Mauro Silingardi

Severe COVID-19 is often associated with coagulopathy and thrombotic complications. The underlying mechanisms are complex and multifactorial, involving platelet activation, dysregulation of the complement cascade, fibrinolytic imbalance, release of pro-inflammatory cytokines, immunothrombosis, antiphospholipid antibodies, and alterations in the von Willebrand factor (vWF)/ADAMTS13 axis. These pathways are also implicated in thrombotic microangiopathies (TMAs), characterized by endothelial injury and widespread microvascular thrombosis. In this prospective monocentric observational study, we investigated whether COVID-19-associated coagulopathy meets the criteria for TMA and evaluated the roles of complement activation and vWF/ADAMTS13 imbalance in disease severity. Forty-three hospitalized COVID-19 patients were enrolled and stratified by disease severity. Blood samples collected at admission were analyzed for hematologic, coagulation, inflammatory, and complement parameters. A 30-day follow-up recorded survival and thrombotic events. All patients showed elevated vWF and factor VIII levels; however, only vWF collagen-binding activity (vWF-CBA) significantly correlated with disease severity. ADAMTS13 activity remained above 60% in all cases, and no schistocytes were detected, arguing against a diagnosis of classical TMA. Nevertheless, the vWF-CBA/ADAMTS13 ratio was significantly higher in severe cases, particularly in unvaccinated individuals, suggesting endothelial dysregulation. Complement analysis revealed increased C5a levels and decreased C3b/iC3b ratios in severe disease, consistent with complement activation and consumption. C2 levels were also lower in these patients. Although complement activation and vWF/ADAMTS13 imbalance did not directly correlate, both pathways showed a similar trend according to disease severity. Overall, our findings indicate that COVID-19-related coagulopathy does not fulfill the criteria for classical TMA but shows features of complement-mediated endothelial injury and vWF dysregulation. The vWF-CBA may serve as a rapid, standardized tool for assessing endothelial dysfunction. Activation of the complement system, particularly via the lectin and alternative pathways, appears central to the prothrombotic state in severe COVID-19.

La terapia antiaggregante nelle sindromi coronariche acute. S. De Servi, A. Landi, C. Montalto, G. Crimi, S. Savonitto La terapia antiaggregante nella vasculopatia cerebrale acuta. M. Giorgi Pierfranceschi Impiego degli anticoagulanti nella fibrillazione atriale. B. Broccatelli, A. Patriarchi, M. Giustozzi, C. Becattini La terapia del tromboembolismo venoso. F. Dentali La terapia anticoagulante nel paziente oncologico. M. Ziliotti, L. Terroni, M.C. Ugolotti, C. Cademartiri La terapia anticoagulante orale nel paziente anziano, fragile o complesso. A. Dellasalda, A.Tedde, D. Arioli

After the anticoagulant withdrawal, a substantial proportion of patients with venous thromboembolism will develop recurrent events. Whether to consider an extended treatment depends on the risk of recurrence and bleeding risk. The assessment of the individual risk profile remains a difficult task. Several basal and post-basal factors modulate the risk of recurrence and may help clinicians to select patients who can benefit from the extended therapy. During the year 2017, new evidence regarding the post-basal factors was provided by the Morgagni and Scope studies. Another interesting novelty was the VTE-BLEED score, the first bleeding risk score that obtained the external validation in venous thromboembolism setting. In secondary prevention, the use of direct oral anticoagulants is growing instead of vitamin K antagonist. Even at lower doses, direct oral anticoagulants showed to be effective and safe, to reduce all-cause mortality and seemed to be superior to placebo for the composite outcome of fatal bleeding and fatal recurrence. After the recently published Einstein-Choice trial, the role of aspirin has become truly marginal as rivaroxaban 10 mg showed a bleeding risk similar to aspirin 100 mg but a greater effectiveness reducing the relative risk of recurrence by about 70%. Another option for secondary prevention could be sulodexide, with a lower protective effect than direct oral anticoagulants but an interesting safety profile. In conclusion, in our opinion, an individual strategy taking into account the risk of recurrence, bleeding risk, therapeutic options and patient preferences is the most appropriate approach to secondary prevention of venous thromboembolism.

