17 results on '"Helge Hartung"'
Search Results
2. Protocol optimization for cardiac and liver iron content assessment using MRI: What sequence should I use?
- Author
-
Christian A. Barrera, Helge Hartung, Suraj D. Serai, David M. Biko, and Hansel J. Otero
- Subjects
Male ,Iron Overload ,Adolescent ,Iron ,Pediatrics ,030218 nuclear medicine & medical imaging ,Breath Holding ,Scan time ,03 medical and health sciences ,0302 clinical medicine ,Clinical Protocols ,Cardiac iron ,Humans ,Liver iron ,Medicine ,Radiology, Nuclear Medicine and imaging ,Child ,business.industry ,Reproducibility of Results ,Heart ,Magnetic Resonance Imaging ,Liver ,Child, Preschool ,030220 oncology & carcinogenesis ,Iron content ,Female ,Nuclear medicine ,business ,Liver parenchyma - Abstract
To determine the optimal MRI protocol and sequences for liver and cardiac iron estimation in children.We evaluated patients ≤18 years with cardiac and liver MRIs for iron content estimation. Liver T2 was determined by a third-party company. Cardiac and Liver T2* values were measured by an observer. Liver T2* values were calculated using the available liver parenchyma in the cardiac MRI. Linear correlations and Bland-Altman plots were run between liver T2 and T2*, cardiac T2* values; and liver T2* on dedicated cardiac and liver MRIs.139 patients were included. Mean liver T2 and T2* values were 8.6 ± 5.4 ms and 4.5 ± 4.1 ms, respectively. A strong correlation between liver T2 and T2* values was observed (r = 0.96, p 0.001) with a bias (+4.1 ms). Mean cardiac bright- and dark-blood T2* values were 26.5 ± 12.9 ms and 27.2 ± 11.9 ms, respectively. Cardiac T2* values showed a strong correlation (r = 0.81, p 0.001) with a low bias (-1.0 ms). The mean liver T2* on liver and cardiac MRIs were 4.9 ± 4.7 ms and 4.6 ± 3.9 ms, respectively. A strong correlation between T2* values was observed (r = 0.96, p 0.001) with a small bias (-0.2 ms).MRI protocols for iron concentration in the liver and the heart can be simplified to avoid redundant information and reduce scan time. In most patients, a single breath-hold GRE sequence can be used to evaluate the iron concentration in both the liver and heart.
- Published
- 2019
3. SPRINTing to Innovation: Children's Hospital of Philadelphia's Strategic Approach to Discovering Its Untapped Innovation Potential
- Author
-
Ryan Brandon Hunter, Joshua Nicklas, Flaura Koplin Winston, Kelsey Oh, Paul Dehel, and Helge Hartung
- Subjects
Adult ,Male ,020205 medical informatics ,Quality Assurance, Health Care ,Health Personnel ,02 engineering and technology ,Commercialization ,Education ,Project manager ,03 medical and health sciences ,0302 clinical medicine ,Resource (project management) ,Health care ,0202 electrical engineering, electronic engineering, information engineering ,Humans ,030212 general & internal medicine ,Project management ,Program Development ,Philadelphia ,business.industry ,General Medicine ,Public relations ,Middle Aged ,Hospitals, Pediatric ,Organizational Innovation ,Outreach ,Sprint ,Female ,Diffusion of Innovation ,business ,Barriers to entry - Abstract
Problem There is a clear and urgent need for health care innovation in the United States. Hospital employees routinely recognize pain points that affect care delivery and are in a unique position to propose innovative and practical solutions, yet leaders rarely solicit ideas for investment and development from frontline providers and staff, revealing an untapped resource with innovation potential. Approach To address these deficiencies, the Children's Hospital of Philadelphia (CHOP) expanded its innovation infrastructure with the competition-based SPRINT program in 2015. All hospital employees are encouraged to apply with early stage innovative ideas, and if selected, are provided with business, legal, technical, and scientific project management support to help accelerate their projects toward commercial viability. SPRINT was modeled around 4 core tenets: (1) small, dynamic, and attentive project manager-led teams; (2) low barriers to entry; (3) emphasis on outreach; and (4) fostering innovators. Outcomes Over its first 4 cycles from 2015 to 2018, 271 innovative teams applied to the SPRINT program, which led to support for 30 projects (11% acceptance rate). About a quarter of the projects each year were submitted by physician-led teams (mean 23%), a third by non-physician clinical providers (mean 33%), and almost half were submitted by employees without direct patient contact (mean 44%). Nurses have emerged as the largest applicant group. Eleven of the SPRINT supported projects (37%) resulted in commercial endpoints. Next steps SPRINT has proven to be an effective model for supporting institution-wide, employee-driven health care innovation, especially among frontline clinical and non-clinical personnel. Critical next steps for the program include a formal cost-benefit analysis and the earlier participation of technology transfer and intellectual property experts to improve the commercialization roadmap for many SPRINT projects.
