ALBERT

Beschreibung: Background: Sickle cell disease (SCD) is a complex genetic disorder affecting mainly people of African origin. A hallmark of SCD is vaso-occlusive crisis (VOC) - this event is acutely painful and the primary cause of hospitalization in SCD patients. VOC can lead to life-threatening complications such as acute chest syndrome. SCD is also associated with chronic complications including pulmonary hypertension, damage to organs and shortened life expectancy. Therefore, effective management and treatment strategies are essential to reduce burden of illness and ensure high quality of life for the patient. Aim: To survey the treatment and management strategies used by patients with SCD, and to determine patient satisfaction levels. Methods: SWAY is an ongoing multi-country, cross-sectional survey of SCD patients, caregivers and treating physicians. The survey, conducted online and in print, includes 6 categories: demographics, symptoms, impact of disease and use of a caregiver, impact on work and finances, disease management/treatment approaches, and patient-physician relationship. Where relevant, questions include a 7-point severity scale for each statement; a score of 5−7 indicates 'high severity/impact'. Patient enrollment is via treating physicians and patient association groups. The enrollment target is approximately 2000 patients. Results: To date, 1513 SCD patients (48% male, mean age 24.1 years, 63% HbSS and 30% HbSC disease) have been surveyed from 11 countries across North and South America, Europe and Africa. When considering the main person responsible for SCD treatment and management, patients primarily reported management by an SCD specialist (59% of patients) or GP/family doctor (20%). Most patients were satisfied with the frequency of interaction with their doctor (78%) and reported they are confident they are being assessed and treated properly (66%; based on high-impact scores 5−7). Accordingly, 60% of patients (scoring 5−7) reported sharing the same goals for SCD management and treatment as their doctor. The most common treatment goals for patients are to improve quality of life (80% of patients), prevent SCD worsening (59%), improve long-term survival (42%) and improve overall symptoms (40%). Patients reported receiving ongoing treatment with folic acid (58%), antibiotics (37%), anti-inflammatories (37%), over-the-counter pain medication (37%), opioids (35%), hydroxyurea (23%), blood transfusions (10%) and L-glutamine (4%). Having surgery or a medical procedure to manage their SCD was reported by 47% of patients, with gall bladder removal (16%), port placement (15%) and splenectomy (11%) being the most frequent. Although 63% of patients (scoring 5−7) indicated satisfaction with their treatment received to manage their SCD, 75% of patients (scoring 5−7) agreed they would like an alternative treatment to their current pain management medication, and 67% of patients would like additional professional emotional support. In the 12 months before survey completion, 7829 VOCs were reported (mean of 5.2 VOCs per patient); 8% of patients experienced 0 VOCs, 51% experienced 1−4 VOCs and 40% experienced ≥5 VOCs. Of these, 38% of VOCs led to overnight hospitalization, 24% were managed at home and 19% were treated in the emergency room. The main reasons that patients chose to manage their VOCs at home include a previous poor experience at hospital (40%), the opinion that medical assistance was not required (28%), the perception that medical professionals do not understand SCD (27%) and the cost of hospital treatment (22%; 41% of patients have no health insurance). Patients who self-managed their VOCs primarily did so with rest/sleep (73%), by drinking fluids (72%) and with opioid-based analgesia (58%). Conclusions: This interim analysis of the SWAY survey suggests that although many patients report satisfaction with their current level of management and treatment, there is still a need for additional healthcare support and alternative treatments. Underlining this, many patients experiencing VOCs do not seek medical assistance despite the potential for life-threatening complications, and 〉75% of patients surveyed are not receiving hydroxyurea even though the majority are cared for by SCD specialists. Further data collection and analysis will highlight any geographic differences in SCD management strategies and help identify any region-specific unmet patient needs. Disclosures James: Novartis: Honoraria; Sickle Cell Society: Employment. Andemariam:NovoNordisk: Membership on an entity's Board of Directors or advisory committees; New Health Sciences: Membership on an entity's Board of Directors or advisory committees; Emmaus: Membership on an entity's Board of Directors or advisory committees; Cyclerion: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Imara: Research Funding; Global Blood Therapeutics: Other: DSMB Member; Community Health Network of Connecticut: Consultancy; Bluebird Bio: Membership on an entity's Board of Directors or advisory committees; Sanofi Genzyme: Membership on an entity's Board of Directors or advisory committees; Terumo BCT: Membership on an entity's Board of Directors or advisory committees. El-Rassi:Novartis Pharmaceuticals: Research Funding. Francis-Gibson:Sickle Cell Disease Association of America: Employment. Nero:Novartis: Consultancy. Minniti:Doris Duke Foundation: Research Funding. Trimnell:Novartis: Consultancy; Global Blood Therapeutics: Consultancy; Cyclerion: Consultancy. Abboud:Novo Nordisk: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Modus: Research Funding; CRSPR Therapeutics: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Research Funding; Amgen: Other: Travel support; Eli Lilly: Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; GBT: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Colombatti:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Addmedica: 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. de Montalembert:AddMedica: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; bluebird bio, Inc: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Jastaniah:Novartis: Consultancy, Honoraria. Nur:Novartis: Consultancy. DeBonnett:Novartis Pharmaceuticals Corporation: Employment. Osunkwo:Micella Biopharma: Other: DSMB Member ; Terumo: Speakers Bureau; Pfizer: Consultancy; Novartis: Consultancy, Speakers Bureau.

