Medical Specialties Commons^™

Β2-Adrenergic Receptor Promoter Haplotype Influences The Severity Of Acute Viral Respiratory Tract Infection During Infancy: A Prospective Cohort Study., Pingsheng Wu, Emma K. Larkin, Sara S Reiss, Kecia N Carroll, Marshall L. Summar, Patricia A Minton, +6 Additional Authors

Pediatrics Faculty Publications

BACKGROUND: Despite the significant interest in β2-Adrenergic receptor (ADRB2) polymorphisms related to asthma, whether ADRB2 genetic variants are similarly associated with acute respiratory tract infections have not been studied. We hypothesized that genetic variants in ADRB2 associated with a response to asthma therapy during an asthma exacerbation were also associated with severity of acute respiratory tract infections.

METHODS: To test this hypothesis, we genotyped 5 common polymorphisms in the promoter region and coding block of the ADRB2 gene (loci -2387, -2274, -1343, +46, and +79) from 374 Caucasian and African American term infants who were enrolled at the time of …

Differential Expression Of The Nrf2-Linked Genes In Pediatric Septic Shock., Jocelyn R Grunwell, Scott L Weiss, Natalie Z Cvijanovich, Geoffrey L Allen, Neal J Thomas, Robert J. Freishtat, +10 Additional Authors

Pediatrics Faculty Publications

INTRODUCTION: Experimental data from animal models of sepsis support a role for a transcription factor, nuclear erythroid-related factor 2 p45-related factor 2 (Nrf2), as a master regulator of antioxidant and detoxifying genes and intermediary metabolism during stress. Prior analysis of a pediatric septic shock transcriptomic database showed that the Nrf2 response is a top 5 upregulated signaling pathway in early pediatric septic shock.

METHODS: We conducted a focused analysis of 267 Nrf2-linked genes using a multicenter, genome-wide expression database of 180 children with septic shock 10 years of age or younger and 53 healthy controls. The analysis involved RNA isolated …

Beyond Cd19: Opportunities For Future Development Of Targeted Immunotherapy In Pediatric Relapsed-Refractory Acute Leukemia., Haneen Shalabi, Anne Angiolillo, Terry J Fry

Pediatrics Faculty Publications

Chimeric antigen receptor (CAR) T cell therapy has been used as a targeted approach in cancer therapy. Relapsed and refractory acute leukemia in pediatrics has been difficult to treat with conventional therapy due to dose-limiting toxicities. With the recent success of CD 19 CAR in pediatric patients with B cell acute lymphoblastic leukemia (ALL), this mode of therapy has become a very attractive option for these patients with high-risk disease. In this review, we will discuss current treatment paradigms of pediatric acute leukemia and potential therapeutic targets for additional high-risk populations, including T cell ALL, AML, and infant ALL.

Intracellular Cd24 Disrupts The Arf-Npm Interaction And Enables Mutational And Viral Oncogene-Mediated P53 Inactivation., Lizhong Wang, Runhua Liu, Peiying Ye, Chunshu Wong, Guo-Yun Chen, Penghui Zhou, +11 Additional Authors

Pediatrics Faculty Publications

CD24 is overexpressed in nearly 70% human cancers, whereas TP53 is the most frequently mutated tumour-suppressor gene that functions in a context-dependent manner. Here we show that both targeted mutation and short hairpin RNA (shRNA) silencing of CD24 retard the growth, progression and metastasis of prostate cancer. CD24 competitively inhibits ARF binding to NPM, resulting in decreased ARF, increase MDM2 and decrease levels of p53 and the p53 target p21/CDKN1A. CD24 silencing prevents functional inactivation of p53 by both somatic mutation and viral oncogenes, including the SV40 large T antigen and human papilloma virus 16 E6-antigen. In support of the …

Acute Glomerular Diseases In Children, Kanwal Kher

Pediatrics Faculty Publications

Glomerulonephritis [GN] is one of the common acquired pediatric renal disorders encountered in clinical practice. The clinical manifestations include gross or microscopic hematuria, proteinuria, and nephrotic syndrome. Renal dysfunction and hypertension may also be present in many patients. Etiopathogenesis of GN can be idiopathic in a large majority, while some may result from infections or known immune disorders. Several of these disorders are now believed to arise from dysfunctions of podocytes and are grouped under the heading of “podocytopathies”. This review focuses on the clinical manifestations and management of the common forms of acute GN encountered in children.

