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1. SETBP1 accumulation induces P53 inhibition and genotoxic stress in neural progenitors underlying neurodegeneration in Schinzel-Giedion syndrome

Author: Angelo Ianielli, Mattia Zaghi, Chiara Di Resta, Federica Banfi, Edoardo Bellini, Mirko Luoni, Luca Massimino, Rocco Piazza, Alicia Rubio, Alessandro Sessa, Anna Bagliani, Vania Broccoli, Giulia Fagnocchi, Cinzia Cancellieri, Maurizio Ferrari, Luca Mologni, Camilla Maffezzini, Banfi, F, Rubio, A, Zaghi, M, Massimino, L, Fagnocchi, G, Bellini, E, Luoni, M, Cancellieri, C, Bagliani, A, Di Resta, C, Maffezzini, C, Ianielli, A, Ferrari, M, Piazza, R, Mologni, L, Broccoli, V, Sessa, A, Banfi, F., Rubio, A., Zaghi, M., Massimino, L., Fagnocchi, G., Bellini, E., Luoni, M., Cancellieri, C., Bagliani, A., Di Resta, C., Maffezzini, C., Ianielli, A., Ferrari, M., Piazza, R., Mologni, L., Broccoli, V., and Sessa, A.
Subjects: Organoid, 0301 basic medicine, General Physics and Astronomy, Craniofacial Abnormalities, 0302 clinical medicine, Neural Stem Cells, Neurological models, Neural Stem Cell, Cells, Cultured, Nuclear Protein, Multidisciplinary, Neurodegenerative diseases, Neurodegeneration, Nuclear Proteins, Phenotype, Organoids, Heredodegenerative Disorders, Nervous System, Hand Deformities, Congenital, Human, Cell death, Programmed cell death, DNA damage, Science, Nails, Malformed, Biology, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, stomatognathic system, Intellectual Disability, medicine, Humans, Abnormalities, Multiple, Progenitor cell, Disease model, Craniofacial Abnormalitie, Schinzel–Giedion syndrome, SETBP1 Gene, General Chemistry, medicine.disease, 030104 developmental biology, Apoptosis, Mutation, Diseases of the nervous system, Tumor Suppressor Protein p53, Carrier Protein, Carrier Proteins, Neuroscience, 030217 neurology & neurosurgery, DNA Damage
Abstract: The investigation of genetic forms of juvenile neurodegeneration could shed light on the causative mechanisms of neuronal loss. Schinzel-Giedion syndrome (SGS) is a fatal developmental syndrome caused by mutations in the SETBP1 gene, inducing the accumulation of its protein product. SGS features multi-organ involvement with severe intellectual and physical deficits due, at least in part, to early neurodegeneration. Here we introduce a human SGS model that displays disease-relevant phenotypes. We show that SGS neural progenitors exhibit aberrant proliferation, deregulation of oncogenes and suppressors, unresolved DNA damage, and resistance to apoptosis. Mechanistically, we demonstrate that high SETBP1 levels inhibit P53 function through the stabilization of SET, which in turn hinders P53 acetylation. We find that the inheritance of unresolved DNA damage in SGS neurons triggers the neurodegenerative process that can be alleviated either by PARP-1 inhibition or by NAD + supplementation. These results implicate that neuronal death in SGS originates from developmental alterations mainly in safeguarding cell identity and homeostasis., Schinzel-Giedion syndrome (SGS) is a fatal developmental syndrome characterized by severe intellectual and physical deficits due, at least in part, to early neurodegeneration. Here the authors introduce a human SGS model that displays disease-relevant phenotypes to demonstrate that neuronal death in SGS originates from developmental alterations mainly in safeguarding cell identity and homeostasis.
Published: 2021

2. Brugada syndrome genetics is associated with phenotype severity

Author: Enrico Petretto, Andrea Bernardini, Gabriele Vicedomini, Andrea Ghiroldi, Žarko Ćalović, Chiara Di Resta, Carlo de Innocentiis, Francesca Santini, Giuseppe Ciconte, Michelle M. Monasky, Valerio Mecarocci, Gabriele Negro, Giorgio Casari, Roberto Rondine, Luigi Giannelli, Beniamino C Mazza, Luigi Anastasia, Ilaria Rivolta, Sara Benedetti, Valeria Borrelli, Carlo Pappone, Vincenzo Santinelli, Emanuele Micaglio, Sara D'Imperio, Emanuela T Locati, Ciconte, G, Monasky, M, Santinelli, V, Micaglio, E, Vicedomini, G, Anastasia, L, Negro, G, Borrelli, V, Giannelli, L, Santini, F, de Innocentiis, C, Rondine, R, Locati, E, Bernardini, A, Mazza, B, Mecarocci, V, Ćalović, Ž, Ghiroldi, A, D'Imperio, S, Benedetti, S, Di Resta, C, Rivolta, I, Casari, G, Petretto, E, Pappone, C, Ciconte, Giuseppe, Monasky, Michelle M, Santinelli, Vincenzo, Micaglio, Emanuele, Vicedomini, Gabriele, Anastasia, Luigi, Negro, Gabriele, Borrelli, Valeria, Giannelli, Luigi, Santini, Francesca, de Innocentiis, Carlo, Rondine, Roberto, Locati, Emanuela T, Bernardini, Andrea, Mazza, Beniamino C, Mecarocci, Valerio, Ćalović, Žarko, Ghiroldi, Andrea, D'Imperio, Sara, Benedetti, Sara, Di Resta, Chiara, Rivolta, Ilaria, Casari, Giorgio, Petretto, Enrico, and Pappone, Carlo
Subjects: Proband, congenital, hereditary, and neonatal diseases and abnormalities, medicine.medical_specialty, Genotype, Arrhythmias, Epicardial arrhythmogenic substrate, 030204 cardiovascular system & hematology, Ventricular tachycardia, Sudden cardiac death, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Medicine, AcademicSubjects/MED00200, Brugada syndrome, cardiovascular diseases, SCN5A, Genetic testing, Fibrillation, medicine.diagnostic_test, Predictors, business.industry, Clnical Research, medicine.disease, Phenotype, Mutation (genetic algorithm), cardiovascular system, Cardiology, medicine.symptom, Cardiology and Cardiovascular Medicine, business, 030217 neurology & neurosurgery, Predictor
Abstract: Aims Brugada syndrome (BrS) is associated with an increased risk of sudden cardiac death due to ventricular tachycardia/fibrillation (VT/VF) in young, otherwise healthy individuals. Despite SCN5A being the most commonly known mutated gene to date, the genotype–phenotype relationship is poorly understood and remains uncertain. This study aimed to elucidate the genotype–phenotype correlation in BrS. Methods and results Brugada syndrome probands deemed at high risk of future arrhythmic events underwent genetic testing and phenotype characterization by the means of epicardial arrhythmogenic substrate (AS) mapping, and were divided into two groups according to the presence or absence of SCN5A mutation. Two-hundred probands (160 males, 80%; mean age 42.6 ± 12.2 years) were included in this study. Patients harbouring SCN5A mutations exhibited a spontaneous type 1 pattern and experienced aborted cardiac arrest or spontaneous VT/VF more frequently than the other subjects. SCN5A-positive patients exhibited a larger epicardial AS area, more prolonged electrograms and more frequently observed non-invasive late potentials. The presence of an SCN5A mutation explained >26% of the variation in the epicardial AS area and was the strongest predictor of a large epicardial area. Conclusion In BrS, the genetic background is the main determinant for the extent of the electrophysiological abnormalities. SCN5A mutation carriers exhibit more pronounced epicardial electrical abnormalities and a more aggressive clinical presentation. These results contribute to the understanding of the genetic determinants of the BrS phenotypic expression and provide possible explanations for the varying degrees of disease expression.
Published: 2020
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3. Impact of smoking, COPD and comorbidities on the mortality of COVID-19 patients

Author: Eugenio Sabato, Giovanna Elisiana Carpagnano, Onofrio Resta, Emanuela Resta, Carla Santomasi, Paolo Fuso, Franco Mastroianni, Donato Lacedonia, Maria Pia Foschino Barbaro, Andrea Portacci, Giulia Scioscia, Giovanni Larizza, and Emanuela Profilo
Subjects: Male, medicine.medical_specialty, Science, Comorbidity, Pathogenesis, Microbiology, Article, Cohort Studies, Pulmonary Disease, Chronic Obstructive, Intensive care, Internal medicine, medicine, Prevalence, Humans, Mortality, Signs and symptoms, Aged, COPD, Multidisciplinary, business.industry, Smoking, COVID-19, Middle Aged, Former Smoker, medicine.disease, Prognosis, respiratory tract diseases, Hospitalization, Pneumonia, Respiratory failure, Italy, Risk factors, Cohort, behavior and behavior mechanisms, Medicine, business, Cohort study
Abstract: The prognosis of the coronavirus disease 2019 (COVID-19) patients is variable and depends on several factors. Current data about the impact of chronic obstructive pulmonary disease (COPD) and smoking on the clinical course of COVID-19 are still controversial. This study evaluated the prevalence and the prognosis of COPD patients and smokers in a cohort of 521 patients admitted to four intermediate Respiratory Intensive Care Units (Puglia, Italy) with respiratory failure due to COVID-19 pneumonia. The prevalence of COPD and current smokers was 14% and 13%, respectively. COPD patients had a higher 30-day all-cause mortality than non-COPD patients. Former smokers compared to never smokers and current smokers had higher 30-day all-cause mortality. COPD patients and former smokers had more comorbidities. This study described the prevalence and the outcomes of COPD patients and smokers in a homogenous cohort of COVID-19 patients. The study showed that the prevalence of COPD and current smokers was not high, suggesting that they were not at increased risk of getting the infection. However, when SARS-CoV-2 infection occurred, COPD patients and former smokers were those with the highest all-cause mortality, which seemed to be mainly related to the presence of comorbidities and not to COPD and smoking itself.
Published: 2021

4. COVID-19 clinical phenotypes and short-term outcomes: differences between the first and the second wave of pandemic in Italy

