Approach to complexity in the COVID-19 era: what are the internist’s tools?

As the main title ‘COVID-19 revolution: a new challenge for the internist’ states, the global coronavirus infection disease 2019 (COVID-19) pandemic represented a new challenge for the internists. This paper is part of a series of articles written during the difficult period of the ongoing global pandemic and published all together in this fourth issue of the Italian Journal of Medicine, with the aim of sharing the direct experiences of those who were the first to face this severe emergency, expressing each point of view in the management of COVID-19 in relation to other diseases. Each article is therefore the result of many efforts and a joint collaboration between many colleagues from the Departments of Internal Medicine or Emergency Medicine of several Italian hospitals, engaged in the front line during the pandemic. These preliminary studies therefore cover diagnostic tools available to health care personnel, epidemiological reflections, possible new therapeutic approaches, discharge and reintegration procedures to daily life, the involvement of the disease not only in the lung, aspects related to various comorbidities, such as: coagulopathies, vasculitis, vitamin D deficiency, gender differences, etc.. The goal is to offer a perspective, as broad as possible, of everything that has been done to initially face the pandemic in its first phase and provide the tools for an increasingly better approach, in the hope of not arriving unprepared to a possible second wave. This paper in particular deals with internist’s tools useful for management of COVID-19 patient

Are multiple-choice questions a good tool for the assessment of clinical competence in Internal Medicine?

There are many feasible tools for the assessment of clinical practice, but there is a wide consensus on the fact that the simultaneous use of several different methods could be strategic for a comprehensive overall judgment of clinical competence. Multiple-choice questions (MCQs) are a well-established reliable method of assessing knowledge. Constructing effective MCQ tests and items requires scrupulous care in the design, review and validation stages. Creating high-quality multiple-choice questions requires a very deep experience, knowledge and large amount of time. Hereby, after reviewing their construction, strengths and limitations, we debate their completeness for the assessment of professional competence

Could clustering of comorbidities be useful for better defining the internal medicine patients’ complexity?

Internal medicine patients are mostly elderly with multiple comorbidities, usually chronic. The high prevalence of comorbidity and multimorbidity has a significant impact on both positive responses to treatment and the occurrence of adverse events. Clustering is the process of nosography grouping into meaningful associations with some index disease, so that the objects within a cluster have high similarity in comparison with one another. In the decision-making process it is imperative that, in addition to understanding the immediate clinical problems, we are able to explicit all the contextual factors that have to be taken into account for the best outcome of care. Cluster analysis could be leveraged in developing better interventions targeted to improve health outcomes in subgroups of patients

Colchicine for COVID-19: targeting NLRP3 inflammasome to blunt hyperinflammation

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is capable of inducing the activation of NACHT, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome, a macromolecular structure sensing the danger and amplifying the inflammatory response. The main product processed by NLRP3 inflammasome is interleukin (IL)-1 beta, responsible for the downstream production of IL-6, which has been recognized as an important mediator in coronavirus disease 2019 (COVID-19). Since colchicine is an anti-inflammatory drug with the ability to block NLRP3 inflammasome oligomerization, this may prevent the release of active IL-1 beta and block the detrimental effects of downstream cytokines, i.e. IL-6. To date, few randomized clinical trials and many observational studies with colchicine have been conducted, showing interesting signals. As colchicine is a nonspecific inhibitor of the NLRP3 inflammasome, compounds specifically blocking this molecule might provide increased advantages in reducing the inflammatory burden and its related clinical manifestations. This may occur through a selective blockade of different steps preceding NLRP3 inflammasome oligomerization as well as through a reduced release of the main cytokines (IL-1 beta and IL-18). Since most evidence is based on observational studies, definitive conclusion cannot be drawn and additional studies are needed to confirm preliminary results and further dissect how colchicine and other NLRP3 inhibitors reduce the inflammatory burden and evaluate the timing and duration of treatment

The continuous challenge of antithrombotic strategies in diabetes: focus on direct oral anticoagulants

Direct oral anticoagulants (DOACs) include dabigatran, which inhibits thrombin, and apixaban, edoxaban, and rivaroxaban, which inhibit factor Xa. They have been extensively studied in large trials involving patients affected by the most common cardiovascular diseases. As the presence of diabetes leads to peculiar changes in primary and secondary hemostasis, in this review we highlight the current evidence regarding DOAC use in diabetic patients included in the majority of recently conducted studies. Overall, in trials involving patients with atrial fibrillation, data seem to confirm at least a similar efficacy and safety of DOACs compared to warfarin in patients with or without diabetes. Furthermore, in diabetic patients, treatment with DOACs is associated with a significant relative reduction in vascular death compared to warfarin. In trials enrolling patients undergoing percutaneous coronary intervention, results concerning bleeding events are consistent in patients with or without diabetes. With regards to the COMPASS study, in patients with diabetes (n\u2009=\u200910,241), addition of rivaroxaban 2.5 mg to aspirin resulted in a significantly lower incidence of major adverse cardiovascular events (HR 0.74, 95% CI 0.61-0.90; interaction p\u2009=\u20090.68) with higher rates of major bleeding expected (HR 1.70, 95% CI 1.25-2.31). The 3287 patients with peripheral artery disease and diabetes receiving rivaroxaban plus aspirin had a twofold higher absolute reduction in the composite endpoint (cardiovascular death, myocardial infarction, and stroke) than patients without diabetes. Finally, we report the involvement of cytochromes or P-glycoprotein on the metabolism of the most commonly prescribed glucose-lowering drugs. No clinically relevant interactions are expected during the concomitant use of DOACs and anti-diabetic agents