- Published
- 2020
4. L-leucine improves anemia and growth in patients with transfusion-dependent Diamond Blackfan anemia: Results from a multicenter pilot phase I/II study from the Diamond Blackfan Anemia Registry
- Author
-
Jason E. Farrar, Anupama Narla, Kelly Walkovich, Helge Hartung, Grzegorz Nalepa, Adrianna Vlachos, Evangelia Atsidaftos, Jeffrey M. Lipton, Mohammad Lutfi Lababidi, Jonathan Bernstein, Ellen Muir, Zora R. Rogers, Thomas W. Loew, Waseem Alhushki, Colin A. Sieff, Bertil Glader, Barbara Gruner, Christine M. Knoll, and Arun R Panigrahi
- Subjects
Adult ,Male ,medicine.medical_specialty ,Adolescent ,Anemia ,medicine.medical_treatment ,Pilot Projects ,Hematopoietic stem cell transplantation ,Short stature ,Gastroenterology ,Article ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Leucine ,Internal medicine ,medicine ,Humans ,Blood Transfusion ,Diamond–Blackfan anemia ,Adverse effect ,Child ,Anemia, Diamond-Blackfan ,business.industry ,Hematology ,Middle Aged ,medicine.disease ,Prognosis ,Combined Modality Therapy ,Hematologic Response ,Clinical trial ,Oncology ,030220 oncology & carcinogenesis ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Erythropoiesis ,Feasibility Studies ,Female ,medicine.symptom ,business ,030215 immunology ,Follow-Up Studies - Abstract
Background Diamond-Blackfan anemia (DBA) is an inherited bone marrow failure syndrome characterized by anemia, short stature, congenital anomalies, and cancer predisposition. Most cases are due to mutations in genes encoding ribosomal proteins (RP) leading to RP haploinsufficiency. Effective treatments for the anemia of DBA include chronic red cell transfusions, long-term corticosteroid therapy, or hematopoietic stem cell transplantation. In a small patient series and in animal models, there have been hematologic responses to L-leucine with amelioration of anemia. The study objectives of this clinical trial were to determine feasibility, safety, and efficacy of L-leucine in transfusion-dependent patients with DBA. Procedure Patients ≥2 years of age received L-leucine 700 mg/m2 orally three times daily for nine months to determine a hematologic response and any improvement in growth (NCT01362595). Results This multicenter, phase I/II study enrolled 55 subjects; 43 were evaluable. There were 21 males; the median age at enrollment was 10.4 years (range, 2.5-46.1 years). No significant adverse events were attributable to L-leucine. Two subjects had a complete erythroid response and five had a partial response. Nine of 25, and 11 of 25, subjects experienced a positive weight and height percentile change, respectively, at the end of therapy. Conclusions L-leucine is safe, resulted in an erythroid response in 16% of subjects with DBA, and led to an increase in weight and linear growth velocity in 36% and 44% of evaluable subjects, respectively. Further studies will be critical to understand the role of L-leucine in the management of patients with DBA.
- Published
- 2020
5. A Standardized Clinical Pathway to Decrease Hospital Admissions Among Febrile Children With Sickle Cell Disease
- Author
-
Angela M. Ellison, Aileen Schast, Therese McKnight, Marlena Kittick, Helge Hartung, Erin Coyne, Cynthia F. Norris, Jane Lavelle, and Kim Smith Whitley
- Subjects
Male ,Emergency Medical Services ,medicine.medical_specialty ,Adolescent ,Fever ,Population ,Anemia, Sickle Cell ,Disease ,Notification system ,Tertiary Care Centers ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Clinical pathway ,Quality of life ,030225 pediatrics ,medicine ,Humans ,Young adult ,Child ,education ,Adverse effect ,education.field_of_study ,business.industry ,Infant ,Hematology ,Emergency department ,Quality Improvement ,Hospitalization ,Oncology ,Child, Preschool ,030220 oncology & carcinogenesis ,Pediatrics, Perinatology and Child Health ,Emergency medicine ,Critical Pathways ,Female ,Emergency Service, Hospital ,business ,Delivery of Health Care - Abstract
Background and objective Recurrent hospital admissions for patients with sickle cell disease (SCD) are costly and contribute to a low quality of life for patients. We implemented a clinical pathway to safely discharge SCD patients with fever who are evaluated in the emergency department (ED) of a large tertiary care center. Methods An interdisciplinary team of ED and hematology physicians, nurses, and an improvement advisor developed a clinical pathway that identified febrile SCD patients at low risk of serious bacterial infection based on historical, clinical, and laboratory criteria who could be discharged from the ED. Phone follow-up was planned through the use of an automated electronic notification that was sent to an established hematology follow-up pool at the time of ED discharge. We conducted two "fake front end" trials in the ED to receive feedback on our process before full implementation. A postpathway implementation quality improvement team monitored discharge rates, phone follow-up rates and adverse events. Results In the first 9 weeks postpathway implementation, 100 SCD patients were evaluated for fever; 84 (24%) met low-risk criteria and were discharged home. This reduction in admission rate has been maintained throughout the 3 years postimplementation. Successful phone follow-up was achieved in all discharged patients within 24 hours and no adverse events were identified. Conclusions Low-risk febrile patients with SCD can be safely discharged from the ED. An automated notification system within the electronic medical record system can facilitate patient follow-up after ED discharge. Future quality improvement efforts aimed to further reduce admissions in this population should target patients with modifiable risk factors for serious bacterial infection.
