Quantitative hepatitis B core antibody and quantitative hepatitis B surface antigen: Novel viral biomarkers for chronic hepatitis B management.

The management of hepatitis B virus (HBV) infection now involves regular and appropriate monitoring of viral activity, disease progression, and treatment response. Traditional HBV infection biomarkers are limited in their ability to predict clinical outcomes or therapeutic effectiveness. Quantitation of HBV core antibodies (qAnti-HBc) is a novel non-invasive biomarker that may help with a variety of diagnostic issues. It was shown to correlate strongly with infection stages, hepatic inflammation and fibrosis, chronic infection exacerbations, and the presence of occult infection. Furthermore, qAnti-HBc levels were shown to be predictive of spontaneous or treatment-induced HBeAg and HBsAg seroclearance, relapse after medication termination, re-infection following liver transplantation, and viral reactivation in the presence of immunosuppression. qAnti-HBc, on the other hand, cannot be relied on as a single diagnostic test to address all problems, and its diagnostic and prognostic potential may be greatly increased when paired with qHBsAg. Commercial qAnti-HBc diagnostic kits are currently not widely available. Because many methodologies are only semi-quantitative, comparing data from various studies and defining universal cut-off values remains difficult. This review focuses on the clinical utility of qAnti-HBc and qHBsAg in chronic hepatitis B management.

Systemic treatment for advanced pancreatic cancer.

Pancreatic cancer is a deadly disease with an extremely poor 5-year survival rate due to treatment resistance and late-stage detection. Despite numerous years of research and pharmaceutical development, these figures have not changed. Treatment options for advanced pancreatic cancer are still limited. This illness is typically detected at a late stage, making curative surgical resection impossible. Chemotherapy is the most commonly utilized technique for treating advanced pancreatic cancer but has poor efficacy. Targeted therapy and immunotherapy have made significant progress in many other cancer types and have been proven to have extremely promising possibilities; these therapies also hold promise for pancreatic cancer. There is an urgent need for research into targeted treatment, immunotherapy, and cancer vaccines. In this review, we emphasize the foundational findings that have fueled the therapeutic strategy for advanced pancreatic cancer. We also address current advancements in targeted therapy, immunotherapy, and cancer vaccines, all of which continue to improve the clinical outcome of advanced pancreatic cancer. We believe that clinical translation of these novel treatments will improve the low survival rate of this deadly disease.

Systemic treatments for resectable carcinoma of the esophagus.

One of the most prevalent malignancies in the world is esophageal cancer (EC). The 5-year survival rate of EC remains pitiful despite treatment advancements. Neoadjuvant chemoradiotherapy in conjunction with esophagectomy is the standard of care for patients with resectable disease. The pathological complete response rate, however, is not acceptable. A distant metastasis or a locoregional recurrence will occur in about half of the patients. To increase the clinical effectiveness of therapy, it is consequently vital to investigate cutting-edge and potent therapeutic modalities. The approach to the management of resectable EC using immunotherapy has been considerably altered by immune checkpoint inhibitors. Systemic immunotherapy has recently been shown to have the potential to increase the survival of patients with resectable EC, according to growing clinical data. A combination of chemotherapy, radiation, and immunotherapy may have a synergistic antitumor impact because, according to mounting evidence, these treatments can stimulate the immune system via a number of different pathways. In light of this, it makes sense to consider the value of neoadjuvant immunotherapy for patients with surgically treatable EC. In this review, we clarify the rationale for neoadjuvant immunotherapy in resectable EC patients, recap the clinical outcomes of these approaches, go through the upcoming and ongoing investigations, and emphasize the difficulties and unmet research requirements.

Immunotherapy for advanced gastric cancer.

Gastric cancer (GC) is believed to be the fifth most common cancer and the third most common cause of death worldwide. Treatment techniques include radiation, chemotherapy, gastrectomy, and targeted treatments are often employed. Some hopeful results from the development of GC immunotherapy have already changed treatment approaches. Along with previous combination medicines, new immunotherapies have been developed that target distinct molecules. Despite ongoing studies into the current therapeutic options and significant improvements in this field, the prognosis for the ailment is poor. Since there are few treatment options and a delay in detection, the illness actually advances, spreads, and metastasizes. The bulk of immunotherapies in use today rely on cytotoxic immune cells, monoclonal antibodies, and gene-transferred vaccines. Immune checkpoint inhibitors have become more popular. In this review, we sought to examine the viewpoint and development of several immunotherapy treatment modalities for advanced GC, as well as the clinical results thus far reported. Additionally, we outlined tumor immune escape and tumor immunosurveillance.

