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Abstract The study aims at defining the factors affecting the clinicians’ decision of changing or confirming the treatment options for frail patients in polytherapy, supporting prescribing patterns, thus also figuring out if the inclination of the clinicians towards digital solutions (INTERCheckWEB) and specific guidelines, could play a role in their decision. A literature review was performed, revealing the main individual, organizational and decisional factors, impacting on the clinicians’ propensity to change the current patients’ therapy: the clinician perceptions of support in case of clinical guidelines use or INTERCheckWEB use were studied. A qualitative approach was implemented, and thirty-five clinicians completed a questionnaire, aimed at evaluating fifteen different clinical cases, defining if they would change the patient’s current therapy depending on the level of information received. Three methodological approaches were implemented. (1) Bivariate correlations to test the relationships between variables. (2) Hierarchical sequential linear regression model to define the predictors of the clinician propensity to change therapy. (3) Fuzzy Qualitative Comparative Analysis—fsQCA, to figure out the combination of variables leading to the outcome. Patient’s age and autonomy (p value = 0.000), as well as clinician’s perception regarding IT ease of use (p value = 0.043) and seniority (p value = 0.009), number of drugs assumed by the patients (p value = 0.000) and number of concomitant diseases (p value = 0.000) are factors influencing a potential change in the current therapy. The fsQCA-crisp confirms that the clinical conditions of the patients are the driving factors that prompt the clinicians towards a therapy change.

Abstract Introduction Discriminating between virus-induced fever from superimposed bacterial infections is a common challenge in intensive care units. Superimposed bacterial infections can be detected in severe SARS-CoV2-infected patients, suggesting the important role of the bacteria in COVID-19 evolution. However, indicators of patients’ immune status may be of help in the management of critically ill subjects. Monocyte CD169 is a type I interferon-inducible receptor that is up-regulated during viral infections, including COVID-19. Monocyte HLA-DR expression is an immunologic status marker, that decreases during immune exhaustion. This condition is an unfavorable prognostic biomarker in septic patients. Neutrophil CD64 upregulation is an established indicator of sepsis. Methods In this study, we evaluated by flow cytometry the expression of cellular markers monocyte CD169, neutrophil CD64, and monocyte HLA-DR in 36 hospitalized patients with severe COVID-19, as possible indicators of ongoing progression of disease and of patients’ immune status. Blood testings started at ICU admission and were carried on throughout the ICU stay and extended in case of transfer to other units, when applicable. The marker expression in mean fluorescence intensity (MFI) and their kinetics with time were correlated to the clinical outcome. Results Patients with short hospital stay (≤15 days) and good outcome showed higher values of monocyte HLA-DR (median 17,478 MFI) than long hospital stay patients (>15 days, median 9590 MFI, p= 0.04) and than patients who died (median 5437 MFI, p= 0.05). In most cases, the recovery of the SARS-CoV2 infection-related signs was associated with the downregulation of monocyte CD169 within 17 days from disease onset. However in three surviving long hospital stay patients, a persistent upregulation of monocyte CD169 was observed. An increased neutrophil CD64 expression was found in two cases with a superimposed bacterial sepsis. Conclusion Monocyte CD169, neutrophil CD64, and monocyte HLA-DR expression can be used as predictive biomarkers of SARS-CoV2 outcome in acutely infected patients. The combined analysis of these indicators can offer a real-time evaluation of patients’ immune status and of viral disease progression versus superimposed bacterial infections. This approach allows to better define the patients’ clinical status and outcome and may be useful to guide clinicians’ decisions. Our study focused on the discrimination between the activity of viral and bacterial infections and on the detection of the development of anergic states that may correlate with an unfavorable prognosis.

Abstract Background Secukinumab has shown high efficacy in randomized controlled trials in both ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Here, we investigated its real-life effectiveness and tolerability in a cohort of AS and PsA patients. Methods We retrospectively analyzed medical records of outpatients with AS or PsA treated with secukinumab between December 2017 and December 2019. ASDAS-CRP and DAS28-CRP scores were used to measure axial and peripheral disease activity in AS and PsA, respectively. Data were collected at baseline and after 8, 24, and 52 weeks of treatment. Results Eighty-five adult patients with active disease (29 with AS and 56 with PsA; 23 males and 62 females) were treated. Overall, mean disease duration was 6.7 years and biologic-naïve patients were 85%. Significant reductions in ASDAS-CRP and DAS28-CRP were observed at all time-points. Body weight (in AS) and disease activity status at baseline (particularly in PsA) significantly affected disease activity changes. ASDAS-defined inactive disease and DAS28-defined remission were achieved in comparable proportions between AS and PsA patients, at both 24 weeks (45% and 46%) and 52 weeks (65.5% and 68%, respectively); male sex was found an independent predictor of positive response (OR 5.16, P = 0.027). After 52 weeks, achievement of at least low disease activity and drug retention were observed in 75% of patients. Secukinumab was well-tolerated and only mild injection-site reactions were recorded in 4 patients. Conclusion In a real-world setting, secukinumab confirmed great effectiveness and safety in both AS and PsA patients. The influence of gender on treatment response deserves further attention.

