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1. Asymptomatic and symptomatic deep venous thrombosis in hospitalized acutely ill medical patients: risk factors and therapeutic implications

Author: Lorenzo Loffredo, Gianpaolo Vidili, Angela Sciacqua, Chiara Cogliati, Rosella Di Giulio, Sciaila Bernardini, Paolo Ciacci, Antonello Pietrangelo, Federica Orlando, Aurora Paraninfi, Maria Boddi, Giovanni Di Minno, Lorenzo Falsetti, Corrado Lodigiani, Angelo Santoliquido, Evaristo Ettorre, Pasquale Pignatelli, Maria Felice Arezzo, Evghenii Gutu, Job Harenberg, Francesco Violi, and AURELIO Study Group
Subjects: Deep venous thrombosis, Asymptomatic deep venous thrombosis, Compression ultrasound, Anticoagulants, Medical patient, Diseases of the blood and blood-forming organs, RC633-647.5
Abstract: Abstract Background Acutely ill medical patients experience deep venous thrombosis (DVT) during the hospitalization, however the time course of DVT is still unclear. Objectives To evaluate risk factors in acutely ill hospitalized medical patients for proximal asymptomatic DVT (ADVT) and symptomatic DVT (SDVT) at admission and discharge. Patients/Methods In this prospective observational study, consecutive acutely ill medical patients (hospitalized mainly for acute medical disease as infections, neoplasm, anemia, heart failure) underwent compression ultrasonography (CUS) of proximal lower limb veins within 48 h from admission and at discharge to diagnose ADVT and SDVT. Covid-19 patients, anticoagulant therapy, surgical procedures, acute SDVT, and acute pulmonary embolism, were exclusion criteria. Biographical characteristics at hospitalization, D-Dimer (assessed by ELISA)) and DD-improve score. Results Of 2,100 patients (1002 females, 998 males, age 71 ± 16 years) 58 (2.7%) had proximal ADVT at admission. Logistic regression analysis showed that age, and active cancer were independently associated with ADVT at admission. The median length of hospitalization was 10 days [interquartile range: 6–15]. During the hospital stay, 6 patients (0.3%) with a negative CUS at admission experienced DVT (2 SDVT and 4 ADVT). In the subgroup of patients (n = 1118), in whom D-dimer was measured at admission, D-Dimer and IMPROVE-DD score were associated with ADVT at admission (n = 37) and with all DVT (n = 42) at discharge. ROC curve defined an IMPROVE-DD score of 2.5 as the optimal cut-off for discriminating patients with and without thrombotic events. Conclusions We provide evidence of early development of ADVT in unselected acutely ill medical patients suggesting the need of investigating patients by CUS immediately after hospital admission (within 48 h). Advanced age, active cancer, known thrombophilia and increased IMPROVE-DD score may identify patients at risk. The benefit of anticoagulation needs to be investigated in patients with these specific risk factors and negative CUS at admission. Trial registration NCT03157843.
Published: 2022
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2. Hepatic encephalopathy increases the risk for mortality and hospital readmission in decompensated cirrhotic patients: a prospective multicenter study

Author: Oliviero Riggio, Ciro Celsa, Vincenza Calvaruso, Manuela Merli, Paolo Caraceni, Sara Montagnese, Vincenzina Mora, Martina Milana, Giorgio Maria Saracco, Giovanni Raimondo, Antonio Benedetti, Patrizia Burra, Rodolfo Sacco, Marcello Persico, Filippo Schepis, Erica Villa, Antonio Colecchia, Stefano Fagiuoli, Mario Pirisi, Michele Barone, Francesco Azzaroli, Giorgio Soardo, Maurizio Russello, Filomena Morisco, Sara Labanca, Anna Ludovica Fracanzani, Antonello Pietrangelo, Gabriele Di Maria, Silvia Nardelli, Lorenzo Ridola, Antonio Gasbarrini, and Calogero Cammà
Subjects: hepatic encephalopathy, decompensated cirrhosis, orthotopic liver transplant, hospital readmission, mortality, Medicine (General), R5-920
Abstract: IntroductionHepatic encephalopathy (HE) affects the survival and quality of life of patients with cirrhosis. However, longitudinal data on the clinical course after hospitalization for HE are lacking. The aim was to estimate mortality and risk for hospital readmission of cirrhotic patients hospitalized for HE.MethodsWe prospectively enrolled 112 consecutive cirrhotic patients hospitalized for HE (HE group) at 25 Italian referral centers. A cohort of 256 patients hospitalized for decompensated cirrhosis without HE served as controls (no HE group). After hospitalization for HE, patients were followed-up for 12 months until death or liver transplant (LT).ResultsDuring follow-up, 34 patients (30.4%) died and 15 patients (13.4%) underwent LT in the HE group, while 60 patients (23.4%) died and 50 patients (19.5%) underwent LT in the no HE group. In the whole cohort, age (HR 1.03, 95% CI 1.01–1.06), HE (HR 1.67, 95% CI 1.08–2.56), ascites (HR 2.56, 95% CI 1.55–4.23), and sodium levels (HR 0.94, 95% CI 0.90–0.99) were significant risk factors for mortality. In the HE group, ascites (HR 5.07, 95% CI 1.39–18.49) and BMI (HR 0.86, 95% CI 0.75–0.98) were risk factors for mortality, and HE recurrence was the first cause of hospital readmission.ConclusionIn patients hospitalized for decompensated cirrhosis, HE is an independent risk factor for mortality and the most common cause of hospital readmission compared with other decompensation events. Patients hospitalized for HE should be evaluated as candidates for LT.
Published: 2023
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3. Challenges in diagnosis and management of acute hepatic porphyrias: from an uncommon pediatric onset to innovative treatments and perspectives

Author: Matteo Marcacci, Andrea Ricci, Chiara Cuoghi, Stefano Marchini, Antonello Pietrangelo, and Paolo Ventura
Subjects: Acute hepatic porphyria, Porphyrias, Givosiran, SiRNA, Neuropathy, Hereditary diseases, Medicine
Abstract: Abstract Acute hepatic porphyrias (AHPs) are a family of four rare genetic diseases resulting from a deficiency in one of the enzymes involved in heme biosynthesis. AHP patients can experience potentially life-threatening acute attacks, characterized by severe abdominal pain, along with other signs and symptoms including nausea, mental confusion, hyponatraemia, hypertension, tachycardia and muscle weakness. Some patients also experience chronic manifestations and long-term complications, such as chronic pain syndrome, neuropathy and porphyria-associated kidney disease. Most symptomatic patients have only a few attacks in their lifetime; nevertheless, some experience frequent attacks that result in ongoing symptoms and a significant negative impact on their quality of life (QoL). Initial diagnosis of AHP can be made with a test for urinary porphobilinogen, $$\delta$$ δ -aminolaevulinic acid and porphyrins using a single random (spot) sample. However, diagnosis is frequently missed or delayed, often for years, because the clinical symptoms of AHP are non-specific and mimic other more common disorders. Delayed diagnosis is of concern as some commonly used medications can trigger or exacerbate acute attacks, and untreated attacks can become severe, potentially leading to permanent neurological damage or fatality. Other attack triggers include hormonal fluctuations in women, stress, alcohol and low-calorie diets, which should be avoided in patients where possible. For the management of attacks, intravenous hemin is approved, whereas new therapeutic approaches are currently being investigated as a baseline therapy for prevention of attacks and improvement of QoL. Among these, a novel siRNA-based agent, givosiran, has shown very promising results in a recently concluded Phase III trial and has been approved for the management of AHPs. Here, we propose a challenging case study-with a very unusual pediatric onset of variegate porphyria-as a starting point to summarize the main clinical aspects (namely, clinical manifestations, diagnostic challenges, and therapeutic management) of AHPs, with a focus on the latest therapeutic innovations.
Published: 2022
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4. Long-term safety and erythroid response with luspatercept treatment in patients with β-thalassemia

Author: Antonio Piga, Filomena Longo, Maria Rita Gamberini, Ersi Voskaridou, Paolo Ricchi, Vincenzo Caruso, Antonello Pietrangelo, Xiaosha Zhang, Jeevan K. Shetty, Kenneth M. Attie, and Immacolata Tartaglione
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Abstract: Background: β-thalassemia is a hereditary blood disorder resulting in ineffective erythropoiesis and anemia. Management of anemia with regular blood transfusions is associated with complications including iron overload. Here, we report long-term safety and efficacy results of the first clinical study of luspatercept in β-thalassemia, initiated in 2013, enrolling adults with both nontransfusion-dependent (NTD) and transfusion-dependent (TD) β-thalassemia. Objectives: The objective was to report long-term safety data, for up to 5 years of treatment, for 64 patients with TD or NTD β-thalassemia, and long-term efficacy data for a subset of 63 patients with β-thalassemia who received high-dose luspatercept (0.6–1.25 mg/kg): 31 NTD and 32 TD patients. Design: The study was a phase 2, noncontrolled, open-label trial comprising a dose-finding base phase and a 5-year extension phase. Methods: Endpoints include safety; erythroid response over a continuous 12-week period [NTD: hemoglobin increase from baseline ⩾1.0 or ⩾1.5 g/dl; TD: red blood cell (RBC) transfusion burden reduction, ⩾20%, ⩾33%, or ⩾50%]; and changes in biomarkers of ineffective erythropoiesis, iron metabolism parameters, Functional Assessment of Chronic Illness Therapy – Fatigue (FACIT-F) scores, and 6-min walking distance. Results: Median duration of luspatercept exposure for NTD and TD patients was 910 days (range, 40–1850) and 433 days (range, 21–1790), respectively. Seventeen of 31 (54.8%) NTD patients achieved a mean hemoglobin increase of ⩾1.5 g/dl and 19 of 32 (59.4%) TD patients achieved ⩾50% reduction in RBC transfusion burden, during any continuous 12-week period. Median cumulative duration of response was 1126 days (range, 127–1790) for NTD patients and 909 days (range, 87–1734) for TD patients. The most common treatment-related adverse events of any grade were bone pain, headache, and myalgia. Conclusion: Long-term assessment of patients with β-thalassemia showed luspatercept was associated with sustained increases in hemoglobin levels in NTD patients and sustained transfusion burden reductions in TD patients. Trial registration: (ClinicalTrials.gov Identifiers: NCT01749540 and NCT02268409). Plain Language Summary Long-term safety and erythroid response with luspatercept treatment in patients with β-thalassemia Background: β-thalassemia is a genetic blood disorder caused by mutations in the β-globin gene, which encodes one of the proteins that comprise hemoglobin, a key constituent of red blood cells. Patients with β-thalassemia experience anemia, the main treatment for which is blood transfusions. Long-term repeated blood transfusions lower patients’ quality of life, use hospital resources, and the resulting accumulation of excess iron can cause organ failure and decrease life expectancy. The severity of the anemia experienced by patients with β-thalassemia varies; patients with transfusion-dependent β-thalassemia require regular blood transfusions, compared with those with nontransfusion-dependent β-thalassemia who require infrequent transfusions, or even none at all, to manage their symptoms. Luspatercept (Reblozyl ® ) is an agent that stimulates the production of red blood cells and is used to treat anemia caused by β-thalassemia. However, the long-term effects of luspatercept treatment on patients with β-thalassemia are not known. Objective: In this study, we report the long-term safety of luspatercept in 64 adult patients with either transfusion-dependent or nontransfusion-dependent β-thalassemia, and the long-term efficacy of high-dose luspatercept (0.6–1.25 mg/kg) in a subset of 63 patients. Results: The average time period that patients were treated with luspatercept was 910 days for nontransfusion-dependent β-thalassemia and 433 days for transfusion-dependent β-thalassemia. We report that in patients with nontransfusion-dependent β-thalassemia, luspatercept treatment was associated with sustained increases, just over 3 years, in hemoglobin levels. Likewise, in transfusion-dependent β-thalassemia, luspatercept treatment was associated with a sustained reduction, 2.5 years, in the amount of blood transfusion required to manage their anemia. Long-term treatment with luspatercept was not associated with any new side effects compared with previous short-term treatment studies. The most common side effects were headache (27 patients), bone pain (20 patients), and muscle pain (14 patients) with more than 90% of these patients experiencing these side effects as mild severity. Conclusion: The results of this study show that in patients with either transfusion-dependent or nontransfusion-dependent β-thalassemia, luspatercept provides lasting reduction in anemia with mostly mild and predictable side effects.
Published: 2022
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5. A Fatal Case of Pseudomonas aeruginosa Community-Acquired Pneumonia in an Immunocompetent Patient: Clinical and Molecular Characterization and Literature Review

Author: Nicole Barp, Matteo Marcacci, Emanuela Biagioni, Lucia Serio, Stefano Busani, Paolo Ventura, Erica Franceschini, Gabriella Orlando, Claudia Venturelli, Ilaria Menozzi, Martina Tambassi, Erika Scaltriti, Stefano Pongolini, Mario Sarti, Antonello Pietrangelo, Massimo Girardis, Cristina Mussini, and Marianna Meschiari
Subjects: community-acquired pneumonia, Pseudomonas aeruginosa, antibiotic therapy, whole genome sequencing, Biology (General), QH301-705.5
Abstract: Rare cases of Pseudomonas aeruginosa community-acquired pneumonia (PA-CAP) were reported in non-immunocompromised patients. We describe a case of Pseudomonas aeruginosa (PA) necrotizing cavitary CAP with a fatal outcome in a 53-year-old man previously infected with SARS-CoV-2, who was admitted for dyspnea, fever, cough, hemoptysis, acute respiratory failure and a right upper lobe opacification. Six hours after admission, despite effective antibiotic therapy, he experienced multi-organ failure and died. Autopsy confirmed necrotizing pneumonia with alveolar hemorrhage. Blood and bronchoalveolar lavage cultures were positive for PA serotype O:9 belonging to ST1184. The strain shares the same virulence factor profile with reference genome PA01. With the aim to better investigate the clinical and molecular characteristics of PA-CAP, we considered the literature of the last 13 years concerning this topic. The prevalence of hospitalized PA-CAP is about 4% and has a mortality rate of 33–66%. Smoking, alcohol abuse and contaminated fluid exposure were the recognized risk factors; most cases presented the same symptoms described above and needed intensive care. Co-infection of PA-influenza A is described, which is possibly caused by influenza-inducing respiratory epithelial cell dysfunction: the same pathophysiological mechanism could be assumed with SARS-CoV-2 infection. Considering the high rate of fatal outcomes, additional studies are needed to identify sources of infections and new risk factors, along with genetic and immunological features. Current CAP guidelines should be revised in light of these results.
Published: 2023
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6. Marked T cell activation, senescence, exhaustion and skewing towards TH17 in patients with COVID-19 pneumonia

Author: Sara De Biasi, Marianna Meschiari, Lara Gibellini, Caterina Bellinazzi, Rebecca Borella, Lucia Fidanza, Licia Gozzi, Anna Iannone, Domenico Lo Tartaro, Marco Mattioli, Annamaria Paolini, Marianna Menozzi, Jovana Milić, Giacomo Franceschi, Riccardo Fantini, Roberto Tonelli, Marco Sita, Mario Sarti, Tommaso Trenti, Lucio Brugioni, Luca Cicchetti, Fabio Facchinetti, Antonello Pietrangelo, Enrico Clini, Massimo Girardis, Giovanni Guaraldi, Cristina Mussini, and Andrea Cossarizza
Subjects: Science
Abstract: COVID-19 is a serious pandemic threat to public health, but insights on the pathophysiological and immunological conditions are only emerging. Here the authors use multi-color flow cytometry to characterize CD4+ and CD8+ T cells in peripheral blood from 39 COVID-19 patients in Italy to report altered T cell activation, function and polarization.
Published: 2020
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7. Idiopathic brain calcification in a patient with hereditary hemochromatosis

Author: Stefania Scarlini, Francesco Cavallieri, Massimo Fiorini, Elisa Menozzi, Francesca Ferrara, Francesca Cavalleri, Chiara Reale, Barbara Garavaglia, Antonello Pietrangelo, Franco Valzania, and Elena Corradini
Subjects: Basal ganglia, Brain calcification, Calcium, Hereditary hemochromatosis, Iron, Neurology. Diseases of the nervous system, RC346-429
Abstract: Abstract Background Detection of brain-MRI T2/T2* gradient echo images (T2*GRE)-hypointensity can be compatible with iron accumulation and leads to a differential diagnosis work-up including neurodegeneration with brain iron accumulation (NBIA) and Wilson Disease. Idiopathic or secondary brain calcification can be also associated with neurological involvement and brain-MRI T2/T2*GRE-hypointensity. Hereditary hemochromatosis (HH), characterized by systemic iron loading, usually does not involve the CNS, and only sporadic cases of neurological abnormalities or brain-MRI T2/T2*GRE-hypointensity have been reported. Case presentation A 59-year-old man came to our observation after a diagnosis of HH carried out in another hospital 2 years before. First-level genetic test had revealed a homozygous HFE p.Cys282Tyr (C282Y) mutation compatible with the diagnosis of HFE-related HH, thus phlebotomy treatment was started. The patient had a history of metabolic syndrome, type-2 diabetes, autoimmune thyroiditis and severe chondrocalcinosis. Brain-MRI showed the presence of bilateral T2*GRE hypointensities within globus pallidus, substantia nigra, dentate nucleus and left pulvinar that were considered expression of cerebral siderosis. No neurological symptoms or family history of neurological disease were reported. Neurological examination revealed only mild right-sided hypokinetic-rigid syndrome. Vitamin D–PTH axis, measurements of serum ceruloplasmin and copper, and urinary copper were within the normal range. A brain computed tomography (CT) was performed to better characterize the suspected and unexplained brain iron accumulation. On the CT images, the hypointense regions in the brain MRI were hyperdense. DNA sequence analysis of genes associated with primary familial brain calcification and NBIA was negative. Conclusions This report highlights the importance of brain CT-scan in ambiguous cases of suspected cerebral siderosis, and suggests that HH patients with a severe phenotype, and likely associated with chondrocalcinosis, may display also brain calcifications. Further studies are needed to confirm this hypothesis. So far, we can speculate that iron and calcium homeostasis could be reciprocally connected within the basal ganglia.
Published: 2020
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8. Do All Critically Ill Patients with COVID-19 Disease Benefit from Adding Tocilizumab to Glucocorticoids? A Retrospective Cohort Study

Author: Cristina Mussini, Alessandro Cozzi-Lepri, Marianna Meschiari, Erica Franceschini, Giulia Burastero, Matteo Faltoni, Giacomo Franceschi, Vittorio Iadisernia, Sara Volpi, Andrea Dessilani, Licia Gozzi, Jacopo Conti, Martina Del Monte, Jovana Milic, Vanni Borghi, Roberto Tonelli, Lucio Brugioni, Elisa Romagnoli, Antonello Pietrangelo, Elena Corradini, Massimo Girardis, Stefano Busani, Andrea Cossarizza, Enrico Clini, and Giovanni Guaraldi
Subjects: COVID-19, tocilizumab, glucocorticoids, Microbiology, QR1-502
Abstract: Background: Treatment guidelines recommend the tocilizumab use in patients with a CRP of >7.5 mg/dL. We aimed to estimate the causal effect of glucocorticoids + tocilizumab on mortality overall and after stratification for PaO2/FiO2 ratio and CRP levels. Methods: This was an observational cohort study of patients with severe COVID-19 pneumonia. The primary endpoint was day 28 mortality. Survival analysis was conducted to estimate the conditional and average causal effect of glucocorticoids + tocilizumab vs. glucocorticoids alone using Kaplan–Meier curves and Cox regression models with a time-varying variable for the intervention. The hypothesis of the existence of effect measure modification by CRP and PaO2/FiO2 ratio was tested by including an interaction term in the model. Results: In total, 992 patients, median age 69 years, 72.9% males, 597 (60.2%) treated with monotherapy, and 395 (31.8%), adding tocilizumab upon respiratory deterioration, were included. At BL, the two groups differed for median values of CRP (6 vs. 7 mg/dL; p < 0.001) and PaO2/FiO2 ratio (276 vs. 235 mmHg; p < 0.001). In the unadjusted analysis, the mortality was similar in the two groups, but after adjustment for key confounders, a significant effect of glucocorticoids + tocilizumab was observed (adjusted hazard ratio (aHR) = 0.59, 95% CI: 0.38–0.90). Although the study was not powered to detect interactions (p = 0.41), there was a signal for glucocorticoids + tocilizumab to have a larger effect in subsets, especially participants with high levels of CRP at intensification. Conclusions: Our data confirm that glucocorticoids + tocilizumab vs. glucocorticoids alone confers a survival benefit only in patients with a CRP > 7.5 mg/dL prior to treatment initiation and the largest effect for a CRP > 15 mg/dL. Large randomized studies are needed to establish an exact cut-off for clinical use.
Published: 2023
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9. An unusual dyspnea in an 87-year old woman affected by Sjögren’s syndrome

Author: Carlo Grendene, Anna Francesca Guerra, Stefania Cerri, Antonello Pietrangelo, and Massimo Fiorini
Subjects: sjögren, lymphocytic, interstitial, pneumonia, cysts, Internal medicine, RC31-1245
Abstract: Primary Sjögren’s syndrome (pSS) is a progressive autoimmune disease and is characterized by eye and mouth dryness due to lymphocytic infiltration in lacrimal and salivary glands leading to tissue destruction, but it can also present systemic manifestations including lung involvement. Respiratory manifestations in pSS have a prevalence of 9-20% and can be due to airway and/or lung parenchyma involvement, such as in particular in interstitial lung diseases like lymphocytic interstitial pneumonia (LIP). LIP is an inflammatory diffuse parenchymal lung disease, which is almost invariably associated with other conditions, such as autoimmune diseases and immunodeficiency states, and usually affects women with a mean age of 50 years. We described a case of patient with LIP who was referred to our Internal Medicine Unit and the diagnostic issues related to the patient age and comorbidities.
Published: 2021
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10. Multicenter observational study on the reliability of the HEART score

Author: Nicola Parenti, Giuseppe Lippi, Maria Letizia Bacchi Reggiani, Antonio Luciani, Mario Cavazza, Antonello Pietrangelo, Alberto Vegetti, Lucio Brugioni, Laura Bonfanti, and Gianfranco Cervellin
Subjects: heart score, heart pathway, chest pain, acute coronary syndrome, emergency service, hospital, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Objective To rapidly and safely identify the risk of developing acute coronary syndrome in patients with chest pain who present to the emergency department, the clinical use of the History, Electrocardiogram, Age, Risk Factors, and Troponin (HEART) scoring has recently been proposed. This study aimed to assess the inter-rater reliability of the HEART score calculated by a large number of Italian emergency physicians. Methods The study was conducted in three academic emergency departments using clinical scenarios obtained from medical records of patients with chest pain. Twenty physicians, who took the HEART score course, independently assigned a score to different clinical scenarios, which were randomly administered to the participants, and data were collected and recorded in a spreadsheet by an independent investigator who was blinded to the study’s aim. Results After applying the exclusion criteria, 53 scenarios were finally included in the analysis. The general inter-rater reliability was good (kappa statistics [κ], 0.63; 95% confidence interval, 0.57 to 0.70), and a good inter-rater agreement for the high- and low-risk classes (HEART score, 7 to 10 and 0 to 3, respectively; κ, 0.60 to 0.73) was observed, whereas a moderate agreement was found for the intermediate-risk class (HEART score, 4 to 6; κ, 0.51). Among the different items of the HEART score, history and electrocardiogram had the worse agreement (κ, 0.37 and 0.42, respectively). Conclusion The HEART score had good inter-rater reliability, particularly among the high- and low-risk classes. The modest agreement for history suggests that major improvements are needed for objectively assessing this component.
Published: 2019
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11. Current challenges in the management of patients with sickle cell disease – A report of the Italian experience

Author: Giovanna Russo, Lucia De Franceschi, Raffaella Colombatti, Paolo Rigano, Silverio Perrotta, Vincenzo Voi, Giovanni Palazzi, Carmelo Fidone, Alessandra Quota, Giovanna Graziadei, Antonello Pietrangelo, Valeria Pinto, Giovan Battista Ruffo, Francesco Sorrentino, Donatella Venturelli, Maddalena Casale, Francesca Ferrara, Laura Sainati, Maria Domenica Cappellini, Antonio Piga, Aurelio Maggio, and Gian Luca Forni
Subjects: Hemoglobin disorder, Hemoglobinopathy, Hydroxyurea, Migrants, Sickle cell screening, Sickle cell disease, Medicine
Abstract: Abstract Sickle cell disease (SCD) is an inherited red blood cell disorder caused by a structural abnormality of hemoglobin called sickle hemoglobin (HbS). Clinical manifestations of SCD are mainly characterized by chronic hemolysis and acute vaso-occlusive crisis, which are responsible for severe acute and chronic organ damage. SCD is widespread in sub-Saharan Africa, in the Middle East, Indian subcontinent, and some Mediterranean regions. With voluntary population migrations, people harboring the HbS gene have spread globally. In 2006, the World Health Organization recognized hemoglobinopathies, including SCD, as a global public health problem and urged national health systems worldwide to design and establish programs for the prevention and management of SCD. Herein we describe the historical experience of the network of hemoglobinopathy centers and their approach to SCD in Italy, a country where hemoglobinopathies have a high prevalence and where SCD, associated with different genotypes including ß-thalassemia, is present in the native population.
Published: 2019
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12. Development and validation of a prediction model for tocilizumab failure in hospitalized patients with SARS-CoV-2 infection.

