Pd-Catalyzed Sequential C–C Bond Formation and Cleavage: Evidence for an Unexpected Generation of Arylpalladium(II) Species

A Pd­(II)-catalyzed reaction engaging alkenyl β-keto esters is reported that leads to the formation of 1-naphthols and an unexpected generation of arylpalladium­(II) species. Interception of the in situ generated arylpalladium­(II) species in a Mizoroki–Heck reaction, together with additional mechanistic studies, provided strong evidence in support of the first <i>aromatization-driven</i> β-carbon elimination process. A single Pd catalyst served to promote a series of both C–C bond forming and cleavage events in an unprecedented manner

Evaluating the efficacy of switching from lamivudine plus adefovir to tenofovir disoproxil fumarate monotherapy in lamivudine-resistant stable hepatitis B patients

<div><p>Background</p><p>The efficacy of switching to tenofovir disoproxil fumarate (TDF) monotherapy from lamivudine (LAM) plus adefovir dipivoxil (ADV) combination therapy (stable switching) in patients with LAM-resistant chronic hepatitis B (CHB) and undetectable hepatitis B virus (HBV) DNA is not clear.</p><p>Methods</p><p>In this non-inferiority trial, patients with LAM-resistant CHB and undetectable serum HBV DNA (<20 IU/mL) for >6 months after initiating LAM+ADV combination therapy were randomized (1:2) either to continue the combination therapy (LAM+ADV group, n = 58) or switched to TDF monotherapy (TDF group, n = 111). They were followed-up with serum biochemistry tests and HBV DNA measurement at 12-week intervals for 96 weeks. The primary endpoint of this study was the proportion of patients with viral reactivation at week 96.</p><p>Results</p><p>Patients with CHB enrolled in this study (n = 169) included 74 patients with compensated liver cirrhosis. In total, 9 patients (4 in the LAM+ADV group and 5 in the TDF group) dropped-out from the study. After a mean follow-up period of 96 weeks, the proportion of HBV reactivation observed was 6.8% (4/58) in the LAM+ADV group and 4.5% (5/111) in the TDF group by using intention-to-treat analysis (difference, -2.3%; 95% CI, -9.84–5.24%). None of the subjects in either group experienced viral reactivation based on per protocol analysis. No serious adverse reactions were observed. In the subgroup analysis for estimated glomerular filtration rate (eGFR) before and after treatment, decreased eGFR was observed only in the TDF group with cirrhosis (85.22 vs. 79.83 mL/min/1.73 m², p = 0.000)</p><p>Conclusions</p><p>Stable switching to TDF monotherapy yielded non-inferior results at 96 weeks compared to the results obtained with LAM+ADV combination therapy in patients with LAM-resistant CHB and undetectable HBV DNA. However, TDF monotherapy in patients with cirrhosis requires close attention with respect to renal function.</p><p>Trial registration</p><p>ClinicalTrials.gov <a href="https://clinicaltrials.gov/ct2/show/NCT01732367" target="_blank">NCT01732367</a></p></div

Comparison between two groups after 96-week follow-up.

<p>Comparison between two groups after 96-week follow-up.</p

LAM-resistance mutation profiles and previous treatment period.

<p>LAM-resistance mutation profiles and previous treatment period.</p

Details of the 25 patients with transient virologic rebound or withdrawal from the trial.

<p>Details of the 25 patients with transient virologic rebound or withdrawal from the trial.</p

Baseline characteristics of patients.

<p>Baseline characteristics of patients.</p