Summary
Background
Data are limited regarding the effectiveness and safety of generic velpatasvir plus sofosbuvir (VEL/SOF) for hepatitis C virus (HCV) in patients with or without human ...immunodeficiency virus (HIV) coinfection.
Aim
To evaluate the effectiveness and safety of generic VEL/SOF‐based therapy for HCV infection in patients with or without HIV coinfection in Taiwan.
Methods
Sixty‐nine HIV/HCV‐coinfected and 159 HCV‐monoinfected patients receiving 12 weeks of generic VEL/SOF with or without ribavirin (RBV) for HCV were prospectively enrolled. The anti‐viral responses and the adverse events (AEs) were compared between the two groups. The characteristics potentially related to sustained virological response 12 weeks off therapy (SVR12) were analysed.
Results
The SVR12 was achieved in 67 HIV/HCV‐coinfected patients (97.1%; 95% CI: 90.0%‐99.2%) and in 156 HCV‐monoinfected patients (98.1%; 95% CI: 94.6%‐99.4%) receiving VEL/SOF‐based therapy, respectively. The SVR12 rates were comparable between HIV/HCV‐coinfected and HCV‐monoinfected patients, regardless of pre‐specified baseline characteristics. One hundred twenty‐two (53.5%) and seven (3.1%) patients had baseline resistance‐associated substitutions (RASs) in HCV NS5A and NS5B regions, but the SVR12 rates were not affected by the presence or absence of RASs. One (1.4%) and five (3.1%) patients in the HIV/HCV‐coinfected and HCV‐monoinfected groups had serious AEs. No patient died or discontinued treatment due to AEs. The eGFR remained stable throughout the course of treatment in HIV/HCV‐coinfected patients receiving anti‐retroviral therapy containing tenofovir disoproxil fumarate (TDF).
Conclusions
Generic VEL/SOF‐based therapy is well‐tolerated and provides comparably high SVR12 rates for HCV infection in patients with and without HIV coinfection.
COVID toe in an adolescent boy: a case report Wong, J S C; Wong, T S; Chua, G T ...
Hong Kong medical journal = Xianggang yi xue za zhi,
04/2022, Volume:
28, Issue:
2
Journal Article
Peer reviewed
Open access
The appearance of chilblain-like lesions was not thought to be associated with a poor disease outcome.2 3 A major limitation of these reports is that only 11% of cases hospitalised tested positive ...for SARS-CoV-2 by polymerase chain reaction (PCR), with the remainder untested or testing negative. Another systematic review also concluded that some, but not all paediatric cases, who developed chilblain-like lesions during the COVID-19 pandemic had positive SARS-CoV-2 PCR, serology or viral particles confirmed in electron microscopy.5 Larger-scale epidemiological study is needed to confirm an association between these chilblain-like lesions and COVID-19 infection. Joshua SC Wong 1 †; TS Wong 1 †; Gilbert T Chua 2 †; Christy Wan 1; SH Lau 1; Samuel CS Ho 1; Jaime S Rosa Duque 2; Ian CK Wong 3,4; Kelvin KW To 5; Winnie WY Tso 2; Christine S Wong 6; Marco HK Ho 2; Janette Kwok 7; CB Chow 1; Paul KH Tam 8,9; Godfrey CF Chan; 2; WH Leung 2; YL Lau 2; Patrick Ip 2; Mike YW Kwan; CUHK 1 1 Department of Paediatrics and Adolescent Medicine, Princess Margaret Hospital, Hong Kong 2 Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong 3 Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong 4 Research Department of Practice and Policy, UCL School of Pharmacy, University College London, United Kingdom 5 Department of Microbiology, Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong 6 Dermatology Division, Department of Medicine, Queen Mary Hospital, Hong Kong 7 Division of Transplantation and Immunogenetics, Department of Pathology, Queen Mary Hospital, Hong Kong 8 Division of Paediatric Surgery, Department of Surgery, The University of Hong Kong, Hong Kong 9 Dr Li Dak-Sum Research Centre, The University of Hong Kong–Karolinska Institutet Collaboration in Regenerative Medicine, The University of Hong Kong, Hong Kong † Co-first authors
Immune checkpoint blockade with Programmed cell death 1 (PD-1)/PD-L1 inhibitors has been effective in various malignancies and is considered as a standard treatment modality for patients with ...non-small-cell lung cancer (NSCLC). However, emerging evidence show that PD-1/PD-L1 blockade can lead to hyperprogressive disease (HPD), a flair-up of tumor growth linked to dismal prognosis. This study aimed to evaluate the incidence of HPD and identify the determinants associated with HPD in patients with NSCLC treated with PD-1/PD-L1 blockade.