Author: Cristina Mussini, Alessandro Cozzi-Lepri, Marianna Menozzi, Marianna Meschiari, Erica Franceschini, Jovana Milic, Lucio Brugioni, Antonello Pietrangelo, Massimo Girardis, Andrea Cossarizza, Roberto Tonelli, Enrico Clini, Marco Massari, Michele Bartoletti, Anna Ferrari, Anna Maria Cattelan, Paola Zuccalà, Miriam Lichtner, Roberto Rossotti, Enrico Girardi, Emanuele Nicastri, Massimo Puoti, Andrea Antinori, Pierluigi Viale, and Giovanni Guaraldi
Subjects: Medicine, Science
Abstract: BackgroundThe aim of this secondary analysis of the TESEO cohort is to identify, early in the course of treatment with tocilizumab, factors associated with the risk of progressing to mechanical ventilation and death and develop a risk score to estimate the risk of this outcome according to patients' profile.MethodsPatients with COVID-19 severe pneumonia receiving standard of care + tocilizumab who were alive and free from mechanical ventilation at day 6 after treatment initiation were included in this retrospective, multicenter cohort study. Multivariable logistic regression models were built to identify predictors of mechanical ventilation or death by day-28 from treatment initiation and β-coefficients were used to develop a risk score. Secondary outcome was mortality. Patients with the same inclusion criteria as the derivation cohort from 3 independent hospitals were used as validation cohort.Results266 patients treated with tocilizumab were included. By day 28 of hospital follow-up post treatment initiation, 40 (15%) underwent mechanical ventilation or died [26 (10%)]. At multivariable analysis, sex, day-4 PaO2/FiO2 ratio, platelets and CRP were independently associated with the risk of developing the study outcomes and were used to generate the proposed risk score. The accuracy of the score in AUC was 0.80 and 0.70 in internal validation and test for the composite endpoint and 0.92 and 0.69 for death, respectively.ConclusionsOur score could assist clinicians in identifying, early after tocilizumab administration, patients who are likely to progress to mechanical ventilation or death, so that they could be selected for eventual rescue therapies.
Published: 2021
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13. Endothelial Dysfunction in Acute Hepatic Porphyrias

Author: Andrea Ricci, Gilda Sandri, Matteo Marcacci, Elena Di Pierro, Francesca Granata, Chiara Cuoghi, Stefano Marchini, Antonello Pietrangelo, and Paolo Ventura
Subjects: porphyria, acute hepatic porphyrias, endothelial dysfunction, nitric oxide, endothelin, hypertension, Medicine (General), R5-920
Abstract: Background Acute hepatic porphyrias (AHPs) are a group of rare diseases caused by dysfunctions in the pathway of heme biosynthesis. Although acute neurovisceral attacks are the most dramatic manifestations, patients are at risk of developing long-term complications, several of which are of a vascular nature. The accumulation of non-porphyrin heme precursors is deemed to cause most clinical symptoms. Aim We measured the serum levels of endothelin-1 (ET-1) and nitric oxide (NO) to assess the presence of endothelial dysfunction (ED) in patients with AHPs. Forty-six patients were classified, according to their clinical phenotype, as symptomatic (AP-SP), asymptomatic with biochemical alterations (AP-BA), and asymptomatic without biochemical alterations (AP-AC). Results Even excluding those under hemin treatment, AP-SP patients had the lowest NO and highest ET-1 levels, whereas no significant differences were found between AP-BA and AP-AC patients. AP-SP patients had significantly more often abnormal levels of ED markers. Patients with the highest heme precursor urinary levels had the greatest alterations in ED markers, although no significant correlation was detected. Conclusions ED is more closely related to the clinical phenotype of AHPs than to their classical biochemical alterations. Some still undefined disease modifiers may possibly determine the clinical picture of AHPs through an effect on endothelial functions.
Published: 2022
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14. Can Disruption of Basal Ganglia-Thalamocortical Circuit in Wilson Disease Be Associated with Juvenile Myoclonic Epilepsy Phenotype?

Author: Jessica Rossi, Francesco Cavallieri, Giada Giovannini, Francesca Benuzzi, Daniela Ballotta, Anna Elisabetta Vaudano, Francesca Ferrara, Sara Contardi, Antonello Pietrangelo, Elena Corradini, Fausta Lui, and Stefano Meletti
Subjects: myoclonic epilepsy, Wilson disease (WD), globus pallidus internus (GPi), thalamocortical circuit, fMRI, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: In this paper, we describe the multimodal MRI findings in a patient with Wilson disease and a seizure disorder, characterized by an electroclinical picture resembling juvenile myoclonic epilepsy. The brain structural MRI showed a deposition of ferromagnetic materials in the basal ganglia, with marked hypointensities in T2-weighted images of globus pallidus internus bilaterally. A resting-state fMRI study revealed increased functional connectivity in the patient, compared to control subjects, in the following networks: (1) between the primary motor cortex and several cortical regions, including the secondary somatosensory cortex and (2) between the globus pallidus and the thalamo-frontal network. These findings suggest that globus pallidus alterations, due to metal accumulation, can lead to a reduction in the normal globus pallidus inhibitory tone on the thalamo-(motor)-cortical pathway. This, in turn, can result in hyperconnectivity in the motor cortex circuitry, leading to myoclonus and tonic-clonic seizures. We suppose that, in this patient, Wilson disease generated a ‘lesion model’ of myoclonic epilepsy.
Published: 2022
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15. Impact of Diabetes Mellitus and Its Comorbidities on Elderly Patients Hospitalized in Internal Medicine Wards: Data from the RePoSi Registry

Author: Christiano Argano, Giuseppe Natoli, Salvatore Mularo, Alessandro Nobili, Marika Lo Monaco, Pier Mannuccio Mannucci, Francesco Perticone, Antonello Pietrangelo, and Salvatore Corrao
Subjects: diabetes, comorbidities, heart rate, cancer, male sex, in-hospital mortality, Medicine
Abstract: Background: Currently, diabetes represents the seventh leading cause of death worldwide, with a significant economic burden. The number and severity of comorbidities increase with age, and are identified as important determinants that influence the prognosis. We aimed to investigate comorbidities and outcomes in a cohort of hospitalized elderly patients affected by diabetes. Methods: In this observational study, we retrospectively analyzed data collected from the REgistro dei pazienti per lo studio delle POlipatologie e politerapie in reparti della rete Simi (RePoSi) registry. Socio-demographic, clinical characteristics, and laboratory findings were considered. The association between variables and in-hospital and 1-year follow-up were analyzed. Results: Among 4708 in-patients, 1378 (29.3%) had a diagnosis of diabetes. Patients with diabetes had more previous hospitalization, a clinically significant disability, and more need for a urinary catheter in comparison with subjects without diabetes. Patients affected by diabetes took more drugs, both at admission, at in-hospital stay, at discharge, and at 1-year follow-up. Thirty-five comorbidities were more frequent in patients with diabetes, and the first five were hypertension (57.1%), ischemic heart disease (31.4%), chronic renal failure (28.8%), atrial fibrillation (25.6%), and chronic obstructive pulmonary disease (22.7%). Heart rate was an independent predictor of in-hospital mortality. At 1-year follow-up, cancer and male sex were strongly independently associated with mortality. Conclusions: Our findings showed the severity of the impact of diabetes and its comorbidities in the real life of internal medicine and geriatric wards, and provide data to be used for a better tailored management of elderly in-patients with diabetes.
Published: 2022
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16. Ferroportin disease: pathogenesis, diagnosis and treatment

Author: Antonello Pietrangelo
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Abstract: Ferroportin Disease (FD) is an autosomal dominant hereditary iron loading disorder associated with heterozygote mutations of the ferroportin-1 (FPN) gene. It represents one of the commonest causes of genetic hyperferritinemia, regardless of ethnicity. FPN1 transfers iron from the intestine, macrophages and placenta into the bloodstream. In FD, loss-of-function mutations of FPN1 limit but do not impair iron export in enterocytes, but they do severely affect iron transfer in macrophages. This leads to progressive and preferential iron trapping in tissue macrophages, reduced iron release to serum transferrin (i.e. inappropriately low transferrin saturation) and a tendency towards anemia at menarche or after intense bloodletting. The hallmark of FD is marked iron accumulation in hepatic Kupffer cells. Numerous FD-associated mutations have been reported worldwide, with a few occurring in different populations and some more commonly reported (e.g. Val192del, A77D, and G80S). FPN1 polymorphisms also represent the gene variants most commonly responsible for hyperferritinemia in Africans. Differential diagnosis includes mainly hereditary hemochromatosis, the syndrome commonly due to either HFE or TfR2, HJV, HAMP, and, in rare instances, FPN1 itself. Here, unlike FD, hyperferritinemia associates with high transferrin saturation, iron-spared macrophages, and progressive parenchymal cell iron load. Abdominal magnetic resonance imaging (MRI), the key non-invasive diagnostic tool for the diagnosis of FD, shows the characteristic iron loading SSL triad (spleen, spine and liver). A non-aggressive phlebotomy regimen is recommended, with careful monitoring of transferrin saturation and hemoglobin due to the risk of anemia. Family screening is mandatory since siblings and offspring have a 50% chance of carrying the pathogenic mutation.
Published: 2017
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17. Osteoarthritis: The Challenge of Establishing a Personalised Treatment

Author: Johanne Martel-Pelletier, Antonello Pietrangelo, Francis Berenbaum, Jean-Pierre Pelletier, and Burkhard Leeb
Subjects: EULAR, European League Against Rheumatism, Diseases of the musculoskeletal system, RC925-935
Abstract: The symposium, co-chaired by Prof Johanne Martel-Pelletier and Prof Antonello Pietrangelo, opened with a discussion of metabolic syndrome-associated osteoarthritis (OA) and a brief overview of treatment options by Prof Francis Berenbaum. Prof Jean-Pierre Pelletier then discussed the use of symptomatic slow-acting drugs for OA (SYSADOA) for knee OA within the context of the new European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) recommendations. Finally, Dr Burkhard Leeb concluded the session by discussing the indications, contraindications, and side-effect management of diacerein.
Published: 2014

18. Sudden Onset of Lower Abdominal Pain Without Peritonitis or Ileus

Author: Stefania Scarlini, Marco Gandolfo, and Antonello Pietrangelo
Subjects: Gas-gangrene, Clostridium septicum, acute abdominal pain., Medicine
Abstract: A patient presented with sudden, unexplained lower abdominal pain without peritonism or signs of infection or inflammatory reaction, but with recent bloody stools and a history of radiation therapy, diabetes and immunosuppression. Plain abdominal x-ray showed only air-fluid levels and air distention of the colon, but a later abdominal CT scan revealed extensive gas gangrene of the colon. The patient’s clinical status rapidly worsened. Elective surgical rectosigmoid debridement did not prevent the patient’s death. In conclusion, the diagnosis of ‘spontaneous’ life-threatening gas gangrene requires a high degree of clinical suspicion and allows life-saving surgical intervention.
Published: 2016
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19. Hypoalbuminemia and Risk of Portal Vein Thrombosis in Cirrhosis

Author: Giuseppe, Palasciano, Felicia, D’Alitto, Ostilio, Palmieri Vincenzo, Daniela, Santovito, Dario, Di Michele, Giuseppe, Croce, David, Sacerdoti, Silvia, Brocco, Silvano, Fasolato, Lara, Cecchetto, Giancarlo, Bombonato, Michele, Bertoni, Tea, Restuccia, Paola, Andreozzi, Livia, Liguori Maria, Francesco, Perticone, Benedetto, Caroleo, Maria, Perticone, Orietta, Staltari, Roberto, Manfredini, Alfredo, De Giorgi, Maurizio, Averna, Antonina, Giammanco, Alessandro, Granito, Irene, Pettinari, Sara, Marinelli, Luigi, Bolondi, Lorenzo, Falsetti, Aldo, Salvi, Emanuele, Durante-Mangoni, Flavio, Cesaro, Vincenza, Farinaro, Enrico, Ragone, Ignazio, Morana, Angelo, Andriulli, Antonio, Ippolito, Angelo, Iacobellis, Grazia, Niro, Antonio, Merla, Giovanni, Raimondo, Sergio, Maimone, Irene, Cacciola, Doriana, Varvara, Davide, Drenaggi, Silvia, Staffolani, Antonio, Picardi, Umberto, Vespasiani-Gentilucci, Giovanni, Galati, Paolo, Gallo, Giovanni, Davì, Cosima, Schiavone, Francesca, Santilli, Claudio, Tana, Anna, Licata, Maurizio, Soresi, Battista, Bianchi Giovanni, Isabella, Carderi, Antonio, Pinto, Antonino, Tuttolomondo, Giovanni, Ferrari, Paolo, Gresele, Tiziana, Fierro, Olivia, Morelli, Giacomo, Laffi, Giulio, Romanelli Roberto, Umberto, Arena, Cristina, Stasi, Antonio, Gasbarrini, Matteo, Gargovich, Assunta, Zocco Maria, Laura, Riccardi, Elena, Ainora Maria, William, Capeci, Pio, Martino Giuseppe, Lorenzo, Nobili, Maurizio, Cavallo, Pierluigi, Frugiuele, Antonio, Greco, Antonello, Pietrangelo, Paolo, Ventura, Chiara, Cuoghi, Matteo, Marcacci, Gaetano, Serviddio, Gianluigi, Vendemiale, Rosanna, Villani, Ruggiero, Gargano, Gianpaolo, Vidili, Valentina, Di Cesare, Maristella, Masala, Giuseppe, Delitala, Pietro, Invernizzi, Giovanni, Di Minno, Antonella, Tufano, Francesco, Purrello, Graziella, Privitera, Alessandra, Forgione, Valentina, Curigliano, Marco, Senzolo, Kryssia Isabel, Rodríguez-Castro, Gianluigi, Giannelli, Carla, Serra, Sergio, Neri, Pietro, Pignataro, Mario, Rizzetto, Wilma, Debernardi Venon, Gianluca, Svegliati Baroni, Gaetano, Bergamaschi, Michela, Masotti, Filippo, Costanzo, Roberto, Corazza Gino, Hugh, Caldwell Stephen, Francesco, Angelico, Ben Maria, Del, Laura, Napoleone, Licia, Polimeni, Marco, Proietti, Valeria, Raparelli, Francesco, Romiti Giulio, Eleonora, Ruscio, Andrea, Severoni, Giovanni, Talerico, Filippo, Toriello, Annarita, Vestri, Cangemi, Roberto, Raparelli, Valeria, Talerico, Giovanni, Basili, Stefania, and Violi, Francesco
Published: 2024
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20. List of Contributors

Author: N. Volkan Adsay, Venancio A.F. Alves, Quentin M. Anstee, Olca Basturk, Christopher O.C. Bellamy, Elizabeth M. Brunt, Alastair D. Burt, Andrew D. Clouston, James M. Crawford, Linda D. Ferrell, Raul S. Gonzalez, Maria Guido, Gillian L. Hale, Stefan G. Hübscher, Prodromos Hytiroglou, Sanjay Kakar, David E. Kleiner, Ansgar W. Lohse, Alessandra Mangia, Yasuni Nakanuma, Valerie Paradis, Antonello Pietrangelo, Alberto Quaglia, Eve A. Roberts, Luigi M. Terracciano, Neil D. Theise, Dina G. Tiniakos, Michael Torbenson, Kay Washington, Aileen Wee, Matthew M. Yeh, Sherif R. Zaki, Yoh Zen, and Jessica Zucman-Rossi
Published: 2024

21. The impact of COVID-19 pandemic on well-being of Italian physicians: a report from the Italian Society of Internal Medicine (SIMI) national survey

Author: Giulio Francesco, Romiti, Leonardo, Bencivenga, Rosanna, Villani, Sebastiano, Cicco, Antonio, Cimellaro, Andrea, Dalbeni, Giovanni, Talerico, Antonello, Pietrangelo, Giorgio, Sesti, and Vincenzo, Zaccone
Subjects: sars-cov-2, covid-19, well-being, work-related stress, Emergency Medicine, Internal Medicine, healthcare
Abstract: Over the past few years, COVID-19 pandemic has imposed a high toll worldwide, with a high burden of morbidity and mortality. Healthcare practitioners (HCPs) have been in the frontline since the beginning of the outbreak, and the high level of stress have affected their physical and mental status, as well as their relationships. We aimed at exploring the self-reported changes in comprehensive well-being in a cohort of Italian physicians. An online-based survey was administered to the members of the Italian Society of Internal Medicine (SIMI) between March and June 2021. The survey was based on 32 multiple-choice questions exploring self-reported physical and mental well-being, as well as changes in workloads, work-related feelings and physicians’ relationship with patients, colleagues and families. 228 physicians (mean age: 35.7 ± 9.8 years) participated in the survey; 120 (52.6%) were residents, 196 (86.0%) worked in COVID-19 units and 65 (28.5%) had COVID-19 during the pandemic. A significant proportion of respondents reported to have experience onset or worsening of physical and mental symptoms, with insomnia/sleep disorders (58.3%) and mood swings (47.8%) being the most common, respectively. The burden of physical and mental consequences was broadly higher among residents compared to specialists, with the former reporting more frequently an increase in the number of worked hours (p = 0.020) and being more frequently infected with COVID-19 (35.0% vs. 21.3, p = 0.032). Moreover, familiar and doctor–patient relationships were also considerably affected. Physicians have been suffering a wide spectrum of physical, mental and relational consequences during COVID-19 pandemic, with youngest doctors being more likely to present several physical and mental health symptoms. Further studies are needed to evaluate long-term consequences of COVID-19 pandemic on the well-being of HCPs, and potential preventive strategies.
Published: 2022

22. Consensus Statement on the definition and classification of metabolic hyperferritinaemia

Author: Luca Valenti, Elena Corradini, Leon A. Adams, Elmar Aigner, Saleh Alqahtani, Marco Arrese, Edouard Bardou-Jacquet, Elisabetta Bugianesi, Jose-Manuel Fernandez-Real, Domenico Girelli, Hannes Hagström, Benjamin Henninger, Kris Kowdley, Guido Ligabue, Donald McClain, Fabrice Lainé, Koji Miyanishi, Martina U. Muckenthaler, Alessia Pagani, Patrizia Pedrotti, Antonello Pietrangelo, Daniele Prati, John D. Ryan, Laura Silvestri, C. Wendy Spearman, Per Stål, Emmanuel A. Tsochatzis, Francesca Vinchi, Ming-Hua Zheng, Heinz Zoller, Università degli Studi di Milano = University of Milan (UNIMI), Università degli Studi di Modena e Reggio Emilia = University of Modena and Reggio Emilia (UNIMORE), The University of Western Australia (UWA), Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), Johns Hopkins University (JHU), Pontificia Universidad Católica de Chile (UC), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Università degli studi di Torino = University of Turin (UNITO), Universitat de Girona [Girona], Universitat de Girona (UdG), Università degli studi di Verona = University of Verona (UNIVR), Karolinska University Hospital [Stockholm], Leopold Franzens Universität Innsbruck - University of Innsbruck, Washington State University (WSU), Wake Forest School of Medicine [Winston-Salem], Wake Forest Baptist Medical Center, Sapporo Medical University School of Medicine, Sapporo Medical University, Heidelberg University, IRCCS Ospedale San Raffaele [Milan, Italy], ASST Great Metropolitan Niguarda / ASST Grande Ospedale Metropolitano Niguarda [Milan, Italia], Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Royal College of Surgeons in Ireland (RCSI), University of Cape Town, University College of London [London] (UCL), Weill Cornell Medicine [New York], The First Affiliated Hospital of Wenzhou Medical University [Wenzhou, China], Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), Ministero della Salute, Ricerca Finalizzata RF-2016-02364358, RC Rete cardiologica ‘CV PREVITAL’, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico ‘Liver BIBLE’ (PR-0391), Innovative Medicines Initiative 2 joint undertaking of European Union’s Horizon 2020 research and innovation programme and EFPIA European Union (EU) Programme Horizon 2020 (under grant agreement No. 777377) for the project LITMUS, H2020 under grant agreement ‘101016726’, the European Union, programme ‘Photonics’ under grant agreement ‘101016726’ for L.V. Fondo Nacional de Ciencia y Tecnología de Chile (FONDECYT #1191145 to M.A.) and from the Agencia Nacional de Investigación y Desarrollo, ANID through ANID ACE 210009 grant for M.A. NIH (P30DK124723), and Veterans Administration (2I01 BX001140) for D.M. SFB1036, SFB1118 and DFG (FerrOs — FOR5146, SPP2306) as well as Marsilius Kolleg for M.U.M. National Natural Science Foundation of China (82070588), High Level Creative Talents from Department of Public Health in Zhejiang Province (S2032102600032) for M.-H.Z. Swedish Cancer Society (170690) and Stockholm County Council (K2017-4579) for P.S., Jonchère, Laurent, Weill Cornell Medicine [Cornell University], and Cornell University [New York]
Subjects: [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, iron, Endocrinology, iron, hyperferritinemia, metabolic syndrome, Endocrinology, Diabetes and Metabolism, hyperferritinemia, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, metabolic syndrome
Abstract: International audience; Hyperferritinaemia is a common laboratory finding that is often associated with metabolic dysfunction and fatty liver. Metabolic hyperferritinaemia reflects alterations in iron metabolism that facilitate iron accumulation in the body and is associated with an increased risk of cardiometabolic and liver diseases. Genetic variants that modulate iron homeostasis and tissue levels of iron are the main determinants of serum levels of ferritin in individuals with metabolic dysfunction, raising the hypothesis that iron accumulation might be implicated in the pathogenesis of insulin resistance and the related organ damage. However, validated criteria for the non-invasive diagnosis of metabolic hyperferritinaemia and the staging of iron overload are still lacking, and there is no clear evidence of a benefit for iron depletion therapy. Here, we provide an overview of the literature on the relationship between hyperferritinaemia and iron accumulation in individuals with metabolic dysfunction, and on the associated clinical outcomes. We propose an updated definition and a provisional staging system for metabolic hyperferritinaemia, which has been agreed on by a multidisciplinary global panel of expert researchers. The goal is to foster studies into the epidemiology, genetics, pathophysiology, clinical relevance and treatment of metabolic hyperferritinaemia, for which we provide suggestions on the main unmet needs, optimal design and clinically relevant outcomes.
Published: 2023

