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293 results on '"DeBaun, Michael"'

1. Digital cognitive behavioral therapy vs education for pain in adults with sickle cell disease

Author

Jonassaint, Charles R., Lalama, Christina M., Carroll, C. Patrick, Badawy, Sherif M., Hamm, Megan E., Stinson, Jennifer N., Lalloo, Chitra, Saraf, Santosh L., Gordeuk, Victor R., Cronin, Robert M., Shah, Nirmish, Lanzkron, Sophie M., Liles, Darla, O’Brien, Julia A., Trimnell, Cassandra, Bailey, Lakiea, Lawrence, Raymona H., Saint Jean, Leshana, DeBaun, Michael, De Castro, Laura M., Palermo, Tonya M., and Abebe, Kaleab Z.

Abstract

•The 6-month change in pain interference did not significantly differ between the digital CBT and digital pain/SCD education arms.•Health coach–supported, digital CBT and pain/SCD education are equally effective adjunct treatments for chronic pain in SCD.

Published
2024
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2. Incremental eligibility criteria for the BMT CTN 1507 haploidentical trial for children with sickle cell disease

Author

John, Tami D., Walters, Mark C., Rangarajan, Hemalatha G., Rahim, Mahvish Q., McKinney, Christopher, Bollard, Catherine M., Abusin, Ghada, Eapen, Mary, Kassim, Adetola A., and DeBaun, Michael R.

Abstract

•With DSMB oversight, we introduce a novel stepwise eligibility strategy for pediatric SCD curative trials based on 4 stages.•A committee assessed eligibility based on pain incidence rate, undertreated asthma, chronic stress, and adherence to maximum medical therapy.

Published
2024
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4. A multilevel mHealth intervention boosts adherence to hydroxyurea in individuals with sickle cell disease

Author

Hankins, Jane S., Brambilla, Donald, Potter, Michael B., Kutlar, Abdullah, Gibson, Robert, King, Allison A., Baumann, Ana A., Melvin, Cathy, Gordeuk, Victor R., Hsu, Lewis L., Nwosu, Chinonyelum, Porter, Jerlym S., Alberts, Nicole M., Badawy, Sherif M., Simon, Jena, Glassberg, Jeffrey A., Lottenberg, Richard, DiMartino, Lisa, Jacobs, Sara, Fernandez, Maria E., Bosworth, Hayden B., Klesges, Lisa M., Shah, Nirmish, Hankins, Jane S., Hodges, Jason, Carroll, Yvonne, Klesges, Lisa, Khan, Hamda, Smeltzer, Matthew, Nwosu, Chinonyelum, Gurney, James, Porter, Jerlym, Alberts, Nicole, French, Reginald, Badawy, Sherif, DeBaun, Michael, Kang, Guolian, Estepp, Jeremie, Wang, Winfred, Owens, Curtis, Debon, Margaret, Osarogiagbon, Ray, Nelson, Marquita, Treadwell, Marsha, Vichinsky, Elliott, Wun, Ted, Potter, Michael, Hessler, Danielle, Hagar, Ward, Marsh, Anne, Neumayr, Lynne, Melvin, Cathy, Kanter, Julie, Phillips, Shannon, Adams, Robert, Mueller, Martina, Abrams, Tina, Davia, Nathalia, Shah, Nirmish, Tanabe, Paula, Bosworth, Hayden, Jackson, George, Johnson, Fred, Richesson, Rachel, Prvu-Bettger, Janet, King, Allison, Baumann, Ana, Calhoun, Cecilia, Kutlar, Abdullah, Gibson, Robert, Snyder, Angie, Fernandez, Maria, Lottenberg, Richard, Richardson, Lynne D., Glassberg, Jeffrey, Simon, Jena, Genes, Nicholas G., Loo, George T., Shapiro, Jason S., Souffront, Kimberly, Clesca, Cindy, Linton, Elizabeth, Ryan, Gery, Kroner, Barbara L, Hendershot, Tabitha, DiMartino, Lisa, Jacobs, Sara, Battestilli, Whitney, Brambilla, Donald, Cox, Lisa, Preiss, Liliana, Pugh, Norma, Li, Sophie, VonLehmden, Annie, Smith, Sharon M, Tonkins, William P., Peters-Lawrence, Marlene, Boyce, Cheryl, Barfield, Whitney, Thompson, Alexis, Gordeuk, Victor, Gutierrez, Melissa, Hirschtick, Jana, Hsu, Lewis, Krishnan, Jerry, Sebro, Nadew, Verda, Larissa, Wandersman, Abe, Berbaum, Michael, Bobba, Kishore, Colla, Joe, Erwin, Kim, Lamont, Andrea, Martin, Molly, Norell, Sarah, Pandit, Ananta, Saving, Kay, Shannon, Robin, Winn, Robert, Zun, Leslie, Hassan, Taif, Lasley, Patricia, Monnard, Kristin, Nocek, Judith, and Roesch, Pamela

Abstract

•Hydroxyurea adherence increased by 19.8% with a tailored mHealth intervention in people with SCD and adherence <80%.•mHealth boosts hydroxyurea adherence and is associated with reduction in self-reported pain and pain admissions rate in SCD.

Published
2023
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5. A feasibility randomized controlled trial of an mHealth app vs booklets for patient-facing guidelines in adults with SCD

Author

Cronin, Robert M., Quaye, Nives, Liu, Xin, Landes, Kristina, Crosby, Lori E., Kassim, Adetola A., Volanakis, Emmanuel J., Schnell, Patrick M., and DeBaun, Michael R.

Abstract

•Adults with SCD will use patient-facing guidelines delivered through an mHealth app.•The results of the trial have implications for improving patient education and reducing hospitalizations for adults with SCD.

Published
2023
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6. Creating an automated contemporaneous cohort in sickle cell anemia to predict survival after disease-modifying therapy

Author

Cronin, Robert M., Wuichet, Kristin, Ghafuri, Djamila L, Hodges, Brock, Chopra, Maya, He, Jing, Niu, Xinnan, Kassim, Adetola A., Wilkerson, Karina, Rodeghier, Mark, and DeBaun, Michael R.

Abstract

•To estimate survival, an automated contemporaneous cohort of children and adults with SCA is feasible and efficient.•Hydroxyurea therapy for at least 1 year is associated with increased survival in adults with SCA compared with no disease-modifying therapy.

Published
2023
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7. Barriers and Facilitators of Premarital Genetic Counseling for Sickle Cell Disease in Northern Nigeria

Author

Galadanci, Aisha A., Estepp, Jeremie H., Khan, Hamda, Farouk, Zubaida L., Caroll, Yvonne, Hodges, Jason, Yarima, Sabiu, Ibrahim, Umma A., Idris, Ibrahim M., Gambo, Awwal, Hussaini, Nafiu, Mukaddas, Aisha, DeBaun, Michael R., and Galadanci, Najibah A.

Abstract

In high-income countries, premarital genetic counseling for Sickle Cell Disease (SCD) is a standard practice. However, in Nigeria, there is no formal premarital genetic counseling program available for SCD. We conducted a series of focus group discussions with health care professionals, patients with SCD, and parents of the patients with or without SCD to gain an understanding of their attitudes and beliefs towards SCD/Sickle Cell Trait and premarital genetic counseling for SCD. Data were analyzed using Charmaz’s constructivist grounded theory approach. Two themes were highlighted in the analysis as follows: (1) the difference between the perception of premarital sickle cell screening among individuals with SCD versus the general population, and (2) the personal beliefs and physical challenges that could lead to the avoidance of premarital screening within the general community. Lack of disease-related knowledge, testing facilities, transportation, and stigma associated with the disease were the most commonly perceived barriers to premarital testing. Also, a willingness to receive premarital testing for SCD exists within our community to reduce the spread of the disease and advocate for improved health-related quality of life of patients with SCD. The content and structure of a premarital genetic counseling program in Kano, Northern Nigeria, needs to be developed.

Published
2023
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9. Defining global strategies to improve outcomes in sickle cell disease: a Lancet HaematologyCommission

Author

Piel, Frédéric B, Rees, David C, DeBaun, Michael R, Nnodu, Obiageli, Ranque, Brigitte, Thompson, Alexis A, Ware, Russell E, Abboud, Miguel R, Abraham, Allistair, Ambrose, Emmanuela E, Andemariam, Biree, Colah, Roshan, Colombatti, Raffaella, Conran, Nicola, Costa, Fernando F, Cronin, Robert M, de Montalembert, Mariane, Elion, Jacques, Esrick, Erica, Greenway, Anthea L, Idris, Ibrahim M, Issom, David-Zacharie, Jain, Dipty, Jordan, Lori C, Kaplan, Zane S, King, Allison A, Lloyd-Puryear, Michele, Oppong, Samuel A, Sharma, Akshay, Sung, Lillian, Tshilolo, Leon, Wilkie, Diana J, and Ohene-Frempong, Kwaku

Published
2023
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10. Underweight children older than 5 years with sickle cell anemia are at risk for early mortality in a low-resource setting

Author

Klein, Lauren J., Abdullahi, Shehu Umar, Gambo, Safiya, Stallings, Virginia A., Acra, Sari, Rodeghier, Mark, and DeBaun, Michael R.

Abstract

•Underweight children aged 5 to 12 years and with SCA are at risk for early death in a low-resource setting.•Weight-for-age z score is a simple measure to screen children older than 5 years with SCA at risk for death in a low-resource setting.

Published
2023
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11. Author Response: Distribution of Silent Cerebral Infarcts in Adults With Sickle Cell Disease

Author

Jordan, Lori C., Jones, R. Sky, Debaun, Michael R., and Ford, Andria L.

