Multi-platform biomarkers of response to an immune checkpoint inhibitor in the neoadjuvant I-SPY 2 trial for early-stage breast cancer.

Only a subset of patients with breast cancer responds to immune checkpoint blockade (ICB). To better understand the underlying mechanisms, we analyze pretreatment biopsies from patients in the I-SPY 2 trial who receive neoadjuvant ICB using multiple platforms to profile the tumor microenvironment. A variety of immune cell populations and markers of immune/cytokine signaling associate with pathologic complete response (pCR).

Compound heterozygote variants: c.848A > G; p.Glu283Gly and c.890C > T; p.Ala297Val, of Isovaleric acid-CoA dehydrogenase gene causing severe Isovaleric acidemia with hyperammonemia.

With the execution of expanded newborn screen (NBS) program nationwide, it is uncommon to see severe hyperammonemia associated with isovaleric acidemia (IVA). We present a seven-day-old boy with severe IVA complicated by hyperammonemia. This child was flagged by NBS at 4 days old, but confirmatory testing was delayed due to COVID19 pandemic and parental skepticism.

Caveolin-1 and Sox-2 are predictive biomarkers of cetuximab response in head and neck cancer.

The epidermal growth factor receptor (EGFR) inhibitor cetuximab is the only FDA-approved oncogene-targeting therapy for head and neck squamous cell carcinoma (HNSCC). Despite variable treatment response, no biomarkers exist to stratify patients for cetuximab therapy in HNSCC. Here, we applied unbiased hierarchical clustering to reverse-phase protein array molecular profiles from patient-derived xenograft (PDX) tumors and revealed 2 PDX clusters defined by protein networks associated with EGFR inhibitor resistance.

Characterizing the Tumor Immune Microenvironment with Tyramide-Based Multiplex Immunofluorescence.

Multiplex immunofluorescence (mIF) allows simultaneous antibody-based detection of multiple markers with a nuclear counterstain on a single tissue section. Recent studies have demonstrated that mIF is becoming an important tool for immune profiling the tumor microenvironment, further advancing our understanding of the interplay between cancer and the immune system, and identifying predictive biomarkers of response to immunotherapy. Expediting mIF discoveries is leading to improved diagnostic panels, whereas it is important that mIF protocols be standardized to facilitate their transition into clinical use.

Progress Toward Identifying Exact Proxies for Predicting Response to Immunotherapies.

Clinical value and utility of checkpoint inhibitors, a drug class targeting adaptive immune suppression pathways (PD-1, PDL-1, and CTLA-4), is growing rapidly and maintains status of a landmark achievement in oncology. Their efficacy has transformed life expectancy in multiple deadly cancer types (melanoma, lung cancer, renal/urothelial carcinoma, certain colorectal cancers, lymphomas, etc.).

Fragile X Syndrome-Associated Emergency Department Visits in the United States, 2006-2011.

Using national data, we examined emergency department (ED) encounters during 2006-2011 for which a diagnosis code for fragile X syndrome (FXS) was present ( = 7,217). Almost half of ED visits coded for FXS resulted in hospitalization, which is much higher than for ED visits not coded for FXS. ED visits among females coded for FXS were slightly more likely to result in hospitalization.

Which one? What kind? How many? Types, causes, and prevalence of disability among U.S. adults.

Background: Quantifying the number of people with and types of disabilities is helpful for medical, policy, and public health planning.

Objective/hypothesis: To update prior estimates on types, prevalence, and main causes of disability among U.S.

Differences in Length of Stay and Costs Between Comparable Hospitalizations of Patients With Spina Bifida With or Without Pressure Injuries.

Objective: To estimate differences in the length of stay and costs for comparable hospitalizations of patients with spina bifida (SB) with and without pressure injuries.

Design: Retrospective, cross-sectional, observational study.

Setting: Nationwide Inpatient Sample from years 2010-2014.

Gender difference in clinical conditions among hospitalized adults with myotonic dystrophy.

Introduction: In this study we examined gender differences in adult hospitalizations with myotonic dystrophy (DM).

