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Background and purpose Sickle cell disease (SCD) is a collection of rare inherited blood disorders affecting approximately 100,000 people in the U.S. and 20–25 million people globally. Individuals with SCD experience recurrent episodes of severe and unpredictable pain that are caused by vaso-occlusive crises (VOCs), a hallmark of the disease. VOCs are the primary cause of hospitalization in SCD, result in missed workdays and school days, and decrease quality of life (QoL). Although VOCs cause significant burden in the lives of individuals with SCD, there is no synthesis on the frequency of VOCs in the real world. This systematic literature review sought to identify literature describing the frequency of VOCs experienced by individuals with SCD in real-world settings. Methods MEDLINE and 6 congresses were searched (date range: January 1, 2000 to June 30, 2020). Studies were reviewed independently by two researchers. Studies assessing frequency or prevalence of VOCs or VOC-related outcomes were included. Results Of 1438 studies identified in the search, 52 met pre-specified inclusion and exclusion criteria. Reported frequency of VOCs varied widely ranging from a mean or median of 0 VOCs/year to 18.2 VOCs/year. The proportion of patients experiencing ≥ 3 VOCs/year ranged from 4 to 67% and the proportion of patients experiencing ≥ 5 VOCs/year ranged from 18 to 59%. Measures of VOC severity were limited, with 13 studies considering frequency of complicated VOCs and only 1 study reporting duration of VOC episodes. Conclusions This is the first study to systematically assess published evidence pertaining to VOCs in real-world settings. Reported VOC frequency in real-world settings varied widely, with a majority of studies only considering VOCs managed in an inpatient or outpatient setting. Studies that considered VOCs managed at home reported a higher frequency of VOCs, suggesting that many studies may underestimate the frequency of VOCs. This systematic literature review (SLR) highlights the need for consistent reporting of (1) self-reported VOCs, including those managed at home, (2) definitions of VOCs, (3) complicated VOCs, and (4) duration of VOC episodes in literature.

Pain is a complex syndrome that is difficult to treat. The increasing numbers of patients living with chronic diseases has led to increasing pain management needs and the rise of opioid use disorder (OUD) as a major and potentially lethal public health concern. Treatment of chronic pain with prescription opioids alone is not always successful, and a multidisciplinary approach is paramount to address the needs of patients at risk of developing or suffering from OUD. Interventional radiologists trained to perform minimally invasive procedures with negligible downtime and postprocedure pain can help stem the tide of opioid-related deaths and disability. This article reviews a wide range of minimally invasive procedures, including vertebral augmentation, sacroplasty, thermal ablation of osseous metastasis, nerve blocks, and gonadal vein embolization, that interventional radiologists are now using successfully to treat chronic pain. The evidence to support use of such procedures is highlighted. This article also briefly discusses emerging techniques such as arterial embolization and ablation for knee and shoulder osteoarthritis that have not yet been fully tested but exhibit strong potential in chronic pain management. By reducing opioid use in patients suffering from chronic pain, these minimally invasive procedures can potentially prevent escalation to OUD.

BACKGROUND Sickle cell disease (SCD) is a complex disease associated with many complications and a shortened lifespan. In 2016, the National Heart, Lung and Blood Institute funded 8 centers in the United States to form the Sickle Cell Disease Implementation Consortium, with the goal of improving SCD care. The aim of our study was to describe SCD self-efficacy, pain interference, and barriers to care from the perspective of persons with SCD in the North Carolina center.METHODS Persons with SCD, aged 15 and older were recruited from a large SCD center in North Carolina. Surveys, focus groups, and interviews were completed.RESULTS Fifty-one people completed a survey, and 14 people completed an interview or focus group. Barriers identified in the survey included self-care barriers, misconceptions related to hydroxyurea (an oral medication that reduces rates of pain crisis), limited provider knowledge, and stigma. Concerning self-efficacy, participants reported that they were able to manage their pain symptoms most of the time. Pain interfered most with the ability to participate in social and day-to-day activities.Common themes from the focus groups and interviews included misconceptions about hydroxyurea, pain, provider knowledge, stigma, co-management, transportation, and insurance. Recommendations to improve care included the use of case managers, utilization of treatment guidelines, individualized pain protocols, and effective co-management by providers.LIMITATIONS Participants were recruited from 1 SCD center and may not be representative of the entire SCD population in North Carolina.CONCLUSIONS Participants described many perceived barriers to care, and their responses suggest a need for improvements in patient hydroxyurea education, provider knowledge, and care coordination.