Abstract

We thank Dr. Machado for his response to our article.1In his comment, Dr. Machado described a case they observed in which a 15-year-old adolescent patient with sickle cell disease (SCD) presented with a minimally conscious state and severe bilateral internal carotid artery (ICA) vasculopathy resulting in massive bihemispheric strokes.2The related images, available in the published case report, show complete occlusion of the patient's intracranial ICAs.2The patient's history indicated that, from the time they were 1 year, they experienced recurrent clinical strokes with loss of consciousness and right and left hemiparesis and that they achieved partial recovery.

Published
2025
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13. Hydroxyurea for secondary stroke prevention in children with sickle cell anemia in Nigeria: a randomized controlled trial

Author

Abdullahi, Shehu U., Sunusi, Surayya, Abba, Mohammed Sani, Sani, Saifuddeen, Inuwa, Hauwau Aminu, Gambo, Safiya, Gambo, Awwal, Musa, Bilya, Covert Greene, Brittany V., Kassim, Adetola A., Rodeghier, Mark, Hussaini, Nafiu, Ciobanu, Mariana, Aliyu, Muktar H., Jordan, Lori C., and DeBaun, Michael R.

Abstract

•Both low and moderate doses of hydroxyurea are efficacious for secondary stroke prevention in low-resource settings.•The median time between the initial stroke and death was less than a year, 0.8 years (interquartile range, 0.2-0.9).

Published
2023
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14. Epidemiology and treatment of priapism in sickle cell disease

Author

Idris, Ibrahim M., Burnett, Arthur L., and DeBaun, Michael R.

Abstract

Ischemic priapism is a common but underrecognized morbidity affecting about 33% of adult men with sickle cell disease (SCD). The onset of priapism occurs in the prepubertal period and tends to be recurrent with increasing age. Significantly, priapism is associated with an unrecognized high burden of mental duress and sexual dysfunctions. The diagnosis of priapism is clinical. Many episodes of priapism will resolve spontaneously, but when an episode lasts longer than 4 hours, the episode is considered a urologic emergency requiring quick intervention with either corporal aspiration or shunt surgery. Only 3 randomized clinical trials (stilbesterol, ephedrine or etilefrine, and sildenafil) have been conducted for secondary priapism prevention in SCD. All 3 trials were limited with small sample sizes, selection biases, and inconclusive results after completion. The current molecular understanding of the pathobiology of priapism suggests a relative nitric oxide (NO) deficiency secondary to chronic hemolysis in SCD and associated phosphodiesterase type 5 dysregulation. We posit an increase in NO levels will restore the normal homeostatic relationship between voluntary erection and detumescence. Currently, 2 randomized phase 2 trials (1 double-blind, placebo-controlled trial and 1 open-label, single-arm intervention) are being conducted for secondary priapism prevention in men at high risk for recurrent priapism (NCT03938454 and NCT05142254). We review the epidemiology and pathobiology of priapism, along with mechanistic therapeutic approaches for secondary prevention of priapism in SCD.

Published
2022
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15. Acute pain episodes, acute chest syndrome, and pulmonary thromboembolism in pregnancy

Author

Asare, Eugenia Vicky, DeBaun, Michael R., Olayemi, Edeghonghon, Boafor, Theodore, and Oppong, Samuel A.

Abstract

Pregnancy in women with sickle cell disease (SCD) is a life-threatening condition. In both high- and low-income countries, there is an 11-fold increased risk of maternal death and a 4-fold increased risk of perinatal death. We highlight the epidemiology of SCD-specific and obstetric complications commonly seen during pregnancy in SCD and propose definitions for acute pain and acute chest syndrome (ACS) episodes during pregnancy. We conducted a systematic review of the recent obstetric and hematology literature using full research articles published within the last 5 years that reported outcomes in pregnant women with SCD. The prevalence of acute pain episodes during pregnancy ranged between 4% and 75%. The prevalence of ACS episodes during pregnancy ranged between 4% and 13%. The estimated prevalence of pulmonary thromboembolism in women with SCD during pregnancy is approximately 0.5 to 1%. ACS is the most common cause of death and is often preceded by acute pain episodes. The most crucial time to develop these complications in pregnancy is during the third trimester and postpartum period. In a pooled analysis from studies in low- and middle-income settings, maternal death in women with SCD is approximately 2393 and 4300 deaths per 100 000 live births with and without multidisciplinary care, respectively. In comparison, in the US and northern Europe, the general maternal mortality rate is approximately 23.8 and 8 deaths per 100 000 live births, respectively. A multidisciplinary SCD obstetrics care approach reduces maternal and perinatal morbidity and mortality in low- and middle-income countries.

Published
2022
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16. Incidence and predictors of priapism events in sickle cell anemia: a diary-based analysis

Author

Idris, Ibrahim M., Abba, Akib, Galadanci, Jamil A., Aji, Sani A., Jibrilla, Atiku U., Rodeghier, Mark, Kassim, Adetola, Burnett, Arthur L., and DeBaun, Michael R.

Abstract

•Men with SCA and ≥3 priapism events in the prior 12 months have an 80% chance of having a priapism episode within the following 3 months.•The sum of priapism events in 3 months predicted a major priapism event.

Published
2022
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20. Hydroxyurea for primary stroke prevention in children with sickle cell anaemia in Nigeria (SPRING): a double-blind, multicentre, randomised, phase 3 trial

Author

Abdullahi, Shehu U, Jibir, Binta W, Bello-Manga, Halima, Gambo, Safiya, Inuwa, Hauwa, Tijjani, Aliyu G, Idris, Nura, Galadanci, Aisha, Hikima, Mustapha S, Galadanci, Najibah, Borodo, Awwal, Tabari, Abdulkadir M, Haliru, Lawal, Suleiman, Aisha, Ibrahim, Jamila, Greene, Brittany C, Ghafuri, Djamila L, Rodeghier, Mark, Slaughter, James C, Kirkham, Fenella J, Neville, Kathleen, Kassim, Adetola, Trevathan, Edwin, Jordan, Lori C, Aliyu, Muktar H, and DeBaun, Michael R

Abstract

In high-income countries, standard care for primary stroke prevention in children with sickle cell anaemia and abnormal transcranial Doppler velocities results in a 92% relative risk reduction of strokes but mandates initial monthly blood transfusion. In Africa, where regular blood transfusion is not feasible for most children, we tested the hypothesis that initial moderate-dose compared with low-dose hydroxyurea decreases the incidence of strokes for children with abnormal transcranial Doppler velocities.

Published
2022
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21. Psychometric Impact of Priapism on Lives of Adolescents and Adults With Sickle Cell Anemia: A Sequential Independent Mixed-Methods Design

Author

Idris, Ibrahim M., Bonnet, Kemberlee, Schlundt, David, Abba, Akib, Galadanci, Jamil, Burnett, Arthur L., and DeBaun, Michael R.

Abstract

Despite priapism being one of the most frequent complications of sickle cell anemia (SCA) in male individuals, little has been reported about the impact of priapism in this population. The authors used a sequential independent mixed-methods design, which used both international multicenter focus group discussions (n=35) and a quantitative patient-reported outcome measure (n=131) to determine the impact of priapism on men with SCA in Nigeria and the United States. The authors analyzed data from focus groups using an iterative inductive-deductive approach. Comparison of the Priapism Impact Profile data was done using the Kruskal-Wallis H test. Our result showed that priapism, across cultures, is associated with shame and embarrassment. These emotions interfere with timely clinical and family communication about priapism symptoms and complications. Participants were dissatisfied with the quality of care at emergency facilities. The quality of life and physical wellness of men with SCA-related priapism were significantly different for the 3 groups: (1) priapism condition getting better, (2) priapism condition getting worse, and (3) priapism condition remain the same (P=0.002 and P=0.019, respectively). Psychological, sexual, and physical wellbeing are all adversely affected by priapism. Evidence-based methods are necessary for adequate medical, educational, and psychological treatment for recurrent priapism.

Published
2022
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22. Establishing Sickle Cell Disease Stroke Prevention Teams in Africa is Feasible: Program Evaluation Using the RE-AIM Framework

Author

Ghafuri, Djamila L., Abdullahi, Shehu U., Dambatta, Abdu H., Galadanci, Jamil, Tabari, Musa A., Bello-Manga, Halima, Idris, Nura, Inuwa, Hauwa, Tijjani, Aliyu, Suleiman, Aisha A., Jibir, Binta W., Gambo, Safiya, Gambo, Awwal I., Khalifa, Yusuf, Haliru, Lawal, Abdulrasheed, Sani, Zakari, Mohammed A., Greene, Brittany C., Trevathan, Edwin, Jordan, Lori C., Aliyu, Muktar H., Baumann, Ana A., and DeBaun, Michael R.

Abstract

We used the Reach, Effectiveness, Adoption, Implementation, and Maintenance(RE-AIM) framework to evaluate a Stroke Prevention Team’s readiness to prevent strokes in children with sickle cell anemia living in northern Nigeria. The NIH sponsored Stroke Prevention Trial in Nigeria included a goal of a sustainable stroke prevention program. The program’s 1-year reachfor transcranial Doppler screening was 14.7% (4710/32,000) of which 6.0% (281/4710) had abnormal velocities (≥200 cm/s). All participants with abnormal transcranial Doppler velocities were started on hydroxyurea (effectiveness). The leaders of all 5 hospitals agreed to adoptthe program. After 1 year, program-implementationand maintenancerates were 100%, demonstrating the program’s feasibility and short-term sustainability.

Published
2022
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23. Academic Medicine’s Journey Toward Racial Equity Must Be Grounded in History: Recommendations for Becoming an Antiracist Academic Medical Center

Author

Wilkins, Consuelo H., Williams, Mamie, Kaur, Karampreet, and DeBaun, Michael R.

