Mixed donor chimerism following stem cell transplantation for sickle cell disease.

Sickle cell disease is a debilitating hemoglobinopathy with high morbidity and mortality. Hematopoietic stem cell transplantation (HCT) is curative, but the presence of mixed donor/recipient chimerism post-HCT raises concerns about disease control long-term. Mixed donor/recipient chimerism is reported in significant numbers even after aggressive HCT conditioning regimens. Post-HCT, adequacy of donor erythropoiesis is crucial for disease control. This review explores the relationship between mixed donor/recipient chimerism and outcomes post-HCT. Serial chimerism analysis in lineage specific manner in erythroid or myeloid cells post-HCT predicts for disease control and HCT success. Adequate and stable donor-derived erythropoiesis is essential for reversing SCD manifestations. Myeloid lineage chimerism mirrors erythropoiesis is commercially available, and a reliable indicator of adequacy. Using this tool, the minimum threshold of donor chimerism is required to prevent SCD-related complications and maintain sickle hemoglobin less than 50% is approximately 20-25% even when a donor has Hb S trait. Curative interventions should, at a minimum, meet this goal long-term. Achieving a balance between successful engraftment while minimizing toxicity is important in patients vulnerable because of age or preexisting morbidity and is the objective of recent clinical trials. As HCT and gene therapies evolve, efficient long-term follow-up that includes durability assessment of mixed donor/recipient chimerism will be crucial.

Understanding Sickle cell disease: Causes, symptoms, and treatment options.

Sickle cell disease (SCD) is a hereditary blood disorder characterized by the production of abnormal hemoglobin molecules that cause red blood cells to take on a crescent or sickle shape. This condition affects millions of people worldwide, particularly those of African, Mediterranean, Middle Eastern, and South Asian descent. This paper aims to provide an overview of SCD by exploring its causes, symptoms, and available treatment options. The primary cause of SCD is a mutation in the gene responsible for producing hemoglobin, the protein that carries oxygen in red blood cells. This mutation has abnormal hemoglobin called hemoglobin S, which causes red blood cells to become stiff and sticky, leading to various health complications. Patients with SCD may experience recurrent pain, fatigue, anemia, and increased infection susceptibility. Treatment options for SCD focus on managing symptoms and preventing complications. This includes pain management with analgesics, hydration, and blood transfusions to improve oxygen delivery. Hydroxyurea, a medication that increases the production of fetal hemoglobin, is commonly used to reduce the frequency and severity of pain crises. Additionally, bone marrow or stem cell transplants can cure select individuals with severe SCD. Finally, understanding the causes, symptoms, and treatment options for SCD is crucial for healthcare professionals, patients, and their families. It enables early diagnosis, effective symptom management, and improved quality of life for individuals with this chronic condition.

Atomic force microscopy reveals involvement of the cell envelope in biomechanical properties of sickle erythrocytes.

BACKGROUND: Intracellular hemoglobin polymerization has been supposed to be the major determinant for the elevated rigidity/stiffness of sickle erythrocytes from sickle cell anemia (SCA) patients. However, the contribution of the cell envelope remains unclear. RESULTS: In this study, using atomic force microscopy (AFM), we compared the normal and sickled erythrocyte surfaces for stiffness and topography. AFM detected that sickle cells had a rougher surface and were stiffer than normal erythrocytes and that sickle cell ghosts had a rougher surface (for both outer and inner surfaces) and were thicker than normal ghosts, the latter implying a higher membrane-associated hemoglobin content/layer in the sickle cell envelope. Compared to healthy subjects, the SCA patients had lower plasma lipoprotein levels. AFM further revealed that a mild concentration of methyl-ß-cyclodextrin (MßCD, a putative cholesterol-depleting reagent) could induce an increase in roughness of erythrocytes/ghosts and a decrease in thickness of ghosts for both normal and sickle cells, implying that MßCD can alter the cell envelope from outside (cholesterol in the plasma membrane) to inside (membrane-associated hemoglobin). More importantly, MßCD also caused a more significant decrease in stiffness of sickle cells than that of normal erythrocytes. CONCLUSIONS: The data reveal that besides the cytosolic hemoglobin fibers, the cell envelope containing the membrane-associated hemoglobin also is involved in the biomechanical properties (e.g., stiffness and shape maintenance) of sickle erythrocytes.

