Medicine and Health Sciences Commons^™

Minimum Quality Threshold In Pre-Clinical Sepsis Studies (Mqtipss): An International Expert Consensus Initiative For Improvement Of Animal Modeling In Sepsis., M. F. Osuchowski, A. Ayala, S. Bahrami, M. Bauer, M. Boros, J. Cavaillon, I. H. Chaudry, C. Deutschman, P. Wang, B. Zingarelli, +21 Additional Authors

Journal Articles

BACKGROUND:Pre-clinical animal studies precede the majority of clinical trials. While the clinical definitions of sepsis and recommended treatments are regularly updated, a systematic review of pre-clinical models of sepsis has not been done and clear modeling guidelines are lacking. OBJECTIVE:To address this deficit, a Wiggers-Bernard Conference on pre-clinical sepsis modeling was held in Vienna in May 2017. The goal of the conference was to identify limitations of pre-clinical sepsis models and to propose a set of guidelines, defined as the "Minimum Quality Threshold in Pre-Clinical Sepsis Studies" (MQTiPSS), to enhance translational value of these models. METHODS:A total of 31 experts …

Microbiota-Sensitive Epigenetic Signature Predicts Inflammation In Crohn's Disease., D. Kelly, M. Kotliar, V. Woo, S. Jagannathan, J. Whitt, J. Moncivaiz, B. J. Aronow, M. C. Dubinsky, J. F. Markowitz, T. Alenghat, +12 Additional Authors

Journal Articles

Altered response to the intestinal microbiota strongly associates with inflammatory bowel disease (IBD); however, how commensal microbial cues are integrated by the host during the pathogenesis of IBD is not understood. Epigenetics represents a potential mechanism that could enable intestinal microbes to modulate transcriptional output during the development of IBD. Here, we reveal a histone methylation signature of intestinal epithelial cells isolated from the terminal ilea of newly diagnosed pediatric IBD patients. Genes characterized by significant alterations in histone H3-lysine 4 trimethylation (H3K4me3) showed differential enrichment in pathways involving immunoregulation, cell survival and signaling, and metabolism. Interestingly, a large subset …

Expanding The Clinical And Molecular Findings In Rasa1 Capillary Malformation-Arteriovenous Malformation, W. L. Wooderchak-Donahue, P. Johnson, J. Mcdonald, F. Blei, A. Berenstein, M. Sorscher, J. Mayer, A. E. Scheuerle, T. Lewis, P. Bayrak-Toydemir, +5 Additional Authors

Journal Articles

No abstract provided.

Correction To: Minimum Quality Threshold In Pre-Clinical Sepsis Studies (Mqtipss): An International Expert Consensus Initiative For Improvement Of Animal Modeling In Sepsis (Infection, (2018), 10.1007/S15010-018-1183-8), M. F. Osuchowski, A. Ayala, S. Bahrami, M. Bauer, M. Boros, J. M. Cavaillon, I. H. Chaudry, C. Deutschman, P. Wang, B. Zingarelli, +21 Additional Authors

Journal Articles

© 2018, The Author(s). The original version of this article unfortunately contained mistakes.

Translational Research: The Model Matters, C. S. Deutschman

Journal Articles

No abstract provided.

An Eqtl Landscape Of Kidney Tissue In Human Nephrotic Syndrome, C. E. Gillies, R. Putler, R. Menon, E. Otto, K. Yasutake, V. Nair, P. Hoover, D. Lieb, C. Sethna, K. Abbott, +89 Additional Authors

Journal Articles

© 2018 American Society of Human Genetics Expression quantitative trait loci (eQTL) studies illuminate the genetics of gene expression and, in disease research, can be particularly illuminating when using the tissues directly impacted by the condition. In nephrology, there is a paucity of eQTL studies of human kidney. Here, we used whole-genome sequencing (WGS) and microdissected glomerular (GLOM) and tubulointerstitial (TI) transcriptomes from 187 individuals with nephrotic syndrome (NS) to describe the eQTL landscape in these functionally distinct kidney structures. Using MatrixEQTL, we performed cis-eQTL analysis on GLOM (n = 136) and TI (n = 166). We used the Bayesian …

