Sickle cell disease (SCD) is associated with substantial morbidity and early mortality in afflicted adults. Cardiopulmonary complications that occur at increased frequency in SCD such as pulmonary embolism, pulmonary arterial hypertension, and acute chest syndrome can acutely worsen right ventricular function and lead to cardiogenic shock. Mechanical circulatory support including venoarterial extracorporeal membrane oxygenation (VA ECMO) is being increasingly utilized to treat hemodynamic collapse in various patient populations. However, a paucity of literature exists to guide the use of mechanical circulatory support in adults with SCD where disease-related sequela and unique hematologic aspects of this disorder may complicate extracorporeal therapy and must be understood. Here, we review the literature and describe three cases of adult patients with SCD who developed cardiogenic shock from acute decompensated right heart failure and were treated clinically with VA ECMO. Using an in vitro ECMO system, we investigate a potential increased risk of systemic fat emboli in patients with SCD who may be experiencing vaso-occlusive events with bone marrow involvement given the high-volume shunting of blood from venous to arterial systems with VA ECMO. The purpose of this study is to describe available extracorporeal life support experiences, review potential complications, and discuss the special considerations needed to further our understanding of the utility of VA ECMO in those with SCD.

BACKGROUND: Despite the huge burden of sickle cell disease (SCD) among Nigerian children, the burden and outcome of respiratory illnesses remain undocumented. Thus, we aimed to describe the spectrum and outcome of respiratory illnesses among SCD childrenand adolescentadmissions in ten Nigerian tertiary hospitals.
METHODS: A retrospective review of the SCD admission records of children and adolescents with a confirmed diagnosis of respiratory illnesses from 2012 to 2021 in ten tertiary health facilities across five geopolitical zones in Nigeria was conducted. The data, collectedbetween March and June 2023, included the age, sex, diagnosis, complications, duration and outcome of hospitalization.
RESULTS: Of the 72,333 paediatric admissions, 7,256 (10.0%) had SCD; the proportion of SCD from the total admission ranged from 2.1 to 16.3% in the facilities. Of the 7,256 children and adolescents with SCD, 1,213 (16.7%) had respiratory morbidities. Lower respiratory disease was the most common (70.0%) respiratory entity and the majority were pneumonia (40.1.0%), followed by acute chest syndrome (26.7%). Seventeen (1.4%) patients died; all had lower respiratory diseases [(acute chest syndrome ACS (11, 64.7%), pneumonia; 5, 29.4%, and asthma (1, 5.9%). Based on the proportion of deaths among overall SCD, the 17 death cases contributed 9.4% (95% CI 5.9 to 14.5). Factors associated with deaths included duration of hospitalization less than 72 hours and lower respiratory tract diseases.
CONCLUSIONS: Sickle cell disease is a major contributor to hospitalization among Nigerian children and adolescents, with high respiratory morbidity and mortality. Pneumonia and acute chest syndrome were associated with mortality, andthe highest risk of death within the first 72 hours.

Sickle cell disease is the most common hemoglobinopathy among humans. As the condition promotes susceptibility to infections, chronic inflammation, and hypercoagulability disorders, several international agencies have included individuals with this disease in the COVID-19 risk group for severe outcomes. However, available information about the subject is not properly systematized yet. This review aimed to understand and summarize the scientific knowledge about the impact of SARS-CoV-2 infection in patients with sickle cell disease. Searches were performed in the Medline, PubMed, and Virtual Health Library databases based on descriptors chosen according to the Medical Subject Headings. We analyzed studies published between 2020 and October 2022, developed with qualitative, quantitative, or mixed methodology, and written in English, Spanish, or Portuguese. The search resulted in 90 articles organized into six categories. There is disagreement in the literature about how different aspects related to sickle cell disease, such as chronic inflammation status, hypercoagulability, hemolytic anemia, use of hydroxyurea, and access to medical care interference with the clinical course of COVID-19. These topics deserve further investigation. It is evident, however, that the infection may manifest in an atypical way and act as a trigger for the development of sickle cell-specific complications, such as acute chest syndrome and vaso-occlusive crises, conditions that are associated with great morbidity and mortality. Therefore, healthcare professionals must be aware of the different forms of presentation of COVID-19 among these individuals. Specific guidelines and therapeutic protocols, as well as public policies for sickle cell individuals, must be considered.
UNASSIGNED: This review (https://doi.org/10.17605/OSF.IO/NH4AS) and the review protocol (https://osf.io/3y649/) are registered in the Open Science Framework platform.