Pain is among the most widespread chronic health condition confronting society today and our inability to manage chronic pain contributes to the opioid abuse epidemic in America. The immune system is known to contribute to acute and chronic pain, but only limited therapeutic treatments such as non-steroid anti-inflammatory drugs have resulted from this knowledge. The last decade has shed light on neuro-immune interactions mediating the development, maintenance, and resolution of chronic pain. Here, we do not aim to perform a comprehensive review of all immune mechanisms involved in chronic pain, but to briefly review the contribution of the main cytokines and immune cells (macrophages, microglia, mast cells and T cells) to chronic pain. Given the urgent need to address the Pain crisis, we provocatively propose to repurpose/reposition FDA-approved immunomodulatory drugs for their potential to alleviate chronic pain. Repositioning or repurposing offers an attractive way to accelerate the arrival of new analgesics.

Microvascular vaso-occlusion driven pain crisis is the hallmark of sickle cell disease with profound morbidity and increased mortality. Selectins, most notably P-selectins have an integral role in this phenomenon. P-selection was first identified in 1989. In 2019, after 3 decades of basic, translational, and clinical work with this pathway, the US Food and Drug Administration approved a P-selectin antibody, crizanlizumab to reduce frequency of pain crisis in patients more than 16 years with sickle cell disease. We review the fundamentals of P-selectin pathobiology, P-selectin blocking agents, clinical data with the use of crizanlizumab and prospects of this novel class of drugs in the context of other treatments for painful vaso-occlusive episodes.

Pain policy is not drug policy. If society wants to improve the lives of people in pain and compress the terrible inequalities in its diagnosis and treatment, we have to tailor policy to the root causes driving our problems in treating pain humanely and equitably. In the United States, we do not. Instead, we have proceeded to conflate drug policy with pain policy, relying on arguably magical thinking for the conclusion that by addressing the drug overdose crisis, we are simultaneously addressing the pain crisis. This is a category error, decades of commitment to which have resulted mostly in a worsening of both public health problems. Disentangling our problems in treating pain fairly and equitably from our problems with drugs and substance use is the only path to humane and ethical policy for each.

A look into the associations of socioeconomic status (SES) with prevalence of various complications in sickle cell disease (SCD) is necessary, for an improvement of societal norms, governmental health policies and strategies. We therefore studied the influence of SES indices on certain hematological and clinical parameters in children with SCD in Saudi Arabia. We included 32 female and 33 male patients aged 5–16 years, who were classified based upon their family income. Family monthly income was divided into 4 categories from lowest to highest, with socioeconomic class1 having low earnings of 5000–10,000 SAR, and class 3 with earnings >10,000–15,000 SAR; and the higher income class 4 with earnings of >15,000 SAR. The assessment indices used were, the frequency of vaso-occlusive crisis (VOC), adverse events, and hematological parameters. A higher percentage of children affected with the disease were from class1, which is the low socio-economic class. It was found that the percentage of frequency of VOC pain crisis, and adverse events was higher in social class 1 patients than in the classes 2, 3, and 4. Also, the age group 5–10 years appeared more susceptible to adverse events and VOC. Our findings suggest the need to conduct future larger studies, to deduce the modifying influence of disparity in SES on certain clinical and hematological indices in children with SCD.