Genetic And Informatic Analyses Implicate Kif12 As A Candidate Gene Within The Mpkd2 Locus That Modulates Renal Cystic Disease Severity In The Cys1cpk Mouse., Michal Mrug, Juling Zhou, Chaozhe Yang, Bruce J Aronow, Xiangqin Cui, Trenton R Schoeb, Gene P Siegal, Bradley K Yoder, Lisa M. Guay-Woodford

Pediatrics Faculty Publications

We have previously mapped the interval on Chromosome 4 for a major polycystic kidney disease modifier (Mpkd) of the B6(Cg)-Cys1cpk/J mouse model of recessive polycystic kidney disease (PKD). Informatic analyses predicted that this interval contains at least three individual renal cystic disease severity-modulating loci (Mpkd1-3). In the current study, we provide further validation of these predicted effects using a congenic mouse line carrying the entire CAST/EiJ (CAST)-derived Mpkd1-3 interval on the C57BL/6J background. We have also generated a derivative congenic line with a refined CAST-derived Mpkd1-2 interval and demonstrated its dominantly-acting disease-modulating effects (e.g., 4.2-fold increase in total cyst area; …

Extraordinary Diversity Of Immune Response Proteins Among Sea Urchins: Nickel-Isolated Sp185/333 Proteins Show Broad Variations In Size And Charge., Lauren S. Sherman, Catherine S. Schrankel, Kristy J. Brown, L. Courtney Smith

Pediatrics Faculty Publications

Effective protection against pathogens requires the host to produce a wide range of immune effector proteins. The Sp185/333 gene family, which is expressed by the California purple sea urchin Strongylocentrotus purpuratus in response to bacterial infection, encodes a highly diverse repertoire of anti-pathogen proteins. A subset of these proteins can be isolated by affinity to metal ions based on multiple histidines, resulting in one to four bands of unique molecular weight on standard Western blots, which vary depending on the individual sea urchin. Two dimensional gel electrophoresis (2DE) of nickel-isolated protein samples followed by Western blot was employed to detect …

Mllt1 Yeats Domain Mutations In Clinically Distinctive Favourable Histology Wilms Tumours., Elizabeth J Perlman, Samantha Gadd, Stefan T Arold, Anand Radhakrishnan, Daniela S Gerhard, Jeffrey S. Dome, +19 Additional Authors

Pediatrics Faculty Publications

Wilms tumour is an embryonal tumour of childhood that closely resembles the developing kidney. Genomic changes responsible for the development of the majority of Wilms tumours remain largely unknown. Here we identify recurrent mutations within Wilms tumours that involve the highly conserved YEATS domain of MLLT1 (ENL), a gene known to be involved in transcriptional elongation during early development. The mutant MLLT1 protein shows altered binding to acetylated histone tails. Moreover, MLLT1-mutant tumours show an increase in MYC gene expression and HOX dysregulation. Patients with MLLT1-mutant tumours present at a younger age and have a high prevalence of precursor intralobar …

A Novel Approach Using Liquid Embolic Agent For The Treatment Of Pancreatic-Cutaneous Fistulas: Report Of A Case, Amye M. Farag, Priti Parikh, Tamer Malik, Shannon L. Kauffman

Department of Surgery Faculty Publications

Pancreatic fistula formation remains one of the most dreadful complications after pancreaticoduodenectomies, resulting in extended hospital stays, increased healthcare costs, along with significantly increased morbidity and mortality. Little is mentioned in the literature about the use of percutaneous techniques to resolve this complication when conservative treatments fail. Thus, we developed a novel technique for treating pancreatic-cutaneous fistulas that develop post-pancreaticoduodenectomy. This work describes a novel approach of using a liquid embolic agent to treat a high-output pancreatic-cutaneous fistula after a Whipple procedure, which to the best of our knowledge after extensive literature searches, has not been performed before.