Author: Emanuela Resta, Lavinia Palma, Andrea Portacci, Maria Grazia Tummolo, Giovanna Elisiana Carpagnano, Francesco Panza, Domenico Claudio Fasano, Onofrio Resta, Vincenzo Solfrizzi, Madia Lozupone, and Carla Santomasi
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, ARDS, Coronavirus disease 2019 (COVID-19), Disease, survival, assisted ventilation, intermediate RICU, Internal medicine, Pandemic, medicine, Humans, Immunology and Allergy, Pandemics, Original Research, SARS-CoV-2, business.industry, pandemic, Mortality rate, Public Health, Environmental and Occupational Health, COVID-19, Retrospective cohort study, medicine.disease, Hospitalization, Critical care, Pneumonia, Phenotype, Italy, Concomitant, business, Research Article
Abstract: Objectives: There are no comparative studies between patients belonging to the first and second waves of the SARS-CoV-2 pandemic, the virus triggering coronavirus disease 2019 (COVID-19). In this retrospective observational study, we analyzed the clinical characteristics and the short-term outcomes of two groups of laboratory-confirmed COVID-19 patients with moderate-to-severe acute respiratory distress syndrome (ARDS) belonging to two different waves of the pandemic. Methods: We analyzed 97 consecutive patients from 11 March 2020 to 31 May 2020 and 52 consecutive patients from 28 August 2020 to 15 October 2020. Results: Patients belonging to the second wave were younger, had a lower number of concomitant chronic conditions (multimorbidity), and had a milder clinical phenotype. Medical treatments and respiratory support use have changed during the COVID-19 pandemic, based on different laboratory results and disease clinical features. Patients in the second wave had better short-term clinical outcomes, with lower death rates and more step-down transfers to a general ward. Conclusion: The present findings show a clear phenotypic difference in patients hospitalized at different stages of the COVID-19 pandemic in Italy. These results can help to stratify clinical risk and to better tailor medical treatments and respiratory support for patients with ARDS and COVID-19 pneumonia.
Published: 2021
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5. Lung ultrasound for the early diagnosis of COVID-19 pneumonia: an international multicenter study

Author: Volpicelli, G., Gargani, L., Perlini, S., Spinelli, S., Barbieri, G., Lanotte, A., Casasola, G. G., Nogue-Bou, R., Lamorte, A., Agricola, E., Villen, T., Deol, P. S., Nazerian, P., Corradi, F., Stefanone, V., Fraga, D. N., Navalesi, P., Ferre, R., Boero, E., Martinelli, G., Cristoni, L., Perani, C., Vetrugno, L., Mcdermott, C., Miralles-Aguiar, F., Secco, G., Zattera, C., Salinaro, F., Grignaschi, A., Boccatonda, A., Giostra, F., Infante, M. N., Covella, M., Ingallina, G., Burkert, J., Frumento, P., Forfori, F., Ghiadoni, L., Fraccalini, T., Vendrame, A., Basile, V., Cipriano, A., Frassi, F., Santini, M., Falcone, M., Menichetti, F., Barcella, B., Delorenzo, M., Resta, F., Vezzoni, G., Bonzano, M., Briganti, D. F., Cappa, G., Zunino, I., Demitry, L., Vignaroli, D., Dipietro, L. S. S., Bazzini, M., Capozza, V., Gonzalez, M. M., Gibal, R. V., Ibarz, R. P., Alfaro, L. M., Alfaro, C. M., Alins, M. G., Brown, A., Dunlop, H., Ralli, M. L., Persona, P., Russel, F. M., Pang, P. S., Rovida, S., Deana, C., Franchini, D., Gargani, Luna, Volpicelli, G., Gargani, L., Perlini, S., Spinelli, S., Barbieri, G., Lanotte, A., Casasola, G. G., Nogue-Bou, R., Lamorte, A., Agricola, E., Villen, T., Deol, P. S., Nazerian, P., Corradi, F., Stefanone, V., Fraga, D. N., Navalesi, P., Ferre, R., Boero, E., Martinelli, G., Cristoni, L., Perani, C., Vetrugno, L., Mcdermott, C., Miralles-Aguiar, F., Secco, G., Zattera, C., Salinaro, F., Grignaschi, A., Boccatonda, A., Giostra, F., Infante, M. N., Covella, M., Ingallina, G., Burkert, J., Frumento, P., Forfori, F., Ghiadoni, L., Fraccalini, T., Vendrame, A., Basile, V., Cipriano, A., Frassi, F., Santini, M., Falcone, M., Menichetti, F., Barcella, B., Delorenzo, M., Resta, F., Vezzoni, G., Bonzano, M., Briganti, D. F., Cappa, G., Zunino, I., Demitry, L., Vignaroli, D., Dipietro, L. S. S., Bazzini, M., Capozza, V., Gonzalez, M. M., Gibal, R. V., Ibarz, R. P., Alfaro, L. M., Alfaro, C. M., Alins, M. G., Brown, A., Dunlop, H., Ralli, M. L., Persona, P., Russel, F. M., Pang, P. S., Rovida, S., Deana, C., and Franchini, D.
Subjects: Adult, medicine.medical_specialty, Multivariate analysis, Letter, Coronavirus disease 2019 (COVID-19), Original, COVID-19, Interstitial pneumonia, Lung ultrasound, SARS-CoV-2, Critical Care and Intensive Care Medicine, 03 medical and health sciences, 0302 clinical medicine, Anesthesiology, Internal medicine, medicine, Humans, Lung, Aged, Ultrasonography, business.industry, 030208 emergency & critical care medicine, Odds ratio, Middle Aged, medicine.disease, Confidence interval, Pneumonia, Early Diagnosis, 030228 respiratory system, Respiratory failure, Observational study, business
Abstract: Purpose To analyze the application of a lung ultrasound (LUS)-based diagnostic approach to patients suspected of COVID-19, combining the LUS likelihood of COVID-19 pneumonia with patient’s symptoms and clinical history. Methods This is an international multicenter observational study in 20 US and European hospitals. Patients suspected of COVID-19 were tested with reverse transcription-polymerase chain reaction (RT-PCR) swab test and had an LUS examination. We identified three clinical phenotypes based on pre-existing chronic diseases (mixed phenotype), and on the presence (severe phenotype) or absence (mild phenotype) of signs and/or symptoms of respiratory failure at presentation. We defined the LUS likelihood of COVID-19 pneumonia according to four different patterns: high (HighLUS), intermediate (IntLUS), alternative (AltLUS), and low (LowLUS) probability. The combination of patterns and phenotypes with RT-PCR results was described and analyzed. Results We studied 1462 patients, classified in mild (n = 400), severe (n = 727), and mixed (n = 335) phenotypes. HighLUS and IntLUS showed an overall sensitivity of 90.2% (95% CI 88.23–91.97%) in identifying patients with positive RT-PCR, with higher values in the mixed (94.7%) and severe phenotype (97.1%), and even higher in those patients with objective respiratory failure (99.3%). The HighLUS showed a specificity of 88.8% (CI 85.55–91.65%) that was higher in the mild phenotype (94.4%; CI 90.0–97.0%). At multivariate analysis, the HighLUS was a strong independent predictor of RT-PCR positivity (odds ratio 4.2, confidence interval 2.6–6.7, p
Published: 2021

6. A Rare Case of Posterior Fossa Tumor and Central Precocious Puberty: Case Presentation and Review of the Literature

Author: Nicola Santoro, Raffaella Messina, Gerardo Cazzato, Giuseppe Ingravallo, Roberta Rana, Mariachiara Resta, Federica Ortolani, Ilenia Perrucci, Massimo Grassi, Francesco Signorelli, Teresa Perrillo, and Sabino Pesce
Subjects: Pediatrics, medicine.medical_specialty, Central nervous system, Central precocious puberty, MEDLINE, Brain tumor, Case Report, Neurosciences. Biological psychiatry. Neuropsychiatry, Ganglioglioma, medicine, Precocious puberty, neuroradiology, Internal medicine, ganglioglioma, Neuroradiology, business.industry, medicine.disease, RC31-1245, medicine.anatomical_structure, Etiology, Medicine, Neurology (clinical), SNC, business, CPP, RC321-571
Abstract: Central precocious puberty (CPP) is a condition that causes early gonadotropin-dependent sexual development; CPP is idiopathic in girls in most cases, whereas more than 50% of boys have an identifiable etiology. We conducted a qualitative systematic review following the ENTREQ (enhancing transparency in reporting the synthesis of qualitative research) framework. A search was made in MEDLINE/Pubmed and MeSH Database using the terms “precocious puberty” AND “brain tumor” OR “posterior fossa tumor” OR “cerebellar tumor” OR “infratentorial tumor”, identifying five cases of pediatric patients with infratentorial tumors and CPP and a case of cerebellar ganglioglioma without hypothalamic−pituitary−gonadal axis involvement and/or intracranial hypertension. Our work highlights the importance of a multidisciplinary approach and extensive central nervous system imaging for patients presenting with CPP in order to detect possible tumor association. Moreover, we believe that this manuscript could contribute to stimulate other research because the exact mechanism of CPP in infratentorial brain lesions has not been understood yet.
Published: 2021

7. Dedifferentiated Melanoma: A Diagnostic Histological Pitfall—Review of the Literature with Case Presentation

Author: Caterina Foti, Francesca Arezzo, Sara Sablone, Antonietta Cimmino, Giuseppe Ingravallo, Vera Loizzi, Roberta Rossi, Leonardo Resta, Paolo Romita, Anna Colagrande, Gennaro Cormio, Aurora Demarco, Lucia Lospalluti, and Gerardo Cazzato
Subjects: Mechanism (biology), business.industry, malignant melanoma (MM), diagnosis, Melanoma, pitfall, dedifferentiated melanoma, Review, Case presentation, Dermatology, Bioinformatics, medicine.disease, RL1-803, immunohistochemistry, medicine, Medical diagnosis, business
Abstract: Dedifferentiated melanoma is a particular form of malignant melanoma with a progressive worsening of the patient’s clinical outcome. It is well known that melanoma can assume different histo-morphological patterns, to which specific genetic signatures correspond, sometimes but not always. In this review we address the diagnostic difficulties in correctly recognizing this entity, discuss the major differential diagnoses of interest to the dermatopathologist, and conduct a review of the literature with particular attention and emphasis on the latest molecular discoveries regarding the dedifferentiation/undifferentiation mechanism and more advanced therapeutic approaches.
Published: 2021

8. Acid‐sensing ion channel 1 contributes to pulmonary arterial smooth muscle cell depolarization following hypoxic pulmonary hypertension

