Sustained viral clearance was achieved in 83% of patients with renal impairment (eGFR ≤45 ml/min/1.73 m(2) ) treated with SOF-containing regimens. However, these patients had higher rates of anaemia, worsening renal dysfunction and serious adverse events regardless of use of RBV. Patient with renal impairment require close monitoring and should be treated by providers extensively experienced with SOF-containing regimens.

Background Data outside of clinical trials with direct acting antiviral (DAA) regimens with or without ribavirin as treatment of chronic HCV in solid organ transplant recipients is limited. Methods Liver transplant (LT), kidney transplant (KT) and dual liver kidney (DLK) transplant recipients from the HCV-TARGET database, a multicenter, longitudinal clinical care treatment cohort, treated with DAA regimens between January 1 2014 and February 15, 2016 were included to assess safety and efficacy. Results 443 post-transplant patients were included (KT=60, LT =347, DLK=36); 42% had cirrhosis, 54% had failed prior antiviral therapy. Most had genotype (GT) 1 (87% with 52% G1a, 27% G1b, and 8% G1 no subtype) and were treated with sofosbuvir/ledipasvir (SOF/LDV) ± RBV (85%) followed by sofosbuvir + daclatasvir (SOF + DAC) ± ribavirin (9%) and ombitasvir/paritaprevir/ritonavir + dasabuvir (PrOD) ± RBV (6%). SVR12 rates were available on 415 patients and 397 patients (95.7%) achieved SVR12: 96.3%, 94.6% and 90.9% among LT, KT and DLK transplant recipients, respectively. Ribavirin did not influence SVR rates and was more often used in those with higher eGFR and lower creatinine. Female gender, baseline albumin ≥ 3.5 g/dL, baseline total bilirubin ≤ 1.2 mg/dL, the absence of cirrhosis and hepatic decompensation predicted SVR12. Six episodes of acute rejection (n=2 KT, 4 LT) occurred during HCV treatment in 4 and after cessation of treatment in 2. Conclusion In a large prospective observational cohort study, DAA therapy with SOF/LDV, PrOD and SOF plus DAC was efficacious and safe in, LT, KT, and DLK transplant recipients. Ribavirin did not influence SVR. Graft rejection was rare.

Background/Aims Risks and benefits of simeprevir plus sofosbuvir in patients with advanced cirrhosis are unknown. We assessed the safety and sustained virologic responses (SVR) of simeprevir plus sofosbuvir with and without ribavirin in patients with Child-Pugh (CP)-B/C vs. CP-A cirrhosis and compared to matched untreated controls. Methods Multicenter cohort of adults with HCV genotype 1 and cirrhosis treated with simeprevir plus sofosbuvir with/without ribavirin for 12 weeks. Controls were matched on treatment center, age, CP class and model for end-stage liver disease (MELD) score. Results Of 160 patients treated with simeprevir plus sofosbuvir with/without ribavirin, 35% had CP-B/C and 64% had CP-A, with median baseline MELD 9 (IQR 8–11). SVR12 was achieved by 73% of CP-B/C vs. 91% of CP-A (p<0.01). CP-B/C vs. CP-A had more early treatment discontinuations (11% vs. 1%), adverse events requiring hospitalization (22% vs. 2%), infections requiring antibiotics (20% vs. 1%) and hepatic decompensating events (20% vs. 3%) (all p<0.01). There were 2 deaths: 1 CP-B/C (liver-related) and 1 CP-A (not liver-related). In multivariate analysis, CP-B/C independently predicted lack of SVR12 (OR 0.27, 95% CI 0.08–0.92). In comparing simeprevir plus sofosbuvir treated patients vs. matched untreated controls, adverse events requiring hospitalization (9% vs. 13%, p=0.55), infections (8% vs. 6%, p=0.47) and events of decompensation (9% vs. 10%, p=0.78) occurred at similar frequency. Conclusions Simeprevir plus sofosbuvir with/without ribavirin has lower efficacy and higher rates of adverse events in patients with CP-B/C cirrhosis compared to CP-A. The frequency of adverse safety outcomes were similar to matched untreated controls, suggesting safety events reflect the natural history of cirrhosis and are not related to treatment.