23. Labile plasma iron and echocardiographic parameters are associated with cardiac events in β ‐thalassemic patients

Author: Francesca Ferrara, Francesca Coppi, Roberta Riva, Paolo Ventura, Andrea Ricci, Anna Vittoria Mattioli, Marisa Talarico, Cinzia Garuti, Mirco Bevini, Vincenzo Rochira, Elena Buzzetti, Antonello Pietrangelo, and Elena Corradini
Subjects: thalassemia, anemia, iron, cardiac complications, labile plasma iron, non-transferrin-bound iron, myocardial hypertrophy, thalassemia, iron, myocardial hypertrophy, labile plasma iron, Clinical Biochemistry, cardiac complications, non-transferrin-bound iron, General Medicine, anemia, Biochemistry
Published: 2023

24. Antihypertensive treatment changes and related clinical outcomes in older hospitalized patients

Author: Sebastiano, Cicco, D'Abbondanza, Marco, Proietti, Marco, Vincenzo, Zaccone, Chiara, Pes, Federica, Caradio, Mattioli, Massimo, Salvatore, Piano, Alberto Maria Marra, Alessandro, Nobili, Pier Mannuccio Mannucci, Antonello, Pietrangelo, Giorgio, Sesti, Elena, Buzzetti, Andrea, Salzano, Antonio, Cimellaro, Francesco, Perticone, Francesco, Violi, Gino Roberto Corazza, Salvatore, Corrao, Alessandra, Marengoni, Francesco, Salerno, Matteo, Cesari, Mauro, Tettamanti, Luca, Pasina, Carlotta, Franchi, Alessio, Novella, Gabriella, Miglio, Alessia Antonella Galbussera, Ilaria, Ardoino, Prisco, Domenico, Elena, Silvestri, Giacomo, Emmi, Alessandra, Bettiol, Irene, Mattioli, Gianni, Biolo, Michela, Zanetti, Giacomo, Bartelloni, Michele, Zaccari, Massimiliano, Chiuch, Massimo, Vanoli, Giulia, Grignani, Edoardo Alessandro Pulixi, Pirro, Matteo, Lupattelli, Graziana, Bianconi, Vanessa, Alcidi, Riccardo, Giotta, Alessia, Massimo, R Mannarino, Domenico, Girelli, Fabiana, Busti, Giacomo, Marchi, Mario, Barbagallo, Ligia, Dominguez, Vincenza, Beneduce, Federica, Cacioppo, Giuseppe, Natoli, Salvatore, Mularo, Massimo, Raspanti, Christiano, Argano, Federica, Cavallaro, Marco, Zoli, Maria Laura Matacena, Giuseppe, Orio, Eleonora, Magnolfi, Serafini, Giovanni, Angelo, Simili, Mattia, Brunori, Ilaria, Lazzari, Cappellini, MARIA DOMENICA, Giovanna, Fabio, Margherita Migone De Amicis, Giacomo De Luca, Natalia, Scaramellini, Valeria Di Stefano, Simona, Leoni, Sonia, Seghezzi, Alessandra Danuto Di Mauro, Diletta, Maira, Marta, Mancarella, Tiziano, Lucchi, Paolo Dionigi Rossi, Marta, Clerici, Alessandra Danuta Di Mauro, Giulia, Bonini, Conti, Federica, Silvia, Prolo, Maddalena, Fabrizi, Miriana, Martelengo, Giulia, Vigani, Antonio Di Sabatino, Emanuela, Miceli, Marco Vincenzo Lenti, Martina, Pisati, Lavinia, Pitotti, Donatella, Padula, Valentina, Antoci, Ginevra, Cambiè, Roberto, Pontremoli, Valentina, Beccati, Giulia, Nobili, Giovanna, Leoncini, Jacopo, Alberto, Federico, Cattaneo, Luigi, Anastasio, Lucia, Sofia, Carbone, LUIGI MARIA, Francesco, Cipollone, Maria Teresa Guagnano, Ilaria, Rossi, Emanuele, Valeriani, Damiani, D'Ardes, Lucia, Esposito, Simona, Sestili, Ermanno, Angelucci, Gerardo, Mancuso, Daniela, Calipari, Mosè, Bartone, Giuseppe, Delitala, Maria, Berria, Alessandro, Delitala, Maurizio, Muscaritoli, Alessio, Molfino, Enrico, Petrillo, Antonella, Giorgi, Christian, Gracin, Giovanni, Imbimbo, Giuseppe, Zuccalà, Gabriella, D'Aurizio, Giuseppe, Romanelli, Andrea, Volpini, Daniela, Lucente, Francesca, Manzoni, Annalisa, Pirozzi, Alberto, Zucchelli, Antonio, Picardi, Umberto Vespasiani Gentilucci, Paolo, Gallo, Chiara, Dell'Unto, Giuseppe, Bellelli, Maurizio, Corsi, Cesare, Antonucci, Chiara, Sidoli, Giulia, Principato, Alessandra, Bonfanti, Hajnalka, Szabo, Mazzola, Paolo, Piazzoli, Andrea, Franco, Arturi, Elena, Succurro, Bruno, Tassone, Federica, Giofrè, Maria Grazia Serra, Maria Antonietta Bleve, Antonio, Brucato, Teresa De Falco, Enrica, Negro, Martino, Brenna, Lucia, Trotta, Giovanni Lorenzo Squintani, Maria Luisa Randi, Fabrizio, Fabris, Irene, Bertozzi, Giulia, Bogoni, Maria Victoria Rabuini, Tancredi, Prandini, Francesco, Ratti, Chiara, Zurlo, Lorenzo, Cerruti, Elisabetta, Cosi, Roberto, Manfredini, Fabio, Fabbian, Benedetta, Boari, Alfredo De Giorgi, Ruana, Tiseo, Giuseppe, Paolisso, Maria Rosaria Rizzo, Claudia, Catalano, Irene Di Meo, Claudio, Borghi, Enrico, Strocchi, Eugenia, Ianniello, Mario, Soldati, Silvia, Schiavone, Alessio, Bragagni, Francesca Giulia Leoni, Valeria De Sando, Sara, Scarduelli, Michela, Cammarosano, Ilenia, Pareo, Carlo, Sabbà, Francesco Saverio Vella, Patrizia, Suppressa, Giovanni Michele De Vincenzo, Alessio, Comitangelo, Emanuele, Amoruso, Carlo, Custodero, Giuseppe, Re, Andrea, Schilardi, Francesca, Loparco, Luigi, Fenoglio, Andrea, Falcetta, Alessia Valentina Giraudo, Salvatore, D'Aniano, Anna, L Fracanzani, Silvia, Tiraboschi, Annalisa, Cespiati, Giovanna, Oberti, Giordano, Sigon, Felice, Cinque, Flora, Peyvandi, Raffaella, Rossio, Giulia, Colombo, Pasquale, Agosti, Erica, Pagliaro, Eleonora, Semproni, Canetta, Ciro, Valter, Monzani, Valeria, Savojardo, Giuliana, Ceriani, Christian, Folli, Giada, Pallini, Fabrizio, Montecucco, Luciano, Ottonello, Lara, Caserza, Giulia, Vischi, Salam, Kassem, Luca, Liberale, Nicola Lucio Liberato, Tiziana, Tognin, Francesco, Purrello, Antonino Di Pino, Salvatore, Piro, Renzo, Rozzini, Lina, Falanga, Maria Stella Pisciotta, Francesco Baffa Bellucci, Stefano, Buffelli, Camillo, Ferrandina, Francesca, Mazzeo, Elena, Spazzini, Giulia, Cono, Giulia, Cesaroni, Giuseppe, Montrucchio, Paolo, Peasso, Edoardo, Favale, Cesare, Poletto, Carl, Margaria, Maura, Sanino, Ludovica, Perri, Luigina, Guasti, Francesca, Rotunno, Luana, Castiglioni, Andrea, Maresca, Alessandro, Squizzato, Leonardo, Campiotti, Alessandra, Grossi, Roberto Davide Diprizio, Francesco, Dentali, Bertolotti, Marco, Chiara, Mussi, Giulia, Lancellotti, Maria Vittoria Libbra, Matteo, Galassi, Yasmine, Grassi, Alessio, Greco, Elena, Bigi, Pellegrini, Elisa, Laura, Orlandi, Giulia, Dondi, Lucia, Carulli, Angela, Sciacqua, Maria, Perticone, Rosa, Battaglia, Raffaele, Maio, Aleandra, Scozzafava, Valentino, Condoleo, Tania, Falbo, Lidia, Colangelo, Marco, Filice, Elvira, Clausi, Vincenzo, Stanghellini, Eugenio, Ruggeri, Sara Del Vecchio, Ilaria, Benzoni, Andrea, Salvi, Leonardi, Roberto, Giampaolo, Damiani, Gianluca, Moroncini, William, Capeci, Giuseppe Pio Martino, Biondi, Lorenzo, Pietro, Pettinari, Monica, Ormas, Emanuele, Filippini, Devis, Benfaremo, Roberto, Romiti, Riccardo, Ghio, Anna Dal Col, Salvatore, Minisola, Luciano, Colangelo, Mirella, Cilli, Giancarlo, Labbadia, Antonella, Afeltra, Benedetta, Marigliano, Maria Elena Pipita, Pietro, Castellino, Luca, Zanoli, Alfio, Gennaro, Agostino, Gaudio, Samuele, Pignataro, Francesca, Mete, Miriam, Gino, Guido, Moreo, Gloria, Pina, Alberto, Ballestrero, Fabio, Ferrando, Roberta, Gonella, Domenico, Cerminara, Paolo, Setti, Chiara, Traversa, Camilla, Scarsi, Bruno, Graziella, Stefano, Baldassarre, Salvatore, Fragapani, Gabriella, Gruden, Franco, Berti, Giuseppe, Famularo, Patrizia, Tarsitani, Roberto, Castello, Michela, Pasino, Marcello Giuseppe Maggio Gian Paolo Ceda, Simonetta, Morganti, Andrea, Artoni, Margherita, Grossi, Stefano Del Giacco, Davide, Firinu, Giulia, Costanzo, Giacomo, Argiolas, Giovanni, Paoletti, Francesca, Losa, Montalto, GIUSEPPE ALBERT, Anna, Licata, Filippo Alessandro Montalto, Francesco, Corica, Giorgio, Basile, Antonino, Catalano, Federica, Bellone, Concetto, Principato, Lorenzo, Malatino, Benedetta, Stancanelli, Valentina, Terranova, Salvatore Di Marca, Rosario Di Quattro, Lara La Malfa, Rossella, Caruso, Mecocci, Patrizia, Ruggiero, Carmelinda, Boccardi, Virginia, Tiziana, Meschi, Andrea, Ticinesi, Antonio, Nouvenne, Pietro, Minuz, Luigi, Fondrieschi, Giandomenico Nigro Imperiale, Sarah, Morellini, Mario, Pirisi, Gian Paolo Fra, Daniele, Sola, Mattia, Bellan, Roberto, Quadri, Erica, Larovere, Marco, Novelli, Emilio, Simeone, Rosa, Scurti, Fabio, Tolloso, Tarquini, Roberto, Alice, Valoriani, Silvia, Dolenti, Giulia, Vannini, Volpi, Riccardo, Pietro, Bocchi, Alessandro, Vignali, Sergio, Harari, Chiara, Lonati, Federico, Napoli, Italia, Aiello, Teresa, Salvatore, Lucio, Monaco, Carmen, Ricozzi, Alberto, Pilotto, Ilaria, Indiano, Federica, Gandolfo, Franco Laghi Pasini, Pier Leopoldo Capecchi, Ranuccio, Nuti, Roberto, Valenti, Martina, Ruvio, Silvia, Cappelli, Alberto, Palazzuoli, Mauro, Bernardi, Silvia Li Bassi, Luca, Santi, Giacomo, Zaccherini, Vittorio, Durante, Daniela, Tirotta, Giovanna, Eusebi, Cattaneo, Marco Natale, Amoruso, MARIA VALENTINA, Paola, Fracasso, Cristina, Fasolino, Moreno, Tresoldi, Enrica, Bozzolo, Sarah, Damanti, Massimo, Porta, Giuseppe, Armentaro, Maria Immacolata Arnone, Milena, Barone, Lorenzo, Bertolino, Sara, Bianco, Nicolò, Binello, Simona, Brancati, Agostino, Buonauro, William, Cordeddu, Curcio, Rosa, Andrea, Dalbeni, Salvatore, D'Agnano, Damiano, D'Ardes, Martina De Feo, Emilia, Donnarumma, Marco, Fei, Carmine Gabriele Gambino, Paolo, Giorgini, Lombardi, Rosa, Giuseppe, Miceli, Paola, Naccarato, Silvia, Noviello, Gaia, Olivieri, Roberta, Parente, Francesca Serena Pignataro, Sonia, Poma, Enrica, Porceddu, Pucci, Giacomo, Marco, Ricchio, Anna, Sabena, Marco, Salice, Claudia, Santarossa, Ambra, Savona, Caterina, Savrié, Roberto, Scicali, Mario, Stabile, Giovanni, Talerico, Michela, Talia, Eliezer Joseph Tassone, Thomas, Teatini, Elisabetta, Tombolini, Matteo, Traversa, Elia, Vettore, Alessandro, Vignal, Luca, Vilardi, Rosanna, Villani, Francesco, Vitale, Cicco, Sebastiano, D Abbondanza, Marco, Proietti, Marco, Zaccone, Vincenzo, Pes, Chiara, Caradio, Federica, Mattioli, Massimo, Piano, Salvatore, Marra, Alberto Maria, Nobili, Alessandro, Mannucci, Pier Mannuccio, Pietrangelo, Antonello, Sesti, Giorgio, Buzzetti, Elena, Salzano, Andrea, Cimellaro, Antonio, Antonio Cimellaro, Salvatore, Corrao, Mario, Barbagallo, Anna, Licata, Giuseppe, Montalto, Paolisso, Giuseppe, Rizzo, Maria Rosaria, and Cimellaro, Antonio - Giovani Internisti Società Italiana di Medicina Interna (GIS-SIMI) and of the REPOSI Investigators
Subjects: cardiovascular events, older patient, hypertension, antihypertensive drugs, older patients, survival, Clinical Biochemistry, antihypertensive drug, General Medicine, Biochemistry, cardiovascular event
Abstract: Background: Hypertension management in older patients represents a challenge, particularly when hospitalized. Objective: The objective of this study is to investigate the determinants and related outcomes of antihypertensive drug prescription in a cohort of older hospitalized patients. Methods: A total of 5671 patients from REPOSI (a prospective multicentre observational register of older Italian in-patients from internal medicine or geriatric wards) were considered; 4377 (77.2%) were hypertensive. Minimum treatment (MT) for hypertension was defined according to the 2018 ESC guidelines [an angiotensin-converting-enzyme-inhibitor (ACE-I) or an angiotensin-receptor-blocker (ARB) with a calcium-channel-blocker (CCB) and/or a thiazide diuretic; if >80 years old, an ACE-I or ARB or CCB or thiazide diuretic]. Determinants of MT discontinuation at discharge were assessed. Study outcomes were any cause rehospitalization/all cause death, all-cause death, cardiovascular (CV) hospitalization/death, CV death, non-CV death, evaluated according to the presence of MT at discharge. Results: Hypertensive patients were older than normotensives, with a more impaired functional status, higher burden of comorbidity and polypharmacy. A total of 2233 patients were on MT at admission, 1766 were on MT at discharge. Discontinuation of MT was associated with the presence of comorbidities (lower odds for diabetes, higher odds for chronic kidney disease and dementia). An adjusted multivariable logistic regression analysis showed that MT for hypertension at discharge was associated with lower risk of all-cause death, all-cause death/hospitalization, CV death, CV death/hospitalization and non-CV death. Conclusions: Guidelines-suggested MT for hypertension at discharge is associated with a lower risk of adverse clinical outcomes. Nevertheless, changes in antihypertensive treatment still occur in a significant proportion of older hospitalized patients.
Published: 2023

25. Post-Covid-19 Irritable Bowel Syndrome

Author: Giovanni, Marasco, Cesare, Cremon, Maria Raffaella, Barbaro, Giulia, Cacciari, Francesca, Falangone, Anna, Kagramanova, Dmitry, Bordin, Vasile, Drug, Egidia, Miftode, Pietro, Fusaroli, Salem Youssef, Mohamed, Chiara, Ricci, Massimo, Bellini, Mohammed Masudur, Rahman, Luigi, Melcarne, Javier, Santos, Beatriz, Lobo, Serhat, Bor, Suna, Yapali, Deniz, Akyol, Ferdane Pirincci, Sapmaz, Yonca Yilmaz, Urun, Tugce, Eskazan, Altay, Celebi, Huseyin, Kacmaz, Berat, Ebik, Hatice Cilem, Binicier, Mehmet Sait, Bugdayci, Munkhtsetseg Banzragch, Yağcı, Husnu, Pullukcu, Berrin Yalınbas, Kaya, Ali, Tureyen, İbrahim, Hatemi, Elif Sitre, Koc, Goktug, Sirin, Ali Riza, Calıskan, Goksel, Bengi, Esra Ergun, Alıs, Snezana, Lukic, Meri, Trajkovska, Keren, Hod, Dan, Dumitrascu, Antonello, Pietrangelo, Elena, Corradini, Magnus, Simren, Jessica, Sjölund, Navkiran, Tornkvist, Uday C, Ghoshal, Olga, Kolokolnikova, Antonio, Colecchia, Jordi, Serra, Giovanni, Maconi, Roberto, De Giorgio, Silvio, Danese, Piero, Portincasa, Antonio, Di Sabatino, Marcello, Maggio, Elena, Philippou, Yeong Yeh, Lee, Daniele, Salvi, Alessandro, Venturi, Claudio, Borghi, Marco, Zoli, Paolo, Gionchetti, Pierluigi, Viale, Vincenzo, Stanghellini, Giovanni, Barbara, and Rosanna F, Cogliandro
Subjects: irritable bowel syndrome, Gastroenterology, COVID-19, COVID-19irritable bowel syndrome
Abstract: Objectives: The long-term consequences of COVID-19 infection on the gastrointestinal tract remain unclear. Here, we aimed to evaluate the prevalence of gastrointestinal symptoms and post-COVID-19 disorders of gut-brain interaction after hospitalisation for SARS-CoV-2 infection. Design: GI-COVID-19 is a prospective, multicentre, controlled study. Patients with and without COVID-19 diagnosis were evaluated on hospital admission and after 1, 6 and 12 months post hospitalisation. Gastrointestinal symptoms, anxiety and depression were assessed using validated questionnaires. Results: The study included 2183 hospitalised patients. The primary analysis included a total of 883 patients (614 patients with COVID-19 and 269 controls) due to the exclusion of patients with pre-existing gastrointestinal symptoms and/or surgery. At enrolment, gastrointestinal symptoms were more frequent among patients with COVID-19 than in the control group (59.3% vs 39.7%, p, Fondazione Cassa di Risparmio in Bologna; Ministero dell’Istruzione, dell’Università e della Ricerca, MIUR; Korean Society of Neurogastroenterology and Mobility, KSNM; Fondazione del Monte di Bologna e Ravenna: H2020, SC1-BHC-01-2019; United European Gastroenterology, UEG; Fondazione Roma, GB’s contribution to this research was partly supported by funding from Fondazione Cassa di Risparmio in Bologna, the Italian Ministry of Education, University and Research; and Fondazione del Monte di Bologna e Ravenna and European Grant H2020, DISCOvERIE, SC1-BHC-01-2019, We thank the European Society of Neurogastroenterology and Motility, the United European Gastroenterology, and the Rome Foundation for supporting this study.
Published: 2023

26. Better prognosis in females with severe COVID-19 pneumonia: possible role of inflammation as potential mediator

Author: Cristina Mussini, Alessandro Cozzi-Lepri, Marianna Menozzi, Marianna Meschiari, Erica Franceschini, Carlotta Rogati, Gianluca Cuomo, Andrea Bedini, Vittorio Iadisernia, Sara Volpi, Jovana Milic, Roberto Tonelli, Lucio Brugioni, Antonello Pietrangelo, Massimo Girardis, Andrea Cossarizza, Enrico Clini, Giovanni Guaraldi, Erica Bacca, Vanni Borghi, Giulia Burastero, Federica Carli, Giacomo Ciusa, Luca Corradi, Margherita Di Gaetano, Matteo Faltoni, Giacomo Franceschi, Gabriella Orlando, Francesco Pellegrino, Cinzia Puzzolante, Alessandro Raimondi, Antonella Santoro, Marco Tutone, Dina Yaacoub, Alberto Andreotti, Emanuela Biagioni, Filippo Bondi, Stefano Busani, Giovanni Chierego, Marzia Scotti, Lucia Serio, Caterina Bellinazzi, Rebecca Borella, Sara De Biasi, Anna De Gaetano, Lucia Fidanza, Lara Gibellini, Anna Iannone, Domenico Lo Tartaro, Marco Mattioli, Annamaria Paolini, Rossella Fogliani, Grazia Righini, and Mario Lugli
Subjects: Male, sex differences, 0301 basic medicine, Microbiology (medical), Mediation (statistics), medicine.medical_specialty, medicine.medical_treatment, 030106 microbiology, Context (language use), Pathogenesis, Cohort Studies, 03 medical and health sciences, Sex Factors, 0302 clinical medicine, Risk Factors, Internal medicine, Humans, Medicine, 030212 general & internal medicine, Respiratory system, female sex, Survival analysis, Aged, Retrospective Studies, Inflammation, Mechanical ventilation, SARS-CoV-2, business.industry, Absolute risk reduction, COVID-19, General Medicine, Middle Aged, Prognosis, medicine.disease, Respiration, Artificial, Hospitalization, Pneumonia, Infectious Diseases, SARS-CoV-2, COVID-19, female sex, prognosis, inflammation, inflammation, Commentary, Female, prognosis, CRP, business, Cohort study
Abstract: Objectives Sex differences in COVID-19 severity and mortality have been described. Key aims of this analysis were to compare the risk of invasive mechanical ventilation (IMV) and mortality by sex and to explore whether variation in specific biomarkers could mediate this difference. Methods This was a retrospective, observational cohort study among patients with severe COVID-19 pneumonia. A survival analysis was conducted to compare time to the composite endpoint of IMV or death by sex. Interaction was formally tested to compare the risk difference by sex in subsets. Mediation analysis with a binary endpoint IMV or death (yes/no) by end of follow-up for a number of inflammation/coagulation biomarkers in the context of counterfactual prediction was also conducted. Results Among 415 patients, 134 were females (32%) and 281 males (67%), median age 66 years (IQR 54-77). At admission, females showed a significantly less severe clinical and respiratory profiles with a higher PaO2/FiO2 (254 mmHg vs 191 mmHg; p=0.023). By 28 days from admission, 49.2% (95% CI: 39.6-58.9%) of males vs. 31.7% (17.9-45.4%) of females underwent IMV or death (log-rank p-value Conclusions Our analysis confirms a difference in the risk of COVID-19 clinical progression by sex and provides a hypothesis for potential mechanisms leading to this. CRP showed a predominant role to mediate the difference in risk by sex.
Published: 2021