Abstract Background Psoriatic arthritis (PsA) is a chronic, immune-mediated, spondyloarthropathy characterised by musculoskeletal signs and symptoms with associated joint pain and tenderness. The average worldwide PsA prevalence is 133/100,000, while in the Italian population is 90–420/100,000. Traditionally, nonsteroidal anti-inflammatory drugs, glucocorticoid, and disease-modifying antirheumatic drugs have been used in the treatment of PsA. However, for those patients who are not adequately controlled with conventional therapies, the new biologics compounds represent a valid option. Biologic therapies have been shown to be more effective but also more expensive than conventional systemic treatments. Based on the CHRONOS study, the economic analyses presented in this paper aim to assess the annualised direct costs and the cost-per-responder of biologics in a real-world context assuming the Italian National Health System perspective. Methods The economic assessments were carried out on the overall cohort of patients, and on the tumour necrosis factor alpha inhibitors (TNFi) and the secukinumab subgroup, the most prescribed biologic therapies within the CHRONOS study. Results The annual economic impact of PsA in the overall group was €12,622, €11,725 in the secukinumab subgroup, and €12,791 in the TNFi subgroup. Biologics absorbed the main expenditure costs in the treatment of PsA accounting for about the 93% of total costs. At 6 months, secukinumab performed better in all the considered outcomes: cost-per-responder according to EULAR DAS28 and ACR50 response criteria were €12,661- €28,975, respectively, while they were €13,356 - €33,368 in the overall cohort and €13,138 - €35,166 in the TNFi subgroup. At 12 months secukinumab remained the subgroup with the lowest cost-per-responder ratio in EULAR DAS28 and ACR50 response criteria, while TNFi subgroup was the lowest one considered the ACR20. Conclusion Despite some potential methodological limitations, our cost-per-response analysis provides physicians and payers additional insights which can complement the traditional risk-benefit profile assessment and drive treatment decisions.

Abstract Background Biologics have demonstrated efficacy in PsA in randomized clinical trials. More evidence is needed on their effectiveness under real clinical practice conditions. The aim of the present work is to provide real-world evidence of the effectiveness of biologics for PsA in the daily clinical practice. Methods CHRONOS was a multicenter, non-interventional, cohort study conducted in 20 Italian hospital rheumatology clinics. Results 399 patients were eligible (56.9% females, mean (SD) age: 52.4 (11.6) years). The mean (SD) duration of PsA and psoriasis was 7.2 (6.9) and 15.3 (12.2) years, respectively. The mean (SD) duration of the biologic treatment under analysis was 18.6 (6.5) months. The most frequently prescribed biologic was secukinumab (40.4%), followed by adalimumab (17.8%) and etanercept (16.5%). The proportion of overall responders according to EULAR DAS28 criteria was 71.8% (95% CI: 66.7–76.8%) out of 308 patients at 6 months and 68.0% (95% CI: 62.7–73.3%) out of 297 patients at 1 year. Overall, ACR20/50/70 responses at 6 months were 41.2% (80/194), 29.4% (57/194), 17.1% (34/199) and at 1-year were 34.9% (66/189), 26.7% (51/191), 18.4% (36/196), respectively. Secondary outcome measures improved rapidly already at 6 months: mean (SD) PASI, available for 87 patients, decreased from 3.2 (5.1) to 0.6 (1.3), the proportion of patients with dactylitis from 23.6% (35/148) to 3.5% (5/142) and those with enthesitis from 33.3% (49/147) to 9.0% (12/133). Conclusions The CHRONOS study provides real-world evidence of the effectiveness of biologics in PsA in the Italian rheumatological practice, confirming the efficacy reported in RCTs across various outcome measures.

ObjectivesMonitoring of SARS-CoV-2 spread and vaccination strategies have relied on antibody (Ab) status as a correlate of protection. We used QuantiFERON™ (QFN) and Activation-Induced Marker (AIM) assays to measure memory T-cell reactivity in unvaccinated individuals with prior documented symptomatic infection (late convalescents) and fully vaccinated asymptomatic donors (vaccinees).MethodsTwenty-two convalescents and 13 vaccinees were enrolled. Serum anti-SARS-CoV-2 S1 and N Abs were measured using chemiluminescent immunoassays. QFN was performed following instructions and interferon-gamma (IFN-γ) measured by ELISA. AIM was performed on aliquots of antigen-stimulated samples from QFN tubes. SARS-CoV-2-specific memory CD4+CD25+CD134+, CD4+CD69+CD137+ and CD8+CD69+CD137+ T-cell frequencies were measured by flow cytometry.ResultsIn convalescents, substantial agreement was observed between QFN and AIM assays. IFN-γ concentrations and AIM+ (CD69+CD137+) CD4+ T-cell frequencies correlated with each other, with Ab levels and AIM+ CD8+ T-cell frequencies, whereas AIM+ (CD25+CD134+) CD4+ T-cell frequencies correlated with age. AIM+ CD4+ T-cell frequencies increased with time since infection, whereas AIM+ CD8+ T-cell expansion was greater after recent reinfection. QFN-reactivity and anti-S1 titers were lower, whereas anti-N titers were higher, and no statistical difference in AIM-reactivity and Ab positivity emerged compared to vaccinees.ConclusionsAlbeit on a limited sample size, we confirm that coordinated, cellular and humoral responses are detectable in convalescents up to 2 years after prior infection. Combining QFN with AIM may enhance detection of naturally acquired memory responses and help stratify virus-exposed individuals in T helper 1-type (TH1)-reactive (QFNpos AIMpos Abshigh), non-TH1-reactive (QFNneg AIMpos Abshigh/low), and pauci-reactive (QFNneg AIMneg Abslow).