Tuberculosis of the spine.

Pott's spine, commonly known as spinal tuberculosis (TB), is an extrapulmonary form of TB caused by Mycobacterium TB. Pott's paraplegia occurs when the spine is involved. Spinal TB is usually caused by the hematogenous spread of infection from a central focus, which can be in the lungs or another location. Spinal TB is distinguished by intervertebral disc involvement caused by the same segmental arterial supply, which can result in severe morbidity even after years of approved therapy. Neurological impairments and spine deformities are caused by progressive damage to the anterior vertebral body. The clinical, radiographic, microbiological, and histological data are used to make the diagnosis of spinal TB. In Pott's spine, combination multidrug antitubercular therapy is the basis of treatment. The recent appearance of multidrug-resistant/extremely drug-resistant TB and the growth of human immunodeficiency virus infection have presented significant challenges in the battle against TB infection. Patients who come with significant kyphosis or neurological impairments are the only ones who require surgical care. Debridement, fusion stabilization, and correction of spinal deformity are the cornerstones of surgical treatment. Clinical results for the treatment of spinal TB are generally quite good with adequate and prompt care.

Paradigm shift of chemotherapy and systemic treatment for biliary tract cancer.

Biliary tract cancers (BTC) are frequently identified at late stages and have a poor prognosis due to limited systemic treatment regimens. For more than a decade, the combination of gemcitabine and cis-platin has served as the first-line standard treatment. There are few choices for second-line chemo-therapy. Targeted treatment with fibroblast growth factor receptor 2 inhibitors, neurotrophic tyrosine receptor kinase inhibitors, and isocitrate dehydrogenase 1 inhibitors has had important results. Immune checkpoint inhibitors (ICI) such as pembrolizumab are only used in first-line treatment for microsatellite instability high patients. The TOPAZ-1 trial's outcome is encouraging, and there are several trials underway that might soon put targeted treatment and ICI combos into first-line options. Newer targets and agents for existing goals are being studied, which may represent a paradigm shift in BTC management. Due to a scarcity of targetable mutations and the higher toxicity profile of the current medications, the new category of drugs may occupy a significant role in BTC therapies.

Systemic treatment for unresectable hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is most commonly found in the context of liver cirrhosis and, in rare cases, in a healthy liver. Its prevalence has risen in recent years, particularly in Western nations, due to the increasing frequency of non-alcoholic fatty liver disease. Advanced HCC has a poor prognosis. For many years, the only proven therapy for unresectable HCC (uHCC) was sorafenib, a tyrosine kinase inhibitor. Recently, the synergistic effect of an immune checkpoint inhibitor, atezolizumab, and bevacizumab outperformed sorafenib alone in terms of survival, making it the recommended first-line therapy. Other multikinase inhibitors, lenvatinib and regorafenib, were also recommended as first and second-line drugs, respectively. Intermediate-stage HCC patients with retained liver function, particularly uHCC without extrahepatic metastasis, may benefit from trans-arterial chemoembolization. The current problem in uHCC is selecting a patient for the best treatment while considering the preexisting liver condition and liver function. Indeed, all study patients had a Child-Pugh class A, and the best therapy for other individuals is unknown. Additionally, in the absence of a medical contraindication, atezolizumab could be combined with bevacizumab for uHCC systemic therapy. Several studies are now underway to evaluate immune checkpoint inhibitors in combination with anti-angiogenic drugs, and the first findings are encouraging. The paradigm of uHCC therapy is changing dramatically, and many obstacles remain for optimum patient management in the near future. The purpose of this commentary review was to give an insight into current systemic treatment options for patients with uHCC who are not candidates for surgery to cure the disease.

Systemic treatment for metastatic colorectal cancer.