Pilot Study Comparing The Childhood Arthritis And Rheumatology Research Alliance Consensus Treatment Plans For Induction Therapy Of Juvenile Proliferative Lupus Nephritis, J. C. Cooper, K. Rouster-Stevens, T. B. Wright, J. J. Hsu, M. S. Klein-Gitelman, S. P. Ardoin, L. E. Schanberg, H. I. Brunner, B. A. Eberhard, E. Von Scheven, +6 Additional Authors

Journal Articles

BACKGROUND: To reduce treatment variability and facilitate comparative effectiveness studies, the Childhood Arthritis and Rheumatology Research Alliance (CARRA) published consensus treatment plans (CTPs) including one for juvenile proliferative lupus nephritis (LN). Induction immunosuppression CTPs outline treatment with either monthly intravenous (IV) cyclophosphamide (CYC) or mycophenolate mofetil (MMF) in conjunction with one of three corticosteroid (steroid) CTPs: primarily oral, primarily IV or mixed oral/IV. The acceptability and in-practice use of these CTPs are unknown. Therefore, the primary aims of the pilot study were to demonstrate feasibility of adhering to the LN CTPs and delineate barriers to implementation in clinical care in …

Age Restriction Warning Label Efficacy And High School Student Consumption Of Highly-Caffeinated Products., J. Goldman, M. Zhu, T. B. Pham, R. Milanaik

Journal Articles

Age restriction warning labels (ARLs) are placed on highly-caffeinated food and drinks, such as Red Bull, to deter consumption by minors who are especially vulnerable to the risks of excessive caffeine consumption. Previous studies have shown that ARLs on media like TV programs and video games fail to discourage minors. However, it is unclear how ARLs on food and drink packages affect minors' purchasing behavior. High school students aged 14 to 17 years (n = 150, M

Realizing Effectiveness Across Continents With Hydroxyurea: Enrollment And Baseline Characteristics Of The Multicenter Reach Study In Sub-Saharan Africa., P. T. Mcgann, T. N. Williams, P. Olupot-Olupot, G. A. Tomlinson, A. Lane, J. Luís Reis Da Fonseca, R. Kitenge, G. Mochamah, B. Aygun, R. E. Ware, +7 Additional Authors

Journal Articles

Despite its well-described safety and efficacy in the treatment of sickle cell anemia (SCA) in high-income settings, hydroxyurea remains largely unavailable in sub-Saharan Africa, where more than 75% of annual SCA births occur and many comorbidities exist. Realizing Effectiveness Across Continents with Hydroxyurea (REACH, ClinicalTrials.gov NCT01966731) is a prospective, Phase I/II open-label trial of hydroxyurea designed to evaluate the feasibility, safety, and benefits of hydroxyurea treatment for children with SCA in four sub-Saharan African countries. Following comprehensive training of local research teams, REACH was approved by local Ethics Committees and achieved full enrollment ahead of projections with 635 participants enrolled …

Delays To Care In Pediatric Lupus Patients: Data From The Childhood Arthritis And Rheumatology Research Alliance Legacy Registry., Tamar B Rubinstein, Wenzhu B Mowrey, Norman T Ilowite, Dawn M Wahezi, L. Abramson, E. Anderson, M. Andrew, N. Battle, J. Chang, B. Gottlieb, +90 Additional Authors

Journal Articles

OBJECTIVE: Prompt treatment for lupus is important to prevent morbidity. A potential barrier to early treatment of pediatric lupus is delayed presentation to a pediatric rheumatologist. To better understand factors contributing to delayed presentation among pediatric lupus patients, we examined differences in demographic and clinical characteristics of lupus patients within the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Legacy Registry with regard to time between symptom onset and presentation to a pediatric rheumatologist.

METHODS: We analyzed data from 598 CARRA Legacy Registry participants for differences between those who presented early (withinonset), between 1-3 months (typical presentation), with moderate delays (3-12 …

Assessment Of A Renal Angina Index For Prediction Of Severe Acute Kidney Injury In Critically Ill Children: A Multicentre, Multinational, Prospective Observational Study., R. K. Basu, A. Kaddourah, S. L. Goldstein, A. Akcan-Arikan, M. Arnold, C. Cruz, J. Schneider, T. Sweberg, A. Kessel, J. Zaritsky, +73 Additional Authors

Journal Articles

Background: Acute kidney injury (AKI) occurs in one in four children admitted to the intensive care unit (ICU) and AKI severity is independently associated with increased patient morbidity and mortality. Early prediction of AKI has the potential to improve outcomes. In smaller, single center populations, we have previously derived and validated the performance of the renal angina index (RAI), a context driven risk stratification system, to predict severe AKI.