27. A small molecule redistributes iron in ferroportin-deficient mice and patient-derived primary macrophages

Author: Stella Ekaputri, Eun-Kyung Choi, Manuela Sabelli, Luisa Aring, Kelsie J. Green, JuOae Chang, Kai Bao, Hak Soo Choi, Shigeki Iwase, Jonghan Kim, Elena Corradini, Antonello Pietrangelo, Martin D. Burke, and Young Ah Seo
Subjects: Multidisciplinary, Iron, Macrophages, ferroportin disease, Transferrin, Tropolone, Mice, iron misdistribution, Ferritins, hinokitiol, Monoterpenes, Animals, Humans, hemoglobinization, iron redistribution, Cation Transport Proteins, Zebrafish
Abstract: Deficiencies of the transmembrane iron-transporting protein ferroportin (FPN1) cause the iron misdistribution that underlies ferroportin disease, anemia of inflammation, and several other human diseases and conditions. A small molecule natural product, hinokitiol, was recently shown to serve as a surrogate transmembrane iron transporter that can restore hemoglobinization in zebrafish deficient in other iron transporting proteins and can increase gut iron absorption in FPN1-deficient flatiron mice. However, whether hinokitiol can restore normal iron physiology in FPN1-deficient animals or primary cells from patients and the mechanisms underlying such targeted activities remain unknown. Here, we show that hinokitiol redistributes iron from the liver to red blood cells in flatiron mice, thereby increasing hemoglobin and hematocrit. Mechanistic studies confirm that hinokitiol functions as a surrogate transmembrane iron transporter to release iron trapped within liver macrophages, that hinokitiol-Fe complexes transfer iron to transferrin, and that the resulting transferrin-Fe complexes drive red blood cell maturation in a transferrin-receptor–dependent manner. We also show in FPN1-deficient primary macrophages derived from patients with ferroportin disease that hinokitiol moves labile iron from inside to outside cells and decreases intracellular ferritin levels. The mobilization of nonlabile iron is accompanied by reductions in intracellular ferritin, consistent with the activation of regulated ferritin proteolysis. These findings collectively provide foundational support for the translation of small molecule iron transporters into therapies for human diseases caused by iron misdistribution.
Published: 2022

28. Hyperglycemia at admission, comorbidities, and in-hospital mortality in elderly patients hospitalized in internal medicine wards: data from the RePoSI Registry

Author: Salvatore, Corrao, Alessandro, Nobili, Giuseppe, Natoli, Pier Mannuccio Mannucci, Francesco, Perticone, Antonello, Pietrangelo, Christiano, Argano, Giuseppe, Licata, Francesco, Violi, Gino Roberto Corazza, Alessandra, Marengoni, Francesco, Salerno, Matteo, Cesari, Mauro, Tettamanti, Luca, Pasina, Carlotta, Franchi, Laura, Cortesi, Gabriella, Miglio, Ilaria, Ardoino, Alessio, Novella, Domenico, Prisco, Elena, Silvestri, Giacomo, Emmi, Alessandra, Bettiol, Cenci, Caterina, Gianni, Biolo, Michela, Zanetti, Martina, Guadagni, Michele, Zaccari, Massimiliano, Chiuch, Massimo, Vanoli, Giulia, Grignani, Edoardo Alessandro Pulixi, Mauro, Bernardi, Silvia Li Bassi, Luca, Santi, Giacomo, Zaccherini, Graziana, Lupattelli, Elmo, Mannarino, Vanessa, Bianconi, Francesco, Paciullo, Riccardo, Alcidi, Ranuccio, Nuti, Roberto, Valenti, Martina, Ruvio, Silvia, Cappelli, Alberto, Palazzuoli, Domenico, Girelli, Fabiana, Busti, Giacomo, Marchi, Mario, Barbagallo, Ligia, Dominguez, Floriana, Cocita, Vincenza, Beneduce, Lidia, Plances, Salvatore, Mularo, Massimo, Raspanti, Marco, Zoli, Ilaria, Lazzari, Mattia, Brunori, Elisa, Fabbri, Donatella, Magalotti, Raffaella, Arnò, Franco Laghi Pasini, Pier Leopoldo Capecchi, Giuseppe, Palasciano, Maria Ester Modeo, Carla Di Gennaro, Maria Domenica Cappellini, Diletta, Maira, Valeria Di Stefano, Giovanna, Fabio, Sonia, Seghezzi, Marta, Mancarella, Margherita Migone De Amicis, Giacomo De Luca, Natalia, Scaramellini, Paolo Dionigi Rossi, Sarah, Damanti, Marta, Clerici, Federica, Conti, Giulia, Bonini, Barbara Brignolo Ottolini, Antonio Di Sabatino, Emanuela, Miceli, Marco Vincenzo Lenti, Martina, Pisati, Costanza Caccia Dominioni, Giovanni, Murialdo, Alessio, Marra, Federico, Cattaneo, Roberto, Pontremoli, Valentina, Beccati, Giulia, Nobili, Maria Beatrice Secchi, Davide, Ghelfi, Luigi, Anastasio, Lucia, Sofia, Maria, Carbone, Francesco, Cipollone, Maria Teresa Guagnano, Emanuele, Valeriani, Ilaria, Rossi, Gerardo, Mancuso, Daniela, Calipari, Mosè, Bartone, Giuseppe, Delitala, Maria, Berria, Chiara, Pes, Alessandro, Delitala, Maurizio, Muscaritoli, Alessio, Molfino, Enrico, Petrillo, Giuseppe, Zuccalà, Gabriella, D'Aurizio, Giuseppe, Romanelli, Alberto, Zucchelli, Francesca, Manzoni, Andrea, Volpini, Antonio, Picardi, Umberto Vespasiani Gentilucci, Paolo, Gallo, Chiara, Dell'Unto, Giorgio, Annoni, Maurizio, Corsi, Giuseppe, Bellelli, Sara, Zazzetta, Paolo, Mazzola, Hajnalka, Szabo, Alessandra, Bonfanti, Franco, Arturi, Elena, Succurro, Mariangela, Rubino, Bruno, Tassone, Giorgio, Sesti, Maria Grazia Serra, Maria Antonietta Bleve, Laura, Gasbarrone, Maria Rosaria Sajeva, Antonio, Brucato, Silvia, Ghidoni, Fabrizio, Fabris, Irene, Bertozzi, Giulia, Bogoni, Maria Victoria Rabuini, Elisabetta, Cosi, Paolo, Scarinzi, Annalisa, Amabile, Elisabetta, Omenetto, Tancredi, Prandini, Manfredini, Roberto, Fabbian, Fabio, Boari, Benedetta, DE GIORGI, Alfredo, Tiseo, Ruana, DE GIORGIO, Roberto, Giuseppe, Paolisso, Maria Rosaria Rizzo, Claudio, Borghi, Enrico, Strocchi, Eugenia, Ianniello, Mario, Soldati, Carlo, Sabbà, Francesco Saverio Vella, Patrizia, Suppressa, Andrea, Schilardi, Francesca, Loparco, Giovanni Michele De Vincenzo, Alessio, Comitangelo, Emanuele, Amoruso, Luigi, Fenoglio, Andrea, Falcetta, Christian, Bracco, Anna, L Fracanzani Silvia Fargion, Silvia, Tiraboschi, Annalisa, Cespiati, Giovanna, Oberti, Giordano, Sigon, Flora, Peyvandi, Raffaella, Rossio, Barbara, Ferrari, Giulia, Colombo, Pasquale, Agosti, Valter, Monzani, Valeria, Savojardo, Christian, Folli, Giuliana, Ceriani, Giada, Pallini, Franco, Dallegri, Luciano, Ottonello, Luca, Liberale, Lara, Caserza, Kassem, Salam, Nicola Lucio Liberato, Tiziana, Tognin, Giovanni Battista Bianchi, Sabrina, Giaquinto, Francesco, Purrello, Antonino Di Pino, Salvatore, Piro, Renzo, Rozzini, Lina, Falanga, Elena, Spazzini, Camillo, Ferrandina, Giuseppe, Montrucchio, Paolo, Petitti, Paolo, Peasso, Edoardo, Favale, Cesare, Poletto, Raffaella, Salmi, Piergiorgio, Gaudenzi, Ludovica, Perri, Raffaele, Landolfi, Massimo, Montalto, Antonio, Mirijello, Luigina, Guasti, Luana, Castiglioni, Andrea, Maresca, Alessandro, Squizzato, Leonardo, Campiotti, Alessandra, Grossi, Marco, Bertolotti, Chiara, Mussi, Giulia, Lancellotti, Maria Vittoria Libbra, Giulia, Dondi, Elisa, Pellegrini, Lucia, Carulli, Matteo, Galassi, Yasmine, Grassi, Maria, Perticone, Rosa, Battaglia, Marco, Filice, Raffaele, Maio, Vincenzo, Stanghellini, Eugenio, Ruggeri, Sara Del Vecchio, Andrea, Salvi, Roberto, Leonardi, Giampaolo, Damiani, William, Capeci, Armando, Gabrielli, Massimo, Mattioli, Giuseppe Pio Martino, Lorenzo, Biondi, Pietro, Pettinari, Riccardo, Ghio, Anna Dal Col, Salvatore, Minisola, Luciano, Colangelo, Mirella, Cilli, Giancarlo, Labbadia, Antonella, Afeltra, Benedetta, Marigliano, Maria Elena Pipita, Pietro, Castellino, Luca, Zanoli, Samuele, Pignataro, Alfio, Gennaro, Julien, Blanco, Valter, Saracco, Marisa, Fogliati, Carlo, Bussolino, Francesca, Mete, Miriam, Gino, Antonio, Cittadini, Carlo, Vigorito, Michele, Arcopinto, Andrea, Salzano, Emanuele, Bobbio, Alberto Maria Marra, Domenico, Sirico, Guido, Moreo, Francesca, Gasparini, Silvia, Prolo, Gloria, Pina, Alberto, Ballestrero, Fabio, Ferrando, Sergio, Berra, Simonetta, Dassi, Maria Cristina Nava, Bruno, Graziella, Stefano, Baldassarre, Salvatore, Fragapani, Gabriella, Gruden, Giorgio, Galanti, Gabriele, Mascherini, Cristian, Petri, Laura, Stefani, Margherita, Girino, Valeria, Piccinelli, Francesco, Nasso, Vincenza, Gioffrè, Maria, Pasquale, Giuseppe, Scattolin, Sergio, Martinelli, Mauro, Turrin, Leonardo, Sechi, Cristina, Catena, Gianluca, Colussi, Nicola, Passariello, Luca, Rinaldi, Franco, Berti, Giuseppe, Famularo, Patrizia, Tarsitani, Roberto, Castello, Michela, Pasino, Gian Paolo Ceda, Marcello Giuseppe Maggio, Simonetta, Morganti, Andrea, Artoni, Stefano Del Giacco, Davide, Firinu, Francesca, Losa, Giovanni, Paoletti, Giulia, Costanzo, Giuseppe, Montalto, Anna, Licata, Valentina, Malerba, Filippo Alessandro Montalto, Antonino, Lasco, Giorgio, Basile, Antonino, Catalano, Lorenzo, Malatino, Benedetta, Stancanelli, Valentina, Terranova, Salvatore Di Marca, Rosario Di Quattro, Lara La Malfa, Rossella, Caruso, Patrizia, Mecocci, Carmelinda, Ruggiero, Virginia, Boccardi, Tiziana, Meschi, Fulvio, Lauretani, Andrea, Ticinesi, Antonio, Nouvenne, Pietro, Minuz, Luigi, Fondrieschi, Mario, Pirisi, Gian Paolo Fra, Daniele, Sola, Massimo, Porta, Piero, Riva, Roberto, Quadri, Erica, Larovere, Marco, Novelli, Giorgio, Scanzi, Caterina, Mengoli, Stella, Provini, Laura, Ricevuti, Emilio, Simeone, Rosa, Scurti, Fabio, Tolloso, Roberto, Tarquini, Alice, Valoriani, Silvia, Dolenti, Giulia, Vannini, Alberto, Tedeschi, Lucia, Trotta, Riccardo, Volpi, Pietro, Bocchi, Alessandro, Vignali, Sergio, Harari, Chiara, Lonati, Mara, Cattaneo, Federico, Napoli., Corrao S, Nobili A, Natoli G, Mannucci PM, Perticone F, Pietrangelo A, Argano C, REPOSI Investigator, Borghi C, Corrao S., Nobili A., Natoli G., Mannucci P.M., Perticone F., Pietrangelo A., Argano C., Licata G., Violi F., Corazza G.R., Marengoni A., Salerno F., Cesari M., Tettamanti M., Pasina L., Franchi C., Cortesi L., Miglio G., Ardoino I., Novella A., Prisco D., Silvestri E., Emmi G., Bettiol A., Caterina C., Biolo G., Zanetti M., Guadagni M., Zaccari M., Chiuch M., Vanoli M., Grignani G., Pulixi E.A., Bernardi M., Bassi S.L., Santi L., Zaccherini G., Lupattelli G., Mannarino E., Bianconi V., Paciullo F., Alcidi R., Nuti R., Valenti R., Ruvio M., Cappelli S., Palazzuoli A., Girelli D., Busti F., Marchi G., Barbagallo M., Dominguez L., Cocita F., Beneduce V., Plances L., Mularo S., Raspanti M., Zoli M., Lazzari I., Brunori M., Fabbri E., Magalotti D., Arno R., Pasini F.L., Capecchi P.L., Palasciano G., Modeo M.E., Di Gennaro C., Cappellini M.D., Maira D., Di Stefano V., Fabio G., Seghezzi S., Mancarella M., De Amicis M.M., De Luca G., Scaramellini N., Rossi P.D., Damanti S., Clerici M., Conti F., Bonini G., Ottolini B.B., Di Sabatino A., Miceli E., Lenti M.V., Pisati M., Dominioni C.C., Murialdo G., Marra A., Cattaneo F., Pontremoli R., Beccati V., Nobili G., Secchi M.B., Ghelfi D., Anastasio L., Sofia L., Carbone M., Cipollone F., Guagnano M.T., Valeriani E., Rossi I., Mancuso G., Calipari D., Bartone M., Delitala G., Berria M., Pes C., Delitala A., Muscaritoli M., Molfino A., Petrillo E., Zuccala G., D'Aurizio G., Romanelli G., Zucchelli A., Manzoni F., Volpini A., Picardi A., Gentilucci U.V., Gallo P., Dell'Unto C., Annoni G., Corsi M., Bellelli G., Zazzetta S., Mazzola P., Szabo H., Bonfanti A., Arturi F., Succurro E., Rubino M., Tassone B., Sesti G., Serra M.G., Bleve M.A., Gasbarrone L., Sajeva M.R., Brucato A., Ghidoni S., Fabris F., Bertozzi I., Bogoni G., Rabuini M.V., Cosi E., Scarinzi P., Amabile A., Omenetto E., Prandini T., Manfredini R., Fabbian F., Boari B., De Giorgi A., Tiseo R., De Giorgio R., Paolisso G., Rizzo M.R., Borghi C., Strocchi E., Ianniello E., Soldati M., Sabba C., Vella F.S., Suppressa P., Schilardi A., Loparco F., De Vincenzo G.M., Comitangelo A., Amoruso E., Fenoglio L., Falcetta A., Bracco C., Fargion A.L.F.S., Tiraboschi S., Cespiati A., Oberti G., Sigon G., Peyvandi F., Rossio R., Ferrari B., Colombo G., Agosti P., Monzani V., Savojardo V., Folli C., Ceriani G., Pallini G., Dallegri F., Ottonello L., Liberale L., Caserza L., Salam K., Liberato N.L., Tognin T., Bianchi G.B., Giaquinto S., Purrello F., Di Pino A., Piro S., Rozzini R., Falanga L., Spazzini E., Ferrandina C., Montrucchio G., Petitti P., Peasso P., Favale E., Poletto C., Salmi R., Gaudenzi P., Perri L., Landolfi R., Montalto M., Mirijello A., Guasti L., Castiglioni L., Maresca A., Squizzato A., Campiotti L., Grossi A., Bertolotti M., Mussi C., Lancellotti G., Libbra M.V., Dondi G., Pellegrini E., Carulli L., Galassi M., Grassi Y., Perticone M., Battaglia R., FIlice M., Maio R., Stanghellini V., Ruggeri E., del Vecchio S., Salvi A., Leonardi R., Damiani G., Capeci W., Gabrielli A., Mattioli M., Martino G.P., Biondi L., Pettinari P., Ghio R., Col A.D., Minisola S., Colangelo L., Cilli M., Labbadia G., Afeltra A., Marigliano B., Pipita M.E., Castellino P., Zanoli L., Pignataro S., Gennaro A., Blanco J., Saracco V., Fogliati M., Bussolino C., Mete F., Gino M., Cittadini A., Vigorito C., Arcopinto M., Salzano A., Bobbio E., Marra A.M., Sirico D., Moreo G., Gasparini F., Prolo S., Pina G., Ballestrero A., Ferrando F., Berra S., Dassi S., Nava M.C., Graziella B., Baldassarre S., Fragapani S., Gruden G., Galanti G., Mascherini G., Petri C., Stefani L., Girino M., Piccinelli V., Nasso F., Gioffre V., Pasquale M., Scattolin G., Martinelli S., Turrin M., Sechi L., Catena C., Colussi G., Passariello N., Rinaldi L., Berti F., Famularo G., Tarsitani P., Castello R., Pasino M., Ceda G.P., Maggio M.G., Morganti S., Artoni A., Del Giacco S., Firinu D., Losa F., Paoletti G., Costanzo G., Montalto G., Licata A., Malerba V., Montalto F.A., Lasco A., Basile G., Catalano A., Malatino L., Stancanelli B., Terranova V., Di Marca S., Di Quattro R., La Malfa L., Caruso R., Mecocci P., Ruggiero C., Boccardi V., Meschi T., Lauretani F., Ticinesi A., Nouvenne A., Minuz P., Fondrieschi L., Pirisi M., Fra G.P., Sola D., Porta M., Riva P., Quadri R., Larovere E., Novelli M., Scanzi G., Mengoli C., Provini S., Ricevuti L., Simeone E., Scurti R., Tolloso F., Tarquini R., Valoriani A., Dolenti S., Vannini G., Tedeschi A., Trotta L., Volpi R., Bocchi P., Vignali A., Harari S., Lonati C., Cattaneo M., Napoli F., Corrao, S., Nobili, A., Natoli, G., Mannucci, P. M., Perticone, F., Pietrangelo, A., Argano, C., Licata, G., Violi, F., Corazza, G. R., Marengoni, A., Salerno, F., Cesari, M., Tettamanti, M., Pasina, L., Franchi, C., Cortesi, L., Miglio, G., Ardoino, I., Novella, A., Prisco, D., Silvestri, E., Emmi, G., Bettiol, A., Caterina, C., Biolo, G., Zanetti, M., Guadagni, M., Zaccari, M., Chiuch, M., Vanoli, M., Grignani, G., Pulixi, E. A., Bernardi, M., Bassi, S. L., Santi, L., Zaccherini, G., Lupattelli, G., Mannarino, E., Bianconi, V., Paciullo, F., Alcidi, R., Nuti, R., Valenti, R., Ruvio, M., Cappelli, S., Palazzuoli, A., Girelli, D., Busti, F., Marchi, G., Barbagallo, M., Dominguez, L., Cocita, F., Beneduce, V., Plances, L., Mularo, S., Raspanti, M., Zoli, M., Lazzari, I., Brunori, M., Fabbri, E., Magalotti, D., Arno, R., Pasini, F. L., Capecchi, P. L., Palasciano, G., Modeo, M. E., Di Gennaro, C., Cappellini, M. D., Maira, D., Di Stefano, V., Fabio, G., Seghezzi, S., Mancarella, M., De Amicis, M. M., De Luca, G., Scaramellini, N., Rossi, P. D., Damanti, S., Clerici, M., Conti, F., Bonini, G., Ottolini, B. B., Di Sabatino, A., Miceli, E., Lenti, M. V., Pisati, M., Dominioni, C. C., Murialdo, G., Marra, A., Cattaneo, F., Pontremoli, R., Beccati, V., Nobili, G., Secchi, M. B., Ghelfi, D., Anastasio, L., Sofia, L., Carbone, M., Cipollone, F., Guagnano, M. T., Valeriani, E., Rossi, I., Mancuso, G., Calipari, D., Bartone, M., Delitala, G., Berria, M., Pes, C., Delitala, A., Muscaritoli, M., Molfino, A., Petrillo, E., Zuccala, G., D'Aurizio, G., Romanelli, G., Zucchelli, A., Manzoni, F., Volpini, A., Picardi, A., Gentilucci, U. V., Gallo, P., Dell'Unto, C., Annoni, G., Corsi, M., Bellelli, G., Zazzetta, S., Mazzola, P., Szabo, H., Bonfanti, A., Arturi, F., Succurro, E., Rubino, M., Tassone, B., Sesti, G., Serra, M. G., Bleve, M. A., Gasbarrone, L., Sajeva, M. R., Brucato, A., Ghidoni, S., Fabris, F., Bertozzi, I., Bogoni, G., Rabuini, M. V., Cosi, E., Scarinzi, P., Amabile, A., Omenetto, E., Prandini, T., Manfredini, R., Fabbian, F., Boari, B., De Giorgi, A., Tiseo, R., De Giorgio, R., Paolisso, G., Rizzo, M. R., Borghi, C., Strocchi, E., Ianniello, E., Soldati, M., Sabba, C., Vella, F. S., Suppressa, P., Schilardi, A., Loparco, F., De Vincenzo, G. M., Comitangelo, A., Amoruso, E., Fenoglio, L., Falcetta, A., Bracco, C., Fargion, A. L. F. S., Tiraboschi, S., Cespiati, A., Oberti, G., Sigon, G., Peyvandi, F., Rossio, R., Ferrari, B., Colombo, G., Agosti, P., Monzani, V., Savojardo, V., Folli, C., Ceriani, G., Pallini, G., Dallegri, F., Ottonello, L., Liberale, L., Caserza, L., Salam, K., Liberato, N. L., Tognin, T., Bianchi, G. B., Giaquinto, S., Purrello, F., Di Pino, A., Piro, S., Rozzini, R., Falanga, L., Spazzini, E., Ferrandina, C., Montrucchio, G., Petitti, P., Peasso, P., Favale, E., Poletto, C., Salmi, R., Gaudenzi, P., Perri, L., Landolfi, R., Montalto, M., Mirijello, A., Guasti, L., Castiglioni, L., Maresca, A., Squizzato, A., Campiotti, L., Grossi, A., Bertolotti, M., Mussi, C., Lancellotti, G., Libbra, M. V., Dondi, G., Pellegrini, E., Carulli, L., Galassi, M., Grassi, Y., Perticone, M., Battaglia, R., Filice, M., Maio, R., Stanghellini, V., Ruggeri, E., del Vecchio, S., Salvi, A., Leonardi, R., Damiani, G., Capeci, W., Gabrielli, A., Mattioli, M., Martino, G. P., Biondi, L., Pettinari, P., Ghio, R., Col, A. D., Minisola, S., Colangelo, L., Cilli, M., Labbadia, G., Afeltra, A., Marigliano, B., Pipita, M. E., Castellino, P., Zanoli, L., Pignataro, S., Gennaro, A., Blanco, J., Saracco, V., Fogliati, M., Bussolino, C., Mete, F., Gino, M., Cittadini, A., Vigorito, C., Arcopinto, M., Salzano, A., Bobbio, E., Marra, A. M., Sirico, D., Moreo, G., Gasparini, F., Prolo, S., Pina, G., Ballestrero, A., Ferrando, F., Berra, S., Dassi, S., Nava, M. C., Graziella, B., Baldassarre, S., Fragapani, S., Gruden, G., Galanti, G., Mascherini, G., Petri, C., Stefani, L., Girino, M., Piccinelli, V., Nasso, F., Gioffre, V., Pasquale, M., Scattolin, G., Martinelli, S., Turrin, M., Sechi, L., Catena, C., Colussi, G., Passariello, N., Rinaldi, L., Berti, F., Famularo, G., Tarsitani, P., Castello, R., Pasino, M., Ceda, G. P., Maggio, M. G., Morganti, S., Artoni, A., Del Giacco, S., Firinu, D., Losa, F., Paoletti, G., Costanzo, G., Montalto, G., Licata, A., Malerba, V., Montalto, F. A., Lasco, A., Basile, G., Catalano, A., Malatino, L., Stancanelli, B., Terranova, V., Di Marca, S., Di Quattro, R., La Malfa, L., Caruso, R., Mecocci, P., Ruggiero, C., Boccardi, V., Meschi, T., Lauretani, F., Ticinesi, A., Nouvenne, A., Minuz, P., Fondrieschi, L., Pirisi, M., Fra, G. P., Sola, D., Porta, M., Riva, P., Quadri, R., Larovere, E., Novelli, M., Scanzi, G., Mengoli, C., Provini, S., Ricevuti, L., Simeone, E., Scurti, R., Tolloso, F., Tarquini, R., Valoriani, A., Dolenti, S., Vannini, G., Tedeschi, A., Trotta, L., Volpi, R., Bocchi, P., Vignali, A., Harari, S., Lonati, C., Cattaneo, M., Napoli, F., Corrao, S, Nobili, A, Natoli, G, Mannucci, P, Perticone, F, Pietrangelo, A, Argano, C, Licata, G, Violi, F, Corazza, G, Marengoni, A, Salerno, F, Cesari, M, Tettamanti, M, Pasina, L, Franchi, C, Cortesi, L, Miglio, G, Ardoino, I, Novella, A, Prisco, D, Silvestri, E, Emmi, G, Bettiol, A, Caterina, C, Biolo, G, Zanetti, M, Guadagni, M, Zaccari, M, Chiuch, M, Vanoli, M, Grignani, G, Pulixi, E, Bernardi, M, Bassi, S, Santi, L, Zaccherini, G, Lupattelli, G, Mannarino, E, Bianconi, V, Paciullo, F, Alcidi, R, Nuti, R, Valenti, R, Ruvio, M, Cappelli, S, Palazzuoli, A, Girelli, D, Busti, F, Marchi, G, Barbagallo, M, Dominguez, L, Cocita, F, Beneduce, V, Plances, L, Mularo, S, Raspanti, M, Zoli, M, Lazzari, I, Brunori, M, Fabbri, E, Magalotti, D, Arno, R, Pasini, F, Capecchi, P, Palasciano, G, Modeo, M, Di Gennaro, C, Cappellini, M, Maira, D, Di Stefano, V, Fabio, G, Seghezzi, S, Mancarella, M, De Amicis, M, De Luca, G, Scaramellini, N, Rossi, P, Damanti, S, Clerici, M, Conti, F, Bonini, G, Ottolini, B, Di Sabatino, A, Miceli, E, Lenti, M, Pisati, M, Dominioni, C, Murialdo, G, Marra, A, Cattaneo, F, Pontremoli, R, Beccati, V, Nobili, G, Secchi, M, Ghelfi, D, Anastasio, L, Sofia, L, Carbone, M, Cipollone, F, Guagnano, M, Valeriani, E, Rossi, I, Mancuso, G, Calipari, D, Bartone, M, Delitala, G, Berria, M, Pes, C, Delitala, A, Muscaritoli, M, Molfino, A, Petrillo, E, Zuccala, G, D'Aurizio, G, Romanelli, G, Zucchelli, A, Manzoni, F, Volpini, A, Picardi, A, Gentilucci, U, Gallo, P, Dell'Unto, C, Annoni, G, Corsi, M, Bellelli, G, Zazzetta, S, Mazzola, P, Szabo, H, Bonfanti, A, Arturi, F, Succurro, E, Rubino, M, Tassone, B, Sesti, G, Serra, M, Bleve, M, Gasbarrone, L, Sajeva, M, Brucato, A, Ghidoni, S, Fabris, F, Bertozzi, I, Bogoni, G, Rabuini, M, Cosi, E, Scarinzi, P, Amabile, A, Omenetto, E, Prandini, T, Manfredini, R, Fabbian, F, Boari, B, De Giorgi, A, Tiseo, R, De Giorgio, R, Paolisso, G, Rizzo, M, Borghi, C, Strocchi, E, Ianniello, E, Soldati, M, Sabba, C, Vella, F, Suppressa, P, Schilardi, A, Loparco, F, De Vincenzo, G, Comitangelo, A, Amoruso, E, Fenoglio, L, Falcetta, A, Bracco, C, Fargion, A, Tiraboschi, S, Cespiati, A, Oberti, G, Sigon, G, Peyvandi, F, Rossio, R, Ferrari, B, Colombo, G, Agosti, P, Monzani, V, Savojardo, V, Folli, C, Ceriani, G, Pallini, G, Dallegri, F, Ottonello, L, Liberale, L, Caserza, L, Salam, K, Liberato, N, Tognin, T, Bianchi, G, Giaquinto, S, Purrello, F, Di Pino, A, Piro, S, Rozzini, R, Falanga, L, Spazzini, E, Ferrandina, C, Montrucchio, G, Petitti, P, Peasso, P, Favale, E, Poletto, C, Salmi, R, Gaudenzi, P, Perri, L, Landolfi, R, Montalto, M, Mirijello, A, Guasti, L, Castiglioni, L, Maresca, A, Squizzato, A, Campiotti, L, Grossi, A, Bertolotti, M, Mussi, C, Lancellotti, G, Libbra, M, Dondi, G, Pellegrini, E, Carulli, L, Galassi, M, Grassi, Y, Perticone, M, Battaglia, R, Filice, M, Maio, R, Stanghellini, V, Ruggeri, E, del Vecchio, S, Salvi, A, Leonardi, R, Damiani, G, Capeci, W, Gabrielli, A, Mattioli, M, Martino, G, Biondi, L, Pettinari, P, Ghio, R, Col, A, Minisola, S, Colangelo, L, Cilli, M, Labbadia, G, Afeltra, A, Marigliano, B, Pipita, M, Castellino, P, Zanoli, L, Pignataro, S, Gennaro, A, Blanco, J, Saracco, V, Fogliati, M, Bussolino, C, Mete, F, Gino, M, Cittadini, A, Vigorito, C, Arcopinto, M, Salzano, A, Bobbio, E, Sirico, D, Moreo, G, Gasparini, F, Prolo, S, Pina, G, Ballestrero, A, Ferrando, F, Berra, S, Dassi, S, Nava, M, Graziella, B, Baldassarre, S, Fragapani, S, Gruden, G, Galanti, G, Mascherini, G, Petri, C, Stefani, L, Girino, M, Piccinelli, V, Nasso, F, Gioffre, V, Pasquale, M, Scattolin, G, Martinelli, S, Turrin, M, Sechi, L, Catena, C, Colussi, G, Passariello, N, Rinaldi, L, Berti, F, Famularo, G, Tarsitani, P, Castello, R, Pasino, M, Ceda, G, Maggio, M, Morganti, S, Artoni, A, Del Giacco, S, Firinu, D, Losa, F, Paoletti, G, Costanzo, G, Montalto, G, Licata, A, Malerba, V, Montalto, F, Lasco, A, Basile, G, Catalano, A, Malatino, L, Stancanelli, B, Terranova, V, Di Marca, S, Di Quattro, R, La Malfa, L, Caruso, R, Mecocci, P, Ruggiero, C, Boccardi, V, Meschi, T, Lauretani, F, Ticinesi, A, Nouvenne, A, Minuz, P, Fondrieschi, L, Pirisi, M, Fra, G, Sola, D, Porta, M, Riva, P, Quadri, R, Larovere, E, Novelli, M, Scanzi, G, Mengoli, C, Provini, S, Ricevuti, L, Simeone, E, Scurti, R, Tolloso, F, Tarquini, R, Valoriani, A, Dolenti, S, Vannini, G, Tedeschi, A, Trotta, L, Volpi, R, Bocchi, P, Vignali, A, Harari, S, Lonati, C, Cattaneo, M, and Napoli, F
Subjects: Registrie, Male, Comorbidity, Diabetes, Disability, Elderly, Hyperglycemia, Mortality, Aged, Aged, 80 and over, Female, Hospital Mortality, Hospitals, Humans, Internal Medicine, Registries, Hospitalization, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Socio-culturale, Renal function, 030204 cardiovascular system & hematology, Diabete, Hospital, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Rating scale, Internal medicine, Diabetes mellitus, 80 and over, medicine, LS4_4, 030212 general & internal medicine, Class III obesity, business.industry, Mortality rate, Comorbidity, Diabetes, Disability, Elderly, Hyperglycemia, Mortality, General Medicine, medicine.disease, Mood disorders, Geriatric Depression Scale, Original Article, business, Human
Abstract: Aims The association between hyperglycemia at hospital admission and relevant short- and long-term outcomes in elderly population is known. We assessed the effects on mortality of hyperglycemia, disability, and multimorbidity at admission in internal medicine ward in patients aged ≥ 65 years. Methods Data were collected from an active register of 102 internal medicine and geriatric wards in Italy (RePoSi project). Patients were recruited during four index weeks of a year. Socio-demographic data, reason for hospitalization, diagnoses, treatment, severity and comorbidity indexes (Cumulative Illness rating Scale CIRS-SI and CIRS-CI), renal function, functional (Barthel Index), and cognitive status (Short Blessed Test) and mood disorders (Geriatric Depression Scale) were recorded. Mortality rates were assessed in hospital 3 and 12 months after discharge. Results Of the 4714 elderly patients hospitalized, 361 had a glycemia level ≥ 250 mg/dL at admission. Compared to subjects with lower glycemia level, patients with glycemia ≥ 250 mg/dL showed higher rates of male sex, smoke and class III obesity. These patients had a significantly lower Barthel Index (p = 0.0249), higher CIRS-SI and CIRS-CI scores (p = 0.0025 and p = 0.0013, respectively), and took more drugs. In-hospital mortality rate was 9.2% and 5.1% in subjects with glycemia ≥ 250 and p = 0.0010). Regression analysis showed a strong association between in-hospital death and glycemia ≥ 250 mg/dL (OR 2.07; [95% CI 1.34–3.19]), Barthel Index ≤ 40 (3.28[2.44–4.42]), CIRS-SI (1.87[1.27–2.77]), and male sex (1.54[1.16–2.03]). Conclusions The stronger predictors of in-hospital mortality for older patients admitted in general wards were glycemia level ≥ 250 mg/dL, Barthel Index ≤ 40, CIRS-SI, and male sex.
Published: 2021

