémoglobine cellulaire (P = 0.03) étaient également significativement associés avec la sévérité de la maladie. L'analyse ROC de la gravité de la maladie était significative pour le ANC, ALC, NLR, LMR, et SII. Le profil de coagulation n'a montré aucune association significative avec la gravité de la maladie dans cette étude. Conclusion: Nos résultats ont identifié les indices hématologiques comme des prédicteurs potentielle à faible coût de la sévérité du COVID-19 au Nigeria. Mots-clés: Profil de coagulation, COVID-19, indices hématologiques, Nigéria, prédicteur.

Use of exchange blood transfusion in the management of severe COVID-19 infection in pregnancy: experience from Lagos, Nigeria.

Coronavirus disease 2019 (COVID-19) presents with symptoms that may be mild or severe. The individual with the severe form of the disease usually presents with a constellation of respiratory symptoms typical of acute respiratory distress syndrome. In this report, we present our experience of the successful management of an oxygen-dependent pregnant woman with severe COVID-19 infection who had 2 sessions of partial exchange blood transfusion. We discussed the principles that informed this intervention and the need to adopt this novel approach in the care of severe COVID-19 infection.

Haematological indices and coagulation profile as predictors of disease severity and associations with clinical outcome among COVID­19 patients in Lagos, Nigeria

Background: This study aims to evaluate the use of haematological indices and coagulation profiles as possible low cost predictors of disease severity and their associations with clinical outcomes in COVID 19 hospitalized patients in Nigeria. Materials and Methods: We carried out a hospital based descriptive 3 month observational longitudinal study of 58 COVID 19 positive adult patients admitted at the Lagos University Teaching Hospital, Lagos, Nigeria. We used a structured questionnaire to obtain the participants' relevant sociodemographic and clinical data, including disease severity. Basic haematologic indices, their derivatives, and coagulation profile were obtained from patients' blood samples. Receiver Operating Characteristic (ROC) analysis was used to compare these laboratory based values with disease severity. A P < 0.05 was considered statistically significant. Results: The mean age of the patients was 54.4 ± 14.8 years. More than half of the participants were males (55.2%, n = 32) and most had at least one comorbidity (79.3%, n = 46). Significantly higher absolute neutrophil count (ANC), neutrophil­lymphocyte ratio (NLR), systemic immune inflammation index (SII), lower absolute lymphocyte count (ALC) and lymphocyte­monocyte ratio (LMR) were associated with severe disease (P< 0.05). Patients' hemoglobin concentration (P= 0.04), packed cell volume (P< 0.001), and mean cell hemoglobin concentration (P= 0.03) were also significantly associated with outcome. Receiver operating characteristic (ROC) analysis of disease severity was significant for the ANC, ALC, NLR, LMR, and SII. The coagulation profile did not show any significant associations with disease severity and outcomes in this study. Conclusion: Our findings identified haematological indices as possible low cost predictors of disease severity in COVID 19 in Nigeria

Use of exchange blood transfusion in the management of severe COVID-19 infection in pregnancy: experience from Lagos, Nigeria

Coronavirus disease 2019 (COVID-19) presents with symptoms that may be mild or severe. The individual with the severe form of the disease usually presents with a constellation of respiratory symptoms typical of acute respiratory distress syndrome. In this report, we present our experience of the successful management of an oxygen-dependent pregnant woman with severe COVID-19 infection who had 2 sessions of partial exchange blood transfusion. We discussed the principles that informed this intervention and the need to adopt this novel approach in the care of severe COVID-19 infection.