Abstract Background Superior Vena Cava (SVC) syndrome, is a quite rare but serious complication after pacemaker lead implantation; most patients are asymptomatic due to the development of adequate venous collateral circulation. Case presentation We report a case of a 75-year-old woman who developed SVC syndrome after transvenous pacemaker implantation with complete resolution of the thrombosis after 3 months of oral anticoagulation. Conclusions Generally other causes as malignancy are considered to be the most common etiology of SVC syndrome, but benign iatrogenic causes, mainly intravascular devices (central vein catheters, cardiac defibrillators and pacemaker wires), are becoming increasingly common. Procedures performed on venous vasculature, causing a possible intimal injury or vein stenosis, provoked by transvenous leads, seem to be the most reasonable explanation for the observed complication.

Objective: To address the lack of information about clinical sequelae of coronavirus disease 2019 (COVID-19). Patients and Methods: Previously hospitalized COVID-19 patients who were attending the outpatient clinic for post–COVID-19 patients (ASST Ovest Milanese, Magenta, Italy) were included in this retrospective study. They underwent blood draw for complete blood count, C-reactive protein, ferritin, D-dimer, and arterial blood gas analysis and chest high-resolution computed tomography (HRCT) scan. The primary endpoint was the assessment of blood gas exchanges after 3 months. Other endpoints included the assessment of symptoms and chest HRCT scan abnormalities and changes in inflammatory biomarkers after 3 months from hospital admission. Results: Eighty-eight patients (n = 65 men; 73.9%) were included. Admission arterial blood gas analysis showed hypoxia and hypocapnia and an arterial partial pressure of oxygen/fractional inspired oxygen ratio of 271.4 (interquartile range [IQR]: 238-304.7) mm Hg that greatly improved after 3 months (426.19 [IQR: 395.2-461.9] mm Hg, P

Abstract Background Differential diagnosis of interstitial lung diseases (ILDs) during the COVID-19 pandemic is difficult, due to similarities in clinical and radiological presentation between COVID-19 and other ILDs on the one hand, and frequent false-negative swab results on the other. We describe a rare form of interstitial and organizing pneumonia resembling COVID-19, emphasizing some key aspects to focus on to get the right diagnosis and treat the patient properly. Case presentation A 76-year-old man presented with short breath and dry cough in the midst of the COVID-19 outbreak. He showed bilateral crackles and interstitial-alveolar opacities on X-ray, corresponding on computed tomography (CT) to extensive consolidations with air bronchograms, surrounded by ground glass opacities (GGO). Although his throat-and-nasopharyngeal swab tested negative, the picture was overall compatible with COVID-19. On the other hand, he showed subacute, rather than hyperacute, clinical onset; few and stable parenchymal consolidations, rather than patchy and rapidly evolving GGO; pleural and pericardial thickening, pleural effusion, and lymph node enlargement, usually absent in COVID-19; and peripheral eosinophilia, rather than lymphopenia, suggestive of hypersensitivity. In the past year, he had been taking amiodarone for a history of ventricular ectopic beats. CT scans, in fact, highlighted hyperattenuation areas suggestive of amiodarone pulmonary accumulation and toxicity. Bronchoalveolar lavage fluid (BALF) investigation confirmed the absence of coronavirus genome in the lower respiratory tract; conversely, high numbers of foamy macrophages, eosinophils, and cytotoxic T lymphocytes with low CD4/CD8 T-cell ratio were detected, confirming the hypothesis of amiodarone-induced cryptogenic organizing pneumonia. Timely discontinuation of amiodarone and initiation of steroid therapy led to resolution of respiratory symptoms, systemic inflammation, and radiographic opacities. Conclusions A comprehensive analysis of medical and pharmacological history, clinical onset, radiologic details, and peripheral and BALF cellularity, is required for a correct differential diagnosis and management of ILDs in the COVID-19 era.

Abstract Background The burden of cardiovascular (CV) complications in patients hospitalised for community-acquired pneumonia (CAP) is still uncertain. Available studies used different designs and different criteria to define CV complications. We assessed the cumulative incidence of acute of CV complications during hospitalisation for CAP in Internal Medicine Units (IMUs). Methods This was a prospective study carried out in 26 IMUs, enrolling patients consecutively hospitalised for CAP. Defined CV complications were: newly diagnosed heart failure, acute coronary syndrome, new onset of supraventricular or ventricular arrhythmias, new onset hemorrhagic or ischemic stroke or transient ischemic attack. Outcome measures were: in-hospital and 30-day mortality, length of hospital stay and rate of 30-day re-hospitalisation. Results A total of 1266 patients were enrolled, of these 23.8% experienced at least a CV event, the majority (15.5%) represented by newly diagnosed decompensated heart failure, and 75% occurring within 3 days. Female gender, a history of CV disease, and more severe pneumonia were predictors of CV events. In-hospital (12.2% vs 4.7%, p

Rheumatoid arthritis (RA) is a systemic inflammatory disease, which primarily causes symmetric polyarthritis. An extrarticolar involvement is common, and the commonly involved organ is lungs. Although cardiac disease is responsible for most RA-related deaths, pulmonary disease is also a major contributor, accounting for ~10–20% of all mortality. Pulmonary disease is a common (60–80% of patients with RA) extra-articular complication of RA. Optimal screening, diagnostic, and treatment strategies of pulmonary disease remain uncertain, which have been the focus of an ongoing investigation. Clinicians should regularly assess patients with RA for the signs and symptoms of pulmonary disease and, reciprocally, consider RA and other connective tissue diseases when evaluating a patient with pulmonary disease of an unknown etiology. RA directly affects all anatomic compartments of the thorax, including the lung parenchyma, large and small airways, pleura, and less commonly vessels. In addition, pulmonary infection and drug-induced lung disease associated with immunosuppressive agents used for the treatment of RA may occur.