Secondary Neoplasms After Hematopoietic Cell Transplant for Sickle Cell Disease.

PURPOSE: To report the incidence and risk factors for secondary neoplasm after transplantation for sickle cell disease. METHODS: Included are 1,096 transplants for sickle cell disease between 1991 and 2016. There were 22 secondary neoplasms. Types included leukemia/myelodysplastic syndrome (MDS; n = 15) and solid tumor (n = 7). Fine-Gray regression models examined for risk factors for leukemia/MDS and any secondary neoplasm. RESULTS: The 10-year incidence of leukemia/MDS was 1.7% (95% CI, 0.90 to 2.9) and of any secondary neoplasm was 2.4% (95% CI, 1.4 to 3.8). After adjusting for other risk factors, risks for leukemia/MDS (hazard ratio, 22.69; 95% CI, 4.34 to 118.66; P = .0002) or any secondary neoplasm (hazard ratio, 7.78; 95% CI, 2.20 to 27.53; P = .0015) were higher with low-intensity (nonmyeloablative) regimens compared with more intense regimens. All low-intensity regimens included total-body irradiation (TBI 300 or 400 cGy with alemtuzumab, TBI 300 or 400 cGy with cyclophosphamide, TBI 200, 300, or 400 cGy with cyclophosphamide and fludarabine, or TBI 200 cGy with fludarabine). None of the patients receiving myeloablative and only 23% of those receiving reduced-intensity regimens received TBI. CONCLUSION: Low-intensity regimens rely on tolerance induction and establishment of mixed-donor chimerism. Persistence of host cells exposed to low-dose radiation triggering myeloid malignancy is one plausible etiology. Pre-existing myeloid mutations and prior inflammation may also contribute but could not be studied using our data source. Choosing conditioning regimens likely to result in full-donor chimerism may in part mitigate the higher risk for leukemia/MDS.

The effect of intensity of conditioning regimen on the outcome of HSCT in children with sickle cell disease.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) provides a cure for patients with sickle cell disease (SCD). This study describes the effect of conditioning regimen intensity on HSCT outcomes among children younger than 14 years with SCD. METHODS: Transplants from HLA-matched related donors (MRD) and unrelated donors (MUD) using either myeloablative conditioning (MAC) regimens or reduced intensity conditioning (RIC) regimens were considered. Event-free survival (EFS) was the primary endpoint. Secondary endpoints included overall survival (OS) and occurrence of GVHD. RESULTS: 48 SCD patients underwent HSCT, 45 (93.8%) patients had MRD, 1 (2.1%) had 9/10 related donor, and 2 (4.1%) had MUD. The median age at transplant was 8.6 years (range, 3.1-13.8). Conditioning regimens were myeloablative (MAC) in 41 (85.4%) patients and of reduced intensity in 7 (14.6%) patients. EFS at 2 years was 100% among MAC group compared to 29% in the RIC group (p < .001). The median follow-up was 43.4 months (range 26.8-134). All events in the RIC group were secondary graft failure. However, OS was 100% in both groups at 2 years. Acute GVHD II-IV was diagnosed in 2 (4.1%) patients. Chronic GVHD occurred in 2 (4.1%) patients. GVHD did not occur in patients who underwent MUD HSCT. CONCLUSIONS: MAC in children with SCD is well tolerated and associated with an excellent outcome for HLA-matched HSCT in SCD. There was a high rate of secondary graft failure with the use of RIC. Future studies are needed to optimize RIC regimens in HSCT of children with SCD.

l-glutamine, crizanlizumab, voxelotor, and cell-based therapy for adult sickle cell disease: Hype or hope?