- Published
- 2018
6. Effects of the COVID-19 Pandemic on Caregivers of Young Children with Sickle Cell Disease Enrolled in the Engage-HU Trial
- Author
-
Charles T. Quinn, Alexis A. Thompson, Anna M Hood, Jasmine Stallworth, Constance A. Mara, Yolanda Johnson, Emily Riehm Meier, Helge Hartung, Lisa M Shook, Lori E. Crosby, Kim Smith-Whitley, Allison A. King, Venee N. Tubman, Stacey M. Gomes, Amber M Yates, Aimee K. Hildenbrand, Jean L. Raphael, Joanna Rebitski, Catharine Whitacre, Sherif M. Badawy, Neha Bhasin, Steven K Reader, and Susan E Creary
- Subjects
Pediatrics ,medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,business.industry ,Immunology ,Cell Biology ,Hematology ,Disease ,Biochemistry ,901.Health Services Research-Non-Malignant Conditions ,Pandemic ,Medicine ,business ,health care economics and organizations - Abstract
Background: Hydroxyurea (HU) is the primary medication used to prevent the significant medical and neurologic morbidities of pediatric sickle cell disease (SCD; HbSS or HbSB0 thalassemia). Despite the benefits of HU, it remains under-utilized likely due to lack of clinician knowledge/training and negative caregiver perceptions. Thus, we developed the Engage-HU randomized controlled trial (NCT03442114) as a novel approach to address HU utilization barriers. Engage-HU is designed to assess how clinicians can engage caregivers in a shared discussion that considers their values, preferences, and scientific evidence about HU. The COVID-19 pandemic has resulted in significant changes to healthcare delivery for children with SCD, as they are at increased risk of severe illness from COVID-19 infection. Given their risk status, it was recommended that patients with SCD complete telehealth visits when possible. Some families also chose to delay care because they feared their child would get infected at hospitals/healthcare clinics that care for COVID-19 positive patients. Since the lives of all families enrolled in the Engage-HU trial have been affected to some extent, we incorporated measures to capture the impact of the COVID-19 pandemic and the usability of telemedicine implementation and services. Methods: Engage-HU is a randomized control trial comparing two dissemination methods for clinicians to facilitate shared decision-making with caregivers of young children with SCD. Study outcomes include caregiver confidence in decision-making and perceptions of experiencing shared decision-making as well as HU uptake and child health outcomes. Eligible children are 0 to 5 years, candidates for HU, and their caregiver has not decided about HU in the past 3 months. The trial is being conducted at 9 sites in the United States and uses a unidirectional crossover design. The primary endpoints are caregiver decisional uncertainty and caregiver perception of shared decision-making measured using validated tools. Data will be analyzed using the intent-to-treat principle, and all participants will remain in the arm to which they were randomized. A multiple group comparison analysis will be performed to assess significant response variable differences by group randomization. The Engage-HU study aims to recruit 174 caregivers who are considering initiating HU. The trial is being conducted at 9 sites in the United States. Data collection is ongoing, and 160 caregiver-participants have been enrolled to date. Since May 2020, caregiver-participants have completed the COVID-19 Exposure and Family Impact Scales (CEFIS), which contain 2 subscales (exposure to potentially traumatic aspects of the pandemic, impact on families), and the COVID-19 telemedicine use survey during a study visit. Results: Currently, 8 of the 9 sites have collected data from 48 caregivers (93.8% mothers), most of whom (93.8%) identify as African American/Black (see Figure 1). Correlations indicated that older caregivers experienced greater exposure (Mean = 7.0, SD = 4.1, range = 1-19) to potentially traumatic aspects of the pandemic (r = .31, p = .04). Distress related to COVID-19 varied widely across the sample, for both caregivers (Mean = 5.9, SD = 2.9, range = 1-10) and children (Mean = 4.1, SD = 3.4, range = 1-10). Scores on the telemedicine usability survey were generally high, indicating that caregivers are happy with the quality of care delivered via telehealth. However, caregivers (r = .30, p = .09) and children (r = .32, p = .07) experiencing more pandemic-related distress reported less satisfaction with telehealth. Conclusion: Although Engage-HU has resumed research operations, recruitment has not reached pre-pandemic targets, as fewer eligible patients are scheduled for routine care visits at SCD clinics. Our preliminary analyses suggest a significant continued impact of