Minerva medica
-
Historically, asthma was considered a disease predominantly of the large airways, but gradually small airways have been recognized as the major site of airflow obstruction. Small airway dysfunction (SAD) significantly contributes to the pathophysiology of asthma, and it is present across all asthma severities. Promising preclinical findings documented enhanced beneficial effects of combination therapies on small airways compared to monocomponents, thus it was questioned whether this could translate into further clinical implications from bench-to-bedside. The aim of this review was to systematically assess the state of the art of small airway involvement in asthma, especially in response to different pharmacological treatments acting on the respiratory system. ⋯ Despite the numerous methodological tools to detect SAD, there is still no gold standard diagnostic method to assess small airways, especially in severe asthma. Further research should be directed to improve primary and secondary prevention strategies by supporting the combined approach of different non-invasive techniques for an early detection of peripheral abnormalities and optimization of asthma therapy.
-
Inhaled corticosteroids are the cornerstone for the treatment of stable asthma, however, when disease severity increases, escalating therapy to combinations of drugs acting on distinct signalling pathways is required. It is advantageous to providing evidence of a synergistic interaction across drug combinations, as it allows optimizing bronchodilation while lowering the dose of single agents. In the respiratory pharmacology field, two statistical models are accepted as gold standard to characterize drug interactions, namely the Bliss Independence criterion and the Unified Theory. In this review, pharmacological interactions across drugs approved for the treatment of asthma have been systematically assessed. ⋯ There is still limited knowledge regarding the mechanistic basis underlying pharmacological interactions across drugs approved for asthma. The synergism elicited by combined agents is an effect of class. Specifically designed clinical trials are needed to confirm the results coming from preclinical evidence, but also to establish the minimal dose for combined agents to induce a synergistic interaction and maximize bronchodilation.
-
Portal vein thrombosis (PVT) is the most frequent among the splanchnic vein thrombosis, accounting for 90% of cases. More than half of PVT are provoked by liver cirrhosis, solid cancer or myeloproliferative neoplasms. The remaining cases are non-malignant non-cirrhotic PVT and include either unprovoked events or thrombosis secondary to other less common risk factors (e.g. abdominal surgery, intrabdominal inflammations/infections, or hormonal stimuli). ⋯ Different treatment options (unfractionated or low molecular weight heparin, vitamin K antagonists and direct oral anticoagulants [DOACs]) can be considered. In this narrative review we will discuss the treatment of PVT in the three most common scenarios (cirrhosis-associated, cancer-associated and non-malignant non-cirrhotic PVT). We will also discuss the role of the DOACs and summarize recent guidelines on this topic.
-
Upper extremity deep vein thrombosis (UEDVT) represents about 5-10% of all cases of deep vein thrombosis (DVT) with a steadily increasing incidence mostly due to the high prevalence of cancer and frequent use of intravascular devices such as central venous catheters and pacemaker. In primary UEDVT, the venous outflow obstruction and subsequent thrombosis are related to congenital or acquired anatomical abnormalities, whereas secondary UEDVT is often associated with malignancy or indwelling lines. ⋯ Despite sharing many similarities with lower extremity DVT, UEDVT has distinctive features requiring specific diagnostic and therapeutic approaches. The present review discusses the latest evidence on the epidemiology, diagnosis, and treatment of UEDVT, and provides management indications which may help guide clinical decision making.
-
Disseminated intravascular coagulation (DIC) has long been understood as a condition where both thrombotic and hemostatic abnormalities coexist. DIC is a difficult complication for clinicians to manage as it is due to multiple underlying complications of pathophysiologic abnormalities in diverse disease states. Ongoing research continues to define the meaning of DIC, evaluate therapeutic options, and how it presents with the complex paradigm of systemic activation of coagulation. In this review we introduce the current topics regarding this difficult situation. ⋯ DIC is recognized as a pathologically triggered and dysregulated systemic activation of coagulation in response to various noxious stimuli. DIC's phenotype and clinical manifestations can vary from prothrombotic to hemorrhagic, depending on the underlying diseases. However, the fundamental mechanisms of systemic and vascular endothelial dysfunction can be explained as different phases of the acute response, with an initial prothrombotic phase that can commonly change to hemostatic insufficiency. Thrombin is the key initiator of the pathophysiologic process along with endothelial injury and initially fibrinolysis activation followed by fibrinolysis suppression. There is no established approach for managing DIC beyond initially treating the underlying disease and replacement therapy for the management of coagulopathy. Targeting anticoagulation therapy with antithrombin concentrates and recombinant thrombomodulin for the prevention of microthrombus formation, and antifibrinolytic therapy using tranexamic acid for the coagulopathy after massive bleeding, continue to be studied as therapeutic options.