29. Asymptomatic deep venous thrombosis in hospitalized acutely ill medical patients: risk factors and therapeutic implications

Author: Lorenzo Loffredo, Gianpaolo Vidili, Angela Sciacqua, Chiara Cogliati, Rosella Di Giulio, Sciaila Bernardini, Paolo Ciacci, Antonello Pietrangelo, Federica Orlando, Aurora Paraninfi, Maria Boddi, Giovanni Di Minno, Lorenzo Falsetti, Corrado Lodigiani, Angelo Santoliquido, Evaristo Ettorre, Pasquale Pignatelli, Maria Felice Arezzo, Job Harenberg, and Francesco Violi
Abstract: Background: Acutely ill medical patients experience deep venous thrombosis (DVT) during the hospitalization, however the time course of DVT is still unclear. Objectives: To evaluate risk factors in acutely ill hospitalized medical patients for asymptomatic DVT (ADVT) and symptomatic DVT (SDVT) within 48 hours from admission and at discharge and comparing prophylaxis treatment with (group A) and without (group B) low-molecular weight heparin (LMWH) Patients/Methods: Consecutive acutely ill medical patients underwent duplex color compression ultrasonography (CUS) of proximal lower limb veins within 48 hours from admission and at discharge to screen for ADVT and to document SDVT. Primary end-point of the multicentric study was the incidence of all DVT. Biographical characteristics at hospitalization, D-Dimer and DD-improve score at entry and at discharge were analyzed by univariate and multivariate analysis to identify variables associated with DVT and compared between groups.Results: Of 2,100 patients (1002 females, 998 males, age 71±16) included 58 (2.7%) (31 females. 27 males, age 77±14) had ADVT at admission. A binary logistic regression analysis showed that age (O.R.: 1.03, 95% C.I. 1.007-1.05, p=0.008), thrombophilia (O.R.: 10,95% C.I. 3-34, pConclusions: The incidence of ADVT and of SDVT was high (3%) upon admission of acutely ill medical patients upon hospitalization. Advanced age, active cancer, thrombophilia, elevated D-dimer and IMPROVE-DD score greater than 2.5 were risk factors for ADVT should analyzed upon hospitalization for decision of treatment with LMWH. The benefit of therapeutic dose of anticoagulation needs to be investigated in patients with ADVT and specific risk factors. Trial registration: NCT03157843
Published: 2022

30. Idiopathic brain calcification in a patient with hereditary hemochromatosis

Author: Francesca Cavalleri, Francesco Cavallieri, Stefania Scarlini, Barbara Garavaglia, Elisa Menozzi, Elena Corradini, Chiara Reale, Antonello Pietrangelo, Massimo Fiorini, Franco Valzania, and Francesca Ferrara
Subjects: Male, Pathology, medicine.medical_specialty, Neurology, Neurodegeneration with brain iron accumulation, Iron, Neurological examination, Case Report, lcsh:RC346-429, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, lcsh:Neurology. Diseases of the nervous system, medicine.diagnostic_test, business.industry, Brain Diseases, Metabolic, Calcinosis, Basal ganglia, Brain calcification, Calcium, Hereditary hemochromatosis, General Medicine, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Dentate nucleus, Neurology (clinical), Hemochromatosis, Differential diagnosis, Siderosis, business, 030217 neurology & neurosurgery, Calcification
Abstract: Background Detection of brain-MRI T2/T2* gradient echo images (T2*GRE)-hypointensity can be compatible with iron accumulation and leads to a differential diagnosis work-up including neurodegeneration with brain iron accumulation (NBIA) and Wilson Disease. Idiopathic or secondary brain calcification can be also associated with neurological involvement and brain-MRI T2/T2*GRE-hypointensity. Hereditary hemochromatosis (HH), characterized by systemic iron loading, usually does not involve the CNS, and only sporadic cases of neurological abnormalities or brain-MRI T2/T2*GRE-hypointensity have been reported. Case presentation A 59-year-old man came to our observation after a diagnosis of HH carried out in another hospital 2 years before. First-level genetic test had revealed a homozygous HFE p.Cys282Tyr (C282Y) mutation compatible with the diagnosis of HFE-related HH, thus phlebotomy treatment was started. The patient had a history of metabolic syndrome, type-2 diabetes, autoimmune thyroiditis and severe chondrocalcinosis. Brain-MRI showed the presence of bilateral T2*GRE hypointensities within globus pallidus, substantia nigra, dentate nucleus and left pulvinar that were considered expression of cerebral siderosis. No neurological symptoms or family history of neurological disease were reported. Neurological examination revealed only mild right-sided hypokinetic-rigid syndrome. Vitamin D–PTH axis, measurements of serum ceruloplasmin and copper, and urinary copper were within the normal range. A brain computed tomography (CT) was performed to better characterize the suspected and unexplained brain iron accumulation. On the CT images, the hypointense regions in the brain MRI were hyperdense. DNA sequence analysis of genes associated with primary familial brain calcification and NBIA was negative. Conclusions This report highlights the importance of brain CT-scan in ambiguous cases of suspected cerebral siderosis, and suggests that HH patients with a severe phenotype, and likely associated with chondrocalcinosis, may display also brain calcifications. Further studies are needed to confirm this hypothesis. So far, we can speculate that iron and calcium homeostasis could be reciprocally connected within the basal ganglia.
Published: 2020

31. First and second waves among hospitalised patients with COVID-19 with severe pneumonia: a comparison of 28-day mortality over the 1-year pandemic in a tertiary university hospital in Italy

Author: Marianna, Meschiari, Alessandro, Cozzi-Lepri, Roberto, Tonelli, Erica, Bacca, Marianna, Menozzi, Erica, Franceschini, Gianluca, Cuomo, Andrea, Bedini, Sara, Volpi, Jovana, Milic, Lucio, Brugioni, Elisa, Romagnoli, Antonello, Pietrangelo, Elena, Corradini, Irene, Coloretti, Emanuela, Biagioni, Stefano, Busani, Massimo, Girardis, Andrea, Cossarizza, Enrico, Clini, Giovanni, Guaraldi, Cristina, Mussini, and Mario, Lugli
Subjects: Male, SARS-CoV-2, COVID-19, Tertiary Care Centers, Intensive Care Units, respiratory infections, Infectious Diseases, Italy, Humans, Female, epidemiology, Hospital Mortality, Pandemics, Aged
Abstract: Objective The first COVID-19–19 epidemic wave was over the period of February–May 2020. Since 1 October 2020, Italy, as many other European countries, faced a second wave. The aim of this analysis was to compare the 28-day mortality between the two waves among COVID-19 hospitalised patients. Design Observational cohort study. Standard survival analysis was performed to compare all-cause mortality within 28 days after hospital admission in the two waves. Kaplan-Meier curves as well as Cox regression model analysis were used. The effect of wave on risk of death was shown by means of HRs with 95% CIs. A sensitivity analysis around the impact of the circulating variant as a potential unmeasured confounder was performed. Setting University Hospital of Modena, Italy. Patients admitted to the hospital for severe COVID-19 pneumonia during the first (22 February–31 May 2020) and second (1 October–31 December 2020) waves were included. Results During the two study periods, a total of 1472 patients with severe COVID-19 pneumonia were admitted to our hospital, 449 during the first wave and 1023 during the second. Median age was 70 years (IQR 56–80), 37% women, 49% with PaO2/FiO2
Published: 2022

32. Phenotyping congestion in patients with acutely decompensated heart failure with preserved and reduced ejection fraction: The Decongestion duRing therapY for acute decOmpensated heart failure in HFpEF vs HFrEF- DRY-OFF study

Author: Massimo Salvetti, Tiziano Perrone, A Pitino, M.L. Muiesan, Antonello Pietrangelo, Elisa Maria Fiorelli, Federica Leidi, Elisa Ceriani, Patrizia Suppressa, M Gori, G De Matteis, Chiara Cogliati, Giovanni Tripepi, Stefano Perlini, Giovanni Gambassi, Carlo Sabbà, F Ferrara, Anna Ludovica Fracanzani, and Nicola Montano
Subjects: medicine.medical_specialty, Acute decompensated heart failure, medicine.medical_treatment, Population, Renal function, Acutely decompensated heart failure, Inferior vena cava, Pulmonary congestion, Reduced ejection fraction, Internal medicine, Internal Medicine, medicine, Humans, Prospective Studies, education, Prospective cohort study, Diuretics, Intravascular congestion, Lung ultrasound, Preserved ejection fraction, Hospitalization, Prognosis, Stroke Volume, Heart Failure, education.field_of_study, Ejection fraction, business.industry, medicine.disease, medicine.vein, Heart failure, Cardiology, Diuretic, business
Abstract: AIMS To evaluate pulmonary and intravascular congestion at admission and repeatedly during hospitalization for acute decompensated heart failure (ADHF) in HFrEF and HFpEF patients using lung (LUS) and inferior vena cava (IVC) ultrasound. METHODS AND RESULTS Three-hundred-fourteen patients (82±9 years; HFpEF =172; HFrEF=142) admitted to Internal Medicine wards for ADHF were enrolled in a multi-center prospective study. At admission HFrEF presented higher indexes of pulmonary and intravascular congestion (LUS-score: 0.9 ± 0.4 vs 0.7 ± 0.4; p
Published: 2022

33. Impact of Diabetes Mellitus and Its Comorbidities on Elderly Patients Hospitalized in Internal Medicine Wards: Data from the RePoSi Registry

