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.

Daclatasvir plus Sofosbuvir for HCV in Patients Coinfected with HIV-1

Abstract: BACKGROUND The combination of daclatasvir, a hepatitis C virus (HCV) NS5A inhibitor, and the NS5B inhibitor sofosbuvir has shown efficacy in patients with HCV monoinfection. Data are lacking on the efficacy and safety of this combination in patients coinfected with human immunodeficiency virus type 1 (HIV-1). METHODS This was an open-label study involving 151 patients who had not received HCV treatment and 52 previously treated patients, all of whom were coinfected with HIV-1. Previously untreated patients were randomly assigned in a 2:1 ratio to receive either 12 weeks or 8 weeks of daclatasvir at a standard dose of 60 mg daily (with dose adjustment for concomitant antiretroviral medications) plus 400 mg of sofosbuvir daily. Previously treated patients were assigned to undergo 12 weeks of therapy at the same doses. The primary end point was a sustained virologic response at week 12 after the end of therapy among previously untreated patients with HCV genotype 1 who were treated for 12 weeks. RESULTS Patients had HCV genotypes 1 through 4 (83% with genotype 1), and 14% had compensated cirrhosis; 98% were receiving antiretroviral therapy. Among patients with genotype 1, a sustained virologic response was reported in 96.4% (95% confidence interval [CI], 89.8 to 99.2) who were treated for 12 weeks and in 75.6% (95% CI, 59.7 to 87.6) who were treated for 8 weeks among previously untreated patients and in 97.7% (95% CI, 88.0 to 99.9) who were treated for 12 weeks among previously treated patients. Rates of sustained virologic response across all genotypes were 97.0% (95% CI, 91.6 to 99.4), 76.0% (95% CI, 61.8 to 86.9), and 98.1% (95% CI, 89.7 to 100), respectively. The most common adverse events were fatigue, nausea, and headache. There were no study-drug discontinuations because of adverse events. HIV-1 suppression was not compromised. CONCLUSIONS Among previously untreated HIV–HCV coinfected patients receiving daclatasvir plus sofosbuvir for HCV infection, the rate of sustained virologic response across all genotypes was 97.0% after 12 weeks of treatment and 76.0% after 8 weeks. (Funded by Bristol-Myers Squibb; ALLY-2 ClinicalTrials.gov number, NCT02032888.)

Pathogenic CD4 T cells in type 1 diabetes recognize epitopes formed by peptide fusion

Abstract: T cell–mediated destruction of insulin-producing β cells in the pancreas causes type 1 diabetes (T1D). CD4 T cell responses play a central role in β cell destruction, but the identity of the epitopes recognized by pathogenic CD4 T cells remains unknown. We found that diabetes-inducing CD4 T cell clones isolated from nonobese diabetic mice recognize epitopes formed by covalent cross-linking of proinsulin peptides to other peptides present in β cell secretory granules. These hybrid insulin peptides (HIPs) are antigenic for CD4 T cells and can be detected by mass spectrometry in β cells. CD4 T cells from the residual pancreatic islets of two organ donors who had T1D also recognize HIPs. Autoreactive T cells targeting hybrid peptides may explain how immune tolerance is broken in T1D.

Acetaminophen overdose. 662 cases with evaluation of oral acetylcysteine treatment.

Abstract: • Six hundred sixty-two consecutive patients with acetaminophen overdoses were evaluated. Those at risk on the basis of their acetaminophen blood levels, as plotted on the study nomogram, were treated with oral acetylcysteine. Statistically significant differences in severity of hepatic toxicity were observed between patients treated within 16 hours after ingestion and those treated between 16 and 24 hours after ingestion. No deaths occurred among patients treated within 24 hours of ingestion, except for one patient who was an alleged gunshot homicide. Seven percent of patients with plasma acetaminophen levels in the potentially toxic range and treated with acetylcysteine within ten hours of ingestion showed transient SGOT level elevations, whereas 29% of those treated between ten and 16 hours after ingestion and 62% of those treated between 16 and 24 hours after ingestion showed such transient toxicity. No consistent difference in hepatotoxicity could be demonstrated between those patients with a history of chronic alcohol use and those patients with no history of chronic alcohol use. Acute alcohol use resulted in less severe toxic reactions than in those patients without acute alcohol use. (Arch Intern Med141:380-385, 1981)

Association Between the MUC5B Promoter Polymorphism and Survival in Patients With Idiopathic Pulmonary Fibrosis

Abstract: Main Outcomes and Measures The primary end point was all-cause mortality. Results ThenumbersofpatientsintheGG,GT,andTTgenotypegroupswere148(34%), 259 (59%), and 31 (7%), respectively, in the INSPIRE cohort and 41 (28%), 98 (66%), and9(6%),respectively,intheChicagocohort.Themedianfollow-upperiodwas1.6years for INSPIRE and 2.1 years for Chicago. During follow-up, there were 73 deaths (36 GG, 35GT,and2TT)amongINSPIREpatientsand64deaths(26GG,36GT,and2TT)among Chicagopatients.Theunadjusted2-yearcumulativeincidenceofdeathwasloweramong patientscarrying1ormorecopiesoftheIPFriskallele(T)inboththeINSPIREcohort(0.25 [95% CI, 0.17-0.32] for GG, 0.17 [95% CI, 0.11-0.23] for GT, and 0.03 [95% CI, 0.000.09] for TT) and the Chicago cohort (0.50 [95% CI, 0.31-0.63] for GG, 0.22 [95% CI, 0.13-0.31] for GT, and 0.11 [95% CI, 0.00-0.28] for TT). In the INSPIRE cohort, the TT andGTgenotypes(riskforIPF)wereassociatedwithimprovedsurvivalcomparedwithGG (hazardratios,0.23[95%CI,0.10-0.52]and0.48[95%CI,0.31-0.72],respectively;P.001). ThisfindingwasreplicatedintheChicagocohort(hazardratios,0.15[95%CI,0.05-0.49] and0.39[95%CI,0.21-0.70],respectively;P.002).TheobservedassociationofMUC5B withsurvivalwasindependentofage,sex,forcedvitalcapacity,diffusingcapacityofcarbon monoxide, MMP-7, and treatment status. The addition of the MUC5B genotype to the survivalmodelssignificantlyimprovedthepredictiveaccuracyofthemodelinboththeINSPIRE cohort (C=0.71 [95% CI, 0.64-0.75] vs C=0.68 [95% CI, 0.61-0.73]; P.001) and the Chicago cohort (C=0.73 [95% CI, 0.62-0.78] vs C=0.69 [95% CI, 0.59-0.75]; P=.01). ConclusionsandRelevance AmongpatientswithIPF,acommonriskpolymorphism in MUC5B was significantly associated with improved survival. Further research is necessarytorefinetheriskestimatesandtodeterminetheclinicalimplicationsofthesefindings.