Increased prevalence of small airways dysfunction in patients with systemic sclerosis as determined by impulse oscillometry.

OBJECTIVES: The prevalence and clinical implications of small airways involvement in SSc are still to be fully elucidated. The goal of the present work is to assess the prevalence of small airways dysfunction by impulse oscillometry and to determine whether it correlates with selected disease-related features and respiratory-related quality of life. METHODS: Ninety-four SSc patients and 93 healthy controls were studied by impulse oscillometry measurements. Small airways dysfunction was defined as the difference between resistance at low frequency, i.e. 5 Hz, and resistance at high frequency, i.e. 20 Hz, termed 'R5-R20', ⩾0.07 kPa/l/s. The St George's Respiratory Questionnaire was used to measure health impairment in SSc patients. Radiological features of small airways disease and parenchymal abnormalities on high resolution CT chest scans were jointly assessed by two thoracic radiologists. RESULTS: Small airways dysfunction was present in 21.5% of the SSc patient cohort, with a prevalence almost 5-fold higher compared with controls, and it was significantly associated with worse respiratory-related quality of life. Radiological features consistent with small airways abnormalities were detected in 25% of SSc patients, mostly in the absence of interstitial lung changes. Combining functional and radiological evaluations, one-third of the SSc cohort showed at least one feature of small airways involvement, which was associated with the lcSSc phenotype and with longer disease duration. CONCLUSION: The current study strengthens the hypothesis that small airway dysfunction might be a feature of SSc-related lung involvement, providing the first data on its significant impact on respiratory-related quality of life. A full assessment of lung function in SSc patients should include impulse oscillometry as a complementary technique, due to potential clinical and therapeutic implications.

Ranolazine in the prevention of anthracycline cardiotoxicity.

Ranolazine is a selective inhibitor of the cardiomyocyte late inward sodium current, INaL, and features anti-ischemic, antiarrhythmic and ATP-sparing actions. Extensive laboratory data show that anthracyclines can induce the production of reactive oxygen species (ROS). Other laboratory data show that ROS can hyperactivate the cardiac isoform of calmodulin-dependent protein kinase II (CaMKII δ), in turn inducing a hyperactivation of the cardiac late sodium current (INaL) and a resulting cytosolic calcium overload. This, as a consequence of the related sodium overload, can induce a mitochondrial calcium depletion that, in turn, triggers a chronic vicious cycle characterized by mitochondrial H2O2 production (increased oxidative stress), and NAD(P)H and ATP depletion (energetic stress), both sustaining ROS production. We hypothesize that anthracyclines may induce both INaL hyperactivation and an oxidative/energetic vicious cycle in cardiomyocytes. These sustained oxidative and energetic stresses may induce low-level cardiomyocyte and cardiac stem cell death by various mechanisms, leading to heart failure in the presence of genetic factors, age, ischemic and arrhythmic events, harmful dietary behaviors, and concomitant diseases. By reducing INaL in a myocardium particularly vulnerable to apoptotic stress and ischemia ranolazine might thus exert cardioprotection interfering with the vicious cycle of anthracycline cardiotoxicity.

First Detection of SARS-CoV-2 by Real-Time Reverse Transcriptase-Polymerase Chain Reaction Assay in Pleural Fluid.

Coronavirus disease 2019 (COVID-19) is a pandemic infection due to the spread of a novel coronavirus (severe acute respiratory syndrome coronavirus 2), resulting in a wide range of clinical features, from asymptomatic carriers to ARDS. The gold standard for diagnosis is nucleic acid detection by real-time reverse transcriptase-polymerase chain reaction in nasopharyngeal swabs. However, due to limitations in this technique's sensitivity, thoracic imaging plays a crucial, complementary role in diagnostic evaluation and also allows for detection of atypical findings and potential alternative targets for sampling (eg, pleural effusion). Although less common, pleural involvement has been described in a minority of patients. This report describes the first case of reverse transcriptase-polymerase chain reaction detection of severe acute respiratory syndrome coronavirus 2 in pleural fluid obtained by means of ultrasound-guided thoracentesis, and its main characteristics are detailed. Pleural effusion is not a common finding in COVID-19 infection, but a prompt recognition of this potential localization may be useful to optimize diagnostic evaluation as well as the management of these patients.

Open-label study on treatment with 20 % subcutaneous IgG administration in polymyositis and dermatomyositis.

UNLABELLED: The objective of this study is to describe the benefit of 20 % subcutaneous infusions of immunoglobulin (SCIg) in patients with dermatomyositis (DM) or polymyositis (PM) after a switch from previous 16 % SCIg treatment. Eight patients with DM or PM, who met the Bohan and Peter's criteria, previously treated with 16 % SCIg, were switched to weekly 20 % SCIg infusions (Hizentra®; CSL Behring) at doses equivalent to their previous subcutaneous treatment. A standardised protocol was used to evaluate patients, disease activity and treatment response. The disease remained stable in three and improved in four other patients, as documented by increased Medical Research Council scores and normal serum CK levels. No relapse of disease occurred. Local reactions were mild and self-limiting. No serious adverse events were reported. The mean duration of infusion per week was significantly lower compared to the mean duration of the 16 % SCIg preparation. A specifically designed questionnaire documented the patients' satisfaction with treatment. The weekly administration of 20 % SCIg is effective in maintaining a quiescent disease in patients with DM or PM with no increased safety concerns. SCIg therapy is particularly attractive for patients because it does not require venous access and hospitalisation and requires less assistance from healthcare provider services. KEY MESSAGES: The administration of 20 % SCIg was beneficial and safe in maintaining a quiescent disease and in inducing a complete remission in moderately active disease in patients with DM or PM. The treatment with 20 % SCIg led to the possibility to discontinue and to reduce the use of glucocorticoids and/or the immunosuppressants. Patients reported their satisfaction in terms of contact with health professionals, quality of treatment-related information and administration convenience, with an improved quality of life.

[Ranolazine in the prevention of anthracycline-related cardiotoxicity]. / La ranolazina nella prevenzione della cardiotossicità da antracicline - presupposti razionali.

Anthracyclines rank among the most effective anticancer drugs. They may however cause a dose-dependent and cumulative cardiotoxicity, eventually leading to heart failure. The antitumoral cytotoxicity of anthracyclines and their cardiotoxicity are believed to be due to different mechanisms, and there is therefore an active search for developing drugs able to protect the heart without impairing their chemotherapeutic efficacy. The foremost hypothesis explaining cardiotoxicity is the anthracycline-dependent production of reactive oxygen species (ROS). A ROS-induced calcium (Ca 2+)-calmodulin-dependent protein kinase II (CaMKII) hyperactivity can cause diastolic Ca2+ overload secondary to the activation of the late sodium (Na+) current (INaL). Furthermore, INaL hyperactivation can initiate a vicious cycle leading to sustained oxidative stress and energetic stress, with serious ATP depletion, similar to that occurring after the exposure of hearts or isolated cardiomyocytes exposed to anthracyclines. We hypothesize that anthracyclines may cause, through a ROS-dependent CaMKII hyperactivation, increased INaL, leading to a vicious cycle that worsens the redox imbalance with resulting mechanical and electrophysiological dysfunction and heart failure. In this light, we here review the molecular and clinical characteristics of ranolazine, the most powerful and selective clinical inhibitor of INaL, and speculate on the possibility that it may be used as an effective drug protecting against anthracycline-related cardiotoxicity.