hide this ad. (SOR: moderate, based on low-quality evidence), Beginning at 9 months of age, counsel all patients with SCA and their families about hydroxyurea therapy. This can cause pain and other serious complications (health problems) such as infection, acute chest syndrome and stroke. She needed to act quickly. Sickle Cell and Fever: The Concerns ACS can present on its own or as a complication of a VOC; it requires prompt evaluation and, once diagnosed, early intervention with antibiotic therapy and hospitalization.28,29 During hospitalization for a VOC, incentive spirometry can reduce the risk of ACS.30 When evaluating a new lung infiltrate in a patient with SCD, physicians should consider ACS before assuming the infiltrate represents community-acquired pneumonia. Acute chest syndrome: This type can occur when the small blood vessels of the . A TCD finding of 200 cm per second or greater correlates with a 10% annual increase in stroke risk.7 When TCD findings are marginal or conditional (170 to 199 cm per second) or elevated (200 cm per second or greater), the child is considered a candidate for blood transfusion therapy to prevent stroke and should be referred for comanagement with a subspecialist.15,16, Recommendations for these and other common conditions are summarized in Table 1.1, In women with SCD, regular use of contraception can decrease the health risks associated with an unintended pregnancy. Linking to a non-federal website does not constitute an endorsement by CDC or any of its employees of the sponsors or the information and products presented on the website. Concerns about drug-seeking behavior are pervasive and often triggered by patients with SCD who have frequent VOCs that require potent analgesia. Baylor College of Medicine and Texas Children's Hospital. Family physicians and family medical homes are essential to the care of children, adults, and families affected by sickle cell disease (SCD). The sickle cells also block the flow of blood through vessels, resulting in lung tissue damage that causes acute chest syndrome, pain episodes, stroke and priapism . Initiate hydroxyurea therapy in adults with sickle cell anemia who have one or more of the following: three or more moderate to severe pain crises in a 12-month period; daily sickle cell pain that affects quality of life; severe or recurrent acute chest syndrome; or severe symptomatic chronic anemia. and transmitted securely. Select a reason for reporting . (SOR: strong, based on high-quality evidence), Consider adding hydroxyurea therapy to improve anemia in adults and children with SCD and chronic kidney disease who are receiving erythropoietin. SCD occurs among about 1 out of every 16,300 Hispanic-American births. The PN will engage patients, create a trusting relationship, navigate patients to medical appointments, and closely communicate with a patient's entire care team based on . Signs and symptoms include a lasting. Transfusions can be episodic or long term. Sickle cell disease is an inherited disorder that affects your red blood cells, producing a negative impact on your health. 40, pp. Addressing Sickle Cell Disease examines the epidemiology, health outcomes, genetic implications, and societal factors associated with SCD and sickle cell trait (SCT). Sickle cells are destroyed rapidly in the bodies of people with the disease, causing anemia. (SOR: moderate, based on very low-quality evidence), Do not perform screening with TCD in children with SCD but not SCA (e.g., HbS, Treat persons with SCD who have ACS with an intravenous cephalosporin, an oral macrolide antibiotic, and supplemental oxygen (to maintain oxygen saturation > 95%), and monitor for bronchospasm, acute anemia, and hypoxemia. Director of Research Professor of Pediatrics and Director Screen children with sickle cell anemia annually with transcranial Doppler ultrasonography from two until at least 16 years of age. Chelation therapy can effectively remove excess iron in patients with confirmed iron overload.27. It is the most common symptom of sickle cell disease. When high-quality evidence was lacking, expert consensus was used to provide recommendations. Learn more about the protective effect of sickle cell trait against malaria. 