Author: Thomas C. Resta, Jay S. Naik, and Nikki L. Jernigan
Subjects: Physiology, Hypertension, Pulmonary, Myocytes, Smooth Muscle, Pulmonary Artery, Article, Muscle, Smooth, Vascular, Mice, chemistry.chemical_compound, Psalmotoxin, medicine, Animals, Humans, Hypoxia, Cells, Cultured, Acid-sensing ion channel, Ion channel, Membrane potential, Chemistry, Depolarization, medicine.disease, Pulmonary hypertension, Rats, Amiloride, Acid Sensing Ion Channels, Biophysics, Calcium, medicine.symptom, Vasoconstriction, medicine.drug
Abstract: Pulmonary hypertension is characterized by sustained vasoconstriction and remodelling of the small pulmonary arteries, which is associated with persistent depolarization of the resting membrane potential (Em ) of pulmonary arterial smooth muscle cells (PASMCs). It is well-known that the underlying mechanism of this depolarization includes inhibition of K+ channels; however, whether other ion channels contribute to this depolarization is unknown. We previously reported that acid-sensing ion channel 1 (ASIC1), a non-selective cation channel (NSCC) that conducts both Na+ and Ca2+ , is present in PASMCs and contributes to the development of chronic hypoxia (CH)-induced pulmonary hypertension. Therefore, we tested the hypothesis that ASIC1-mediated Na+ influx contributes to PASMC Em regulation following CH-induced pulmonary hypertension. Using sharp electrode intracellular recordings in isolated, pressurized small pulmonary arteries from rats and mice, we show that exposure to CH leads to PASMC membrane depolarization compared with control animals, and this is independent of intraluminal pressure-induced depolarization. In addition to a decrease in PASMC whole-cell K+ currents following CH, we demonstrate that whole-cell NSCC currents are increased and essential to the persistent CH-induced Em depolarization in PASMCs. Both the specific inhibitor of ASIC1, psalmotoxin 1, and global knockout of ASIC1 (Asic1-/- ) prevents CH-induced Em depolarization and largely inhibits whole-cell NSCC currents, without affecting whole-cell K+ currents. Our results show a combination of factors, including inhibition of K+ efflux and augmented Na+ influx, mediate CH-induced PASMC depolarization. Furthermore, this study demonstrates a novel role for ASIC1 in the regulation of Em in PASMCs during CH-induced pulmonary hypertension. KEY POINTS: In pulmonary hypertensive patients and animal models of pulmonary hypertension, the resting membrane potential (Em ) of pulmonary arterial smooth muscle cells (PASMCs) is persistently depolarized. In addition to the well-established reduction of K+ conductance, we show that non-selective cation channel currents are increased and essential to the persistent Em depolarization in PASMCs following chronic hypoxia (CH)-induced pulmonary hypertension. The current study provides novel evidence that acid-sensing ion channel 1 (ASIC1)-mediated Na+ influx induces membrane depolarization and regulates Em in PASMCs following CH exposure. Although fairly quiescent under control conditions, our findings demonstrate a pathological function of ASIC1 in the development of chronic hypoxia-induced pulmonary hypertension.
Published: 2021
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9. Importance of clinical suspicion and multidisciplinary management for early diagnosis of a cardiac laminopathy patient: A case report

Author: Maria Carella, Carlotta Ranieri, Martino Pepe, Andrea Igoren Guaricci, Cinzia Forleo, Francesco Loizzi, Nicoletta Resta, Nicola Bozza, Alfredo Ranauro, Vincenzo Ezio Santobuono, Eugenio Carulli, and Stefano Favale
Subjects: Cardiolaminopathy, medicine.medical_specialty, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Ventricular Tachyarrhythmias, business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), COVID-19, Laminopathy, General Medicine, medicine.disease, Remote-monitoring, Lamin A/C-mutation, Multidisciplinary approach, Case report, medicine, Ventricular tachyarrhythmias, Intensive care medicine, business
Abstract: BACKGROUND Laminopathies are rare diseases, whose cardiac manifestations are heterogeneous and, especially in their initial stage, similar to those of more common conditions, such as ischemic heart disease. Early diagnosis is essential, as these conditions can first manifest themselves with sudden cardiac death. Electrical complications usually appear before structural complications; therefore, it is important to take into consideration these rare genetic disorders for the differential diagnosis of brady and tachyarrhythmias, even when left ventricle systolic function is still preserved. CASE SUMMARY A 60-year-old man, without history of previous disorders, presented in September 2019 to the emergency department because of the onset of syncope associated with hypotension. The patient was diagnosed with a high-grade atrioventricular block. A dual chamber pacemaker was implanted, but after the onset of a sustained ventricular tachycardia during physical exertion, a drug eluting stent was implanted on an intermediate stenosis on the left anterior descending artery, which had previously been considered non-haemodynamically significant. During the follow-up, the treating cardiologist, suspicious of the overall clinical picture, recommended a genetic test for the diagnosis of cardiomyopathies, which tested positive for a pathogenetic mutation of the lamin A/C gene. While awaiting the result of the genetic test and, later, the pacemaker to be upgraded to a biventricular defibrillator, a remote monitoring device was given to the patient in order to minimize in-person clinical evaluations during the coronavirus disease 2019-related lockdown. CONCLUSION This case aims to raise awareness of the cardiological manifestations of laminopathies, which can be dangerously misdiagnosed as other, more common conditions.
Published: 2021
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10. Kaposiform hemangioendothelioma further broadens the phenotype of <scp>PIK3CA</scp> ‐related overgrowth spectrum

Author: Paola Coppo, Roberta La Selva, Giovanni Battista Ferrero, Paola Francia di Celle, Alessandro Mussa, Rosaria Manicone, Federica Santoro, Silvia Kalantari, Simona Cardaropoli, Nicoletta Resta, Franca Fagioli, Carlotta Ranieri, and Diana Carli
Subjects: Male, Pathology, medicine.medical_specialty, Genotype, Class I Phosphatidylinositol 3-Kinases, Biopsy, Kasabach-Merritt Syndrome, Vascular anomaly, Genetics, Humans, PROS, Medicine, Genetic Predisposition to Disease, Sarcoma, Kaposi, Alleles, Genetic Association Studies, Growth Disorders, Genetics (clinical), PI3K/AKT/mTOR pathway, business.industry, Kaposiform hemangioendothelioma, mixed vascular-lymphatic malformations, PIK3CA, PIK3CA-related overgrowth spectrum, Infant, medicine.disease, Immunohistochemistry, Phenotype, Lymphangiogenesis, Radiography, Lymphatic system, Amino Acid Substitution, Kaposiform Hemangioendothelioma, Hemangioendothelioma, Mutation, Vascular tumor, business
Abstract: Kaposiform hemangioendothelioma (KHE) is a rare locally aggressive mixed vascular tumor, with typical onset in early childhood and characterized by progressive angio- and lymphangiogenesis. Its etiopathogenesis and molecular bases are still unclear. Here, we report the first case of congenital KHE harboring a PIK3CA mosaic pathogenic variant (c.323G > A, p.Arg108His) in a boy with very subtle PIK3CA-related overgrowth spectrum (PROS) features. This finding provides insights into the pathophysiology of KHE, offering targeted therapeutic options by inhibition of the PI3K/Akt/mTOR pathway. We propose the inclusion of this mixed lymphatic and vascular anomaly within the PROS.
Published: 2021
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11. Effectiveness and Safety of A Nutraceutical Formulation for the Treatment of Functional Dyspepsia in Primary Care

Author: Giuseppe Sica, Maria Santa Alfieri, Antonio Pio Palieri, Pasquale Zecchillo, Luigi Mazzilli, Antonio Tursi, Francesco Detommasi, Fabrizio Bossa, Marcello Picchio, Giovanni Brandimarte, Leonardo Allegretta, Vincenzo De Cristofaro, Giovanni Sbarra, Michele Manfredi, Giovanni Messa, Antonio Penna, Pietro Derenzio, Basilio Paolo Colucci, Rocco Demauro, Saverio Nappi, Michele Fazio, Francesco Maurichi, Federica Greco, Francesco Monterisi, Alessio Gallo, Mario Tarallo, Pasquale Bellomo, Costantino Vigilante, Vito Lisco, Walter Elisei, Vincenzo Ferrari, Francesco Lore, Pasquale Saponaro, Antonio Elefante, Natale Antonino, Giorgio Marsano, Giancarlo Torelli, Anna Rosa Resta, Carlo Autorino, Ludovico Abenavoli, Giuseppe Pranzo, Simone Di Bella, Giulio Minoretti, Pierluigi Benedicenti, Stefano Gallina, Carlo Casamassima, Pasquale Mascoli, Salvatore Scutifero, Giovanni Luca Rizzo, Donatella Greco, Pasquale Misciagna, and Vincenzo Selvaggio
Subjects: Male, medicine.medical_specialty, Population, Primary care, Epigastric pain, Drug treatment, Nutraceutical, Internal medicine, medicine, Humans, Dyspepsia, education, Retrospective Studies, Pharmacology, Thymus extract, education.field_of_study, Primary Health Care, business.industry, General Medicine, Middle Aged, medicine.disease, Obesity, Abdominal Pain, Dietary Supplements, Large study, Female, business
Abstract: Background: Although FD may affect up to 10% of the general population, the therapy for FD is not standard. Recently, ginger-based food supplements have been proposed in order to restore FD symptoms. Our aim was to assess the efficacy of a new nutraceutical formulation containing extract of gingerol and thymus as a possible natural treatment in managing the symptoms of functional dyspepsia (FD). Methods: We retrospectively analyzed the efficacy and safety profiles of a nutraceutical formulation containing Zingiber officinalis root extract and a standardized Thymus extract. It was administered as 1 ml/day twice a day for 90 days. Patients were assessed at baseline and after 1, 2 and 3 months of treatment, following a month of pharmacological washout by completing a questionnaire reporting the trend of the following symptoms: epigastric pain, epigastric heaviness, early satiety, belching, and regurgitation. Every symptom was assessed by a Visual Analogic Scale (VAS), ranging from 0= absence to 10= maximal severity. Results: We enrolled 272 patients (99 males and 173 females; median IQR age 49.5, 36-64 yrs). Obesity (BMI>30) was present in 28 (12.5%) patients; smokers were 83 (30.5%); and comorbidities were present in 107 (39.3%) patients. Improvement of symptom scores during treatment and one month after its suspension was extremely significant (p Conclusion: This large study found that nutraceutical formulation could be one of the tools for an empirical approach to treat patients with FD, especially when a non-conventional drug treatment is preferable for the patient and considered suitable by the physician.
Published: 2021
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12. Combined Renal-Pulmonary Extracorporeal Support with Low Blood Flow Techniques: A Retrospective Observational Study (CICERO Study)

