424 results match your criteria: "the University of Pennsylvania Perelman School of Medicine[Affiliation]"

Background: Alagille syndrome (ALGS) is a multisystem cholestatic disorder. Maralixibat is approved for the treatment of cholestatic pruritus in ALGS with limited data in adults.

Methods: Participants were included if they received ≥ 2 doses of maralixibat at age ≥ 16 years in one of the three previously published maralixibat ALGS clinical trials.

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Objectives: ImPACTS (Improving Acute Care Through Simulation) is a collaborative simulation-based program partnering pediatric specialty centers ("hubs") with general emergency departments (GEDs) to improve pediatric acute care. Objective measurements of ImPACTS, such as evaluating Pediatric Readiness Score (PRS) and simulation-based outcome improvements, have been reported previously. Barriers to and facilitators of program involvement and the downstream effects of the program have not been previously described.

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Relapsed childhood T-cell acute lymphoblastic leukemia and lymphoblastic lymphoma.

Haematologica

January 2025

Division of Oncology, the Children's Hospital of Philadelphia, Philadelphia, PA, USA; Department of Pediatrics, the University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.

While outcomes for pediatric acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) have improved dramatically in recent decades, relapsed and refractory disease remain a significant therapeutic challenge. This is particularly true for patients with T-cell ALL and LBL, where survival for patients with relapsed/refractory disease remains dismal. Recent efforts to comprehensively profile the genomics of T-ALL/LBL to improve understanding of disease biology have enhanced our ability to identify high-risk patients at diagnosis who are more likely to relapse and have also identified novel targets for precision medicines.

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Background: Modern techniques in lower extremity amputation have made significant advances to improve prosthetic control and soft-tissue envelopes through various techniques, including medial thighplasties. These advances are necessary to enhance the fit and functionality of the prosthesis in transfemoral amputations.

Methods: We performed a retrospective review of all thighplasties performed at our institution in patients with ipsilateral transfemoral amputation from November 2017 to December 2021.

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Objective: SCN2A encodes the voltage-gated sodium (Na+) channel α subunit Na1.2, which is important for the generation and forward and back propagation of action potentials in neurons. Genetic variants in SCN2A are associated with a spectrum of neurodevelopmental disorders.

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Low Penetrance Sarcomere Variants Contribute to Additive Risk in Hypertrophic Cardiomyopathy.

Circulation

December 2024

Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor. (E.D.S., Y.-C.T., B.E., A.B., O.M., S.S., A.S.H.).

Article Synopsis
  • - Hypertrophic cardiomyopathy (HCM) was traditionally seen as caused by rare, high-risk single-gene changes, but new research indicates common low-risk variants (LowSVs) also play a significant role in the disease.
  • - In a study of over 6000 patients, 12 LowSVs were discovered, which are relatively common in the general population and more prevalent in HCM patients, suggesting they may influence disease severity and risk.
  • - While LowSVs alone are linked to a later onset of HCM and fewer complications, their presence alongside more severe genetic variants increases health risks significantly.
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Article Synopsis
  • The study investigates the effectiveness of enoxaparin, a medication for preventing blood clots, in critically ill children, focusing on differences in response based on age, particularly between older children and infants.
  • It consists of two simultaneous clinical trials: one for older children aged 1-17 years, and another for infants under 1 year, with specific dosing protocols for each group.
  • The trials are set in multiple pediatric intensive care units across the U.S., using methods like randomization, ultrasonography, and blood analysis to assess outcomes and monitor safety.
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Lung Transplantation.

N Engl J Med

November 2024

From the Division of Pulmonary Allergy and Critical Care Medicine, Center for Clinical Epidemiology and Biostatistics, Lung Biology Institute at the University of Pennsylvania Perelman School of Medicine, Philadelphia (J.D.C.); the Department of Thoracic Surgery, University Hospitals Leuven, and the Laboratory of Respiratory Diseases and Thoracic Surgery, Department of Chronic Diseases and Metabolism, KU Leuven University - both in Leuven, Belgium (D.V.R.); and the Department of Transplantation and Regenerative Medicine, Newcastle University Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom (A.J.F.).

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Long-Term Effects of Empagliflozin in Patients with Chronic Kidney Disease.