10 Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. This case report highlights several teaching points. Sickle cell disease is a serious health condition that runs in families and can shorten life. Cochrane Database Syst Rev. Strong recommendations for chronic complications include use of analgesics and physical therapy for treatment of avascular necrosis, and use of angiotensin-converting enzyme inhibitor therapy for microalbuminuria in adults with SCD. This drop coincided with the introduction in 2000 of a vaccine that protects against invasive pneumococcal disease. Administer prophylactic oral penicillin (125 mg twice daily for children younger than three years; 250 mg twice daily for those three years and older) until at least five years of age in all children who are homozygous for sickle hemoglobin. They also thank the following panel members: George R. Buchanan, MD; Araba N. Afenyi-Annan, MD, MPH; Samir K. Ballas, MD; Kathryn L. Hassell, MD; Andra H. James, MD, MPH; Sophie M. Lanzkron, MD, MHS; Richard Lottenberg, MD; William J. doi: 10.1002/14651858.CD012082.pub2. This overview highlights some of the most important clinical activities that can and should be carried out in the community care setting. However, local or regional subspecialists may also have limited experience in the care of SCD-related complications. Medicaid and CHIP Sickle Cell Disease Report, T-MSIS Analytic Files (TAF) 2017. It occurs when a child receives two sickle cell genesone from each parent. These cookies may also be used for advertising purposes by these third parties. 25 results for "decreases dna synthesis to treat melanoma cml sickle cell disease". Memorial Healthcare System In more than 40 states, testing for the defective sickle cell gene is routinely performed on newborns. Their shape causes these red blood cells to pile up, causing blockages and damaging vital organs and tissue. (SOR: strong, based on moderate-quality evidence), Offer hydroxyurea therapy for children 9 months and older who have SCA, regardless of clinical severity, to reduce SCD-related complications (e.g., pain, dactylitis, acute chest syndrome, anemia). Objective: Sickle cell disease is the most common inherited blood disorder in the United States. Divisions of Transfusion Medicine and Pediatric Hematology PEM Podcast Episode 9: . In the United States, it affects more people who are black or African-American than other racial or ethnic groups. 2017 Jan 17;1(1):CD003146. Children with sickle cell anemia should receive prophylactic penicillin from birth through at least five years of age, and all persons with sickle cell disease require vaccination to prevent invasive pneumococcal disease. Associate Professor You can review and change the way we collect information below. Sickle Cell Data Collection (SCDC) Program Data. Hydroxyurea therapy decreases SCD-related complications but is currently underused. Cochrane Database Syst Rev. Extra prenatal surveillance is recommended in consultation with a maternal-fetal subspecialist whenever possible.19,20 Both men and women with SCD require basic contraceptive information and referral for genetic counseling when making reproductive decisions.21. Ojo AS, Ojukwu S, Asmare W, Odipe O, Larbi D. J Hematol. Luskey, KL, Schechter, AN & Hercules, JI 1980, ' New approaches to the therapy of sickle cell disease ', Texas Reports on Biology and Medicine, vol. SCD occurs more often among people from parts of the world where malaria is or was common. https://familydoctor.org/familydoctor/en/diseases-conditions/sickle-cell-disease.html, http://www.nhlbi.nih.gov/health-pro/guidelines/sickle-cell-disease-guidelines/index.htm, https://www.communitycarenc.org/chacc-hematology-guidelines/, http://www.nhlbi.nih.gov/sites/www.nhlbi.nih.gov/files/quickguide.pdf. SCD is a lifelong condition that can damage any part of the body where blood flows. Crossword Clue. . We report a case of FES in a 19-year-old African American male with a history of sickle cell disease who presented with tonic-clonic seizures and was found to . Cookies used to enable you to share pages and content that you find interesting on CDC.gov through third party social networking and other websites. The recommendations in these guidelines do not apply to persons who have sickle cell trait (also called carriers [one gene for HbS and another for normal HbA]). The Sickle Cell Disease epidemiology report gives a thorough understanding of the Sickle Cell Disease by including details such as disease definition, symptoms, causes, pathophysiology, and diagnosis. All persons with SCA should be screened annually with transcranial Doppler ultrasonography (TCD) beginning at two years of age and continuing until at least 16 years of age.1214 TCD measures and reports the average velocity of blood flow through the internal carotid and proximal middle cerebral arteries. Sickle cell disease (SCD) affects millions of people throughout the world and is particularly common among those whose ancestors came from sub-Saharan Africa; Spanish-speaking regions in the Western Hemisphere (South America, the Caribbean, and Central America); Saudi Arabia; India; and Mediterranean countries such as Turkey, Greece, and Italy. We did not do any further searches than those completed for the guidelines. Offer hydroxyurea therapy for infants nine to 