Liver Sinusoid On A Chip: Long-Term Layered Co-Culture Of Primary Rat Hepatocytes And Endothelial Cells In Microfluidic Platforms, Young Bok (Abraham) Kang, Temitope R. Sodunke, Jason Lamontagne, Joseph Cirillo, Caroline Rajiv, Michael J. Bouchard, Moses Noh

Faculty Publications - Biomedical, Mechanical, and Civil Engineering

We describe the generation of microfluidic platforms for the co-culture of primary hepatocytes and endothelial cells; these platforms mimic the architecture of a liver sinusoid. This paper describes a progressional study of creating such a liver sinusoid on a chip system. Primary rat hepatocytes (PRHs) were co-cultured with primary or established endothelial cells in layers in single and dual microchannel configurations with or without continuous perfusion. Cell viability and maintenance of hepatocyte functions were monitored and compared for diverse experimental conditions. When primary rat hepatocytes were co-cultured with immortalized bovine aortic endothelial cells (BAECs) in a dual microchannel with continuous …

Double Inferior Venacava With Anomalous Hemiazygos Vein – A Case Report, Sumathilatha Sakthi Velavan, Bedia Castellanos, Sushama Rich, Robert B. Goldberg, Carlos Quinteros, Ramona Baez

Touro College of Osteopathic Medicine (New York) Publications and Research

Objective: Duplication of the inferior vena cava (IVC) is a rare variation that is caused by an alteration in the embryogenesis of the cardinal venous system. It is found in 0.3 to 3% of the population. There are various types of double IVC and this case is reported since it is unique among them. Materials and methods: During dissection of an eighty seven year old female cadaver, presence of an IVC was noted on either side of the abdominal aorta. The course and the termination of both the IVCs were dissected. The azygos and the hemiazygos veins were traced into …

Pulmonary Rehabilitation And Exercise In Pulmonary Arterial Hypertension: An Underutilized Intervention, Sonu Sahni, Barbara Capozzi, Asma Iftikhar, Vasiliki Sgouras, Marcin Ojrzanowski, Arunabh Talwar

Touro College of Osteopathic Medicine (New York) Publications and Research

Pulmonary arterial hypertension (PAH) is a rare and devastating disease characterized by progressive increases in pulmonary arterial pressure and pulmonary vascular resistance which eventually leads to right ventricular failure and death. Early thought process was that exercise and increased physical activity may be detrimental to PAH patients however many small cohort trials have proven otherwise. In addition to the many pharmaceutical options, exercise and pulmonary rehabilitation have also been shown to increase exercise capacity as well as various aspects of psychosomatic health. As pulmonary and exercise rehabilitation become more widely used as an adjuvant therapy patient outcomes improve and physicians …

Clinical Relevance Of The Incidentaloma: A Clinician’S Viewpoint, Sonu Sahni, Sameer Verma, Reeju S. Thomas, Barbara Capozzi, Arunabh Talwar

Touro College of Osteopathic Medicine (New York) Publications and Research

Background: CT scanning remains one of the most routinely used diagnostic tools in a setting of InterstitialLung Disease (ILD). New and improved technologies, such as High Resolution Computer Tomography (HRCT) have revolutionized the quality of imaging, leading to a prominent increase in number of incidental findings that may or may not be of any clinical significance. The aim of this study was to evaluate the prevalence of incidental findings on thoracic CT and their clinical significance.

Methods: Retrospective analysis was conducted on a cohort of 84 patients referred to our academic center as cases of ILD. Patients were …

Caregiver Perceptions Of Their Influence On Cancer Treatment Decision Making: Intersections Of Language, Identity, And Illness, Janice L. Krieger, Angela L. Palmer-Wackerly, Jessica L. Krok-Schoen, Phokeng M. Dailey, Julianne C. Wojno, Nancy Schoenberg, Electra D. Paskett, Mark Dignan

Department of Communication Studies: Faculty Publications

Serious illness of a loved one can disrupt a caregiver’s sense of self and relationships. We examined the language caregivers use to describe the cancer treatment decision making of a loved one to understand how caregivers frame their own identity relative to a patient’s illness. We analyzed transcripts from in-depth interviews conducted with caregivers (N = 58) of cancer patients to examine the intersection among language, identity, and illness. Caregivers with a patient-level personal identity frame used phrases such as their body, their decision. Caregivers with a relational identity frame used plural pronouns such as we or our when describing …