Significant progress has been achieved in the treatment of metastatic colorectal cancer (mCRC) patients during the last 20 years. There are currently numerous treatments available for the first-line treatment of mCRC. Sophisticated molecular technologies have been developed to reveal novel prognostic and predictive biomarkers for CRC. The development of next-generation sequencing and whole-exome sequencing, which are strong new tools for the discovery of predictive molecular biomarkers to facilitate the delivery of customized treatment, has resulted in tremendous breakthroughs in DNA sequencing technology in recent years. The appropriate adjuvant treatments for mCRC patients are determined by the tumor stage, presence of high-risk pathologic characteristics, microsatellite instability status, patient age, and performance status. Chemotherapy, targeted therapy, and immunotherapy are the main systemic treatments for patients with mCRC. Despite the fact that these novel treatment choices have increased overall survival for mCRC, survival remains optimal for individuals with non-metastatic disease. The molecular technologies currently being used to support our ability to practice personalized medicine; the practical aspects of applying molecular biomarkers to regular clinical practice; and the evolution of chemotherapy, targeted therapy, and immunotherapy strategies for the treatment of mCRC in the front-line setting are all reviewed here.

Circulating angiotensin converting enzyme 2 and COVID-19.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has triggered a widespread outbreak since December 2019. The SARS-CoV-2 infection-related illness has been dubbed the coronavirus disease 2019 (COVID-19) by the World Health Organization. Asymptomatic and subclinical infections, a severe hyper-inflammatory state, and mortality are all examples of clinical signs. After attaching to the angiotensin converting enzyme 2 (ACE2) receptor, the SARS-CoV-2 virus can enter cells through membrane fusion and endocytosis. In addition to enabling viruses to cling to target cells, the connection between the spike protein (S-protein) of SARS-CoV-2 and ACE2 may potentially impair the functionality of ACE2. Blood pressure is controlled by ACE2, which catalyzes the hydrolysis of the active vasoconstrictor octapeptide angiotensin (Ang) II to the heptapeptide Ang-(1-7) and free L-Phe. Additionally, Ang I can be broken down by ACE2 into Ang-(1-9) and metabolized into Ang-(1-7). Numerous studies have demonstrated that circulating ACE2 (cACE2) and Ang-(1-7) have the ability to restore myocardial damage in a variety of cardiovascular diseases and have anti-inflammatory, antioxidant, anti-apoptotic, and anti-cardiomyocyte fibrosis actions. There have been some suggestions for raising ACE2 expression in COVID-19 patients, which might be used as a target for the creation of novel treatment therapies. With regard to this, SARS-CoV-2 is neutralized by soluble recombinant human ACE2 (hrsACE2), which binds the viral S-protein and reduces damage to a variety of organs, including the heart, kidneys, and lungs, by lowering Ang II concentrations and enhancing conversion to Ang-(1-7). This review aims to investigate how the presence of SARS-CoV-2 and cACE2 are related. Additionally, there will be discussion of a number of potential therapeutic approaches to tip the ACE/ACE-2 balance in favor of the ACE-2/Ang-(1-7) axis.

Human-induced pluripotent stem cell-atrial-specific cardiomyocytes and atrial fibrillation.

Patient-specific human-induced pluripotent stem cell-derived atrial cardiomyocytes (hiPSC-aCMs) may be produced, genome-edited, and differentiated into multiple cell types for regenerative medicine, disease modeling, drug testing, toxicity screening, and three-dimensional tissue fabrication. There is presently no complete model of atrial fibrillation (AF) available for studying human pharmacological responses and evaluating the toxicity of potential medication candidates. It has been demonstrated that hiPSC-aCMs can replicate the electrophysiological disease phenotype and genotype of AF. The hiPSC-aCMs, however, are immature and do not reflect the maturity of aCMs in the native myocardium. Numerous laboratories utilize a variety of methodologies and procedures to improve and promote aCM maturation, including electrical stimulation, culture duration, biophysical signals, and changes in metabolic variables. This review covers the current methods being explored for use in the maturation of patient-specific hiPSC-aCMs and their application towards a personalized approach to the pharmacologic therapy of AF.

Potassium-competitive acid blockers and gastroesophageal reflux disease.