Abstract

The harsh realities of racial inequities related to COVID-19 and civil unrest following police killings of unarmed Black men and women in the United States in 2020 heightened awareness of racial injustices around the world. Racism is deeply embedded in academic medicine, yet the nobility of medicine and nursing has helped health care professionals distance themselves from racism.Vanderbilt University Medical Center (VUMC), like many U.S. academic medical centers, affirmed its commitment to racial equity in summer 2020. A Racial Equity Task Force was charged with identifying barriers to achieving racial equity at the medical center and medical school and recommending key actions to rectify long-standing racial inequities. The task force, composed of students, staff, and faculty, produced more than 60 recommendations, and its work brought to light critical areas that need to be addressed in academic medicine broadly. To dismantle structural racism, academic medicine must: (1) confront medicine’s racist past, which has embedded racial inequities in the U.S. health care system; (2) develop and require health care professionals to possess core competencies in the health impacts of structural racism; (3) recognize race as a sociocultural and political construct, and commit to debiologizing its use; (4) invest in benefits and resources for health care workers in lower-paid roles, in which racial and ethnic minorities are often overrepresented; and (5) commit to antiracism at all levels, including changing institutional policies, starting at the executive leadership level with a vision, metrics, and accountability.

Published
2021
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24. Progressive Silent Cerebral Infarcts Are Prevalent in Adults with Sickle Cell Anemia but Moderate-Severe Cognitive Abnormalities Are Independent of Preexisting Silent Cerebral Infarcts

Author

Idris, Ibrahim Musa, Gwarzo, Dalha H, Iguda, Shamsu, Aminu, Faruk, Hikima, Mustapha Shuaibu, Saleh, Mohammed Kabir, Suwaid, Mohammad Abba, Ibrahim, Aliyu, Ibrahim, Hauwa, Kana, Shehu, Haruna, Rabia Abubakar, Galadanci, Jamil Aliyu, Hussain, Nafiu, Rodeghier, Mark, Hyacinth, Hyacinth I, King, Allison A., and DeBaun, Michael R.

Published
2022
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25. Interim Analysis of a Phase 2 Trial to Assess the Efficacy and Safety of Crizanlizumab in Sickle Cell Disease Patients with Priapism (SPARTAN)

Author

Anderson, Alan, El Rassi, Fuad, DeBaun, Michael R., Idowu, Modupe, Kanter, Julie, Adam, Soheir, Curtis, Susanna, Liles, Darla, Andemariam, Biree, McLemore, Morgan L., Nickel, Robert Sheppard, Ramadas, Poornima, Paulose, Jincy, Laine, Dramane I, Khan, Mahmudul, Darbari, Deepika S., and Burnett, Arthur L.

Published
2022
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27. Rationale and Design of a Randomized Controlled Double-Blind Internal Pilot Trial for Prevention of Recurrent Ischemic Priapism in Men with Sickle Cell Disease (PIN Trial)

Author

Idris, Ibrahim Musa, Yusuf, Aminu Abba, Ismail, Ismail Isa, Borodo, Awwal Musa, Hikima, Mustapha Shuaibu, Kana, Shehu, Aji, Sani A, Kuliya_Gwarzo, Aisha, Kabir, Mohammad, Galadanci, Jamil Aliyu, Alkassim, Rukayya, Hussain, Nafiu, Rodeghier, Mark, Burnett, Aurthur, and DeBaun, Michael R.

Published
2022
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28. Outcomes of Non-Myeloablative HLA-Haploidentical Bone Marrow Transplant with Thiotepa and Post-Transplant Cyclophosphamide in Children and Adults with Sickle Cell Disease, a Phase II Trial: Vanderbilt Global Haploidentical Transplant Learning Collaborative (VGC2)

Author

Kassim, Adetola A., Wilkerson, Karina, de la Fuente, Josu, Seber, Adriana, Gouveia, Roseane V, Bonfim, Carmem, Simões, Belinda Pinto, Nur, Erfan, Horn, Biljana N., Eckrich, Michael, Hanna, Rabi, Dhedin, Nathalie, Almhareb, Fahed, Aljurf, Mahmoud, Rangarajan, Hemalatha G., Gatwood, Katie S., Connelly, James P, Alzahrani, Mohsen, Alahmari, Ali, Rodeghier, Mark, and DeBaun, Michael R.

Published
2022
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29. Leukemia after gene therapy for sickle cell disease: insertional mutagenesis, busulfan, both, or neither

Author

Jones, Richard J. and DeBaun, Michael R.

Abstract

Recently, encouraging data provided long-awaited hope for gene therapy as a cure for sickle cell disease (SCD). Nevertheless, the transient suspension of the bluebird bio gene therapy trial (clinicaltrials.gov: NCT02140554) after participants developed acute myeloid leukemia/myelodysplastic syndrome (AML/MDS) raised concerns. Potential possibilities for these cases include busulfan, insertional mutagenesis, both, or neither. Busulfan was considered the cause in the first reported case because the transgene was not present in the AML/MDS. However, busulfan is unlikely to have contributed to the most recent case. The transgene was present in the patient's malignant cells, indicating they were infused after busulfan treatment. Several lines of evidence suggest an alternative explanation for events in the bluebird bio trial, including that SCD population studies show an increased relative, but a low absolute, risk of AML/MDS. We propose a new hypothesis: after gene therapy for SCD, the stress of switching from homeostatic to regenerative hematopoiesis by transplanted cells drives clonal expansion and leukemogenic transformation of preexisting premalignant clones, eventually resulting in AML/MDS. Evidence validating our hypothesis will support prescreening individuals with SCD for preleukemic progenitors before gene therapy. While presumed viable, safe strategy has been implemented to resume gene therapy in adults with severe SCD, reasonable alternative curative therapy should be considered for children and adults with severe SCD. Currently, open multicenter clinical trials are incorporating nonmyeloablative conditioning, related haploidentical donors, and posttransplantation cyclophosphamide. Preliminary results from these trials appear promising, and National Institutes of Health–sponsored trials are ongoing in individuals with SCD using this platform.

Published
2021
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30. A polygenic score for acute vaso-occlusive pain in pediatric sickle cell disease

Author

Rampersaud, Evadnie, Kang, Guolian, Palmer, Lance E., Rashkin, Sara R., Wang, Shuoguo, Bi, Wenjian, Alberts, Nicole M., Anghelescu, Doralina, Barton, Martha, Birch, Kirby, Boulos, Nidal, Brandow, Amanda M., Brooke, Russell John, Chang, Ti-Cheng, Chen, Wenan, Cheng, Yong, Ding, Juan, Easton, John, Hodges, Jason R., Kanne, Celeste K., Levy, Shawn, Mulder, Heather, Patel, Ashwin P., Puri, Latika, Rosencrance, Celeste, Rusch, Michael, Sapkota, Yadav, Sioson, Edgar, Sharma, Akshay, Tang, Xing, Thrasher, Andrew, Wang, Winfred, Yao, Yu, Yasui, Yutaka, Yergeau, Donald, Hankins, Jane S., Sheehan, Vivien A., Downing, James R., Estepp, Jeremie H., Zhang, Jinghui, DeBaun, Michael, Wu, Gang, and Weiss, Mitchell J.

Abstract

Individuals with monogenic disorders can experience variable phenotypes that are influenced by genetic variation. To investigate this in sickle cell disease (SCD), we performed whole-genome sequencing (WGS) of 722 individuals with hemoglobin HbSS or HbSβ0-thalassemia from Baylor College of Medicine and from the St. Jude Children’s Research Hospital Sickle Cell Clinical Research and Intervention Program (SCCRIP) longitudinal cohort study. We developed pipelines to identify genetic variants that modulate sickle hemoglobin polymerization in red blood cells and combined these with pain-associated variants to build a polygenic score (PGS) for acute vaso-occlusive pain (VOP). Overall, we interrogated the α-thalassemia deletion −α3.7 and 133 candidate single-nucleotide polymorphisms (SNPs) across 66 genes for associations with VOP in 327 SCCRIP participants followed longitudinally over 6 years. Twenty-one SNPs in 9 loci were associated with VOP, including 3 (BCL11A, MYB, and the β-like globin gene cluster) that regulate erythrocyte fetal hemoglobin (HbF) levels and 6 (COMT, TBC1D1, KCNJ6, FAAH, NR3C1, and IL1A) that were associated previously with various pain syndromes. An unweighted PGS integrating all 21 SNPs was associated with the VOP event rate (estimate, 0.35; standard error, 0.04; P = 5.9 × 10−14) and VOP event occurrence (estimate, 0.42; standard error, 0.06; P = 4.1 × 10−13). These associations were stronger than those of any single locus. Our findings provide insights into the genetic modulation of VOP in children with SCD. More generally, we demonstrate the utility of WGS for investigating genetic contributions to the variable expression of SCD-associated morbidities.

Published
2021
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32. Men with sickle cell disease experience greater sexual dysfunction when compared with men without sickle cell disease

Author

Idris, Ibrahim M., Abba, Akib, Galadanci, Jamil A., Mashi, Sharfuddeen A., Hussaini, Nafiu, Gumel, Sagir Ahmed, Burnett, Arthur L., and DeBaun, Michael R.

Abstract

Recurrent ischemic priapism is a common complication of sickle cell disease (SCD). We assessed the burden, characteristics, and types of priapism, including sexual dysfunction, in a cohort of men with and those without SCD, to test the hypothesis that sexual dysfunction is more prevalent in men with SCD. In Kano, Nigeria, we conducted a comparative cross-sectional survey that included 500 and 250 men 18 to 40 years of age, with and without SCD, respectively. The survey used the Priapism Questionnaire and the International Index of Erectile Function for sexual function assessment. All eligible participants approached for the study gave informed consent and were enrolled. Stuttering and major priapism were defined based on the average duration of priapism experiences that lasted ≤4 and >4 hours, respectively. The prevalence of priapism was significantly higher in men with SCD than in those without it (32.6% vs 2%; P < .001). Stuttering priapism accounted for 73.6% of the priapism episodes in men with SCD. Nearly 50% of the participants with SCD-related priapism had never sought medical attention for this complication. The majority of the men with SCD-related priapism used exercise as a coping mechanism. Priapism affected the self-image of the men with SCD, causing sadness, embarrassment, and fear. The percentage of the men with SCD who had erectile dysfunction was more than twofold higher than that of those without SCD who had erectile dysfunction (P = .01). The men with SCD had a higher prevalence of priapism and sexual dysfunction than the men without SCD.