Methods: A prospective, observational study (AWARE

Findings: The 1590 patients studied were 55% male and had median age of 54.5 months. 286 patients (17.9%) were RA+. AKI

Interpretation: Earlier, better prediction …

Congenital Adrenal Hyperplasia Due To Steroid 21-Hydroxylase Deficiency: An Endocrine Society Clinical Practice Guideline, P. W. Speiser, W. Arlt, R. J. Auchus, L. S. Baskin, G. S. Conway, D. P. Merke, H. F. Meyer-Bahlburg, W. L. Miller, M. H. Murad, S. E. Oberfield, P. C. White

Journal Articles

Objective: To update the congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency clinical practice guideline published by the Endocrine Society in 2010.Conclusions: The writing committee presents updated best practice guidelines for the clinical management of congenital adrenal hyperplasia based on published evidence and expert opinion with added considerations for patient safety, quality of life, cost, and utilization.

Management Of Acute Pancreatitis In The Pediatric Population: A Clinical Report From The North American Society For Pediatric Gastroenterology, Hepatology And Nutrition Pancreas Committee., M. Abu-El-Haija, S. Kumar, J. A. Quiros, K. Balakrishnan, B. Barth, S. Bitton, J. F. Eisses, E. J. Foglio, V. Fox, V. D. Morinville, +10 Additional Authors

Journal Articles

BACKGROUND:Although the incidence of acute pancreatitis (AP) in children is increasing, management recommendations rely on adult published guidelines. Pediatric-specific recommendations are needed. METHODS:The North American Society for Pediatric Gastroenterology, Hepatology and Nutrition Pancreas committee performed a MEDLINE review using several preselected key terms relating to management considerations in adult and pediatric AP. The literature was summarized, quality of evidence reviewed, and statements of recommendations developed. The authorship met to discuss the evidence, statements, and voted on recommendations. A consensus of at least 75% was required to approve a recommendation. RESULTS:The diagnosis of pediatric AP should follow the published INternational Study …

Management Of Acute Pancreatitis In The Pediatric Population: A Clinical Report From The North American Society For Pediatric Gastroenterology, Hepatology And Nutrition Pancreas Committee, M. Abu-El-Haija, S. Kumar, J. A. Quiros, K. Balakrishnan, B. Barth, S. Bitton, J. F. Eisses, E. J. Foglio, V. Fox, V. D. Morinville, +14 Additional Authors

Journal Articles

No abstract provided.

Development Of A Novel Renal Activity Index Of Lupus Nephritis In Children & Young Adults, H. I. Brunner, M. Bennett, K. Abulaban, M. Klein-Gitelman, K. O'Neil, L. Tucker, S. Ardoin, K. Rouster-Stevens, B. A. Eberhard, P. Devarajan, +8 Additional Authors

Journal Articles

BACKGROUND: Noninvasive estimation of the degree of inflammation seen on kidney biopsy with lupus nephritis (LN) remains difficult. The objective of this study was to develop a Renal Activity Index for Lupus (RAIL) that, based solely on laboratory measures, accurately reflects histological LN activity. METHODS: We assayed traditional LN laboratory tests and 16 urine biomarkers (UBMs) in children (n=47) at the time of kidney biopsy. Histological LN activity was measured by the NIH Activity Index (NIH-AI) and the Tubulointerstitial Activity Index (TIAI). High LN-activity status (vs. moderate/low) was defined as NIH-AI scores > 10 (vs.5 (vs.92% accuracy and LN-activityTIAI status with …

Impact Of The 2008 Beijing Olympics On The Risk Of Pregnancy Complications, V. Assibey-Mensah, K. Liu, S. W. Thurston, T. P. Stevens, J. Zhang, C. Kane, Y. Pan, B. Weinberger, D. Q. Rich, +2 Additional Authors