the pandemic on families and general satisfaction with the quality of healthcare delivered via telemedicine. These findings indicate that targeted screenings to identify and intervene for those who demonstrate more COVID-19 pandemic-related distress are needed. Figure 1 Figure 1. Disclosures Quinn: Forma Therapeutics: Consultancy; Aruvant: Research Funding; Novo Nordisk: Consultancy; Emmaus Medical: Research Funding. Yates: Agios Pharmaceuticals: Current Employment. Badawy: Sanofi Genzyme: Consultancy; Vertex Pharmaceuticals Inc: Consultancy; Bluebird Bio Inc: Consultancy. Thompson: bluebird bio, Inc.: Consultancy, Research Funding; Baxalta: Research Funding; Biomarin: Research Funding; Celgene/BMS: Consultancy, Research Funding; CRISPR Therapeutics: Research Funding; Vertex: Research Funding; Editas: Research Funding; Graphite Bio: Research Funding; Novartis: Research Funding; Agios: Consultancy; Beam: Consultancy; Global Blood Therapeutics: Current equity holder in publicly-traded company. Smith-Whitley: Global Blood Therapeutics: Current Employment. King: National Cancer Institute: Research Funding; National Heart, Lung, and Blood Institute: Research Funding; Health Resources and Services Administration: Research Funding; Global Blood Therapeutics: Research Funding. Meier: CVS Caremark: Consultancy; Forma Therapeutic: Membership on an entity's Board of Directors or advisory committees; NovoNordisk: Membership on an entity's Board of Directors or advisory committees; Novartis,: Other: Data Safety Monitoring Board membership; NHLBI: Other: Data Safety Monitoring Board membership; Global Blood Therapeutics: Other: Steering Committee membership, grant funding; CDC,: Other: grant funding; Indiana Department of Health: Other: grant funding . Tubman: Global Blood Therapeutics: Consultancy, Research Funding; Novartis Pharmaceuticals: Honoraria, Research Funding; Forma Pharmaceuticals: Consultancy; Perkin Elmer: Honoraria. Crosby: Forma Therapeutics: Honoraria; PCORI: Research Funding; HRSA: Research Funding; Global Blood Therapeutics Panel: Honoraria; Children's Hospital of Philadelphia: Honoraria; Professional Resource Exchange: Patents & Royalties: $30-$60 every other year; SCDAA: Honoraria; NHLBI: Other: Payment for review of LRP Proposals, Research Funding. OffLabel Disclosure: Hydroxyurea has been FDA approved for the treatment of sickle cell disease for patients ages 2 years and above but NHLBI and ASH Guidelines recommend it be offered to children as young as age 9 months.
- Published
- 2021
7. Metformin for Treatment of Cytopenias in Children and Young Adults with Fanconi Anemia
- Author
-
Jacob Bledsoe, Farid Boulad, Annette S. Kim, Laurie E. Cohen, Kaitlyn Ballotti, Elissa M. Furutani, Maggie Malsch, Marcin W. Wlodarski, Amy Hont, María José Ramírez, Erica B. Esrick, Alexis A. Thompson, Edie Weller, Jessica A. Pollard, Alan D. D'Andrea, Jordi Surrallés, Ashley Kuniholm, Ashley Galvin, Towia A. Libermann, Clinton Carroll, Akiko Shimamura, Kun Lu, Lisa A. Moreau, Shanshan Liu, Helge Hartung, Daria V. Babushok, Sei-Gyung K. Sze, Yu Zhou, Myriam Armant, Markus Grompe, Taizo A. Nakano, and Timothy S. Olson
- Subjects
Pediatrics ,medicine.medical_specialty ,business.industry ,Immunology ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Metformin ,Fanconi anemia ,medicine ,Young adult ,business ,medicine.drug - Abstract
Fanconi anemia (FA), a genetic disorder affecting DNA repair, is characterized by bone marrow failure and cancer susceptibility. In FA mouse models, metformin (N,N-dimethylguanide) a biguanide metabolic agent, improves blood counts and delays tumor development. Given these findings, we conducted a single institution pilot study of metformin in non-diabetic patients with FA to assess feasibility, tolerability, and impact of metformin on hematologic response as defined by modified MDS International Working Group (IWG) criteria (Table 1). Fourteen of 15 patients with at least 1 cytopenia (hemoglobin Figure 1 Figure 1. Disclosures Pollard: Kura Oncology: Membership on an entity's Board of Directors or advisory committees; Syndax: Membership on an entity's Board of Directors or advisory committees. Furutani: Keros Therapeutics: Current Employment, Current equity holder in publicly-traded company. Esrick: bluebird bio: Consultancy. Nakano: Novartis: Consultancy. Thompson: Celgene: Consultancy, Research Funding; bluebird bio: Consultancy, Research Funding; Biomarin: Research Funding; Vertex: Research Funding; Graphite Bio: Research Funding; Baxalta: Research Funding; CRISPR Therapeutics: Research Funding; Novartis: Research Funding; Agios Pharmaceuticals: Consultancy; Beam Therapeutics: Consultancy; Global Blood Therapeutics: Current equity holder in publicly-traded company. OffLabel Disclosure: metformin- use in Fanconi anemia in an effort to improve hematopoiesis
