Is Bio-Identical Hormone Replacement Therapy Safer than Traditional Hormone Replacement Therapy?

Recent clinical trials have demonstrated an increase in the risk of cardiovascular disease (CVD) in women using oral hormone replacement therapy (HRT). Bio-identical HRT (BHRT) is widely used by alternative healthcare practitioners for the treatment of symptoms of menopause, with the prevailing assumption that BHRT provides the benefits of HRT while attenuating the risks. However, considering the serious risks of HRT, the use of any form of HRT, including BHRT, without sufficient scientific evaluation may create considerable risk.The main hormone found in BHRT is estriol. Estriol is used alone or in combination with estradiol and estrone. The total daily oral dose of BHRT used is, on average, ten times higher than that used in HRT, and both oral and topical forms are used for bio-identical hormone administration. The clinical trials that have examined cardiovascular outcomes associated with estriol therapy are limited, and there is evidence to demonstrate variable effects on markers associated with cardiovascular risk.Based on the current evidence, the same cardiovascular risks that have recently been found to be associated with oral HRT may also be associated with the administration of oral estriol in BHRT. The use of oral bio-identical hormones cannot be promoted until further evidence is available to demonstrate its safety.     

Gene Therapy for Liver Diseases

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Lipid-Lowering Therapy in Patients 75 Years and Older: Clinical Priority or Superfluous Therapy?

The incidence and prevalence of cardiovascular (CV)-related morbidity and mortality significantly increase with age. In the elderly, hypercholesterolemia with elevated total and low-density-lipoprotein cholesterol is a significant predictor of incident and recurrent CV disease. Multiple lines of evidence have established the benefit of statin therapy to lower cholesterol levels and reduce the risk of CV events as well as prevent progression of subclinical atherosclerotic disease. Elderly patients, particularly those older than 75 years, have not been well represented in randomized clinical trials evaluating lipid lowering therapy. The limited available data from clinical trials do support the benefit of statin therapy in the elderly population. Based upon these data, cholesterol treatment guidelines endorse statin therapy as the primary treatment of hypercholesterolemia in elderly patients, though caution is recommended given the greater number of co-morbid conditions and concern for poly-pharmacy common in the elderly. Additional research is needed to better establish the benefit of statin therapy in the elderly within the context of reducing CV risk, minimizing side effects, and improving overall quality of life.     

Biventricular Pacing Therapy for Heart Failure

Heart failure is a disease with high morbidity and mortality. It is also the commonest cause of medical ward admission. The incidence of heart failure has been increasing world - wide in the past decade. Studies observed that about 25-50 % of patients with     

Hepatocellular carcinoma： Therapy and prevention

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. The major etiologies and risk factors for the development of HCC are well defined and some of the multiple steps involved in hepatocarcinogenesis have been elucidated in recent years. Despite these scientific advances and the implementation of measures for the early detection of HCC in patients at risk, patient survival has not improved during the last three decades. This is due to the advanced stage of the disease at the time of clinical presentation and limited therapeutic options. The therapeutic options fall into five main categories: surgical interventions including tumor resection and liver transplantation, percutaneous interventions including ethanol injection and radiofrequency thermal ablation, transarterial interventions including embolization and chemoembolization, radiation therapy and drugs as well as gene and immune therapies. These therapeutic strategies have been evaluated in part in randomized controlled clinical trials that are the basis for therapeutic recommendations. Though surgery, percutaneous and transarterial interventions are effective in patients with limited disease (1-3 lesions, <5 cm in diameter) and compensated underlying liver disease (cirrhosis Child A), at the time of diagnosis more than 80% patients present with multicentric HCC and advanced liver disease or comorbidities that restrict the therapeutic measures to best supportive care. In order to reduce the morbidity and mortality of HCC, early diagnosis and the development of novel systemic therapies for advanced disease, including drugs, gene and immune therapies as well as primary HCC prevention are of paramount importance. Furthermore, secondary HCC prevention after successful therapeutic interventions needs to be improved in order to make an impact on the survival of patients with HCC. New technologies, including gene expression profiling and proteomic analyses, should allow to further elucidate the molecular events underlying HCC development and to identify novel diagnostic markers as well as therapeutic and preventive targets.     