Author: Paolo Isoni, Marco Resta, Claudio Ronco, Debora Saggioro, Diego Atzeni, Lucia Zamidei, Franco Turani, Gloria Boscolo, and Guglielmo Consales
Subjects: ARDS, Acute exacerbation of chronic obstructive pulmonary disease, medicine.medical_treatment, Kidney, Extracorporeal, law.invention, law, medicine, Humans, Renal replacement therapy, Lung, Mechanical ventilation, Respiratory Distress Syndrome, business.industry, Hematology, General Medicine, Carbon Dioxide, medicine.disease, Respiration, Artificial, Intensive care unit, Respiratory acidosis, medicine.anatomical_structure, Nephrology, Anesthesia, business
Abstract: Background: Critically ill patients with acute respiratory failure frequently present concomitant lung and kidney injury, within a multiorgan failure condition due to local and systemic mediators. To face this issue, extracorporeal carbon dioxide removal (ECCO2R) systems have been integrated into continuous renal replacement therapy (CRRT) platforms to provide a combined organ support, with efficient clearance of CO2 with very low extracorporeal blood flows (Objectives: To evaluate efficacy and safety of combined ECCO2R-CRRT support with PrismaLung®-Prismaflex® in patients affected by hypercapnic respiratory acidosis associated with AKI in a second level intensive care unit. Methods: We carried out a retrospective observational study enrolling patients submitted to PrismaLung®-Prismaflex® due to mild to moderate acute respiratory distress syndrome (ARDS) or acute exacerbation of chronic obstructive pulmonary disease (aeCOPD). The primary endpoints were the shift to protective ventilation and extubation of mechanically ventilated patients and the shift to invasive mechanical ventilation of patients receiving noninvasive ventilation (NIV). Clinical-laboratoristic data and operational characteristics of ECCO2R-CRRT were recorded. Results: Overall, 12/17 patients on mechanical ventilation shifted to protective ventilation, CO2 clearance was satisfactorily maintained during the whole observational period, and pH was rapidly corrected. Treatment prevented NIV failure in 4 out of 5 patients. No treatment-related complications were recorded. Conclusion: ECCO2R-CRRT was effective and safe in patients with aeCOPD and ARDS associated with AKI.
Published: 2021
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13. The Multiple Faces of Nodular Trichoblastoma: Review of the Literature with Case Presentation

Author: Giuseppe Ingravallo, Antonietta Cimmino, Gerardo Cazzato, Lucia Lospalluti, Anna Colagrande, Sara Sablone, Francesca Arezzo, Teresa Lettini, and Leonardo Resta
Subjects: Pathology, medicine.medical_specialty, skin, Adnexal neoplasm, Review, Case presentation, Dermatology, Lesion, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, medicine, Basal cell carcinoma, dermatopathology, business.industry, medicine.disease, Pathological anatomy, trichoblastoma, Adnexal tumors, Trichoblastoma, 030220 oncology & carcinogenesis, adnexal tumors, RL1-803, Dermatopathology, medicine.symptom, business
Abstract: Trichoblastoma (TB) is a rare biphasic benign adnexal neoplasm originating from follicular germ cells but clinically, it can simulate basal cell carcinoma (BCC), making the diagnosis more difficult. There are several variants of Trichoblastoma and a good knowledge of these is essential for correct diagnosis and management. We report two new cases observed in the last year at our Pathological Anatomy Operative Unit, and conduct a careful review of the literature, from the first description of this lesion by Headington in 1970 to the most recent classifications.
Published: 2021

14. Angiomatoid Fibrous Histiocytoma: Case Presentation with Review of Literature

Author: Anna Colagrande, Mariella Silecchia, Teresa Lettini, Gerardo Cazzato, Leonardo Resta, Giuseppe Ingravallo, and Antonietta Cimmino
Subjects: Pathology, medicine.medical_specialty, Angiomatoid fibrous histiocytoma, business.industry, Case presentation, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, medicine, Surgical excision, Clinical case, Differential diagnosis, business, 030217 neurology & neurosurgery
Abstract: Angiomatoid fibrous histiocytoma is a rare neoplasm with an intermediate malignant potential, that mostly occurs in the subcutis and features varying proportions of epithelioid, ovoid and spindle cells in a nodular and syncytial growth pattern, with hemorrhagic pseudovascular spaces. Here, we report the clinical case of a 68-year-old man who presented with AFH on the right arm; the disease relapsed a few years after surgical excision. We also conduct a brief review of the literature, focusing on the biological and genetic characteristics and the differential diagnosis from other more or less similar entities.
Published: 2021
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15. Peritoneal Tuberculosis Mimicking Ovarian Cancer: Gynecologic Ultrasound Evaluation with Histopathological Confirmation

Author: Gerardo Cazzato, Gennaro Cormio, Francesca Arezzo, Giuseppe Ingravallo, Leonardo Resta, and Vera Loizzi
Subjects: Pathology, medicine.medical_specialty, gynecologic ultrasound, Tuberculosis, peritoneal tuberculosis, RC799-869, Mycobacterium tuberculosis, 03 medical and health sciences, 0302 clinical medicine, Lower abdominal pain, medicine, Hepatology, biology, business.industry, Ultrasound, Gastroenterology, Diseases of the digestive system. Gastroenterology, Gynecologic ultrasound, medicine.disease, biology.organism_classification, ovarian cancer, peritoneal disease, 030220 oncology & carcinogenesis, Differential diagnosis, Ovarian cancer, business, Peritoneal tuberculosis, 030217 neurology & neurosurgery
Abstract: Peritoneal tuberculosis (TBP) is a very rare condition, accounting for about 1–2% of all tuberculosis cases. The diagnosis of TBP can be easily mistaken for advanced ovarian cancer (AOC) or peritoneal carcinoma because of overlapping laboratory and clinical findings. We reported the ultrasound characteristics of a case of TBP in a 67-year-old woman who presented to our institute with a 1-month history of intermittent lower abdominal pain, fever, and asthenia. Overall, 20 biopsy-retrieved specimen histopathological features were suggestive of peritoneal tuberculosis. Gynecologic ultrasound revealed increased adnexa with multiple nodular formations spread across the surface, suggestive of caseous nodules. Although this is a rare occurrence, clinicians should consider TBP as a differential diagnosis of ovarian or peritoneal cancer.
Published: 2021
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16. Postprandial glucose and HbA1c are associated with severity of obstructive sleep apnoea in non-diabetic obese subjects

Author: Angelo Cignarelli, Luigi Laviola, Vito Antonio Falcone, Vitaliano Nicola Quaranta, S. Kounaki, Sebastio Perrini, Maria Pia Foschino Barbaro, Francesco Giorgino, Onofrio Resta, Alessandro Ciavarella, A Di Trani, and Annalisa Natalicchio
Subjects: Adult, Blood Glucose, Male, medicine.medical_specialty, Waist, Endocrinology, Diabetes and Metabolism, Polysomnography, 030209 endocrinology & metabolism, Type 2 diabetes, Gastroenterology, Severity of Illness Index, Body Mass Index, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Risk Factors, Internal medicine, medicine, Prevalence, Humans, Obesity, Glycated Hemoglobin, Sleep Apnea, Obstructive, medicine.diagnostic_test, business.industry, Postprandial, Sleep apnea, Fasting, Glucose Tolerance Test, medicine.disease, Postprandial Period, respiratory tract diseases, Blood pressure, Hyperglycemia, Obese subjects, Original Article, Female, Glycemia, business, 030217 neurology & neurosurgery
Abstract: Introduction Obstructive sleep apnoea (OSA) is an underdiagnosed condition frequently associated with glycaemic control impairment in patients with type 2 diabetes. Aim To assess the relationship between glycometabolic parameters and OSA in obese non-diabetic subjects. Methods Ninety consecutive subjects (mean age 44.9 ± 12 years, mean BMI 42.1 ± 9 kg/m2) underwent polysomnography and a 2-h oral glucose tolerance test (OGTT). Results OSA was identified in 75% of subjects, with a higher prevalence of males compared to the group of subjects without OSA (62% vs 32%, p = 0.02). Patients with OSA had comparable BMI (42.8 kg/m2 vs 39.4 kg/m2), a higher average HbA1c (5.8% vs 5.4%, p p = 0.009) and diastolic blood pressure (81.1 mmHg vs 76.2 mmHg, p = 0.046) than obese subjects without OSA. HbA1c and 2 h-PG were found to be correlated with the apnoea-hypopnoea index (AHI; r = 0.35 and r = 0.42, respectively) and with percent of sleep time with oxyhaemoglobin saturation r = 0.44 and r = 0.39, respectively). Further, in a linear regression model, ST90 and AHI were found to be the main determinants of 2 h-PG (β = 0.81, p β = 0.75, p = 0.02, respectively) after controlling for age, sex, waist circumference, physical activity, and C-reactive protein. Similarly, ST90 and AHI persisted as independent determinants of HbA1c (β = 0.01, p = 0.01 and β = 0.01, p = 0.01, respectively). Conclusion Beyond the traditional clinical parameters, the presence of a normal-high value of 2 h-PG and HbA1c should raise suspicion of the presence of OSA in obese subjects.
Published: 2021

17. Transcatheter Therapies in Challenging Aortic Ailments

Author: Alfredo Marchese, Giuseppe Tarantini, Fabrizio Resta, and Antonio Tito
Subjects: 0301 basic medicine, medicine.medical_specialty, Transcatheter aortic, Aortic root, medicine.medical_treatment, 030105 genetics & heredity, complex aortic coarctation. snare-assisted TAVR, 03 medical and health sciences, 0302 clinical medicine, Valve replacement, Internal medicine, CoA, coarctation of the aorta, medicine, TF, transfemoral, Case Report: Technical Corner, TAVR, transcatheter aortic valve replacement, business.industry, Mini-Focus Issue: Transcatheter Interventions, aortic stenosis, MSCT, multislice computed tomography, medicine.disease, aortic ailments, Stenosis, Cardiology, cardiovascular system, TAVR -transcatheter aortic valve replacement, Cardiology and Cardiovascular Medicine, business, 030217 neurology & neurosurgery
Abstract: Transcatheter aortic valve replacement (TAVR) for severe aortic stenosis in older adults may be challenging because of additional aortic comorbidities such as aortic coarctation (CoA). We report successful snared-assisted transfemoral TAVR in a patient with an extremely horizontal ventriculoaortic axis that was worsened by a previous endovascular repair of complex CoA. (Level of Difficulty: Advanced.), Central Illustration
Published: 2021

18. The Great Mime: Three Cases of Melanoma with Carcinoid-Like and Paraganglioma-Like Pattern with Emphasis on Differential Diagnosis