**Background/Objectives:** Among sickle cell disease (SCD) patients, vaso-occlusive crises (VOCs) are recurrent and unpredictable attacks of acute pain. These pain crises are often treated with analgesics, including opioids, which have been associated with misuse and overdose. The aim of this study was to examine the association between VOC events and opioid use and assess the association between opioid prescriptions and health care resource utilization among SCD patients. **Methods:** This was a retrospective cohort study using Texas Medicaid medical and prescription claims between September 2011 and August 2016. The index date was the first SCD diagnosis. Patients (2–63 years) with at least one inpatient or two outpatient SCD diagnoses, who were continuously enrolled during 12 months postindex, were included in the study. The primary outcome was number of opioid prescriptions, while the independent variable was number of VOC events. Covariates included age, gender, nonopioid medication use, nonstudy SCD-related medication (penicillin and folic acid) use, evidence of blood transfusions, number of SCD-related complications, number of SCD-related comorbid conditions, and Charlson Comorbidity Index score. Negative binomial regression analysis was used to address study objectives. **Results:** Of 3368 included patients, 1978 (58.7%) had at least one opioid prescription with a mean of 4.2 (SD=7.2). Overall, 2071 (61.5%) had at least one VOC event with an average of 2.9 (SD=4.4). The results from the negative binomial regression showed that for every increase in VOC events, the number of opioid prescriptions increased by 9.5% (Incidence rate ratio=1.095, 95% CI: 1.078–1.111; _P_ ≤ 0.0001). Other significant covariates associated with higher opioid use included age (13 and older compared to 2–12) and increase in the number of nonopioid pain medications, nonstudy SCD-related medications, and SCD-related complications. **Conclusions:** The majority of SCD patients had at least one VOC event and were prescribed opioids during the 12-month study period. We found that each VOC event was associated with a 9.5% increase in the use of opioids. SCD guidelines recommend opioids for the treatment of VOC-related pain. Payers and providers should be aware of opioid use in this population, consider appropriate VOC prevention measures, and provide SCD patients with access to appropriate pain management.

A 64-year-old female with sickle cell (hemoglobin SC) disease and prior embolic strokes was admitted for vaso-occlusive pain crisis and developed sudden onset coma. Hyperacute brain MRI showed only small areas of mismatch between diffusion weighted imaging (DWI) and T2 fluid attenuated inversion recovery (T2 FLAIR) sequences that were insufficient to explain her profoundly altered level of consciousness. Repeat MRI 24 hours later showed innumerable foci of restricted diffusion and petechial microhemorrhage, confirming a diagnosis of cerebral fat embolism due to sickle cell crisis.

This review outlines the current clinical research investigating how the haptoglobin (Hp) genetic polymorphism and stroke occurrence are implicated in sickle cell disease (SCD) pathophysiology. Hp is a blood serum glycoprotein responsible for binding and removing toxic free hemoglobin from the vasculature. The role of Hp in patients with SCD is critical in combating blood toxicity, inflammation, oxidative stress, and even stroke. Ischemic stroke occurs when a blocked vessel decreases oxygen delivery in the blood to cerebral tissue and is commonly associated with SCD. Due to the malformed red blood cells of sickle hemoglobin S, blockage of blood flow is much more prevalent in patients with SCD. This review is the first to evaluate the role of the Hp polymorphism in the incidence of stroke in patients with SCD. Overall, the data compiled in this review suggest that further studies should be conducted to reveal and evaluate potential clinical advancements for gene therapy and Hp infusions.