Journal Articles

Taking advantage of the natural experiment of the 2008 Beijing Olympics (August 8 to September 24), when air pollution levels decreased by 13% to 60%, the authors assessed whether having >/=1 pregnancy month during the Olympics was associated with decreased risks of hypertensive disorders (HDs) and/or fetal-placental conditions (FPCs). Singleton births to mothers with >/=1 pregnancy month in 2008 or 2009 (N = 56,155) were included. Using generalized additive models, the authors estimated the risk of HDs and FPCs associated with (1) the 2008 Olympics compared with the same dates in 2009, and (2) increased mean ambient PM10 (particulate matter …

Endocrine Dysfunction In Diamond-Blackfan Anemia (Dba): A Report From The Dba Registry (Dbar), A. Lahoti, Y. T. Harris, P. W. Speiser, E. Atsidaftos, J. M. Lipton, A. Vlachos

Journal Articles

BACKGROUND: Diamond-Blackfan anemia (DBA) is a rare inherited bone marrow failure syndrome. The mainstays of treatment involve chronic red cell transfusions, long-term glucocorticoid therapy, and stem cell transplantation. Systematic data concerning endocrine function in DBA are limited. We studied patients in the DBA Registry (DBAR) of North America to assess the prevalence of various endocrinopathies. PROCEDURE: In a pilot study, retrospective data were collected for 12 patients with DBA. Subsequently, patients with DBA aged 1-39 years were recruited prospectively. Combined, 57 patients were studied; 38 chronically transfused, 12 glucocorticoid-dependent, and seven in remission. Data were collected on anthropometric measurements, systematic …

Hydroxyurea Therapy For Children With Sickle Cell Anemia In Sub-Saharan Africa: Rationale And Design Of The Reach Trial, P. T. Mcgann, L. Tshilolo, B. Santos, G. A. Tomlinson, S. Stuber, T. Latham, B. Aygun, S. K. Obaro, P. Olupot-Olupot, R. E. Ware, +2 Additional Authors

Journal Articles

BACKGROUND: Sickle cell anemia (SCA) is an inherited hematological disorder that causes a large but neglected global health burden, particularly in Africa. Hydroxyurea represents the only available disease-modifying therapy for SCA, and has proven safety and efficacy in high-resource countries. In sub-Saharan Africa, there is minimal use of hydroxyurea, due to lack of data, absence of evidence-based guidelines, and inexperience among healthcare providers. PROCEDURE: A partnership was established between investigators in North America and sub-Saharan Africa, to develop a prospective multicenter research protocol designed to provide data on the safety, feasibility, and benefits of hydroxyurea for children with SCA. RESULTS: …

Hydroxycarbamide Versus Chronic Transfusion For Maintenance Of Transcranial Doppler Flow Velocities In Children With Sickle Cell Anaemia-Tcd With Transfusions Changing To Hydroxyurea (Twitch): A Multicentre, Open-Label, Phase 3, Non-Inferiority Trial, R. E. Ware, B. R. Davis, W. H. Schultz, R. C. Brown, B. Aygun, S. Sarnaik, I. Odame, B. Fuh, R. J. Adams, +36 Additional Authors

Journal Articles

BACKGROUND: For children with sickle cell anaemia and high transcranial doppler (TCD) flow velocities, regular blood transfusions can effectively prevent primary stroke, but must be continued indefinitely. The efficacy of hydroxycarbamide (hydroxyurea) in this setting is unknown; we performed the TWiTCH trial to compare hydroxyurea with standard transfusions. METHODS: TWiTCH was a multicentre, phase 3, randomised, open-label, non-inferiority trial done at 26 paediatric hospitals and health centres in the USA and Canada. We enrolled children with sickle cell anaemia who were aged 4-16 years and had abnormal TCD flow velocities (>/=200 cm/s) but no severe vasculopathy. After screening, eligible …

Non-Invasive Assessment Of Endothelial Function In Children With Obesity And Lipid Disorders, L. C. Hudgins, V. Annavajjhala, A. Kovanlikaya, M. D. Frank, A. Solomon, T. S. Parker, R. S. Cooper