Acting on the cytokine cascade is key to preventing disease progression and death in hospitalised patients with COVID-19. Among anti-cytokine therapies, interleukin (IL)-6 inhibitors have been the most used and studied since the beginning of the pandemic. Going through previous observational studies, subsequent randomised controlled trials, and meta-analyses, we focused on the baseline characteristics of the patients recruited, identifying the most favourable features in the light of positive or negative study outcomes; taking into account the biological significance and predictivity of IL-6 and other biomarkers according to specific thresholds, we ultimately attempted to delineate precise windows for therapeutic intervention. By stimulating scavenger macrophages and T-cell responsivity, IL-6 seems protective against viral replication during asymptomatic infection; still protective on early tissue damage by modulating the release of granzymes and lymphokines in mild-moderate disease; importantly pathogenic in severe disease by inducing the proinflammatory activation of immune and endothelial cells (through trans-signalling and trans-presentation); and again protective in critical disease by exerting homeostatic roles for tissue repair (through cis-signalling), while IL-1 still drives hyperinflammation. IL-6 inhibitors, particularly anti-IL-6R monoclonal antibodies (e.g., tocilizumab, sarilumab), are effective in severe disease, characterised by baseline IL-6 concentrations ranging from 35 to 90 ng/mL (reached in the circulation within 6 days of hospital admission), a ratio of partial pressure arterial oxygen (PaO2) and fraction of inspired oxygen (FiO2) between 100 and 200 mmHg, requirement of high-flow oxygen or non-invasive ventilation, C-reactive protein levels between 120 and 160 mg/L, ferritin levels between 800 and 1600 ng/mL, D-dimer levels between 750 and 3000 ng/mL, and lactate dehydrogenase levels between 350 and 500 U/L. Granulocyte-macrophage colony-stimulating factor inhibitors might have similar windows of opportunity but different age preferences compared to IL-6 inhibitors (over or under 70 years old, respectively). Janus kinase inhibitors (e.g., baricitinib) may also be effective in moderate disease, whereas IL-1 inhibitors (e.g., anakinra) may also be effective in critical disease. Correct use of biologics based on therapeutic windows is essential for successful outcomes and could inform future new trials with more appropriate recruiting criteria.

Background Venous 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. Methods We 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. Results 257 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, PaO2/FiO2, 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). Conclusions UEDVT 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.

Background: in the current pandemic emergency, increased attention has given to treating symptoms that cause suffering in patients with COVID-19. This study aims to describe the role of palliative care in the management of these patients. Methods: palliative consultation was requested by the staff as per protocol. In brief, the criteria for referring patients to a palliative care physician or to undergo palliative care were left to the discretion of the physician in charge. We recorded data regarding age, gender, length of stay, type of discharge (dead or alive, and transfer to long-term or hospice facilities). Results: Between March 18 to May 8, 2020, 412 patients with COVID-19 were admitted to the Internal Medicine wards of Magenta Hospital, Italy. The palliative care physician was directly involved in 105 cases (25.5%) and performed 236 consultations. Of the 105 patients who received palliative care counselling, 66 (63%) died. The average number of days in care was 2.26 days. The principal reason for counseling was controlling symptoms (54%) and 12% deal with the end of life management. The prevalent symptom, among those which led to the counseling, was restlessness/agitation (41%), followed by emotional issues (26%) such as anxiety, fear, and demoralization. In only 20% of cases, dyspnoea was the reason for symptomatic treatment. Conclusions: A large number of hospitalized Covid-19 patients are at high risk of clinical deterioration and death. This leads to the opportunity to integrate a palliative physician into the staff, who treat these patients. There is an urgent need for protocol standardization and formal trials to verify the effectiveness of this approach.

18-F-fluorodeoxyglucose positron emission tomography/computed tomography (18-FDG-PET/CT) is a functional imaging technique which is an established tool in oncology, and has also demonstrated a role in the field of inflammatory diseases, such as large vessel vasculitis (LVV). In the last few years, it is known that atherosclerotic lesions with inflammation, detected by FDG-PET, are high-risk structural features and more likely to lead to subsequent progression of atherosclerosis with more clinical complications.

Immune checkpoint inhibitors (ICIs) targeting cytotoxic Tlymphocyte associated protein-4 (CTLA-4), programmed cell death protein-1 (PD-1), and its ligand PD-L1 are established cancer immunotherapies for solid tumor and hematologic malignancies. These therapies are involved in immune-related adverse events (irAE), both general and rheumatic ones. In general, immune- related adverse events (irAE) management includes drugholding, tapering doses of corticosteroids, and specific immunosuppression for clinically severe cases, such as infliximab or mycophenolate.

Paget disease (PD) is a chronic disorder resulting in enlarged and misshapen bones, caused by disorganized bone remodeling. This case involves a 64-year-old man with prostatic adenocarcinoma and PD of some skeletal areas with increased uptake shown on 18 F-fluoro-methyl-choline (FMC) positron emission tomography/ computed tomography (PET/CT) performed for cancer restaging. Besides this feature, Paget disease may mimic metastases on PET/CT using various radiotracers, including 18 F-FMC PET/CT. In particular, this case highlights the potential of multiparametric disease characterization on PET. Therefore, in suspected cases, in which differential diagnosis is difficult, histology can be a helpful tool for diagnostic purposes.

