BACKGROUND & AIMS: The effect of hepatitis C viral (HCV) infection on patient and allograft survival after orthotopic liver transplantation is controversial. Hepatitis C recurrence after transplant is inevitable, but studies to date have not found a survival difference between recipients with and without HCV. METHODS: Using data from the United Network for Organ Sharing, we performed a retrospective cohort study of 11,036 patients who underwent 11,791 liver transplants between 1992 and 1998. The hazard rates of patient and allograft survival for patients who were HCV-positive as compared with patients who were HCV-negative were assessed by proportional-hazards analysis, with adjustment for potential confounding variables, including donor, recipient, and transplant center characteristics. RESULTS: Liver transplantation in HCV-positive recipients was associated with an increased rate of death (hazard ratio, 1.23; 95% confidence interval [CI], 1.12-1.35) and allograft failure (hazard ratio, 1.30; 95% CI, 1.21-1.39), as compared with transplantation in HCV-negative recipients. This reduction in survival persisted after adjusting for potential confounders. There was an interaction between HCV and sex (P < 0.001) with the effect of HCV on survival being most pronounced in female recipients (patient survival hazard ratio, 1.56; 95% CI, 1.35-1.81; allograft survival hazard ratio, 1.51; 95% CI, 1.34-1.70). CONCLUSIONS: HCV infection significantly impairs patient and allograft survival after liver transplantation. 相似文献
BackgroundPatients with coronavirus disease 2019 (COVID-19) have a high prevalence of detectable troponin and myocardial injury. In addition, a subset of patients with COVID-19 has detectable severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral loads. The objective of this study was to understand the relationship among SARS-CoV-2 viremia, detectable troponin, and myocardial injury in hospitalized patients with COVID-19.MethodsSARS-CoV-2 plasma viral load was measured in plasma samples drawn from patients hospitalized for COVID-19 at 2 academic medical centers. Baseline characteristics and clinically obtained high-sensitivity cardiac troponin T (hs-cTnT) values were abstracted from the medical record. The main outcome was detectable hs-cTnT (≥6 ng/mL) and myocardial injury (hs-cTnT ≥14 ng/mL; >99th percentile for assay).ResultsA total of 70 hospitalized patients with COVID-19 were included in this study, with 39% females and median age 58 ± 17 years; 21 patients (30%) were found to have detectable SARS-CoV-2 viral load and were classified in the viremia group. Patients with viremia were significantly older than those without viremia. All of the patients with viremia (100%) had detectable troponin during hospitalization compared with 59% of patients without viremia (P = 0.0003). Myocardial injury was seen in 76% of patients with viremia and 38% of those patients without viremia (P = 0.004).ConclusionsHospitalized patients with COVID-19 with SARS-CoV-2 viremia have a significantly higher prevalence of detectable troponin and myocardial injury during their hospitalization compared with patients who did not. This first report of the relationship among SARS-CoV-2 viremia, detectable troponin, and myocardial injury in patients with COVID-19 points to additional mechanistic pathways that require deeper study to understand the complex interplay among these unique findings, cardiovascular outcomes, and mortality in COVID-19. 相似文献
Carbohydrate functionalization of nanoparticles allows for targeting of C-type lectin receptors. This family of pattern recognition receptors expressed on innate immune cells, such as macrophages and dendritic cells, can be used to modulate immune responses. In this work, the in vivo safety profile of carbohydrate-functionalized polyanhydride nanoparticles was analyzed following parenteral and intranasal administration in mice. Polyanhydride nanoparticles based on 1,6-bis-(p-carboxyphenoxy)hexane and 1,8-bis-(p-carboxyphenoxy)-3,6-dioxaoctane were used. Nanoparticle functionalization with di-mannose (specifically carboxymethyl-α-d-mannopyranosyl-(1,2)-d-mannopyranoside), galactose (specifically carboxymethyl-β-galactoside), or glycolic acid induced no adverse effects after administration based on histopathological evaluation of liver, kidneys, and lungs. Regardless of the polymer formulation, there was no evidence of hepatic or renal damage or dysfunction observed in serum or urine samples. The histological profile of cellular infiltration and the cellular distribution and kinetics in the lungs of mice administered with nanoparticle treatments followed similar behavior as that observed in the lungs of animals administered with saline. Cytokine and chemokine profiles in bronchoalveolar lavage fluid indicated surface chemistry dependence on modest secretion of IL-6, IP-10, and MCP-1; however, there was no evidence of any deleterious histopathological changes. Based on these analyses, carbohydrate-functionalized nanoparticles are safe for in vivo applications. These results provide foundational information towards the evaluation of the capabilities of these surface-modified nanoparticles as vaccine delivery formulations.KEY WORDS: biocompatibility, carbohydrate, nanoparticles, polyanhydride, safety相似文献
Introduction: Hepatitis B virus (HBV) reactivation after ‘resolved’ infection can occur in the setting of immunosuppression, including iatrogenically induced by anti-CD20 antibodies. The presence of antibodies against the HBV core antigen (anti-HBc) is a marker of risk for this phenomenon. The risk of this occurring in patients with circulating HBV surface antigen (HBsAg) is well characterized, but is less well characterized in patients who are HBsAg negative.
Areas covered: This article reviews the literature regarding HBV reactivation in the context of rituximab therapy. We have limited our review to HBsAg-negative patients, and clinical outcomes following HBV reactivation.
Expert opinion: We have recommended prophylactic anti-viral therapy for all HBsAg-negative/anti-HBc-positive patients undergoing rituximab therapy in combination with other immunosuppressive therapy. 相似文献
Patients with chronic cough are typically female and have a mean age of?~?60 years. However, initial pharmacokinetic (PK) characterization of the P2X3-receptor antagonist gefapixant, developed to treat refractory or unexplained chronic cough, was performed in healthy participants who were predominantly younger adult males. The objective of this Phase 1 study was to assess the safety, tolerability, and PK of gefapixant in younger (18–55 years) and older (65–80 years) males and females.
Methods
A randomized, double-blind, placebo-controlled study was conducted. Healthy adult participants were stratified into 4 cohorts by age and sex (younger males/females and older males/females) and randomized 4:1 (younger adults) or 3:1 (older adults) to receive gefapixant 300 mg twice daily (BID) for 1 week, followed by gefapixant 600 mg BID for 2 weeks or placebo. Safety, tolerability, and PK were assessed.
Results
Of 36 randomized and treated participants, 28 (100%) receiving gefapixant and 6 (75%) receiving placebo reported?≥?1 adverse event (AE). The most common treatment-related AEs in the gefapixant group were taste related. Predefined renal/urologic AEs were reported by 7 (25%) participants receiving gefapixant (all mild to moderate in severity). Gefapixant exposure was generally lower in younger males compared with younger females and older adults; however, differences may have been due to estimated glomerular filtration rate.
Conclusion
The safety profile of gefapixant 300–600 mg BID was generally consistent with previous studies. Additional characterization of gefapixant PK as a function of age and sex using population PK modeling is warranted.
