Instructions on appropriate fasting prior to phlebotomy; effects on patient awareness, preparation, and biochemical parameters.

Objectives: This study investigated the effect of appropriate pre-phlebotomy instructions on patients' awareness of the need to fast, their fasting status at phlebotomy, and the measurement of specific biochemical analytes and indices.

Methods: While booking their phlebotomy appointments, two-hundred outpatients, with a wide range of pre-existing medical conditions, were recruited and randomly assigned to either control or intervention groups. The control group received no instructions while the intervention group was verbally instructed to fast for precisely 12 h prior to their appointment.

The histone demethylase PHF8 regulates TGFβ signaling and promotes melanoma metastasis.

The contribution of epigenetic dysregulation to metastasis remains understudied. Through a meta-analysis of gene expression datasets followed by a mini-screen, we identified Plant Homeodomain Finger protein 8 (PHF8), a histone demethylase of the Jumonji C protein family, as a previously unidentified prometastatic gene in melanoma. Loss- and gain-of-function approaches demonstrate that PHF8 promotes cell invasion without affecting proliferation in vitro and increases dissemination but not subcutaneous tumor growth in vivo, thus supporting its specific contribution to the acquisition of metastatic potential.

Timing of enterostomy closure for neonatal isolated intestinal perforation.

Purpose: No consensus guidelines exist for timing of enterostomy closure in neonatal isolated intestinal perforation (IIP). This study evaluated neonates with IIP closed during the initial admission (A1) versus a separate admission (A2) comparing total length of stay and total hospital cost.

Methods: Using 2012 to 2017 Pediatric Health information System (PHIS) data, 359 neonates with IIP were identified who underwent enterostomy creation and enterostomy closure.

In-hospital Pediatric Endoscopic Retrograde Cholangiopancreatography Is Associated With Shorter Hospitalization for Children With Choledocholithiasis.

Objectives: Children with choledocholithiasis are frequently managed at tertiary children's hospitals that do not have available endoscopic retrograde cholangiopancreatography (ERCP) proceduralists. We hypothesized that patients treated at hospitals without ERCP proceduralists would have a longer hospital length of stay (LOS) than those with ERCP proceduralists.

Methods: Charts were reviewed for patients who underwent cholecystectomy and ERCP at 3 tertiary children's hospitals over 10 years.

24-hour and 30-day perioperative mortality in pediatric surgery.

Purpose: The low perioperative mortality rate in pediatric surgery precludes effective analysis of mortality at individual institutions. Therefore, analysis of multi-institutional data is essential to determine any patterns of perioperative death in children. The aim of this study was to determine diagnoses associated with 24-hour and 30-day perioperative mortality.

Resource utilization and indications for helicopter transport of head-injured children.

Introduction: Helicopter emergency medical services (HEMS) have provided benefit for severely injured patients. However, HEMS are likely overused for the transportation of both adult and pediatric trauma patients. In this study, we aim to evaluate the degree of overuse of helicopter as a mode of transport for head-injured children.

Barriers to Breastfeeding in Female Physicians.

Background: Breast milk is considered the normative nutrition for human infants, and exclusive breastfeeding for the first 6 months of life is recommended by several national and global societies. Female physicians are a high-risk group for early unintended weaning. We aimed to assess and compare the most common barriers to successful breastfeeding perceived by female physicians in various stages of training and practice.

Pediatric Perioperative Cardiac Arrest, Death in the Off Hours: A Report From Wake Up Safe, The Pediatric Quality Improvement Initiative.

Background: Pediatric perioperative cardiac arrest (CA) is a rare but catastrophic event. This case-control study aims to analyze the causes, incidence, and outcomes of all pediatric CA reported to Wake Up Safe. Factors associated with CA and mortality after arrest are examined and possible strategies for improving outcomes are considered.

Characteristics of deposits and pump exchange in the Berlin Heart EXCOR ventricular assist device: Experience with 67 cases.

Pump exchanges are frequently required in the Berlin Heart EXCOR VAD. We intended to describe the characteristics of pump deposits in a larger patient series and evaluate if changes in our exchange procedure over time have led to increased complications. We reviewed all EXCOR pump exchanges in our institution from July 2004 to October 2014.

Baseline antibody profiles predict toxicity in melanoma patients treated with immune checkpoint inhibitors.

Background: Immune checkpoint inhibitors (anti-CTLA-4, anti-PD-1, or the combination) enhance anti-tumor immune responses, yielding durable clinical benefit in several cancer types, including melanoma. However, a subset of patients experience immune-related adverse events (irAEs), which can be severe and result in treatment termination. To date, no biomarker exists that can predict development of irAEs.

Pediatric vascular trauma practice patterns and resource availability: A survey of American College of Surgeon-designated pediatric trauma centers.

Background: Variation exists in pediatric vascular trauma management. We aim to determine practice patterns for vascular trauma management at American College of Surgeons verified pediatric trauma centers and evaluate the resources available for management of vascular trauma at both freestanding children's hospitals (FSCH) and pediatric hospitals within general adult hospitals.

Methods: Pediatric surgeons and trauma medical directors at American College of Surgeons designated pediatric surgery trauma centers completed a survey designed to evaluate anticipated management of traumatic arterial injuries and resource availability.