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Background For patients with sickle cell disease (SCD), shared learning, understanding, and decision-making with their healthcare providers (HCPs) is critical for achieving treatment goals. Using a validated collaborative learning model (Sapir 2017), we evaluated patient and HCP perceptions of shared decision-making (SDM) related to SCD treatment. Methods In June 2020, 113 patients/caregivers of patients with SCD and 30 HCPs participated in 3 live, virtual collaborative learning sessions developed with the Sickle Cell Disease Association of America (Table 1). Before and after the sessions, patients and their HCPs completed tethered surveys to assess alignments and discordances in preferences, experiences, and concerns around SCD treatment and SDM. Results Patients and HCPs held discordant beliefs about the degree of patients' progress toward treatment goals. While HCPs estimated that only 29% of their patients are on track to meet their goals, 85% of patients reported that they felt somewhat (39%) or fully (46%) on track. The magnitude of this discrepancy suggests that patients may not be aware of treatment milestones they are not reaching. Participants differed in their perceptions of how often HCPs engage patients in SDM (Figure 1). Relative to patients' estimates, HCPs were more likely to report that they usually or always: ask about the patient's goals for treatment (41% vs 61%), work with the patient to create a treatment plan (47% vs 55%), explain their own goals for the patient's treatment (47% vs 55%), and explain the pros/cons of each treatment choice (47% vs 55%). The biggest missed opportunity for SDM involved how often HCPs ask patients about stigma related to opioids for pain management (28% vs 35%). The reported lack of communication around stigma may contribute to providers' underestimation of how often their patients encounter stigma. HCPs estimated that 47% of their patients have faced barriers to adequate pain management in the ER due to opioid stigma and/or poor knowledge of pain crises among ER staff. By comparison, 74% of patients reported ever feeling that ER doctors, nurses, or staff questioned their need for pain medication during a pain crisis (20% once; 54% more than once). When asked why patients are not more involved in SDM (Figure 2), HCPs were more likely to select patient factors: feeling too overwhelmed to make treatment decisions (52% HCPs, 14% patients), low health literacy (49% HCPs, 12% patients), and lack of confidence in validity of opinions/concerns (44% HCPs, 10% patients). In contrast, patients were more likely to report that they are completely involved in treatment decisions (40% patients, 4% HCPs) and that they trust their care team to make decisions on their behalf (37% patients, 30% HCPs). Regarding adjusting SCD therapy, HCPs overestimated how many patients were concerned about learning a new routine/schedule (23% HCPs, 7% patients), but underestimated concerns about being able to pay for it (4% HCPs, 9% patients). HCPs correctly estimated concerns about knowing whether treatment will work (33% HCPs, 34% patients), fear of side effects (29% HCPs, 25% patients), and knowing how to manage a pain episode (9% HCPs, 9% patients). Overall, HCPs underestimated how many patients would not worry about switching treatment (1% HCPs, 9% patients). Following the collaborative learning sessions, patients made commitments to talk to their care team about their treatment goals (52%), consider treatment options more closely (50%), take a more active role in decision-making (46%), and notify their care team with concerns (41%). HCPs set goals to increase the types of educational materials they provide (57%), attempt to ease the transition to the adult care setting (50%), engage their patients more frequently in SDM (47%), and train colleagues on how to conduct additional learning sessions (34%). The full data set with 2 additional learning sessions (Aug 2020) will be presented. Conclusions Patients with SCD and their care teams differed in their experiences and beliefs related to SDM. Collaborative education can reveal opportunities for greater understanding and facilitate improved patient-provider communication, leading to greater engagement in SDM around SCD treatment. Study Sponsor Statement The study reported in this abstract was funded by an independent educational grant from bluebird bio. The grantor had no role in the study design, execution, analysis, or reporting. Disclosures Smith-Whitley: Prime: Other: Education material; Novartis: Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees.

PURPOSE: A key challenge regarding the current opioid epidemic is understanding how concerns regarding opioid-related harms affect access to pain management, an essential element of cancer care. In certain regions of the United States where disproportionately high cancer mortality and opioid fatality rates coexist (such as southwest Virginia in central Appalachia), this dilemma is particularly pronounced. METHODS: This longitudinal, exploratory, secondary analysis used the Commonwealth of Virginia All Payer Claims Database to describe prescription opioid medication (POM) prescribing patterns and potential harms for adult patients with cancer living in rural southwest Virginia between 2011 and 2015. Descriptive and inferential statistical analyses were conducted at the patient, prescriber, and prescription levels to identify patterns and predictors of POM prescribing and potential harms. To explore geographic patterns, choropleth and heat maps were created. RESULTS: Of the total sample of patients with cancer (n = 4,324), less than 25% were prescribed a Controlled Substance Schedule II POM at least three times in any study year. More than 60% of patients never received a Controlled Substance Schedule II POM prescription. Six hundred fifty-two patients (15.1%) experienced 1,599 hospitalizations for any reason; 10 or fewer patients were admitted for 11 opioid use disorder–related hospitalizations. The main findings suggest potential undertreatment of cancer-related pain; no difference in risk for opioid-related hospitalization on the basis of frequency of POM prescriptions; and geographic disparities where opioid overdoses are occurring versus where POM prescription use is highest. CONCLUSION: These findings have significant opioid policy and practice implications related to the need for cancer-specific prescribing guidelines, how to optimally allocate health delivery services, and the urgent need to improve data interoperability and access related to POMs.

