Optimal oral anticoagulant therapy in patients with nonrheumatic atrial fibrillation and recent cerebral ischemia

A number of studies have demonstrated the efficacy of oral anticoagulant therapy in reducing the risk of stroke and systemic embolism in patients with nonrheumatic atrial fibrillation. However, both the targeted and the actual levels of anticoagulation differed widely among the studies, and a number of studies failed to report standardized prothrombin-time ratios as international normalized ratios (INRs). We therefore performed an analysis to determine the intensity of oral anticoagulant therapy in nonrheumatic atrial fibrillation that provides the best balance between the prevention of thromboembolism and the occurrence of bleeding complications

The diagnosis of transient ischemic attacks

The diagnosis of transient ischemic attack (TIA) is fraught with difficulty, since the diagnosis rests entirely upon the history of the patient's symptoms and the neurologist's skill in questioning the patient. The aim of this thesis is to investigate various measures to improve the reliability in making this diagnosi

Idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a progressive devastating lung disease with substantial morbidity. It is associated with cough, dyspnea and impaired quality of life. If left untreated, IPF has a median survival of 3 years. IPF affects ∼3 million people worldwide, with increasing incidence in older patients. The current concept of pathogenesis is that pulmonary fibrosis results from repetitive injury to the lung epithelium, with fibroblast accumulation, myofibroblast activation, and deposition of matrix. These injuries, in combination with innate and adaptive immune responses, dysregulated wound repair and fibroblast dysfunction, lead to recurring tissue remodeling and self-perpetuating fibrosis as seen in IPF. The diagnostic approach includes the exclusion of other interstitial lung diseases or underlying conditions and depends on a multidisciplinary team-based discussion combining radiological and clinical features and well as in some cases histology. In the last decade, considerable progress has been made in the understanding of IPF clinical management, with the availability of two drugs, pirfenidone and nintedanib, that decrease pulmonary lung function decline. However, current IPF therapies only slow disease progression and prognosis remains poor. Fortunately, there are multiple clinical trials ongoing with potential new therapies targeting different disease pathways. This review provides an overview of IPF epidemiology, current insights in pathophysiology, diagnostic and therapeutic management approaches. Finally, a detailed description of current and evolving therapeutic approaches is also provided.</p

IMPORTANZA CLINICA DELLA TIPIZZAZIONE SIEROLOGICA E MOLECOLARE DELLE VARIANTI DELL'ANTIGENE RhD

Il sistema Rh, dopo quello ABO, è il sistema gruppo-ematico eritrocitario più immunogeno dell’uomo. Infatti all’esecuzione del gruppo ABO si accompagna sistematicamente la contemporanea determinazione del fenotipo Rh. L’antigene più importante del sistema Rh, l’antigene D, è molto più efficace di qualunque altro antigene eritrocitario nel determinare una risposta anticorpale quando venga introdotto in un soggetto che ne è privo. Esso è presente sugli eritrociti dell’85% delle persone di razza bianca ed in percentuale ancora più alta in quelle di razza nera . Quindi dopo gli antigeni A e B, il D è il più importante nella pratica trasfusionale. Diversamente dagli antigeni A e B, tuttavia, le persone che non possiedono l’antigene D sui propri eritrociti non presentano, regolarmente, l’anti-D. La formazione dell’anticorpo anti-D origina dall’esposizione, per motivi trasfusionali o gravidanze, ad emazie che presentano l’antigene D. E’ stato stimato che dal 30 all’85% delle persone D negative che ricevono una trasfusione D positiva svilupperà l’anti-D. Per questo motivo, tutti i riceventi e tutti i donatori di sangue vengono esaminati, nelle procedure di routine, per la presenza dell’antigene D, al fine di assicurare che i riceventi D negativi vengano identificati e ricevano sangue D negativo. L’antigene D è stato da sempre oggetto di studio dell’immunoematologia. L’interesse verso tale antigene è aumentato dopo la scoperta che alcuni individui RhD positivi producevano in seguito a trasfusioni anticorpi anti-D. Successivi studi portarono alla scoperta del mosaicismo dell’antigene RhD e rivelarono la sua grande variabilità (D partial e D weak). In passato, i limiti delle metodiche sierologiche non consentirono di identificare le molte varianti dell’antigene D, che perciò venivano identificate come D negativo. Questo non rappresentava un problema nell’individuo ricevente la trasfusione, dato che veniva trasfuso con sangue RhD negativo (come riceventi alcune varianti sono tutt’ora trattate come RhD negative), ma creava un problema se l’individuo era un donatore di sangue, in quanto i soggetti D variant, possono determinare nel ricevente RhD negativo la produzione di alloanticorpi . La corretta identificazione delle varianti dell’antigene RhD è fondamentale anche per le donne gravide RhD negative, in quanto vanno sottoposte ad immunoprofilassi se il neonato è un D variant e quindi può stimolare la produzione di anticorpi che potrebbero causare una malattia emolitica del neonato (MEN) in una successiva gravidanza con feto RhD positivo. Nei servizi trasfusionali (SIT) nasce quindi l’esigenza di dover correttamente tipizzare individui che, dai test sierologici, risultano negativi, in modo da determinare possibili D variant per evitare alloimmunizzazioni da trasfusione e programmare immunoprofilassi MEN nelle donne gravide quando richiesto

901-97 Stroke and Long-term Anticoagulant Therapy in 3404 Post-Myocardial Infarction Patients

In a randomized, double-blind, placebo controlled trial (ASPECT) we studied 3404 post-myocardial infarction patients who suffered a stroke during long-term anticoagulant therapy. The duration of treatment ranged from 1 day to six years. Three years following randomization, 2% of the patients on anticoagulant therapy had a stroke compared to 4% in placebo.The incidence of stroke analyzed on “intention-to-treat” was 0.7 per 100 patient-years in the anticoagulant group and 1.2 per 100 patient-years in placebo, a hazard ratio (HR) of 0.60 with a 95% confidence interval (Cl) of 0.40 to 0.90, a 40% reduction in the risk of stroke in the anticoagulated group. A total of 19 intracranial bleeding was observed. The risk of hemorrhages was 8 times greater for anticoagulated patients compared to placebo. Eight of the 17 bleedings were fatal in the anticoagulant group and no fatal hemorrhages occurred in placebo. A total of 15 cerebral infarctions occurred in the anticoagulated group and 43 in placebo. Of the 14 hemorrhagic strokes, 6 were within INR 3.0–4.0 and 8 with an INR&gt;4.0, Of the 7 non-hemorrhagic strokes, 2 were at INR&lt;2, 3 within INR 3.0–4.0, 1 at INR&gt;4.0, and no measurement was available in one patient. The total number of patients who died or were severely disabled as a result of cerebral stroke amounted to 13 in the anticoagulated group, compared to 18 in placebo.ConclusionThe results of the ASPECT trial indicated that long-term anticoagulant therapy substantially reduced the risk of stroke in post-myocardial infarction patients. The increased risk of bleeding complications associated with anticoagulant therapy was offset by a marked reduction in ischemic events