Published
2020
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33. Risk for postterm delivery after previous postterm delivery

Author

Kistka, Zachary A.-F., Palomar, Lisanne, Boslaugh, Sarah E., DeBaun, Michael R., DeFranco, Emily A., and Muglia, Louis J.

Subjects
Health
Abstract

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ajog.2006.10.873 Byline: Zachary A.-F. Kistka, Lisanne Palomar, Sarah E. Boslaugh, Michael R. DeBaun, Emily A. DeFranco, Louis J. Muglia Keywords: birth timing; parturition; population-based cohort; postterm birth Abstract: We examined the hypothesis that the risk for subsequent postterm birth is increased in women with an initial postterm birth. Author Affiliation: Washington University School of Medicine, Center for Preterm Birth Research, Departments of Pediatrics and Obstetrics and Gynecology, and St Louis Children's Hospital, St Louis, MO. Article Note: (footnote) Supported by grants from the March of Dimes (Dr Muglia), Doris Duke Clinical Research Fellowship (Mr Kistka), and Howard Hughes Medical Institute (Ms Palomar). Cite this article as: Kistka ZA-F, Palomar L, Boslaugh SE, DeBaun MR, DeFranco EA, Muglis LJ. Risk for postterm delivery after previous postterm delivery. Am J Obstet Gynecol 2007;196:241.e1-241.e6.

Published
2007

34. Phase 2 trial of montelukast for prevention of pain in sickle cell disease

Author

Field, Joshua J., Kassim, Adetola, Brandow, Amanda, Embury, Stephen H., Matsui, Neil, Wilkerson, Karina, Bryant, Valencia, Zhang, Liyun, Simpson, Pippa, and DeBaun, Michael R.

Abstract

Cysteinyl leukotrienes (CysLTs) are lipid mediators of inflammation. In patients with sickle cell disease (SCD), levels of CysLTs are increased compared with controls and associated with a higher rate of hospitalization for pain. We tested the hypothesis that administration of the CysLT receptor antagonist montelukast would improve SCD-related comorbidities, including pain, in adolescents and adults with SCD. In a phase 2 randomized trial, we administered montelukast or placebo for 8 weeks. The primary outcome measure was a >30% reduction in soluble vascular cell adhesion molecule 1 (sVCAM), a marker of vascular injury. Secondary outcome measures were reduction in daily pain, improvement in pulmonary function, and improvement in microvascular blood flow, as measured by laser Doppler velocimetry. Forty-two participants with SCD were randomized to receive montelukast or placebo for 8 weeks. We found no difference between the montelukast and placebo groups with regard to the levels of sVCAM, reported pain, pulmonary function, or microvascular blood flow. Although montelukast is an effective treatment for asthma, we did not find benefit for SCD-related outcomes. This clinical trial was registered at www.clinicaltrials.govas #NCT01960413.

Published
2020
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35. End points for sickle cell disease clinical trials: patient-reported outcomes, pain, and the brain

Author

Farrell, Ann T., Panepinto, Julie, Carroll, C. Patrick, Darbari, Deepika S., Desai, Ankit A., King, Allison A., Adams, Robert J., Barber, Tabitha D., Brandow, Amanda M., DeBaun, Michael R., Donahue, Manus J., Gupta, Kalpna, Hankins, Jane S., Kameka, Michelle, Kirkham, Fenella J., Luksenburg, Harvey, Miller, Shirley, Oneal, Patricia Ann, Rees, David C., Setse, Rosanna, Sheehan, Vivien A., Strouse, John, Stucky, Cheryl L., Werner, Ellen M., Wood, John C., and Zempsky, William T.

Abstract

To address the global burden of sickle cell disease (SCD) and the need for novel therapies, the American Society of Hematology partnered with the US Food and Drug Administration to engage the work of 7 panels of clinicians, investigators, and patients to develop consensus recommendations for clinical trial end points. The panels conducted their work through literature reviews, assessment of available evidence, and expert judgment focusing on end points related to: patient-reported outcomes (PROs), pain (non-PROs), the brain, end-organ considerations, biomarkers, measurement of cure, and low-resource settings. This article presents the findings and recommendations of the PROs, pain, and brain panels, as well as relevant findings and recommendations from the biomarkers panel. The panels identify end points, where there were supporting data, to use in clinical trials of SCD. In addition, the panels discuss where further research is needed to support the development and validation of additional clinical trial end points.

Published
2019
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36. 2019 sickle cell disease guidelines by the American Society of Hematology: methodology, challenges, and innovations

Author

Murad, M. Hassan, Liem, Robert I., Lang, Eddy S., Akl, Elie A., Meerpohl, Joerg J., DeBaun, Michael R., Tisdale, John F., Brandow, Amanda M., Lanzkron, Sophie M., Chou, Stella T., Webb, Starr, and Mustafa, Reem A.

Abstract

The American Society of Hematology (ASH) convened 5 guideline panels to develop clinical practice recommendations addressing 5 management areas of highest importance to individuals living with sickle cell disease: pain, cerebrovascular complications, pulmonary and kidney complications, transfusion, and hematopoietic stem cell transplant. Panels were multidisciplinary and consisted of patient representatives, content experts, and methodologists. The Mayo Clinic Evidence-Based Practice Center conducted systematic reviews based on a priori selected questions. In this exposition, we describe the process used by ASH, including the GRADE approach (Grades of Recommendations, Assessment, Development and Evaluation) for rating certainty of the evidence and the GRADE Evidence to Decision Framework. We also describe several unique challenges faced by the guideline panels and the specific innovations and solutions used to address them, including a curriculum to train patients to engage in guideline development, dealing with the opioid crisis, and working with indirect and noncomparative evidence.

Published
2019
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37. Whole Genome Sequencing Identifies CRISPLD2as a Lung Function Gene in Children With Asthma