Is Cardiac Resynchronization Therapy an Antiarrhythmic Therapy for Atrial Fibrillation? A Systematic Review and Meta-Analysis

The impact of cardiac resynchronization therapy (CRT) on atrial fibrillation (AF) burden is poorly characterized. To assess the influence of CRT on AF, we performed a systematic literature search in MEDLINE using the MeSH headings “cardiac resynchronization therapy” or “cardiac pacing, artificial” and “atrial fibrillation.” Selected studies were peer-reviewed and written in English. Most studies enrolled patients meeting traditional CRT criteria. Ten observational studies and two secondary analyses of clinical trials were identified. Although ten studies suggest that CRT favorably impacts AF, one secondary analysis of a clinical trial showed no effect of CRT on new-onset AF. In a meta-analysis of three studies examining the effect of CRT on persistent or permanent AF, the combined rate of conversion from persistent or permanent AF to sinus rhythm was 0.107 (95 % confidence interval 0.069-0.163). Prospective studies, particularly among patients not meeting traditional CRT criteria, are needed.     

New Developments in Therapy for Hepatic Fibrosis

Over the past 30 years, methods have been developed for isolating the principal cell types of the liver. These have made it possible to analyze quantitatively and in detail the injury response of the liver, which underlies the scarring process known as fibrosis. Attention has focused in particular on hepatic stellate cells because of their dynamic response to injury, termed activation. Metabolically quiescent in the normal liver, stellate cells in injury rapidly display properties of myofibroblasts, including expression de novo of smooth muscle proteins,     

Dysphagia Management: An Analysis of Patient Outcomes Using VitalStim™ Therapy Compared to Traditional Swallow Therapy

This study compares the outcomes using VitalStim™ therapy to outcomes using traditional swallowing therapy for deglutition disorders. Twenty-two patients had an initial and a followup videofluoroscopic swallowing study or fiberoptic endoscopic evaluation of swallowing and were divided into an experimental group that received VitalStim treatments and a control group that received traditional swallowing therapy. Outcomes were analyzed for changes in oral and pharyngeal phase dysphagia severity, dietary consistency restrictions, and progression from nonoral to oral intake. Results of χ² analysis showed no statistically significant difference in outcomes between the experimental and control groups. This work was performed at the Forsyth Rehabilitation Center locations, Winston-Salem, NC 27103     

Interferon-λ in HCV Infection and Therapy

Chronic infection with hepatitis C virus (HCV) is associated with significant liver disease and is therefore an important public health problem. The current standard-of-care therapy for chronic HCV infection consists of a combination of pegylated (PEG) interferon (IFN)-α and ribavirin. Although this therapy effectively generates a sustained viral response in approximately half of treated individuals, it is associated with significant hematological and neurological side effects. A new family of IFN-related proteins (IFN-λ1, 2, and 3; or alternately, IL-29, 28A, 28B, respectively) possesses properties that may make these cytokines superior to PEG-IFN-α for HCV therapy. Genetic studies have also implicated these proteins in both the natural and therapy-induced resolution of HCV infection. This review summarizes the basic aspects of IFN-λ biology, the potential role of these cytokines in HCV infection, and the outlook for their therapeutic application.     

Liver Gene Therapy in the New Century

Gene Therapy refers to targeted transfer of selected nucleic acids into tissue cells in vivo. The fiver is a preferred organ for this therapeutic procedure because of its relatively easy accessibility and its enormous range of synthetic, metabolic, regulatory and excretory functions. Although gene transfer into the human liver still is in its infancy, imaginative novel technologies, sophisticated refinements of methodology and suggested therapeutic indications are proliferating at such a rate that in the new centtLry, liver-directed gene therapy without question will emerge as a favored therapeutic modality for a large number of diseases.     