Temporary Circulatory Support in U.S. Children Awaiting Heart Transplantation.

Background: Extracorporeal membrane oxygenation (ECMO) has long served as the standard of care for short-term mechanical circulatory support in pediatrics. It is unknown whether newer-generation temporary circulatory support (TCS) devices afford children a meaningful survival advantage over ECMO.

Objectives: This study sought to determine whether bridge-to-heart transplant survival with a TCS device is superior to ECMO after adjusting for patient differences.

Long-Term Pediatric Ventricular Assist Device Therapy: A Case Report of 2100+ Days of Support.

Ventricular assist devices (VADs) have been placed as destination therapy in adults for more than 20 years, but have only recently been considered an option in a subset of pediatric patients. A 2016 report from the Pediatric Interagency Registry for Mechanical Circulatory Support revealed only eight pediatric patients implanted with a VAD as destination therapy. Herein, we report the case of an adolescent male with Becker muscular dystrophy who underwent VAD placement in 2011 as bridge to candidacy.

Collateralization of projections from the rostral ventrolateral medulla to the rostral and caudal thoracic spinal cord in felines.

Stimulation of vestibular receptors elicits distinct changes in blood flow to the forelimb and hindlimb, showing that the nervous system has the capacity to produce changes in sympathetic outflow which are specific for a particular region of the body. However, it is unclear whether the rostral ventrolateral medulla (RVLM), the primary region of the brainstem that regulates sympathetic outflow to vascular smooth muscle, has the appropriate connectivity with sympathetic preganglionic neurons to generate anatomically patterned responses. To make this determination, the retrograde fluorescent tracer Fast Blue was injected into the T(4) spinal cord segment of cats, which regulates upper body blood flow, whereas Fluoro-Ruby was injected into the T(10) segment to label projections to a region of the spinal cord that regulates lower body blood flow.

Selectively engaging β-arrestins at the angiotensin II type 1 receptor reduces blood pressure and increases cardiac performance.

Biased G protein-coupled receptor ligands engage subsets of the receptor signals normally stimulated by unbiased agonists. However, it is unclear whether ligand bias can elicit differentiated pharmacology in vivo. Here, we describe the discovery of a potent, selective β-arrestin biased ligand of the angiotensin II type 1 receptor.

Antagonists of the calcium receptor. 2. Amino alcohol-based parathyroid hormone secretagogues.

When administered as a single agent to rats, the previously reported calcium receptor antagonist 3 elicited a sustained elevation of plasma PTH resulting in no increase in overall bone mineral density. The lack of a bone building effect for analogue 3 was attributed to the large volume of distribution (V(dss)(rat) = 11 L/kg), producing a protracted plasma PTH profile. Incorporation of a carboxylic acid functionality into the amino alcohol template led to the identification of 12 with a lower volume of distribution (V(dss)(12) = 1.

An orally active calcium-sensing receptor antagonist that transiently increases plasma concentrations of PTH and stimulates bone formation.

Daily subcutaneous administration of exogenous parathyroid hormone (PTH) promotes bone formation in patients with osteoporosis. Here we describe two novel, short-acting calcium-sensing receptor antagonists (SB-423562 and its orally bioavailable precursor, SB-423557) that elicit transient PTH release from the parathyroid gland in several preclinical species and in humans. In an ovariectomized rat model of bone loss, daily oral administration of SB-423557 promoted bone formation and improved parameters of bone strength at lumbar spine, proximal tibia and midshaft femur.

Antagonists of the calcium receptor I. Amino alcohol-based parathyroid hormone secretagogues.

Functional screening of the former SmithKline Beecham compound collection against the human calcium receptor (CaR) resulted in the identification of the amino alcohol-based hit 2 (IC(50) = 11 microM). Structure-activity studies of 2 focused on the optimization of the right- and left-hand side aromatic moieties as well as the amino alcohol linker region. Critical to the optimization of this antagonist template was the discovery that the chirality of the C-2 secondary alcohol played a key role in enhancing both CaR potency as well as selectivity over the beta-adrenergic receptor subtypes.

Method for quantitative protein-ligand affinity measurements in compound mixtures.

This manuscript describes an affinity selection-mass spectrometry (AS-MS) method for quantitative protein-ligand binding affinity (Kd) measurements in large compound libraries. The ability of a titrant ligand to displace a target-bound library member-as measured by MS-reveals the affinity ranking of the mixture component relative to "internal affinity calibrants", compounds of known affinity for the target. This technique does not require that the precise concentration of each ligand is known; therefore, unpurified products of mixture-based combinatorial synthesis may be used for affinity optimization and developing structure-activity relationships.

A highly potent inhibitor of cathepsin K (relacatib) reduces biomarkers of bone resorption both in vitro and in an acute model of elevated bone turnover in vivo in monkeys.

Cathepsin K is an osteoclast-derived cysteine protease that has been implicated as playing a major role in bone resorption. A substantial body of evidence indicates that cathepsin K is critical in osteoclast-mediated bone resorption and suggests that its pharmacological inhibition should result in inhibition of bone resorption in vivo. Here we report the pharmacological characterization of SB-462795 (relacatib) as a potent and orally bioavailable small molecule inhibitor of cathepsin K that inhibits bone resorption both in vitro in human tissue and in vivo in cynomolgus monkeys.