Proton pump inhibitors (PPIs), the most commonly used antisecretory medi-cations in the management of reflux illness, virtually eliminate elective surgery for ulcer disease, and relegate anti-reflux surgery to patients with gastroesophageal reflux disease (GERD) who are inadequately managed by medical therapy. However, PPI medications still leave some therapeutic demands of GERD unmet. Furthermore, up to 40%-55% of daily PPI users have chronic symptoms, due to PPI refractoriness. Potassium-competitive acid blockers (P-CABs) transcend many of the problems and limits of PPIs, delivering quick, powerful, and extended acid suppression and allowing for treatment of numerous unmet needs. Recently, it has become clear that compromised mucosal integrity plays a role in the etiology of GERD. As a result, esophageal mucosal protection has emerged as a novel and potential treatment approach. An increasing body of research demonstrates that when P-CABs are used as primary drugs or add-on drugs (to regular treatment), they provide a considerable extra benefit, particularly in alleviating symptoms that do not respond to PPI therapy.

COVID-19 vaccination and cardiac dysfunction.

The coronavirus disease 2019 (COVID-19) mRNA vaccine against severe acute respiratory syndrome coronavirus 2 infections has reduced the number of symptomatic patients globally. A case series of vaccine-related myocarditis or pericarditis has been published with extensive vaccination, most notably in teenagers and young adults. Men seem to be impacted more often, and symptoms commonly occur within 1 wk after immunization. The clinical course is mild in the majority of cases. Based on the evidence, a clinical framework to guide physicians to examine, analyze, identify, and report suspected and confirmed cardiac dysfunction cases is needed. A standardized workup for every patient with strongly suspicious symptoms associated with the COVID-19 mRNA vaccine comprises serum cardiac troponin measurement and a 12-lead electrocardiogram (ECG). For patients with unexplained elevation of cardiac troponin and pathologic ECG, echocardiography is recommended. Consultation with a cardiovascular expert and hospitalization should be considered in this group of patients. Treatment is primarily symptomatic and supportive. Deferring a 2nd dose of the COVID-19 mRNA vaccination in individuals with suspected myocarditis or pericarditis after the 1st dose is suggested until further safety data become available.

Chronic hepatitis B: New potential therapeutic drugs target.

Chronic hepatitis B (CHB) infection remains the most causative agent of liver-related morbidity and mortality worldwide. It impacts nearly 300 million people. The current treatment for chronic infection with the hepatitis B virus (HBV) is complex and lacks a durable treatment response, especially hepatitis B surface antigen (HBsAg) loss, necessitating indefinite treatment in most CHB patients due to the persistence of HBV covalently closed circular DNA (cccDNA). New drugs that target distinct steps of the HBV life cycle have been investigated, which comprise inhibiting the entry of HBV into hepatocytes, disrupting or silencing HBV cccDNA, modulating nucleocapsid assembly, interfering HBV transcription, and inhibiting HBsAg release. The achievement of a functional cure or sustained HBsAg loss in CHB patients represents the following approach towards HBV eradication. This review will explore the up-to-date advances in the development of new direct-acting anti-HBV drugs. Hopefully, with the combination of the current antiviral drugs and the newly developed direct-acting antiviral drugs targeting the different steps of the HBV life cycle, the ultimate eradication of CHB infection will soon be achieved.

Dengue hemorrhagic fever and the liver.

Dengue hemorrhagic fever (DHF) is one of the most rapidly emerging infections of tropical and subtropical regions worldwide. It affects more rural and urban areas due to many factors, including climate change. Although most people with dengue viral infection are asymptomatic, approximately 25% experience a self-limited febrile illness with mild to moderate biochemical abnormalities. Severe dengue diseases develop in a small proportion of these patients, and the common organ involvement is the liver. The hepatocellular injury was found in 60%-90% of DHF patients manifested as hepatomegaly, jaundice, elevated aminotransferase enzymes, and critical condition as an acute liver failure (ALF). Even the incidence of ALF in DHF is very low (0.31%-1.1%), but it is associated with a relatively high mortality rate (20%-68.3%). The pathophysiology of liver injury in DHF included the direct cytopathic effect of the DENV causing hepatocytes apoptosis, immune-mediated hepatocyte injury induced hepatitis, and cytokine storm. Hepatic hypoperfusion is another contributing factor in dengue shock syndrome. The reduction of morbidity and mortality in DHF with liver involvement is dependent on the early detection of warning signs before the development of ALF.