Left Ventricular Assist Device Therapy for Destination Therapy: Is Less Invasive Surgery a Safe Alternative?

Introduction and objectives

The number of older patients with congestive heart failure has dramatically increased. Because of stagnating cardiac transplantation, there is a need for an alternative therapy, which would solve the problem of insufficient donor organ supply. Left ventricular assist devices (LVADs) have recently become more commonly used as destination therapy (DT). Assuming that older patients show a higher risk-profile for LVAD surgery, it is expected that the increasing use of less invasive surgery (LIS) LVAD implantation will improve postoperative outcomes. Thus, this study aimed to assess the outcomes of LIS-LVAD implantation in DT patients.

Functional Dyspepsia： from Pathogenesis to Therapy

Functional dyspepsia is the most common upper gastrointestinal functional disorder, def‘med as chronic or recurrent epigastric pain, fullness, discomfort centered in the upper abdomen without evidence of structural diseases. It significantly impacts on patient‘s quality of life and costs a lot in many patients.     

Combining Antiplatelet and Antithrombotic Therapy (Triple Therapy): What Are the Risks and Benefits?

Most patients with mechanical heart valves and many patients with atrial fibrillation will require long-term anticoagulation therapy. For patients with mechanical prosthetic valves, only warfarin is indicated. However, for patients with nonvalvular atrial fibrillation who are at increased risk for embolic stroke, one of the newer antithrombotic medications, such as rivaroxaban, dabigatran, and apixaban, also can be used. Patients with indications for antithrombotic therapy often will have coexisting vascular disease, such as coronary artery disease, requiring concomitant antiplatelet therapy with aspirin alone or more commonly with a dual antiplatelet regimen, aspirin and clopidogrel, or prasugrel or ticagrelor. The risks and benefits of this approach are still not well defined, and current guidelines have included recommendations based primarily on expert opinion.     

Cardiac Resynchronization Therapy—Emerging Therapeutic Approaches

Cardiac resynchronization therapy (CRT) is an important therapeutic tool in the management of patients with heart failure and electrical dyssynchrony. In appropriately selected patients, landmark randomized controlled trials have demonstrated morbidity and mortality benefit beyond standard goal-directed medical therapy. Current guidelines emphasize the greatest clinical efficacy of CRT in patients with symptomatic heart failure, left bundle branch block, and wide QRS duration (>?150 ms). Other relevant considerations include the presence of atrial fibrillation, the presence of AV block, the etiology of cardiomyopathy, the presence of masked left-sided conduction delay, and the impact of comorbidities that might predict poor clinical response. At the time of CRT implantation, key considerations include targeting of the left ventricular (LV) lead to sites of greatest electrical and/or mechanical delay, the use of quadripolar versus bipolar LV pacing leads, evaluation of multiple pacing vectors to maximize electrical resynchronization, and in select instances pre-procedure imaging of the coronary venous anatomy to help guide decision-making at the time implant. Post-implant care includes the selective use of atrio-ventricular and inter-ventricular optimization algorithms, mitigation of right ventricular pacing, recognition, and treatment of suboptimal biventricular pacing, as well as management by a multi-disciplinary team of cardiovascular specialists. Emerging therapeutic strategies for patients eligible for CRT include the use of endocardial LV pacing, novel LV pacing options including multi-point pacing, His bundle pacing, and the integration of remote monitoring platforms that may identify patients at risk for clinical worsening.     

Adjunct Therapy for Sepsis: How Early?

Sepsis is a leading cause of death worldwide. The management of patients is primarily based on curing the infectious process with anti-infective drugs and/or surgical drainage. Simultaneously, treatment includes optimization of oxygen use by tissues via appropriate oxygen therapy and respiratory and hemodynamic management. At best, initiating appropriate anti-infective and symptomatic treatments should lead to patient improvement within a few hours. Activated protein C and hydrocortisone are the only two available adjunct therapies for sepsis. These treatments should optimally be started within 24 hours of the onset of shock. They should be initiated in those patients who did not adequately respond after 6 hours of optimal anti-infective and symptomatic treatments.