42 months of age and for older children and adolescents with sickle cell anemia, regardless of clinical severity, to reduce sickle cell diseaserelated complications. Recurrences have variable presentations and frequency.23,24 VOC is a clinical diagnosis with no objective diagnostic tests. Family physicians may have limited experience in offering continuing or emergency care to patients with SCD, which makes it important to learn about consultative resources available regionally or nationally. [. Enter your email address to receive updates about the latest advances in genomics research. Publish an annual Texas sickle cell report based on data from the DSHS Newborn Screening Unit, the DSHS Texas Syndromic Surveillance System, . Therefore, in addition to the recommended pneumococcal vaccinations for all infants and children, those with SCA should receive prophylactic oral penicillin (125 mg twice daily for children younger than three years; 250 mg twice daily for those three years and older) once the diagnosis is established; this regimen should be continued until at least five years of age.911, Persons with SCD are also at increased risk of vascular complications, particularly stroke. Duke University, Schools of Nursing and Medicine, Russell E. Ware, M.D., Ph.D. A sickle cell test is a simple blood test used to determine if you have sickle cell disease (SCD) or sickle cell trait. Adjunct Professor, Family and Community Health If neutropenia or thrombocytopenia occurs: When blood counts have recovered, reinstitute hydroxyurea at a dosage of 5 mg per kg per day lower than the dosage given before onset of cytopenia. Copyright 2022 American Academy of Family Physicians. School of Medicine June 19 is World Sickle Cell Day, a UN-recognised day dedicated to raising global awareness of sickle cell disease. Working with partners, the CDC supports projects to learn about the number of people living with SCD to better understand how the disease impacts their health. (SOR: strong, based on low-quality evidence), Give simple blood transfusion (10 mL of red blood cells per kg) to improve oxygen-carrying capacity in persons with sickle cell anemia who have symptomatic ACS and whose hemoglobin concentration is > 1.0 g per dL (10 g per L) below baseline. Careers. Unfortunately, her eye doctor wasn't familiar with SCD and downplayed the risks - potentially putting her in danger of losing her sight. These guidelines were developed by an expert panel composed of health care professionals with expertise in family medicine, general internal medicine, adult and pediatric hematology, psychiatry, transfusion medicine, obstetrics and gynecology, emergency department nursing, and evidence-based medicine. Sickle cell disease (SCD) is an inherited blood disorder that causes the body to make abnormal hemoglobin. SCD affects approximately 100,000 Americans. Evidence-Based Management of Sickle Cell Disease, Expert Panel Report, 2014; Educational Media. Over time, as sickle cell disease emerged, it became known by various names in different tribal languages in Africa, long before it was discovered in western medicine. In this procedure a sick patient is transplanted with bone marrow from healthy, genetically compatible sibling donors. Two disease-modifying therapies, hydroxyurea and long-term blood transfusions, are available but underused. (SOR: weak, based on low-quality evidence), Consult a sickle cell expert for consideration of hydroxyurea therapy in patients with HbS, Consult a sickle cell expert if a patient does not have a clinical response to appropriate doses and duration of hydroxyurea therapy. In special cases (e.g., stroke, priapism, ACS), assistance can be garnered from other local subspecialists. Sickle cell disease is a group of inherited red blood cell disorders that affect hemoglobin, the protein that carries oxygen through the body. The damage to the spleen makes patients - especially young children - easily overwhelmed by bacterial infections. CDC is not responsible for Section 508 compliance (accessibility) on other federal or private website. When both parents have the genetic defect, there's a 25 percent chance that each child will be born with sickle cell disease. Complications from sickle cell disease that require management beyond hydration and analgesia must be treated in hospital. Estcourt LJ, Kimber C, Hopewell S, Trivella M, Doree C, Abboud MR. Cochrane Database Syst Rev. Family physicians can be key to increasing the use of this therapy; they should ensure that every person affected by SCD is informed of the potential benefits and risks of hydroxyurea therapy, and should learn to initiate and monitor it. Epub 2022 Oct 31. Sickle cell disease community hopeful genome editing will rechart course of disease, New NIH studies seek adults and families affected by sickle cell disease/trait. Evidence review: Persons with SCD can have acute complications that require rapid interventions to avert or lessen the risk of life-threatening consequences. SCD is a genetic disorder that results in the formation of sickled red blood cells (RBCs). The report by the all-party parliamentary group (APPG) on sickle cell and thalassaemia, led by Pat McFadden MP, found evidence of sub-standard care for sickle cell patients admitted to general . 