Search Results (43)

Background: Sickle cell disease (SCD) is a rare autosomal recessive disorder that is common in countries with consanguineous marriages. It leads to various complications, including painful episodes, infections, delayed growth, stroke, and organ damage, which contribute to high healthcare utilization and costs. In Saudi Arabia, the prevalence of SCD is notably high, largely due to the frequency of consanguineous marriages. However, there has not yet been a study estimating the direct medical costs of managing SCD based on real-world data. This study aims to assess these costs in Saudi Arabia. Methods: Data were collected from electronic medical records (EMRs) at a university-affiliated tertiary care center. A micro-costing approach was used to estimate the direct medical costs (e.g., laboratory tests, imaging, emergency department visits, hospitalizations, prescription medications, outpatient visits, etc.) retrospectively over a 12-month follow-up period. The baseline characteristics of the patients were presented using frequencies and percentages. The costs of different healthcare services were analyzed using means and the 95% confidence intervals. A generalized linear model (GLM) with a gamma distribution was utilized to examine the association between the overall costs and patient characteristics (e.g., age, gender, duration of illness, surgeries, blood transfusions, etc.), allowing for the estimation of the adjusted mean costs. Results: A total of 100 patients met the inclusion criteria and were included in the analysis. The mean age of the patients was 10.21 years (±6.87 years); 53% were male, and a substantial majority (96%) had the HbSS genotype. Sixty-one percent of the patients had undergone at least one red blood cell (RBC) exchange transfusion, while 21% had undergone surgical procedures, including tonsillectomy, splenectomy, and cholecystectomy. Additionally, 45% had experienced at least one vaso-occlusive crisis (VOC), and 59% had been hospitalized at least once in the past 12 months. Factors such as the frequency of laboratory tests and imaging studies, the length of hospital stay (LOS), the rate of emergency department (ED) visits, surgical procedures, the number of prescription medications, and the frequency of blood transfusions were all significant predictors of higher direct medical costs (p < 0.05). The estimated mean annual direct medical costs per patient were USD 26,626.45 (95% CI: USD 22,716.89–USD 30,536.00). After adjusting for various factors, including age, gender, duration of illness, frequency of lab and imaging tests, LOS, ED visits, surgical procedures, number of prescription medications, rates of VOCs, and RBC exchange transfusions, the adjusted mean annual direct medical cost per patient was calculated to be USD 14,604.72 (95% CI: USD 10,943.49–USD 19,525.96). Conclusions: The results of this study emphasize the substantial direct medical costs linked to sickle cell disease (SCD), which are greatly affected by the frequency of related complications. These insights should motivate policymakers and healthcare researchers to assess both the national direct and indirect costs associated with SCD, especially given the significant number of SCD patients in Saudi Arabia. Full article

Acute cardiovascular disorders are incriminated in up to 33% of maternal deaths, and the presence of sickle cell anemia (SCA) aggravates the risk of peripartum complications. Herein, we present a 24-year-old Caribbean woman with known SCA who developed a vaso-occlusive crisis at 36 weeks of gestation that required emergency Cesarean section. In the early postpartum period, she experienced fever with rapid onset of acute respiratory distress in the context of COVID-19 infection that required tracheal intubation and mechanical ventilatory support with broad-spectrum antibiotics and blood exchange transfusion. Shortly thereafter, transthoracic echocardiography documented severe biventricular dysfunction associated with raising levels of cardiac troponin and ECG signs of myocardial ischemia. Medical treatment with incremental dobutamine and noradrenaline infusion failed to improve cardiac output and blood gas exchange. After consultation with the regional cardiac center, a prompt decision was made to provide cardiac and respiratory support via implantation of femoral cannula and initiation of veno-arterial extracorporeal membrane oxygenation (ECMO, Cardiohelp^®). Under stable ECMO, the patient was transferred by helicopter to a specialized cardiac center. There were no signs of ongoing hemolysis, and progressive recovery of the right and left ventricular function facilitated forward blood flow through the aortic valve. Three days after implantation, ECMO was weaned, and the cannula were removed. One day later, the patient’s chest X-rays showed partial resolution of lung edema. The patient was successfully extubated, and non-invasive ventilation with pulmonary rehabilitation was initiated to speed up her functional recovery. Full article