N Engl J Med

October 2024

From the Renal Studies Group, Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom (W.G.H., N.S., N.A., C.W., J.R.E., D.P., P.J., D.Z., R. Dayanandan, R.A., K.J.M., S.Y.A.N., E.S., W.S., K.W., M.H., M.J.L., C.B., R.H.); the University Clinic of Würzburg, Würzburg (C.W., S.B.), Boehringer Ingelheim International (S.J.H., D.S., M.B.), Elderbrook Solutions (D.M.), and the Fifth Department of Medicine, University Medical Center Mannheim (S.J.H.) and the First Department of Medicine, Faculty of Medicine Mannheim (M.B.), University of Heidelberg, Mannheim, and the Department of Nephrology, Hospital Rechts der Isar, Technical University of Munich, Munich (D.S.) - all in Germany; Duke Clinical Research Institute, Durham, NC (J.B.G.); the University of Utah, Salt Lake City (A.K.C.); the National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing (Z.-H.L.), and Fuwai Hospital, Chinese Academy of Medical Sciences, National Center for Cardiovascular Diseases, Beijing (J.L.) - both in China; Hospital Sultanah Aminah, Johor Bahru, Malaysia (L.S.H., W.L.); the University of Tokyo School of Medicine/Toranomon Hospital (T.K.) and the University of Tokyo School of Medicine (M.N.), Tokyo, and Tokai University School of Medicine, Isehara (S.G.) - all in Japan; the University of British Columbia, Vancouver (A.L.), and the University of Toronto, Toronto (D.Z.I.C.) - both in Canada; Università degli Studi and IRCCS Ospedale Policlinico San Martino di Genova, Genoa (R.P.), and Associazione Nazionale Medici Cardiologi Ospedalieri Research Center, Florence (A.P.M.) - both in Italy; the University of Pennsylvania Perelman School of Medicine, Philadelphia (R. Deo); Providence Health Care and University of Washington, Seattle (K.R.T.); and Hospital Universitario Son Espases, Health Research Institute of the Balearic Islands, Universitat Illes Balears, Palma de Mallorca, Spain (X.R.).

Article Synopsis
  • The EMPA-KIDNEY trial examined the effects of empagliflozin, an SGLT2 inhibitor, on patients with chronic kidney disease at risk for progression, assessing outcomes during and after the trial.
  • A total of 6609 patients were randomized, with 4891 participating in a follow-up period after the trial where they were observed for an additional 2 years, without trial medication but allowed to use other SGLT2 inhibitors.
  • Results showed that fewer primary outcome events (like kidney disease progression or cardiovascular death) occurred in the empagliflozin group (26.2%) compared to the placebo group (30.3%), suggesting lasting benefits of the drug even after the trial ended. *
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DDX17 is an RNA helicase shown to be involved in critical processes during the early phases of neuronal differentiation. Globally, we compiled a case-series of 11 patients with neurodevelopmental phenotypes harbouring de novo monoallelic variants in DDX17. All 11 patients in our case series had a neurodevelopmental phenotype, whereby intellectual disability, delayed speech and language, and motor delay predominated.

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Article Synopsis
  • The pathogenic variant -p.Ala421Val (A421V) is linked to severe developmental and epileptic issues, including treatment-resistant epilepsy with various seizure types, but the exact disease mechanisms remain unclear.
  • This study created a transgenic mouse model carrying the A421V variant, revealing that its expression leads to epilepsy and early death, along with decreased functions in key inhibitory neurons in the brain.
  • Findings showed that the A421V variant disrupts potassium channel expression and neuronal excitability, causing network dysfunction that underlies the observed epileptic encephalopathy.
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Nucleoside-modified mRNA-LNP vaccines have revolutionized vaccine development against infectious pathogens due to their ability to elicit potent humoral and cellular immune responses. In this article, we present the results of the first norovirus vaccine candidate employing mRNA-LNP platform technology. The mRNA-LNP bivalent vaccine encoding the major capsid protein VP1 from GI.

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Galactic cosmic radiation (GCR) is an unavoidable risk to astronauts that may affect mission success. Male rodents exposed to 33-beam-GCR (33-GCR) show short-term cognitive deficits but reports on female rodents and long-term assessment are lacking. We asked: What are the longitudinal behavioral effects of 33-GCR on female mice? Also, can an antioxidant/anti-inflammatory compound (CDDO-EA) mitigate the impact of 33-GCR? Mature (6-month-old) C57BL/6J female mice received CDDO-EA (400 μg/g of food) or a control diet (vehicle, Veh) for 5 days and Sham-irradiation (IRR) or whole-body 33-GCR (0.

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The generation and maintenance of protective immunity is a dynamic interplay between host and environment that is impacted by age. Understanding fundamental changes in the healthy immune system that occur over a lifespan is critical in developing interventions for age-related susceptibility to infections and diseases. Here, we use multi-omic profiling (scRNA-seq, proteomics, flow cytometry) to examined human peripheral immunity in over 300 healthy adults, with 96 young and older adults followed over two years with yearly vaccination.

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Health Disparities in the Management and Outcomes of Critically Ill Children and Neonates: A Scoping Review.