Author: Leonardo Resta, Lucia Lospalluti, Aurora Demarco, Giuseppe Ingravallo, Antonietta Cimmino, Francesca Arezzo, Gerardo Cazzato, and Anna Colagrande
Subjects: medicine.medical_specialty, computer.internet_protocol, carcinoid-like, media_common.quotation_subject, Case Report, Dermatology, pattern, MIME, 030207 dermatology & venereal diseases, 03 medical and health sciences, Presentation, 0302 clinical medicine, Paraganglioma, melanoma, medicine, neoplasms, media_common, business.industry, Melanoma, medicine.disease, RL1-803, 030220 oncology & carcinogenesis, Differential diagnosis, business, paraganglioma-like, computer, Emphasis (typography)
Abstract: Melanoma is among the most aggressive tumors, with different histological patterns of presentation ranging from the usual and easily diagnosable pictures to complex patterns of difficult diagnostic interpretation. Here, we present three cases of a very rare melanoma variant described as “carcinoid-like” and “paraganglioma-like” in the literature, and a brief review of the current literature of the very few cases described to date.
Published: 2021
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19. A Unique Case of Bilateral Thalamic High-Grade Glioma in a Pediatric Patient with LI-Fraumeni Syndrome: Case Presentation and Review of the Literature

Author: Gerardo Cazzato, Vita Stagno, Mariachiara Resta, Francesco De Leonardis, Giuseppe Ingravallo, Raffaella Messina, Valeria Blè, Nicola Santoro, Teresa Perillo, and Francesco Signorelli
Subjects: Pediatrics, medicine.medical_specialty, MEDLINE, Neurosciences. Biological psychiatry. Neuropsychiatry, embryonal rhabdomyosarcoma, Review, 03 medical and health sciences, 0302 clinical medicine, Germline mutation, Glioma, medicine, Li-Fraumeni syndrome, Internal medicine, p53 protein, Pathological, High-Grade Glioma, high-grade bithalamic glioma, business.industry, medicine.disease, RC31-1245, Pediatric patient, Li–Fraumeni syndrome, 030220 oncology & carcinogenesis, Medicine, Neurology (clinical), Embryonal rhabdomyosarcoma, NTRK genes, business, 030217 neurology & neurosurgery, RC321-571
Abstract: Li-Fraumeni syndrome (LFS) is a rare high-penetrance and autosomal-dominant pathological condition caused by the germline mutation of the TP53 gene, predisposing to the development of tumors from pediatric age. We conducted a qualitative systematic review following the ENTREQ (Enhancing Transparency in Reporting the Synthesis of Qualitative Research) framework. A search was made in MEDLINE/Pubmed and MeSH Database using the terms “Li-Fraumeni” AND “pediatric high-grade glioma (HGG)”, identifying six cases of HGGs in pediatric patients with LFS. We added a further case with peculiar features such as no familiar history of LFS, association of embryonal rhabdomyosarcoma and bithalamic HGG, whose immunohistochemical profile was accurately defined by Next Generation Sequencing. Knowledge synthesis and case analysis grounded the discussion about challenges in the management of this pathology in pediatric age.
Published: 2021
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20. Late gadolinium enhancement role in arrhythmic risk stratification of patients with LMNA cardiomyopathy: results from a long-term follow-up multicentre study

Author: Arnaldo Scardapane, Paolo Della Bella, Martino Pepe, Cinzia Forleo, Giovanni Peretto, Chiara Di Resta, Andrea Igoren Guaricci, Anna Santoni, Michele Emdin, Vincenzo Ezio Santobuono, Andrea Barison, Antonio Esposito, Simone Sala, Sara Benedetti, Maurizio Ferrari, Stefano Favale, Anna Palmisano, Giovanni Donato Aquaro, Nicoletta Resta, Peretto, Giovanni, Barison, Andrea, Forleo, Cinzia, Di Resta, Chiara, Esposito, Antonio, Aquaro, Giovanni Donato, Scardapane, Arnaldo, Palmisano, Anna, Emdin, Michele, Resta, Nicoletta, Santoni, Anna, Guaricci, Andrea Igoren, Santobuono, Vincenzo Ezio, Pepe, Martino, Favale, Stefano, Ferrari, Maurizio, Benedetti, Sara, Della Bella, Paolo, and Sala, Simone
Subjects: Male, Cardiac magnetic resonance, Cardiomyopathy, Contrast Media, Gadolinium, 030204 cardiovascular system & hematology, Late gadolinium enhancement, Ventricular Function, Left, 030218 nuclear medicine & medical imaging, Sudden cardiac death, LMNA, 0302 clinical medicine, Risk Factors, Clinical endpoint, LMNA mutation, Ejection fraction, Middle Aged, Lamin Type A, Defibrillators, Implantable, embryonic structures, cardiovascular system, Cardiology, Female, Cardiology and Cardiovascular Medicine, Cardiomyopathies, Adult, medicine.medical_specialty, Adolescent, Risk Assessment, 03 medical and health sciences, Young Adult, Ventricular arrhythmias, Linear gingival erythema, Predictive Value of Tests, Physiology (medical), Internal medicine, medicine, Humans, cardiovascular diseases, Risk stratification, business.industry, Stroke Volume, medicine.disease, Ventricular fibrillation, Implant, business, Follow-Up Studies
Abstract: Aims We aimed at addressing the role of late gadolinium enhancement (LGE) in arrhythmic risk stratification of LMNA-associated cardiomyopathy (CMP). Methods and results We present data from a multicentre national cohort of patients with LMNA mutations. Of 164 screened cases, we finally enrolled patients with baseline cardiac magnetic resonance (CMR) including LGE sequences [n = 41, age 35 ± 17 years, 51% males, mean left ventricular ejection fraction (LVEF) by echocardiogram 56%]. The primary endpoint of the study was follow-up (FU) occurrence of malignant ventricular arrhythmias [MVA, including sustained ventricular tachycardia (VT), ventricular fibrillation, and appropriate implantable cardioverter-defibrillator (ICD) therapy]. At baseline CMR, 25 subjects (61%) had LGE, with non-ischaemic pattern in all of the cases. Overall, 23 patients (56%) underwent ICD implant. By 10 ± 3 years FU, eight patients (20%) experienced MVA, consisting of appropriate ICD shocks in all of the cases. In particular, the occurrence of MVA in LGE+ vs. LGE− groups was 8/25 vs. 0/16 (P = 0.014). Of note, no significant differences between LGE+ and LGE− patients were found in currently recognized risk factors for sudden cardiac death (male gender, non-missense mutations, baseline LVEF 0.05. Conclusions In LMNA-CMP patients, LGE at baseline CMR is significantly associated with MVA. In particular, as suggested by this preliminary experience, the absence of LGE allowed to rule-out MVA at 10 years mean FU.
Published: 2020

21. Novel SCN5A p.W697X Nonsense Mutation Segregation in a Family with Brugada Syndrome

Author: Giuseppe Ciconte, Emanuela T Locati, Luigi Giannelli, Nicoletta Resta, Luigi Anastasia, Valeria Borrelli, Michelle M. Monasky, Gabriele Vicedomini, Andrea Ghiroldi, Chiara Di Resta, Rosanna Bagnulo, Sara Benedetti, Maurizio Ferrari, Carlo Pappone, Emanuele Micaglio, Micaglio, E, Monasky, M M, Resta, N, Bagnulo, R, Ciconte, G, Gianelli, L, Locati, E T, Vicedomini, G, Borrelli, V, Ghiroldi, A, Anastasia, L, Benedetti, S, Di Resta, C, Ferrari, M, and Pappone, C
Subjects: 0301 basic medicine, Male, Genetic testing, family, Case Report, 030204 cardiovascular system & hematology, Sudden cardiac death, NAV1.5 Voltage-Gated Sodium Channel, lcsh:Chemistry, 0302 clinical medicine, Channelopathy, lcsh:QH301-705.5, Spectroscopy, SCN5A, Brugada syndrome, Genetics, medicine.diagnostic_test, Sodium channel, scn5a, General Medicine, Middle Aged, Computer Science Applications, Pedigree, Codon, Nonsense, Mutation (genetic algorithm), Female, Arrhythmia, point-nonsense mutation, Human, sodium channel, Adult, Nonsense mutation, Biology, arrhythmia, Catalysis, sudden cardiac death, genetic testing, Inorganic Chemistry, 03 medical and health sciences, channelopathy, medicine, Family, Functional studies, Physical and Theoretical Chemistry, Molecular Biology, Gene, Organic Chemistry, fungi, Point-nonsense mutation, medicine.disease, 030104 developmental biology, lcsh:Biology (General), lcsh:QD1-999, Mutation, mutation, brugada syndrome
Abstract: Brugada syndrome (BrS) is marked by an elevated ST-segment elevation and increased risk of sudden cardiac death. Variants in the SCN5A gene are considered to be molecular confirmation of the syndrome in about one third of cases, while the genetics remain a mystery in about half of the cases, with the remaining cases being attributed to variants in any of a number of genes. Before research models can be developed, it is imperative to understand the genetics in patients. Even data from humans is complicated, since variants in the most common gene in BrS, SCN5A, are associated with a number of pathologies, or could even be considered benign, depending on the variant. Here, we provide crucial human data on a novel NM_198056.2:c.2091G>A (p.Trp697X) point-nonsense heterozygous variant in the SCN5A gene, as well as its segregation with BrS. The results herein suggest a pathogenic effect of this variant. These results could be used as a stepping stone for functional studies to better understand the molecular effects of this variant in BrS.
Published: 2019

22. New molecular approaches to Alzheimer's disease

Author: Maurizio Ferrari, Chiara Di Resta, Di Resta, C., and Ferrari, M.
Subjects: Big Data, Epigenomics, Proteomics, Gerontology, 030213 general clinical medicine, Genetic risk loci, Clinical Biochemistry, Disease, 030204 cardiovascular system & hematology, Medical care, 03 medical and health sciences, 0302 clinical medicine, Alzheimer Disease, Humans, Metabolomics, Medicine, Dementia, Diagnostic, Risk factor, Clinical implication, business.industry, High-Throughput Nucleotide Sequencing, General Medicine, Alzheimer's disease, Omics, Precision medicine, medicine.disease, Omics sciences, Older people, business, AD pathogenesi
Abstract: Alzheimer's disease is a neurodegenerative disorder and the most common and devastating form of dementia. It affects mainly older people, accounting for 50-80% of dementia cases. The age is the main associated risk factor and based on the onset age, early-onset (EOAD) or late-onset (LOAD) forms are distinguished. AD has a strong impact both on the life-style of patients and their families and on the society, due to the high costs related to social and medical care. So far, despite the great advances in understanding of the AD pathogenesis, there is no a cure for this form of dementia and current available treatments are limited to temporarily relieve symptoms. In this review, firstly we give an overview of the current knowledge of the genetic basis of both forms of AD with a particular emphasis on the insights in the understanding of the pathogenic mechanisms of this disorder. Then we discuss the promising relevance of "omics sciences" and the open challenges of the application of Big Data in promoting precision medicine for AD.
Published: 2019
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23. Inhaled Corticosteroids And Risk Of Tuberculosis In Patients With Obstructive Lung Diseases: A Systematic Review And Meta-Analysis Of Non-randomized Studies

