Oral immune dysfunction is associated with the expansion of FOXP3+PD-1+Amphiregulin+ T cells during HIV infection.

Residual systemic inflammation and mucosal immune dysfunction persist in people living with HIV, despite treatment with combined anti-retroviral therapy, but the underlying immune mechanisms are poorly understood. Here we report that the altered immune landscape of the oral mucosa of HIV-positive patients on therapy involves increased TLR and inflammasome signaling, localized CD4+ T cell hyperactivation, and, counterintuitively, enrichment of FOXP3+ T cells. HIV infection of oral tonsil cultures in vitro causes an increase in FOXP3+ T cells expressing PD-1, IFN-γ, Amphiregulin and IL-10. These cells persist even in the presence of anti-retroviral drugs, and further expand when stimulated by TLR2 ligands and IL-1ß. Mechanistically, IL-1ß upregulates PD-1 expression via AKT signaling, and PD-1 stabilizes FOXP3 and Amphiregulin through a mechanism involving asparaginyl endopeptidase, resulting in FOXP3+ cells that are incapable of suppressing CD4+ T cells in vitro. The FOXP3+ T cells that are abundant in HIV-positive patients are phenotypically similar to the in vitro cultured, HIV-responsive FOXP3+ T cells, and their presence strongly correlates with CD4+ T cell hyper-activation. This suggests that FOXP3+ T cell dysregulation might play a role in the mucosal immune dysfunction of HIV patients on therapy.

Stable Angina Medical Therapy Management Guidelines: A Critical Review of Guidelines from the European Society of Cardiology and National Institute for Health and Care Excellence.

Most patients with stable angina can be managed with lifestyle changes, especially smoking cessation and regular exercise, along with taking antianginal drugs. Randomised controlled trials show that antianginal drugs are equally effective and none of them reduced mortality or the risk of MI, yet guidelines prefer the use of beta-blockers and calcium channel blockers as a first-line treatment. The European Society of Cardiology guidelines for the management of stable coronary artery disease provide classes of recommendation with levels of evidence that are well defined. The National Institute for Health and Care Excellence (NICE) guidelines for the management of stable angina provide guidelines based on cost and effectiveness using the terms first-line and second-line therapy. Both guidelines recommend using low-dose aspirin and statins as disease-modifying agents. The aim of this article is to critically appraise the guidelines' pharmacological recommendations for managing patients with stable angina.

Drug Therapy for Stable Angina Pectoris.

Chronic stable angina pectoris refers to the predictable, reproducible occurrence of pressure or a choking sensation in the chest or adjacent areas caused by myocardial ischemia in association with physical or emotional stress, and cessation of exertion and or sublingual nitroglycerin invariably relieves the discomfort. It is a common presenting symptom of severe narrowing of one or more coronary arteries, non-obstructive coronary arteries, or even when the coronary arteries are angiographically normal. Patients often avoid activities which precipitate symptoms and have impaired quality of life. Most patients with angina pectoris can be managed with lifestyle changes, especially abstinence from smoking and regular exercise, and anti-anginal drugs. However, the choice of initial or combination antianginals as recommended in the guidelines is not evidence based. In addition, patients with stable angina due to coronary artery disease should also receive aspirin and a statin. Treatment of patients with angina and normal coronary arteries remains to be established. The aim of this article is to provide the readers not only with a guideline-based approach, which varies from one country to another, but also an individual-based approach, which takes into consideration circulatory status and the presence or absence of comorbidities in the treatment decision-making process. This manuscript primarily deals with drug therapy of stable angina pectoris and not coronary artery revascularization, which also provides angina relief but is usually reserved for patients who fail to respond to adequate drug therapy.

The risk of cardiovascular side effects with anti-anginal drugs.

INTRODUCTION: Angina pectoris is a common presenting symptom of underlying coronary artery disease or reduced coronary flow reserve. Patients with angina have impaired quality of life; and need to be treated optimally with antianginal drugs to control symptoms and improve exercise performance. A wide range of antianginal medications are approved for the treatment of angina, and often more than one class of antianginal drugs are used to adequately control the symptoms. This expert opinion highlights the likely cardiac adverse effects of available antianginal drugs, and how to minimize these in individual patients and especially during combination treatment. Areas covered: All approved antianginal drugs, including the older and newly approved medications with different mechanism of action to the older drugs as well as some of the unapproved herbal medications. The safety profiles and potential cardiac side effects of these medications when used as monotherapy or as combination therapy are discussed and highlighted. Expert opinion: Because of the different cardiac safety profiles and possible side effects, we recommend selection of initial drug or adjustment of therapy based on the resting heart rate; blood pressure, hemodynamic status; and resting left ventricular function, concomitant medications and any associated comorbidities.

Transcatheter closure of a pulmonary arteriovenous malformation in a patient with hereditary hemorrhagic telangiectasia.