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The bone marrow edema syndrome (BMES) is a severely disabling pain syndrome without a definite treatment and refers to transient clinical conditions with unknown pathogenic mechanism, such as transient osteoporosis of the hip, regional migratory osteoporosis, and reflex sympathetic dystrophy. Magnetic resonance imaging is used for early diagnosis and monitoring of its progression. Early differentiation from other aggressive conditions with longterm sequelae is essential in order to avoid unnecessary treatment. The aim of this monocentric trial was to test the efficacy and the safety of amino-bisphosphonate neridronate administered in two different regimens in patients with BMES. 192 patients with BMES secondary to osteoarthritis localized in the knee, hip, wrist or foot were randomly assigned to intravenous (iv) infusion of 100 mg neridronate given four times over 10 days (Group A, 72 subjects) or alternatively to iv infusions of 100 mg every 21 days over 3 months (Group B, 120 subjects). Magnetic resonance image (MRI) was performed at baseline and after 180 days. We assessed a 0-100 mm pain visual analogue scale (VAS) in each patient, too. Outcomes were MRI changes and VAS changes. A control group (35 patients) was enrolled too, treated conservatively with non-steroidal anti-inflammatory drugs and articular rest. We observed a significant improvement in MRI with the resolution of bone marrow lesions present at the baseline (P0.1). Both groups showed a significant clinical and radiologic improvement compared with the control group (P

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.

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.

Background: Most studies on SARS-CoV-2 infection show that people who have recovered from COVID-19 have antibodies to the virus. No study has evaluated whether the presence of antibodies to SARS-CoV-2 confers immunity to the infection relapse but however, to date, no human reinfections with SARS-CoV-2 have been confirmed. Material and methods: In our prospective, multicenter, cohort study we investigated within three months all patients, with confirmed COVID-19, discharged from two Hospitals (Legnano and Magenta Hospitals), in an area of Italy severely affected by the infection. Telephone follow-up at 1 and 2 months and clinical contact within 3 months was initiated; demographic, clinical, radiologic and laboratory data were recorded in electronic medical records and updated. Results: Of 1081 patients involved, 804 (74.3%) were discharged alive. For all these patients we obtained follow-up data. At 1 and 2 months none has died and none has had any signs of recurrence of infectious at both telephone interview and clinical visit. Conclusion: Our clinical observation have confirmed two basic points: the reinfection is very unlikely and any antibody immunity protects against recurrence, at least in the short term.

Good’s syndrome (GS) or thymomaassociated immunodeficiency is a rare clinical entity that should be ruled out in patients with thymoma who develop severe, recurrent bacterial infections and opportunistic viral and fungal infections. There are no treatment protocols established, hence, early recognition is imperative to avoid complications. We report the case of a 42-year-old female, known for a previous thymectomy for giant thymoma who has suffered for a long time from recurrent pulmonary and urinary tract infections and cold sores. In March 2016 she referred to our unit complaining of fever, cough, chest pain, and cold sores due to Herpes simplex virus (HSV), confirmed serologically as HSV-1. Chest X-ray showed left pneumonia due to Streptococcus pneumoniae. She started antibiotics (amoxicillin/clavulanic acid associated with azithromycin) with gradual improvement. Given her history she was studied for an underlying immunodeficiency: IgG, IgA, and IgM were significantly low or absent, as well as all IgG subclasses; blood and bone marrow aspirate leucocyte immunophenotyping showed complete absence of B lymphocytes and reduced CD4+ T cells. In light of: i) thymoma; ii) B lymphocyte deficit; iii) hypogammaglobulinemia; iv) recurrent infections, GS was diagnosed and pre-emptive immunoglobulin treatment, associated with HSV and Pneumocystis jiroveci prophylaxis (Acyclovir for HSV and Sulfamethoxazole- Trimethoprim for P. jiroveci) were started. Since then the patient has no longer presented any infectious episodes.

BackgroundRecently we defined a user-friendly tool (FADOI-COMPLIMED scores-FCS) to assess complexity of patients hospitalized in medical wards. FCS-1 is an average between the Barthel Index and the Exton-Smith score, while FCS-2 is obtained by using the Charlson score. The aim of this paper is to assess the ability of the FCS to predict mortality in-hospital and after 1-3-6-12-months. In this perspective, we performed comparisons with the validated Multidimensional Prognostic Index (MPI).MethodsIt is a multicenter, prospective observational study, enrolling patients aged over 40, suffering from at least two chronic diseases and consecutively admitted to Internal Medicine departments. For each patient, data from 13 questionnaires were collected. Survival follow-up was conducted at 1-3-6-12 months after discharge. The relationships between cumulative incidences of death with FCS were investigated with logistic regression analyses. ROC curve analyses were performed in order to compare the predictiveness of the logistic models based on FCS with respect to those with MPI taken as reference.ResultsA cohort of 541 patients was evaluated. A 10-point higher value for FCS-1 and FCS-2 leads to an increased risk of 1-year death equal to 25.0% and 27.1%, respectively. In case of in-hospital mortality, the relevant percentages were 63.1% and 15.3%. The logistic model based on FCS is significantly more predictive than the model based on MPI (which requires an almost doubled number of items) for all the time-points considered.ConclusionsAssessment of prognosis of patients has the potential to guide clinical decision-making and lead to better care. We propose a new, efficient and easy-to-use instrument based on FCS, which demonstrated a good predictive power for mortality in patients hospitalized in medical wards. This tool may be of interest for clinical practice, since it well balances feasibility (requiring the compilation of 34 items, taking around 10 minutes) and performance.