Beschreibung: Splenectomy is frequently performed for diagnostic purposes in patients with suspected or known lymphoma, including assessment for possible transformation. The ability to predict splenectomy findings (and potentially avoid associated morbidity and mortality) would be valuable. The purpose of this study was to determine whether preoperative18F-fluorodeoxyglucose positron emission tomography (FDG-PET) results correlate with pathologic diagnosis from splenectomy. Methods: One hundred sixty-five patients who had undergone a splenectomy at New York Presbyterian Hospital from January 2004 to July 2006 were identified from the pathology database. Records of these patients were searched and 11 with suspected or known lymphoma as an indication for splenectomy and who had a pre-splenectomy PET scan were identified. A nuclear medicine physician performed a blinded review and assigned each PET scan to one of the following categories based on splenic FDG standardized uptake values (SUV): low splenic metabolic activity (correlated with maximum SUV range 2-3.7), intermediate splenic metabolic activity (maximum SUV range 6–7), and high splenic metabolic activity (maximum SUV range 26–29). Findings were correlated with splenectomy pathologic diagnosis. Results: Subjects (n=11, 4 female, 7 male) had a median age of 48 years (range 21–72); four had suspected lymphoma pre-splenectomy, while 7 had a prior diagnosis and had splenectomy for diagnostic (to rule out transformation) or other purposes. Median time between PET and splenectomy was 1.25 months. Of 5 patients with low metabolic activity on PET; three had benign findings at splenectomy and two had splenic involvement of previously known mantle cell lymphoma. Three patients had intermediate metabolic activity on PET; all subsequently demonstrated marginal zone lymphoma at splenectomy. Three patients had high metabolic activity on PET; all were found to have diffuse large B cell lymphoma at splenectomy. Conclusions: This study to our knowledge comprises the largest series to evaluate splenic FDG-PET uptake in patients with suspected or known lymphoma, followed by subsequent pathologic confirmation. Patients with low splenic SUVs appear to be less likely to have splenic involvement of lymphoma, while intermediate and high values may correlate with lymphoma histology. Our findings support a potential role for FDG-PET as a tool for use, in conjunction with clinical and laboratory assessment, in consideration of the need for splenectomy in these settings.