Author: Christiano, Argano, Giuseppe, Natoli, Salvatore, Mularo, Alessandro, Nobili, Marika Lo Monaco, Pier Mannuccio Mannucci, Francesco, Perticone, Antonello, Pietrangelo, Salvatore, Corrao, Domenico, Prisco, Elena, Silvestri, Giacomo, Emmi, Alessandra, Bettiol, Irene, Mattioli, Gianni, Biolo, Michela, Zanetti, Giacomo, Bartelloni, Massimo, Vanoli, Giulia, Grignani, Edoardo Alessandro Pulixi, Graziana, Lupattelli, Vanessa, Bianconi, Riccardo, Alcidi, Domenico, Girelli, Fabiana, Busti, Giacomo, Marchi, Mario, Barbagallo, Ligia, Dominguez, Vincenza, Beneduce, Federica, Cacioppo, Massimo, Raspanti, Marco, Zoli, Maria Laura Matacena, Giuseppe, Orio, Eleonora, Magnolfi, Giovanni, Serafini, Angelo, Simili, Giuseppe, Palasciano, Maria Ester Modeo, Carla Di Gennaro, Maria Domenica Cappellini, Giovanna, Fabio, Margherita Migone De Amicis, Giacomo De Luca, Natalia, Scaramellini, Matteo, Cesari, Paolo Dionigi Rossi, Sarah, Damanti, Marta, Clerici, Simona, Leoni, Alessandra Danuta Di Mauro, Antonio Di Sabatino, Emanuela, Miceli, Marco Vincenzo Lenti, Martina, Pisati, Costanza Caccia Dominioni, Roberto, Pontremoli, Valentina, Beccati, Giulia, Nobili, Giovanna, Leoncini, Luigi, Anastasio, Maria, Carbone, Francesco, Cipollone, Maria Teresa Guagnano, Ilaria, Rossi, Gerardo, Mancuso, Daniela, Calipari, Mosè, Bartone, Giuseppe, Delitala, Maria, Berria, Alessandro, Delitala, Maurizio, Muscaritoli, Alessio, Molfino, Enrico, Petrillo, Antonella, Giorgi, Christian, Gracin, Giuseppe, Zuccalà, Gabriella, D’Aurizio, Giuseppe, Romanelli, Alessandra, Marengoni, Andrea, Volpini, Daniela, Lucente, Antonio, Picardi, Umberto Vespasiani Gentilucci, Paolo, Gallo, Giuseppe, Bellelli, Maurizio, Corsi, Cesare, Antonucci, Chiara, Sidoli, Giulia, Principato, Franco, Arturi, Elena, Succurro, Bruno, Tassone, Federica, Giofrè, Maria Grazia Serra, Maria Antonietta Bleve, Antonio, Brucato, Teresa De Falco, Fabrizio, Fabris, Irene, Bertozzi, Giulia, Bogoni, Maria Victoria Rabuini, Tancredi, Prandini, Manfredini, Roberto, Fabbian, Fabio, Benedetta, Boari, DE GIORGI, Alfredo, Ruana, Tiseo, Giuseppe, Paolisso, Maria Rosaria Rizzo, Claudia, Catalano, Claudio, Borghi, Enrico, Strocchi, Eugenia, Ianniello, Mario, Soldati, Silvia, Schiavone, Alessio, Bragagni, Carlo, Sabbà, Francesco Saverio Vella, Patrizia, Suppressa, Giovanni Michele De Vincenzo, Alessio, Comitangelo, Emanuele, Amoruso, Carlo, Custodero, Luigi, Fenoglio, Andrea, Falcetta, Fracanzani, Anna L., Silvia, Tiraboschi, Annalisa, Cespiati, Giovanna, Oberti, Giordano, Sigon, Flora, Peyvandi, Raffaella, Rossio, Giulia, Colombo, Pasquale, Agosti, Valter, Monzani, Valeria, Savojardo, Giuliana, Ceriani, Francesco, Salerno, Giada, Pallini, Fabrizio, Montecucco, Luciano, Ottonello, Lara, Caserza, Giulia, Vischi, Nicola Lucio Liberato, Tiziana, Tognin, Francesco, Purrello, Antonino Di Pino, Salvatore, Piro, Renzo, Rozzini, Lina, Falanga, Maria Stella Pisciotta, Francesco Baffa Bellucci, Stefano, Buffelli, Giuseppe, Montrucchio, Paolo, Peasso, Edoardo, Favale, Cesare, Poletto, Carl, Margaria, Maura, Sanino, Francesco, Violi, Ludovica, Perri, Luigina, Guasti, Luana, Castiglioni, Andrea, Maresca, Alessandro, Squizzato, Leonardo, Campiotti, Alessandra, Grossi, Roberto Davide Diprizio, Marco, Bertolotti, Chiara, Mussi, Giulia, Lancellotti, Maria Vittoria Libbra, Matteo, Galassi, Yasmine, Grassi, Alessio, Greco, Angela, Sciacqua, Maria, Perticone, Rosa, Battaglia, Raffaele, Maio, Vincenzo, Stanghellini, Eugenio, Ruggeri, Sara del Vecchio, Andrea, Salvi, Roberto, Leonardi, Giampaolo, Damiani, William, Capeci, Massimo, Mattioli, Giuseppe Pio Martino, Lorenzo, Biondi, Pietro, Pettinari, Riccardo, Ghio, Anna Dal Col, Salvatore, Minisola, Luciano, Colangelo, Mirella, Cilli, Giancarlo, Labbadia, Antonella, Afeltra, Benedetta, Marigliano, Maria Elena Pipita, Pietro, Castellino, Luca, Zanoli, Alfio, Gennaro, Agostino, Gaudio, Valter, Saracco, Marisa, Fogliati, Carlo, Bussolino, Francesca, Mete, Miriam, Gino, Carlo, Vigorito, Antonio, Cittadini, Guido, Moreo, Silvia, Prolo, Gloria, Pina, Alberto, Ballestrero, Fabio, Ferrando, Roberta, Gonella, Domenico, Cerminara, Sergio, Berra, Simonetta, Dassi, Maria Cristina Nava, Bruno, Graziella, Stefano, Baldassarre, Salvatore, Fragapani, Gabriella, Gruden, Giorgio, Galanti, Gabriele, Mascherini, Cristian, Petri, Laura, Stefani, Margherita, Girino, Valeria, Piccinelli, Francesco, Nasso, Vincenza, Gioffrè, Maria, Pasquale, Leonardo, Sechi, Cristiana, Catena, Gianluca, Colussi, Alessandro, Cavarape, Andea Da Porto, Nicola, Passariello, Luca, Rinaldi, Franco, Berti, Giuseppe, Famularo, Patrizia, Tarsitani, Roberto, Castello, Michela, Pasino, Gian Paolo Ceda, Marcello Giuseppe Maggio, Simonetta, Morganti, Andrea, Artoni, Margherita, Grossi, Stefano Del Giacco, Davide, Firinu, Giulia, Costanzo, Giacomo, Argiolas, Giuseppe, Montalto, Anna, Licata, Filippo Alessandro Montalto, Francesco, Corica, Giorgio, Basile, Antonino, Catalano, Federica, Bellone, Concetto, Principato, Lorenzo, Malatino, Benedetta, Stancanelli, Valentina, Terranova, Salvatore Di Marca, Rosario Di Quattro, Lara La Malfa, Rossella, Caruso, Patrizia, Mecocci, Carmelinda, Ruggiero, Virginia, Boccardi, Tiziana, Meschi, Andrea, Ticinesi, Antonio, Nouvenne, Pietro, Minuz, Luigi, Fondrieschi, Giandomenico Nigro Imperiale, Mario, Pirisi, Gian Paolo Fra, Daniele, Sola, Mattia, Bellan, Massimo, Porta, Piero, Riva, Roberto, Quadri, Erica, Larovere, Marco, Novelli, Giorgio, Scanzi, Caterina, Mengoli, Stella, Provini, Laura, Ricevuti, Emilio, Simeone, Rosa, Scurti, Fabio, Tolloso, Roberto, Tarquini, Alice, Valoriani, Silvia, Dolenti, Giulia, Vannini, Riccardo, Volpi, Pietro, Bocchi, Alessandro, Vignali, Sergio, Harari, Chiara, Lonati, Federico, Napoli, Italia, Aiello, Raffaele, Landolfi, Massimo, Montalto, Antonio, Mirijello, Silvia, Ghidoni, Teresa, Salvatore, Lucio, Monaco, Carmen, Ricozzi, Alberto, Pilotto, Ilaria, Indiano, Federica, Gandolfo., Argano C., Natoli G., Mularo S., Nobili A., Lo Monaco M., Mannucci P.M., Perticone F., Pietrangelo A., and Corrao S.
Subjects: Leadership and Management, 1-year mortality, cancer, comorbidities, diabetes, heart rate, in-hospital mortality, male sex, Heart rate, Socio-culturale, Health Informatics, comorbidities, Article, Comorbidities, Health Information Management, diabetes, heart rate, cancer, male sex, in-hospital mortality, 1-year mortality, Cancer, Diabetes, In-hospital mortality, Male sex, LS4_4, Health Policy, Medicine, 1-year mortality, Cancer, Comorbidities, Diabetes, Heart rate, In-hospital mortality, Male
Abstract: Background: Currently, diabetes represents the seventh leading cause of death worldwide, with a significant economic burden. The number and severity of comorbidities increase with age, and are identified as important determinants that influence the prognosis. We aimed to investigate comorbidities and outcomes in a cohort of hospitalized elderly patients affected by diabetes. Methods: In this observational study, we retrospectively analyzed data collected from the REgistro dei pazienti per lo studio delle POlipatologie e politerapie in reparti della rete Simi (RePoSi) registry. Socio-demographic, clinical characteristics, and laboratory findings were considered. The association between variables and in-hospital and 1-year follow-up were analyzed. Results: Among 4708 in-patients, 1378 (29.3%) had a diagnosis of diabetes. Patients with diabetes had more previous hospitalization, a clinically significant disability, and more need for a urinary catheter in comparison with subjects without diabetes. Patients affected by diabetes took more drugs, both at admission, at in-hospital stay, at discharge, and at 1-year follow-up. Thirty-five comorbidities were more frequent in patients with diabetes, and the first five were hypertension (57.1%), ischemic heart disease (31.4%), chronic renal failure (28.8%), atrial fibrillation (25.6%), and chronic obstructive pulmonary disease (22.7%). Heart rate was an independent predictor of in-hospital mortality. At 1-year follow-up, cancer and male sex were strongly independently associated with mortality. Conclusions: Our findings showed the severity of the impact of diabetes and its comorbidities in the real life of internal medicine and geriatric wards, and provide data to be used for a better tailored management of elderly in-patients with diabetes.
Published: 2022

34. Development of post-COVID-19 cardiovascular events: an analysis of clinical features and risk factors from a single hospital retrospective study

Author: Gianluca, Cuomo, Cinzia, Puzzolante, Vittorio, Iadisernia, Antonella, Santoro, Marianna, Menozzi, Federica, Carli, Margherita, Digaetano, Gabriella, Orlando, Erica, Franceschini, Andrea, Bedini, Marianna, Meschiari, Lisa, Manzini, Luca, Corradi, Jovana, Milic, Vanni, Borghi, Lucio, Brugioni, Antonello, Pietrangelo, Enrico, Clini, Massimo, Girardis, Giovanni, Guaraldi, and Cristina, Mussini
Subjects: Microbiology (medical), Cardiovascular diseases, Infectious Diseases, SARS-CoV-2, COVID-19, Original Article
Abstract: Cardiovascular complications after a SARS-CoV-2 infection are a phenomenon of relevant scientific interest. The aim of this study was to analyze the onset of post-COVID-19 cardiovascular events in patients hospitalized in a tertiary care center. This is a retrospective study conducted on patients hospitalized over a period of three months. The patients were older than 18 years of age and had a diagnosis of COVID-19 infection confirmed from a nasopharyngeal swab sample. Anamnestic and clinical-laboratory data were collected. Cardiovascular events at 30 days were defined as follows: arrhythmias, myocardial infarction, myocarditis, and pulmonary embolism. Univariate analysis (Student’s t-test or Mann-Whitney U test, as appropriate) and multivariate analysis (multinomial logistic regression) were applied to the data. A total of 394 patients were included; they were mostly males and had a median age of 65.5 years. Previous cardiovascular disease was present in 14.7% of patients. Oxygen therapy was required for 77.9%, and 53% received anticoagulant therapy. The overall 30-day mortality was 20.3%. A cardiovascular event developed in 15.7% of the subjects. These were mainly pulmonary embolism (9.4%), followed by arrhythmias (3.3%), myocardial infarction (2.3%), and myocarditis (0.8%). Patients who developed cardiovascular events upon univariate analysis were significantly older, with major comorbidities, a more compromised respiratory situation, and a higher mortality rate. Multivariate analysis revealed independent factors that were significantly associated with the development of cardiovascular events: hypertension, endotracheal intubation, and age older than 75 years. In patients with COVID-19, the development of a cardiovascular event occurs quite frequently and is mainly seen in elderly subjects with comorbidities (especially hypertension) in the presence of a severe respiratory picture.
Published: 2021

35. Internists or specialists-that is the question!

Author: Antonello Pietrangelo
Subjects: Humans, Internal Medicine, Physicians, Specialization
Published: 2022

36. An unusual dyspnea in an 87-year old woman affected by Sjögren’s syndrome

Author: Stefania Cerri, Antonello Pietrangelo, Anna Francesca Guerra, Massimo Fiorini, and Carlo Grendene
Subjects: Autoimmune disease, medicine.medical_specialty, Lung, business.industry, respiratory system, medicine.disease, Dermatology, stomatognathic diseases, Pneumonia, medicine.anatomical_structure, stomatognathic system, Parenchyma, medicine, General Earth and Planetary Sciences, Respiratory system, business, Airway, Immunodeficiency, General Environmental Science, Lymphocytic interstitial pneumonia
Abstract: Primary Sjögren’s syndrome (pSS) is a progressive autoimmune disease and is characterized by eye and mouth dryness due to lymphocytic infiltration in lacrimal and salivary glands leading to tissue destruction, but it can also present systemic manifestations including lung involvement. Respiratory manifestations in pSS have a prevalence of 9-20% and can be due to airway and/or lung parenchyma involvement, such as in particular in interstitial lung diseases like lymphocytic interstitial pneumonia (LIP). LIP is an inflammatory diffuse parenchymal lung disease, which is almost invariably associated with other conditions, such as autoimmune diseases and immunodeficiency states, and usually affects women with a mean age of 50 years. We described a case of patient with LIP who was referred to our Internal Medicine Unit and the diagnostic issues related to the patient age and comorbidities.
Published: 2021

37. Multicenter observational study on the reliability of the HEART score

Author: Lucio Brugioni, Laura Bonfanti, Nicola Parenti, Giuseppe Lippi, Maria Letizia Bacchi Reggiani, Alberto Vegetti, Antonello Pietrangelo, Gianfranco Cervellin, Antonio Luciani, and Mario Cavazza
Subjects: medicine.medical_specialty, Acute coronary syndrome, 030204 cardiovascular system & hematology, Emergency Nursing, Chest pain, 03 medical and health sciences, HEART score, 0302 clinical medicine, Cohen's kappa, Emergency service, hospital, medicine, hospital, Reliability (statistics), business.industry, Medical record, 030208 emergency & critical care medicine, Emergency department, medicine.disease, Confidence interval, HEART pathway, Emergency Medicine, Physical therapy, Observational study, Original Article, medicine.symptom, business, Emergency service
Abstract: Objective To rapidly and safely identify the risk of developing acute coronary syndrome in patients with chest pain who present to the emergency department, the clinical use of the History, Electrocardiogram, Age, Risk Factors, and Troponin (HEART) scoring has recently been proposed. This study aimed to assess the inter-rater reliability of the HEART score calculated by a large number of Italian emergency physicians. Methods The study was conducted in three academic emergency departments using clinical scenarios obtained from medical records of patients with chest pain. Twenty physicians, who took the HEART score course, independently assigned a score to different clinical scenarios, which were randomly administered to the participants, and data were collected and recorded in a spreadsheet by an independent investigator who was blinded to the study's aim. Results After applying the exclusion criteria, 53 scenarios were finally included in the analysis. The general inter-rater reliability was good (kappa statistics [κ], 0.63; 95% confidence interval, 0.57 to 0.70), and a good inter-rater agreement for the high- and low-risk classes (HEART score, 7 to 10 and 0 to 3, respectively; κ, 0.60 to 0.73) was observed, whereas a moderate agreement was found for the intermediate-risk class (HEART score, 4 to 6; κ, 0.51). Among the different items of the HEART score, history and electrocardiogram had the worse agreement (κ, 0.37 and 0.42, respectively). Conclusion The HEART score had good inter-rater reliability, particularly among the high- and low-risk classes. The modest agreement for history suggests that major improvements are needed for objectively assessing this component.
Published: 2019

38. Serum HBsAg and ddPCR HBV-DNA as predictive parameters of HBsAg loss after nucleo (s)tide analogue (NA) treatment discontinuation in non-cirrhotic patients with chronic hepatitis B

Author: Anna Francesca Guerra, Giovanni Tomassoli, Lorenzo Piermatteo, Stefano D’Anna, Romina Salpini, Valentina Svicher, Paolo Ventura, Gian Luca Abbati, and Antonello Pietrangelo
Subjects: Hepatology
Published: 2022

39. Hyperhomocysteinemia in patients with acute porphyrias: a possible effect of ALAS1 modulation by siRNAm therapy and its control by vitamin supplementation

Author: Matteo Marcacci, Antonello Pietrangelo, Andrea Ricci, Paolo Ventura, and Chiara Cuoghi
Subjects: medicine.medical_specialty, Hyperhomocysteinemia, Homocysteine, Heme, chemistry.chemical_compound, Folic Acid, Internal medicine, Internal Medicine, Medicine, Humans, In patient, Givosiran, Vitamin supplementation, business.industry, ALAS1 siRNAm, Vitamins, medicine.disease, ALAS1, Acute porphyrias, Vitamin B 12, Endocrinology, Vitamin B6, chemistry, Porphyria, Acute Intermittent, Dietary Supplements, Vitamin b6, business
Published: 2021

40. Ataxia-Myoclonus Syndrome in Patients with SARS-CoV-2 Infection

Author: Paolo Ventura, Franco Valzania, Stefano Meletti, Ilaria Martinelli, Matteo Marcacci, Anna Francesca Guerra, Antonello Pietrangelo, Francesco Cavallieri, Vittorio Rispoli, and Silvia Nizzoli
Subjects: Myoclonus, 2019-20 coronavirus outbreak, Movement disorders, Ataxia, Coronavirus disease 2019 (COVID-19), Cerebellar Ataxia, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Sars-cov-2, Medicine, Humans, In patient, Letter to the Editor, Para-infectious, business.industry, SARS-CoV-2, COVID-19, General Medicine, Syndrome, Virology, Neurology, Neurology (clinical), medicine.symptom, business
Published: 2021

41. Renal Function, Cardiovascular Diseases, Appropriateness of Drug Prescription and Outcomes in Hospitalized Older Patients

Author: Antonietta, Gigante, Marco, Proietti, Enrico, Petrillo, Pier Mannuccio Mannucci, Alessandro, Nobili, Maurizio, Muscaritoli, Antonello, Pietrangelo, Francesco, Perticone, Francesco, Violi, Gino Roberto Corazza, Salvatore, Corrao, Alessandra, Marengoni, Francesco, Salerno, Matteo, Cesari, Mauro, Tettamanti, Luca, Pasina, Carlotta, Franchi, Laura, Cortesi, Gabriella, Miglio, Ilaria, Ardoino, Alessio, Novella, Domenico, Prisco, Elena, Silvestri, Giacomo, Emmi, Alessandra, Bettiol, Irene, Mattioli, Gianni, Biolo, Michela, Zanetti, Giacomo, Bartelloni, Massimo, Vanoli, Giulia, Grignani, Edoardo Alessandro Pulixi, Graziana, Lupattelli, Vanessa, Bianconi, Riccardo, Alcidi, Domenico, Girelli, Fabiana, Busti, Giacomo, Marchi, Mario, Barbagallo, Ligia, Dominguez, Vincenza, Beneduce, Federica, Cacioppo, Giuseppe, Natoli, Salvatore, Mularo, Massimo, Raspanti, Marco, Zoli, Maria Laura Matacena, Giuseppe, Orio, Eleonora, Magnolfi, Giovanni, Serafini, Angelo, Simili, Giuseppe, Palasciano, Maria Ester Modeo, Carla Di Gennaro, Maria Domenica Cappellini, Giovanna, Fabio, Margherita Migone De Amicis, Giacomo De Luca, Natalia, Scaramellini, Paolo Dionigi Rossi, Sarah, Damanti, Marta, Clerici, Simona, Leoni, Alessandra Danuta Di Mauro, Antonio Di Sabatino, Emanuela, Miceli, Marco Vincenzo Lenti, Martina, Pisati, Costanza Caccia Dominioni, Roberto, Pontremoli, Valentina, Beccati, Giulia, Nobili, Giovanna, Leoncini, Luigi, Anastasio, Maria, Carbone, Francesco, Cipollone, Maria Teresa Guagnano, Ilaria, Rossi, Gerardo, Mancuso, Daniela, Calipari, Mosè, Bartone, Giuseppe, Delitala, Maria, Berria, Alessandro, Delitala, Alessio, Molfino, Antonella, Giorgi, Christian, Gracian, Giuseppe, Zuccalà, Gabriella, D’Aurizio, Giuseppe, Romanelli, Andrea, Volpini, Daniela, Lucente, Antonio, Picardi, Umberto Vespasiani Gentilucci, Paolo, Gallo, Giorgio, Annoni, Maurizio, Corsi, Giuseppe, Bellelli, Alessandra, Bonfanti, Franco, Arturi, Elena, Succurro, Bruno, Tassone, Federica, Giofrè, Maria Grazia Serra, Maria Antonietta Bleve, Antonio, Brucato, Teresa De Falco, Fabrizio, Fabris, Irene, Bertozzi, Giulia, Bogoni, Maria Victoria Rabuini, Tancredi, Prandini, Manfredini, Roberto, Fabbian, Fabio, Boari, Benedetta, DE GIORGI, Alfredo, Ruana, Tiseo, Giuseppe, Paolisso, Maria Rosaria Rizzo, Claudia, Catalano, Claudio, Borghi, Enrico, Strocchi, Eugenia, Ianniello, Mario, Soldati, Silvia, Schiavone, Alessio, Bragagni, Carlo, Sabbà, Francesco Saverio Vella, Patrizia, Suppressa, Giovanni Michele De Vincenzo, Alessio, Comitangelo, Emanuele, Amoruso, Carlo, Custodero, Luigi, Fenoglio, Andrea, Falcetta, Fracanzani, Anna L., Silvia, Tiraboschi, Annalisa, Cespiati, Giovanna, Oberti, Giordano, Sigon, Flora, Peyvandi, Raffaella, Rossio, Giulia, Colombo, Pasquale, Agosti, Valter, Monzani, Valeria, Savojardo, Giuliana, Ceriani, Giada, Pallini, Fabrizio, Montecucco, Luciano, Ottonello, Lara, Caserza, Giulia, Vischi, Nicola Lucio Liberato, Tiziana, Tognin, Francesco, Purrello, Antonino Di Pino, Salvatore, Piro, Renzo, Rozzini, Lina, Falanga, Maria Stella Pisciotta, Francesco Baffa Bellucci, Stefano, Buffelli, Giuseppe, Montrucchio, Paolo, Peasso, Edoardo, Favale, Cesare, Poletto, Carl, Margaria, Maura, Sanino, Ludovica, Perri, Luigina, Guasti, Luana, Castiglioni, Andrea, Maresca, Alessandro, Squizzato, Leonardo, Campiotti, Alessandra, Grossi, Roberto Davide Diprizio, Marco, Bertolotti, Chiara, Mussi, Giulia, Lancellotti, Maria Vittoria Libbra, Matteo, Galassi, Yasmine, Grassi, Maria, Perticone, Rosa, Battaglia, Marco, Filice, Raffaele, Maio, Vincenzo, Stanghellini, Eugenio, Ruggeri, Sara del Vecchio, Andrea, Salvi, Roberto, Leonardi, Giampaolo, Damiani, William, Capeci, Massimo, Mattioli, Giuseppe Pio Martino, Lorenzo, Biondi, Pietro, Pettinari, Salvatore, Minisola, Luciano, Colangelo, Mirella, Cilli, Giancarlo, Labbadia, Antonella, Afeltra, Benedetta, Marigliano, Maria Elena Pipita, Pietro, Castellino, Luca, Zanoli, Alfio, Gennaro, Agostino, Gaudio, Valter, Saracco, Marisa, Fogliati, Carlo, Bussolino, Francesca, Mete, Miriam, Gino, Carlo, Vigorito, Antonio, Cittadini, Guido, Moreo, Silvia, Prolo, Gloria, Pina, Alberto, Ballestrero, Fabio, Ferrando, Sergio, Berra, Simonetta, Dassi, Maria Cristina Nava, Bruno, Graziella, Stefano, Baldassarre, Salvatore, Fragapani, Gabriella, Gruden, Giorgio, Galanti, Gabriele, Mascherini, Cristian, Petri, Laura, Stefani, Margherita, Girino, Valeria, Piccinelli, Francesco, Nasso, Vincenza, Gioffrè, Maria, Pasquale, Leonardo, Sechi, Cristiana, Catena, Gianluca, Colussi, Alessandro, Cavarape, Andea Da Porto, Nicola, Passariello, Luca, Rinaldi, Franco, Berti, Giuseppe, Famularo, Patrizia, Tarsitani, Roberto, Castello, Michela, Pasino, Gian Paolo Ceda, Marcello Giuseppe Maggio, Simonetta, Morganti, Andrea, Artoni, Margherita, Grossi, Stefano Del Giacco, Davide, Firinu, Giulia, Costanzo, Giacomo, Argiolas, Giuseppe, Montalto, Anna, Licata, Filippo Alessandro Montalto, Francesco, Corica, Giorgio, Basile, Antonino, Catalano, Federica, Bellone, Concetto, Principato, Lorenzo, Malatino, Benedetta, Stancanelli, Valentina, Terranova, Salvatore Di Marca, Rosario Di Quattro, Lara La Malfa, Rossella, Caruso, Patrizia, Mecocci, Carmelinda, Ruggiero, Virginia, Boccardi, Tiziana, Meschi, Andrea, Ticinesi, Antonio, Nouvenne, Pietro, Minuz, Luigi, Fondrieschi, Giandomenico Nigro Imperiale, Mario, Pirisi, Gian Paolo Fra, Daniele, Sola, Mattia, Bellan, Massimo, Porta, Piero, Riva, Roberto, Quadri, Erica, Larovere, Marco, Novelli, Giorgio, Scanzi, Caterina, Mengoli, Stella, Provini, Laura, Ricevuti, Emilio, Simeone, Rosa, Scurti, Fabio, Tolloso, Roberto, Tarquini, Alice, Valoriani, Silvia, Dolenti, Giulia, Vannini, Riccardo, Volpi, Pietro, Bocchi, Alessandro, Vignali, Sergio, Harari, Chiara, Lonati, Federico, Napoli, Italia, Aiello, Raffaele, Landolfi, Massimo, Montalto, Antonio, Mirijello, Silvia, Ghidoni, Teresa, Salvatore, Lucio, Monaco, Carmen, Ricozzi, Alberto, Pilotto, Ilaria, Indiano, and Federica, Gandolfo.
Subjects: Drug, medicine.medical_specialty, Hospitalized patients, media_common.quotation_subject, Renal function, Socio-culturale, Kidney, Kidney Function Tests, Drug Prescriptions, Older patients, PEOPLE, Internal medicine, Atrial Fibrillation, Humans, Medicine, Pharmacology (medical), LS4_4, Medical prescription, Aged, media_common, CHRONIC KIDNEY DISEASE, POLYPHARMACY, FRAILTY POPULATION, PEOPLE, ADULTS, DEATH, business.industry, CHRONIC KIDNEY DISEASE, FRAILTY POPULATION, DEATH, ADULTS, Cardiovascular Diseases, Observational study, POLYPHARMACY, Geriatrics and Gerontology, business
Abstract: Reduced estimated creatinine clearance (eCrCl) is prevalent in older patients and impacts on drug prescription. In this study, the burden of eCrCl reduction and its associated factors and impact on outcomes were analyzed. Moreover, the rate of inappropriate drug prescription according to eCrCl and its impact on outcomes were described.Data were obtained from "REgistro POliterapie SIMI" (REPOSI), a prospective observational register enrolling hospitalized patients aged ≥ 65 years. Patients enrolled from 2010-2016 with available data to calculate eCrCl according to the Cockcroft-Gault formula were included in this analysis.A total of 5046 patients were available for analysis. Among these, we found an eCrCl of 45-59 mL/min in 1163 patients (23.0%), an eCrCl of 30-44 mL/min in 1128 (22.4%), an eCrCl of 15-29 mL/min in 702 (13.9%), and an eCrCl 15 mL/min in 152 (3.0%), with several clinical factors associated with decreasing eCrCl. During follow-up, a progressively higher risk for all-cause death, cardiovascular (CV) death, any death/re-hospitalization, and CV death/re-hospitalization was found across the renal function classes. Among patients with hypertension, diabetes mellitus, atrial fibrillation, coronary artery disease, and heart failure, 476 (10.9%) were inappropriately prescribed medications according to eCrCl. During follow-up, inappropriate prescription was associated with increased risk of all-cause death (odds ratio [OR] 1.49, 95% confidence interval [CI] 1.13-1.97) and any death/re-hospitalization (OR 1.30, 95% CI 1.03-1.63).In older hospitalized patients, impaired eCrCl is prevalent and associated with several factors, polypharmacy in particular. Patients with reduced eCrCl have a higher risk of major clinical outcomes, and 10% of them are prescribed an inappropriate drug, with a higher risk for major clinical outcomes.
Published: 2021