We enrolled patients with recurrent and/or metastatic NSCLC treated with PD-1/PD-L1 inhibitors between April 2014 and November 2018. Clinicopathologic variables, dynamics of tumor growth, and treatment outcomes were analyzed in patients with NSCLC who received PD-1/PD-L1 blockade. HPD was defined according to tumor growth kinetics (TGK), tumor growth rate (TGR), and time to treatment failure (TTF). Immunophenotyping of peripheral blood CD8+ T lymphocytes was conducted to explore the potential predictive biomarkers of HPD.
A total of 263 patients were analyzed. HPD was observed in 55 (20.9%), 54 (20.5%), and 98 (37.3%) patients according to the TGK, TGR, and TTF. HPD meeting both TGK and TGR criteria was associated with worse progression-free survival hazard ratio (HR) 4.619; 95% confidence interval (CI) 2.868–7.440 and overall survival (HR, 5.079; 95% CI, 3.136–8.226) than progressive disease without HPD. There were no clinicopathologic variables specific for HPD. In the exploratory biomarker analysis with peripheral blood CD8+ T lymphocytes, a lower frequency of effector/memory subsets (CCR7−CD45RA− T cells among the total CD8+ T cells) and a higher frequency of severely exhausted populations (TIGIT+ T cells among PD-1+CD8+ T cells) were associated with HPD and inferior survival rate.
HPD is common in NSCLC patients treated with PD-1/PD-L1 inhibitors. Biomarkers derived from rationally designed analysis may successfully predict HPD and worse outcomes, meriting further investigation of HPD.
Aim
To assess the connection between mitophagy and hypoxia‐induced apoptosis in osteoblasts and whether simvastatin alleviates bone resorption in apical periodontitis through modulation of ...mitophagy‐related apoptosis.
Methodology
Hypoxia‐induced generation of reactive oxygen species in mitochondria and changes in mitochondrial membrane potential were evaluated, respectively, by MitoSOX and JC‐1 fluorescence dye signalling. Accumulation of mitophagy markers PTEN‐induced putative kinase 1 (PINK1) and Parkin in mitochondria was examined by Western blotting and immunofluorescence microscopy. Osteoblast apoptosis was assessed by Western analysis of cleaved‐poly (adenosine diphosphate ribose) polymerase (PARP). In a rat model of induced apical periodontitis, the therapeutic effect of simvastatin and its action on osteoblast mitophagy and apoptosis were examined. anova, Fisher's and Student's t‐test were used for data analysis.
Results
Hypoxia‐induced mitochondrial dysfunction and stimulated mitophagy in osteoblasts. Hypoxia also provoked apoptosis in osteoblasts and inhibition of mitophagy decreased hypoxia‐augmented apoptotic activity. Simvastatin alleviated hypoxia‐induced mitochondrial dysfunction, mitophagy and apoptosis. The protective action of simvastatin against apoptosis was related to its antimitophagy activity. Experiments in the rat model of induced apical periodontitis supported the laboratory findings. Simvastatin treatment mitigated periapical bone loss and reduced the activities of apoptosis and mitophagy in regional osteoblasts.
Conclusions
The results suggest that modulation of osteoblast mitophagy may help diminish bone loss associated with inflammation and has potential as an auxiliary therapy for apical periodontitis.