Journal Articles

BACKGROUND: Digital tonometry is designed to non-invasively screen for endothelial dysfunction by the detection of impaired flow-induced reactive hyperaemia in the fingertip. We determined whether digital reactive hyperaemia correlated with risk factors for atherosclerosis in two groups of children at increased risk for endothelial dysfunction. METHODS: A total of 15 obese children and 23 non-obese, dyslipidaemic children, 8-21 years of age, were enrolled, and their medical histories, anthropometric measurements, carotid wall thickness by means of ultrasonography, and fasting blood samples for cardiovascular risk factors were obtained. The standard endoPAT index of digital reactive hyperaemia was modified to reflect the true …

Organ Iron Accumulation In Chronically Transfused Children With Sickle Cell Anaemia: Baseline Results From The Twitch Trial, J. C. Wood, A. R. Cohen, S. L. Pressel, B. Aygun, H. Imran, L. Luchtman-Jones, A. A. Thompson, B. Fuh, W. H. Schultz, R. E. Ware, +1 Additional Author

Journal Articles

Transcranial Doppler (TCD) With Transfusions Changing to Hydroxyurea (TWiTCH) trial is a randomized, open-label comparison of hydroxycarbamide (also termed hydroxyurea) versus continued chronic transfusion therapy for primary stroke prevention in patients with sickle cell anaemia (SCA) and abnormal TCD. Severity and location of iron overload is an important secondary outcome measure. We report the baseline findings of abdominal organ iron burden in 121 participants. At enrollment, patients were young (9.8 +/- 2.9 years), predominantly female (60:40), and previously treated with transfusions (4.1 +/- 2.4 years) and iron chelation (3.1 +/- 2.1 years). Liver iron concentration (LIC; 9.0 +/- 6.6 mg/g …

Validation Of The Lupus Nephritis Clinical Indices In Childhood-Onset Systemic Lupus Erythematosus, R. Mina, K. Abulaban, M. Klein-Gitelman, A. Eberhard, S. Ardoin, N. Singer, K. Onel, L. Tucker, K. O'Neil, H. I. Brunner, +8 Additional Authors

Journal Articles

OBJECTIVE: To validate clinical indices of lupus nephritis (LN) activity and damage when used in children against the criterion standard of kidney biopsy findings. METHODS: In 83 children requiring kidney biopsy the SLE Disease Activity Index Renal Domain (SLEDAI-R); British Isles Lupus Assessment Group index Renal Domain (BILAG-R), Systemic Lupus International Collaborating Clinics Renal Activity (SLICC-RAS) and Damage Index Renal Domain (SDI-R) were measured. Fixed effect and logistic models were done to predict International Society of Nephrology/Renal Pathology Society (ISN/RPS) class; low/moderate vs. high LN-activity [NIH Activity Index (NIH-AI) score:10; Tubulointerstitial Activity Index (TIAI) score:5) or the absence vs. presence …

Increased Hepcidin In Transferrin-Treated Thalassemic Mice Correlates With Increased Liver Bmp2 Expression And Decreased Hepatocyte Erk Activation, H. Chen, T. Choesang, H. Li, S. Sun, P. Pham, W. Bao, M. Feola, M. Westerman, L. Blanc, Y. Z. Ginzburg, +4 Additional Authors

Journal Articles

Iron overload results in significant morbidity and mortality in beta-thalassemic patients. Insufficient hepcidin is implicated in parenchymal iron overload in beta-thalassemia and approaches to increase hepcidin have therapeutic potential. We have previously shown that exogenous apo-transferrin markedly ameliorates ineffective erythropoiesis and increases hepcidin expression in Hbb(th1/th1) (thalassemic) mice. We utilize in vivo and in vitro systems to investigate effects of exogenous apo-transferrin on Smad and ERK1/2 signaling, pathways that participate in hepcidin regulation. Our results demonstrate that apo-transferrin increases hepcidin expression in vivo despite decreased circulating and parenchymal iron concentrations and unchanged liver Bmp6 mRNA expression in thalassemic mice. Hepatocytes …

Presurgical Ct Evaluation Of Congenital Aural Atresia, V. T. Nguyen, G. Paek, J. Hu, L. P. Smith