Author: Carlo Castellana, Emanuela Resta, Marco Castellana, Giuseppe Castellana, Onofrio Resta, Mauro Carone, and Giorgio Castellana
Subjects: medicine.medical_specialty, Tuberculosis, Population, Review, Risk Assessment, Pulmonary Disease, Chronic Obstructive, 03 medical and health sciences, 0302 clinical medicine, Adrenal Cortex Hormones, Internal medicine, Administration, Inhalation, Epidemiology, obstructive lung disease, Humans, Medicine, 030212 general & internal medicine, Risk factor, education, Tuberculosis, Pulmonary, COPD, education.field_of_study, business.industry, Clinical Studies as Topic, General Medicine, medicine.disease, infection control, Obstructive lung disease, meta-analysis, tuberculosis, 030228 respiratory system, Meta-analysis, Attributable risk, inhaled corticosteroids, business
Abstract: Background An association between systemic corticosteroids and tuberculosis (TB) is reported in the literature. Here within, we conducted a systematic review and meta-analysis to evaluate the effects of inhaled corticosteroids (ICS) on the risk of TB in patients with obstructive lung diseases. Methods The review was registered on PROSPERO (CRD42018095874). PubMed, CENTRAL, Scopus and Web of Science were searched from inception to September 2018. Papers reporting cases of incident TB in patients with obstructive lung diseases were included; studies without data on ICS use were excluded. Simultaneous use of oral corticosteroids (OCS) and population attributable fraction (PAF) for TB from ICS exposure were also assessed. Data were analyzed using a generic inverse variance method with a random-effects model. ORs with 95% CI were estimated. Results Out of 4044 retrieved papers, 9 articles evaluating adult patients only were included in the review. 36,351 patients were prescribed ICS, while 147,171 were not. Any ICS use was associated with an increased risk of TB versus no ICS use (OR=1.46; 95% CI 1.06 to 2.01; p=0.02; I2=96%). A similar result was also found for current ICS use versus prior/no ICS use, as well as for high, moderate and low ICS dose versus no ICS. When simultaneous OCS use was evaluated, the independent contribution of ICS was confirmed only in patients not on OCS (OR=1.63; 95% CI 1.05 to 2.52; p=0.03; I2=94%). Only 0.49% of all TB cases could be attributable to ICS exposure. Conclusions Despite the association between ICS and TB, the contribution of this risk factor to the epidemiology of TB seems to be limited. As a consequence, no population-based interventions are warranted. Rather, this risk should be taken into account on an individual basis, particularly in those patients with a high risk of progression from LTBI to TB.
Published: 2019
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24. The Surgical Management of Acute Gastric Volvulus: Clinical Outcomes and Quality of Life Assessment

Author: Savino Occhionorelli, Giorgio Cavallesco, Chiara Vigolo, S. Marino, Giuseppe Resta, Gabriele Anania, Serena Rubino, Nicola Tamburini, Marcello Sanzi, Giorgio Vasquez, and Ciro Andolfi
Subjects: Male, musculoskeletal diseases, medicine.medical_specialty, Stomach Volvulus, NO, Hiatal hernia, Postoperative Complications, Quality of life, Recurrence, Surveys and Questionnaires, parasitic diseases, Humans, Medicine, stomach diseases, Postoperative Period, Laparoscopy, Aged, Retrospective Studies, Aged, 80 and over, Gastric volvulus, stomach volvulus, laparoscopy, stomach diseases, hiatal hernia, quality of life, medicine.diagnostic_test, business.industry, Middle Aged, medicine.disease, digestive system diseases, Surgery, Hernia, Hiatal, Treatment Outcome, Patient Satisfaction, Acute Disease, Quality of Life, Female, Acute gastric volvulus, business, hiatal hernia
Abstract: Background: Surgery is the mainstay of treatment for gastric volvulus. Despite its rarity, early experience from recent publications suggests that laparoscopy is a safe and effective approach for t...
Published: 2021
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25. EBV DNA increase in COVID-19 patients with impaired lymphocyte subpopulation count

Author: Stefania Paolucci, Irene Cassaniti, Federica Novazzi, Loretta Fiorina, Antonio Piralla, Giuditta Comolli, Raffaele Bruno, Renato Maserati, Roberto Gulminetti, Stefano Novati, Francesco Mojoli, Fausto Baldanti, R Bruno, M Mondelli, E Brunetti, A Di Matteo, E Seminari, L Maiocchi, V Zuccaro, L Pagnucco, B Mariani, S Ludovisi, R Lissandrin, A Parisi, P Sacchi, SFA Patruno, G Michelone, R Gulminetti, D Zanaboni, S Novati, R Maserati, P Orsolini, M Vecchia, M Sciarra, E Asperges, M Colaneri, A Di Filippo, M Sambo, S Biscarini, M Lupi, S Roda, TC Pieri, I Gallazzi, M Sachs, P Valsecchi, S Perlini, C Alfano, M Bonzano, F Briganti, G Crescenzi, AG Falchi, R Guarnone, B Guglielmana, E Maggi, I Martino, P Pettenazza, S Pioli di Marco, F Quaglia, A Sabena, F Salinaro, F Speciale, I Zunino, M De Lorenzo, G Secco, L Dimitry, G Cappa, I Maisak, B Chiodi, M Sciarrini, B Barcella, F Resta, L Moroni, G Vezzoni, L Scattaglia, E Boscolo, C Zattera, MF Tassi, V Capozza, D Vignaroli, M Bazzini, G Iotti, F Mojoli, M Belliato, L Perotti, S Mongodi, G Tavazzi, G Marseglia, A Licari, I Brambilla, D Barbarini, A Bruno, P Cambieri, G Campanini, C. Cavanna, G Comolli, M Corbella, R Daturi, M Furione, P Marone, E Monzillo, S Paolucci, M Parea, E Percivalle, A Piralla, F Rovida, A Sarasini, M Zavattoni, G Adzasehoun, M Ardizzone, L Bellotti, V Brunco, E Cabano, G Casali, L Capella, D Devitis, L Dossena, G Frisco, G Garbagnoli, F Gardellini, A Girello, A Guerrizio, V Landini, C Lucchelli, V Maliardi, P Piemontese, S Pezzaia, M Premoli, C Rebuffa, C Zanello, J Bagnarino, F Bergami, A Bonetti, G Caneva, I Cassaniti, A Corcione, R Di Martino, A Di Napoli, A Ferrari, G Ferrari, L Fiorina, A Gallone, F Giardina, A Girardi, A Mercato, C Merla, F Novazzi, G Ratano, B Rossi, G Saveriaempillai, IM Sciabica, M Tallarita, E Vecchio Nepita, J Vitali, A Cerino, S Varchetta, B Oliviero, S Mantovani, D Mele, M Calvi, M Tizzoni, C Nicora, A Triarico, V Petronella, C Marena, A Muzzi, P Lago, S Cutti, V Novelli, F Comandatore, G BatistiBiffignandi, S Gaiarsa, M Rettani, and C Bandi
Subjects: Male, 0301 basic medicine, Human cytomegalovirus, Herpesvirus 4, Human, Epstein-Barr Virus Infections, viruses, Lymphocyte, COVID-19, EBV DNA, Lymphocyte subpopulation, Aged, Aged, 80 and over, CD8-Positive T-Lymphocytes, DNA, Viral, Female, Humans, Intensive Care Units, Killer Cells, Natural, Lymphocyte Count, Lymphocyte Subsets, Middle Aged, Opportunistic Infections, Real-Time Polymerase Chain Reaction, SARS-CoV-2, Viral Load, law.invention, 0302 clinical medicine, law, 80 and over, Killer Cells, Cytotoxic T cell, Viral, 030212 general & internal medicine, biology, musculoskeletal, neural, and ocular physiology, General Medicine, Intensive care unit, Infectious Diseases, medicine.anatomical_structure, Natural, Human herpesvirus 6, Human, Microbiology (medical), 030106 microbiology, macromolecular substances, Article, Virus, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, medicine, lcsh:RC109-216, Parvovirus, business.industry, Herpesvirus 4, DNA, biology.organism_classification, medicine.disease, nervous system, Immunology, business, CD8
Abstract: Highlights • EBV reactivation was observed in patients with COVID-19. • NK + and CD8 + T cell reduction was related to the severity of COVID-19 infection. • An increase of B cells in patients with severe symptoms was documented., Objectives The immunologic profile and opportunistic viral DNA increase were monitored in Italian patients with COVID-19 in order to identify markers of disease severity. Methods A total of 104 patients infected with SARS-CoV-2 were evaluated in the study. Of them, 42/104 (40.4%) were hospitalized in an intensive care unit (ICU) and 62/104(59.6%) in a sub-intensive care unit (SICU). Human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV), Parvovirus B19 and Human Herpesvirus 6 virus reactivations were determined by real-time PCR, and lymphocyte subpopulation counts were determined by flow cytometry. Results Among opportunistic viruses, only EBV was consistently detected. EBV DNA was observed in 40/42 (95.2%) of the ICU patients and in 51/61 (83.6%) of the SICU patients. Comparing the two groups of patients, the EBV DNA median level among ICU patients was significantly higher than that observed in SICU patients. In parallel, a significant reduction of CD8 T cell and NK count in ICU patients as compared with SICU patients was observed (p
Published: 2021
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26. Lung ultrasound presentation of COVID-19 patients: phenotypes and correlations