An amendment to this paper has been published and can be accessed via the original article.

Improved care for acute diseases has increased mean age and the proportion of people affected by multiple chronic diseases, while mutated socioeconomic conditions augmented the number of elderly and socially frail subjects. Multi-morbid patients who require a global approach not-fragmented-care interventions and a close connection between health and social services are progressively growing. Acute Complex Care Model (ACCM) is a model of integrated management of the frail patients when they need acute hospital care. The name of our model - ACCM - just recalls the chronic care model (CCM), designed for the de-hospitalization of chronic patients by preventing acute exacerbations, representing the hospital counterpart of the CCM. The target population is made up of acutely ill complex and poly-pathological patients (AICPPs), admitted to hospital and requiring high technological resources and continuous monitoring; the mission is to improve the management of medical admissions through pre-defined intra-hospital tracks and a global, multidisciplinary, patient-centered approach. Nowadays, multiple uncoordinated specialists care for AICPPs who move from one ward to another, with dangerous loss of information and continuity. ACCM tries to overcome these problems by putting the internal medicine specialist as the only referent for that patient and the coordinator of the care team. According to a model of future hospital organized with different intensity settings, the Internal Medicine Wards, caring for AICPPS, are organized in High Dependency Areas and Ordinary Areas. For both we present organizational and personnel standards that are lacking in daily practice. The epidemiological transition leading to a progressive increase in AICPPs requiring frequent hospitalization enhances the role of hospital internal medicine specialist in the coordination and delivery of care. The ACCM represents a practical response to this epochal change of roles. Medical and nursing staff standards and competencies have to be reviewed to ensure adequate care for these patients.

The Schnitzler syndrome (SCS) is a rare, late-onset acquired autoinflammatory syndrome often underdiagnosed. The diagnosis is based on the Lipsker and recently on validated Strasbourg diagnostic criteria (chronic urticarial rash, monoclonal gammopathy, intermittent fever, arthritis, arthralgia, bone involvement, hepatomegaly, splenomegaly, lymphadenopathy, dermal infiltration of neutrophils and laboratory markers of inflammation). Conventional therapies including anti-histamines, anti-inflammatory drugs, corticosteroids and immunosuppressive drugs that are usually ineffective. Recently the gold standard therapy of SCS are considered IL-1 blocking agents as anakinra, canakinumab, rilonacept that led to a significant control of clinical symptoms, even if a relapse could appear at suspension of the treatment. We report a case of a 63-year-old man with a recent diagnosis of SCS - after 6 years of symptoms of disease - refractory to several conventional immunosuppressive therapies and treated with anakinra, with sustained remission of clinic manifestations during treatment at 24 months of follow up.

The complex patient, who has often multiple, chronic and progressive disorders, who has undergone polytherapy, should be evaluated totally with respect not only to medical side, but also to psychological and clinical side. The shortage of specialists in disciplines that require technical skills, obtained by training and performing a sufficient number of annual procedures, contributes to the need for reorganizing health care; in this background the Internist devolves less time to charitable activities in favor of competences related to the processes. The knowledge of the clinical governance (CG) should be the common heritage of all the actors of the health system, that need to be made up of professionals able to coordinate and make easy the implementation and the spread the CG culture. At least initially we propose to focus the testing strictly on the medical department. As already mentioned above, the natural Internist predisposition, cultural and training, leads him to a multidisciplinary vision of medicine that allows acquiring more easily the tools that make up the structure of CG, being able to facilitate the application. The acquisitions of professional competence and clinical governance play a key role in the Internist culture. The purpose of an Internist with professional skills and managerial capacity, is to act within the department to facilitate and simplify the horizontal interaction among other similar corporate structures and to help the Management to improve structural and clinical appropriateness in Hospital and to better the relations between hospital and territory, identifying the critical issues and the possible solutions.

Capillaroscopy is an actual inexpensive imaging technique, used to examine, non-invasively and safely, the morphology of nailfold dermal papillary capillaries. Many studies agree in the statement that the capillaroscopy is one of the gold standard methods for non-invasive examination of the microcirculation and it plays an important role in screening in Raynaud’s phenomenon and in monitoring of systemic sclerosis and other rheumatologic diseases. There are also many reports on the possible use of nailfold capillaroscopy in the diagnosis and monitoring of many other diseases in internal medicine.

Amplification in health expectations, increase in new technologies, decrease in economic resources and the breakdown of traditional control systems have led to the development of clinical governance (CG). The aim of the present pilot study was to investigate the application of CG tools in significant sample of Italian internal medicine wards (IMW). A 37-item questionnaire was developed and administered to 39 physicians, within 33 IMWs throughout Italy. Thanks to the data analysis, the perceived usefulness, the utilization rate of CG tools, the correlations between CG use, wards characteristics, and/or localization were studied. We identified at what organizational level the CG tools were applied and used. fifty-two percent of the studied tools were being used in the investigated hospitals. The average utility and utilization rate was different depending on the region of provenance. This research showed that CG is a methodology often used by Italian hospitals physicians, especially for inpatient care. The encouraging results of this pilot study could suggest opportunities to extend the survey at national level, to generalize the results.

