University of Colorado Denver

About: University of Colorado Denver is a education organization based out in Denver, Colorado, United States. It is known for research contribution in the topics: Population & Health care. The organization has 27444 authors who have published 57213 publications receiving 2539937 citations. The organization is also known as: CU Denver & UCD.

Exome sequencing identifies GRIN2A as frequently mutated in melanoma

Abstract: The incidence of melanoma is increasing more than any other cancer, and knowledge of its genetic alterations is limited. To systematically analyze such alterations, we performed whole-exome sequencing of 14 matched normal and metastatic tumor DNAs. Using stringent criteria, we identified 68 genes that appeared to be somatically mutated at elevated frequency, many of which are not known to be genetically altered in tumors. Most importantly, we discovered that TRRAP harbored a recurrent mutation that clustered in one position (p. Ser722Phe) in 6 out of 167 affected individuals (∼4%), as well as a previously unidentified gene, GRIN2A, which was mutated in 33% of melanoma samples. The nature, pattern and functional evaluation of the TRRAP recurrent mutation suggest that TRRAP functions as an oncogene. Our study provides, to our knowledge, the most comprehensive map of genetic alterations in melanoma to date and suggests that the glutamate signaling pathway is involved in this disease.

Antibiotic Therapy for Reduction of Infant Morbidity After Preterm Premature Rupture of the Membranes: A Randomized Controlled Trial

Abstract: Context. —Intrauterine infection is thought to be one cause of preterm premature rupture of the membranes (PPROM). Antibiotic therapy has been shown to prolong pregnancy, but the effect on infant morbidity has been inconsistent. Objective. —To determine if antibiotic treatment during expectant management of PPROM will reduce infant morbidity. Design. —Randomized, double-blind, placebo-controlled trial. Setting. —University hospitals of the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Patients. —A total of 614 of 804 eligible gravidas with PPROM between 24 weeks' and 0 days' and 32 weeks' and 0 days' gestation who were considered candidates for pregnancy prolongation and had not received corticosteroids for fetal maturation or antibiotic treatment within 1 week of randomization. Intervention. —Interavenous ampicillin (2-g dose every 6 hours) and erythromycin (250-mg dose every 6 hours) for 48 hours followed by oral amoxicillin (250-mg dose every 8 hours) and erythromycin base (333-mg dose every 8 hours) for 5 days vs a matching placebo regimen. Group B streptococcus (GBS) carriers were identified and treated. Tocolysis and corticosteroids were prohibited after randomization. Main Outcome Measures. —The composite primary outcome included pregnancies complicated by at least one of the following: fetal or infant death, respiratory distress, severe intraventricular hemorrhage, stage 2 or 3 necrotizing enterocolitis, or sepsis within 72 hours of birth. These perinatal morbidities were also evaluated individually and pregnancy prolongation was assessed. Results. —In the total study population, the primary outcome (44.1% vs 52.9%;P=.04), respiratory distress (40.5% vs 48.7%;P=.04), and necrotizing enterocolitis (2.3% vs 5.8%;P=.03) were less frequent with antibiotics. In the GBS-negative cohort, the antibiotic group had less frequent primary outcome (44.5% vs 54.5%;P=.03), respiratory distress (40.8% vs 50.6%;P=.03), overall sepsis (8.4% vs 15.6%;P=.01), pneumonia (2.9% vs 7.0%;P=.04), and other morbidities. Among GBS-negative women, significant pregnancy prolongation was seen with antibiotics (P Conclusions. —We recommend that women with expectantly managed PPROM remote from term receive antibiotics to reduce infant morbidity.

Pathophysiology of cisplatin-induced acute kidney injury.

Abstract: Cisplatin and other platinum derivatives are the most widely used chemotherapeutic agents to treat solid tumors including ovarian, head and neck, and testicular germ cell tumors. A known complication of cisplatin administration is acute kidney injury (AKI). The nephrotoxic effect of cisplatin is cumulative and dose-dependent and often necessitates dose reduction or withdrawal. Recurrent episodes of AKI may result in chronic kidney disease. The pathophysiology of cisplatin-induced AKI involves proximal tubular injury, oxidative stress, inflammation, and vascular injury in the kidney. There is predominantly acute tubular necrosis and also apoptosis in the proximal tubules. There is activation of multiple proinflammatory cytokines and infiltration of inflammatory cells in the kidney. Inhibition of the proinflammatory cytokines TNF-α or IL-33 or depletion of CD4+ T cells or mast cells protects against cisplatin-induced AKI. Cisplatin also causes endothelial cell injury. An understanding of the pathogenesis of cisplatin-induced AKI is important for the development of adjunctive therapies to prevent AKI, to lessen the need for dose decrease or drug withdrawal, and to lessen patient morbidity and mortality.

Hospital Readmissions Reduction Program

Abstract: Hospital readmission measures have been touted not only as a quality measure but also as a means to bend the healthcare cost curve. The Affordable Care Act (ACA) established the Hospital Readmission Reduction Program (HRRP) in 2012. Under this program, hospitals are financially penalized if they have higher-than-expected risk-standardized 30-day readmission rates for acute myocardial infarction, heart failure, and pneumonia. The HRRP has garnered significant attention from the medical community, both positive and negative. Here, we describe the reasons the HRRP was implemented, the penalties levied, the impact it has had on transitional care and readmissions, the pros and cons of the policy, and its future. Hospital readmissions are associated with unfavorable patient outcomes and high financial costs.1,2 Causes of readmissions are multifactorial, and rates vary substantially by institution.3,4 Historically, nearly 20% of all Medicare discharges had a readmission within 30 days.1 The Medicare Payment Advisory Commission has estimated that 12% of readmissions are potentially avoidable. Preventing even 10% of these readmissions could save Medicare $1 billion.5 Therefore, reducing hospital readmissions has been made a national priority. In 2008, the Medicare Payment Advisory Commission recommended to Congress that the Centers for Medicare & Medicaid Services (CMS) begin confidentially reporting readmission rates and resource use to hospitals and physicians.6 In 2009, CMS began publicly reporting hospital-level readmission rates, which were added to the Hospital Compare Web site.7 Before 2012, hospitals had little direct financial incentive to reduce readmissions. For Medicare beneficiaries with inpatient stays, hospitals receive payment with the inpatient prospective payment system (IPPS). This payment, based on a diagnosis-related group (DRG), covers the inpatient stay and any outpatient diagnostic and admission-related outpatient nondiagnostic services provided by the institution on the date of the patient’s admission or within 3 days immediately …