Author: Francesco Mojoli, Bruno Barcella, Lorenzo Demitry, Stefano Perlini, Giulia Vezzoni, Flavia Resta, Francesco Salinaro, Caterina Zattera, Giovanni Cappa, Gianmarco Secco, Fausto Baldanti, Anna Sabena, Federica Briganti, Francesca Zugnoni, Marzia Delorenzo, Raffaele Bruno, and Marco Bonzano
Subjects: medicine.medical_specialty, Lung, Coronavirus disease 2019 (COVID-19), business.industry, Ultrasound, 030208 emergency & critical care medicine, Interstitial pattern, 030204 cardiovascular system & hematology, medicine.disease, Gastroenterology, Lung ultrasound, 03 medical and health sciences, Pneumonia, Lung structure, 0302 clinical medicine, medicine.anatomical_structure, Internal medicine, Cohort, Emergency Medicine, Internal Medicine, Medicine, business
Abstract: Bedside lung ultrasound (LUS) can play a role in the setting of the SarsCoV2 pneumonia pandemic. To evaluate the clinical and LUS features of COVID-19 in the ED and their potential prognostic role, a cohort of laboratory-confirmed COVID-19 patients underwent LUS upon admission in the ED. LUS score was derived from 12 fields. A prevalent LUS pattern was assigned depending on the presence of interstitial syndrome only (Interstitial Pattern), or evidence of subpleural consolidations in at least two fields (Consolidation Pattern). The endpoint was 30-day mortality. The relationship between hemogasanalysis parameters and LUS score was also evaluated. Out of 312 patients, only 36 (11.5%) did not present lung involvment, as defined by LUS score 13 had a 77.2% sensitivity and a 71.5% specificity (AUC 0.814; p R2 0.68; p 2 = 21% (R2 0.59; p
Published: 2021
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27. Clinical experience with the AKT1 inhibitor miransertib in two children with PIK3CA-related overgrowth syndrome

Author: David Rea, M. Hinton, Katrina A. Andrews, Olga Kubassova, Karina Forde, Nicoletta Resta, Veronika Dvorakova, Carlotta Ranieri, Alan D. Irvine, Robert K. Semple, Irvine, Alan D [0000-0002-9048-2044], and Apollo - University of Cambridge Repository
Subjects: 0301 basic medicine, medicine.medical_specialty, Hemimegalencephaly, Class I Phosphatidylinositol 3-Kinases, Lipomatosis, PIK3CA-related overgrowth spectrum (PROS), Aminopyridines, lcsh:Medicine, Dysfunctional family, AKT inhibitor, Phosphatidylinositol 3-Kinases, 03 medical and health sciences, 0302 clinical medicine, Quality of life, Targeted treatment, Internal medicine, medicine, Humans, Pharmacology (medical), Child, Obstructive uropathy, Genetics (clinical), business.industry, Research, lcsh:R, Imidazoles, Chronic pain, General Medicine, medicine.disease, Proteus syndrome, 3. Good health, 030104 developmental biology, Next generation sequencing (NGS), 030220 oncology & carcinogenesis, Overgrowth syndrome, Mutation, Quality of Life, business, Proto-Oncogene Proteins c-akt, Miransertib
Abstract: Background PIK3CA-related overgrowth spectrum (PROS) refers to a group of rare disorders, caused by somatic activating mutations in PIK3CA, resulting in abnormal PI3K-AKT-mTOR pathway signalling. Significant associated morbidity is frequently observed, and approved treatments are lacking. Miransertib (ARQ 092) is a novel, orally available, selective pan-AKT inhibitor with proven in vitro efficacy. Following recent results of the use of AKT inhibitors in Proteus syndrome (PS) and AKT-mutant cancers, we investigated its therapeutic use in two patients with severe PROS who had exhausted conventional treatment methods. Results Two patients, one with CLOVES variant (P1) and one with facial infiltrating lipomatosis and hemimegalencephaly (P2), were commenced on miransertib treatment on a compassionate use basis. In patient one, intra-abdominal and paraspinal overgrowth had resulted in respiratory compromise, obstructive uropathy, dysfunctional seating and lying postures, and chronic pain. In patient two, hemifacial overgrowth and hemimegalencephaly had caused difficulties with articulation and oral function, and refractory epilepsy. Miransertib treatment was continued for a median duration of 22 months (range 22–28). In patient one, alleviation of respiratory compromise was observed and functionally, seating and lying postures improved. Serial volumetric MRI analysis revealed 15% reduction in calculated volumes of fatty overgrowth between treatment commencement and end. In patient two, reduction in seizure burden and improved parent-reported quality of life measures were reported. Treatment was discontinued in both patients due to lack of sustained response, and poor compliance in year two of treatment (P2). No significant toxicities were reported. Conclusion We report the first paediatric case series of the use of miransertib in two children with PROS. Objective clinical response was observed in patient one, and improvement in key qualitative outcomes was reported in patient two. Treatment was well tolerated with no significant toxicities reported. This case series highlights the potential therapeutic utility of miransertib in selected paediatric patients with severe PROS, and further demonstrates the potential for re-purposing targeted therapies for the treatment of rare diseases. An open label, Phase 1/2 study of miransertib in children with PROS and PS is underway to more accurately assess the efficacy of miransertib in the treatment of PROS disorder (NCT03094832).
Published: 2021
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28. Are there overlapping clinical features between thoracic radiotherapy side effects and covid-19 pneumonia? Radiation pneumonitis outside the radiation ports: Three case reports

Author: Ernesto D’Ettorre, Michelle Magli, Grazia Lazzari, Elda Chiara Resta, and Giovanni Silvano
Subjects: medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), RILI, Thoracic radiotherapy, R895-920, Bronchiolitis obliterans, Case Report, Disease, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, Medical physics. Medical radiology. Nuclear medicine, 0302 clinical medicine, medicine, Radiology, Nuclear Medicine and imaging, Respiratory system, RC254-282, Pneumonitis, Lung, business.industry, BAL fluid, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, respiratory tract diseases, RT-BOOP, medicine.anatomical_structure, Oncology, Hypersensitivity Pneumonitis, 030220 oncology & carcinogenesis, Radiology, business, Hypersensitivity pneumonitis
Abstract: Highlights • Chest CT has shown high sensitivity in diagnosis of Covid-19 pneumonia. • CT findings display a variety of pictures not specific of Covid-19 pneumonia. • Atypical radiation pneumonitis occurring after thoracic radiotherapy as Hypersensivity pneumonitis and RT-BOOP mimic images pictures of several Covid-19 pneumonia scenarios., Respiratory involvement of Covid-19 infection, presenting as a mild flu-like illness to potentially lethal acute respiratory distress syndrome is the main clinical manifestation in adults. Chest imaging shows a pictorial fashion of images due to the severity and stage of the disease, starting from focal nodular or mass-like opacities with air bronchogram to areas of ground glass consolidation or whited out lung. However, at the Covid-19 pandemic time, CT findings could yield confounding reporting in case of cancer patients previously treated with thoracic radiotherapy (tRT) due to atypical radiation pneumonitis occurring outside the radiation ports. Hypersensitivity pneumonitis and radiation induced bronchiolitis obliterans organizing pneumonitis (RT-BOOP) are accounted in this report.
Published: 2020

29. Membrane depolarization is required for pressure‐dependent pulmonary arterial tone but not enhanced vasoconstriction to endothelin‐1 following chronic hypoxia

Author: Charles E. Norton, Nikki L. Jernigan, Benjimen R. Walker, and Thomas C. Resta
Subjects: 0301 basic medicine, Pulmonary and Respiratory Medicine, lcsh:Diseases of the circulatory (Cardiovascular) system, 030204 cardiovascular system & hematology, Pharmacology, 03 medical and health sciences, Ca2+ sensitization, 0302 clinical medicine, medicine, Original Research Article, Receptor, Rho-associated protein kinase, lcsh:RC705-779, Membrane potential, business.industry, Depolarization, lcsh:Diseases of the respiratory system, medicine.disease, Pulmonary hypertension, Endothelin 1, 030104 developmental biology, lcsh:RC666-701, Src kinases, membrane potential, medicine.symptom, business, Vasoconstriction, Proto-oncogene tyrosine-protein kinase Src
Abstract: Enhanced vasoconstriction is increasingly identified as an important contributor to the development of pulmonary hypertension. Chronic hypoxia results in enhanced Rho kinase mediated Ca 2+ sensitization contributing to pressure-dependent pulmonary arterial tone as well as augmented vasoconstriction to endothelin-1 and depolarizing stimuli. We sought to investigate the interaction between these vasoconstrictor stimuli in isolated, pressurized, pulmonary arteries. We used the K + ionophore, valinomycin, to clamp membrane potential (V m ) to investigate the role of membrane depolarization in endothelin-1 and pressure-dependent constriction, and endothelin-1 receptor inhibitors to determine whether membrane depolarization or stretch signal through endothelin-1 receptors. Clamping V m prevented pressure-dependent tone, but not enhanced vasoconstriction to endothelin-1 following chronic hypoxia. Furthermore, endothelin-1 receptor inhibition had no effect on either pressure-dependent tone or vasoconstriction to KCl. As Src kinases contribute to both pressure-dependent tone and enhanced endothelin-1 vasoconstriction following chronic hypoxia, we further investigated their role in depolarization-induced vasoconstriction. Inhibition of Src kinases attenuated enhanced vasoconstriction to KCl. We conclude that membrane depolarization contributes to pressure-dependent tone but not enhanced vasoconstriction to ET-1, and that Src kinases serve as upstream mediators facilitating enhanced Rho kinase-dependent vasoconstriction following chronic hypoxia.
Published: 2020
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30. Resectoscopic Metroplasty with Uterine Septum Excision: A Histologic Analysis of the Uterine Septum

Author: Vera Loizzi, Fabiana Divina Fascilla, Ettore Cicinelli, Attilio Di Spiezio Sardo, Stefano Bettocchi, Leonardo Resta, Domenico De Palma, Rossella Cannone, Oronzo Ceci, and Rudi Campo
Subjects: Adult, Metroplasty, Uterus, Hysteroscopy, Cohort Studies, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Pregnancy, medicine, Humans, Myocyte, Ultrasonography, Uterine septum, Uterine Diseases, 030219 obstetrics & reproductive medicine, medicine.diagnostic_test, business.industry, Obstetrics and Gynecology, Histology, Anatomy, Plastic Surgery Procedures, medicine.disease, medicine.anatomical_structure, Italy, Fundus (uterus), Urogenital Abnormalities, 030220 oncology & carcinogenesis, Female, Uterine cavity, business
Abstract: Study Objective To evaluate the histology of the uterine septum after its complete hysteroscopic excision. Design Case series. Setting II Gynecological and Obstetric Unit of the University of Bari, Italy and Pathological Anatomy Department of the University of Bari, Italy. Patients 35 patients between 25 and 41 years old diagnosed with uterine septum by 3D ultrasound as per ESHRE/ESGE 2013/Salim 2003 criteria. Office hysteroscopy was also performed to define the anatomy of the uterine cavity and to exclude the presence of other endometrial pathology. Interventions Operative hysteroscopic septum resection was performed. The septum was initially incised with a “L shape” bipolar electrode with the 5 mm Bipolar Mini-Resectoscope (Karl Storz, Germany). Then, using the bipolar loop, two triangles of the septum were excised in parallel, obtaining uninterrupted entire septum-long strips, from the fundus to the apex of the septum. The strips were immediately removed from the uterus and reassembled “in vitro” in order to reconstruct the macroscopic 3D structure of the septum for a complete morphological and histological evaluation. Measurements and Main Results Patients presented an average BMI of 24,8 and were all nulliparous. Histologic evaluation of the uterine septa showed a different conformation of the muscle bundles along the septum. In the apex and edges of the septum, the muscle cells were arranged in nodules circumscribed by a thin area of collagen fibers. Medium size vessels were distributed in the collagen fibers around the muscle cells. Only few capillary vessels are present in the muscle nodules. This pattern is very similar to the cell arrangement of leiomyomas. In the core of the septa, near the base, the muscle bundles show a linear course, with concurrent collagen fibers and vessels. All the above-mentioned characteristics were consistently present in every patient. On high-power histological fields (200x), the muscle portion ranged from 48,3 ± 1,8% (mean 6,0) in the apex and borders, to 48,5 ± 1,3% (mean 6,0) in the core. The collagen fibers ranged from 27.1 ± 1.1% (mean 4,0) in the apex and borders, to 26.7 ± 1.3% (mean 5,0) in the core. Conclusion This study allowed us, by removing the entire septum as a whole structure, to redefine the concept of the septum as a complex structure based on islands of muscle fibers irregularly arranged in vertex, in a context of collagen tissue, similar to the structure of myomas. It appears to deeply involve the anterior and posterior uterine wall, resembling a “reverse letter H”.
Published: 2020
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31. Treatment of fistula-in-ano: Outcome comparison between traditional surgery and novel approaches. A retrospective cohort study in a single center