- Published
- 2021
8. Red blood cell alloimmunization in transfused patients with bone marrow failure syndromes
- Author
-
Helge Hartung, Devin Cohen, Perry Evans, David F. Friedman, and Stella T. Chou
- Subjects
medicine.medical_specialty ,biology ,business.industry ,Anemia ,Immunology ,Autoantibody ,Bone marrow failure ,Retrospective cohort study ,Hematology ,030204 cardiovascular system & hematology ,medicine.disease ,03 medical and health sciences ,Regimen ,0302 clinical medicine ,030220 oncology & carcinogenesis ,ABO blood group system ,Internal medicine ,medicine ,biology.protein ,Immunology and Allergy ,Hemoglobinuria ,Antibody ,business - Abstract
BACKGROUND Red blood cell (RBC) alloimmunization is a concern for patients who receive multiple or chronic transfusions. Alloimmunization prevalence in transfused patients with bone marrow failure syndrome (BMFS) is unknown. This study aimed to determine physician practice for RBC antigen matching, immunization rates, and antibody specificities in patients with BMFS. STUDY DESIGN AND METHODS The clinical records of all patients with BMFS seen at the Children's Hospital of Philadelphia between 2001 and 2015 were reviewed. Immunization rate was determined per 100 units transfused. RESULTS ABO/D, C, E, and K (CEK) RBC matching was requested for 21.8% of patients. A total of 3782 RBC units were transfused to 87 patients, of which 2551 (67.5%) were CEK matched and 1231 (32.5%) were ABO/D only matched. The majority of units transfused to patients on a chronic transfusion regimen were CEK matched (89.6% of 2728 units). No anti-C, -E, or -K antibodies formed in any patient during the 14-year study period. Two alloantibodies and two autoantibodies formed, resulting in a rate of 0.05 alloantibodies and 0.05 autoantibodies per 100 units transfused. The prevalence of alloimmunization was 2.3%. CONCLUSION The rate and prevalence of RBC alloimmunization were low in patients with BMFS. CEK matching avoided alloimmunization to these antigens in chronically transfused patients.
- Published
- 2016
9. Disrupted lymphocyte homeostasis in hepatitis‐associated acquired aplastic anemia is associated with short telomeres
- Author
-
Helge Hartung, Monica Bessler, Yimei Li, Hongbo Xie, Jamie Atienza, Ho Sun Lam, Timothy S. Olson, Anne Laure Grignon, and Daria V. Babushok
- Subjects
0301 basic medicine ,Male ,Adolescent ,Anemia ,Lymphocyte ,Population ,Hepatitis ,03 medical and health sciences ,0302 clinical medicine ,Lymphocyte homeostasis ,medicine ,Humans ,Aplastic anemia ,education ,Child ,In Situ Hybridization, Fluorescence ,Telomere Shortening ,education.field_of_study ,business.industry ,Bone marrow failure ,Anemia, Aplastic ,Infant ,Telomere Homeostasis ,Hematology ,Original Articles ,medicine.disease ,Flow Cytometry ,Lymphocyte Subsets ,3. Good health ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Child, Preschool ,Immunology ,Cytogenetic Analysis ,Original Article ,Female ,business ,Dyskeratosis congenita - Abstract
Hepatitis‐associated aplastic anemia (HAA) is a variant of acquired aplastic anemia (AA) in which immune‐mediated bone marrow failure (BMF) develops following an acute episode of seronegative hepatitis. Dyskeratosis congenita (DC) is an inherited BMF syndrome characterized by the presence of short telomeres, mucocutaneous abnormalities, and cancer predisposition. While both conditions may cause BMF and hepatic impairment, therapeutic approaches are distinct, making it imperative to establish the correct diagnosis. In clinical practice, lymphocyte telomere lengths (TL) are used as a first‐line screen to rule out inherited telomeropathies before initiating treatment for AA. To evaluate the reliability of TL in the HAA population, we performed a retrospective analysis of TL in 10 consecutively enrolled HAA patients compared to 19 patients with idiopathic AA (IAA). HAA patients had significantly shorter telomeres than IAA patients (P = 0.009), including four patients with TL at or below the 1st percentile for age‐matched controls. HAA patients had no clinical features of DC and did not carry disease‐causing mutations in known genes associated with inherited telomere disorders. Instead, short TLs were significantly correlated with severe lymphopenia and skewed lymphocyte subsets, features characteristic of HAA. Our results indicate the importance of caution in the interpretation of TL measurements in HAA, because, in this patient population, short telomeres have limited specificity. Am. J. Hematol. 91:243–247, 2016. © 2015 The Authors. American Journal of Hematology Published by Wiley Periodicals, Inc.