Pulmonary arteriovenous malformations (PAVM) are rare pulmonary vascular anomalies. Over 50 % of the cases are associated with hereditary hemorrhagic telangiectasia or Osler-Weber-Rendu Syndrome. Untreated PAVMs progressively enlarge and can cause significant right-to-left shunting. Surgical- and catheter-based approaches have been used in the management of PAVM. We report a case of a 74-year-old man who presented with dyspnea and hypoxia and was found to have a large right-sided PAVM. He underwent percutaneous closure of the PAVM with an Amplatzer device with significant improvement of his symptoms.

Impact of diabetes mellitus on clinical characteristics, management, and in-hospital outcomes in patients with acute myocardial infarction (from the NCDR).

Patients with diabetes mellitus (DM) presenting with acute myocardial infarction (AMI) have worse outcomes versus those without DM. Comparative contemporary data in patients presenting with AMI with insulin-requiring diabetes mellitus (IRDM), noninsulin-requiring diabetes mellitus (NIRDM), and newly identified DM (hemoglobin A1C level >6.5%) versus patients without DM are limited. This observational study from the National Cardiovascular Data Registry (NCDR) Acute Coronary Treatment and Intervention Outcomes Network-Get with the Guidelines (ACTION Registry-GWTG consisted of 243,861 patients with AMI from 462 US sites identified from January 2007 to March 2011 entered into the registry. Clinical characteristics, management, and in-hospital outcomes were analyzed. Patients with DM with non-ST-segment elevation myocardial infarction (NSTEMI; n = 53,094, 35%) were less likely to undergo diagnostic angiography or revascularization, whereas those with ST-segment elevation myocardial infarction (STEMI) (n = 21,507, 23%) were less likely to undergo reperfusion therapy compared with patients without DM. There was an increased adjusted risk of in-hospital mortality in the DM group in both the NSTEMI (odds ratio [OR] 1.14, 95% confidence interval [CI] 1.06 to 1.22) and STEMI (OR 1.17, 95% CI 1.07 to 1.27) population. In patients with DM, the risk-adjusted in-hospital mortality was higher in patients with IRDM than those with NIRDM in the NSTEMI group (OR 1.12, 95% CI 1.01 to 1.24) but not in the STEMI group (OR 1.12, 95% CI 0.95 to 1.32). Newly diagnosed patients with DM presenting with AMI had similar unadjusted in-hospital outcomes compared with patients without DM. In conclusion, patients with DM presenting with AMI have a higher mortality risk than patients without DM. In patients with DM, those with IRDM presenting with NSTEMI had an increased mortality than those with NIRDM.

Two different presentations of sinus of valsalva aneurysm.

Sinus of Valsalva aneurysm (SVA) is a rare cardiac anomaly that can be congenital or acquired. We report 2 cases of SVA. The first case involves a 59-year-old male presenting with frequent syncope. Echocardiogram revealed a large right SVA obstructing the right ventricular outflow tract (RVOT). The second case involves a 21-year-old female presenting with sudden onset chest pain and a continuous machinery murmur. Echocardiogram revealed a ruptured right SVA into the right atrium. Although advanced percutaneous techniques have been implemented in the correction of this anomaly, open-heart surgery with or without aortic valve replacement remains the treatment of choice.

Coronary slow flow--prevalence and clinical correlations.

BACKGROUND: Coronary slow flow phenomenon (CSFP) is defined as delayed coronary opacification in the absence of obstructive coronary artery disease. In the present study, we sought to define its prevalence and clinical features. METHODS AND RESULTS: The 1,741 consecutive patients who underwent coronary angiography (CAG) were identified. Those with normal left ventricular ejection fraction and normal coronary arteries were included in the study (n=158). TIMI frame counts were calculated, and data on demographics, comorbidities, and medication use were collected. CSFP was defined as frame count > 27. Multivariate logistic regression analysis was used to identify independent predictors of CSFP. CSFP was identified in 96 (5.5%) subjects referred for CAG. Subjects with CSFP were more obese (body mass index [BMI] 33.9 vs. 29.8 kg/m², P=0.003) and had lower high-density lipoprotein levels (39.7 vs. 45.7 mg/dl, P=0.04). In the CSFP group, total cholesterol, low-density lipoprotein and frame counts increased significantly with increasing vessel involvement (1-, vs. 2-, vs. 3-vessel involvement; P<0.05 for each variable). By multivariate analysis, male sex (odds ratio 3.36, 95% confidence interval 1.17-8.61, P=0.02) and higher BMI independently predicted the presence of CSFP (odds ratio 1.09, 95% confidence interval 1.03-1.15, P=0.003). CONCLUSIONS: CSFP is associated with male sex and obesity. Multivessel involvement may be a marker of more severe, diffuse disease. Further studies are needed to investigate this hypothesis.