For more than two decades, hydroxyurea was the only therapeutic agent approved by the Food and Drug Administration (FDA) for sickle cell disease (SCD). Although curative allogeneic hematopoietic stem cell transplants (allo-HSCT) were also available, only very few patients underwent the procedure due to lack of matched-related donors. However, therapeutic options for SCD patients increased dramatically in the last few years. Three new agents, l-glutamine, crizanlizumab, and voxelotor, were approved by the FDA for use in SCD patients. The number of SCD patients who underwent allo-HSCT also increased as a result of advances in the prevention of graft failure and graft-versus-host disease from using mismatched donor HSC. More recently gene therapy was made available on clinical trials. The increased treatment options for SCD have led to a sense of optimism and excitement among many physicians that these new approaches would alter the clinical course and disease burden. Although these newer agents do provide hope to SCD patients, the hyped-up responses need to be evaluated in the context of reality. In this review, we will discuss and compare these new agents and cell-based therapy, evaluate their clinical and economic impacts, and examine their roles in reducing the disease burden.

Mortality and Causes of Death From Sickle Cell Disease in The Netherlands, 1985-2017.

In the Netherlands, between 1985 and 2007 secular changes in the health care of patients with sickle cell disease (SCD) have taken place, such as penicillin prophylaxis, vaccination programs and stroke prevention. We investigated the number and causes of death in a cohort of 298 SCD patients, established in 2007, before introduction of neonatal screening, to determine preventable deaths. All patients were diagnosed with SCD before the age of 18 (median age at diagnosis 5.1 y). Their vital status was determined up to January 2017. After a total follow-up period of 4565 patient years and a median time of follow-up of 15 years for all patients, 230 patients (77%) were still alive, 45 patients (15%) were lost to follow-up and a total of 23 patients (8%) had died. Estimated survival to 18 years was 92% with a global mortality rate of 0.48 deaths/100 patient years. Leading causes of death were infection (35%) followed by neurologic complications (22%) and death in the course of a painful episode (13%). Nine of the 20 known causes of death were preventable. These results strongly suggest the benefit of comprehensive care measures for patients with SCD in the Netherlands to further prevent morbidity and mortality.

Management of sickle cell disease: current practices and challenges in a northeastern region of the Democratic Republic of the Congo.

BACKGROUND: The Democratic Republic of the Congo (DRC) is the third most affected country worldwide by sickle cell disease (SCD). However, this disease is still orphaned in the country; large-scale control actions are rare, and little is known about its management. OBJECTIVE: To assess current practices in the management of SCD in Kisangani, DRC. METHODS: This cross-sectional study was conducted in six health facilities in Kisangani. It involved 198 presumed sickle cell patients attending the above health facilities. The study focused on the sociodemographic and clinical data of the participants, obtained through a clinical examination and their medical records. Diagnostic confirmation of SCD was made by high-performance liquid chromatography coupled to mass spectrometry. Data were analyzed using SPSS 20.0. RESULTS: The diagnosis of SCD was confirmed in 194 (98.0%; 95% CI: 94.9-99.2) participants, while it was not confirmed in 4 (2.0%; 95% CI: 0.8-5.1) participants. The diagnosis was mainly made by the Emmel test (42.9%). 45.8% of participants had previously been transfused with the blood of their parents. Folic acid was taken by 48.5% of participants and the previous intake of hydroxyurea was reported in 5.1% of participants. The participants vaccinated against Pneumococcus were 13.6% and against Haemophilus influenzae type b 28.3%. Penicillin prophylaxis was received by only 1.5% and malaria prophylaxis by 11.6% of participants. CONCLUSION: Standard-care practices for SCD patients in Kisangani are insufficient. The Congolese government should regard this disease as a health priority and consider actions to improve its management.

Ineffective erythropoiesis in sickle cell disease: new insights and future implications.