Methods: From the Nationwide Inpatient Sample (NIS) 2010-2014, we identified 1,891 adult hospitalizations with a DM diagnosis and constructed a comparison group of hospitalizations without DM using propensity score matching. We calculated relative risk by gender for 44 clinical diagnoses that each accounted for at least 5% of DM hospitalizations.

Evaluating Implementation of the Updated Care Considerations for Duchenne Muscular Dystrophy.

Care Considerations for Duchenne Muscular Dystrophy were published in 2010. However, little is known about the extent to which these considerations were implemented after publication. With this article, we provide direction on evaluating the uptake of the 2018 Duchenne Muscular Dystrophy Care Considerations.

Muscular Dystrophy Surveillance, Tracking, and Research Network pilot: Population-based surveillance of major muscular dystrophies at four U.S. sites, 2007-2011.

Background: For 10 years, the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet) conducted surveillance for Duchenne and Becker muscular dystrophy (DBMD). We piloted expanding surveillance to other MDs that vary in severity, onset, and sources of care.

Methods: Our retrospective surveillance included individuals diagnosed with one of nine eligible MDs before or during the study period (January 2007-December 2011), one or more health encounters, and residence in one of four U.

Diagnosis and management of Duchenne muscular dystrophy, part 2: respiratory, cardiac, bone health, and orthopaedic management.

A coordinated, multidisciplinary approach to care is essential for optimum management of the primary manifestations and secondary complications of Duchenne muscular dystrophy (DMD). Contemporary care has been shaped by the availability of more sensitive diagnostic techniques and the earlier use of therapeutic interventions, which have the potential to improve patients' duration and quality of life. In part 2 of this update of the DMD care considerations, we present the latest recommendations for respiratory, cardiac, bone health and osteoporosis, and orthopaedic and surgical management for boys and men with DMD.

Safety Evaluation of Lipid Nanoparticle-Formulated Modified mRNA in the Sprague-Dawley Rat and Cynomolgus Monkey.

The pharmacology, pharmacokinetics, and safety of modified mRNA formulated in lipid nanoparticles (LNPs) were evaluated after repeat intravenous infusion to rats and monkeys. In both species, modified mRNA encoding the protein for human erythropoietin (hEPO) had predictable and consistent pharmacologic and toxicologic effects. Pharmacokinetic analysis conducted following the first dose showed that measured hEPO levels were maximal at 6 hours after the end of intravenous infusion and in excess of 100-fold the anticipated efficacious exposure (17.

Clinical Follow-Up for Duchenne Muscular Dystrophy Newborn Screening: A Proposal.

New developments in the rapid diagnosis and treatment of boys with Duchenne muscular dystrophy (DMD) have led to growing enthusiasm for instituting DMD newborn screening (NBS) in the United States. Our group has been interested in developing clinical guidance to be implemented consistently in specialty care clinics charged with the care of presymptomatically identified newborns referred after DMD-NBS. We reviewed the existing literature covering patient-centered clinical follow-up after NBS, educational material from public health and advocacy sites, and federal recommendations on effective NBS follow-up.

MLN8054 and Alisertib (MLN8237): Discovery of Selective Oral Aurora A Inhibitors.

The Aurora kinases are essential for cell mitosis, and the dysregulation of Aurora A and B have been linked to the etiology of human cancers. Investigational agents MLN8054 (8) and alisertib (MLN8237, 10) have been identified as high affinity, selective, orally bioavailable inhibitors of Aurora A that have advanced into human clinical trials. Alisertib (10) is currently being evaluated in multiple Phase II and III clinical trials in hematological malignancies and solid tumors.

Predicting the composition of red wine blends using an array of multicomponent Peptide-based sensors.

Differential sensing using synthetic receptors as mimics of the mammalian senses of taste and smell is a powerful approach for the analysis of complex mixtures. Herein, we report on the effectiveness of a cross-reactive, supramolecular, peptide-based sensing array in differentiating and predicting the composition of red wine blends. Fifteen blends of Cabernet Sauvignon, Merlot and Cabernet Franc, in addition to the mono varietals, were used in this investigation.