Beschreibung: Background: Renal disease is a common end organ complication of sickle cell disease(SCD). Risk factors of sickle cell nephropathy include age, genotype, and anemia. We have investigated and discovered Lower Hemoglobin Oxygen Saturation levels associated with microalbuminuria. To further investigate this, we investigated a patient's history of asthma as a risk factor of renal disease. Asthma has been linked to increased mortality in adult and children with SCD from the National Cooperative SCD Study Group. In our ongoing International CASIRE Renal Cohort study, we investigated the clinical history of asthma and laboratory correlates of albuminuria and proteinuria as measured by Urine Protein/Creatinine and Urine Albumin/Creatinine . Methods: 538pediatric and adult SCD (3-59 y/o) patients were recruited at baseline from 6 Centers (USA: Univ of Michigan, Case Medical Center/Rainbow Babies, Albert Einstein-Montefiore Medical Center, Univ of Connecticut; Italy: Univ. of Padova, Univ of Naples;). Clinical history and laboratory studies, including Pain crisis patterns, SBP, DBP, BMI, CBC, Serum Crt, Urine ph, Urine SG were collected. For this report, we concentrated on patient's comorbidities and sickle cell medical history, specifically pain crisis patterns, acute chest history and asthma. Urine Microalbumin/Crt(UMA) (mg/gm) was obtained in 172 patients and we categorized patients into No Albuminuria: (No UMA)300mg/gm.334 subjects answered the question of medical history of asthma and of those 172 had Urine Microalbumin (UMA) levels. 75% of SCD-Asthma group (N=56) and 78% of SCD-NoAsthma group (N=204) had severe SCD (SS or SBeta Zero). Children (

Beschreibung: Introduction: Millions are affected by Sickle Cell Disease (SCD) worldwide with the greatest burden in sub-saharan Africa. Its origin thought to lie within the malaria belt of the world, SCD continues to affect thousands of lives worldwide partly due to the migration patterns of the human race to different continents. We created the Consortium for the Advancement of Sickle Cell Research (CASiRe) to better understand the different phenotypes of SCD and compare the clinical profiles of patients living in different environments through a validated questionnaire and medical chart review, standardized across 4 countries (United States[U.S.] United Kingdom[U.K.], Italy and Ghana). For this report, we recorded the multi-generational ethnic and racial background of 877 SCD patients across the CASIRE cohort for our final analysis. Methods: CASiRe included 6 sites in the U.S. (Univ. of Michigan, Rainbow Babies & Children's Hospital, Promedica Toledo Children's Hospital, Children's Hospital at Montefiore, Connecticut Children's Medical Center, Univ.of Connecticut Health Center), 2 in Ghana(Ghana Institute of Clinical Genetics, Pediatric SCD Clinic at Korle Bu Teaching Hospital), 2 in Italy( Univ. of Campania Luigi Vanvitelli, Univ. of Padua, Italy), and U.K.(Guys & St. Thomas Hospital, Evelina Children's Hosp). Between 2011 and 2017, after obtaining IRB approval at each site and written informed consent, demographic, clinical and laboratory data were collected by interviewing the patient and/or parent/guardian At the 2 sites (Guys and St Thomas Hospital, UK; Univ. of Padua, Italy) with existing IRB approved SCD registries data were abstracted directly from their respective databases. Descriptive statistics were performed on a subset of demographic data that included: age, race, gender, sickle cell genotype, country of birth of patient, parents, and grandparents. The geographic region and country of origin was based on parents' country of birth and separated into 10 regions: W.Africa, C.Africa, N Africa, Caribbean, C. America, N America, Europe, S America, Asia, Middle East. Results: 877 patients were enrolled with a median age 19.3 years. 451 (51.4%) patients were children, 424 (48.3%) male. Ghanaians represented 41.6% (365) of patients, while 254 patients (29%) were from the U.S. Italy enrolled 81 patients (9.2%), and 177 patients (20.2%) were from the U.K. West Africa represented the largest geographic region of origin of(577/65.8%), followed by N. America (184/21%), Caribbean (51/5.8%), Europe (27/3.1%), and Central Africa (24/2.7%). Overall(Fig. 1), 75% of patients (658) had Hgb SS, 168 patients (19.2%) had Sickle C disease, 29 (3.3%) had Sβ+thal and 22 patients (2.5%) of patients had Sβ0 thal. Racially, 820 patients (93.5%) identified themselves as African American or Black, while 30 patients (3.4%) identified themselves as Caucasian and 21 patients (2.4%) identified themselves as Latino or Hispanic. All Ghanaians identified as Black, while in the US and UK, over 90% of patients identified themselves as Black, and about 3% reported themselves as Caucasian. In comparison, in Italy, over 76% of patients reported a Black racial background, while 21% reported Caucasian background. (Table 1 and 2)〉98%Ghanaian patients and their parents were born in Ghana. In contrast, 66.7% of patients and 90% of patients were born within the US; Parents of patients were born in America 70% of the time. Caribbean (12.5%) and West African countries(9.5%) were the next highest parent countries of origin. 32 different countries of origin were reported within our cohort with the US leading with 22 different countries. Conclusion: This study is the first to describe the geographic distribution of these migrations in a very large cohort of nearly 900 patients with SCD.West Africa represented the largest geographic region of origin for SCD patients in Europe while Caribbean was the leading Non-US geographic region of origin in American patients. The diverse ethnic backgrounds observed in our cohort raises the possibility of how genetic and environmental heterogeneity within each SCD population subgroup can have implications on the clinical phenotype and clinical research outcomes. Disclosures Campbell: Novartis: Research Funding; Cyclerion: Consultancy, Research Funding; Global Blood Therapeutics: Consultancy, Research Funding. Colombatti:Novartis: Consultancy; Global Blood Therapeutics: Consultancy; AddMedica: Consultancy. Andemariam:NovoNordisk: Membership on an entity's Board of Directors or advisory committees; New Health Sciences: Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Other: DSMB Member; Bluebird Bio: Membership on an entity's Board of Directors or advisory committees; Emmaus: Membership on an entity's Board of Directors or advisory committees; Cyclerion: Membership on an entity's Board of Directors or advisory committees; Imara: Research Funding; Sanofi Genzyme: Membership on an entity's Board of Directors or advisory committees; Community Health Network of Connecticut: Consultancy; Terumo BCT: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Strunk:Novartis: Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Speakers Bureau. Piccone:Hemex Health, Inc.: Patents & Royalties. Manwani:GBT: Consultancy, Research Funding; Novartis: Consultancy; Pfizer: Consultancy. Perrotta:Novartis: Honoraria, Research Funding; Acceleron Pharma: Research Funding.