In recent years, the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Adult Cancer Pain have undergone substantial revisions focusing on the appropriate and safe prescription of opioid analgesics, optimization of nonopioid analgesics and adjuvant medications, and integration of nonpharmacologic methods of cancer pain management. This selection highlights some of these changes, covering topics on management of adult cancer pain including pharmacologic interventions, nonpharmacologic interventions, and treatment of specific cancer pain syndromes. The complete version of the NCCN Guidelines for Adult Cancer Pain addresses additional aspects of this topic, including pathophysiologic classification of cancer pain syndromes, comprehensive pain assessment, management of pain crisis, ongoing care for cancer pain, pain in cancer survivors, and specialty consultations.

In people with sickle cell disease (SCD), oral abscesses are concerning clinical conditions and carry a high risk of postoperative sickle cell complications. We present an unusual case of a 14-year-old girl with SCD whose initial presentation of facial swelling, headaches, jaw pain, and paresthesia mimicked an odontogenic abscess. She was diagnosed with vaso-occlusive crisis in the mandibular bone and successfully managed noninvasively. This is among the youngest cases of paresthesia in the lower lip in SCD, which provided a clue that postponing invasive aspiration or biopsy was possible under empiric antibiotics and close observation.

Pain is the most common symptom experienced by patients with sickle cell disease (SCD) and is associated with poor quality of life. We investigated the association between grey matter volume (GMV) and the frequency of pain crises in the preceding 12 months and SCD-specific quality of life (QOL) assessed by the PedsQLTM SCD module in 38 pediatric patients with SCD. Using voxel-based morphometry methodology, high-resolution T1 structural scans were preprocessed using SPM and further analyzed in SPSS. The whole brain multiple regression analysis identified that perigenual anterior cingulate cortex (ACC) GMV was negatively associated with the frequency of pain crises (r = -0.656, P = 0.003). A two-group t-test analysis showed that the subgroup having pain crisis/crises in the past year also showed significantly lower GMV at left supratemporal gyrus than the group without any pain crisis (p=0.024). The further 21 pain-related regions of interest (ROI) analyses identified a negative correlation between pregenual ACC (r = -0.551, P = 0.001), subgenual ACC (r = -0.540, P = 0.001) and the frequency of pain crises. Additionally, the subgroup with poorer QOL displayed significantly reduced GMV in the parahippocampus (left: P = 0.047; right: P = 0.024). The correlations between the cerebral structural alterations and the accentuated pain experience and QOL suggests a possible role of central mechanisms in SCD pain.