- Published
- 2016
10. Leucine for the Treatment of Transfusion Dependence in Patients with Diamond Blackfan Anemia
- Author
-
Barbara Gruner, Kelly Walkovich, Christine M. Knoll, Mohammad Lufti Lababidi, Jason E. Farrar, Anupama Narla, Helge Hartung, Zora R. Rogers, Waseem Alhushki, Evangelia Atsidaftos, Ellen Muir, Bertil Glader, Arun R Panigrahi, Colin A. Sieff, Jeffrey M. Lipton, Adrianna Vlachos, and Grzegorz Nalepa
- Subjects
medicine.medical_specialty ,Blood transfusion ,Red Cell ,Anemia ,business.industry ,medicine.medical_treatment ,Immunology ,Cell Biology ,Hematology ,Hematopoietic stem cell transplantation ,030204 cardiovascular system & hematology ,medicine.disease ,Biochemistry ,Gastroenterology ,Pancytopenia ,Transplantation ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,Liver function ,Diamond–Blackfan anemia ,business - Abstract
Diamond Blackfan anemia (DBA) is a rare, inherited bone marrow failure syndrome characterized by anemia, congenital anomalies and a predisposition to cancer. The patients usually present during infancy or early childhood, but can also present in adulthood. In the majority of cases DBA is due to a mutation in a small or large ribosomal protein (RP) subunit leading to RP haploinsufficiency. The only treatments for the anemia of DBA are red cell transfusions (accompanied by iron chelation), oral corticosteroid therapy or stem cell transplantation. Pospisilova et al. (Haematologica 2007; 92(5):e66-67) reported one complete and two partial erythroid responses after the use of the branched chain amino acid L-leucine in 6 select patients. In skeletal muscle, leucine supplementation can upregulate components of the protein synthetic machinery, including ribosomal proteins, promoting protein translation. Mouse and fish models of DBA respond with amelioration of anemia to L-leucine. We therefore proposed to study the effect of L-leucine on transfusion dependence and growth in subjects with DBA. Methods: The primary objectives were to determine the feasibility of administering L-leucine in subjects with DBA who are red cell transfusion-dependent and to determine the efficacy of L-leucine to produce a hematologic and growth response. The secondary objective was to determine the safety profile of L-leucine. Twelve study sites were involved in this multi-center, Phase I/II study with an anticipated accrual of 50 subjects. A dose of 700 mg/M2 orally three times per day for 9 months was used. Inclusion criteria included age > 2 years, the diagnosis of DBA and transfusion dependence with adequate kidney and liver function. Response was evaluated at 9 months with Complete Response (CR) defined as no further transfusions required and Hb >9; Partial Response (PR): Hb < 9 gm/dL with an increase in reticulocyte count and transfusion interval; and No Response (NR): no change in transfusion needs, Hb or reticulocyte count . Growth percentiles were evaluated at baseline and at completion of 9 months of treatment and the growth velocity change was calculated. Results: The study opened July 2014 and closed February 2017; 55 subjects were consented; 12 were screen failures; 43 subjects were evaluable. There were 21 males; the median age was 9 years 1 month (2 years 5 months - 46 years 1 month). There were no untoward side effects experienced by any subject that were attributable to the L-leucine. Two subjects had an erythroid CR and 1 subject had a PR. The CRs occurred at 1 month and 3 months after start of L-leucine. The subject with PR had an elevated reticulocyte count but was not able to maintain a Hb >9 gm/dL without a transfusion and thus was not transfusion independent. Of the 30 subjects with growth potential who received L-leucine 10 experienced a positive growth velocity change at 9 months of therapy compared to baseline. At a median age of 7.5 years, the mean pre-leucine height percentile was 27 +/- 17.9 and the post-leucine height percentile was 35 +/- 19.9 (p Conclusions: The administration of L-leucine is safe. L-leucine administration resulted in an erythroid response in 7% of subjects and an increased growth velocity in 33% of growing subjects. Based upon extrapolation from animal models, it is likely that this dose was suboptimal. We hypothesize that higher doses of L-leucine will lead to hematologic responses in more subjects who are transfusion dependent. The potential benefit of added growth in children with DBA may improve final adult height. Disclosures Glader: Agios: Consultancy, Research Funding.