UNASSIGNED: Allogeneic hematopoietic stem cell transplant (HSCT) and gene therapy (GT) are two potentially curative approaches for sickle cell disease (SCD), but they have never been compared in clinical trials.
UNASSIGNED: To compare the safety and efficacy of HSCT and GT to assist clinicians and patients in making informed treatment decisions.
UNASSIGNED: Phase I-III clinical trials and case reports/series were included. Regimens included HSCT from all stem cell sources, lentiviral gene therapy, and gene editing, with any conditioning regimen. We searched Medline and EMBASE databases as of 1st June 2020 for studies reporting HSCT and GT outcomes in SCD. The Newcastle-Ottawa scale was used to assess the risk of bias. Descriptive statistics and post-hoc imputation for standard deviations of mean change in FEV1 and FVC were performed.
UNASSIGNED: In total, 56 studies (HSCT, n = 53; GT, n = 3) representing 1,198 patients met inclusion criteria (HSCT, n = 1,158; GT, n = 40). Length of follow-up was 3,881.5 and 58.7 patient-years for HSCT and GT, respectively. Overall quality of evidence was low, with no randomized controlled trials identified. Two-year overall survival for HSCT was 91%; mortality was 2.5% for GT. Acute chest syndrome and vaso-occlusive episodes were reduced post-HSCT and GT. Meta-analysis was not possible due to lack of comparator and heterogeneity in outcome measures reporting. Very few studies reported post-transplant end-organ function. Six secondary malignancies (5 post-HSCT, 1 post-GT) were reported.
UNASSIGNED: Reporting of SCD-related complications and patient-important outcomes is lacking for both strategies. We advocate for standardized reporting to better compare outcomes within and between treatment groups.

BACKGROUND: Acute chest syndrome (ACS) is a leading cause of death in patients with sickle cell disease. Lung ultrasound (LUS) is emerging as a point-of-care method to diagnose ACS, allowing for more rapid diagnosis in the ED setting and sparing patients from ionizing radiation exposure.
OBJECTIVE: What is the diagnostic accuracy of LUS for ACS diagnosis, using the current reference standard of chest radiography?
METHODS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed for this systematic review and meta-analysis. Embase, MEDLINE, Web of Science, and Google Scholar were used to compile all relevant studies. Two reviewers screened the studies for inclusion in this review. Cases of discrepancy were resolved by a third reviewer. Meta-analyses were conducted using both metadta and midas STATA software packages to retrieve summary receiver operating characteristic curves, sensitivities, and specificities. Three reviewers scored the studies with QUADAS-2 for risk of bias assessment.
RESULTS: From a total of 713 unique studies retrieved, six studies were included in the final quantitative synthesis. Of these, five studies were in pediatric EDs. Two studies were conference abstracts and not published manuscripts. Data were available for 625 possible ACS cases (97% of cases in patients aged ≤ 21 years) and 95 confirmed ACS diagnoses (pretest probability of 15.2%). The summary sensitivity was 0.92 (95% CI, 0.68-0.98) and the summary specificity was 0.89 (95% CI, 0.69-0.97) with an area under the curve of the summary receiver operating characteristic curve of 0.96 (95% CI, 0.94-0.97).
CONCLUSIONS: LUS has excellent sensitivity and very good specificity for ACS diagnosis and may serve as an initial point-of-care test to facilitate rapid treatment of ACS and spare pediatric patients from ionizing radiation; however, further research is warranted to improve the generalizability to the adult sickle cell disease population.

Sickle cell disease (SCD) is the most frequent inherited disorder in the world. It is caused by a single amino acid mutation on the beta-globin chain, which lead to red blood cell deformation, haemolysis, and chronic inflammation. Clinical consequences are vaso-occlusives crisis, acute chest syndrome, thrombosis, infection, and chronic endothelial injury.
Corticosteroids are an old therapeutic class, that are inexpensive and widely available, which can be administered in different forms. Their adverse effects are numerous and well-known. This class could appear to be useful in SCD treatment due to its anti-inflammatory effect. Moreover, corticosteroids remain an essential therapeutic class for many indications, besides SCD. Although specific adverse effects of corticosteroids have been suspected in SCD patients for decades, recent papers has reported strong evidence of specific and severe adverse effects in this population. Based on a literature review, we will discuss pathophysiological considerations, consequences, and practical use of corticosteroids in SCD.
High corticosteroid doses, for any indication , induce vaso-occlusive crises, acute chest syndrome, and re-hospitalization in patients with SCD. There is no evidence of any benefits of corticosteroid use in the SCD acute events. Prevention by hydroxyurea and/or red blood cell transfusion or exchange should be discussed when corticosteroid use is indispensable.