Background: Sickle cell disease (SCD) is characterized by frequent, unpredictable pain episodes and other vaso-occlusive crises (VOCs) leading to significant healthcare utilization. VOC frequency is often an endpoint in clinical trials investigating novel therapies for this devastating disease. Procedure: The Consortium for the Advancement of Sickle Cell Research (CASiRe) is an international collaboration investigating clinical severity in SCD using a validated questionnaire and medical chart review standardized across four countries (United States, United Kingdom, Italy and Ghana). Results: This study, focused on pain crisis incidence and healthcare utilization, included 868 patients, equally represented according to age and gender. HgbSS was the most common genotype. Patients from Ghana used the Emergency Room/Day Hospital for pain more frequently (annualized mean 2.01) than patients from other regions (annualized mean 1.56 U.S.;1.09 U.K.; 0.02 Italy), while U.K. patients were hospitalized for pain more often (annualized mean: U.K. 2.98) than patients in other regions (annualized mean 1.98 U.S.; 1.18 Ghana; Italy 0.54). Italy’s hospitalization rate for pain (annualized mean: 0.57) was nearly 20 times greater than its emergency room/day hospital only visits for pain (annualized mean: 0.03). When categorized by genotype and age, similar results were seen. Conclusions: Geographic differences in pain crisis frequency and healthcare utilization may correlate with variable organization of healthcare systems among countries and should be considered regarding trial design, endpoints, and analysis of results when investigating novel agents for clinical benefit. Funding: This study was supported in part by research funding from Grant # NIMHD T37MD001425 to AC. Declaration of Interest: A Campbell: research funding and consultancy from Global Blood Therapeutics (GBT), Novartis; and consultancy for bluebird bio; D Manwani: research funding from Grifols; consultancy for Novartis, Pfizer, Global Blood Therapeutics; B Andemariam: consultancy for Bluebird bio, CRISPR/Vertex, Forma Therapeutics, Global Blood Therapeutics, Hemanext, Novartis, NovoNordisk, Cyclerion, Terumo, Roche, Sanofi-Genzyme; research funding from Global Blood Therapeutics, Imara, Novartis; B Inusa: education funding from Novartis AstraZeneca, Global Blood Therapeutics, Celgene, Vertex; C Strunk: consultancy for Global Blood Therapeutics, Forma Therapeutics, Novartis and Medunik USA; R Colombatti: research funding from Global Blood Therapeutics, BlueBird Bio; consultancy for Novartis, Addmedica, NovoNordisk; C Piccone: consultancy for Global Blood Therapeutics and Novartis; W Zempsky: consultancy for Glycomimetics and GlaxoSmithKleine. No disclosures to declare from the other co-authors. Ethical Approval: This study received IRB approval at each institution.

Pain is a hallmark of Sickle Cell Disease (SCD) affecting patients throughout their life; the first pain crisis may occur at any age and is often the first presentation of the disease. Universal newborn screening identifies children with SCD at birth, significantly improving morbidity and mortality. Without early screening, diagnosis is generally made after disease manifestations appear. The Consortium for the Advancement of Sickle Cell Research (CASiRe) is an international collaborative group evaluating the clinical severity of subjects with SCD using a validated questionnaire and medical chart review, standardized across 4 countries (United States, United Kingdom, Italy and Ghana). We investigated the age of first pain crisis in 555 sickle cell subjects, 344 adults and 211 children. Median age of the first crisis in the whole group was 4 years old, 5 years old among adults and 2 years old among children. Patients from the United States generally reported the first crisis earlier than Ghanaians. Experiencing the first pain crisis early in life correlated with the genotype and disease severity. Early recognition of the first pain crisis could be useful to guide counseling and management of the disease.

INTRODUCTION The National Heart, Lung, and Blood Institute guidelines for sickle cell disease (SCD) pain crisis management recommend opioids within 60 minutes of emergency department (ED) registration and every 30 minutes thereafter until acute pain is managed. These guidelines are based on expert opinion without published, supporting data. OBJECTIVE To evaluate the association between timely ED opioid administration and hospitalization rates in children with SCD. METHODS Retrospective cohort of children presenting to a children's hospital ED with SCD pain between January 1, 2014, and April 30, 2018. Visits were extracted using ICD codes, chief complaints, and receipt of at least one opioid, and then reviewed to confirm the visit was an uncomplicated pain crisis. The primary outcome was hospitalization, yes or no. Generalized estimating equations were used to determine adjusted odds of hospitalization for the timely administration of initial and second doses of opioids. RESULTS Of the 902 eligible visits, 368 (40.8%) resulted in hospitalization. The mean (SD) age was 11.9 (± 5.2) years. The first opioid was administered within 60 minutes of arrival in 601 (66.6%) visits. The second opioid was administered within 30 minutes of the first in 84 (12.3%) visits. Receipt of the first opioid within 60 minutes of arrival was not associated with decreased hospitalization (1.30 [0.96-1.76]). However, receipt of the second dose within 30 minutes of the first was associated with decreased hospitalization (0.56 [0.33-0.94]). CONCLUSION This study suggests an association between children with SCD receiving a second dose within 30 minutes of the first opioid dose and decreased hospitalizations.