Beschreibung: Introduction Sickle cell anemia is the most common single gene defect in the United States, affecting approximately 100,000 individuals (Hassel Am J Prev Med 2010). It is characterized by chronic hemolysis, unpredictable vaso-occlusive episodes (VOEs), and chronic organ damage leading to early death in patients affected by the disorder. Hydroxyurea, a small molecule chemotherapeutic agent, has been used to treat patients with severe sickle cell disease since 1984 (Brawley Ann Intern Med 2008). Two randomized controlled trials, the Multicenter Study of Hydroxyurea (Charache N Engl J Med 1995) in adults and the Baby HUG trial (Wang Lancet 2011) in children, showed that hydroxyurea reduced the number of VOEs and hospital admissions, while simultaneously increasing hemoglobin and fetal hemoglobin in patients with sickle cell anemia. The goal of this study was to determine the clinical effectiveness of hydroxyurea in reducing the number VOEs and hospitalizations in unselected patients with sickle cell anemia. Methods The CASIRE group is an international multi-institutional collaborative group evaluating the clinical severity of patients with sickle cell anemia through a validated questionnaire, chart review and laboratory studies. Patients were enrolled on the CASIRE study after informed consent and assent was obtained from either the parent or patient when appropriate. The study was approved at each participating institution's IRB. A questionnaire was answered by the parents and/or patient, and baseline and current laboratory studies were collected. Patients were stratified into those who were not on hydroxyurea, and those who were currently on hydroxyurea. Number of VOEs, admissions, baseline and current fetal hemoglobin, and change in hemoglobin and MCV were compared. Results There were 349 patients in this study (134 on hydroxyurea). Baseline laboratory data are reported in table 1. Hemoglobin level and MCV were not statistically different in patients prior to and after taking hydroxyurea (table 2). Fetal hemoglobin in adults increased 2.7 times baseline, whereas in children it was unchanged. All patients on hydroxyurea had a reduction of VOEs, ED visits and admissions compared to prior to hydroxyurea (see table 3). Table 1. Baseline laboratory data Baseline data Patients on Hydroxyurea Patients not on Hydroxyurea Pediatric Adult Pediatric Adult N 78 56 140 75 Age 10 26.9 8.6 28.3 Hemoglobin (g/dL) 8.7 9.7 9.39 9.4 MCV (fL) 91 91.5 79 86 Fetal Hemoglobin (%) 15.1 12.4 9.6 5 Table 2. Clinical data for patients on HU Patients on Hydroxyurea Pediatric (78) Adult (56) Dose of HU (mg/kg) 23.8 20.5 # doses missed/wk 1 1.55 Fetal Hemoglobin on HU (%) 14.5 13.8 D MCV from baseline (fL) +5.4 +0.1 D Hgb from baseline (g/dL) +0.23 +0.4 Table 3. Number of pain episodes in patients on HU. Prior to HU In last year on HU 2 tailed paired t test Pediatric patients (N = 78) # pain episodes/year 25 12.9 0.62 # requiring ED/year 2.66 1 0.93 # requiring admission/year 4.28 1.79 0.017 Adult patients (N = 56) # pain episodes/year 36.7 28.6 0.021 # requiring ED/year 5.7 2.4 0 # requiring admission/year 6.6 3.15 0.117 Conclusion The Multicenter Study of Hydroxyurea and the BABY HUG study showed that hydroxyurea is efficacious for patients with sickle cell anemia. No previous study has evaluated the effectiveness of hydroxyurea in clinical practice. Our study suggests that, although baseline and current laboratory values are similar in patients prior to versus after taking hydroxyurea, there was a clear reduction in the number of VOEs and admissions, similar to the Baby HUG and MSH studies. These results suggest that the reduction of VOEs could be the product of a generalized decrease in overall inflammation and hemolysis or increased nitric oxide production rather than an increase in fetal hemoglobin by itself. Reasons for the similarity in laboratory values could include the length of time patients have been on hydroxyurea or that hydroxyurea was not escalated to maximum tolerated dose. Another reason may be the degree of compliance of patients in a clinical setting. We noted that 1/3 of our pediatric and ½ of our adult patients missed at least 1 dose of hydroxyurea per week suggesting that even partial compliance with hydroxyurea may prove beneficial clinically. This study demonstrates that hydroxyurea is effective in reducing the number of VOEs and admissions for unselected patients with sickle cell anemia. Disclosures No relevant conflicts of interest to declare.