Hematological emergencies are critical medical conditions that require immediate attention due to their rapid progression and life-threatening nature. As various examples, hypercalcemia, often associated with cancers such as multiple myeloma, can lead to severe neurological and cardiac dysfunction. Hyperleukocytosis, common in acute myeloid leukemias, increases the risk of leukostasis and multiorgan failure. Sickle cell crisis, a common complication in sickle cell disease, results from vaso-occlusion, leading to acute pain and tissue ischemia. Tumor lysis syndrome, reported in cases of rapid destruction of cancer cells, causes electrolyte imbalances and acute kidney injury. Acute transfusion reactions, fundamental in hematological conditions, can range from mild allergic responses to severe hemolysis and shock, requiring prompt management. Disseminated intravascular coagulation, involving excessive coagulation and bleeding, is commonly triggered by hematological malignancies, common in the first phases of acute promyelocytic leukemia. Recently, in the era of bispecific antibodies and chimeric antigen receptor T cells, cytokine release syndrome is a manifestation that must be recognized and promptly treated. Understanding the pathophysiology, recognizing the clinical manifestations, and ensuring adequate diagnostic strategies and management approaches for each condition are central to early intervention in improving patient outcomes and reducing mortality. Full article

In 2015, Catalonia introduced sickle cell disease (SCD) screening in its newborn screening (NBS) program along with standard-of-care treatments like penicillin, hydroxyurea, and anti-pneumococcal vaccination. Few studies have assessed the clinical impact of introducing NBS programs on SCD patients. We analyzed the incidence of SCD and related hemoglobinopathies in Catalonia and the change in clinical events occurring after introducing NBS. Screening 506,996 newborns from 2015 to 2022, we conducted a retrospective multicenter study including 100 screened (SG) and 95 unscreened (UG) SCD patients and analyzed SCD-related clinical events over the first six years of life. We diagnosed 160 cases of SCD, with an incidence of 1 in 3169 newborns. The SG had a significantly lower median age at diagnosis (0.1 y vs. 1.68 y, p < 0.0001), and initiated penicillin prophylaxis (0.12 y vs. 1.86 y, p < 0.0001) and hydroxyurea treatment earlier (1.42 y vs. 4.5 y, p < 0.0001). The SG experienced fewer median SCD-related clinical events (vaso-occlusive crisis, acute chest syndrome, infections of probable bacterial origin, acute anemia requiring transfusion, acute splenic sequestration, and pathological transcranial Doppler echography) per year of follow-up (0.19 vs. 0.77, p < 0.0001), a reduced number of annual emergency department visits (0.37 vs. 0.76, p < 0.0001), and fewer hospitalizations (0.33 vs. 0.72, p < 0.0001). SCD screening in Catalonia’s NBS program has effectively reduced morbidity and improved affected children’s quality of life. Full article

Background and Objectives: In sickle cell disease (SCD), hepatopathy is a cumulative consequence of ischemia/reperfusion (I/R) injury from a vaso-occlusive crisis, tissue inflammation, and iron overload due to blood transfusion. Hepatopathy is a major contributing factor of shortened life span in SCD patients. We hypothesized that the voxelotor, a hemoglobin allosteric modifier, ameliorates sickle hepatopathy. Materials and Methods: Townes SCD mice and their controls were treated with either chow containing GBT1118, a voxelotor analog, or normal chow. We evaluated inflammation, fibrosis, apoptosis and ferroptosis in their livers using qPCR, ELISA, histology, and immunohistochemistry. Results: GBT1118 treatment resulted in reduced hemolysis, iron overload and inflammation in the liver of SCD mice. There were significant reductions in the liver enzyme levels and bile acids. Furthermore, GBT1118-treated mice exhibited reduced apoptosis, necrosis, and fibrosis. Increased ferroptosis as evident from elevated 4-hydroxynonenal (4-HNE) staining, malondialdehyde (MDA) levels, and expression of Ptgs2 and Slc7a11 mRNAs, were also significantly reduced after GBT1118 treatment. To explain the increased ferroptosis, we evaluated iron homeostasis markers in livers. SCD mice showed decreased expression of heme oxygenase-1, ferritin, hepcidin, and ferroportin mRNA levels. GBT1118 treatment significantly increased expressions of these genes. Conclusions: Our results suggest GBT1118 treatment in SCD confers the amelioration of sickle hepatopathy by reducing inflammation, fibrosis, apoptosis, iron overload and ferroptosis. Full article