Sickle cell disease is prevalent in several parts of the world. Most hospitalizations of these patients are related to pain crisis episodes. Moreover, levels of hemoglobin are lower in sickle cell disease patients as compared with the general population. Complications related to sickle cell disease are managed with blood transfusions, hydroxyurea, and opioids. Despite these therapies, patients with sickle cell disease experience multiple pain crisis episodes leading to hospitalizations and end-organ damage. The US Food and Drug Administration has approved three new drugs-L-glutamine, voxelotor, and crizanlizumab-for the prophylaxis and treatment of complications related to sickle cell disease. This review was aimed at assessing the efficacy and safety of recently approved drugs for the treatment of sickle cell disease. A comprehensive search was made on PubMed and clinicaltrials.gov to look for clinical trials reporting the efficacy and safety of recently approved drugs for sickle cell disease. Based on the results of clinical trials, L-glutamine, voxelotor, and crizanlizumab were well tolerated by sickle cell disease patients. L-Glutamine and crizanlizumab reduced the number of sickle cell crisis episodes, while voxelotor improved the level of hemoglobin in sickle cell disease patients. These drugs were effective alone and in combination with hydroxyurea.

In sickle cell disease (SCD), hemoglobin S (HbS) red blood cells (RBCs) are characteristically deformed and inflexible. Often breaking down in the circulation, they exhibit increased adhesive properties with the endothelium and activated neutrophils and platelets, increasing the risk of occlusion of the microcirculation. SCD is categorized into two sub-phenotypes: hyperhemolytic, associated with priapism, leg ulcers, pulmonary hypertension, and stroke, and high hemoglobin/viscosity, which may promote vaso-occlusion-associated pain, acute chest syndrome, and osteonecrosis.The sub-phenotypes are not completely distinct. Hemolysis may trigger vaso-occlusion, contributing to vascular complications. Targeting P-selectin, a key mediator of cross-talk between hyperhemolysis and vaso-occlusion, may be beneficial for vascular and vaso-occlusion-associated complications. English-language articles from PubMed on the topic of SCD and vaso-occlusive crises (VOCs) were reviewed from 1 January 2000 to 1 January 2019 using the search terms 'sickle cell disease,' 'vaso-occlusive crises,' and 'selectin.'Besides targeting P-selectin, other strategies to counter VOCs and RBC sickling are being pursued. These include platelet inhibition to counter aggregation, intercellular adhesion, and thrombosis during VOCs; gene therapy to correct the homozygous missense mutation in the β-globin gene, causing polymerization of HbS; L-glutamine, possibly reducing oxidative stress in sickled RBCs; and fetal hemoglobin inducers.

Acute painful crisis is the most frequent complication of sickle cell disease (SCD) in children. Recurrent vaso-occlusion may be associated with cardiac injury. The study aimed to assess silent myocardial injuries for sickle cell children during acute painful crisis by measuring serum level of troponin I and galectin-3. The study included 87 participates; study group (n = 44) sickle cell children presented at Jeddah hospitals in Saudi Arabia by painful crisis or acute illness as fever or cough (2017–2018). The controls were healthy children (n = 43). Demographic and history data were collected from the cases. Troponin I and galectin-3 were measured. Galectin-3 values were higher among cases with significant difference when compared to controls (7.5 ± 3.1 versus 3.2 ± 1.6, 5.1 ng/ml, the sensitivity was 88.64 and specificity was 88.37. Galectin-3 levels were higher for the pain crisis subgroup in comparison to acute illness group with significant difference (r 0.551*, p