Single-Portal Arthroscopy Of The Central Compartment Of The Hip, S. Mannava, E. A. Howse, T. J. Kelsey, R. H. Barnes, A. Antunes, A. J. Stubbs

Journal Articles

Since hip arthroscopy has become a standard of orthopaedic practice, the indications have continued to expand as it has proved to be a helpful diagnostic, as well as therapeutic, tool. Access to the hip joint, however, remains challenging for the orthopaedic surgeon who does not routinely perform hip arthroscopy. We present a single-portal arthroscopic technique, showing the feasibility of single-portal arthroscopic access to the hip joint, as well as describing basic indications and instrumentation for single-portal hip arthroscopy. Single-portal hip arthroscopy is ideal for the patient who needs to undergo diagnostic hip arthroscopy or for treatment in patients with simple …

What Is The Prevalence And Success Of Remediation Of Emergency Medicine Residents?, M. Silverberg, M. Weizberg, T. Murano, J. L. Smith, J. C. Burkhardt, S. A. Santen

Journal Articles

INTRODUCTION: The primary objective of this study was to determine the prevalence of remediation, competency domains for remediation, the length, and success rates of remediation in emergency medicine (EM). METHODS: We developed the survey in Surveymonkey with attention to content and response process validity. EM program directors responded how many residents had been placed on remediation in the last three years. Details regarding the remediation were collected including indication, length and success. We reported descriptive data and estimated a multinomial logistic regression model. RESULTS: We obtained 126/158 responses (79.7%). Ninety percent of programs had at least one resident on remediation …

Arthroscopic Excision Of Acetabular Osteoid Osteoma: Computer Tomography-Guided Approach, C. Tamam, E. A. Howse, M. Tamam, R. H. Barnes, T. J. Kelsey, B. Perry, A. J. Stubbs

Journal Articles

Osteoid osteoma is a benign osteoblastic tumor that occurs in the subcortical shaft and metaphysis of the long bones of the lower extremities; however, intra-articular lesions are also possible. Intra-articular osteoid osteomas are rare, and clinical symptoms are often less specific and, thereby, may lead to misdiagnosis. The definitive treatment for osteoid osteoma is the excision of the nidus. We present the case of a 23-year-old man with a 4-year history of right anterior hip pain, subsequently diagnosed with a subarticular osteoid osteoma located in the right anterior acetabulum. Hip arthroscopic excision of the juxta-articular osteoid osteoma is presented as …

An Ongoing Search For Potential Targets And Therapies For Lethal Sepsis, G. Q. Bao, L. He, D. Lee, J. D'Angelo, H. C. Wang

Journal Articles

Sepsis, which refers to a systemic inflammatory response syndrome resulting from a microbial infection, represents the leading cause of death in intensive care units. The pathogenesis of sepsis remains poorly understood although it is attributable to dysregulated immune responses orchestrated by innate immune cells that are sequentially released early (e.g., tumor necrosis factor(TNF), interleukin-1(IL-1), and interferon-gamma(IFN-gamma)) and late (e.g., high mobility group box 1(HMGB1)) pro-inflammatory mediators. As a ubiquitous nuclear protein, HMGB1 can be passively released from pathologically damaged cells, thereby converging infection and injury on commonly dysregulated inflammatory responses. We review evidence that supports extracellular HMGB1 as a late …

Bedside Echocardiography For Undifferentiated Hypotension: Diagnosis Of A Right Heart Thrombus, J. F. Kenny, X. Zhong, C. Brown, D. Das, B. Royall, M. Kapoor

Journal Articles

A free-floating right heart thrombus is often a harbinger of a massive pulmonary embolism and must be diagnosed and treated rapidly in order to avoid significant adverse sequelae. We present the case of an 84-year-old female who presented with two days of dyspnea and was hypotensive on arrival. Bedside ultrasound was performed by the emergency physician and showed a large, mobile right heart thrombus leading to immediate administration of a thrombolytic. In this case, bedside ultrasound was utilized to help further delineate clinical care in a progressively worsening patient, leading to a potentially lifesaving treatment.