Upper extremity deep vein thrombosis in COVID-19: Incidence and correlated risk factors in a cohort of non-ICU patients

BackgroundVenous thromboembolism is a frequent complication of COVID-19 infection. Less than 50% of pulmonary embolism (PE) is associated with the evidence of deep venous thrombosis (DVT) of the lower extremities. DVT may also occur in the venous system of the upper limbs especially if provoking conditions are present such as continuous positive airway pressure (CPAP). The aim of this study was to evaluate the incidence of UEDVT in patients affected by moderate-severe COVID-19 infection and to identify potential associated risk factors for its occurrence.MethodsWe performed a retrospective analysis of all patients affected by moderate-severe COVID-19 infection admitted to our unit. In accordance with the local protocol, all patients had undergone a systematic screening for the diagnosis of UEDVT, by vein compression ultrasonography (CUS). All the patients were receiving pharmacological thromboprophylaxis according to international guidelines recommendations. Univariate and multivariate analyses were used to identify risk factors associated with UEDVT.Results257 patients were included in the study, 28 patients were affected by UEDVT with an incidence of 10.9% (95% CI, 7.1-14.7). At univariate analysis UEDVT appeared to be significantly associated (p< 0.05) with pneumonia, ARDS, Pa02/Fi02, D-dimer value higher than the age adjusted cut off value and need for CPAP ventilation. Multivariate analysis showed a significant association between UEDVT and the need for CPAP ventilation (OR 5.95; 95% IC 1.33-26.58). Increased mortality was found in patients affected by UEDVT compared to those who were not (OR 3.71; 95% CI, 1.41-9.78).ConclusionsUEDVT can occur in COVID-19 patients despite adequate prophylaxis especially in patients undergoing helmet CPAP ventilation. Further studies are needed to identify the correct strategy to prevent DVT in these patients

High-dose dexamethasone treatment for COVID-19 severe acute respiratory distress syndrome: a retrospective study

Low-dose dexamethasone reduces mortality in patients with coronavirus disease 2019 (COVID-19)-related acute respiratory distress syndrome (ARDS). We retrospectively analyzed the efficacy of high-dose dexamethasone in patients with COVID-19-related ARDS and evaluated factors affecting the composite outcome (death or invasive mechanical ventilation). From March 4th to April 1st 2020, 98 patients with COVID-19 pneumonia were included. Those who after at least 7 days from symptom onset presented a worsening of the respiratory function or of inflammatory biomarkers were started on intravenous high-dose dexamethasone (20 mg daily for 5 days, followed by 10 mg daily for 5 days). Most patients were males (62%) with a mean age of 69 years. Hypertension and cardiovascular disease (CVD) were prevalent. Following dexamethasone treatment, a significant improvement in PaO2/FiO2 (277.41 [178.5\u2013374.8] mmHg vs. 146.75 [93.62\u2013231.16] mmHg, p < 0.001), PaO2 (88.15 [76.62\u2013112.0] mmHg vs. 65.65 [57.07\u201381.22] mmHg, p < 0.001), and SpO2 (96 [95\u201398]% vs. 94 [90\u201396]%, p < 0.001) was observed. A concomitant decrease in C-reactive protein and ferritin levels was found (132.25 [82.27\u2013186.5] mg/L vs. 7.3 [3.3\u201324.2] mg/L and 1169 [665\u20132056] ng/mL vs. 874.0 [569.5\u20131434] ng/mL, respectively; p < 0.001 for both vs. baseline). CVD was found to increase the risk of the composite outcome (RR 7.64, 95% CI 1.24\u201347.06, p = 0.028). In hospitalized patients with COVID-19-related ARDS, high-dose dexamethasone rapidly improves the clinical status and decreases inflammatory biomarkers. CVD was found to increase the risk of the composite outcome. These data support the importance of randomized clinical trials with high-dose dexamethasone in COVID-19 patient

The strategic alliance between clinical and molecular science in the war against SARS-CoV-2, with the rapid-diagnostics test as an indispensable weapon for front line doctors

Our work concerns the actual problem of spread of SARS- CoV-2 outbreak which requires fast and correct as possible answer. In current scenario, the need of rapid answer put away the imperative of proper methodology. We focus on the serogical immunoassay for diagnosis of Covid-19 as an important weapon not only for diagnostic purpose, but also for epidemiologic one. The right equilibrium between high speed, low cost and accuracy is obtained with easy-to-use decentralized point-of-care test as the colloidal gold-based immunochromatographic strip assay which detects IgM and IgG antibodies directed against SARS-CoV-2. As our aim is to evaluate the efficacy of Covid-19 rapid tests and of serological assays in real-life settings, we designed a research protocol aimed to establish how to use correctly these diagnostics, taking into account the different possible clinical and epidemiological scenarios