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OBJECTIVE To evaluate the susceptibility to coronavirus disease 2019 (COVID-19) in patients with autoimmune conditions treated with antimalarials in a population-based study. METHODS All residents treated with chloroquine (CQ)/hydroxychloroquine (HCQ) from July through December 2019 and living in 3 provinces of Regione Emilia-Romagna were identified by drug prescription registries and matched with the registry containing all residents living in the same areas who have had swabs and tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. RESULTS A total of 4,408 patients were identified. The prevalence of patients receiving antimalarials was 0.85 per 1,000 men and 3.3 per 1,000 women. The cumulative incidence of testing during the study period was 2.7% in the general population and 3.8% among those receiving CQ or HCQ, while the cumulative incidence of testing positive was 0.55% in the general population and 0.70% among those receiving CQ/HCQ. Multivariate models showed that those receiving CQ/HCQ had a slightly higher probability of being tested compared to the general population (OR 1.09 [95% CI 0.94-1.28]), the same probability of being diagnosed as having COVID-19 (OR 0.94 [95% CI 0.66-1.34]), and a slightly lower probability of being positive once tested (OR 0.83 [95% CI 0.56-1.23]). None of the differences were significant. CONCLUSION Our findings do not support the use of antimalarials as a prophylactic treatment of COVID-19.

Internal medicine (IM) patients are mostly elderly, with multiple complex co-morbidities, usually chronic. The complexity of these patients involves the intricate entanglement of two or more systems (e.g. body and disease, family-socio-economic and environmental status, coordination of care and therapies) and this requires comprehensive, multi-dimensional assessment (MDA). Despite attempts to improve management of chronic conditions, and the availability of several MDA tools, defining the complex patient is still problematic. The complex profile of our patients can only be described through the best assessment tools designed to identify their characteristics. In order to do this, the Federation of Associations of Hospital Doctors on Internal Medicine FADOI has created its own vision of IM. This involves understanding the different needs of the patient, and analyzing diseases clusters and the possible relationships between them. By exploring the real complexity of our patients and selecting their real needs, we can exercise holistic, anthropological and appropriate choices for their treatment and care. A simpler assessment approach must be adopted for our complex patients, and alternative tools should be used to improve clinical evaluation and prognostic stratification in a hierarchical selection of priorities. Further investigation of complex patients admitted to IM wards is needed.

Background: Internal medicine has been defined as the specialty of the adult medical complex patients. Complexity science suggests that illness (and health) results from complex, dynamic, and unique interactions between different components of the overall system. In a patient, complexity involves the intricate entanglement of two or more systems (e.g.; body-diseases, family, socioeconomic status, therapies). Aim of the study: To evaluate the real applicability of Evidence Based Medicne (EBM) in clinical Departments of Internal Medicine and its critical perspectives. Discussion: Habitually the internist takes decisions in these situations: a) certainty (the ideal decision is adopted and the corresponding strategy follows), b) risk (the more suitable alternative selected can be the determination of the probable value or mathematical hope) and c) uncertainty, in which decisions linked to triple agents: beliefs and personal values of the doctors (I) for their patients (II) in the society (III). In the medical decisions there are often different factors that go beyond the field of technical and scientific knowledge (family, social, economic problems, etc.) and demanding an ethical analysis of the decision. Conclusions: The ‘‘evidence-based medicine’’, as other models of care, has — in itself — some limitations. ‘‘No evidence in medicine’’ matters that the postulates of the EBM are not always applicable to the real patients of Internal Medicine wards, mostly elderly, frail, complex, with comorbidities and polipharmacy, often with cognitive dysfunction and limitation of autonomy, with psycho-emotional, social and economic problems. The interacting effects of overall involved diseases/factors and their management require more complex and individualised care than simply the sum of separate guideline components. Further innovation is required to resolve the need to enhance integration of evidence with our patients’ values at the ‘‘bedside and/or clinic’’ management.

Introduction: Subcutaneous manifestations of severe acute pancreatitis (Cullen’s sign, Gray- Turner’s sign, Fox’s sign, and Bryant’s sign) are often discussed in journals and textbooks, but seldom observed. Although historically associated with acute pancreatitis, these clinical signs have been described in various other conditions associated with retroperitoneal hemorrhage. Case report: We describe the case of a 61-year-old male with no history of alcohol intake, who was admitted for epigastric pain, vomiting, and increasing serum amylase and lipase levels. Five days after admission, ecchymotic skin discoloration was noted over both flanks (Gray-Turner’s sign) and the upper third of the thighs (Fox’s sign). Ten days later, he developed multiorgan failure and was transferred to the ICU for 5 days. Computed tomography revealed a large pancreatic fluid collection, which was subjected to EUS-guided drainage. Cholecystectomy was later performed for persistent obstructive jaundice. After more than 4 months of hospitalization, he died as a result of severe gastrointestinal bleeding. Discussion and conclusions: Skin manifestations of retroperitoneal hemorrhage in a patient with acute pancreatitis indicate a stormy disease course and poor prognosis. The severity of acute pancreatitis is currently estimated with validated scoring systems based on clinical, laboratory, and imaging findings. However, skin signs like the ones discussed above can represent a simple and inexpensive parameter for evaluating the severity and prognosis of this disease.