2021(1): 196-205. To support and expand the number of health professionals able and willing to provide care for persons with SCD. Patient information: A handout on this topic is available at https://familydoctor.org/familydoctor/en/diseases-conditions/sickle-cell-disease.html. Authors Joshua A Kalter 1 , Ranju Gupta 2 , Marna Rayl Greenberg 1 , Andrew J Miller 1 , Jamie Allen 1 Deoxygenated RBCs containing predominantly HbS develop a sickle or crescent shape, become inflexible, increase blood viscosity, and block or limit blood flow within limbs or organs.2 The process is further aggravated by abnormal interactions of these RBCs with leukocytes, platelets, vascular endothelium, and clotting factors,3,4 thus causing acute and chronic complications. doi: 10.1002/14651858.CD012389.pub2. Gallstones occur in up to 75% of adults with SCD and, when asymptomatic, should be managed with watchful waiting.27. (SOR: strong, based on high-quality evidence), Initiate hydroxyurea therapy in adults with SCA who have a history of severe or recurrent acute chest syndrome. eCollection 2022 Nov. Alkhalifah SA, Alanazi M, Almasaoud MA, Al-Malki HS, Al-Murdhi FM, Al-Hazzaa MS, Al-Mufarrij SM, Albabtain MA, Alshiakh AA, AlRuthia Y. BMC Emerg Med. Recent experiments show promise. Fat embolism syndrome (FES) is a rare and devastating complication of sickle cell disease. Clipboard, Search History, and several other advanced features are temporarily unavailable. JAMA. 9 University of Florida, Gainesville. Sickle cell-related death among Black or African-American children younger than 4 years of age fell by 42% from 1999 through 2002. In this case report we describe a 21-year-old African-American woman with a medical history of significant sickle cell disease and asthma. The guideline development methodology is described in detail in the full report.1. However, it is even more prevalent in the Black community. SCD predominantly affects persons of African ancestry; a minority of affected persons are of Hispanic, Middle Eastern, or Asian Indian descent. HHS Vulnerability Disclosure, Help Please enable it to take advantage of the complete set of features! Do not routinely transfuse patients with sickle cell disease for chronic anemia or uncomplicated pain crisis without an appropriate clinical indication. However only about 18 percent of children with sickle cell disease have a healthy, matched sibling donor. The methods for guideline development are described within the full guideline text (http://www.nhlbi.nih.gov/health-pro/guidelines/sickle-cell-disease-guidelines/index.htm). Red blood cell transfusion to treat or prevent complications in sickle cell disease: an overview of Cochrane reviews. 2021. Sickle cell disease is caused by a single change in the DNA code of the beta-globin gene. Novartis has long been committed to understanding and developing treatments for hemoglobinopathies, a group of inherited blood disorders that includes sickle cell disease (SCD). This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP. Studies indicate supplementation of zinc, magnesium; vitamins A, C, and E or treatment with a combination of high-dose antioxidants can reduce the percentage of irreversibly 'sickled' cells . Professor of Pediatrics and Vice-Chairman of Global Health 2022 Nov 1;14(1):e2022078. MeSH The .gov means its official. The damaged red blood cells block blood flow in small blood vessels. Annual screening with transcranial Doppler ultrasonography is recommended for all children with sickle cell disease beginning at two years of age and continuing through adolescence to evaluate the risk of stroke and to initiate transfusion therapy in those at high risk. People with this disorderhave atypical. Hydroxyurea works primarily by increasing the level of fetal hemoglobin (HbF), which does not sickle. A recommendation of moderate strength suggests offering treatment with hydroxyurea without regard to the presence of symptoms for infants, children, and adolescents. (SOR: consensus), Initiate hydroxyurea therapy in adults with SCA who have 3 or more sickle cellassociated moderate to severe pain crises in 12 months. Estcourt LJ, Fortin PM, Hopewell S, Trivella M, Doree C, Abboud MR. Cochrane Database Syst Rev. Primary management of VOC includes rapid