Serum Amyloid A Stimulates Pkr Expression And Hmgb1 Release Possibly Through Tlr4/Rage Receptors, W. Li, S. Zhu, J. Li, J. D'Amore, J. D'Angelo, H. Yang, P. Wang, K. J. Tracey, H. Wang

Journal Articles

Serum amyloid A proteins (SAAs) have been suggested as surrogate markers of sepsis, but their pathogenic roles remain poorly elucidated. Here we provide evidence to support a possible role of SAA as a pathogenic mediator of lethal sepsis. In a subset of septic patients whose serum HMGB1 levels paralleled with the clinical scores, some anti-HMGB1 antibodies detected a 12 kDa protein belonging to the SAA family. In contrast to the most abundant SAA1, human SAA induced PKR expression and HMGB1 release in the wild-type, but not TLR4/RAGE-deficient, macrophages. Pharmacological inhibition of PKR phosphorylation blocked SAA-induced HMGB1 release, suggesting an important …

Cannabinoid Cb2 Receptors In A Mouse Model Of A Beta Amyloidosis: Immunohistochemical Analysis And Suitability As A Pet Biomarker Of Neuroinflammation, A. V. Savonenko, T. Melnikova, Y. C. Wang, H. Ravert, Y. J. Gao, J. Koppel, D. Lee, P. Davies, M. G. Pomper, A. G. Horti, +6 Additional Authors

Journal Articles

In Alzheimer's disease (AD), one of the early responses to A beta amyloidosis is recruitment of microglia to areas of new plaque. Microglial receptors such as cannabinoid receptor 2 (CB2) might be a suitable target for development of PET radiotracers that could serve as imaging biomarkers of A beta-induced neuroinflammation. Mouse models of amyloidosis (J20APPswe/ind and APPswe/PS1 Delta E9) were used to investigate the cellular distribution of CB2 receptors. Specificity of CB2 antibody (H60) was confirmed using J20APPswe/ind mice lacking CB2 receptors. APPswe/PS1 Delta E9 mice were used in small animal PET with a CB2-targeting radiotracer, [C-11]A836339. These studies revealed …

Achilles Tendon Rupture, S. P. Stickles, L. Friedman, M. Demarest, C. Raio

Journal Articles

No abstract provided.

Choledochal Cyst Mimicking Gallbladder With Stones In A Six-Year-Old With Right-Sided Abdominal Pain, R. Subramony, N. Kittisarapong, I. Barata, M. Nelson

Journal Articles

Choledochal cysts are rare but serious bile duct abnormalities are found in young children, usually during the first year of life.1 They require urgent surgical intervention due to the risk of developing cholangiocarcinoma.2 Clinicians should consider this diagnosis and perform a point-of-care ultrasound (POCUS) when a child presents to the emergency department (ED) with findings of jaundice, abdominal pain, and the presence of an abdominal mass. We present the case of a six-year-old child presenting only with abdominal pain upon arrival to our ED and was ultimately diagnosed by POCUS to have a choledochal cyst.

Have First-Year Emergency Medicine Residents Achieved Level 1 On Care-Based Milestones?, M. Weizberg, M. C. Bond, M. Cassara, C. Doty, J. Seamon

Journal Articles

BACKGROUND: Residents in Accreditation Council for Graduate Medical Education accredited emergency medicine (EM) residencies were assessed on 23 educational milestones to capture their progression from medical student level (Level 1) to that of an EM attending physician (Level 5). Level 1 was conceptualized to be at the level of an incoming postgraduate year (PGY)-1 resident; however, this has not been confirmed. OBJECTIVES: Our primary objective in this study was to assess incoming PGY-1 residents to determine what percentage achieved Level 1 for the 8 emergency department (ED) patient care-based milestones (PC 1-8), as assessed by faculty. Secondary objectives involved assessing …

Novel Mechanisms Of Herbal Therapies For Inhibiting Hmgb1 Secretion Or Action, A. H. Wu, L. He, W. Long, Q. Zhou, S. Zhu, P. Wang, S. Fan, H. Wang

Journal Articles

High mobility group box 1 (HMGB1) is an evolutionarily conserved protein and is constitutively expressed in virtually all types of cells. In response to microbial infections, HMGB1 is secreted from activated immune cells to orchestrate rigorous inflammatory responses. Here we review the distinct mechanisms by which several herbal components inhibit HMGB1 action or secretion, such as by modulating inflammasome activation, autophagic degradation, or endocytic uptake. In light of the reciprocal interactions between these cellular processes, it is possible to develop more effective combinational herbal therapies for the clinical management of inflammatory diseases.