Introduction: Chronic obstructive pulmonary disease (COPD) is the second leading cause of hospitalization in Internal Medicine departments in Italy and the fourth leading cause of death all over the word. By 2020, COPD will be the third leading cause of death and the fifth leading cause of disability. It is — along with chronic congestive heart failure — one of the most common causes of unscheduled hospital readmissions, and as such it represents a significant economic burden for the health-care system. Exacerbations of COPD are important events in the natural history of this prevalent condition. Discussion: This review provides a comprehensive state-of-the-art look at prevention and management of COPD exacerbations. Treatment of these episodes has to be tailored to the severity of the clinical presentation. We now have a wide range of therapeutic available options, based on the results of clinical trials. Management of the acute event should include the necessary measures (mainly the administration of inhaled short-acting bronchodilators, inhaled or oral corticosteroids, and antibiotics), with or without oxygen and ventilator support. Conclusions: To improve the management of COPD exacerbations, the focus of care must be shifted from the episodic acute complications to their systematic prevention. The management of COPD, which is often associated with multiple co-morbidities, is complex and requires a tailored, multifaceted and multidisciplinary approach. Integrated care for COPD also requires that patients be informed about their condition, that they participate actively in their care, and that they have easy access to the necessary health-care services.

Introduction Ortner's syndrome, also known as cardiovocal syndrome, is a rare clinical entity with hoarseness due to left recurrent laryngeal nerve (RLN) palsy owing to a cardiovascular disease. Norbert Ortner ascribed hoarseness of voice RLN palsy in patients with several mitral stenosis, postulating that an enlarged left atrium could be responsible for the recurrent laryngeal nerve palsy. Case report A 63-year-old man with a history of progressive hoarseness of voice developed since over three months. Flexible laryngoscopy revealed a fixed left vocal cord in the paramedian position. The chest enhanced axial computed tomography confirmed a large left ventricular aneurysm. Conclusions Hoarseness has significant public health implications. Patients suffer from social deprivation, depression and a poor quality of life. Several underlying conditions are associated with the cardiovocal syndrome, including iatrogenic, congenital, mitral valve disorders, aortic and ventricular aneurysms. Laryngoscopy is indicated for the assessment of hoarseness if symptoms fail to improve or resolve within three months, or at any time when the clinician suspects a serious underlying disorder.

Summary Introduction Ortner's syndrome, also known as cardiovocal syndrome, is a rare clinical entity with hoarseness due to left recurrent laryngeal nerve (RLN) palsy owing to a cardiovascular disease. Norbert Ortner ascribed hoarseness of voice RLN palsy in patients with several mitral stenosis, postulating that an enlarged left atrium could be responsible for the recurrent laryngeal nerve palsy. Case report A 63-year-old man with a history of progressive hoarseness of voice developed since over three months. Flexible laryngoscopy revealed a fixed left vocal cord in the paramedian position. The chest enhanced axial computed tomography confirmed a large left ventricular aneurysm. Conclusions Hoarseness has significant public health implications. Patients suffer from social deprivation, depression and a poor quality of life. Several underlying conditions are associated with the cardiovocal syndrome, including iatrogenic, congenital, mitral valve disorders, aortic and ventricular aneurysms. Laryngoscopy is indicated for the assessment of hoarseness if symptoms fail to improve or resolve within three months, or at any time when the clinician suspects a serious underlying disorder.

Summary Introduction Chronic obstructive pulmonary disease (COPD) is the second leading cause of hospitalization in Internal Medicine departments in Italy and the fourth leading cause of death all over the word. By 2020, COPD will be the third leading cause of death and the fifth leading cause of disability. It is – along with chronic congestive heart failure – one of the most common causes of unscheduled hospital readmissions, and as such it represents a significant economic burden for the health-care system. Exacerbations of COPD are important events in the natural history of this prevalent condition. Discussion This review provides a comprehensive state-of-the-art look at prevention and management of COPD exacerbations. Treatment of these episodes has to be tailored to the severity of the clinical presentation. We now have a wide range of therapeutic available options, based on the results of clinical trials. Management of the acute event should include the necessary measures (mainly the administration of inhaled short-acting bronchodilators, inhaled or oral corticosteroids, and antibiotics), with or without oxygen and ventilator support. Conclusions To improve the management of COPD exacerbations, the focus of care must be shifted from the episodic acute complications to their systematic prevention. The management of COPD, which is often associated with multiple co-morbidities, is complex and requires a tailored, multifaceted and multidisciplinary approach. Integrated care for COPD also requires that patients be informed about their condition, that they participate actively in their care, and that they have easy access to the necessary health-care services.

