The role of different viral biomarkers on the management of chronic hepatitis B

Chronic hepatitis B infection is a major public health challenge. With the advancement in technology, various components of the viral cycle can now be measured in the blood to assess viral activity. In this review article, we summarize the relevant data of how antiviral therapies impact viral biomarkers, and discuss their potential implications. Viral nucleic acids including hepatitis B virus (HBV) double-stranded deoxy-ribonucleic acid (DNA) and to a lesser extent, pre-genomic RNA, are readily suppressed by nucleos(t)ide analogues (NUCs). The primary role of these markers include risk prediction for hepatocellular carcinoma (HCC) and risk stratification for partial cure, defined as off-therapy virological control, or functional cure, defined as hepatitis B surface antigen (HBsAg) seroclearance plus undetectable serum HBV DNA for ≥6 months. Viral translational products including hepatitis e antigen, quantitative HBsAg and hepatitis B core-related antigen can be reduced by NUCs and pegylated interferon a. They are important in defining disease phase, delineating treatment endpoints, and predicting clinical outcomes including HCC risk and partial/functional cure. As the primary outcome of phase III trials in chronic hepatitis B is set as HBsAg seroclearance, appropriate viral biomarkers can potentially inform the efficacy of novel compounds. Early viral biomarker response can help with prioritization of subjects into clinical trials. However, standardization and validation studies would be crucial before viral biomarkers can be broadly implemented in clinical use

A Randomized Controlled Trial of Auricular Transcutaneous Electrical Nerve Stimulation for Managing Posthysterectomy Pain

Background. A patient- and assessor-blinded randomized controlled trial was conducted to examine the effectiveness of auricular transcutaneous electrical nerve stimulation (TENS) in relieving posthysterectomy pain. Method. Forty-eight women who had undergone a total abdominal hysterectomy were randomly assigned into three groups (n = 16 each) to receive either (i) auricular TENS to therapeutic points (the true TENS group), (ii) auricular TENS to inappropriate points (the sham TENS group), or (iii) 20 minutes of bed rest with no stimulation (the control group). The intervention was delivered about 24 hours after the operation. A visual analogue scale was used to assess pain while resting (VAS-rest) and upon huffing (VAS-huff) and coughing (VAS-cough), and the peak expiratory flow rate (PEFR) was assessed before and at 0, 15, and 30 minutes after the intervention. Result. As compared to the baseline, only the true TENS group reported a significant reduction in VAS-rest (P = .001), VAS-huff (P = .004), and VAS-cough (P = .001), while no significant reduction in any of the VAS scores was seen in the sham TENS group (all P > .05). In contrast, a small rising trend was observed in the VAS-rest and VAS-huff scores of the control group, while the VAS-cough score remained largely unchanged during the period of the study. A between-group comparison revealed that all three VAS scores of the true TENS group were significantly lower than those of the control group at 15 and 30 minutes after the intervention (all P < .02). No significant between-group difference was observed in PEFR at any point in time. Conclusion. A single session of auricular TENS applied at specific therapeutic points significantly reduced resting (VAS-rest) and movement-evoked pain (VAS-huff, VAS-cough), and the effects lasted for at least 30 minutes after the stimulation. The analgesic effects of auricular TENS appeared to be point specific and could not be attributed to the placebo effect alone. However, auricular TENS did not produce any significant improvement in the performance of PEFR

Clinical practice guidelines and real-life practice on hepatocellular carcinoma: the Hong Kong perspective

Hepatocellular carcinoma (HCC) is a major public health burden in Hong Kong, and chronic hepatitis B is the most common HCC etiology in our region. With the high case load, extensive local expertise on HCC has been accumulated. This article summarized local guidelines and real-life practice on HCC management in Hong Kong. For HCC surveillance, liver ultrasound and serum alpha-fetoprotein for periodic screening is recommended in viral hepatitis or cirrhotic patients, and this is adhered to in clinical practice. HCC diagnosis is not covered in local guidelines, yet our practice is in-line with regional guidelines, where diagnosis is usually achieved by cross-sectional imaging and without the need for histology. Our guidelines recommend using the Hong Kong Liver Cancer Staging for pre-treatment staging, yet we routinely use other widely-adopted systems such as the Barcelona Clinic Liver Cancer Staging and the Tumor-Node-Metastasis Staging as well. Our local guidelines have provided clear treatment algorithms for the whole range of HCC therapies, including resection, ablation, transplant, transarterial chemoembolization, transarterial radioembolization, stereotactic body radiation therapy, targeted therapy, and immunotherapy. Real-life treatment choices are largely in line with the guidelines, although treatment protocols are individualized, and availability of specific therapies can vary between centers. Overall, HCC guidelines in Hong Kong are tailored based on local expertise and our unique patient population. The guidelines are up-to-date and provide practical pathways to assist our routine practice. Regular updates of local guidelines are warranted to account for the rapidly evolving paradigm of HCC management