Currently we observe a gap between theory and practices of patient engagement. If both scholars and health practitioners do agree on the urgency to realize patient engagement, no shared guidelines exist so far to orient clinical practice. Despite a supportive policy context, progress to achieve greater patient engagement is patchy and slow and often concentrated at the level of policy regulation without dialoguing with practitioners from the clinical field as well as patients and families. Though individual clinicians, care teams and health organizations may be interested and deeply committed to engage patients and family members in the medical course, they may lack clarity about how to achieve this goal. This contributes to a wide “system” inertia—really difficult to be overcome—and put at risk any form of innovation in this filed. As a result, patient engagement risk today to be a buzz words, rather than a real guidance for practice. To make the field clearer, we promoted an Italian Consensus Conference on Patient Engagement (ICCPE) in order to set the ground for drafting recommendations for the provision of effective patient engagement interventions. The ICCPE will conclude in June 2017. This document reports on the preliminary phases of this process. In the paper, we advise the importance of “fertilizing a patient engagement ecosystem”: an oversimplifying approach to patient engagement promotion appears the result of a common illusion. Patient “disengagement” is a symptom that needs a more holistic and complex approach to solve its underlined causes. Preliminary principles to promote a patient engagement ecosystem are provided in the paper.

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.

Introduction: Iloprost is a potent prostacyclin (PGI2) analogue that is effective in the treatment of peripheral arterial disease, vasculitis, pulmonary hypertension, and secondary Raynaud’s phenomenon. Intravenous infusions are generally administered with the aid of a peristaltic pump to reduce the risk of adverse reactions caused by unintentional increases in the infusion rate. This increases the cost of care in terms of equipment and personnel and may limit the use of this drug. Materials and methods: We retrospectively analyzed 18,432 iloprost infusions administered between 1999 and 2009 to 272 patients with systemic sclerosis (n = 253) and 19 with peripheral arterial disease (n = 19). All infusions were administered in the day hospital over 6 h with a normal IV set-up with a roller flow regulator. Flow rates were set to deliver iloprost at 1-2 ng/kg/min. Rates were verified by direct drop counts during the first 15-20 minutes of the infusion and at each subsequent check. Results: There were no adverse events that were fatal, life-threatening, or associated with prolongation of hospitalization and very few events requiring intensive care or continuous monitoring. The latter included 4 cases of tachycardia/arrhythmia (extrasystoles in most cases), 3 cases of hypotension (systolic pressure < 80 mmHg), and 2 cases of hypertension (BP > 170/100 mmHg). All other adverse reactions were mild, reversible, and similar to those seen with iloprost infusion with peristaltic pump. Only one patient had to be switched to another prostanoid (due to intolerance). Discussion: Iloprost infusion administered with a normal IV flow regulator appears to be as safe, well tolerated, and effective as traditional infusion with a peristaltic pump.

Background: Though venous thromboembolism (VTE) frequently occurs in non-surgical setting, epidemiology and risk factors for VTE in unselected medical inpatients have not been extensively studied, and uncertainties remain about the prophylactic strategy in these patients. Materials and methods: In a prospective, observational, multicenter study we aimed to contemporarily assess the epidemiology of symptomatic VTE in consecutive patients hospitalized in Internal Medicine, to evaluate the impact of potential risk factors, and the attitude of internists towards thromboprophylaxis. A total of 4,846 patients were included, during the period March-September 2006. Results: Symptomatic VTE was registered in 177 (3.65%) patients; of these, 26 cases (0.55%) occurred with onset of symptoms > 48 hours after admission (‘‘hospital-acquired’’ events, primary study end-point). Previous VTE and bed resting were significantly associated with venous thromboembolism, while a trend for increased risk was documented in cancer patients. During hospital stay antithrombotic prophylaxis was globally administered in 41.6% of patients, and in 58.4% of those for which prophylaxis was recommended according to 2004 guidelines by the American College of Chest Physicians. The choice of administering tromboprophylaxis appeared qualitatively adherent to indications from randomized trials and international guidelines, and bed rest was the strongest determinant of the use of prophylaxis. Conclusions: Data from our real-world study confirm that VTE is a quite common finding in patients admitted to Internal Medicine departments, and recommended tromboprophylaxis is still underused, in particular in some patients groups. Further efforts are needed to better define the risk profile and to optimize prophylaxis in the heterogeneous setting of medical patients.

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.

All countries are facing the question of how to maintain quality of care with shrinking health budgets, in the presence of a persistent increase in life expectancy, and with a significant growing demand for health care from aging populations and chronically ill patients. Current implementation of legislative measures is largely presented as a cost-cutting policy. With this political approach, there is a risk of services and the number of hospital beds being drastically reduced, mainly to detriment of the most vulnerable groups of the population and without considering the results obtained by each regional healthcare organization according to explicit evaluation markers. In our Scientific Society of Internal Medicine (the Federation of Associations of Hospital Doctors on Internal Medicine, FADOI), we want to support good medical practice because essential medicine is still a goal to be achieved throughout medical hospital care. We are looking for original ways to implement a sustainable and frugal hospital Internal Medicine policy by searching for wise and efficient clinical methodology to be applied in the care of patients admitted to internal medicine wards according to their real needs. We firmly believe that reinforcing a common agenda between medicine and public health, and sharing a common vision among professionals and decision makers in the planning of care, may be the greatest opportunity for any every health care reform. The future of the health care system cannot be restricted to mere cost reduction, but should aim to deliver better health care in relation to the money spent. Even in this period of austerity, new opportunities can still be found and doctors must lead efforts to meet this challenge.