PURPOSE OF REVIEW: Sickle cell disease (SCD) is a hemolytic anemia caused by a point mutation in the ß globin gene leading to the expression of an abnormal hemoglobin (HbS) that polymerizes under hypoxic conditions driving red cell sickling. Circulating red cells have been extensively characterized in SCD, as their destruction and removal from peripheral blood are the major contributors to anemia. However, few reports showed cellular abnormalities during erythropoiesis in SCD, suggesting that anemia could also be influenced by defects of central origin. RECENT FINDINGS: El Hoss et al. demonstrated ineffective erythropoiesis (IE) in SCD and deciphered the molecular mechanism underlying cell death during the hemoglobin synthesis phase of terminal differentiation. They showed that HbS polymerization induces apoptosis of differentiating erythroblasts and that fetal hemoglobin rescues these cells through its antipolymerization function. SUMMARY: IE is the major cause of anemia in ß-thalassemia patients, and it is generally surmised that it contributes little to anemia of SCD. Recent reports demonstrate the occurrence of IE in SCD patients and show important alterations in the hematopoietic and erythroid niches, both in SCD patients and in the humanized Townes SCD mouse model. This implies that therapeutic strategies initially designed to improve red cell survival in the circulation of SCD patients would also positively impact erythropoiesis and bone marrow cellularity.

Complement in sickle cell disease and targeted therapy: I know one thing, that I know nothing.

Sickle cell disease (SCD) is a common inherited clinical syndrome, characterized by the presence of hemoglobin S. Anemia, susceptibility to infections and episodes of vaso-occlusive crisis (VOC) are among its features. Since SCD complications (VOC or delayed hemolytic transfusion reaction/DHTR) lead to significant morbidity and mortality, a number of studies have addressed their pathophysiology Although SCD pathophysiology has been mainly attributed to the interaction between sickle cells and neutrophils, platelets or endothelial cells in small vessels leading to hemolysis, the role of complement activation has been increasingly investigated. Importantly, complement inhibition with eculizumab has shown beneficial effects in DHTR. Given the unmet clinical need of novel therapeutics in SCD, our review summarizes current understanding of (a) complement system for the clinician, (b) complement activation in SCD both in asymptomatic state and severe clinical manifestations, (c) probable underlying mechanisms of complement activation in SCD, and (d) new therapeutic perspective of complement inhibition.

Proteinuric and nonproteinuric chronic kidney disease among patients with sickle cell anaemia (HbSS) attending a tertiary hospital in north-eastern Nigeria.

OBJECTIVE/BACKGROUND: Individuals with sickle cell anaemia (SCA) may manifest various forms of renal abnormalities. Proteinuria is an early marker of renal dysfunction and a strong risk factor for chronic kidney disease (CKD) progression in both patients with SCA and non-SCA population. Currently, the degree of attention given to proteinuric CKD far exceeds that of nonproteinuric CKD, and risk factors that might trigger a progressive decline of the glomerular filtration rate (GFR) in the absence of proteinuria have not been well evaluated in SCA. The aim of this study was to compare the clinical and laboratory parameters among SCA patients with proteinuric and nonproteinuric CKD. METHODS: This was a cross-sectional study conducted at the University of Maiduguri Teaching Hospital in north-eastern Nigeria between January 2013 and April 2018. Clinical variables including age of diagnosis of SCA, frequency of vaso-occlusive crises, number of hospitalizations per annum and transfusion therapy were collected. Laboratory data including haematological profile and renal function test were obtained from routine blood sampling. RESULTS: A total of 257 patients with SCA (HbSS) were enrolled during the study period of which 42 had proteinuric CKD, and 48 had nonproteinuric CKD. The two groups were matched for the number of hospital admission (p = .063) and blood transfusion per year (p = .450), frequency of painful crisis (p = .210), systolic blood pressure (p = .084) and diastolic blood pressure (p = .400). In the proteinuric CKD group, the mean serum creatinine was higher (332.17 µmol/L, p = .001) and the estimated GFR was lower (31.88 mL/min, p = .046). The serum alkaline phosphatase was higher in the nonproteinuric CKD group (81.81 IU/L, p = .012). CONCLUSION: Nonproteinuric CKD was more frequent than proteinuric CKD in our study population; however, the proteinuric group presented with more advanced disease.