Beschreibung: Introduction: Adults living with sickle cell disease (SCD) have high utilization of emergency departments (ED) and hospitals, and utilization typically is skewed with a subgroup with very high utilization. We sought to promote a shift from ED/hospital utilization to ambulatory care (Amb) services in our state through ED/hospital visit-prompted communication with ED/hospital and Amb practitioners. Methods: The Community Health Network of Connecticut, Inc. (CHNCT) is the medical administrative services organization (contractor) for the physical health benefit of the state's Medicaid Program, HUSKY Health. Among HUSKY members ages 16 years and older (16+) with Medicaid-only insurance and with at least one Medicaid payment claim with a primary or secondary ICD-9/ICD-10 diagnosis of sickle cell disease from Feb 28, 2016 thru Feb 25, 2017, we identified high ED/hospital utilizing members. CHNCT monitored high utilizing 16+ member ED/hospital visits in real time using admission, discharge, and transfer data, and provided practitioner team members with individual member utilization data (mUD) to be shared via telephone contact with ED/hospital and Amb practitioners when 16+ members visited an ED or were hospitalized. Shared mUD included numbers of ED/hospital visits, names of ED/hospital facilities visited, and information about Amb services visits. ED/hospital practitioners were encouraged to advise members to seek regular care from one of the state's hospital-based SCD programs or other practitioners. No formal hypotheses were declared for testing for statistical significance. Differences in utilization were compared with the Mann-Whitney U test. Results: We identified 705 16+ members living with SCD. In phase 1, high utilizing members (HUM1) were defined as individuals with 12+ ED visits or 8+ hospital visits in the reference year. We identified 45 (6%) HUM1 who accounted for approximately half of all 16+ member ED visits [1364 (56%) of 2436] and hospital visits [368 (47%) of 788]. Among HUM1, the distribution of visits was highly skewed with individual HUM1 accounting for up to 184 ED and up to 27 hospital visits. HUM1 used up to 27 facilities, some out-of-state. In phase 2, we identified an additional 47 members (HUM2) with 6+ ED visits or 4+ hospital visits in the reference year. From Aug 2017 to Jun 2019, CHNCT notified clinical team members of 504 ED/hospital visits involving 51 HUM, and clinical team members shared mUD with practitioners on 342 (68%) occasions. For data analysis, the HUM1 pre-information sharing period was defined as 1/1/16 thru 11/9/16; the post-information sharing period was defined as 7/11/16 thru 7/10/17. For HUM2, pre- 6/6/17 thru 6/5/18, and post- 6/6/18 thru 12/13/18. As the duration of time periods differed, data were expressed as visits (or dollars) per year. ED visit rates fell by one third for HUM1 (33%), but were little changed for HUM2 (see Table 1). Hospitalization rates fell by about one third for both HUM1 (39%) and HUM2 (32%). P values for changes in ED visit rates for HUM1 and HUM2 and in hospitalization rates for HUM2 ranged from 0.005 to 0.01. Medicaid ED and hospital expenditures per year fell more than one third (35%), or about $2.2M. Conclusions: Six percent of CT Medicaid members 16 years and older living with SCD accounted for approximately half of all those members ED and hospital utilization. Visit-prompted sharing of utilization data of these high utilizing members with ED, hospital, and Amb practitioners coupled with a recommendation to advise these members to seek regular Amb services led to decreases in ED visits, hospitalizations, and total expenditures by about one third. The same intervention applied to a cohort of the next highest utilizing members resulted in a similar change in hospitalizations but minimal change in ED visits. Medicaid expenditures for ED visits and hospitalizations for the groups combined fell by about one third, or $2.2 million per year. It will be important to ascertain whether information sharing changed utilization of Amb services. This quality improvement project is HIPAA compliant; no institutional review board approval was required. Table Disclosures Roberts: Community Health Network of Connecticut: Consultancy; Truven Health Analytics: Consultancy. Andemariam:Emmaus: Membership on an entity's Board of Directors or advisory committees; New Health Sciences: Membership on an entity's Board of Directors or advisory committees; Sanofi Genzyme: Membership on an entity's Board of Directors or advisory committees; Terumo BCT: Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Other: DSMB Member; Imara: Research Funding; Cyclerion: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; NovoNordisk: Membership on an entity's Board of Directors or advisory committees; Bluebird Bio: Membership on an entity's Board of Directors or advisory committees; Community Health Network of Connecticut: Consultancy. Latham:Community Health Network of Connecticut: Employment. Cyr:Community Health Network of Connecticut: Employment. Magras:Community Health Network of Connecticut: Employment.