Introduction: Several studies show that physical activity can reduce the risk of cardiovascular disease, but the vast majority of these focus on the short- to intermediate-term benefits or refer to very specific populations. This observational study was conducted to determine whether physical activity performed during the third or fourth decade of life influences the occurrence of cardiovascular events in patients aged 65-75 years. Materials and methods: We studied a cohort of 2191 unselected patients admitted to Internal Medicine Departments. Data were collected on the patients’ medical history and their physical activity level when they were 20 to 40 years old. For the latter purpose, we used a specific questionnaire to assess the levels of physical activity related to the patients’ job, daily life, leisure time, and sports. Results: Almost half (44.2%) of the patients we evaluated reported moderate-intense physical activity when they were 20-40 years old. Around one third (35.8%) of the patients had experienced at least one major cardiovascular event, and there was a slight trend towards fewer cardiovascular events in patients with histories of physical activity (mean risk reduction: 4%, multivariate analysis). More evident benefits were observed in the subgroup of patients with diabetes, where cardiovascular outcomes were much better in patients who had been physically active than in those with sedentary life-styles (mean risk reduction: 24%). Conclusions: Given its design, our study may have underestimated the cardiovascular benefits of physical activity. Nonetheless, our results suggest that moderate-intense exercise during young adulthood may have limited beneficial effects on cardiovascular disease in old age, except in specific high-risk populations (diabetic patients). More evident benefits are probably associated with regular physical activity throughout life.

Introduction: There are few data on the prevalence of depression among acute patients with comorbidities. The current study aimed to determine the prevalence of depressive symptoms in hospitalized patients admitted to Internal Medicine Units and the correlation between these symptoms and comorbidities and disability indexes. Materials and methods: All consecutive patients admitted to 26 Internal Medicine Units of the Italian National Public Health System in Sicily, Italy, from September 2001 to March 2002 were screened. Within 24 hours of admission, patients were administered the Geriatric Depression Scale (GDS), Mini-Mental State Examination, Activities of Daily Living (ADL), Instrumental Activities of Daily Living (IADL) and Charlson’s Comorbidity Index. Results: 1,947 subjects were included in the analyses. Of the patients, 509 (26.1%) showed depressive symptoms (indicated by GDS score > 15). Depression was significantly associated (univariate analyses) with hypertension (OR 1.45; CI 95% 1.18-1.79), diabetes (OR 1.48, CI 95% 1.17-1.87), cerebrovascular disease (OR 1.50, CI 95% 1.08-2.07), cirrhosis (OR 1.49, CI 95% 1.01- 2.19), ADL score (OR 0.72: CI 95% 0.63-0.82), and IADL score (OR 0.83; CI 95% 0.78-0.87), but not with Charlson’s Comorbidity Index (OR 1.04; CI 95% 0.98-1.10). Multivariate analysis showed that independent predictive factors for depression were age (OR 1.02, CI 95% 1.01-1.02), female gender (OR 2.29, CI 95% 1.83 - 2.87), and IADL score (OR 0.86, CI 95% 0.81 - 0.93). Conclusions: The data suggest that depressive symptoms are not linked to worse clinical conditions but are associated with the loss of autonomy in Instrumental Activities of Daily Living.

IntroductionThe extreme variability of clinical severity in medical admitted patients is diluted in a “average” standard of care, that may be stronger than the real needs for someone, but clearly inadequate, sometimes even dangerous, for other ones, critically ill.DiscussionThe model of a differentiated intensity of hospital care can be defined as the organizational model structured to areas/sectors dedicated to patients with homogeneous needs of care. The intermediate care unit (“High dependency units”, “sub-intensive care areas” – “high care units”) are particularly suitable for patients who have a lower risk compared to patients treated in intensive care, but liable to develop complications and needing a close monitoring much more than the “standard”, “routine” care. The implementation of the a new organizational model must be careful and consider the possible enlargement errors that can be made. The analysis of the context is necessary for assess prerequisites, excluding the elements opposed to the success of the proposed model (i.e.: wards congestion and overcrowding, with a consequential with increased risk of adverse events). Before implementing and admitting patients in new “models”, we have to define the epidemiological population characteristics, their level of complexity/criticality/instability and the current assessment tools.ConclusionsAny new proposal of hospital management change has, as first obligation, to explicit the basic visions and primary goals for “the added value” resulting to the patient and the whole organization, with the evidence of an “health technology assessment” approach, for the professional hospital overall governance. But without the presumption, or worse, the apodictic assertion, to proclaim the implementation of structures with “differentiated intensity of hospital care” organizations that are not.

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Background Iloprost, prostacyclin (PGI2) analogue, effective in treatment of peripheral arterial disease, secondary Raynaud's phenomenon (RP) to connective tissue disease (CTD), vasculitis, pulmonary hypertension, is usually infused through peristaltic pump, or recently through a flow regulator.Materials and methods We tested a new portable syringe pump (Pompa Infonde®, Italfarmaco S.p.A., Cinisello Balsamo, Milano) on 120 patients affected by RP to CTD and cryoglobulinaemia, in iloprost therapy with a flow regulator.Results Iloprost infused through portable syringe pump is better tolerated, better appreciated by the patients and nurses and no difference was observed on therapeutic effects, with a lower incidence of side effects statistically significant. Only 3 patients were unable to tolerate the device (2 for changes in pressure and 1 for fear) and shifted to traditional method of iloprost infusion.Conclusions Iloprost infusion through the portable syringe Pompa Infonde® appears to be safe, better tolerated, more acceptable and equally effective compared to infusion through a flow regulator.