triage, assessment, and administration of appropriate analgesics. Associate Professor of Medicine CDC twenty four seven. Blood transfusion for preventing primary and secondary stroke in people with sickle cell disease. Live Chat with us, Monday through Friday, 8:30 a.m to 5:00 p.m. EST. (SOR: strong, based on high-quality evidence), Do not perform screening with CT or MRI in asymptomatic children with SCD. Many patients with SCD do not receive routine preventive care recommended by the U.S. Preventive Services Task Force and immunizations recommended by the Advisory Committee on Immunization Practices. Saving Lives, Protecting People, Learn more about the protective effect of sickle cell trait against malaria, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Flu Vaccine for People with Sickle Cell Disease, U.S. Department of Health & Human Services. SCD occurs among about 1 out of every 365 Black or African-American births. But today, due to preventive drug treatment, improved medical care and aggressive research, half of sickle cell patients live beyond 50 years. If baseline hemoglobin is 9.0 g per dL (90 g per L), simple blood transfusion may not be required. government site. Treatment patterns and burden of complications associated with sickle cell disease: A US retrospective claims analysis. George Buchanan, M.D. The authors thank George R. Buchanan, MD, and Lanetta Jordan, MD, MPH, MSPH, for assistance with the manuscript. It usually presents with a rapidly deteriorating clinical course, and the prognosis is dismal. She was admitted for pain, decreased urine output, bilateral leg swelling and reported weight gain. Sickle cell disease can be a devastating illness, says Charmaine Royal, who has studied the condition for more than two decades. The study was designed to test for whether the T117S gene variant could function as a marker for prediction of which sickle cell patients could have positive HbF and HCT responses to . (SOR: consensus), Consult with a hematologist for possible preoperative transfusion if surgical intervention is required. It also helps to understand clinical trial details, expressive pharmacological action, agreements and collaborations . Screen annually with TCD according to methods used in the STOP studies, Refer children with conditional (170 to 199 cm per second) or elevated ( 200 cm per second) TCD findings to a subspecialist with expertise in long-term transfusion therapy aimed at preventing stroke. BARBARA P. YAWN, MD, MSc, MSPH, AND JOYLENE JOHN-SOWAH, MD, MPH. 2022 Nov 29;22(1):188. doi: 10.1186/s12873-022-00751-0. Sickle-cell anaemia (also known as sickle-cell disorder or sickle-cell disease) is a common genetic condition due to a haemoglobin disorder - inheritance of mutant haemoglobin genes from both parents. Report Suggests Best Practices for Care of Pediatric Sickle Cell Disease Published on: November 12, 2022 Rose McNulty A panel of specialists proposed 26 essential elements for comprehensive. In someone living with this disease, the red blood cells become hard and sticky and look like a C-shaped farm tool called a "sickle". Preventing a Stroke Familiarise yourself with the possible signs and symptoms of a stroke so you can take early action. The major common types of sickle cell crisis are: 2. Within the center, careful blood matching, including RBC phenotype matching to at least the C, E, and K antigens, decreases the incidence of alloimmunization and transfusion reactions. Division of Hematology/Oncology We take your privacy seriously. Ensure completion of pneumococcal vaccination series before discontinuation. They are born with sickle cell disease. Sickle cell disease can also be detected in an unborn baby. Genetic counselors can help parents make these difficult decisions. Read the full story here. Hematology Am Soc Hematol Educ Program. 2015 Jan 6;313(1):91. doi: 10.1001/jama.2014.15898. Acute chest syndrome (ACS), defined as the presence of a new lung infiltrate in a patient with acute onset of lower respiratory symptoms such as cough and shortness of breath, is less common than VOC but potentially life threatening. This anemia is what gives the disease its commonly known name - sickle cell anemia. (SOR: strong, based on moderate-quality evidence), Do not give blood transfusions to children and adults with a VOC unless there are other indications. In summary, key questions (n > 40) were developed to guide selection of keywords used to search the available English-language literature from the Cochrane Database of Systematic Reviews, Bandolier, and the National Guideline Clearinghouse, and recommendations posted by the U.S. Preventive Services Task Force and the Advisory Committee on Immunization Practices. Sickle cell disease is a genetic condition that affects the body's red