Abstract
Harnessing the spin–momentum locking of topological surface states in conjunction with magnetic materials is the first step to realize novel topological insulator-based devices. Here, we ...report strong interfacial coupling in Bi
2
Se
3
/yttrium iron garnet (YIG) bilayers manifested as large interfacial in-plane magnetic anisotropy (IMA) and enhancement of damping probed by ferromagnetic resonance. The interfacial IMA and damping enhancement reaches a maximum when the Bi
2
Se
3
film approaches its two-dimensional limit, indicating that topological surface states play an important role in the magnetization dynamics of YIG. Temperature-dependent ferromagnetic resonance of Bi
2
Se
3
/YIG reveals signatures of the magnetic proximity effect of
T
C
as high as 180 K, an emerging low-temperature perpendicular magnetic anisotropy competing the high-temperature IMA, and an increasing exchange effective field of YIG steadily increasing toward low temperature. Our study sheds light on the effects of topological insulators on magnetization dynamics, essential for the development of topological insulator-based spintronic devices.
Linking topology in oligocarbazoles (see figure) has a strong influence on their electronic properties. 3(6),9′‐linked oligocarbazoles exhibit unusual suppression of electronic coupling between ...units, leading to localized excited states and very small reduction of triplet energies (compared to the monomer). Coupled with their excellent morphological stability, this makes them suitable as host materials for blue electrophosphorescence devices.
Optimized opportunistic multicast scheduling (OMS) is studied for cellular networks, where the problem of efficiently transmitting a common set of fountain-encoded data from a single base station to ...multiple users over quasi-static fading channels is examined. The proposed OMS scheme better balances the tradeoff between multiuser diversity and multicast gain by transmitting to a subset of users in each time slot using the maximal data rate that ensures successful decoding by these users. We first analyze the system delay in homogeneous networks by capitalizing on extreme value theory and derive the optimal selection ratio (i.e., the portion of users that are selected in each time slot) that minimizes the delay. Then, we extend results to heterogeneous networks where users are subject to different channel statistics. By partitioning users into multiple approximately homogeneous rings, we turn a heterogeneous network into a composite of smaller homogeneous networks and derive the optimal selection ratio for the heterogeneous network. Computer simulations confirm theoretical results and illustrate that the proposed OMS can achieve significant performance gains in both homogeneous and heterogeneous networks as compared with the conventional unicast and broadcast scheduling.
Abstract Background Surgical excision of papillary breast lesions with atypia diagnosed using core needle biopsy (CNB) has been accepted; however, the management of benign papillary lesions (without ...atypia) has been controversial. The purpose of this study was to evaluate the surgical outcome of nonmalignant papillary lesions diagnosed by ultrasound-guided 14-gauge CNB, and to establish clear guidelines on management of these lesions. Methods We retrospectively identified 268 nonmalignant papillary breast lesions, including 203 benign lesions and 65 atypical lesions, diagnosed by CNB and subsequently surgically excised in 250 women at our institution between July 2004 and October 2010. For each lesion, medical records and radiologic and pathologic reports were reviewed and coded. We compared the histological upgrade among the collected variables. Results On histological examination after surgical excision, 15.4% atypical papillary lesions and 5.9% benign lesions were upgraded to malignant, and 20.2% benign lesions were upgraded to atypical. Atypia ( P = 0.015) was significantly associated with malignant upgrade at excision. No clinical or radiologic variable was helpful in predicting the possibility of histological upgrade of CNB-diagnosed nonmalignant papillary lesions. Conclusions Nonmalignant papillary lesions diagnosed with CNB showed an unacceptable pathological upgrade rate after excision. Therefore, surgical excision should be performed for all papillary lesions of the breast for definitive diagnosis.
Vascular endothelial growth factor (VEGF) receptor 3 (VEGFR-3) (also called VEGFR-3) is activated by its specific ligand, VEGF-C, which promotes cancer progression. The VEGF-C/VEGFR-3 axis is ...expressed not only by lymphatic endothelial cells but also by a variety of human tumour cells. Activation of the VEGF-C/VEGFR-3 axis in lymphatic endothelial cells can facilitate metastasis by increasing the formation of lymphatic vessels (lymphangiogenesis) within and around tumours. The VEGF-C/VEGFR-3 axis plays a critical role in leukaemic cell proliferation, survival, and resistance to chemotherapy. Moreover, activation of the VEGF-C/VEGFR-3 axis in several types of solid tumours enhances cancer cell mobility and invasion capabilities, promoting cancer cell metastasis. In this review, we discuss the novel function and molecular mechanism of the VEGF-C/VEGFR-3 axis in cancer progression.
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