- Published
- 2018
11. Pancytopenia in a patient with methylmalonic acidemia
- Author
-
Suzanne P. MacFarland and Helge Hartung
- Subjects
congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,Pediatrics ,Pancytopenia ,Immunology ,Acquired hypothyroidism ,Methylmalonic acidemia ,Bone Marrow Cells ,Biochemistry ,Viral infection ,medicine ,Humans ,Intensive care medicine ,Amino Acid Metabolism, Inborn Errors ,business.industry ,nutritional and metabolic diseases ,Metabolic acidosis ,Cell Biology ,Hematology ,medicine.disease ,Hematopoietic Stem Cells ,Child, Preschool ,Failure to thrive ,Female ,medicine.symptom ,business - Abstract
[Figure][1] A 4-year-old girl with a known history of methylmalonic acidemia (MMA) complicated by acquired hypothyroidism, failure to thrive, and developmental delay developed pancytopenia during an admission for emesis and metabolic acidosis. She had no symptoms of a viral infection, and
- Published
- 2015
12. Dehydrated hereditary stomatocytosis masquerading as MDS
- Author
-
Michele Paessler and Helge Hartung
- Subjects
Male ,Pathology ,medicine.medical_specialty ,Anemia ,Hydrops Fetalis ,Immunology ,Anemia, Hemolytic, Congenital ,Biochemistry ,Ion Channels ,Young Adult ,Bone Marrow ,hemic and lymphatic diseases ,medicine ,Hypercellular marrow ,Humans ,Diagnostic Errors ,Germ-Line Mutation ,Genes, Dominant ,Homeodomain Proteins ,business.industry ,Second opinion ,Erythroid Hyperplasia ,Cell Biology ,Hematology ,medicine.disease ,medicine.anatomical_structure ,Myelodysplastic Syndromes ,Dehydrated hereditary stomatocytosis ,Bone marrow ,business ,Biopsy findings - Abstract
[Figure][1] A 23-year-old man presented to our clinic for a second opinion. He was given the diagnosis of myelodysplastic syndrome (MDS) years prior, based on a history of iron overload and bone marrow biopsy findings of a hypercellular marrow with erythroid hyperplasia and
- Published
- 2015
13. Acquired aplastic anemia in children
- Author
-
Helge Hartung, Timothy S. Olson, and Monica Bessler
- Subjects
Pediatrics ,medicine.medical_specialty ,Bone marrow transplantation ,business.industry ,Treatment outcome ,Bone marrow failure ,Anemia, Aplastic ,Disease ,medicine.disease ,Article ,Survival Rate ,Treatment Outcome ,Pediatrics, Perinatology and Child Health ,Etiology ,Medicine ,Humans ,Acquired aplastic anemia ,business ,Child ,Survival rate ,Immunosuppressive Agents ,Bone Marrow Transplantation - Abstract
This article provides a practice-based and concise review of the etiology, diagnosis, and management of acquired aplastic anemia in children. Bone marrow transplantation, immunosuppressive therapy, and supportive care are discussed in detail. The aim is to provide the clinician with a better understanding of the disease and to offer guidelines for the management of children with this uncommon yet serious disorder.
- Published
- 2013
14. Clinical Pathway to Decrease Hospital Admissions Among Febrile Patients with Sickle Cell Disease
- Author
-
Jane Lavelle, Therese McKnight, Helge Hartung, Erin Coyne, Cynthia F. Norris, Marlena Kittick, Aileen Schast, Kim Smith Whitley, and Angela M. Ellison
- Subjects
medicine.medical_specialty ,Clinical pathway ,business.industry ,Pediatrics, Perinatology and Child Health ,medicine ,Disease ,Intensive care medicine ,business - Published
- 2016
15. NUP98-HOX translocations lead to myelodysplastic syndrome in mice and men
- Author
-
Peter D. Aplan, Linda Wolff, Zhenhua Zhang, Helge Hartung, Ying Wei Lin, and Christopher Slape
- Subjects
Cancer Research ,Oncogene Proteins, Fusion ,Mice, Transgenic ,Translocation, Genetic ,Article ,Mice ,hemic and lymphatic diseases ,medicine ,Animals ,Humans ,Ineffective Hematopoiesis ,Chromosome Aberrations ,Homeodomain Proteins ,Acute leukemia ,Leukopenia ,business.industry ,Myelodysplastic syndromes ,Myeloid leukemia ,General Medicine ,medicine.disease ,Nuclear Pore Complex Proteins ,Haematopoiesis ,Disease Models, Animal ,medicine.anatomical_structure ,Oncology ,Dysplasia ,Myelodysplastic Syndromes ,Immunology ,Cancer research ,Bone marrow ,medicine.symptom ,business ,Transcription Factors - Abstract
The myelodysplastic syndromes (MDS) are a group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis, peripheral blood cytopenias, dysplasia and a propensity for transformation to acute myeloid leukemia (AML). A wide spectrum of genetic aberrations has been associated with MDS, including chromosomal translocations involving the NUP98 gene, most commonly leading to fusions of NUP98 with abd-b group HOX genes, including HOXD13. We used vav regulatory elements to direct expression of a NUP98-HOXD13 (NHD13) fusion gene in hematopoietic tissues. NHD13 transgenic mice faithfully recapitulate all of the key features of MDS, including peripheral blood cytopenias, bone marrow dysplasia and apoptosis, and transformation to acute leukemia. The MDS that develops in NHD13 transgenic mice is highly lethal; within 14 months, 90% of the mice died of either leukemic transformation or severe anemia and leukopenia due to progressive MDS. These mice provide a pre-clinical model that can be used for the evaluation of MDS therapy and biology.