Sickle cell disease (SCD) is the most common hemoglobinopathy in the world. Sickle cell vaso-occlusive episodes (VOEs) are very painful acute events and the most common complication as well as reason for hospitalization. SCD pain is best evaluated holistically with a pain functional assessment to aid in focusing pain management on reducing pain in addition to improving function. Patients with SCD have long endured structural racism and negative implicit bias surrounding the management of pain. Thus, it is important to approach the management of inpatient pain systematically with the use of multi-modal medications and nonpharmacologic treatments. Furthermore, equitable pain management care can be better achieved with standardized pain plans for an entire system and individualized pain plans for patients who fall outside the scope of the standardized pain plans. In this article, we discuss the best practices to manage SCD VOEs during an inpatient hospitalization. Full article

Background/Objectives: Sickle cell disease (SCD) impacts about 100,000 people in the US. SCD increases the risk of cholelithiasis and microvascular ischemia, which could increase the risk of acute pancreatitis (AP). Abdominal pain is a common presenting symptom of AP and sickle cell vaso-occlusive crisis. The purpose of our systematic review is to estimate the prevalence and determine the severity of AP in individuals with SCD compared to the general population. Methods: Multiple electronic databases were searched. We included studies that included children and adults (population) and addressed the association of SCD (exposure) with AP (outcome) compared to the same population without SCD (control). Two authors screened titles and abstracts independently, and data were abstracted in duplication from included studies. We registered this protocol in PROSPERO-CRD42023422397. Results: Out of 296 studies screened from multiple electronic databases, we identified 33 studies. These studies included 17 case reports, one case series, and 15 retrospective cohort studies, and 18 studies included children. Eight of the AP case reports were in patients with HbSS genotype, two with sickle beta thalassemia, and one with HbSoArab, and in six case reports, a genotype was not specified. Complications were reported in 11 cases—respiratory complication (in at least four cases), splenic complications (three cases), pancreatic pseudocyst (two cases) and death from AP (one case). Of the four AP cases in the case series, three had HbSS genotype, and two cases had complications and severe pancreatitis. AP prevalence in SCD was estimated to be 2% and 7% in two retrospective studies, but they lacked a comparison group. In retrospective studies that evaluated the etiology of AP in children, biliary disease caused mostly by SCD was present in approximately 12% and 34%, respectively. Conclusions: Data on the prevalence of AP in individuals with SCD are limited. Prospectively designed studies aiming to proactively evaluate AP in individuals with SCD who present with abdominal pain are needed to improve timely diagnosis of AP in SCD and outcomes. Full article

Sickle cell disease is an orphan disease affecting ethnic minorities and characterized by profound systemic manifestations. Although around 100,000 individuals with SCD are living in the US, the exact number of individuals is unknown, and it is considered an orphan disease. This single-gene disorder leads to red blood cell sickling and the deoxygenation of hemoglobin, resulting in hemolysis. SCD is associated with acute complications such as vaso-occlusive crisis, infections, and chronic target organ complications such as pulmonary disease and renal failure. While genetic therapy holds promise to alter the fundamental disease process, the major challenge in the field remains the target end organ damage and ways to mitigate or reverse it. Here, we provide an overview of the clinical manifestations and pathogenesis with a focus on end-organ damage and current therapeutic options, including recent FDA-approved stem cell and gene editing therapies. Full article

Background/Objectives: This study investigated vaso-occlusive crises (VOCs) in sickle cell disease in Lubumbashi, Democratic Republic of Congo, aiming to understand the disease complexities amidst limited resources. With sickle cell hemoglobinopathies on the rise in sub-Saharan Africa, this nine-year study explored factors associated with VOCs and hematological components. Methods: This study comprised 838 patients, analyzing VOCs and hematological changes over time. Demographic characteristics and blood composition changes were carefully categorized. A total of 2910 crises were observed and managed, with analyses conducted on severity, localization, and age groups using statistical methods. Results: The majority of crises were mild or moderate, primarily affecting osteoarticular regions. Statistical analysis revealed significant disparities in crisis intensity based on location and age. The association between blood samples and the number of comorbidities was investigated. Significant positive associations were found for all parameters, except monocytes, indicating a potential link between blood variables and complication burden. Survival analysis using Cox regression was performed to predict the probability of experiencing a second crisis. No significant effects of medication or localization were observed. However, intensity (p < 0.001), age (p < 0.001), and gender (p < 0.001) showed significant effects. Adjusted Hazard Ratios indicated increased risk with age and male gender and reduced risk with mild or severe crisis intensity compared to light. Conclusions: This research sheds light on the complexities of VOCs in resource-limited settings where sickle cell disease is prevalent. The intricate interplay between clinical, laboratory, and treatment factors is highlighted, offering insights for improved patient care. It aims to raise awareness of patient challenges and provide valuable information for targeted interventions to alleviate their burden. Full article