Beschreibung: Background: Sickle cell disease (SCD) is a multi-system disease affecting millions of people. The disease is characterized by vaso-occlusive crises (VOCs), resulting in acute and chronic pain, end-organ damage and life-threatening complications. The symptoms experienced by patients, caused largely by multi-cellular adhesion leading to vaso-occlusion and vasculopathy, significantly affect their quality of life (QoL) and ability to work/study. Understanding the effect of SCD on patients' daily lives can inform management of the disease and improve patients' QoL. Aims: To assess the impact of SCD on patients' daily lives, including physical symptoms, emotional wellbeing and economic burden, based on the worldwide SWAY survey. Methods: SWAY is an ongoing multi-country, cross-sectional survey of SCD patients, caregivers and treating physicians. Data are collected using self-completed or proxy surveys and categories include demographics, symptoms and impact of disease (physical, emotional and financial) and need for a caregiver. Where relevant, questions include a 7-point severity scale for each statement, with a score of 5 to 7 indicating 'high severity/impact'. Patient enrollment is via treating physicians and patient association groups. The enrollment target is approximately 2000 patients. Results: To date, 1513 SCD patients (48% male, mean age 24.1 years, 63% HbSS and 30% SC disease) have been surveyed from countries across the world, including the USA (365), UK (299), Nigeria (264), Ghana (255), Brazil (160) and Germany (91). The most commonly experienced symptoms of SCD were bone aches (63%), difficulty concentrating (49%), difficulty gaining weight (49%) and joint stiffness (41%). For these symptoms, 67%, 53%, 70% and 59% of patients rated them as 'high severity' on the 7-point scale, respectively. Background pain was present on an average of 2.9 days per week (standard deviation [SD]=2.2). Commonly experienced complications of SCD include fever (65%), joint issues (55%) and infections (55%). Patients reported a total of 7829 VOCs, with a mean of 5.2 VOCs per patient (SD=5.07) in the 12 months before survey completion; 38% of these VOCs resulted in overnight hospitalization, 24% were managed at home, 19% were treated in the emergency room and 19% of patients sought medical assistance in the community. A high impact on emotional wellbeing was reported by 61% of patients. The highest impact was caused by frustration with symptoms (60%), worry about disease worsening (59%) and worry about family/friends/children who care for them (54%). Only 42% of patients have received professional emotional support (eg psychiatrist, psychologist, counseling), but 67% reported a desire to receive this support. A high impact on household daily activities (eg food preparation, housework, childcare) and on family or social life was reported by 39% and 43% of patients, respectively, with 34% stating a high impact in terms of sexual desire/activity and 35% a high impact on relationships with spouse/partner. Physical activity was also affected in patients with SCD, with 60% reporting they avoid intense physical activity and 30% avoiding even mild physical activity, most commonly because of concerns about pain, exhaustion and dehydration (58%, 57% and 50%, respectively). Of the patients surveyed, 32% were employed, 8% not working but seeking employment, 6% not working and not seeking employment, 36% students, 1% retired, 13% on disability pay and 1% long-term sick leave. Employed patients reported SCD had a high impact on their ability to work, with 57% reducing their hours and 47% considering leaving their job. An average of 6.3 hours missed from work was reported in the 7 days prior to survey completion due to SCD. Half of patients believe that their income would be higher if they did not have SCD, 60% reported often missing school in the past and 52% felt that their disease has had a negative impact on their academic achievements. Conclusions: The acute and chronic symptoms associated with SCD have a substantial impact on patients' daily lives, including emotional and physical wellbeing, relationships and school/work. In addition, the acute symptoms associated with VOCs occur several times a year, resulting in frequent hospitalizations. Improved management of