Editorial Comment: Symposium: Biologics And Tissue Healing In Orthopaedics, A. Bedi, J. Dines

Journal Articles

No abstract provided.

Minimally Invasive Scoliosis Surgery: A Novel Technique In Patients With Neuromuscular Scoliosis, V. Sarwahi, T. Amaral, S. Wendolowski, R. Gecelter, M. Gambassi, C. Plakas, B. Liao, S. Kalantre, C. Katyal

Journal Articles

Minimally invasive surgery (MIS) has been described in the treatment of adolescent idiopathic scoliosis (AIS) and adult scoliosis. The advantages of this approach include less blood loss, shorter hospital stay, earlier mobilization, less tissue disruption, and relatively less pain. However, despite these significant benefits, MIS approach has not been reported in neuromuscular scoliosis patients. This is possibly due to concerns with longer surgery time, which is further increased due to more levels fused and instrumented, challenges of pelvic fixation, size and number of incisions, and prolonged anesthesia. We modified the MIS approach utilized in our AIS patients to be implemented …

Systemic Lupus Erythematosus Is Not A Risk Factor For Poor Outcomes After Total Hip And Total Knee Arthroplasty, U. H. Shah, L. A. Mandl, C. Mertelsmann-Voss, Y. Y. Lee, M. M. Alexiades, M. P. Figgie, S. M. Goodman

Journal Articles

OBJECTIVES: Historically, arthroplasty in systemic lupus erythematosus (SLE) patients has been less successful than for patients with osteoarthritis (OA). It is not known if SLE remains an independent risk factor for poor arthroplasty outcomes or if other factors, such as avascular necrosis (AVN), continue to play a role. METHODS: A case-control study using data from a single-institution arthroplasty registry compared SLE total hip arthroplasty (THA) and total knee arthroplasty (TKA) with OA controls matched by age, gender and presence of AVN. Baseline, two-year administrative and self-report data, and diagnosis leading to arthroplasty were evaluated. RESULTS: A total of 54 primary …

Doha Agreement Meeting On Terminology And Definitions In Groin Pain In Athletes, A. Weir, P. Brukner, E. Delahunt, J. Ekstrand, G. Lovell, T. Tyler, G. Verrall, R. J. De Vos, Z. Vuckovic, P. Holmich, +14 Additional Authors

Journal Articles

Background Heterogeneous taxonomy of groin injuries in athletes adds confusion to this complicated area. Aim The 'Doha agreement meeting on terminology and definitions in groin pain in athletes' was convened to attempt to resolve this problem. Our aim was to agree on a standard terminology, along with accompanying definitions. Methods A one-day agreement meeting was held on 4 November 2014. Twenty-four international experts from 14 different countries participated. Systematic reviews were performed to give an up-to-date synthesis of the current evidence on major topics concerning groin pain in athletes. All members participated in a Delphi questionnaire prior to the meeting. …

Platelet-Rich Plasma And Other Cellular Strategies In Orthopedic Surgery, P. N. Williams, G. Moran, J. P. Bradley, N. S. Elattrache, J. S. Dines

Journal Articles

The use of biologics in the treatment of musculoskeletal disease has become increasingly more common as research studies continue to provide further elucidation of their mechanisms in healing. Platelet-rich plasma, patches, growth factors, and stem cells are among the many biologics under active investigation and have varying levels of success in augmenting surgical or nonoperative interventions. However, the limitations of these treatments exist, and clear guidelines for their indications and application have yet to be established. Well-designed clinical trials will help determine the appropriate future use of biologics to ensure consistent outcomes.