Novel pharmacologic therapy of heart failure

Opinion statement The prevalence of congestive heart failure is progressively increasing and despite recent advances in therapeutics, there is a continuing need for novel effective therapies. New, investigational treatment strategies include inotropic drugs, neurohormonal antagonists, anticytokine and anti-inflammatory strategies, hormonal therapies, and nutritional supplements. Current positive inotropes (eg, dobutamine and phosphodiesterase inhibitors) provide symptomatic relief, but newer agents may have a better adverse effect profile. Angiotensin-converting enzyme (ACE) inhibitors should remain first-line treatment with angiotensin receptor blockers used in ACE inhibitor-intolerant patients. Many new neurohormonal antagonists have recently been investigated and eplerenone has demonstrated clinical benefit. New hormonal, anticytokine, and anti-inflammatory therapies have shown benefit in small trials, but results in larger trials have been disappointing. Other approaches are currently being tested in large trials that will clarify their role. Nutritional supplements need to be tested in a large prospective trial before they can be recommended.     

Cost efficiency of nuclear cardiology services in the modern health care environment

More than a decade of dramatic changes in US and global health care has affected the practice of and payment for nuclear cardiology services. The clear diagnostic and prognostic power of nuclear cardiology procedures to detect coronary artery disease and predict patient outcomes has resulted in the rapid growth of these procedures in clinical practice. This has focused the attention of public and private payers on the high use of medical resources required to carry out nuclear cardiology testing. Two recent, major multicenter trials, one in the United States and another in Europe, have demonstrated the cost effectiveness of stress myocardial perfusion imaging strategies compared with coronary angiography in patients with known or suspected coronary artery disease, across the spectrum of pretest risks and both sexes. These studies, and more extensive data from more than 10 years of decision analysis, have reinforced the value of nuclear cardiology in modern cardiovascular health care. Future challenges will include assurance of provider and laboratory quality in the burgeoning outpatient imaging centers across the country, and wider acceptance by payers and expert panels of the evidence supporting the cost effectiveness of nuclear cardiology in most clinical settings.     

A very frequent mutation and remarkable association of R761H with M694V mutations in Turkish familial Mediterranean fever patients

Familial Mediterranean fever (FMF) is an autosomal-recessive disease. It is characterized by recurring fever, abdominal pain, and serositis. The Mediterranean fever (MEFV) gene is localized on 16p13.3 and more than 35 mutations have been described to date. There are some differences in the gene mutations of FMF in the various ethnic groups. The aim of this study is to determine the frequency of the mutations which has been reported comparatively rare, to define the most effective mutation set, and to select the most suitable DNA analysis system for Turkish FMF patients. Mutations in 330 Turkish FMF patients with typical phenotypes from various regions of Turkey were evaluated for the research purposes. These patients were analyzed for six MEFV gene mutations by the NanoChip® Molecular Genetics Workstation. The most frequent mutation was M694V, identified in 50.00% of the alleles examined; M680I followed with 14.10% and V726A—9.70%. Consequently, we determined that R761H (n?=?23; 3.48%) was the most frequent rare mutations in Turkish FMF patients. Frequency of the rare mutations were R761H (3.48%), E148Q (1.36%), and M694I (1.21%). All of these mutations were in the compound heterozygote state. Our study showed that R761H mutations were higher than it has been reported in literature until now and were mainly associated with M694V. We suggest that mutation R761H should be included in the mutation scanning analysis researches or considered if the patient has M694V/? mutation especially in Turkish FMF patients. Larger serial studies need to be done to investigate the rate and coexistence of these mutations.     

A Clinical Guide to Combination Lipid-Lowering Therapy

Purpose of Review

We provide an overview of our current understanding of combination lipid-lowering therapies intended for dyslipidemia treatment and cardiovascular disease prevention. First, we analyze recent statin and non-statin combination therapy guidelines and clinical studies since the publication of 2013 American College of Cardiology Cholesterol Guidelines. Second, we examine the clinical utility of non-statin agents alone and in combination in terms of LDL-C lowering and ASCVD risk reduction.

Recent Findings

Medical societies, including the American College of Cardiology (ACC), National Lipid Association (NLA), and American Association of Clinical Endocrinologists (AACE), have released guidelines to address the appropriate use of non-statin therapies. The guidelines incorporated new evidence, including the IMPROVE-IT and FOURIER clinical trials, which demonstrate that the combination of statin therapy with other non-statin agents such as ezetimibe and PCSK9 inhibitors has a significant clinical benefit. Increasing evidence that aggressive low-density lipoprotein cholesterol (LDL-C) lowering leads to lower cardiovascular disease risk supports the need for continued exploration of the role of combination lipid-lowering therapies.

Summary

A review of guidelines and clinical trials evaluating non-statin agents illuminates the growing base of evidence and expert opinion supporting the use of combination lipid-lowering therapies. While the majority of clinical trial data utilizes dyslipidemia monotherapy, especially statins, combination therapies represent an opportunity for individualized, patient-centered approach to LDL-C lowering and atherosclerotic cardiovascular disease (ASCVD) risk reduction. The overview provides a perspective on lipid management intended for clinicians who seek additional information and guidance on the use of combination therapies.

     

Non-tuberculous Mycobacterial Infections in Thoracic Transplant Candidates and Recipients

Purpose of Review

To review and discuss the epidemiology, risk factors, clinical presentation, diagnosis, and treatment of non-tuberculous mycobacteria (NTM) in thoracic transplantation.