- Published
- 2008
16. A neurologic presentation of familial hemophagocytic lymphohistiocytosis which mimicked septic emboli to the brain
- Author
-
Kaleb Yohay, Robert J. Arceci, L. Christine Turtzo, Peter B. Barker, Helge Hartung, and Doris D. M. Lin
- Subjects
Male ,Pore Forming Cytotoxic Proteins ,Pathology ,medicine.medical_specialty ,Heterozygote ,Fulminant ,Encephalopathy ,Compound heterozygosity ,Polymorphism, Single Nucleotide ,Lymphohistiocytosis, Hemophagocytic ,Sepsis ,Diagnosis, Differential ,03 medical and health sciences ,0302 clinical medicine ,030225 pediatrics ,medicine ,Humans ,Bone Marrow Transplantation ,Hemophagocytic lymphohistiocytosis ,Membrane Glycoproteins ,biology ,business.industry ,Perforin ,Infant ,Familial Hemophagocytic Lymphohistiocytosis ,medicine.disease ,Magnetic Resonance Imaging ,Treatment Outcome ,Intracranial Embolism ,Pediatrics, Perinatology and Child Health ,Immunology ,biology.protein ,Neurology (clinical) ,Immunotherapy ,Differential diagnosis ,business ,030217 neurology & neurosurgery ,Follow-Up Studies - Abstract
Familial hemophagocytic lymphohistiocytosis is an inherited deficiency of natural killer cell function and excessive cytokine activity, which predominantly presents in early childhood. The initial symptoms of familial hemophagocytic lymphohistiocytosis are often nonspecific but may be predominantly neurologic. The case presented here describes an 18-month-old boy who initially presented with fever, encephalopathy, and hemiparesis. He had innumerable brain lesions visualized on magnetic resonance imaging scans. An infectious etiology was excluded, and brain, liver, and bone marrow biopsies were nonspecific but consistent with hemophagocytic lymphohistiocytosis. Cells were sent for flow cytometry perforin analysis, which demonstrated defective natural killer cell function. A diagnosis of familial hemophagocytic lymphohistiocytosis was confirmed by mutation analysis and decreased expression of the perforin gene, in the patient and immediate family members. These results showed the patient to be a compound heterozygote for perforin mutations. His case illustrates the potential for a fulminant neurological presentation of familial hemophagocytic lymphohistiocytosis with widespread lesions in the brain.
- Published
- 2007
17. Elevated Systolic Blood Pressure and Low Fetal Hemoglobin Are Risk Factors for Silent Cerebral Infarcts in Children with Sickle Cell Anemia
- Author
-
Thomas H. Howard, Helge Hartung, Janet L. Kwiatkowski, Mark E. Heiny, Brian W. Berman, Gerald M. Woods, Baba Inusa, Allison A. King, Karen Kalinyak, Rathi V. Iyer, Françoise Bernaudin, Gladstone Airewele, Paul Telfer, Suzanne Saccente, Charles D. Scher, Melanie Kirby-Allen, Alexis A. Thompson, Hernan Sabio, Fenella J. Kirkham, Bruce A. Barton, Beng Fuh, Michael R. DeBaun, James F. Casella, Scott T. Miller, Rupa Redding-Lallinger, Michele Afif, Julie A. Panepinto, Sharada A. Sarnaik, Melissa Rhodes, Thomas D. Coates, and Charles T. Quinn
- Subjects
medicine.medical_specialty ,Pediatrics ,business.industry ,Thalassemia ,Immunology ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Sickle cell anemia ,Blood pressure ,medicine.anatomical_structure ,Internal medicine ,White blood cell ,Fetal hemoglobin ,Hemoglobin F ,Cardiology ,Medicine ,Hemoglobin ,business ,Oxygen saturation (medicine) - Abstract
Abstract 262 Introduction: The most common cause of neurological injury in sickle cell anemia is silent cerebral infarcts (SCI). In the Silent Cerebral Infarct Multi-Center Clinical Trial (SIT Trial) cohort, we sought to identify risk factors associated with SCI. Patients and Methods: In this cross-sectional study, we evaluated the clinical history, baseline laboratory values and performed magnetic resonance imaging of the brain. For those children with SCI-like lesions, a pediatric neurologist examined the child and neuroradiology and neurology committees adjudicated the presence of SCI. Children between the ages of 5 and 15 years with hemoglobin SS or S-beta° thalassemia and no history of overt strokes or seizure were evaluated. Results: A total of 542 children were evaluated; 173 (31.9%) had SCI. The mean age of the children was 9.3 years, with 280 males (51.7%). In a multivariate logistic analysis, two covariates were significant: a single systolic blood pressure (SBP) obtained during a baseline well-visit, p = 0.015 and hemoglobin F (Hgb F) level obtained after three years of age, p = 0.038. Higher values of SBP and lower values of Hgb F increased the odds of SCI; Figure. Baseline values of white blood cell count, hemoglobin level, oxygen saturation, reticulocytes, pain, or ACS event rates were not associated with SCI. Conclusion: SBP and Hgb F level are two previously unidentified risk factors for SCI in children with sickle cell disease. Modulation of SBP and Hgb F levels might decrease the risk of SCI. Disclosures: No relevant conflicts of interest to declare.
- Published
- 2009
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.