SCD would enhance patients' quality of life both at home and at school/work, likely leading to improved emotional wellbeing and a positive economic effect. Disclosures Osunkwo: Micella Biopharma: Other: DSMB Member ; Novartis: Consultancy, Speakers Bureau; Pfizer: Consultancy; Terumo: Speakers Bureau. Andemariam:Bluebird Bio: Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Other: DSMB Member; Imara: Research Funding; NovoNordisk: Membership on an entity's Board of Directors or advisory committees; Sanofi Genzyme: Membership on an entity's Board of Directors or advisory committees; Terumo BCT: Membership on an entity's Board of Directors or advisory committees; Cyclerion: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Emmaus: Membership on an entity's Board of Directors or advisory committees; New Health Sciences: Membership on an entity's Board of Directors or advisory committees; Community Health Network of Connecticut: Consultancy. El-Rassi:Novartis Pharmaceuticals: Research Funding. Francis-Gibson:Sickle Cell Disease Association of America: Employment. Nero:Novartis: Consultancy. Minniti:Doris Duke Foundation: Research Funding. Trimnell:Global Blood Therapeutics: Consultancy; Novartis: Consultancy; Cyclerion: Consultancy. Abboud:AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; CRSPR Therapeutics: Membership on an entity's Board of Directors or advisory committees; Modus: Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Eli Lilly: Research Funding; GBT: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Other: Travel support; Novo Nordisk: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Colombatti:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Addmedica: 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. de Montalembert:AddMedica: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; bluebird bio, Inc: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Jastaniah:Novartis Pharmaceuticals: Consultancy, Honoraria. Nur:Novartis Pharmaceuticals: Consultancy. DeBonnett:Novartis Pharmaceuticals Corporation: Employment. James:Sickle Cell Society: Employment; Novartis: Honoraria.

Beschreibung: Background The prevalence of renal disease in sickle cell disease (SCD) is strikingly high and is associated with morbidity and mortality (Becker et al 2010, Powars et al 2005). In SCD children there is initially hyperfiltration with high GFRs followed by increasing proteinuria in the adolescent and adult SCD pts. (Becker at al 2010). Historically, hypertension (HTN) has been associated with Renal Disease in the general population and a few adult sickle cell nephropathy studies. HTN has been associated with Stroke in SCD. In an ongoing multicenter, international Renal SCD Cohort Study, we investigated the association Microalbuminuria and Macroalbuminuria to Patients Blood Pressure (SBP and DBP), Hypertension based on CSSCD Group Age Defined BP for SCD patients 〉90%tile (Pegelow et al 1997), and Family history (FH) of Hypertension and Renal Disease in a Crossectional (Peds and Adults), International, Multicenter group of SCD patients. Methods 272 pediatric and adult SCD (3-59 y/o) patients were recruited at baseline from 6 Centers (USA: Univ of Michigan, Case Medical Center/Rainbow Babies, Albert Einstein-Montefiore Medical Center, Univ of Connecticut; Italy: Univ. of Padova, Univ of Naples; Ghana: Korle-Bu Teaching Hospital). 88%(N=236) were severe SCD (SSorSBeta Zero) and 12%(N=31) were Mild Phenotype (SC or SBetaPlus). 58% were Children (18y/o) adults. FH of HTN and Renal Disease were obtained in 1st and 2nddegree relatives. Clinical history and laboratory studies including Pain crises patterns, SBP, DBP, BMI, CBC, Serum Crt, were collected. We obtained Urine Microalbumin/Crt(UMA) (mg/gm) obtained in 169 patients and categorized patients into 1) No Microalbuminuria(No UMA) 90%tile for each specifically defined age group( Pegelow et al 1997). Results In our SCD Renal Cohort Study, NoUMA in 71%(110/169), MicroUMA in 29%(48/169), MacroUMA in 2.2%(6/169) were observed. We also found NoUProt in 75%(N=75) and MacroUProt in 25%(n=25) within our cohort. Severe SCD pts represented 96%(n=46) of the MicroUMA pts, 100% or MacroUMA pts(N=6), and 92% MacroUProt pts(N=23). Proteinuria was disproportionately represented within the Adult SCD pts : 50% of