Summary Introduction Subcutaneous manifestations of severe acute pancreatitis (Cullen's sign, Gray-Turner's sign, Fox's sign, and Bryant's sign) are often discussed in journals and textbooks, but seldom observed. Although historically associated with acute pancreatitis, these clinical signs have been described in various other conditions associated with retroperitoneal hemorrhage. Case report We describe the case of a 61-year-old male with no history of alcohol intake, who was admitted for epigastric pain, vomiting, and increasing serum amylase and lipase levels. Five days after admission, ecchymotic skin discoloration was noted over both flanks (Gray-Turner's sign) and the upper third of the thighs (Fox's sign). Ten days later, he developed multiorgan failure and was transferred to the ICU for 5 days. Computed tomography revealed a large pancreatic fluid collection, which was subjected to EUS-guided drainage. Cholecystectomy was later performed for persistent obstructive jaundice. After more than 4 months of hospitalization, he died as a result of severe gastrointestinal bleeding. Discussion and conclusions Skin manifestations of retroperitoneal hemorrhage in a patient with acute pancreatitis indicate a stormy disease course and poor prognosis. The severity of acute pancreatitis is currently estimated with validated scoring systems based on clinical, laboratory, and imaging findings. However, skin signs like the ones discussed above can represent a simple and inexpensive parameter for evaluating the severity and prognosis of this disease.

Summary Background Internal medicine has been defined as the specialty of the adult medical complex patients. Complexity science suggests that illness (and health) results from complex, dynamic, and unique interactions between different components of the overall system. In a patient, complexity involves the intricate entanglement of two or more systems (e.g.; body-diseases, family, socioeconomic status, therapies). Aim of the study To evaluate the real applicability of Evidence Based Medicne (EBM) in clinical Departments of Internal Medicine and its critical perspectives. Discussion Habitually the internist takes decisions in these situations: a) certainty (the ideal decision is adopted and the corresponding strategy follows), b) risk (the more suitable alternative selected can be the determination of the probable value or mathematical hope) and c) uncertainty, in which decisions linked to triple agents: beliefs and personal values of the doctors (I) for their patients (II) in the society (III). In the medical decisions there are often different factors that go beyond the field of technical and scientific knowledge (family, social, economic problems, etc.) and demanding an ethical analysis of the decision. Conclusions The “evidence-based medicine”, as other models of care, has – in itself – some limitations. “No evidence in medicine” matters that the postulates of the EBM are not always applicable to the real patients of Internal Medicine wards, mostly elderly, frail, complex, with comorbidities and polipharmacy, often with cognitive dysfunction and limitation of autonomy, with psycho-emotional, social and economic problems. The interacting effects of overall involved diseases/factors and their management require more complex and individualised care than simply the sum of separate guideline components. Further innovation is required to resolve the need to enhance integration of evidence with our patients’ values at the “bedside and/or clinic” management.

A woman with progressive bilateral Mooren's ulcer developed recurrent corneal perforations and melting requiring tectonic grafts, despite conventional immunosuppressant therapy. Following treatment with infliximab, an anti-tumour necrosis factor agent, the patient showed marked reduction in conjunctival inflammation and no further recurrence of corneal thinning and perforation during 2-year follow up on maintaining treatment.

uman osteoarthritis (OA) is a heterogeneous andmultifactorialdiseasewithmultiplepathogeneticmech-anism implicated in its development and progression. Carti-lage degradation and loss are the major features of OA; de-generative changes include fibrillation, chondrocyteproliferation into cell clusters, and matrix disruption. Al-though biomechanical factors are strongly implicated, it isunclear which stimuli regulate the hyperactive phenotype ofOAchondrocytes,includingtheirabilitytoexpresscartilage-degradingproteinases(1).Recentstudieshaveimplicatedtheupregulation of several matrix-degrading metalloproteinases(MMPs)inOAcartilageandhavesuggestedthatchondrocyteproduction of MMPs in OA cartilage reflects local synthesisthat varies with the extent of cartilage degeneration. Thedemonstration of chondrocytes producing interleukin-1and tumor necrosis factor Theseverityofcartilagelesionshasbeenassessedusinganwithin the superficial zones ofOA cartilage supports the concept that cytokine-MMP asso-ciations contribute to a highly catabolic state, chondrocyteapoptosis, and the resultant progressive degeneration of ar-ticular cartilage (2-6).