Author

Kachroo, Priyadarshini, Hecker, Julian, Chawes, Bo L., Ahluwalia, Tarunveer S., Cho, Michael H., Qiao, Dandi, Kelly, Rachel S., Chu, Su H., Virkud, Yamini V., Huang, Mengna, Barnes, Kathleen C., Burchard, Esteban G., Eng, Celeste, Hu, Donglei, Celedón, Juan C., Daya, Michelle, Levin, Albert M., Gui, Hongsheng, Williams, L. Keoki, Forno, Erick, Mak, Angel C.Y., Avila, Lydiana, Soto-Quiros, Manuel E., Cloutier, Michelle M., Acosta-Pérez, Edna, Canino, Glorisa, Bønnelykke, Klaus, Bisgaard, Hans, Raby, Benjamin A., Lange, Christoph, Weiss, Scott T., Lasky-Su, Jessica A., Abe, Namiko, Abecasis, Goncalo, Albert, Christine, Palmer Allred, Nicholette (Nichole), Almasy, Laura, Alonso, Alvaro, Ament, Seth, Anderson, Peter, Anugu, Pramod, Applebaum-Bowden, Deborah, Arking, Dan, Arnett, Donna K., Ashley-Koch, Allison, Aslibekyan, Stella, Assimes, Tim, Auer, Paul, Avramopoulos, Dimitrios, Barnard, John, Barnes, Kathleen, Barr, R. Graham, Barron-Casella, Emily, Beaty, Terri, Becker, Diane, Becker, Lewis, Beer, Rebecca, Begum, Ferdouse, Beitelshees, Amber, Benjamin, Emelia, Bezerra, Marcos, Bielak, Larry, Bis, Joshua, Blackwell, Thomas, Blangero, John, Boerwinkle, Eric, Borecki, Ingrid, Bowler, Russell, Brody, Jennifer, Broeckel, Ulrich, Broome, Jai, Bunting, Karen, Burchard, Esteban, Cardwell, Jonathan, Carty, Cara, Casaburi, Richard, Casella, James, Chaffin, Mark, Chang, Christy, Chasman, Daniel, Chavan, Sameer, Chen, Bo-Juen, Chen, Wei-Min, Chen, Yii-Der Ida, Cho, Michael H., Choi, Seung Hoan, Chuang, Lee-Ming, Chung, Mina, Cornell, Elaine, Correa, Adolfo, Crandall, Carolyn, Crapo, James, Cupples, L. Adrienne, Curran, Joanne, Curtis, Jeffrey, Custer, Brian, Damcott, Coleen, Darbar, Dawood, Das, Sayantan, David, Sean, Davis, Colleen, Daya, Michelle, de Andrade, Mariza, DeBaun, Michael, Deka, Ranjan, DeMeo, Dawn, Devine, Scott, Do, Ron, Duan, Qing, Duggirala, Ravi, Durda, Peter, Dutcher, Susan, Eaton, Charles, Ekunwe, Lynette, Ellinor, Patrick, Emery, Leslie, Farber, Charles, Farnam, Leanna, Fingerlin, Tasha, Flickinger, Matthew, Fornage, Myriam, Franceschini, Nora, Fu, Mao, Fullerton, Stephanie M., Fulton, Lucinda, Gabriel, Stacey, Gan, Weiniu, Gao, Yan, Gass, Margery, Gelb, Bruce, Geng, Xiaoqi (Priscilla), Germer, Soren, Gignoux, Chris, Gladwin, Mark, Glahn, David, Gogarten, Stephanie, Gong, Da-Wei, Goring, Harald, Gu, C. Charles, Guan, Yue, Guo, Xiuqing, Haessler, Jeff, Hall, Michael, Harris, Daniel, Hawley, Nicola, He, Jiang, Heavner, Ben, Heckbert, Susan, Hernandez, Ryan, Herrington, David, Hersh, Craig, Hidalgo, Bertha, Hixson, James, Hokanson, John, Holly, Kramer, Hong, Elliott, Hoth, Karin, (Agnes) Hsiung, Chao, Huston, Haley, Hwu, Chii Min, Irvin, Marguerite Ryan, Jackson, Rebecca, Jain, Deepti, Jaquish, Cashell, Jhun, Min A., Johnsen, Jill, Johnson, Andrew, Johnson, Craig, Johnston, Rich, Jones, Kimberly, Kachroo, Priyadarshini, Kang, Hyun Min, Kaplan, Robert, Kardia, Sharon, Kathiresan, Sekar, Kaufman, Laura, Kelly, Shannon, Kenny, Eimear, Kessler, Michael, Khan, Alyna, Kinney, Greg, Konkle, Barbara, Kooperberg, Charles, Krauter, Stephanie, Lange, Christoph, Lange, Ethan, Lange, Leslie, Laurie, Cathy, Laurie, Cecelia, LeBoff, Meryl, Lee, Seunggeun Shawn, Lee, Wen-Jane, LeFaive, Jonathon, Levine, David, Levy, Dan, Lewis, Joshua, Li, Yun, Lin, Honghuang, Lin, Keng Han, Liu, Simin, Liu, Yongmei, Loos, Ruth, Lubitz, Steven, Lunetta, Kathryn, Luo, James, Mahaney, Michael, Make, Barry, Manichaikul, Ani, Manson, JoAnn, Margolin, Lauren, Martin, Lisa, Mathai, Susan, Mathias, Rasika, McArdle, Patrick, McDonald, Merry-Lynn, McFarland, Sean, McGarvey, Stephen, Mei, Hao, Meyers, Deborah A., Mikulla, Julie, Min, Nancy, Minear, Mollie, Minster, Ryan L., Mitchell, Braxton, Montasser, May E., Musani, Solomon, Mwasongwe, Stanford, Mychaleckyj, Josyf C., Nadkarni, Girish, Naik, Rakhi, Natarajan, Pradeep, Nekhai, Sergei, Nickerson, Deborah, North, Kari, O'Connell, Jeff, O'Connor, Tim, Ochs-Balcom, Heather, Pankow, James, Papanicolaou, George, Parker, Margaret, Parsa, Afshin, Penchev, Sara, Peralta, Juan Manuel, Perez, Marco, Perry, James, Peters, Ulrike, Peyser, Patricia, Phillips, Lawrence S., Phillips, Sam, Pollin, Toni, Post, Wendy, Becker, Julia Powers, Boorgula, Meher Preethi, Preuss, Michael, Prokopenko, Dmitry, Psaty, Bruce, Qasba, Pankaj, Qiao, Dandi, Qin, Zhaohui, Rafaels, Nicholas, Raffield, Laura, Ramachandran, Vasan, Rao, D.C., Rasmussen-Torvik, Laura, Ratan, Aakrosh, Redline, Susan, Reed, Robert, Regan, Elizabeth, Reiner, Alex, Rice, Ken, Rich, Stephen, Roden, Dan, Roselli, Carolina, Rotter, Jerome, Ruczinski, Ingo, Russell, Pamela, Ruuska, Sarah, Ryan, Kathleen, Sakornsakolpat, Phuwanat, Salimi, Shabnam, Salzberg, Steven, Sandow, Kevin, Sankaran, Vijay, Scheller, Christopher, Schmidt, Ellen, Schwander, Karen, Schwartz, David, Sciurba, Frank, Seidman, Christine, Seidman, Jonathan, Sheehan, Vivien, Shetty, Amol, Shetty, Aniket, Sheu, Wayne Hui-Heng, Shoemaker, M. Benjamin, Silver, Brian, Silverman, Edwin, Smith, Jennifer, Smith, Josh, Smith, Nicholas, Smith, Tanja, Smoller, Sylvia, Snively, Beverly, Sofer, Tamar, Sotoodehnia, Nona, Stilp, Adrienne, Streeten, Elizabeth, Sung, Yun Ju, Su-Lasky, Jessica, Sylvia, Jody, Szpiro, Adam, Sztalryd, Carole, Taliun, Daniel, Tang, Hua, Taub, Margaret, Taylor, Kent, Taylor, Simeon, Telen, Marilyn, Thornton, Timothy A., Tinker, Lesley, Tirschwell, David, Tiwari, Hemant, Tracy, Russell, Tsai, Michael, Vaidya, Dhananjay, VandeHaar, Peter, Vrieze, Scott, Walker, Tarik, Wallace, Robert, Walts, Avram, Wan, Emily, Wang, Fei Fei, Watson, Karol, Weeks, Daniel E., Weir, Bruce, Weiss, Scott, Weng, Lu-Chen, Willer, Cristen, Williams, Kayleen, Williams, L. Keoki, Wilson, Carla, Wilson, James, Wong, Quenna, Xu, Huichun, Yanek, Lisa, Yang, Ivana, Yang, Rongze, Zaghloul, Norann, Zekavat, Maryam, Zhang, Yingze, Zhao, Snow Xueyan, Zhao, Wei, Zheng, Xiuwen, Zhi, Degui, Zhou, Xiang, Zody, Michael, and Zoellner, Sebastian

Abstract

Asthma is a common respiratory disorder with a highly heterogeneous nature that remains poorly understood. The objective was to use whole genome sequencing (WGS) data to identify regions of common genetic variation contributing to lung function in individuals with a diagnosis of asthma.

Published
2019
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38. Is allogeneic transplantation for sickle cell disease still relevant in the era of gene therapy?

Author

Jones, Richard J., Kassim, Adetola A., Brodsky, Robert A., and DeBaun, Michael R.

Abstract

Sickle cell disease (SCD) is the most common inherited blood disease. Disease-modifying therapy and supportive care have improved the survival of children with SCD in the United States and Europe. Yet, adults with SCD continue to have high risks of morbidity and early death. Recently, 2 US Food and Drug Administration–approved genetic therapies offer the potential for a short-term decrease in acute vaso-occlusive pain events if not cure. Allogeneic hematopoietic cell transplantation (allo-HCT) is also curative but, until recently, was constrained by limited donor availability and the risks of graft-versus-host disease, graft rejection, and death. Importantly, recent advances have attenuated these barriers. Here, we discuss the current state of therapies with curative intent for SCD. Both genetic therapy and allo-HCT offer the potential for cure for most with SCD. However, the cost (∼5 times higher), the current need for myeloablation, and associated late-health effects may make genetic therapies less favorable choices than allo-HCT.

Published
2024
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39. The use of abstract animations and a graphical body image for assessing pain outcomes among adults with sickle cell disease

Author

O’Brien, Julia A., Jonassaint, Charles R., Parchuri, Ektha, Lalama, Christina M., Badawy, Sherif M., Hamm, Megan E., Stinson, Jennifer N., Lalloo, Chitra, Carroll, C. Patrick, Saraf, Santosh L., Gordeuk, Victor R., Cronin, Robert M., Shah, Nirmish, Lanzkron, Sophie M., Liles, Darla, Trimnell, Cassandra, Bailey, Lakiea, Lawrence, Raymona, Jean, Leshana Saint, DeBaun, Michael, De Castro, Laura M., Palermo, Tonya M., and Abebe, Kaleab Z.

Abstract

Painimation, a novel digital pain assessment tool, allows patients to communicate their pain quality, intensity, and location using abstract animations and a paintable body image. This study determined the construct validity of pain animations and body image measures by testing correlations with validated pain outcomes in adults with sickle cell disease (SCD). Analyses used baseline data from a multisite randomized trial of 359 adults with SCD and chronic pain. Participants completed questionnaires on demographics, pain severity, frequency and interference, catastrophizing, opioid use, mood and quality of life, plus the Painimation app. Participants were categorized by selected pain animations, and were split into groups based on the proportion of painted body image. The “shooting” pain animation and greater body image scores associated with poorer pain outcomes in univariate analyses, except “happy” mood days. Potential confounding was evaluated by age, gender, race, education, disability, site, depression, and anxiety. Only depression scores significantly covaried in multivariate models, accounting for the effect of greater body image score and shooting animation on all outcomes except daily pain intensity. Both pain animations and body image measures correlated with validated pain outcomes, quality of life and mental health measures. This demonstrates animations and body image data can assess SCD pain severity, potentially with more accuracy than a 0-10 scale. In exploratory analyses, depression scores accounted for the association between Painimation and other pain outcomes. Future research will explore whether Painimation can differentiate biological and psychosocial pain components.

Published
2024
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41. An international learning collaborative phase 2 trial for haploidentical bone marrow transplant in sickle cell disease

Author

Kassim, Adetola A., de la Fuente, Josu, Nur, Erfan, Wilkerson, Karina L., Alahmari, Ali D., Seber, Adriana, Bonfim, Carmem, Simões, Belinda Pinto, Alzahrani, Mohsen, Eckrich, Michael J., Horn, Biljana, Hanna, Rabi, Dhedin, Nathalie, Rangarajan, Hemalatha G., Gouveia, Roseane Vasconcelos, Almohareb, Fahad, Aljurf, Mahmoud, Essa, Mohammed, Alahmari, Bader, Gatwood, Katie, Connelly, James A., Dovern, Elisabeth, Rodeghier, Mark, and DeBaun, Michael R.

Abstract

•For most adults with sickle cell disease, haploidentical BMT with thiotepa + PTCy is now a widely available option with limited BMT–related mortality and morbidity.•For children, haploidentical BMT with thiotepa + PTCy requires additional strategies to decrease graft failure rates.