Sickle cell disease (SCD) imposes a significant health burden, particularly in low- and middle-income countries where healthcare professionals and resources are scarce. This opinion paper delves into the management strategies employed for vaso-occlusive crises (VOCs) in pediatric patients with SCD, advocating for the adoption of a transformative strategy. We explore the integration of functional assessment approaches into existing procedures, highlighting the potential of technology-assisted rehabilitation, including wearable sensors and digital biomarkers, to enhance the effectiveness of managing and preventing VOCs. Rehabilomics, as a comprehensive framework, merges rehabilitation-related data with biomarkers, providing a basis for personalized therapeutic interventions. Despite the promising advantages of these approaches, persistent obstacles such as the limited availability of rehabilitation programs, especially in resource-limited settings, pose challenges. This paper underscores the importance of a collaborative strategy to effectively address the unique obstacles faced by patients with SCD. This collaborative approach involves improving accessibility to rehabilitation services, incorporating technology-supported therapy, and fostering focused research endeavors. The primary objective of this comprehensive approach is to enhance the overall care of SCD patients, with a specific focus on preventing VOCs, as well as providing tailored (neuro)rehabilitation services in resource-limited settings. By examining the current state of SCD management and proposing transformative strategies, this opinion paper seeks to inspire collective action and collaboration to improve outcomes for pediatric SCD patients globally. Full article

Sickle cell disease (SCD), a distinctive and often overlooked illness in the 21st century, is a congenital blood disorder characterized by considerable phenotypic diversity. It comprises a group of disorders, with sickle cell anemia (SCA) being the most prevalent and serious genotype. Although there have been some systematic reviews of global data, worldwide statistics regarding SCD prevalence, morbidity, and mortality remain scarce. In developed countries with a lower number of sickle cell patients, cutting-edge technologies have led to the development of new treatments. However, in developing settings where sickle cell disease (SCD) is more prevalent, medical management, rather than a cure, still relies on the use of hydroxyurea, blood transfusions, and analgesics. This is a disease that affects red blood cells, consequently affecting most organs in diverse manners. We discuss its etiology and the advent of new technologies, but the aim of this study is to understand the various types of nutrition-related studies involving individuals suffering from SCD, particularly in Africa. The interplay of the environment, food, gut microbiota, along with their respective genomes collectively known as the gut microbiome, and host metabolism is responsible for mediating host metabolic phenotypes and modulating gut microbiota. In addition, it serves the purpose of providing essential nutrients. Moreover, it engages in direct interactions with host homeostasis and the immune system, as well as indirect interactions via metabolites. Nutrition interventions and nutritional care are mechanisms for addressing increased nutrient expenditures and are important aspects of supportive management for patients with SCD. Underprivileged areas in Sub-Saharan Africa should be accompanied by efforts to define and promote of the nutritional aspects of SCD. Their importance is key to maintaining well-being and quality of life, especially because new technologies and products remain limited, while the use of native medicinal plant resources is acknowledged. Full article

Background and Objectives: Pain management poses a significant challenge for patients experiencing vaso-occlusive crisis (VOC) in sickle cell disease (SCD). While opioid therapy is highly effective, its efficacy can be impeded by undesirable side effects. Local regional anesthesia (LRA), involving the deposition of a perineural anesthetic, provides a nociceptive blockade, local vasodilation and reduces the inflammatory response. However, the effectiveness of this therapeutic approach for VOC in SCD patients has been rarely reported up to now. The objective of this study was to assess the effectiveness of a single-shot local regional anesthesia (LRA) in reducing pain and consequently enhancing the management of severe vaso-occlusive crisis (VOC) in adults with sickle cell disease (SCD) unresponsive to conventional analgesic therapy. Materials and Methods: We first collected consecutive episodes of VOC in critical care (ICU and emergency room) for six months in 2022 in a French University hospital with a large population of sickle cell patients in the West Indies population. We also performed a systematic review of the use of LRA in SCD. The primary outcome was defined using a numeric pain score (NPS) and/or percentage of change in opioid use. Results: We enrolled nine SCD adults (28 years old, 4 females) for ten episodes of VOC in whom LRA was used for pain management. Opioid reduction within the first 24 h post block was −75% (50 to 96%). Similarly, the NPS decreased from 9/10 pre-block to 0–1/10 post-block. Five studies, including one case series with three patients and four case reports, employed peripheral nerve blocks for regional anesthesia. In general, local regional anesthesia (LRA) exhibited a reduction in pain and symptoms, along with a decrease in opioid consumption post-procedure. Conclusions: LRA improves pain scores, reduces opioid consumption in SCD patients with refractory pain, and may mitigate opioid-related side effects while facilitating the transition to oral analgesics. Furthermore, LRA is a safe and effective procedure. Full article