A Preliminary Investigation of the Underlying Mechanism Associating Daily Sleep Continuity Disturbance and Prescription Opioid Use Among Individuals With Sickle Cell Disease.

BACKGROUND: There are emerging data indicating that sleep disturbance may be linked with an increase in opioid use. The majority of sickle cell disease (SCD) patients experience sleep disturbances, which can elevate pain severity and pain catastrophizing, both of which are important predictors of opioid consumption. PURPOSE: We conducted a preliminary investigation on the association between previous night sleep disturbance and short-acting opioid use, as well as the potential mediating roles of pain severity and pain catastrophizing. Because sex is associated with sleep disturbance, pain-related experiences, and opioid use, we also explored the potential moderating role of sex. METHODS: Participants were 45 SCD patients who were prescribed opioids. For 3 months, sleep diaries were collected immediately upon participants' awakening. Daily pain severity, pain catastrophizing, and prescription opioid use measures were collected before bedtime. RESULTS: Multilevel structural equation modeling revealed that wake time after sleep onset (WASO) during the previous night (Time 1) predicted greater short-acting opioid use during the next day (Time 2). Pain severity and pain catastrophizing measured during the next day (Time 2) also mediated the association between the two. Sex moderation analysis showed that the positive association between WASO and pain severity was largely driven by women. CONCLUSION: These findings provide some preliminary evidence as to the mechanism linking sleep continuity disturbance and opioid requirement in SCD patients. Future studies should replicate and extend these findings with clearer temporal information and employing more refined measures of sleep continuity and prescription opioid use in a larger sample.

Case Series and Review of Hematological and Non-Hematological Malignancies in Aging Patients with Sickle Cell Disease in the Hydroxyurea Era.

Survival of adult patients with sickle cell disease has increased progressively since the 1970s. Aging patients with sickle cell disease are at risk of developing comorbidities that are not due to sickle cell disease itself, including malignancies. Many studies tried to assess the incidence of malignancy in patients with sickle cell disease. However, no studies have been done to evaluate cancer incidences in aging sickle cell patients, especially in the hydroxyurea (HU) era. In this review, we assessed the prevalence of malignancies in aging patients with sickle cell disease at our institution with or without HU therapy. Retrospective analysis of hospital records identified patients who had been diagnosed to carry sickle cell disease and malignancies before 2020 using the International Statistical Classification of Diseases and Related Health Problems (ICD-10) coding. Four hundred and eighty-three sickle cell disease patients were seen in our inpatients/outpatients offices. Among these, 12 sickle cell disease patients had a confirmed diagnosis of malignancy. The patients were classified into three categories based on age groups: four patients who were 60 years and older had multiple myeloma. Solid tumors were found in 5/6 patients, aged 40-60 who had the Hb S (HBB: c.20A>T) (ßS/ßS) genotype with signs of iron overload. Two patients, aged 25 and 35, had hematological malignancies. The number of patients on HU was too small to make any comment on relationship to malignancy or mortality. This study is only one institution's experience, further investigation on a larger scale is needed to look into cancer incidences in this population.

Transcranial Doppler Velocities among Sickle Cell Disease Patients in Steady State.