Recent Findings

Non-tuberculous mycobacteria are ubiquitous but are an uncommon cause of disease after solid organ transplantation. The incidence of infection is higher in thoracic transplant recipients than in abdominal transplant recipients, with most cases seen after lung transplantation. It is associated with increased morbidity and, occasionally, mortality. Infection in the pre-transplant setting can occur in lung transplant candidates, often posing a dilemma regarding transplant listing. Disease manifestations are diverse, and pulmonary disease is the most common. Diagnosis requires a high index of suspicion. Treatment requires a multiple-drug combination and is limited by drug-drug interactions and tolerability. Mycobacterium abscessus is a challenge in lung transplant recipients, due to its intrinsic resistance and propensity to relapse even after prolonged therapy. Mycobacterium chimaera is an emerging pathogen associated with contamination of heater-cooler units and is described to cause disease months after cardiothoracic surgery.

Summary

NTM infections in thoracic organ transplant recipients are uncommon but are associated with substantial morbidity and mortality. Data from larger multicenter studies is needed to better define the epidemiology of NTM in thoracic transplantation, best treatment options, and the management of infected transplant candidates.

     

Acid-suppression Therapy Offers Varied Laryngopharyngeal and Esophageal Symptom Relief in Laryngopharyngeal Reflux Patients

It is widely accepted that laryngopharyngeal reflux requires more aggressive and prolonged therapy than gastro-esophageal reflux disease. Otolaryngologists often observe that laryngopharyngeal symptoms, such as throat clearing, hoarseness, cough, and globus pharyngeus, are slower to resolve than esophageal symptoms, such as heartburn and regurgitation. The aim of this was to provide empirical evidence to support this observation and to carry out a detailed investigation of the differences between these symptoms. Forty-five patients with laryngopharyngeal and esophageal symptoms received acid-suppression therapy that involved the continuous administration of a proton-pump inhibitor for up to 6 months. We investigated the differences in response to acid-suppression therapy between patients suffering from laryngopharyngeal and esophageal symptoms, respectively, who received upper gastrointestinal endoscopy and were assayed for serum Helicobacter pylori antibodies. The significance of the rate of symptom improvement was estimated by Kaplan-Meier analysis and the logrank test. Laryngopharyngeal symptoms improved significantly more slowly than esophageal symptoms following acid-suppression therapy (49.8 vs. 78.3%, 60 days after the start of acid suppression; P = 0.003). These differences were observed both in patients with erosive esophagitis (P = 0.008) and in H. pylori-seronegative patients (P = 0.001).     

Suprasellar granular cell tumor of the neurohypophysis: surgical outcome of a very rare tumor

Purpose

Granular cell tumors of the neurohypophysis are rare, solitary lesions, mostly presenting in the adult age. They rarely grow to a sufficient size to cause mass effect related symptoms and they may be found in most cases incidentally at autopsy. Because of their rarity as of now they have been described only as case reports or included in small clinical series.

Methods

We report a series of 11 patients, who underwent surgery for granular cell tumors of the neurohypophysis between 1996 and 2013 in a single center.

Results

Mean follow-up time after treatment was 92.2 months (range 9–231 months). Mean age at surgery was 40.7 years (range 12–66 years). There were 7 males (63.6 %) and 4 females (36.4 %). Main symptoms at presentation were: hyperprolactinemia (72.7 %), visual impairment (45.5 %) and headache (36 %). Except for 2 patients, all the others underwent surgery as primary treatment at our Institution, through a transsphenoidal (54.5 %) or a transcranial approach (45.5 %). Overall- and progression-free survival times for the entire series (calculated from the time of diagnosis) were 112.9 and 100.5 months respectively. There was one case of perioperative death in a patient who had undergone repeat transcranial surgery for residual tumor.

Conclusions

Although extremely rare, granular cell tumors of the neurohypophysis have to be considered in the differential diagnosis of suprasellar masses, to avoid misleading interpretation and consequent wrong therapeutic management. Early diagnosis, extensive tumor removal, opportune indication of adjuvant radiotherapy are the keys to manage these cases.

     

Food allergy and related risk factors in 2540 preschool children: an epidemiological survey in Guangdong Province,southern China

Background

Although the number of studies on allergic diseases in the general population of southern China is increasing, only a few have addressed food allergy (FA) in children in this region. The present study aimed to investigate the prevalence, clinical manifestations, spectrum of allergens, and related risk factors of FA in preschool children in Guangdong Province, southern China.

Methods

A random cluster-sampling method was used to select 24 kindergartens from 12 cities in Guangdong Province. The parents or guardians of the children were requested to complete a questionnaire on general information and data regarding FA diagnosis and symptoms in the children and their first-degree relatives. Thereafter, the Chi-square test, multivariate regression analysis, and Spearman’s rank-order correlation coefficient analysis were performed to identify statistically significant differences.

Results

Analysis of 2540 valid questionnaires revealed an FA prevalence rate of 4%. Adverse food reactions were due to the consumption of shrimp (4.4%), crab (3.2%), mango (2.3%), cow’s milk and dairy products (1.9%), and eggs (1.4%). Logistic regression analysis indicated that a history of FA and a history of allergic rhinitis in the first-degree relatives were the major factors leading to FA in children.

Conclusions

The incidence of FA in children in Guangdong Province is higher than that commonly believed. An individual’s genetic background is an important risk factor for FA. Hence, mitigation of the impact of lifestyle and environmental factors should be carefully considered to reduce the incidence of childhood FA.