People with sickle cell disease (SCD) are at greater risk of severe illness and death from respiratory infections, including COVID-19, than people without SCD (Centers for Disease Control and Prevention, USA). Vaso-occlusive crises (VOC) in SCD and severe SARS-CoV-2 infection are both characterized by thrombo-inflammation mediated by endothelial injury, complement activation, inflammatory lipid storm, platelet activation, platelet-leukocyte adhesion, and activation of the coagulation cascade. Notably, lipid mediators, including thromboxane A₂, significantly increase in severe COVID-19 and SCD. In addition, the release of thromboxane A₂ from endothelial cells and macrophages stimulates platelets to release microvesicles, which are harbingers of multicellular adhesion and thrombo-inflammation. Currently, there are limited therapeutic strategies targeting platelet-neutrophil activation and thrombo-inflammation in either SCD or COVID-19 during acute crisis. However, due to many similarities between the pathobiology of thrombo-inflammation in SCD and COVID-19, therapies targeting one disease may likely be effective in the other. Therefore, the preclinical and clinical research spurred by the COVID-19 pandemic, including clinical trials of anti-thrombotic agents, are potentially applicable to VOC. Here, we first outline the parallels between SCD and COVID-19; second, review the role of lipid mediators in the pathogenesis of these diseases; and lastly, examine the therapeutic targets and potential treatments for the two diseases. Full article

Advanced mitochondrial multi-omics indicate a multi-facet involvement of mitochondria in the physiology of the cell, changing the perception of mitochondria from being just the energy-generating organelles to organelles that highly influence cell structure, function, signaling, and cell fate. This sets mitochondrial dysfunction in the centerstage of numerous acquired and genetic diseases. Sickle cell disease is also being increasingly associated with mitochondrial anomalies and the pathophysiology of sickle cell disease finds mitochondria at crucial intersections in the pathological cascade. Altered mitophagy, increased ROS, and mitochondrial DNA all contribute to the condition and its severity. Such mitochondrial aberrations lead to consequent mitochondrial retention in red blood cells in sickle cell diseases, increased oxidation in the cellular environment, inflammation, worsened vaso-occlusive crisis, etc. There are increasing studies indicating mitochondrial significance in sickle cell disease, consequently providing an opportunity to target it for improving the outcomes of treatment. Identification of the impaired mitochondrial attributes in sickle cell disease and their modulation by therapeutic interventions can impart a better management of the disease. This review aims to describe the mitochondria in the perspective of sicke cell disease so as to provide the reader an overview of the emerging mitochondrial stance in sickle cell disease. Full article

A real-world analysis was conducted in Italy among sickle cell disease (SCD) patients to evaluate the epidemiology of SCD, describe patients’ characteristics and the therapeutic and economic burden. A retrospective analysis of administrative databases of various Italian entities was carried out. All patients with ≥1 hospitalization with SCD diagnosis were included from 01/2010-12/2017 (up to 12/2018 for epidemiologic analysis). The index date corresponded to the first SCD diagnosis. In 2018, SCD incidence rate was 0.93/100,000, the prevalence was estimated at 13.1/100,000. Overall, 1816 patients were included. During the 1st year of follow-up, 50.7% of patients had one all-cause hospitalization, 27.8% had 2, 10.4% had 3, and 11.1% had ≥4. Over follow-up, 6.1–7.2% of patients were treated with SCD-specific, 58.4–69.4% with SCD-related, 60.7–71.3% with SCD-complications-related drugs. Mean annual number per patient of overall treatments was 14.9 ± 13.9, hospitalizations 1.1 ± 1.1, and out-patient services 5.3 ± 7.6. The total mean direct cost per patient was EUR 7918/year (EUR 2201 drugs, EUR 3320 hospitalizations, and EUR 2397 out-patient services). The results from this real-world analysis showed a high disease burden for SCD patients with multiple hospitalizations during the follow-up. High healthcare resource utilization and costs were associated with patient’ management and were most likely underestimated since indirect costs and Emergency Room admissions were not included. Full article