Tra il Mito di Titone e la sindrome di Odisseo/Ulisse del Malato Complesso A. Fontanella Profilo biosociale del paziente ospedalizzato del XXI secolo R. Nardi, G. Mathieu, M. La Regina C’è bisogno di una nuova figura professionale? M. Silingardi Analisi dei modelli esistenti: future hospital program F. Orlandini Analisi dei modelli esistenti: Acute Complex Care Model (ACCM) F. Pietrantonio Analisi dei modelli esistenti: hospitalist V. Verdiani On being a hospitalist M. Affinati La nuova figura professionale italiana: profilo, attività e modelli organizzativi F. Orlandini, M. La Regina, V. Verdiani, D. Manfellotto Il percorso formativo G. Murialdo, A. Testi, G. Torre, P. Gnerre, F. Orlandini La certificazione L. Marchionni, M. Campanini, C. Nozzoli, A. Mazzone Hospitalist: SWOT analysis M. La Regina, F. Orlandini, V. Verdiani Considerazioni conclusive sulla figura dell’Hospitalist D. Manfellotto

Emphysematous pancreatitis associated with penetrating duodenal ulcer

Orthopnea is a sensation of shortness of breath, which occurs in recumbent position and is usually improved by standing or sitting. The authors report a case of an 81-year-old woman presented to the Emergency Department with a two-week history of orthopnea, fever and low back pain resistant to analgesics. Radiological findings confirm the presence of a diafragmatic hernia, and clinicians should pay attention to any history of trauma, because their absence in symptomatic adult patients directs towards a congenital cause. A surgical repair should be promptly obtained to avoid further general and respiratory deterioration.

The direct oral anticoagulants (DOACs) are drugs used in clinical practice since 2009 for the prevention of stroke or systemic embolism in non-valvular atrial fibrillation, and for the treatment and secondary prevention of venous thromboembolism. The four DOACs, including the three factor Xa inhibitors (rivaroxaban, apixaban and edoxaban) and one direct thrombin inhibitor (dabigatran) provide oral anticoagulation therapy alternatives to Vitamin K antagonists (VKAs). Despite their clear advantages, the DOACs require on the part of the internist a thorough knowledge of their pharmacokinetic and pharmacodynamic characteristics to ensure their correct use, laboratory monitoring and the appropriate management of adverse events. This document represents a consensus paper on the use of DOACs by representatives of three Italian scientific societies: the Italian Society of Internal Medicine (SIMI), the Federation of the Associations of Hospital Managers (FADOI), and the Society for the Study of Haemostasis and Thrombosis (SISET). This document formulates expert opinion guidance for pragmatic managing, monitoring and reversing the anticoagulant effect of DOACs in both chronic and emergency settings. This practical guidance may help the internist to create adequate protocols for patients hospitalized ion internal medicine wards, where patients are often elderly subjects affected by poly-morbidities and renal insufficiency, and, thus, require particular attention to drug–drug interactions and peri-procedural protocols.

Sarcoidosis is an insidious disorder that virtually affects every body organ. Lungs are the site most often affected (in up to 90% of patients) followed by intra thoracic more often than peripheral lymph nodes and other sites can be involved in different percentages. The evaluation of pulmonary sarcoidosis is best performed with high-resolution computed tomography (HRCT), as traditional chest X-ray has a low resolution and can be negative or give non-significant results. Disorders such as interstitial lung diseases (ILDs), tuberculosis, lung cancer and lymphangitis carcinomatosis can manifest with similar radiological findings that can deceive clinics and radiologists. The need of a clear distinction between these conditions is important not only for diagnostic purposes but also because treatment differs significantly in different conditions. However, conventional Ultrasound (US) can be negative if small lesions are present and false negative images can result if US is not followed by a contrast-imaging technique. Contrast enhanced computed tomography (CECT) and magnetic resonance imaging (CEMRI) are preferred to detect single or multiple masses, which appear hypodense and hypointense after contrast agent administration, respectively. We think that a correct algorithm should include a thorough clinical and radiological evaluation, a definite biopsy of affected tissues revealing classical non-caseating granulomas and a certain exclusion of conditions that can give similar clinical/histophatological patterns before considering the diagnosis of sarcoidosis. Only in these cases, a diagnosis of sarcoidosis can be sufficiently achieved before starting an appropriate treatment.