Transcranial Doppler (TCD) screening is an established tool to identify children with sickle cell disease at high risk of stroke. Our objective was to study TCD velocities among sickle cell disease patients while in a steady state. This cross-sectional study included 78 steady state sickle cell disease patients [31 Hb SS (ßS/ßS) (sickle cell anemia), 47 Hb S/ß-thalassemia (HBB: c.20A>T/ß-thal)], attending the Pediatric Hematology Clinic at Cairo University Children's Hospital, Cairo, Egypt. All patients underwent TCD velocity assessment as per the Stroke Prevention Trial in Sickle Cell Anemia (STOP) protocol. In our cohort, TCD velocities were comparable among Hb S/ß-thal vs. SS patients. Hemolysis indicators correlated significantly to TCD velocities in Hb S/ß-thal patients; positive correlation was found between total bilirubin level and right middle cerebral artery (MCA) and right distal internal carotid artery (dICA) TCD velocities (r = 0.428, p = 0.00, r = 0.360, p = 0.01), respectively as well as between reticulocyte count and right MCA, right dICA and right anterior cerebral artery (ACA) TCD velocities (r = 0.424, p = 0.01), (r = 0.40, p = 0.00), (r = 0.303, p = 0.04), respectively. On the other hand, statistically significant negative correlations were found between hemoglobin (Hb) level and right ACA, right dICA TCD velocities (r = -0.290, p = 0.05), (r = -0.324, p = 0.03). Although Hb F is considered an ameliorating factor for disease severity; hemolysis stands as an indicator of risk for TCD velocity elevation, and in turn, risk for stroke among sickle cell disease patients.

The Sickle Cell Disease Ontology: Enabling Collaborative Research and Co-Designing of New Planetary Health Applications.

Sickle cell disease (SCD) is one of the most common blood disorders impacting planetary health. Over 300,000 newborns are diagnosed with SCD each year globally, with an increasing trend. The sickle cell disease ontology (SCDO) is the most comprehensive multidisciplinary SCD knowledge portal. The SCDO was collaboratively developed by the SCDO working group, which includes experts in SCD and data standards from across the globe. This expert review presents highlights and lessons learned from the fourth SCDO workshop that marked the beginning of applications toward planetary health impact, and with an eye to empower and cultivate multisite SCD collaborative research. The workshop was organized by the Sickle Africa Data Coordinating Center (SADaCC) and attended by 44 participants from 14 countries, with 2 participants connecting remotely. Notably, from the standpoint of democratizing and innovating scientific meeting design, an SCD patient advocate also presented at the workshop, giving a broader real-life perspective on patients' aspirations, needs, and challenges. A major component of the workshop was new approaches to harness SCDO to harmonize data elements used by different studies. This was facilitated by a web-based platform onto which participants uploaded data elements from previous or ongoing SCD-relevant research studies before the workshop, making multisite collaborative research studies based on existing SCD data possible, including multisite cohort, SCD global clinical trials, and SCD community engagement approaches. Trainees presented proposals for systematic literature reviews in key SCD research areas. This expert review emphasizes potential and prospects of SCDO-enabled data standards and harmonization to facilitate large-scale global SCD collaborative initiatives. As the fields of public and global health continue to broaden toward planetary health, the SCDO is well poised to play a prominent role to decipher SCD pathophysiology further, and co-design diagnostics and therapeutics innovation in the field.

Managing patients with sickle cell disease in primary care.

Sickle cell disease (SCD) is a group of disorders affecting the hemoglobin in erythrocytes. SCD is associated with significant morbidity and mortality and occurs most commonly among people of African ancestry. In 2014, the National Heart, Lung, and Blood Institute updated its guidelines for the management of SCD. These guidelines were implemented to provide evidence-based recommendations to assist primary care clinicians in the proper management of patients with SCD. This article reviews the current practice guidelines for SCD, with attention to health maintenance and hydroxyurea.

How I Treat Acute Chest Syndrome in Asthmatic Children with Sickle Cell Disease. A Practical Review.

