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The Interplay of Long Non‐Coding RNAs and Hepatitis B Virus

alexandrossfakianakis shared this article with you from Inoreader The Interplay of Long Non‐Coding RNAs and Hepatitis B Virus via Journal of Medical Virology ABSTRACT Hepatitis B Virus (HBV) infections remain a major global health burden with an estimated 296 million people living with a chronic infection and 884,00 HBV-related deaths annually. Notably, patients with a chronic hepatitis B (CHB) infection are at a 30-fold greater risk of developing hepatocellular carcinoma (HCC), the 3rd deadliest cancer worldwide. Several groups have assessed HBV-related aberrant expression of host-cell long non-coding RNAs (lncRNAs) and how altered expression of specific lncRNAs affects HBV replication and progression to associated disease states. Given the challenges in establishing effective HBV models and analyzing transcriptomic data, this review focuses on lncRNA expression data primarily collected from clinical patient samples and primary human hepatocytes (PHHs), with subsequent mechanism of action analysis in cell lines or other model systems. Ultimately, understanding HBV-induced lncRNA-expression dysregulation could lead to new treatments and biomarkers for HBV infection and its associated diseases. This article is protected by copyright. All rights reserved. View on Web

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A Two-stage Approach for Rapid Assessment of the Proportion Achieving Viral Suppression Using Routine Clinical Data

alexandrossfakianakis shared this article with you from Inoreader A Two-stage Approach for Rapid Assessment of the Proportion Achieving Viral Suppression Using Routine Clinical Data via Epidemiology - Featured Articles - Featured Articles Background: Improving viral suppression among people with HIV reduces morbidity, mortality, and transmission. Accordingly, monitoring the proportion of patients with a suppressed viral load is important to optimizing HIV care and treatment programs. But viral load data are often incomplete in clinical records. We illustrate a two-stage approach to estimate the proportion of treated people with HIV who have a suppressed viral load in the Dominican Republic. Methods: Routinely collected data on viral load and patient characteristics were recorded in a national database, but 74% of patients on treatment at the time of the study did not have a recent viral load measurement. We recruited a subset of these patients for a rapid assessment that obtained additional viral load measurements. We combined results from the rapid assessment and main database using a two-stage weighting approach and compared results to estimates obtained using standard approaches to account for missing data. Results: Of patients with recent routinely collected viral load data, 60% had a suppressed viral load. Results were similar after applying standard approaches to account for missing data. Using the two-stage approach, we estimated that 77% (95% confidence interval [CI] = 74, 80) of those on treatment had a suppressed viral load. Conclusions: When assessing the proportion of people on treatment with a suppressed viral load using routinely collected data, applying standard approaches to handle missing data may be inadequate. In these settings, augmenting routinely collected data with data collected through sampling-based approaches could allow more accurate and efficient monitoring of HIV treatment program effectiveness. View on Web

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A Phase I/II Study of Intrathecal Trastuzumab in HER-2 Positive Cancer with Leptomeningeal Metastases: Safety, Efficacy, and Cerebrospinal Fluid Pharmacokinetics

alexandrossfakianakis shared this article with you from Inoreader A Phase I/II Study of Intrathecal Trastuzumab in HER-2 Positive Cancer with Leptomeningeal Metastases: Safety, Efficacy, and Cerebrospinal Fluid Pharmacokinetics via Neuro-Oncology Advance Access Abstract Background Patients with human epidermal growth factor receptor 2-positive (HER2-positive) cancers have a high incidence of central nervous system (CNS) spread, but unfortunately systemic trastuzumab which targets the HER2 receptor has little CNS penetration. The purpose of this study was to determine the maximum tolerated dose of intrathecal trastuzumab and its efficacy in patients with HER2-positive LMD. Methods This multicenter study enrolled 34 LMD patients in a combined Phase I/II study in treating patients with intrathecal trastuzumab. Any HER2-positive histology was allowed in the Phase I; the Phase II was limited to HER2-positive breast cancer. Results Intrathecal trastuzumab was well tolerated, with one dose limiting toxicity of grade 4 (arachnoiditis) occurring at the 80 mg twice weekly dose. The recommended Phase II dose was 80 mg intrathecally twice weekly. Twenty-six patients at dose level 80mg w ere included in evaluation for efficacy: partial response was seen in 5 (19.2%) patients, stable disease was observed in 13 (50.0%), and 8 (30.8%) of the patients had progressive disease. Median overall survival (OS) for Phase 2 dose treated patients was 8.3 months (95% CI 5.2 to 19.6). The Phase II HER2-positive breast cancer patients median OS was 10.5 months (95% CI 5.2 to 20.9). Pharmacokinetic (PK) studies were limited in the setting of concurrent systemic trastuzumab administration, however, did show stable CSF concentrations with repeated dosing suggest that trastuzumab does not accumulate in the CSF in toxic concentrations. Conclusion This study suggests promise for potentially improved outcomes of HER-positive LMD patients when treated with intrathecal trastuzumab while remaining safe and well-tolerated for patients. View on Web

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