Published
2024
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42. A genetic-association study of circulating coagulation factor VIII and von Willebrand factor levels

Author

de Vries, Paul S., Reventun, Paula, Brown, Michael R., Heath, Adam S., Huffman, Jennifer E., Le, Ngoc-Quynh, Bebo, Allison, Brody, Jennifer A., Temprano-Sagrera, Gerard, Raffield, Laura M., Ozel, Ayse Bilge, Thibord, Florian, Jain, Deepti, Lewis, Joshua P., Rodriguez, Benjmain A. T., Pankratz, Nathan, Taylor, Kent D., Polasek, Ozren, Chen, Ming-Huei, Yanek, Lisa R., Carrasquilla, German D., Marioni, Riccardo E., Kleber, Marcus E., Trégouët, David-Alexandre, Yao, Jie, Li-Gao, Ruifang, Joshi, Peter K., Trompet, Stella, Martinez-Perez, Angel, Ghanbari, Mohsen, Howard, Tom E., Reiner, Alex P., Arvanitis, Marios, Ryan, Kathleen A., Bartz, Traci M., Rudan, Igor, Faraday, Nauder, Linneberg, Allan, Ekunwe, Lynette, Davies, Gail, Delgado, Graciela E., Suchon, Pierre, Guo, Xiuqing, Rosendaal, Frits R., Klaric, Lucija, Noordam, Raymond, van Rooij, Frank, Curran, Joanne E., Wheeler, Marsha M., Osburn, William O., O'Connell, Jeffrey R., Boerwinkle, Eric, Beswick, Andrew, Psaty, Bruce M., Kolcic, Ivana, Souto, Juan Carlos, Becker, Lewis C., Hansen, Torben, Doyle, Margaret F., Harris, Sarah E., Moissl, Angela P., Deleuze, Jean-François, Rich, Stephen S., van Hylckama Vlieg, Astrid, Campbell, Harry, Stott, David J., Soria, Jose Manuel, de Maat, Moniek P. M., Almasy, Laura, Brody, Lawrence C., Auer, Paul L., Abe, Namiko, Abecasis, Gonçalo, Aguet, Francois, Albert, Christine, Almasy, Laura, Alonso, Alvaro, Ament, Seth, Anderson, Peter, Anugu, Pramod, Applebaum-Bowden, Deborah, Ardlie, Kristin, Arking, Dan, Arnett, Donna K, Ashley-Koch, Allison, Aslibekyan, Stella, Assimes, Tim, Auer, Paul, Avramopoulos, Dimitrios, Ayas, Najib, Balasubramanian, Adithya, Barnard, John, Barnes, Kathleen, Barr, R. Graham, Barron-Casella, Emily, Barwick, Lucas, Beaty, Terri, Beck, Gerald, Becker, Diane, Becker, Lewis, Beer, Rebecca, Beitelshees, Amber, Benjamin, Emelia, Benos, Takis, Bezerra, Marcos, Bielak, Larry, Bis, Joshua, Blackwell, Thomas, Blangero, John, Blue, Nathan, Boerwinkle, Eric, Bowden, Donald W., Bowler, Russell, Brody, Jennifer, Broeckel, Ulrich, Broome, Jai, Brown, Deborah, Bunting, Karen, Burchard, Esteban, Bustamante, Carlos, Buth, Erin, Cade, Brian, Cardwell, Jonathan, Carey, Vincent, Carrier, Julie, Carson, April P., Carty, Cara, Casaburi, Richard, Casas Romero, Juan P, Casella, James, Castaldi, Peter, Chaffin, Mark, Chang, Christy, Chang, Yi-Cheng, Chasman, Daniel, Chavan, Sameer, Chen, Bo-Juen, Chen, Wei-Min, Ida Chen, Yii-Der, Cho, Michael, Choi, Seung Hoan, Chuang, Lee-Ming, Chung, Mina, Chung, Ren-Hua, Clish, Clary, Comhair, Suzy, Conomos, Matthew, Cornell, Elaine, Correa, Adolfo, Crandall, Carolyn, Crapo, James, Cupples, L. Adrienne, Curran, Joanne, Curtis, Jeffrey, Custer, Brian, Damcott, Coleen, Darbar, Dawood, David, Sean, Davis, Colleen, Daya, Michelle, de Andrade, Mariza, de las Fuentes, Lisa, de Vries, Paul, DeBaun, Michael, Deka, Ranjan, DeMeo, Dawn, Devine, Scott, Dinh, Huyen, Doddapaneni, Harsha, Duan, Qing, Dugan-Perez, Shannon, Duggirala, Ravi, Durda, Jon Peter, Dutcher, Susan K., Eaton, Charles, Ekunwe, Lynette, El Boueiz, Adel, Ellinor, Patrick, Emery, Leslie, Erzurum, Serpil, Farber, Charles, Farek, Jesse, Fingerlin, Tasha, Flickinger, Matthew, Fornage, Myriam, Franceschini, Nora, Frazar, Chris, Fu, Mao, Fullerton, Stephanie M., Fulton, Lucinda, Gabriel, Stacey, Gan, Weiniu, Gao, Shanshan, Gao, Yan, Gass, Margery, Geiger, Heather, Gelb, Bruce, Geraci, Mark, Germer, Soren, Gerszten, Robert, Ghosh, Auyon, Gibbs, Richard, Gignoux, Chris, Gladwin, Mark, Glahn, David, Gogarten, Stephanie, Gong, Da-Wei, Goring, Harald, Graw, Sharon, Gray, Kathryn J., Grine, Daniel, Gross, Colin, Gu, C. Charles, Guan, Yue, Guo, Xiuqing, Gupta, Namrata, Haessler, Jeff, Hall, Michael, Han, Yi, Hanly, Patrick, Harris, Daniel, Hawley, Nicola L., He, Jiang, Heavner, Ben, Heckbert, Susan, Hernandez, Ryan, Herrington, David, Hersh, Craig, Hidalgo, Bertha, Hixson, James, Hobbs, Brian, Hokanson, John, Hong, Elliott, Hoth, Karin, Hsiung, Chao (Agnes), Hu, Jianhong, Hung, Yi-Jen, Huston, Haley, Hwu, Chii Min, Irvin, Marguerite Ryan, Jackson, Rebecca, Jain, Deepti, Jaquish, Cashell, Johnsen, Jill, Johnson, Andrew, Johnson, Craig, Johnston, Rich, Jones, Kimberly, Kang, Hyun Min, Kaplan, Robert, Kardia, Sharon, Kelly, Shannon, Kenny, Eimear, Kessler, Michael, Khan, Alyna, Khan, Ziad, Kim, Wonji, Kimoff, John, Kinney, Greg, Konkle, Barbara, Kooperberg, Charles, Kramer, Holly, Lange, Christoph, Lange, Ethan, Lange, Leslie, Laurie, Cathy, Laurie, Cecelia, LeBoff, Meryl, Lee, Jiwon, Lee, Sandra, Lee, Wen-Jane, LeFaive, Jonathon, Levine, David, Levy, Dan, Lewis, Joshua, Li, Xiaohui, Li, Yun, Lin, Henry, Lin, Honghuang, Lin, Xihong, Liu, Simin, Liu, Yongmei, Liu, Yu, Loos, Ruth J. F., Lubitz, Steven, Lunetta, Kathryn, Luo, James, Magalang, Ulysses, Mahaney, Michael, Make, Barry, Manichaikul, Ani, Manning, Alisa, Manson, JoAnn, Martin, Lisa, Marton, Melissa, Mathai, Susan, Mathias, Rasika, May, Susanne, McArdle, Patrick, McDonald, Merry-Lynn, McFarland, Sean, McGarvey, Stephen, McGoldrick, Daniel, McHugh, Caitlin, McNeil, Becky, Mei, Hao, Meigs, James, Menon, Vipin, Mestroni, Luisa, Metcalf, Ginger, Meyers, Deborah A, Mignot, Emmanuel, Mikulla, Julie, Min, Nancy, Minear, Mollie, Minster, Ryan L, Mitchell, Braxton D., Moll, Matt, Momin, Zeineen, Montasser, May E., Montgomery, Courtney, Muzny, Donna, Mychaleckyj, Josyf C, Nadkarni, Girish, Naik, Rakhi, Naseri, Take, Natarajan, Pradeep, Nekhai, Sergei, Nelson, Sarah C., Neltner, Bonnie, Nessner, Caitlin, Nickerson, Deborah, Nkechinyere, Osuji, North, Kari, O'Connell, Jeff, O'Connor, Tim, Ochs-Balcom, Heather, Okwuonu, Geoffrey, Pack, Allan, Paik, David T., Palmer, Nicholette, Pankow, James, Papanicolaou, George, Parker, Cora, Peloso, Gina, Peralta, Juan Manuel, Perez, Marco, Perry, James, Peters, Ulrike, Peyser, Patricia, Phillips, Lawrence S, Pleiness, Jacob, Pollin, Toni, Post, Wendy, Becker, Julia Powers, Boorgula, Meher Preethi, Preuss, Michael, Psaty, Bruce, Qasba, Pankaj, Qiao, Dandi, Qin, Zhaohui, Rafaels, Nicholas, Raffield, Laura, Rajendran, Mahitha, Ramachandran, Vasan S., Rao, D. C., Rasmussen-Torvik, Laura, Ratan, Aakrosh, Redline, Susan, Reed, Robert, Reeves, Catherine, Regan, Elizabeth, Reiner, Alex, Reupena, Muagututi‘a Sefuiva, Rice, Ken, Rich, Stephen, Robillard, Rebecca, Robine, Nicolas, Roden, Dan, Roselli, Carolina, Rotter, Jerome, Ruczinski, Ingo, Runnels, Alexi, Russell, Pamela, Ruuska, Sarah, Ryan, Kathleen, Sabino, Ester Cerdeira, Saleheen, Danish, Salimi, Shabnam, Salvi, Sejal, Salzberg, Steven, Sandow, Kevin, Sankaran, Vijay G., Santibanez, Jireh, Schwander, Karen, Schwartz, David, Sciurba, Frank, Seidman, Christine, Seidman, Jonathan, Sériès, Frédéric, Sheehan, Vivien, Sherman, Stephanie L., Shetty, Amol, Shetty, Aniket, Hui-Heng Sheu, Wayne, Shoemaker, M. Benjamin, Silver, Brian, Silverman, Edwin, Skomro, Robert, Smith, Albert Vernon, Smith, Jennifer, Smith, Josh, Smith, Nicholas, Smith, Tanja, Smoller, Sylvia, Snively, Beverly, Snyder, Michael, Sofer, Tamar, Sotoodehnia, Nona, Stilp, Adrienne M., Storm, Garrett, Streeten, Elizabeth, Su, Jessica Lasky, Sung, Yun Ju, Sylvia, Jody, Szpiro, Adam, Taliun, Daniel, Tang, Hua, Taub, Margaret, Taylor, Kent D., Taylor, Matthew, Taylor, Simeon, Telen, Marilyn, Thornton, Timothy A., Threlkeld, Machiko, Tinker, Lesley, Tirschwell, David, Tishkoff, Sarah, Tiwari, Hemant, Tong, Catherine, Tracy, Russell, Tsai, Michael, Vaidya, Dhananjay, Van Den Berg, David, VandeHaar, Peter, Vrieze, Scott, Walker, Tarik, Wallace, Robert, Walts, Avram, Wang, Fei Fei, Wang, Heming, Wang, Jiongming, Watson, Karol, Watt, Jennifer, Weeks, Daniel E., Weinstock, Joshua, Weir, Bruce, Weiss, Scott T, Weng, Lu-Chen, Wessel, Jennifer, Willer, Cristen, Williams, Kayleen, Williams, L. Keoki, Wilson, Carla, Wilson, James, Winterkorn, Lara, Wong, Quenna, Wu, Joseph, Xu, Huichun, Yanek, Lisa, Yang, Ivana, Yu, Ketian, Zekavat, Seyedeh Maryam, Zhang, Yingze, Zhao, Snow Xueyan, Zhao, Wei, Zhu, Xiaofeng, Ziv, Elad, Zody, Michael, Zoellner, Sebastian, Lindstrom, Sara, Wang, Lu, Smith, Erin N., Gordon, William, van Hylckama Vlieg, Astrid, de Andrade, Mariza, Brody, Jennifer A., Pattee, Jack W., Haessler, Jeffrey, Brumpton, Ben M., Chasman, Daniel I., Suchon, Pierre, Chen, Ming-Huei, Turman, Constance, Germain, Marine, Wiggins, Kerri L., MacDonald, James, Braekkan, Sigrid K., Armasu, Sebastian M., Pankratz, Nathan, Jackson, Rabecca D., Nielsen, Jonas B., Giulianini, Franco, Puurunen, Marja K., Ibrahim, Manal, Heckbert, Susan R., Bammler, Theo K., Frazer, Kelly A., McCauley, Bryan M., Taylor, Kent, Pankow, James S., Reiner, Alexander P., Gabrielsen, Maiken E., Deleuze, Jean-François, O'Donnell, Chris J., Kim, Jihye, McKnight, Barbara, Kraft, Peter, Hansen, John-Bjarne, Rosendaal, Frits R., Heit, John A., Psaty, Bruce M., Tang, Weihong, Kooperberg, Charles, Hveem, Kristian, Ridker, Paul M., Morange, Pierre-Emmanuel, Johnson, Andrew D., Kabrhel, Christopher, AlexandreTrégouët, David, Smith, Nicholas L., Mitchell, Braxton D., Ben-Shlomo, Yoav, Fornage, Myriam, Hayward, Caroline, Mathias, Rasika A., Kilpeläinen, Tuomas O., Lange, Leslie A., Cox, Simon R., März, Winfried, Morange, Pierre-Emmanuel, Rotter, Jerome I., Mook-Kanamori, Dennis O., Wilson, James F., van der Harst, Pim, Jukema, J. Wouter, Ikram, M. Arfan, Blangero, John, Kooperberg, Charles, Desch, Karl C., Johnson, Andrew D., Sabater-Lleal, Maria, Lowenstein, Charles J., Smith, Nicholas L., and Morrison, Alanna C.