42. Impact of implementing a Choosing Wisely educational intervention into clinical practice: The CW-SIMI study (a multicenter-controlled study)

Author: Alessandro Squizzato, Raffaello Furlan, Anna Ludovica Fracanzani, Teresa Salvatore, Roberto Manetti, Vanessa Nunziata, Giovanni Gambassi, Antonello Pietrangelo, Stefania Sella, Christian Bracco, Alfonso Piccoli, Raffaele Manna, Nicola Montano, Gian Marco Podda, Chiara Cogliati, Moreno Tresoldi, Francesco Perticone, Giorgio Costantino, Maria Domenica Cappellini, Alberto Moggi Pignone, Ludovico Furlan, Giovanni Casazza, and Gino Roberto Corazza
Subjects: medicine.medical_specialty, medicine.drug_class, Proton pump inhibitors, medicine.medical_treatment, Proton-pump inhibitor, Antibiotics, Appropriateness, Choosing wisely, Cvc, Less is more, Intervention (counseling), medicine, Internal Medicine, Humans, Medical prescription, business.industry, Anti-Bacterial Agents, Clinical Practice, Italy, Emergency medicine, Administration, Administration, Intravenous, Proton Pump Inhibitors, business, Intravenous, Central venous catheter
Abstract: Objectives To evaluate the impact of an educational intervention based on the Italian Society of Internal Medicine Choosing Wisely (CW-SIMI) recommendations. Design Multicenter, interventional, controlled study. Setting Twenty-three acute-care hospital wards in Italy. Participants 303 Physicians working in internal medicine wards. Intervention An online educational course. Main outcomes The rate of proton pump inhibitor (PPI) prescriptions, the number of days of central venous catheter (CVC) usage, and the duration of intravenous (IV) antibiotic prescriptions evaluated at one month (T1) and at six months (T2) after course completion. Patients admitted and discharged during a 30-day period before the educational intervention (T0, one year before T2) were considered the comparison group. Results A total of 232 physicians completed the course, while 71 did not attend the course. Data from 608, 662, and 555 patients were analyzed at T0, T1, and T2, respectively. The rate of PPI prescriptions declined at one month (RR: 0.67, 95% CI: 0.52–0.87, p = 0.0005) and at six months (RR: 0.62, 95% CI: 0.46–0.84, p = 0.003), and the number of days of CVC usage was reduced at six months (9.13 days at T0 vs. 5.52 days at T2, p = 0.007). The duration of IV antibiotic prescriptions displayed a decreasing trend (7.94 days at T0 vs. 7.42 days at T2, p = 0.081). Conclusions A simple online educational intervention based on the CW-SIMI recommendations was associated with a clinically relevant reduction in the usage of PPIs and CVCs. Further studies are needed to confirm these findings and a possible benefit on patients’ outcomes.
Published: 2021

43. Ceruloplasmin gene variants are associated with hyperferritinemia and increased liver iron in patients with {NAFLD}

Author: Paola Dongiovanni, Antonello Pietrangelo, Raffaela Rametta, Stefania Scarlini, Luca Valenti, Angela Caleffi, Anna Ludovica Fracanzani, Silvia Fargion, Paolo Ventura, Serena Pelusi, Elena Tenedini, Elena Buzzetti, Elena Corradini, Isabella Bernardis, and Enrico Tagliafico
Subjects: 0301 basic medicine, medicine.medical_specialty, Cirrhosis, Anemia, Ferroportin, Gastroenterology, 03 medical and health sciences, Liver disease, 0302 clinical medicine, iron, Internal medicine, medicine, next generation sequencing, Hepatology, biology, business.industry, Fatty liver, ferritin, ceruloplasmin, non-alcoholic fatty liver disease, medicine.disease, Ferritin, 030104 developmental biology, biology.protein, 030211 gastroenterology & hepatology, Liver cancer, Ceruloplasmin, business
Abstract: Background & Aims Non-alcoholic fatty liver disease (NAFLD) is a multifactorial disorder resulting from genetic and environmental factors. Hyperferritinemia has been associated with increased hepatic iron stores and worse outcomes in patients with NAFLD. The aim of this study was to evaluate the prevalence of variants of iron-related genes and their association with hyperferritinemia, hepatic iron stores and liver disease severity in patients with NAFLD. Methods From a cohort of 328 individuals with histological NAFLD, 23 patients with ferritin >750 ng/ml and positive iron staining, and 25 controls with normal ferritin and negative iron staining, were selected. Patients with increased transferrin saturation, anemia, inflammation, β-thalassemia trait, HFE genotype at risk of iron overload and ferroportin mutations were excluded. A panel of 32 iron genes was re-sequenced. Literature and in silico predictions were employed for prioritization of pathogenic mutations. Results Patients with hyperferritinemia had a higher prevalence of potentially pathogenic rare variants (73.9% vs. 20%, p = 0.0002) associated with higher iron stores and more severe liver fibrosis (p Conclusions Variants in non-HFE iron genes, particularly ceruloplasmin, are associated with hyperferritinemia and increased hepatic iron stores in patients with NAFLD. Carriers of such variants have more severe liver fibrosis, suggesting that genetic predisposition to hepatic iron deposition may translate into liver disease. Lay summary Non-alcoholic fatty liver disease (NAFLD) is a common disease which can progress to cirrhosis and liver cancer. Increased levels of serum ferritin are often detected in patients with NAFLD and have been associated with altered iron metabolism and worse patient outcomes. We found that variants of genes related to iron metabolism, particularly ceruloplasmin, are associated with high ferritin levels, hepatic iron deposition and more severe liver disease in an Italian cohort of patients with NAFLD.
Published: 2021

44. Development and validation of a prediction model for tocilizumab failure in hospitalized patients with SARS-CoV-2 infection

Author: Cristina Mussini, Alessandro Cozzi-Lepri, Marianna Menozzi, Marianna Meschiari, Erica Franceschini, Jovana Milic, Lucio Brugioni, Antonello Pietrangelo, Massimo Girardis, Andrea Cossarizza, Roberto Tonelli, Enrico Clini, Marco Massari, Michele Bartoletti, Anna Ferrari, Anna Maria Cattelan, Paola Zuccalà, Miriam Lichtner, Roberto Rossotti, Enrico Girardi, Emanuele Nicastri, Massimo Puoti, Andrea Antinori, Pierluigi Viale, Giovanni Guaraldi, Mussini C., Cozzi-Lepri A., Menozzi M., Meschiari M., Franceschini E., Milic J., Brugioni L., Pietrangelo A., Girardis M., Cossarizza A., Tonelli R., Clini E., Massari M., Bartoletti M., Ferrari A., Cattelan A.M., Zuccala P., Lichtner M., Rossotti R., Girardi E., Nicastri E., Puoti M., Antinori A., Viale P., Guaraldi G., Mussini, C, Cozzi-Lepri, A, Menozzi, M, Meschiari, M, Franceschini, E, Milic, J, Brugioni, L, Pietrangelo, A, Girardis, M, Cossarizza, A, Tonelli, R, Clini, E, Massari, M, Bartoletti, M, Ferrari, A, Cattelan, A, Zuccala, P, Lichtner, M, Rossotti, R, Girardi, E, Nicastri, E, Puoti, M, Antinori, A, Viale, P, and Guaraldi, G
Subjects: Male, Viral Diseases, Pulmonology, Epidemiology, Physiology, Biochemistry, Cohort Studies, Medical Conditions, Mathematical and Statistical Techniques, Retrospective Studie, Animal Cells, SARS-CoV-2, COVID-19, tocilizumab, tocilizumab failure, Medicine and Health Sciences, Multicenter Studies as Topic, tocilizumab failure, C reactive protein, Pharmaceutics, Statistics, Middle Aged, Body Fluids, Hospitalization, Treatment Outcome, Infectious Diseases, Blood, Physical Sciences, Medicine, Female, Anatomy, Cellular Types, Human, Research Article, Platelets, Death Rates, Science, Antibodies, Monoclonal, Humanized, Research and Analysis Methods, tocilizumab, Population Metrics, Drug Therapy, Humans, Statistical Methods, Aged, Retrospective Studies, Blood Cells, Population Biology, SARS-CoV-2, COVID-19, Biology and Life Sciences, Covid 19, Cell Biology, Pneumonia, COVID-19 Drug Treatment, monoclonal antibody, Medical Risk Factors, Cohort Studie, Biomarkers, Mathematics, Forecasting
Abstract: BackgroundThe aim of this secondary analysis of the TESEO cohort is to identify, early in the course of treatment with tocilizumab, factors associated with the risk of progressing to mechanical ventilation and death and develop a risk score to estimate the risk of this outcome according to patients' profile.MethodsPatients with COVID-19 severe pneumonia receiving standard of care + tocilizumab who were alive and free from mechanical ventilation at day 6 after treatment initiation were included in this retrospective, multicenter cohort study. Multivariable logistic regression models were built to identify predictors of mechanical ventilation or death by day-28 from treatment initiation and β-coefficients were used to develop a risk score. Secondary outcome was mortality. Patients with the same inclusion criteria as the derivation cohort from 3 independent hospitals were used as validation cohort.Results266 patients treated with tocilizumab were included. By day 28 of hospital follow-up post treatment initiation, 40 (15%) underwent mechanical ventilation or died [26 (10%)]. At multivariable analysis, sex, day-4 PaO2/FiO2 ratio, platelets and CRP were independently associated with the risk of developing the study outcomes and were used to generate the proposed risk score. The accuracy of the score in AUC was 0.80 and 0.70 in internal validation and test for the composite endpoint and 0.92 and 0.69 for death, respectively.ConclusionsOur score could assist clinicians in identifying, early after tocilizumab administration, patients who are likely to progress to mechanical ventilation or death, so that they could be selected for eventual rescue therapies.
Published: 2020