Crit Care Clin

October 2024

Division of Critical Care, Department of Anesthesiology and Critical Care Medicine, Children's Hospital of Philadelphia, 3401 Civic Center Boulevard, Main Hospital, Ninth Floor, Room 9NW102, Philadelphia, PA 19104, USA; Department of Anesthesiology and Critical Care, The University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.

Article Synopsis
  • Health disparities in critically ill children have mostly been examined within individual ICU types, limiting broader collaboration to improve care.
  • This scoping review aims to summarize existing research on health disparities across three main ICU settings: neonatal, pediatric, and cardiac ICUs in the United States.
  • The review includes over 50 studies that highlight disparities based on race, ethnicity, insurance status, socioeconomic factors, language, and geographic distance.
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In recent years, we and others have identified a number of enhancers that, when incorporated into rAAV vectors, can restrict the transgene expression to particular neuronal populations. Yet, viral tools to access and manipulate fine neuronal subtypes are still limited. Here, we performed systematic analysis of single cell genomic data to identify enhancer candidates for each of the cortical interneuron subtypes.

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Real-world application of the pediatric Glucocorticoid Toxicity Index in childhood-onset lupus.

Semin Arthritis Rheum

October 2024

Division of Immunology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA; Division of Rheumatology, Children's Hospital of Philadelphia and the University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. Electronic address:

Article Synopsis
  • - The pediatric Glucocorticoid Toxicity Index (pGTI) is a tool developed to measure the negative effects of glucocorticoids on children's health, specifically in those with pediatric-onset systemic lupus erythematosus (pSLE).
  • - A study of 126 pSLE patients over several years found that many experienced significant toxicity, with the most frequent issues being high blood pressure (47%), mood disturbances (25%), and weight gain (21%).
  • - The findings suggest that younger age, higher BMI, and the use of rituximab when beginning glucocorticoid treatment may increase the risk of cumulative toxicity, highlighting the need for tailored assessments to improve treatment strategies for
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Pharmacologic Analgesia for Cesarean Section: An Update in 2024.

Curr Pain Headache Rep

October 2024

Department of Anesthesiology, Maternal and Child Health Hospital of Hubei Province, NO.745 Wuluo Road, Hongshan District, Wuhan, Hubei, China, 430070.

Purpose Of The Review: With the increasing prevalence of cesarean section globally, the importance of perioperative analgesia for cesarean section is becoming increasingly evident. This article provides an overview and update on the current status of cesarean section worldwide and associated analgesic regimens.

Recent Findings: Some recent studies unveiled potential association of neuraxial analgesia might be associated with children's autism, pharmacologic analgesia in obstetric will potentially gain some more attention.

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Impairment of the central nervous system (CNS) poses a significant health risk for astronauts during long-duration space missions. In this study, we employed an innovative approach by integrating single-cell multiomics (transcriptomics and chromatin accessibility) with spatial transcriptomics to elucidate the impact of spaceflight on the mouse brain in female mice. Our comparative analysis between ground control and spaceflight-exposed animals revealed significant alterations in essential brain processes including neurogenesis, synaptogenesis and synaptic transmission, particularly affecting the cortex, hippocampus, striatum and neuroendocrine structures.

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Article Synopsis
  • - Pediatric point-of-care ultrasonography (POCUS) is increasingly important in pediatric acute care, expanding beyond initial uses like assessing shock and trauma.
  • - Recent guidelines have been published to help healthcare professionals implement POCUS effectively in clinical settings.
  • - The review covers new uses and debates around POCUS in areas such as thoracic, hemodynamic, neurologic, and ocular care for children.
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Federal and state governments mandate some health care organizations to implement antibiotic stewardship programs (ASPs). Some early adopters developed model ASPs that have helped set industry standards; other benchmarks will likely be forged in subsequent regulation, legislation, and jurisprudence. This article considers how ASP designs can affect professional autonomy, especially of frontline antibiotic stewards who are usually physicians and pharmacists.

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Phase 2 Clinical Trial of VGT-309 for Intraoperative Molecular Imaging During Pulmonary Resection.

Ann Thorac Surg

May 2024

Department of Surgery, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; Division of Thoracic Surgery, Department of Surgery, University of Pennsylvania Perelman School of Medicine Philadelphia, Pennsylvania. Electronic address:

Background: Advances in intraoperative molecular imaging (IMI) may improve surgical outcomes when resecting tumors in the lung. A single-center trial was conducted using VGT-309, a cathepsin-targeted near-infrared imaging agent that causes lung nodules to fluoresce during surgical resection. The end point of this phase 2 study was to evaluate the frequency that IMI with VGT-309 resulted in a clinically significant event (CSE): localization of pulmonary nodules, discovery of unsuspected additional cancers, or identification of positive margins.

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