Journal Articles

Congenital aural atresia occurs in approximately 1 in 10,000‐20,000 births and may be surgically repaired if the middle ear malformation is limited in character. External auditory canal atresia is difficult to repair surgically, with significant risks and complications. Surgical candidacy in congenital aural atresia is based on multiple factors, central to which are the anatomy of the temporal bone and audiometric findings. High-resolution multidetector CT is the imaging technique of choice for anatomy delineation, although there are some specific indications for MR imaging in presurgical assessment. Various CT grading systems have been developed to determine surgical candidacy and are described …

Poly(I:C) Induces Controlled Release Of Il-36gamma From Keratinocytes In The Absence Of Cell Death, A. A. Rana, A. V. Lucs, J. Devoti, L. Blanc, J. Papoin, R. Wu, C. J. Papayannakos, A. Abramson, V. R. Bonagura, B. M. Steinberg

Journal Articles

The epithelium is part of an integrated immune system where cytokines, toll-like receptors and their ligands, and extracellular vesicles play a crucial role in initiating an innate immune response. IL-36gamma is a pro-inflammatory member of the IL-1 family that is mainly expressed by epithelial cells, but regulation of its expression and release are only beginning to be understood. Previous studies reported that IL-36gamma is abundant in recurrent respiratory papillomatosis, a rare but devastating disease caused by human papillomaviruses (HPV) types 6 and 11, in which papillomas recurrently grow in and block the airway. Despite the overexpression of IL-36gamma, papilloma tissues …

Neurologic Recovery After An Exam Consistent With Brain Death In An Adolescent With Severe Asthma, L. B. Glater-Welt, A. D. Kessel

Journal Articles

No abstract provided.

Not Just Painless Bleeding: Meckel's Diverticulum As A Cause Of Small Bowel Obstruction In Children-Two Cases And A Review Of The Literature, K. Itriyeva, M. Harris, J. Rocker, R. Gochman

Journal Articles

Physicians are educated with the classical teaching that symptomatic patients with Meckel's diverticulum (MD) most often present with painless rectal bleeding. However, a review of the literature reveals that young patients with MD will most commonly present with signs of intestinal obstruction, an etiology not frequency considered in patients presenting to the emergency department with obstruction. We present two cases of intestinal obstruction diagnosed in our emergency department, with Meckel's diverticulum being the etiology.

First Human Treatment With Investigational Rhgus Enzyme Replacement Therapy In An Advanced Stage Mps Vii Patient, J. E. Fox, L. Volpe, J. Bullaro, E. D. Kakkis, W. S. Sly

Journal Articles

Mucopolysaccharidosis type VII (MPS VII, Sly syndrome) is a very rare lysosomal storage disease caused by a deficiency of the enzyme beta-glucuronidase (GUS), which is required for the degradation of three glycosaminoglycans (GAGs): dermatan sulfate, heparan sulfate, and chondroitin sulfate. Progressive accumulation of these GAGs in lysosomes leads to increasing dysfunction in numerous tissues and organs. Enzyme replacement therapy (ERT) has been used successfully for other MPS disorders, but there is no approved treatment for MPS VII. Here we describe the first human treatment with recombinant human GUS (rhGUS), an investigational therapy for MPS VII, in a 12-year old boy …

Alemtuzumab Pharmacokinetics In Hematopoietic Stem Cell Transplants For Nonmalignant Genetic Diseases, A. Jain, I. Sahdev

Journal Articles

No abstract provided.

Assessing The Associations Of Sodium Intake With Long-Term All-Cause And Cardiovascular Mortality In A Hypertensive Cohort, P. Singer, H. Cohen, M. Alderman

Journal Articles

BACKGROUND: Although higher sodium intake is known to increase blood pressure, its association with cardiovascular mortality is less established. We examined the association of baseline sodium intake in a hypertensive cohort with all-cause and cardiovascular mortality over a mean follow-up of 18.6 years. METHODS: Three thousand five hundred five subjects were participants in a worksite hypertension program. Sodium intake was estimated by 24-hour urine excretion. Mortality data were obtained from the U.S. National Death Index. Unadjusted and multivariable-adjusted associations between sodium quartiles (quartile I (QI) to quartile IV (QIV)) and mortality were assessed using Cox models. RESULTS: Estimated mean +/- …