45. Pain and Frailty in Hospitalized Older Adults

Author: Ardoino, Ilaria, Franchi, Carlotta, Nobili, Alessandro, Mannucci, Pier Mannuccio, Corli, Oscar, Pier Mannuccio Mannucci, Alessandro, Nobili, Antonello, Pietrangelo, Francesco, Perticone, Giuseppe, Licata, Francesco, Violi, Gino Roberto Corazza, Salvatore, Corrao, Alessandra, Marengoni, Francesco, Salerno, Matteo, Cesari, Mauro, Tettamanti, Luca, Pasina, Carlotta, Franchi, Laura, Cortesi, Gabriella, Miglio, Ilaria, Ardoino, Alessio, Novella, Domenico, Prisco, Elena, Silvestri, Giacomo, Emmi, Alessandra, Bettiol, Irene, Mattioli, Gianni, Biolo, Michela, Zanetti, Giacomo, Bartelloni, Massimo, Vanoli, Giulia, Grignani, Edoardo Alessandro Pulixi, Graziana, Lupattelli, Vanessa, Bianconi, Riccardo, Alcidi, Domenico, Girelli, Fabiana, Busti, Giacomo, Marchi, Mario, Barbagallo, Ligia, Dominguez, Vincenza, Beneduce, Federica, Cacioppo, Giuseppe, Natoli, Salvatore, Mularo, Massimo, Raspanti, Marco, Zoli, Maria Laura Matacena, Giuseppe, Orio, Eleonora, Magnolfi, Giovanni, Serafini, Angelo, Simili, Giuseppe, Palasciano, Maria Ester Modeo, Carla Di Gennaro, Maria Domenica Cappellini, Giovanna, Fabio, Margherita Migone De Amicis, Giacomo De Luca, Natalia, Scaramellini, Paolo Dionigi Rossi, Sarah, Damanti, Marta, Clerici, Simona, Leoni, Alessandra Danuta Di Mauro, Antonio Di Sabatino, Emanuela, Miceli, Marco Vincenzo Lenti, Martina, Pisati, Costanza Caccia Dominioni, Roberto, Pontremoli, Valentina, Beccati, Giulia, Nobili, Giovanna, Leoncini, Luigi, Anastasio, Maria, Carbone, Francesco, Cipollone, Maria Teresa Guagnano, Ilaria, Rossi, Gerardo, Mancuso, Daniela, Calipari, Mosè, Bartone, Giuseppe, Delitala, Maria, Berria, Alessandro, Delitala, Maurizio, Muscaritoli, Alessio, Molfino, Enrico, Petrillo, Antonella, Giorgi, Christian, Gracin, Giuseppe, Zuccalà, Gabriella, D'Aurizio, Giuseppe, Romanelli, Andrea, Volpini, Daniela, Lucente, Antonio, Picardi, Umberto Vespasiani Gentilucci, Paolo, Gallo, Giuseppe, Bellelli, Maurizio, Corsi, Cesare, Antonucci, Chiara, Sidoli, Giulia, Principato, Franco, Arturi, Elena, Succurro, Bruno, Tassone, Federica, Giofrè, Maria Grazia Serra, Maria Antonietta Bleve, Antonio, Brucato, Teresa De Falco, Fabrizio, Fabris, Irene, Bertozzi, Giulia, Bogoni, Maria Victoria Rabuini, Tancredi, Prandini, Roberto, Manfredini, Fabio, Fabbian, Benedetta, Boari, Alfredo De Giorgi, Ruana, Tiseo, Giuseppe, Paolisso, Maria Rosaria Rizzo, Claudia, Catalano, Claudio, Borghi, Enrico, Strocchi, Eugenia, Ianniello, Mario, Soldati, Silvia, Schiavone, Alessio, Bragagni, Carlo, Sabbà, Francesco Saverio Vella, Patrizia, Suppressa, Giovanni Michele De Vincenzo, Alessio, Comitangelo, Emanuele, Amoruso, Carlo, Custodero, Luigi, Fenoglio, Andrea, Falcetta, Anna, L Fracanzani, Silvia, Tiraboschi, Annalisa, Cespiati, Giovanna, Oberti, Giordano, Sigon, Flora, Peyvandi, Raffaella, Rossio, Giulia, Colombo, Pasquale, Agosti, Valter, Monzani, Valeria, Savojardo, Giuliana, Ceriani, Giada, Pallini, Montecucco, Fabrizio, Luciano, Ottonello, Lara, Caserza, Giulia, Vischi, Nicola Lucio Liberato, Tiziana, Tognin, Francesco, Purrello, Antonino Di Pino, Salvatore, Piro, Renzo, Rozzini, Lina, Falanga, Maria Stella Pisciotta, Francesco Baffa Bellucci, Stefano, Buffelli, Giuseppe, Montrucchio, Paolo, Peasso, Edoardo, Favale, Cesare, Poletto, Carl, Margaria, Maura, Sanino, Ludovica, Perri, Luigina, Guasti, Luana, Castiglioni, Andrea, Maresca, Alessandro, Squizzato, Leonardo, Campiotti, Alessandra, Grossi, Roberto Davide Diprizio, Marco, Bertolotti, Chiara, Mussi, Giulia, Lancellotti, Maria Vittoria Libbra, Matteo, Galassi, Yasmine, Grassi, Alessio, Greco, Angela, Sciacqua, Maria, Perticone, Rosa, Battaglia, Raffaele, Maio, Vincenzo, Stanghellini, Eugenio, Ruggeri, Sara Del Vecchio, Andrea, Salvi, Roberto, Leonardi, Giampaolo, Damiani, William, Capeci, Massimo, Mattioli, Giuseppe Pio Martino, Lorenzo, Biondi, Pietro, Pettinari, Riccardo, Ghio, Anna Dal Col, Salvatore, Minisola, Luciano, Colangelo, Mirella, Cilli, Giancarlo, Labbadia, Antonella, Afeltra, Benedetta, Marigliano, Maria Elena Pipita, Pietro, Castellino, Luca, Zanoli, Alfio, Gennaro, Agostino, Gaudio, Valter, Saracco, Marisa, Fogliati, Carlo, Bussolino, Francesca, Mete, Miriam, Gino, Carlo, Vigorito, Antonio, Cittadini, Guido, Moreo, Silvia, Prolo, Gloria, Pina, Alberto, Ballestrero, Fabio, Ferrando, Gonella, Roberta, Domenico, Cerminara, Sergio, Berra, Simonetta, Dassi, Maria Cristina Nava, Bruno, Graziella, Stefano, Baldassarre, Salvatore, Fragapani, Gabriella, Gruden, Giorgio, Galanti, Gabriele, Mascherini, Cristian, Petri, Laura, Stefani, Margherita, Girino, Valeria, Piccinelli, Francesco, Nasso, Vincenza, Gioffrè, Maria, Pasquale, Leonardo, Sechi, Cristiana, Catena, Gianluca, Colussi, Alessandro, Cavarape, Andea Da Porto, Nicola, Passariello, Luca, Rinaldi, Franco, Berti, Giuseppe, Famularo, Patrizia, Tarsitani, Roberto, Castello, Michela, Pasino, Gian Paolo Ceda, Marcello Giuseppe Maggio, Simonetta, Morganti, Andrea, Artoni, Margherita, Grossi, Stefano Del Giacco, Davide, Firinu, Giulia, Costanzo, Giacomo, Argiolas, Giuseppe, Montalto, Anna, Licata, Filippo Alessandro Montalto, Francesco, Corica, Giorgio, Basile, Antonino, Catalano, Federica, Bellone, Concetto, Principato, Lorenzo, Malatino, Benedetta, Stancanelli, Valentina, Terranova, Salvatore Di Marca, Rosario Di Quattro, Lara La Malfa, Rossella, Caruso, Patrizia, Mecocci, Carmelinda, Ruggiero, Virginia, Boccardi, Tiziana, Meschi, Andrea, Ticinesi, Antonio, Nouvenne, Pietro, Minuz, Luigi, Fondrieschi, Giandomenico Nigro Imperiale, Mario, Pirisi, Gian Paolo Fra, Daniele, Sola, Mattia, Bellan, Massimo, Porta, Piero, Riva, Roberto, Quadri, Erica, Larovere, Marco, Novelli, Giorgio, Scanzi, Caterina, Mengoli, Stella, Provini, Laura, Ricevuti, Emilio, Simeone, Rosa, Scurti, Fabio, Tolloso, Roberto, Tarquini, Alice, Valoriani, Silvia, Dolenti, Giulia, Vannini, Riccardo, Volpi, Pietro, Bocchi, Alessandro, Vignali, Sergio, Harari, Chiara, Lonati, Federico, Napoli, Italia, Aiello, Raffaele, Landolfi, Massimo, Montalto, Antonio, Mirijello, Nome, E Cognome Del Primario, Silvia, Ghidoni, Teresa, Salvatore, Lucio, Monaco, Carmen, Ricozzi, Alberto, Pilotto, Ilaria, Indiano, Federica, Gandolfo, Reposi, Investigator, Ardoino I., Franchi C., Nobili A., Mannucci P.M., Corli O., Pietrangelo A., Perticone F., Licata G., Violi F., Corazza G.R., Corrao S., Marengoni A., Salerno F., Cesari M., Tettamanti M., Pasina L., Cortesi L., Miglio G., Novella A., Prisco D., Silvestri E., Emmi G., Bettiol A., Mattioli I., Biolo G., Zanetti M., Bartelloni G., Vanoli M., Grignani G., Pulixi E.A., Lupattelli G., Bianconi V., Alcidi R., Girelli D., Busti F., Marchi G., Barbagallo M., Dominguez L., Beneduce V., Cacioppo F., Natoli G., Mularo S., Raspanti M., Zoli M., Matacena M.L., Orio G., Magnolfi E., Serafini G., Simili A., Palasciano G., Modeo M.E., Di Gennaro C., Cappellini M.D., Fabio G., De Amicis M.M., De Luca G., Scaramellini N., Rossi P.D., Damanti S., Clerici M., Leoni S., Di Mauro A.D., Di Sabatino A., Miceli E., Lenti M.V., Pisati M., Dominioni C.C., Pontremoli R., Beccati V., Nobili G., Leoncini G., Anastasio L., Carbone M., Cipollone F., Guagnano M.T., Rossi I., Mancuso G., Calipari D., Bartone M., Delitala G., Berria M., Delitala A., Muscaritoli M., Molfino A., Petrillo E., Giorgi A., Gracin C., Zuccala G., D'Aurizio G., Romanelli G., Volpini A., Lucente D., Picardi A., Gentilucci U.V., Gallo P., Bellelli G., Corsi M., Antonucci C., Sidoli C., Principato G., Arturi F., Succurro E., Tassone B., Giofre F., Serra M.G., Bleve M.A., Brucato A., De Falco T., Fabris F., Bertozzi I., Bogoni G., Rabuini M.V., Prandini T., Manfredini R., Fabbian F., Boari B., De Giorgi A., Tiseo R., Paolisso G., Rizzo M.R., Catalano C., Borghi C., Strocchi E., Ianniello E., Soldati M., Schiavone S., Bragagni A., Sabba C., Vella F.S., Suppressa P., De Vincenzo G.M., Comitangelo A., Amoruso E., Custodero C., Fenoglio L., Falcetta A., Fracanzani A.L., Tiraboschi S., Cespiati A., Oberti G., Sigon G., Peyvandi F., Rossio R., Colombo G., Agosti P., Monzani V., Savojardo V., Ceriani G., Pallini G., Montecucco F., Ottonello L., Caserza L., Vischi G., Liberato N.L., Tognin T., Purrello F., Di Pino A., Piro S., Rozzini R., Falanga L., Pisciotta M.S., Bellucci F.B., Buffelli S., Montrucchio G., Peasso P., Favale E., Poletto C., Margaria C., Sanino M., Perri L., Guasti L., Castiglioni L., Maresca A., Squizzato A., Campiotti L., Grossi A., Diprizio R.D., Bertolotti M., Mussi C., Lancellotti G., Libbra M.V., Galassi M., Grassi Y., Greco A., Sciacqua A., Perticone M., Battaglia R., Maio R., Stanghellini V., Ruggeri E., del Vecchio S., Salvi A., Leonardi R., Damiani G., Capeci W., Mattioli M., Martino G.P., Biondi L., Pettinari P., Ghio R., Col A.D., Minisola S., Colangelo L., Cilli M., Labbadia G., Afeltra A., Marigliano B., Pipita M.E., Castellino P., Zanoli L., Gennaro A., Gaudio A., Saracco V., Fogliati M., Bussolino C., Mete F., Gino M., Vigorito C., Cittadini A., Moreo G., Prolo S., Pina G., Ballestrero A., Ferrando F., Gonella R., Cerminara D., Berra S., Dassi S., Nava M.C., Graziella B., Baldassarre S., Fragapani S., Gruden G., Galanti G., Mascherini G., Petri C., Stefani L., Girino M., Piccinelli V., Nasso F., Gioffre V., Pasquale M., Sechi L., Catena C., Colussi G., Cavarape A., Da Porto A., Passariello N., Rinaldi L., Berti F., Famularo G., Tarsitani P., Castello R., Pasino M., Ceda G.P., Maggio M.G., Morganti S., Artoni A., Grossi M., Del Giacco S., Firinu D., Costanzo G., Argiolas G., Montalto G., Licata A., Montalto F.A., Corica F., Basile G., Catalano A., Bellone F., Principato C., Malatino L., Stancanelli B., Terranova V., Di Marca S., Di Quattro R., La Malfa L., Caruso R., Mecocci P., Ruggiero C., Boccardi V., Meschi T., Ticinesi A., Nouvenne A., Minuz P., Fondrieschi L., Imperiale G.N., Pirisi M., Fra G.P., Sola D., Bellan M., Porta M., Riva P., Quadri R., Larovere E., Novelli M., Scanzi G., Mengoli C., Provini S., Ricevuti L., Simeone E., Scurti R., Tolloso F., Tarquini R., Valoriani A., Dolenti S., Vannini G., Volpi R., Bocchi P., Vignali A., Harari S., Lonati C., Napoli F., Aiello I., Landolfi R., Montalto M., Mirijello A., del Primario N.C., Ghidoni S., Salvatore T., Monaco L., Ricozzi C., Pilotto A., Indiano I., Gandolfo F., Ardoino, Ilaria, Franchi, Carlotta, Nobili, Alessandro, Mannucci, Pier Mannuccio, Corli, Oscar, Borghi C, Stanghellini V, Ardoino, I, Franchi, C, Nobili, A, Mannucci, P, Corli, O, Bellelli, G, Ardoino, I., Franchi, C., Nobili, A., Mannucci, P. M., Corli, O., Pietrangelo, A., Perticone, F., Licata, G., Violi, F., Corazza, G. R., Corrao, S., Marengoni, A., Salerno, F., Cesari, M., Tettamanti, M., Pasina, L., Cortesi, L., Miglio, G., Novella, A., Prisco, D., Silvestri, E., Emmi, G., Bettiol, A., Mattioli, I., Biolo, G., Zanetti, M., Bartelloni, G., Vanoli, M., Grignani, G., Pulixi, E. A., Lupattelli, G., Bianconi, V., Alcidi, R., Girelli, D., Busti, F., Marchi, G., Barbagallo, M., Dominguez, L., Beneduce, V., Cacioppo, F., Natoli, G., Mularo, S., Raspanti, M., Zoli, M., Matacena, M. L., Orio, G., Magnolfi, E., Serafini, G., Simili, A., Palasciano, G., Modeo, M. E., Di Gennaro, C., Cappellini, M. D., Fabio, G., De Amicis, M. M., De Luca, G., Scaramellini, N., Rossi, P. D., Damanti, S., Clerici, M., Leoni, S., Di Mauro, A. D., Di Sabatino, A., Miceli, E., Lenti, M. V., Pisati, M., Dominioni, C. C., Pontremoli, R., Beccati, V., Nobili, G., Leoncini, G., Anastasio, L., Carbone, M., Cipollone, F., Guagnano, M. T., Rossi, I., Mancuso, G., Calipari, D., Bartone, M., Delitala, G., Berria, M., Delitala, A., Muscaritoli, M., Molfino, A., Petrillo, E., Giorgi, A., Gracin, C., Zuccala, G., D'Aurizio, G., Romanelli, G., Volpini, A., Lucente, D., Picardi, A., Gentilucci, U. V., Gallo, P., Bellelli, G., Corsi, M., Antonucci, C., Sidoli, C., Principato, G., Arturi, F., Succurro, E., Tassone, B., Giofre, F., Serra, M. G., Bleve, M. A., Brucato, A., De Falco, T., Fabris, F., Bertozzi, I., Bogoni, G., Rabuini, M. V., Prandini, T., Manfredini, R., Fabbian, F., Boari, B., De Giorgi, A., Tiseo, R., Paolisso, G., Rizzo, M. R., Catalano, C., Borghi, C., Strocchi, E., Ianniello, E., Soldati, M., Schiavone, S., Bragagni, A., Sabba, C., Vella, F. S., Suppressa, P., De Vincenzo, G. M., Comitangelo, A., Amoruso, E., Custodero, C., Fenoglio, L., Falcetta, A., Fracanzani, A. L., Tiraboschi, S., Cespiati, A., Oberti, G., Sigon, G., Peyvandi, F., Rossio, R., Colombo, G., Agosti, P., Monzani, V., Savojardo, V., Ceriani, G., Pallini, G., Montecucco, F., Ottonello, L., Caserza, L., Vischi, G., Liberato, N. L., Tognin, T., Purrello, F., Di Pino, A., Piro, S., Rozzini, R., Falanga, L., Pisciotta, M. S., Bellucci, F. B., Buffelli, S., Montrucchio, G., Peasso, P., Favale, E., Poletto, C., Margaria, C., Sanino, M., Perri, L., Guasti, L., Castiglioni, L., Maresca, A., Squizzato, A., Campiotti, L., Grossi, A., Diprizio, R. D., Bertolotti, M., Mussi, C., Lancellotti, G., Libbra, M. V., Galassi, M., Grassi, Y., Greco, A., Sciacqua, A., Perticone, M., Battaglia, R., Maio, R., Stanghellini, V., Ruggeri, E., del Vecchio, S., Salvi, A., Leonardi, R., Damiani, G., Capeci, W., Mattioli, M., Martino, G. P., Biondi, L., Pettinari, P., Ghio, R., Col, A. D., Minisola, S., Colangelo, L., Cilli, M., Labbadia, G., Afeltra, A., Marigliano, B., Pipita, M. E., Castellino, P., Zanoli, L., Gennaro, A., Gaudio, A., Saracco, V., Fogliati, M., Bussolino, C., Mete, F., Gino, M., Vigorito, C., Cittadini, A., Moreo, G., Prolo, S., Pina, G., Ballestrero, A., Ferrando, F., Gonella, R., Cerminara, D., Berra, S., Dassi, S., Nava, M. C., Graziella, B., Baldassarre, S., Fragapani, S., Gruden, G., Galanti, G., Mascherini, G., Petri, C., Stefani, L., Girino, M., Piccinelli, V., Nasso, F., Gioffre, V., Pasquale, M., Sechi, L., Catena, C., Colussi, G., Cavarape, A., Da Porto, A., Passariello, N., Rinaldi, L., Berti, F., Famularo, G., Tarsitani, P., Castello, R., Pasino, M., Ceda, G. P., Maggio, M. G., Morganti, S., Artoni, A., Grossi, M., Del Giacco, S., Firinu, D., Costanzo, G., Argiolas, G., Montalto, G., Licata, A., Montalto, F. A., Corica, F., Basile, G., Catalano, A., Bellone, F., Principato, C., Malatino, L., Stancanelli, B., Terranova, V., Di Marca, S., Di Quattro, R., La Malfa, L., Caruso, R., Mecocci, P., Ruggiero, C., Boccardi, V., Meschi, T., Ticinesi, A., Nouvenne, A., Minuz, P., Fondrieschi, L., Imperiale, G. N., Pirisi, M., Fra, G. P., Sola, D., Bellan, M., Porta, M., Riva, P., Quadri, R., Larovere, E., Novelli, M., Scanzi, G., Mengoli, C., Provini, S., Ricevuti, L., Simeone, E., Scurti, R., Tolloso, F., Tarquini, R., Valoriani, A., Dolenti, S., Vannini, G., Volpi, R., Bocchi, P., Vignali, A., Harari, S., Lonati, C., Napoli, F., Aiello, I., Landolfi, R., Montalto, M., Mirijello, A., del Primario, N. C., Ghidoni, S., Salvatore, T., Monaco, L., Ricozzi, C., Pilotto, A., Indiano, I., Gandolfo, F., Corli, Oscar, Paolisso, Giuseppe, and Rizzo, Maria Rosaria
Subjects: medicine.medical_specialty, Pain medicine, Socio-culturale, Chronic pain, Osteoarthritis, Affect (psychology), Internal medicine and geriatric wards, Musculoskeletal diseases, Older population, Chronic pain, Internal medicine and geriatric wards, Musculoskeletal diseases, Quality of life, Musculoskeletal disease, Anesthesiology, Internal medicine, medicine, RD78.3-87.3, LS4_4, Original Research, business.industry, medicine.disease, Internal medicine and geriatric ward, Anesthesiology and Pain Medicine, Rheumatoid arthritis, Neurology (clinical), Ordered logit, business
Abstract: Introduction Pain and frailty are prevalent conditions in the older population. Many chronic diseases are likely involved in their origin, and both have a negative impact on quality of life. However, few studies have analysed their association. Methods In light of this knowledge gap, 3577 acutely hospitalized patients 65 years or older enrolled in the REPOSI register, an Italian network of internal medicine and geriatric hospital wards, were assessed to calculate the frailty index (FI). The impact of pain and some of its characteristics on the degree of frailty was evaluated using an ordinal logistic regression model after adjusting for age and gender. Results The prevalence of pain was 24.7%, and among patients with pain, 42.9% was regarded as chronic pain. Chronic pain was associated with severe frailty (OR = 1.69, 95% CI 1.38–2.07). Somatic pain (OR = 1.59, 95% CI 1.23–2.07) and widespread pain (OR = 1.60, 95% CI 0.93–2.78) were associated with frailty. Osteoarthritis was the most common cause of chronic pain, diagnosed in 157 patients (33.5%). Polymyalgia, rheumatoid arthritis and other musculoskeletal diseases causing chronic pain were associated with a lower degree of frailty than osteoarthritis (OR = 0.49, 95%CI 0.28–0.85). Conclusions Chronic and somatic pain negatively affect the degree of frailty. The duration and type of pain, as well as the underlying diseases associated with chronic pain, should be evaluated to improve the hospital management of frail older people. Electronic Supplementary Material The online version of this article (10.1007/s40122-020-00202-3) contains supplementary material, which is available to authorized users.
Published: 2020

46. Comorbidity does not mean clinical complexity: evidence from the RePoSI register

Author: Pier Mannuccio Mannucci, Francesco Perticone, Antonello Pietrangelo, Christiano Argano, Salvatore Corrao, Alessandro Nobili, Giuseppe Natoli, Corrao S., Natoli G., Nobili A., Mannucci P.M., Pietrangelo A., Perticone F., and Argano C.
Subjects: Male, medicine.medical_specialty, Cumulative illness rating scale, Comorbidity, Disease, 030204 cardiovascular system & hematology, Age and sex, Severity of Illness Index, 03 medical and health sciences, 0302 clinical medicine, Number of comorbidities, Risk Factors, Rating scale, Cause of Death, Internal Medicine, Humans, Medicine, Clinical significance, Hospital Mortality, Registries, 030212 general & internal medicine, Geriatric Assessment, Aged, Retrospective Studies, Aged, 80 and over, business.industry, Multimorbidity, Length of Stay, medicine.disease, Clinical complexity, Clinical Practice, Italy, Emergency medicine, Emergency Medicine, Female, Multiple Chronic Conditions, business, Comorbidity index
Abstract: In the last 2–3decades internists have confronted dramatic changes in the pattern of patients acutely admitted to hospital wards. Internists observed a shift from younger subjects affected by a single organ disease to more complex patients, usually older, with multiple chronic conditions, attended by different specialists, with poor integration and treated with multiple drugs. In this regard, the concept of complex patients is addressed daily in clinical practice even if there is no agreed definition of patient complexity. To try to evaluate clinical complexity different instruments have been proposed. Among these, the number of comorbidities (NoC) was considered a marker of clinical complexity. However, this instrument would not give information about the clinical relevance of each condition. On the contrary, cumulative illness rating scale (CIRS) addresses the problem calculating both CIRS severity index (CIRS-SI) and CIRS comorbidity index (CIRS-CI). In light of this, 4714 patients from the RePoSI register were retrospectively analyzed to show if CIRS assessment of comorbidity burden is different from the simple count of comorbidities in predicting the length of hospital stay (LOS) and all-cause of mortality in hospitalized elderly patients and if NoC could be a valid tool to measure patient’s complexity. CIRS-SI resulted the best predictor of all-cause in-hospital mortality [OR: 2.66 (1.88–3.77)] in comparison with NoC that did not result statistically significant (p = 0.551). CIRS-SI was also the best predictor of all-cause of post-discharge mortality corrected for age and sex [OR: 2.12 (1.53–2.95)]. CIRS-SI (coefficient ± standard error: 1.23 ± 0.59; p < 0.0381) and CIRS-CI (coefficient ± standard error: 0.27 ± 0.10; p < 0.011) were strong predictors of LOS in comparison with NoC that did not result statistically significant (coefficient ± standard error: 0.04 ± 0.06 p < 0.0561). In conclusion, CIRS assessment of comorbidity burden is a better clinical tool in comparison with the simple count of comorbidities especially considering the length of hospital stay and all-cause mortality in hospitalized elderly patients.
Published: 2020

47. Hyperhomocysteinemia in patients with acute porphyrias: A potentially dangerous metabolic crossroad?

Author: Matteo Marcacci, Paolo Ventura, Elena Di Pierro, Antonello Pietrangelo, Stefano Marchini, Elena Corradini, Elena Buzzetti, and Chiara Cuoghi
Subjects: medicine.medical_specialty, Hyperhomocysteinemia, Homocysteine, Variegate porphyria, Cystathionine beta-Synthase, 030204 cardiovascular system & hematology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Acute Porphyrias, Ala-Synthase1, Vitamin B6, Internal medicine, Porphobilinogen, Internal Medicine, medicine, Humans, 030212 general & internal medicine, Heme, Acute intermittent porphyria, biology, business.industry, medicine.disease, Cystathionine beta synthase, ALAS1, Vitamin B 12, Endocrinology, chemistry, Porphyria, Acute Intermittent, biology.protein, business
Abstract: Background Acute porphyrias (AP) are characterized by heme deficiency and induction of hepatic 5-aminolevulinate synthase (ALAS1). Hyperhomocysteinemia (HHcy) is associated with endothelial damage, neurotoxicity and increased risk for vascular diseases. Interestingly, both heme biosynthesis and sulphur amino acid metabolism require vitamin B6, (Pyridoxal-phosphate, PLP) an important cofactor of ALAS1 and of cystathionine β-synthase (CBS) and cystathionine γ-lyase (CGL) enzymes that catabolize homocysteine (Hcy). Moreover, heme itself is an important cofactor for CBS. Aim to assess plasma Hcy status and HHcy main determinants in patients with AP. Materials and methods A total of 46 patients with AP (31 with Acute Intermittent Porphyria,15 with Variegate Porphyria) were assessed for clinical status (symptomatic vs. asymptomatic), serum Hcy, Cysteine (Cys), Vit.B6, Vit.B12, red blood cell folates and urinary delta-aminolevulinic acid (ALA) and porphobilinogen(PBG) levels (mean of six measurements). Results Symptomatic AP patients had significantly higher urinary ALA and PBG levels, plasma Hcy, HHcy prevalence and Hcy/Cys ratio when compared to asymptomatic carriers of AP. Even though no significant correlation was observed between ALA/PBG urinary levels and serum Hcy levels, patients with higher levels of ALA and PBG had significantly higher levels of Hcy, a higher prevalence of moderate-to severe HHcy and serum PLP levels below the 25th percentile of a reference assessment with 300 healthy Italian subjects( Conclusions Most patients with symptomatic AP present HHcy resulting from alterations in sulphur amino acid metabolism. HHcy may represent an indirect marker of ALAS1 induction and its prevalence may be suggestive of a role of HHcy in the pathogenesis and/or comorbidities of AP.
Published: 2020

48. Tocilizumab in patients with severe COVID-19: a retrospective cohort study

Author: Ivana Castaniere, Jovana Milic, Marianna Menozzi, Maddalena Giannella, Marianna Meschiari, Lucio Brugioni, Alessandro Cozzi-Lepri, Massimo Girardis, Cinzia Puzzolante, Enrico Clini, Margherita Di Gaetano, Vanni Borghi, Sara K. Tedeschi, Erica Franceschini, Michele Bartoletti, Gabriella Orlando, Luca Tabbì, Antonella Santoro, Andrea Bedini, Carlo Salvarani, Federica Carli, Federico Pea, Antonello Pietrangelo, Luca Corradi, Gianluca Cuomo, Roberto Tonelli, Pierluigi Viale, Riccardo Fantini, Andrea Cossarizza, Giovanni Guaraldi, Renato Pascale, Cristina Mussini, Marco Massari, Giovanni Dolci, Guaraldi G., Meschiari M., Cozzi-Lepri A., Milic J., Tonelli R., Menozzi M., Franceschini E., Cuomo G., Orlando G., Borghi V., Santoro A., Di Gaetano M., Puzzolante C., Carli F., Bedini A., Corradi L., Fantini R., Castaniere I., Tabbi L., Girardis M., Tedeschi S., Giannella M., Bartoletti M., Pascale R., Dolci G., Brugioni L., Pietrangelo A., Cossarizza A., Pea F., Clini E., Salvarani C., Massari M., Viale P.L., and Mussini C.
Subjects: Mechanical ventilation, medicine.medical_specialty, medicine.drug_class, business.industry, medicine.medical_treatment, Immunology, Low molecular weight heparin, Retrospective cohort study, Azithromycin, medicine.disease, Article, chemistry.chemical_compound, Pneumonia, Tocilizumab, chemistry, Rheumatology, Internal medicine, severe covid-19, tocilizumab, medicine, Clinical endpoint, Immunology and Allergy, business, Letters to the Editor, Cohort study, medicine.drug
Abstract: Background: No therapy is approved for COVID-19 pneumonia. The aim of this study was to assess the role of tocilizumab in reducing the risk of invasive mechanical ventilation and death in patients with severe COVID-19 pneumonia who received standard of care treatment. Methods: This retrospective, observational cohort study included adults (≥18 years) with severe COVID-19 pneumonia who were admitted to tertiary care centres in Bologna and Reggio Emilia, Italy, between Feb 21 and March 24, 2020, and a tertiary care centre in Modena, Italy, between Feb 21 and April 30, 2020. All patients were treated with the standard of care (ie, supplemental oxygen, hydroxychloroquine, azithromycin, antiretrovirals, and low molecular weight heparin), and a non-randomly selected subset of patients also received tocilizumab. Tocilizumab was given either intravenously at 8 mg/kg bodyweight (up to a maximum of 800 mg) in two infusions, 12 h apart, or subcutaneously at 162 mg administered in two simultaneous doses, one in each thigh (ie, 324 mg in total), when the intravenous formulation was unavailable. The primary endpoint was a composite of invasive mechanical ventilation or death. Treatment groups were compared using Kaplan-Meier curves and Cox regression analysis after adjusting for sex, age, recruiting centre, duration of symptoms, and baseline Sequential Organ Failure Assessment (SOFA) score. Findings: Of 1351 patients admitted, 544 (40%) had severe COVID-19 pneumonia and were included in the study. 57 (16%) of 365 patients in the standard care group needed mechanical ventilation, compared with 33 (18%) of 179 patients treated with tocilizumab (p=0·41; 16 [18%] of 88 patients treated intravenously and 17 [19%] of 91 patients treated subcutaneously). 73 (20%) patients in the standard care group died, compared with 13 (7%; p
Published: 2020

49. Genetic iron overload disorders

Author: Elena Buzzetti, Elena Corradini, and Antonello Pietrangelo
Subjects: 0301 basic medicine, Iron Overload, Iron, Clinical Biochemistry, Cellular functions, Disease, Bioinformatics, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, Tissue damage, Genetics, Medicine, Humans, Iron overload, Molecular Biology, Pathological, Ferroportin disease, Hemochromatosis, Hyperferritinemia, business.industry, Mechanism (biology), General Medicine, medicine.disease, Micronutrient, 030104 developmental biology, 030220 oncology & carcinogenesis, Molecular Medicine, business
Abstract: Due to its pivotal role in orchestrating vital cellular functions and metabolic processes, iron is an essential component of the human body and a main micronutrient in the human diet. However, excess iron causes an increased production of reactive oxygen species leading to cell dysfunction or death, tissue damage and organ disease. Iron overload disorders encompass a wide spectrum of pathological conditions of hereditary or acquired origin. A number of 'iron genes' have been identified as being associated with hereditary iron overload syndromes, the most common of which is hemochromatosis. Although linked to at least five different genes, hemochromatosis is recognized as a unique syndromic entity based on a common pathogenetic mechanism leading to excessive entry of unneeded iron into the bloodstream. In this review, we focus on the pathophysiologic basis and clinical aspects of the most common genetic iron overload syndromes in humans.
Published: 2020

50. Hyperferritinemia and diagnosis of type 1 Gaucher disease

Author: Fabiana Busti, Giacomo Marchi, Alberto Piperno, Elena Corradini, Antonello Pietrangelo, Irene Motta, Domenico Girelli, Maria Domenica Cappellini, Francesca Carubbi, Fabio Nascimbeni, Marchi, G, Nascimbeni, F, Motta, I, Busti, F, Carubbi, F, Cappellini, M, Pietrangelo, A, Corradini, E, Piperno, A, and Girelli, D
Subjects: Male, gaucher disease, Humans, Medicine, transferrin, glucosylceramidase, chemistry.chemical_classification, Ferritin, Gaucher Disease, biology, business.industry, ferritin, Type 1 Gaucher Disease, Hematology, Middle Aged, Glucosylceramidase, chemistry, Transferrin, Ferritins, Immunology, biology.protein, hyperferritinemia, Gaucher, Hyperferritinemia, business, Lisosomal storage disease
Published: 2020

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