Prevalence of Duchenne and Becker muscular dystrophies in the United States.

Objective: To estimate prevalence of childhood-onset Duchenne and Becker muscular dystrophies (DBMD) in 6 sites in the United States by race/ethnicity and phenotype (Duchenne muscular dystrophy [DMD] or Becker muscular dystrophy [BMD]).

Methods: In 2002, the Centers for Disease Control and Prevention established the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet) to conduct longitudinal, population-based surveillance and research of DBMD in the United States. Six sites conducted active, multiple-source case finding and record abstraction to identify MD STARnet cases born January 1982 to December 2011.

Measuring quality of life in muscular dystrophy.

Objectives: The objectives of this study were to develop a conceptual model of quality of life (QOL) in muscular dystrophies (MDs) and review existing QOL measures for use in the MD population.

Methods: Our model for QOL among individuals with MD was developed based on a modified Delphi process, literature review, and input from patients and patient advocacy organizations. Scales that have been used to measure QOL among patients with MD were identified through a literature review and evaluated using the COSMIN (Consensus-Based Standards for the Selection of Health Measurement Instruments) checklist.

The path from childhood behavioural disorders to felony offending: Investigating the role of adolescent drinking, peer marginalisation and school failure.

Background: Although a pathway from childhood behavioural disorders to criminal offending is well established, the aetiological processes remain poorly understood. Also, it is not clear if attention deficit hyperactivity disorder (ADHD) is predictive of crime in the absence of comorbid disruptive behaviour disorder (DBD).

Hypothesis: We examined two research questions: (1) Does ADHD have a unique effect on the risk of criminal offending, independently of DBD? (2) Is the effect of childhood behavioural disorders on criminal offending direct or mediated by adolescent processes related to school experience, substance misuse and peers?

Method: Structural equation modelling, with latent variables, was applied to longitudinally collected data on 4644 men from the 1986 Northern Finland Birth Cohort Study.

Characteristics and survival of patients with end stage renal disease and spina bifida in the United States renal data system.

Purpose: We describe the characteristics, treatments and survival of patients with spina bifida in whom end stage renal disease developed from 2004 through 2008 in the United States Renal Data System.

Materials And Methods: We used ICD-9-CM code 741.* to identify individuals with spina bifida using hospital inpatient data from 1977 to 2010, and physician and facility claims from 2004 to 2008.

Use of state administrative data sources to study adolescents and young adults with rare conditions.

Background: Effective care of young people with rare conditions requires ongoing coordinated medical treatment as well as educational and social support services. However, information on treatment is often lacking due to limited data. South Carolina has a repository of comprehensive health and human service data with which individuals may be tracked across the data systems of multiple state agencies and organizations.

A comparison of family financial and employment impacts of fragile X syndrome, autism spectrum disorders, and intellectual disability.

This study compares the family financial and employment impacts of having a child with fragile X syndrome (FXS), autism spectrum disorder (ASD), or intellectual disabilities (ID). Data from a 2011 national survey of families of children with FXS were matched with data from the National Survey of Children with Special Health Care Needs 2009-2010 to form four analytic groups: children with FXS (n=189), children with special health care needs with ASD only (n=185), ID only (n=177), or both ASD and ID (n=178). Comparable percentages of parents of children with FXS (60%) and parents of children with both ASD and ID (52%) reported that their families experienced a financial burden as a result of the condition, both of which were higher than the percentages of parents of children with ASD only (39%) or ID only (29%).

Mutation of NRAS but not KRAS significantly reduces myeloma sensitivity to single-agent bortezomib therapy.

Various translocations and mutations have been identified in myeloma, and certain aberrations, such as t(4;14) and del17, are linked with disease prognosis. To investigate mutational prevalence in myeloma and associations between mutations and patient outcomes, we tested a panel of 41 known oncogenes and tumor suppressor genes in tumor samples from 133 relapsed myeloma patients participating in phase 2 or 3 clinical trials of bortezomib. DNA mutations were identified in 14 genes.