Abstract

•We identified 7 new genetic regions for factor VIII levels, 1 for von Willebrand factor levels, and 3 in a combined analysis.•Silencing B3GNT2and CD36reduced factor VIII release in vitro.Silencing B3GNT2, CD36, and PDIA3reduced von Willebrand factor release.

Published
2024
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45. Silent infarcts in sickle cell disease occur in the border zone region and are associated with low cerebral blood flow

Author

Ford, Andria L., Ragan, Dustin K., Fellah, Slim, Binkley, Michael M., Fields, Melanie E., Guilliams, Kristin P., An, Hongyu, Jordan, Lori C., McKinstry, Robert C., Lee, Jin-Moo, and DeBaun, Michael R.

Abstract

Silent cerebral infarcts (SCIs) are associated with cognitive impairment in sickle cell anemia (SCA). SCI risk factors include low hemoglobin and elevated systolic blood pressure; however, mechanisms underlying their development are unclear. Using the largest prospective study evaluating SCIs in pediatric SCA, we identified brain regions with increased SCI density. We tested the hypothesis that infarct density is greatest within regions in which cerebral blood flow is lowest, further restricting cerebral oxygen delivery in the setting of chronic anemia. Neuroradiology and neurology committees reached a consensus of SCIs in 286 children in the Silent Infarct Transfusion (SIT) Trial. Each infarct was outlined and coregistered to a brain atlas to create an infarct density map. To evaluate cerebral blood flow as a function of infarct density, pseudocontinuous arterial spin labeling was performed in an independent pediatric SCA cohort. Blood flow maps were aligned to the SIT Trial infarct density map. Mean blood flow within low, moderate, and high infarct density regions from the SIT Trial were compared. Logistic regression evaluated clinical and imaging predictors of overt stroke at 3-year follow-up. The SIT Trial infarct density map revealed increased SCI density in the deep white matter of the frontal and parietal lobes. A relatively small region, measuring 5.6% of brain volume, encompassed SCIs from 90% of children. Cerebral blood flow was lowest in the region of highest infarct density (P < .001). Baseline infarct volume and reticulocyte count predicted overt stroke. In pediatric SCA, SCIs are symmetrically located in the deep white matter where minimum cerebral blood flow occurs.

Published
2018
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46. An APOOPseudogene on Chromosome 5q Is Associated With Low-Density Lipoprotein Cholesterol Levels