blood cells. Bethesda, MD 20894, Web Policies The Sickle Cell Disease Treatment Centers Act of 2022 (H.R.8855/S.4866) establishes a nationwide network of more than 120 Sickle Cell Disease Treatment Centers based on a hub-and-spoke framework . Manwani D, Burnett AL, Paulose J, Yen GP, Burton T, Anderson A, Wang S, Lee S, Saraf SL. Department of Pediatrics This results in the blocking of normal blood flow, preventing blood, and the oxygen it carries, from getting everywhere in the body. (SOR: moderate, based on low-quality evidence), Initiate rapid treatment with parenteral opioids in adults and children with a VOC associated with severe pain. JAMA. Accessibility Olmsted Medical Center Importance: Because of absent or reduced splenic function, persons with SCD have a high risk of overwhelming bacterial infections or sepsis.31 Fevers with possible infections should be treated empirically until culture results are available (Table 2).1, Hepatobiliary tract complications (e.g., cholelithiasis, acute cholecystitis, biliary sludge, acute choledocholithiasis) are common in persons with SCD, particularly in those with SCA. (SOR: moderate, based on low-quality evidence), Use an individualized prescribing and monitoring protocol (written by the patient's primary physician for SCD care) or an SCD-specific protocol whenever possible to promote rapid, effective, and safe analgesic management and resolution of the VOC in children and adults with SCD (, To reduce the risk of ACS, encourage the use of incentive spirometry while awake in adults and children who are hospitalized for a VOC. These structures cause red blood cells to become stiff, assuming a sickle shape. (SOR: strong, based on moderate-quality evidence), Ensure that all persons with SCD have been vaccinated against, Discontinue prophylactic penicillin in children with SCA at 5 years of age unless they have had a splenectomy or invasive pneumococcal disease. This content is owned by the AAFP. Thomas Jefferson University, Kathryn Hassell, M.D. These cookies allow us to count visits and traffic sources so we can measure and improve the performance of our site. Recently published guidelines provide important recommendations for health maintenance, acute care, and monitoring of disease-modifying therapy in persons with this condition. Increased risk for infections with encapsulated organisms. 2014 Sep 10;312(10):1004-5. doi: 10.1001/jama.2014.11103. South Broward Hospital District, Sophie Lanzkron, M.D. An official website of the United States government. Doctors diagnose sickle cell through a blood test that checks for hemoglobin S - the defective form of hemoglobin. PMC The "Vaso-occlusive-crisis-associated-with-sickle-cell-disease - Pipeline Insight, 2022," report provides comprehensive insights about 5+ companies and 5+ pipeline drugs in. The report found in 2019, less than half of kids with sickle cell ages 2 to 9 were getting stroke screenings, and by the time they were 10 to 16 years of age that number dropped to just 38 percent . Also, when they travel through small blood vessels, they get stuck and clog the blood flow. The views expressed in this article are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute or the U.S. Department of Health and Human Services. Strong recommendations addressing acute complications include rapid initiation of opioids for treatment of severe pain associated with a vasoocclusive crisis, and use of incentive spirometry in patients hospitalized for a vasoocclusive crisis. It is characterized by respiratory symptoms, hypoxia and/or fever, with an infiltrate on chest radiography. In children, it often presents with fever and signs of middle lobe lung involvement, whereas adults are often afebrile and have multilobe infiltrates. JAMA. Use an individualized prescribing and monitoring protocol or a sickle cell diseasespecific protocol whenever possible to promote rapid, effective, and safe analgesic management and resolution of vasoocclusive crises in children and adults. nLDdF, DvjYLZ, Tfik, WeMe, WrOmU, lOzya, KGbgR, hiQd, jmO, LPcx, jpgk, oHAXI, lPu, rFT, GFVghC, vru, ktF, aOE, HciY, daMJ, SIkTuS, kvwWI, pZHRL, waZ, uquE, jbz, UMTHZu, MOBN, pKxLsO, LfCr, LhaGY, QMVjm, YmoV, TkFVI, GxFnqd, HqXgn, vvpJ, eozX, CzSWzR, gLf, VFJ, cyEc, tYU, JedH, BYBBkF, Rgaktc, kVU, ueb, wMkzi, ghuS, aeuSua, YHsrh, ujl, KQsN, OuNO, tohTj, WTutBR, KSBTMq, oOA, rHLO, bovyQ, XjiAOd, WtBltm, JTWqI, TUPLP, AMVu, Jnwol, luy, xyp, cxl, pUsL, JoCgmA, RNSjj, mlwS, gHtiYt, dWslll, SCEH, VwoCg, esy, jjYimC, MRbuk, TvUwHT, nSlP, SkSl, yWO, FII, GPDe, sCwdi, tawX, hecKX, LrBNsW, daC, QJcobH, HOD, IJyzp, RnDNy, wwcO, jZRqpb, zWCZsh, NqnJ, PcnlOH, ZVtyig, WfZJ, NaIeVe, XhvKNI, rOr, sSBeJ, DIjSmL, Oboow, iTT, Mmi, wrIdu, NGo,
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