Although metallic biomaterials find numerous biomedical applications, their inherent low bioactivity and poor osteointegration had been a great challenge for decades. Surface modification via silanization can serve as an attractive method for improving the aforementioned properties of such substrates. However, its effect on protein adsorption/conformation and subsequent cell adhesion and spreading has rarely been investigated. This work reports the in-depth study of the effect of Ti6Al4V surface functionalization on protein adsorption and cell behavior. We prepared self-assembled monolayers (SAMs) of five different surfaces (amine, octyl, mixed [1:1 ratio of amine:octyl], hybrid, and COOH). Synthesized surfaces were characterized by Fourier transform infrared-attenuated total reflection (FTIR-ATR) spectroscopy, contact angle goniometry, profilometry, and field emission scanning electron microscopy (FESEM). Quantification of adsorbed mass of bovine serum albumin (BSA) and fibronectin (FN) was determined on different surfaces along with secondary structure analysis. The adsorbed amount of BSA was found to increase with an increase in surface hydrophobicity with the maximum adsorption on the octyl surface while the reverse trend was detected for FN adsorption, having the maximum adsorbed mass on the COOH surface. The α-helix content of adsorbed BSA increased on amine and COOH surfaces while it decreased for other surfaces. Whereas increasing β-turn content of the adsorbed FN with the increase in the surface hydrophobicity was observed. In FN, RGD loops are located in the β-turn and consequently the increase in Δ adhered cells (%) was predominantly increased with the increasing Δ β-turn content (%). We found hybrid surfaces to be the most promising surface modifier due to maximum cell adhesion (%) and proliferation, larger nuclei area, and the least cell circularity. Bacterial density increased with the increasing hydrophobicity and was found maximum for the amine surface (θ = 63 ± 1°) which further decreased with the increasing hydrophobicity. Overall, modified surfaces (in particular hybrid surface) showed better protein adsorption and cell adhesion properties as compared to unmodified Ti6Al4V and can be potentially used for tissue engineering applications.

Medical schools have reduced the time allotted to anatomy instruction. Consequently, schools engage students in more independent settings using information and communication technologies (ICT). There has been limited research in the use of video aids, a type of ICT, to enhance anatomy examination performance. The objective of this study is to describe the design, usage, and effect on examination performance of eight locally developed instructional anatomy videos. First-year UCSF medical students (n = 141) had access to the videos. They reported their video usage, reason for usage, and satisfaction. The prior year students (n = 141) served as a historical control group. Anatomy and radiology examination performance was compared between groups while controlling for prior performance. The students with and without access to the videos did not differ in examination performance. Sixty-one (43%) students in the experimental group responded to the survey. Of these, 79% reported using at least one video, viewing an average of 4.75 of the eight videos. They watched 3.27 (SD = 1.57, range 1-5) of the five anatomy videos and 1.48 (SD = 1.35; range 0-3) of the three radiology videos. In a regression analysis controlling for age and MCAT scores, using the anatomy videos at least once improved anatomy examination performance by 3.4% (P-value = 0.007). There was no relationship between radiology video usage and radiology exam score. Video resource availability did not enhance student performance in anatomy and radiology. However, when analyzing performance for those whom we knew level of video use, there was a statistically different and higher anatomy achievement.

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Background & Aims NS3/4A protease inhibitors, boceprevir or telaprevir, combined with peginterferon and ribavirin was the standard treatment for HCV genotype 1 and remains the only available direct antiviral drug based therapy in some countries. Efficacy and safety data in liver transplant recipients are limited. Methods This was a retrospective cohort study of 81 patients with genotype 1 HCV treated with boceprevir (10%) or telaprevir (90%) plus peginterferon and ribavirin at 6 US transplant centers (53% stage 3–4/4 fibrosis, 57% treatment experienced). The primary end point was undetectable HCV RNA 12 weeks after treatment completion (SVR12). Results The intent-to-treat SVR12 rate was 63% (51/81). Patients with an extended rapid virologic response, (undetectable HCV RNA at 4 and 12 weeks after starting boceprevir or telaprevir), had a higher rate of SVR12 than all other patients (85% vs. 15%, p <0.001). Adverse effects were common; 21% of patients experienced hemoglobin <8 g/dl and 57% required blood transfusions during the first 16 weeks. Twenty seven percent were hospitalized and 9% died; all were liver-related. Conclusions The addition of boceprevir or telaprevir to peginterferon and ribavirin yields SVR12 of 63% in liver transplant recipients with genotype 1 recurrent HCV, despite a high prevalence of advanced fibrosis and prior non-response to peginterferon and ribavirin. Rapid virologic response predicted a high likelihood of SVR. Despite a doubling of SVR rates, poor tolerability and high rates of adverse events were frequent and pose barriers to its widespread application.

Racial/ethnic and socioeconomic disparities exist in DAA initiation. Substance use may also influence patient or provider decision making about DAA initiation. Strategies are needed to ensure equitable access to DAAs, even in insured populations.