Author

Montasser, May E., O’Hare, Elizabeth A., Wang, Xiaochun, Howard, Alicia D., McFarland, Rebecca, Perry, James A., Ryan, Kathleen A., Rice, Kenneth, Jaquish, Cashell E., Shuldiner, Alan R., Miller, Michael, Mitchell, Braxton D., Zaghloul, Norann A., Chang, Yen-Pei C., Abe, Namiko, Abecasis, Goncalo, Albert, Christine, Allred, Nicholette P., Almasy, Laura, Alonso, Alvaro, Ament, Seth, Anderson, Peter, Anugu, Pramod, Applebaum-Bowden, Debora, Arking, Dan, Arnett, Donna K, Ashley-Koch, Allison, Aslibekyan, Stella, Assimes, Tim, Auer, Paul, Avramopoulos, Dimitrios, Barnard, John, Barnes, Kathleen, Graham Barr, R., Barron-Casella, Emily, Beaty, Terri, Becker, Diane, Becker, Lewis, Beer, Rebecca, Begum, Ferdouse, Beitelshees, Amber, Benjamin, Emelia, Bezerra, Marcos, Bielak, Larry, Bis, Joshua, Blackwell, Thomas, Blangero, John, Boerwinkle, Eric, Borecki, Ingrid, Bowler, Russel, Brody, Jennifer, Broeckel, Ulrich, Broome, Jai, Bunting, Karen, Burchard, Esteban, Cardwell, Jonathan, Carlson, Sara, Carty, Cara, Casaburi, Richard, Casella, James, Chaffin, Mark, Chang, Christy, Chasman, Daniel, Chavan, Sameer, Chen, Bo-Juen, Chen, Wei-Min, Ida Chen, Yii-Der, Cho, Michael, Choi, Seung Hoan, Chuang, Lee-Ming, Chung, Mina, Cornell, Elaine, Correa, Adolfo, Crandall, Carolyn, Crapo, James, Cupples, L Adrienne, Curran, Joanne, Curtis, Jeffrey, Custer, Brian, Damcott, Coleen, Darbar, Dawood, Das, Sayantan, David, Sean, Davis, Colleen, Daya, Michelle, de Andrade, Mariza, DeBaun, Michael, Deka, Ranjan, DeMeo, Dawn, Devine, Scott, Do, Ron, Duan, Qing, Duggirala, Ravi, Durda, Peter, Dutcher, Susan, Eaton, Charles, Ekunwe, Lynette, Ellinor, Patrick, Emery, Leslie, Farber, Charles, Farnam, Leanna, Fingerlin, Tasha, Flickinger, Matthew, Fornage, Myriam, Franceschini, Nora, Fu, Mao, Fullerton, Malia, Fulton, Lucinda, Gabriel, Stacey, Gan, Weiniu, Gao, Yan, Gass, Margery, Gelb, Bruce, Geng, Xiaoqi (Priscilla), Germer, Soren, Gignoux, Chris, Gladwin, Mark, Glahn, David, Gogarten, Stephanie, Gong, Da-Wei, Goring, Harald, Charles Gu, C., Guan, Yue, Guo, Xiuqing, Haessler, Jeff, Hall, Michael, Harris, Daniel, Hawley, Nicola, He, Jiang, Heavner, Ben, Heckbert, Susan, Hernandez, Ryan, Herrington, David, Hersh, Craig, Hidalgo, Bertha, Hixson, James, Hokanson, John, Hong, Elliott, Hoth, Karin, Hsiung, Chao (Agnes), Huston, Haley, Hwu, Chii Min, Irvin, Marguerite, Jackson, Rebecca, Jain, Deepti, Jaquish, Cashell, Jhun, Min A, Johnsen, Jill, Johnson, Andrew, Johnson, Craig, Johnston, Rich, Jones, Kimberly, Kang, Hyun Min, Kaplan, Robert, Kardia, Sharon, Kathiresan, Sekar, Kaufman, Laura, Kelly, Shannon, Kenny, Eimear, Kessler, Michael, Khan, Alyna, Kinney, Greg, Konkle, Barbara, Kooperberg, Charles, Kramer, Holly, Krauter, Stephanie, Lange, Christoph, Lange, Ethan, Lange, Leslie, Laurie, Cathy, Laurie, Cecelia, LeBoff, Meryl, Lee, Seunggeun, Lee, Wen-Jane, LeFaive, Jonathon, Levine, David, Levy, Dan, Lewis, Joshua, Li, Yun, Lin, Honghuang, Lin, Keng Han, Liu, Simin, Liu, Yongmei, Loos, Ruth, Lunetta, Kathryn, Luo, James, Mahaney, Michael, Make, Barry, Manichaikul, Ani, Manson, JoAnn, Margolin, Lauren, Martin, Lisa, Mathai, Susan, Mathias, Rasika, McArdle, Patrick, McDonald, Merry-Lynn, McFarland, Sean, McGarvey, Stephen, Mei, Hao, Meyers, Deborah, Mikulla, Julie, Min, Nancy, Minear, Mollie, Minster, Ryan L, Mitchell, Braxton, Musani, Solomon, Mwasongwe, Stanford, Mychaleckyj, Josyf C, Nadkarni, Girish, Naik, Rakhi Johns, Natarajan, Pradeep, Nekhai, Sergei, Nickerson, Deborah, North, Kari, O’Connell, Jeff, O’Connor, Tim, Heather, Ochs-Balcom, Pankow, James, Papanicolaou, George, Parker, Margaret, Parsa, Afshin, Pattison, Jessica Tangarone, Penchev, Sara, Peralta, Juan Manuel, Perez, Marco, Perry, James, Peters, Ulrike, Peyser, Patricia, Phillips, Larry, Phillips, Sam, Pollin, Toni, Post, Wendy, Becker, Julia Powers, Boorgula, Meher Preethi, Preuss, Michael, Prokopenko, Dmitry, Psaty, Bruce, Qasba, Pankaj, Qiao, Dandi, Qin, Zhaohui, Rafaels, Nicholas, Raffield, Laura, Ramachandran, Vasan, Rao, D.C., Rasmussen-Torvik, Laura, Ratan, Aakrosh, Redline, Susan, Reed, Robert, Regan, Elizabeth, Reiner, Alex, Rice, Ken, Rich, Stephen, Roden, Dan, Roselli, Carolina, Rotter, Jerome, Ruczinski, Ingo, Russell, Pamela, Ruuska, Sarah, Ryan, Kathleen, Sakornsakolpat, Phuwanat, Salimi, Shabnam, Salzberg, Steven, Sandow, Kevin, Sankaran, Vijay, Scheller, Christopher, Schmidt, Ellen, Schwander, Karen, Schwartz, David, Sciurba, Frank, Seidman, Christine, Sheehan, Vivien, Shetty, Amol, Shetty, Aniket, Hui-Heng Sheu, Wayne, Benjamin Shoemaker, M., Silver, Brian, Silverman, Edwin, Smith, Jennifer, Smith, Josh, Smith, Nicholas, Smith, Tanja, Smoller, Sylvia, Snively, Beverly, Sofer, Tamar, Sotoodehnia, Nona, Stilp, Adrienne, Streeten, Elizabeth, Sung, Yun Ju, Sylvia, Jody, Szpiro, Adam, Sztalryd, Carole, Taliun, Daniel, Tang, Hua, Taub, Margaret, Taylor, Kent, Taylor, Simeon, Telen, Marilyn, Thornton, Timothy A., Tinker, Lesley, Tirschwell, David, Tiwari, Hemant, Tracy, Russell, Tsai, Michael, Vaidya, Dhananjay, VandeHaar, Peter, Vrieze, Scott, Walker, Tarik, Wallace, Robert, Walts, Avram, Wan, Emily, Fei Wang, Fei, Watson, Karol, Weeks, Daniel E., Weir, Bruce, Weiss, Scott, Weng, Lu-Chen, Willer, Cristen, Williams, Kayleen, Keoki Williams, L., Wilson, Carla, Wilson, James, Wong, Quenna, Xu, Huichun, Yanek, Lisa, Yang, Ivana, Yang, Rongze, Zaghloul, Norann, Zhang, Yingze, Zhao, Snow Xueyan, Zhao, Wei, Zheng, Xiuwen, Zhi, Degui, Zhou, Xiang, Zody, Michael, and Zoellner, Sebastian

Abstract

Supplemental Digital Content is available in the text.

Published
2018
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47. Key Components of Pain Management for Children and Adults with Sickle Cell Disease

Author

Brandow, Amanda M. and DeBaun, Michael R.

Abstract

Sickle cell disease pain manifests as severe acute pain episodes and a debilitating chronic pain syndrome. Acute pain episodes are the most common reason for health care use; however, acute pain episodes are also frequently managed at home. Chronic pain syndrome develops in 30% to 40% of individuals with sickle cell disease, with an increasing incidence and severity with age. We review the critical aspects of pain management that are integral to the comprehensive approach to sickle cell disease pain and are rooted in the biopsychosocial model. The review focuses on opioid pharmacology and psychosocial comorbidities.

Published
2018
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48. The Epidemiology and Management of Lung Diseases in Sickle Cell Disease

Author

Willen, Shaina M. and DeBaun, Michael R.

Abstract

Although sickle cell disease and cystic fibrosis are two of the most common monogenic diseases presenting in childhood worldwide, cystic fibrosis and sickle cell disease enjoy vastly different funding and collaborative research efforts. Pulmonary complications in cystic fibrosis have well established guidelines and multidisciplinary involvement focusing on comorbidities, routine monitoring, infectious complications, nutrition, and treatment recommendations. These guidelines can provide a framework on which to build knowledge of lung disease in sickle cell disease.

Published
2018
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49. Reduced Intensity Haploidentical Bone Marrow Transplantation in Adults with Severe Sickle Cell Disease: BMT CTN 1507

Author

Kassim, Adetola A., Walters, Mark C., Eapen, Mary, Ritzau, Nicole, Smith, Madoc, Solh, Melhem M., McKinney, Christopher, Nieder, Michael, Ross, Maureen, Kent, Michael, Abusin, Ghada, Mallhi, Kanwaldeep K., Silva, Jorge Galvez, Shaughnessy, Paul, Kanter, Julie, Haines, Hilary, Farah, Rafic J, Khaled, Yasser, Abraham, Allistair, Bollard, Catherine M., Cooke, Kenneth R., de La Fuente, Josu, Hanna, Rabi, Horowitz, Mary M., Jordan, Lori C, Krishnamurti, Lakshmanan, Leifere, Eric, Mahadeo, Kris Michael, Shenoy, Shalini, Ritzau, Nicole M., DeBaun, Michael R., and Brodsky, Robert A.

Abstract

Background:Allogeneic hematopoietic stem-cell transplantation has curative potential for sickle cell disease (SCD). Event-free survival (EFS) in children with SCD is >90% after a bone marrow transplant (BMT) from a myeloablative matched sibling donor (MSD). Unfortunately, <15% of patients with SCD have MSD, and myeloablative conditioning can be prohibitively toxic in adults with SCD. Reduced intensity HLA-haploidentical BMT with post-transplant cyclophosphamide (PTCy) has been shown in small studies to expand the donor pool with encouraging results. Still, concerns about graft failure and graft-versus-host disease (GVHD) persist. We present the results of a Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 1507, multi-center single-arm, phase-II, prospective clinical trial (clinicaltrials.gov #NCT03263559) of haploidentical-BMT with PTCy to estimate EFS at 2-years in adults with severe SCD. Pediatric stratum data is not included in the data presentation and will be available in 2-years.

Published
2023
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50. Localization of Silent Cerebral Infarcts in Children with Sickle Cell Disease Impacts Structural Disconnection

Author

Mirro, Amy, Binkley, Michael M., Power, Landon C., Guilliams, Kristin P., Fellah, Slim, DeBaun, Michael R., Ford, Andria L., Lee, Jin-Moo, and Fields, Melanie E.

Abstract

Silent cerebral infarcts (SCIs) occur in 40% of children with sickle cell disease (SCD) by 18 years of age and are associated with cognitive dysfunction. SCIs localize to the border zone of the brain, but the significance of this localization is unclear. In adults with stroke, an infarct's disruption of white matter (WM) tracts, or structural disconnection, is more strongly associated with the functional impact of the infarct than the size of the lesion. We aim to define the WM tracts disconnected by SCIs and the relationship between structural disconnection and functional connectivity (FC) in SCD. Simulated and real-world data were used to test the hypothesis that specific WM tracts are vulnerable to disconnection if an infarct occurs in the region at highest risk for SCIs, and that FC will decrease with increased structural disconnection in SCD.

Published
2023
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