Asthma is associated with increased rate of acute chest syndrome (ACS), pain episodes and premature death. Differentiating between an acute asthma exacerbation and ACS is a challenge clinically as they can present with similar symptoms. Clinicians should be aware of symptoms of asthma or broncho spasm in any children with sickle cell disease, as adequate treatments are required. In this mini-review, we selected 16 clinical studies, published in English between 2004 and 2016, and reviewed all of the abstracts and references of the selected articles. We subsequently selected articles that were focused on asthma in children with sickle cell disease. Given the pathophysiological mechanisms of ACS and the association between asthma and sickle cell disease, the management approach of asthmatic children should be clarified. Bronchodilators should be used if there are clinical features suggestive of a history of asthma or evidence of acute broncho spasm. The indication for cortisone should be reassessed. This literature review failed to conclude on therapeutic modalities of ACS in asthmatic children with sickle cell disease. Only a well designed, multicenter adequately-powered randomized controlled study of each of them will allow assessing their real benefits and risks.

Epidemiology and Predictors of all-cause 30-Day readmission in patients with sickle cell crisis.

The 30-day readmission rate after hospitalization for a sickle cell crisis (SCC) is extremely high. Accurate information on readmission diagnoses, total readmission costs and factors associated with readmission is required to effectively plan resource allocation and to plan interventions to reduce readmission rates. The present study aimed to examine readmission diagnoses and factors associated with all-cause 30-day readmission after hospitalization for SCC. We analyzed 2016 nationwide readmission database (NRD) to identify patterns of 30-day readmission by patient demographic characteristics and time after hospitalization for SCC. We estimated the percentage and most common readmission diagnoses for 30-day and 7-day readmissions after discharge. We studied the relationship between risk factors and readmission and the impact of readmission on patient outcomes and resulting financial burden on health care in dollars. In 2016, of 67,887 discharges after index hospitalizations, 18099 (26.9%) were readmitted within 30-days. Of all readmissions, 5166 (7.6%) were readmitted within 7 days. The spectrum of readmission diagnoses was largely similar in both 30-day and 7-day readmission with more than 80% patients in both time periods readmitted with diagnoses related to SCC. The mean length of stay for readmitted patients was significantly longer than the index hospitalization (5.3 days (5.1-5.5) vs 4.9 days (CI 4.8-5.1, p < 0.01). Also, the mean cost of hospitalization in readmitted patients $8485 was significantly higher than the index hospitalization $8064 p < 0.01. In 2016, readmission among patients with SCC incurred an additional 95,445 hospitalization days resulting a total charge of $609 million and a total cost of $152 million in the US. On Multivariate analysis, age group 18-30 years, discharge against medical advice, higher Charlson comorbidity index, low socioeconomic status and admission at high volume centers were associated with a higher likelihood of 30-day readmission. Among patients hospitalized for SCC, 30-day readmissions were frequent throughout the month post hospitalization and resulted in an enormous financial burden on the United States healthcare system.

Systematic Review: Pain and Emotional Functioning in Pediatric Sickle Cell Disease.

The objective of this systematic review was to assess the relationship between pain (frequency/intensity/duration, impairment, coping) and emotional functioning in pediatric Sickle Cell Disease, and evaluate the state of the literature. Studies were included if they met each of the following criteria: (a) primarily pediatric sample of youth or young adults up to age 21 years with SCD, (b) examined emotional functioning including anxiety and/or depressive and/or internalizing symptoms, and/or affect, (c) examined pain intensity/frequency/duration and/or pain-related impairment and/or pain coping as it relates to emotional functioning, as defined above. Using the established guidelines for systematic reviews, we searched PsycINFO, PubMED, and CINAHL databases for studies published through June 2018. Screening resulted in 33 studies meeting inclusion criteria. Study data were extracted and evaluated for scientific merit, resulting in four studies being removed. 29 studies were included in the final synthesis. Studies provide strongest evidence of a relationship between increased pain frequency and higher depressive and anxiety symptoms. There are moderate-to-strong associations between pain-related impairment and depressive symptoms, and small-to-strong associations between pain-related impairment and anxiety. When examining pain-coping strategies, maladaptive cognitive strategies show the strongest association with emotional functioning. There is a need for more adequately powered, prospective studies based on theoretical frameworks in order to advance our understanding of the relationship between pain and emotional functioning in pediatric SCD.