Oxidative Stress and Respiratory System: Pharmacological and Clinical Reappraisal of N-Acetylcysteine

The large surface area for gas exchange makes the respiratory system particularly susceptible to oxidative stress-mediated injury. Both endogenous and exogenous pro-oxidants (e.g. cigarette smoke) trigger activation of leukocytes and host defenses. These mechanisms interact in a “multilevel cycle” responsible for the control of the oxidant/antioxidant homeostasis. Several studies have demonstrated the presence of increased oxidative stress and decreased antioxidants (e.g. reduced glutathione [GSH]) in subjects with chronic obstructive pulmonary disease (COPD), but the contribution of oxidative stress to the pathophysiology of COPD is generally only minimally discussed. The aim of this review was to provide a comprehensive overview of the role of oxidative stress in the pathogenesis of respiratory diseases, particularly COPD, and to examine the available clinical and experimental evidence on the use of the antioxidant N-acetylcysteine (NAC), a precursor of GSH, as an adjunct to standard therapy for the treatment of COPD. The proposed concept of “multilevel cycle” helps understand the relationship between respiratory diseases and oxidative stress, thus clarifying the rationale for using NAC in COPD. Until recently, antioxidant drugs such as NAC have been regarded only as mucolytic agents. Nevertheless, several clinical trials indicate that NAC may reduce the rate of COPD exacerbations and improve small airways function. The most plausible explanation for the beneficial effects observed in patients with COPD treated with NAC lies in the mucolytic and antioxidant effects of this drug. Modulation of bronchial inflammation by NAC may further account for these favorable clinical results.     

Severe bradyarrhythmia linked to left atrial dysfunction in Fabry disease—A cross‐sectional study

Background

Fabry disease (FD) is a lysosomal storage disorder caused by an enzymatic deficiency. Conduction abnormalities and bradyarrhythmias are common and can occur prior to the onset of left ventricular (LV) hypertrophy. We aimed to describe the clinical, electrocardiographic and echocardiographic, including left atrial (LA) function, determinants of bradyarrhythmic events in FD.

Hypothesis

Bradyarrhythmic events are frequent in patients with FD and are associated with LA dysfunction.

Methods

We designed a cross‐sectional study that includes 53 FD patients (mean age, 45 years; 42% male). Clinical characteristics and electrocardiographic and echocardiographic data were collected. LA function was measured using biplane volumes and 2D speckle‐tracking echocardiography. Bradyarrhythmic events were defined as pause of more than 2 seconds (sinus pause or atrioventricular block) recorded on Holter, severe bradycardia (≤ 40 bpm on ECG) or implantation of a permanent pacemaker.

Results

Six (11%) patients had installation of a pacemaker, 4 (8%) patients had cardiac pause and 2 (4%) patients had an episode of severe bradycardia. Patients with bradyarrhythmic events were older and had a lower resting heart rate. On echocardiography, a significantly higher LV mass, a lower LV ejection fraction, and a more affected LA reservoir function were found in those with bradyarrhythmic events. Patients also experienced tachyarrhythmias frequently. Atrial fibrillation occurred in 11 (21%) patients and ventricular tachycardia in 4 (8%) patients.

Conclusions

Bradyarrhythmia are common manifestations of cardiac involvement in FD. Age, LV mass, LV ejection fraction and LA reservoir dysfunction can be useful markers associated with bradyarrhythmia.     

Clinical outcomes of primary arterial embolization in severe hepatic trauma: A systematic review

Purpose

This purpose of this systematic review was to determine the safety and efficacy of arterial embolization as the primary treatment for grade III-V liver trauma, excluding the postoperative use of arterial embolization.

Beta-Blockers and Ivabradine in Chronic Heart Failure: From Clinical Trials to Clinical Practice

Beta-blockers have become one of the cornerstones of treatment of patients with heart failure (HF) and depressed left ventricular function, but in clinical practice only 30–35 % of patients achieve the therapeutic target dose as established in randomized clinical trials. Moreover, high resting heart rate (HR) has emerged as a simple but relevant risk factor for cardiovascular events, including coronary artery disease and HF; also, it was found to have an independent prognostic value in patients with HF. Evidence that HR could be considered a good parameter to evaluate the quality of treatment in patients with HF has been suggested; of note, many patients maintain a resting HR ≥70 beats per minute despite optimal beta-blocker therapy. In recent years, a new drug able to reduce HR, ivabradine, has been introduced in clinical practice, and its use in the clinical setting of HF patients has been recommended by current European Society of Cardiology (ESC) guidelines. Here we review the evidence of the prognostic role of HR in systolic HF and the potential relationship between HR lowering and the beneficial effects of beta-blockers; we will also analyze the reasons why an appropriate use of these drugs is seldom achieved in clinical practice, and review the evidence for the use of ivabradine in systolic HF in the clinical setting.     

Cervical mass as the first clinical manifestation of unsuspected metastatic seminoma

The authors reported a case of a 27‐year‐old man with a nontender left neck mass that had grown quite rapidly within few weeks. FNAB and CT were not consistent to establish the definite diagnosis. After excisional biopsy, the histopathological examination and the immunohistochemical study of the specimen revealed a cervical metastasis of seminoma. The patient was treated with chemotherapy with a complete clinical remission. This uncommon case-report can represent a great diagnostic and therapeutic challenge and should be considered in the differential diagnosis of every cervical masses occurring in young males patients. Diagnostic delays are unfortunately common and may lead to metastatic spread and worse prognosis.