Adults with MicroUMA(n=31) while only 16%(n=17) of Peds. UMA Mean Adult levels was 102(mean) vs. Peds UMA levels of 22(mean),(p=0.009); Also, Adult UProtCrt=0.21(mean)levels were 〉Peds=0.16, (p90%tile or DBP 〉90%tile was present in 30%of the subjects(n=77).Thirty-One Percent(n=32) of Adults and 30%(n=45) of Peds pts had HTN. In a Bivariate Analysis(Pearson’s Correlation), HTN was not associated with UMA levels(p=0.919) or UPrtCrt levels(p=0.330). Further, mean UMA was lower in HTN SCD pts( m=24) vs NonHTN(SBP) pts(m=51). Mean UProt levels lower in the HTN group(0.15 ) vs NonHTN(0.20). SBP alone was not associated with UMA( p=0.083), UPrt( p=0.804) levels, MicroUMA(p=0.596). While FH of HTN was common in 75% of pts, FH HTN was not associated with UMA and UProtCrt levels, MicroUMA, MacroUMA, MacroUProt( p〉0.05) patients. FH of Renal Disease was not associated with Proteinuria within our Cohort. However, Age( p90%tile from the CSSCD Group, FH of HTN was not associated with Micro or Macroproteinuria based on UProtCrt and UMA levels in an international, cross-sectional cohort of SCD patients. Hemoglobin level and older age were strongly associated with proteinuria within our cohort of patients, consistent with previously well established studies. These findings are supportive of other factors outside of HTN including those intrinsic to SCD contributing to early onset SCD nephropathy. Disclosures: Perrotta: Novartis: Research Funding.

Beschreibung: Introduction Healthy and pathological human red blood cells (RBCs) express surface adhesion receptors which mediate interactions with the endothelium, platelets, and white blood cells. The adhesive properties of RBCs are defined by the density and distribution of adhesion receptors, and the binding force to specific ligands. In sickle cell disease (SCD), cytoadherence of RBCs to the vascular endothelium and subendothelial matrix is thought to be a major contributor to and possibly the primary cause of vasculopathy in SCD1. Painful vaso-occlusive episodes (VOEs), the hallmark of SCD, result from the blockage of small vessels. Here, we establish a molecular-level technique, based on atomic force microscopy (AFM), to measure the binding force between a specific ligand and its corresponding receptor on a single RBC. Using AFM, we can compare the frequency and localization of adhesion receptors present on the membrane of RBCs collected from healthy human volunteers and SCD patients. We focused on the interaction between basal cell adhesion molecule and its isoform Lutheran (BCAM/Lu) on the RBC and the subendothelial matrix protein laminin-5. Sickle RBCs (SS RBCs) overexpress BCAM/Lu and are more adherent to laminin-5 than healthy RBCs. Importantly, by using a flow adhesion assay, Hines et al2 demonstrated that the interaction between BCAM/Lu and laminin-5 is mediated by cyclic adenosine monophosphate (cAMP) which activates protein kinase A (PKA) and BCAM/Lu receptors. Because PKA binding can be mediated by A-kinase anchoring proteins (AKAPs), which sequester PKA to subcellular sites3, here we investigate whether AKAPs play a role in BCAM/Lu receptor activation on RBCs from healthy volunteers and SCD patients. Methods Peripheral blood RBCs were collected from consenting healthy volunteers (n=5) and individuals with SCD (n=4). RBCs were separated from whole blood using centrifugation. AFM was employed to quantify the frequency of active BCAM/Lu receptors on a single RBC. Molecular interactions were quantified by recording force v. distance curves between a laminin-5 functionalized probe and a 1μm2 area of the RBC surface with a lateral resolution of 30nm. Detected binding forces represent adhesive events between BCAM/Lu and laminin-5, which translate to the percentage of active BCAM/Lu receptors on the RBC surface. To detect the presence of AKAPs, RBCs were treated with St-Ht31 inhibitor peptide (83nM bath), which inhibits the interaction between the regulatory subunits of PKA and AKAP in cells. As a negative control, RBCs were treated with St-Ht31P control peptide (83nM bath), which is the inactive form of the St-Ht31 inhibitor peptide. Results Our experiments reveal that following treatment with St-Ht31, the frequency of active BCAM/Lu receptors is significantly lower on healthy RBCs (from 5.71±1.23% to 3.15±1.09%; p