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Mimicking multiple sclerosis - Ghost tumor that comes and goes in different parts of the brain without any treatment

Lesions that spontaneously come and go in central nervous system without any treatment at different time points and at different locations (CNS) usually lead ones to think of the possibilities of multiple sclerosis. However, sometimes there are exceptions. Surgical biopsy remains an important tool for definitive diagnosis in difficult cases. We report a case of intracranial diffuse large B cell lymphoma that spontaneously disappeared without any treatment and then reappeared at different time points and different locations

Anti-HBc: a significant host predictor of spontaneous HBsAg seroclearance in chronic hepatitis B patients - a retrospective longitudinal study

Abstract Background and Aim : In chronic hepatitis B infection (CHB), seroclearance of hepatitis B surface antigen (HBsAg) is associated with favourable clinical outcomes compared to those with persistent HBsAg seropositivity, and thus considered as a desired treatment endpoint. This current study explores the possibility of serum antibody to hepatitis B core antigen (anti-HBc) as a potential predictive factor of HBsAg seroclearance. Methods This is a retrospective study that analyzed the plasma samples of CHB patients using the LUMIPULSE® G1200 analyzer. The longitudinal anti-HBc level between patients who subsequently achieved HBsAg seroclearance (S-losers) and those with persistent HBsAg-positivity (controls) were compared at multiple time points before the event. Results A total of 240 subjects (120 S-losers and 120 controls; age- and gender-matched) were included (mean age 56.42 ± 10.81, 65% male). Compared to controls, S-losers had significantly lower plasma anti-HBc levels prior to HBsAg seroclearance, with a significant trend of declining plasma anti-HBc 8–5 years prior to HBsAg seroclearance (p < 0.01), while such trend was not observed in controls. ROC curve analysis revealed that plasma anti-HBc at multiple time points before HBsAg seroclearance return AUC greater than 0.7. Plasma anti-HBc level at the cut-off value of 82.50 COI was 68.3% sensitive and 90% specific for HBsAg seroclearance within 1 year. Combining with quantitative HBsAg < 100 IU/mL, anti-HBc < 82.5 COI identified 88.2% patients who would develop HBsAg seroclearance within 1 year. Conclusion Plasma anti-HBc level began to decline 10 years prior to HBsAg seroclearance and can serve as a potential predictor for subsequent HBsAg seroclearance

Targeted Sequencing Approach and Its Clinical Applications for the Molecular Diagnosis of Human Diseases

The outbreak of COVID-19 has positively impacted the NGS market recently. Targeted sequencing (TS) has become an important routine technique in both clinical and research settings, with advantages including high confidence and accuracy, a reasonable turnaround time, relatively low cost, and fewer data burdens with the level of bioinformatics or computational demand. Since there are no clear consensus guidelines on the wide range of next-generation sequencing (NGS) platforms and techniques, there is a vital need for researchers and clinicians to develop efficient approaches, especially for the molecular diagnosis of diseases in the emergency of the disease and the global pandemic outbreak of COVID-19. In this review, we aim to summarize different methods of TS, demonstrate parameters for TS assay designs, illustrate different TS panels, discuss their limitations, and present the challenges of TS concerning their clinical application for the molecular diagnosis of human diseases

Targeted Sequencing Approach and Its Clinical Applications for the Molecular Diagnosis of Human Diseases

The outbreak of COVID-19 has positively impacted the NGS market recently. Targeted sequencing (TS) has become an important routine technique in both clinical and research settings, with advantages including high confidence and accuracy, a reasonable turnaround time, relatively low cost, and fewer data burdens with the level of bioinformatics or computational demand. Since there are no clear consensus guidelines on the wide range of next-generation sequencing (NGS) platforms and techniques, there is a vital need for researchers and clinicians to develop efficient approaches, especially for the molecular diagnosis of diseases in the emergency of the disease and the global pandemic outbreak of COVID-19. In this review, we aim to summarize different methods of TS, demonstrate parameters for TS assay designs, illustrate different TS panels, discuss their limitations, and present the challenges of TS concerning their clinical application for the molecular diagnosis of human diseases