Hemoglobin D-Los Angeles is a variant of hemoglobin that can polymerize in the deoxygenated state. When co-inherited with Hemoglobin S (HbSD-Los Angeles disease) a severe sickling syndrome similar to HbSS can result. Corona virus infectious disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome-corona virus-2. It has been associated with acute chest syndrome (ACS) in individuals with sickle cell disease (SCD), but this complication has not previously been reported in patients with HbSD-Los Angeles. Dexamethasone has been shown to improve outcomes in non-SCD patients with severe acute respiratory syndrome-corona virus-2 pneumonia or acute respiratory distress syndrome; however, its use in SCD patients with ACS is controversial due to a reported increased risk of complications including vaso-occlusive painful episodes. Herein, we reported a patient with HbSD-Los Angeles and COVID-19-associated ACS whom we treated with dexamethasone without transfusion. The patient experienced a rapid recovery without sequelae from steroid use. To further evaluate the use of steroids, we conducted a literature review focusing on the management of pediatric SCD patients with COVID-19-associated ACS. We identified a total of 39 pediatric patients with SCD and COVID-19, of whom 21 (54%) had ACS. Packed red blood cell transfusion (n=11), exchange transfusion (n=4), or a combination of exchange transfusion and packed red blood cell transfusion (n=4) were the most frequently reported treatment, with hydroxychloroquine (n=5), remdesivir (n=1), and tocilizumab (n=1) also being reported. Three patients were treated with dexamethasone. All patients recovered and no adverse outcomes from steroid use were reported. Even though transfusion is considered the standard of care for children with ACS and steroids are not routinely recommended, our experience suggested that COVID-19-associated ACS may be an important exception, especially for patients who refuse transfusion or are in resource-poor nations where blood transfusions may not be readily available. Further studies are warranted to confirm these observations.

UNASSIGNED: Acute chest syndrome (ACS) accounts for the highest mortality in Sickle cell disease patients. Early diagnosis and timely management of ACS results in better outcomes. However, the effectiveness of most treatment modalities for ACS management has not been established.
UNASSIGNED: To review the treatment modalities management protocols and highlight the effectiveness of each option a literature search was done. Randomized controlled trials that assessed the efficacy of different treatment modalities in ACS management in SCD patients were chosen and reviewed.
UNASSIGNED: 11 randomized controlled trials were found that evaluated the efficacy of incentive spirometry, positive expiratory pressure device, intravenous dexamethasone, oral vs. intravenous morphine, inhaled nitric oxide, unfractionated heparin, and blood transfusion in the prevention or treatment of ACS. Although there are guidelines for ACS treatment, the available evidence is very limited to delineating the effectiveness of various interventions in ACS management. More high-quality studies and trials with a larger patient population can benefit this area to support the recommendations with stronger evidence.

UNASSIGNED: the spectrum of pulmonary complications in sickle cell anemia (SCA) comprises mainly of acute chest syndrome (ACS), pulmonary hypertension (PH) and airway hyper-responsiveness (AHR). This study was conducted to examine the abnormalities in pulmonary function tests (PFTs) seen in children with SCA.
UNASSIGNED: electronic databases (Cochrane library, PubMed, EMBASE, Scopus, Web of Science) were used as data sources. Two authors independently reviewed studies. All case-control studies with PFT performed in patients with SCA and normal controls were reviewed. Pulmonary functions were assessed with the help of spirometry, lung volume and gas diffusion findings.
UNASSIGNED: nine studies with 788 SCA children and 1101 controls were analyzed. For all studies, the pooled mean difference for forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, peak expiratory flow rate (PEFR), total lung capacity (TLC) and carbon mono-oxide diffusing capacity (DLCO) were -12.67, (95% CI: -15.41,-9.94), -11.69, (95% CI: -14.24, -9.14), -1.90, (95% CI: -4.32, 0.52), -3.36 (95% CI: -6.69, -0.02), -7.35, (95% CI: -14.97, -0.27) and -4.68, (95% CI -20.64, -11.29) respectively. FEV1 and FVC and were the only parameters found to be significantly decreased.
UNASSIGNED: sickle cell anemia was associated with lower FEV1 and FVC, thus, supporting the role of routine monitoring for the progression of lung function decline in children with SCA with ACS. We recommend routine screening and lung function monitoring for early recognition of pulmonary function decline.

Sickle cell disease (SCD) is associated with vaso-occlusive episodes that affect different organs. Pulmonary involvement is a major cause of morbidity and mortality in this patient population. We performed a literature search in the PubMed database for articles addressing SCD and pulmonary diseases. Acute chest syndrome is defined as a new radiodensity on chest radiograph imaging with a history consistent of the disease. Management includes broad spectrum antibiotics, pain control, and blood transfusions. Microvasculature infarcts lead to functional asplenia, which in turn increases the risk of being infected with encapsulated organisms. Universal vaccinations and antibiotic prophylaxis play a significant role in decreasing mortality from pulmonary infections. Venous thromboembolism in patients with SCD should be treated in the same manner as in the general population. Pulmonary hypertension in patients with SCD also increases mortality. The American Thoracic Society treatment modalities are based on the underlying etiology which is either directed at treating SCD itself, using vasodilator medications if the patient is in group 1, or using long-term anticoagulation if the patient is group 4 (in terms of etiology). Patients with SCD are more likely to suffer from asthma in comparison to controls. Sleep disorders of breathing should be considered in patients with unexplained nocturnal and daytime hypoxemia, or recurrentvaso-occlusive events. Lastly, the utility of pulmonary function tests still needs to be established.