Author: Francesco D'Urbano, Giuseppe Resta, Simona Ascanelli, Giorgio Cavallesco, Nicolò Fabbri, and Paolo Carcoforo
Subjects: fistulotomy, Anal fistula, Anal fistula, Fistulotomy, Fistulectomy, Seton, VAAFT, Lipogems®, Micro-fragmented adipose tissue, Medicine (General), medicine.medical_specialty, RD1-811, Fistula, Single Center, NO, R5-920, medicine, anal fistül, LS7_4, mikro parçalanmış adipoz doku, Gynecology, vaaft, business.industry, lipogems®, seton, medicine.disease, micro-fragmented adipose tissue, fistülotomi, anal fistula, Medicine, Surgery, fistulectomy, business, fistülektomi
Abstract: Amac: Anal fistul iyi tanimlanmis bir hastaliktir ancak kesin bir cerrahi teknik gelistirilmemistir. Hastanemizde 2012-2018 yillari arasinda perianal fistul nedeniyle cerrahi tedavi uygulanan hastalari degerlendirmek icin tek merkezli, retrospektif bir kohort calismasi yuruttuk. Calismanin amaci, farkli cerrahi tekniklerin (Fistulotomi / fistulektomi ve seton, Video Destekli Anal Fistul Tedavisi (VAAFT), Mikro-parcalanmis yag dokusu enjeksiyonu, Lipogems®) sonuclarini karsilastirmakti. Yontemler: Elektif cerrahi icin uygun olan anal fistullu 103 hastadan olusan bir kohort, 2012 ve 2018 yillari arasinda Ferrara'daki Sant’Anna Hastanesi’nde opere edildi. Tum hastalara fistul traktini ve ic acikligi belirlemek icin ameliyat oncesi rektal tuse ve manyetik rezonans goruntuleme (MRI) uygulandi. Hastalar, gecirdikleri her ameliyat icin birer tane olmak uzere 4 gruba ayrildi: Fistulotomi / fistulektomi ve seton, Video Destekli Anal Fistul Tedavisi (VAAFT), Mikro parcali yag dokusu enjeksiyonu, Lipogems®). Ameliyattan bir hafta sonra oznel agriyi degerlendirmek icin sayisal derecelendirme olcegi (NRS) kullanildi ve sonuclar kaydedildi. Puanlar, 0, hic agri yok, ile 10, karsilasilan en siddetli agri, arasinda degismekteydi. Birincil sonlanim noktasi, 1 yillik takipte fistul rekurrensiydi. Ikincil sonlanim noktasi, ameliyat sonrasi agrinin degerlendirilmesiydi. Bulgular: Ortanca yasi 50 olan (aralik 21-89 yas) 71 erkek ve 32 kadin calismaya dahil edildi. Bunlardan 79 hastaya yeni teshis konulmus, diger 24 hasta daha once ameliyat olmus ve nuksetmisti. Anal fistul icin toplam 118 cerrahi operasyon yapildi. Takip suresince VAAFT sonrasi 13 hastada, Mikro parcali yag dokusu enjeksiyonu sonrasi 3 hastada, fistulotomi sonrasi 4 hastada, fistulotomi sonrasi 12 hastada, seton yerlestirme sonrasinda 10 hastada ve Lipogems® tekniginden sonra 8 hastada anal fistul rekurrensi gozlendi. Ameliyattan bir hafta sonra agri tum hastalar tarafindan 0 ile 10 arasinda bir olcekte degerlendirildi. VAAFT, mikro parcali yag dokusu enjeksiyonu, fistulotomi, fistulektomi, seton yerlestirme ve Lipogems® teknigi uygulanan hastalarin ortalama skorlari sirasiyla 1 (0- 5), 1.5 (0-8), 5 (3-8), 6.8 (5-9), 4.2 (2-6) ve 0’di (0-2). Sonuc: Bu calisma anal fistul yonetimindeki zorluklari ve cesitli cerrahi secenekleri sunmaktadir. VAAFT ve Mikro-parcalanmis yag dokusu enjeksiyonu, anal fistul yonetiminde guvenli ve uygulanabilir secenekler gibi gorunmektedir ve kisa sureli iyilesme oranlari, kontinans uzerinde kalici bir etki olmaksizin kabul edilebilirdir. Bununla birlikte, uzun vadeli sonuclari olan guvenilir veri yetersizligi oldugundan, bu teknikler, bu nedenle memnuniyetle karsilanmaktadir. Lipogems ® teknigi guvenli ve tekrarlanabilir bir islemdir, ancak ne yazik ki deneyimlerimize gore, tekrarlayan sfinkterik anal fistulu olan hastalarda fistul iyilesmesini desteklememektedir. Bu teknigin birinci basamak tedavi olarak kullanilmasini onermiyoruz.
Published: 2020
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32. The procoagulant pattern of patients with COVID‐19 acute respiratory distress syndrome

Author: Marco Dei Poli, Andrea Ballotta, Umberto Di Dedda, Marco Ranucci, Mara Falco, Giovanni Albano, Ekaterina Bayshnikova, Lorenzo Menicanti, and Marco Resta
Subjects: Male, medicine.medical_specialty, ARDS, medicine.drug_class, Pneumonia, Viral, Low molecular weight heparin, 030204 cardiovascular system & hematology, Fibrinogen, Gastroenterology, Betacoronavirus, 03 medical and health sciences, 0302 clinical medicine, Fibrinolytic Agents, Interquartile range, Internal medicine, D-dimer, medicine, Humans, Prospective Studies, Blood Coagulation, Pandemics, Aged, Blood coagulation test, SARS-CoV-2, business.industry, Antithrombin, Anticoagulants, COVID-19, Hematology, Blood Coagulation Disorders, Middle Aged, medicine.disease, COVID-19 Drug Treatment, Pulmonary embolism, Treatment Outcome, Host-Pathogen Interactions, Female, Blood Coagulation Tests, Coronavirus Infections, business, Biomarkers, medicine.drug
Abstract: Background Few observations exist with respect to the pro-coagulant profile of patients with COVID-19 acute respiratory distress syndrome (ARDS). Reports of thromboembolic complications are scarce but suggestive for a clinical relevance of the problem. Objectives Prospective observational study aimed to characterize the coagulation profile of COVID-19 ARDS patients with standard and viscoelastic coagulation tests and to evaluate their changes after establishment of an aggressive thromboprophylaxis. Methods Sixteen patients with COVID-19 ARDS received a complete coagulation profile at the admission in the intensive care unit. Ten patients were followed in the subsequent 7 days, after increasing the dose of low molecular weight heparin, antithrombin levels correction, and clopidogrel in selected cases. Results At baseline, the patients showed a pro-coagulant profile characterized by an increased clot strength (CS, median 55 hPa, 95% interquartile range 35-63), platelet contribution to CS (PCS, 43 hPa; interquartile range 24-45), fibrinogen contribution to CS (FCS, 12 hPa; interquartile range 6-13.5) elevated D-dimer levels (5.5 μg/mL, interquartile range 2.5-6.5), and hyperfibrinogenemia (794 mg/dL, interquartile range 583-933). Fibrinogen levels were associated (R2 = .506, P = .003) with interleukin-6 values. After increasing the thromboprophylaxis, there was a significant (P = .001) time-related decrease of fibrinogen levels, D-dimers (P = .017), CS (P = .013), PCS (P = .035), and FCS (P = .038). Conclusion The pro-coagulant pattern of these patients may justify the clinical reports of thromboembolic complications (pulmonary embolism) during the course of the disease. Further studies are needed to assess the best prophylaxis and treatment of this condition.
Published: 2020
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33. Emergency Department and Out-of-Hospital Emergency System (112—AREU 118) integrated response to Coronavirus Disease 2019 in a Northern Italy centre

Author: Perlini, S., Canevari, F., Cortesi, S., Sgromo, V., Brancaglione, A., Contri, E., Pettenazza, P., Salinaro, F., Speciale, F., Sechi, G., Mare, C., Cutti, S., Novelli, V., Marena, C., Muzzi, A., Bruno, R., Palo, A., Mondelli, M. U., Brunetti, E., Di Matteo, A., Seminari, E., Maiocchi, L., Zuccaro, V., Pagnucco, L., Mariani, B., Ludovisi, S., Lissandrin, R., Parisi, A., Sacchi, P., Patruno, S. F. A., Michelone, G., Gulminetti, R., Zanaboni, D., Novati, S., Maserati, R., Orsolini, P., Vecchia, M., Sciarra, M., Asperges, E., Colaneri, M., Di Filippo, A., Sambo, M., Biscarini, S., Lupi, M., Roda, S., Pieri, T. C., Gallazzi, I., Sachs, M., Valsecchi, P., Alfano, C., Bonzano, M., Briganti, F., Crescenzi, G., Falchi, A. G., Guarnone, R., Guglielmana, B., Maggi, E., Martino, I., di Marco, S. P., Quaglia, F., Sabena, A., Zunino, I., Furlan, N., Savioli, G., De Lorenzo, M., Secco, G., Dimitry, L., Cappa, G., Maisak, I., Chiodi, B., Sciarrini, M., Barcella, B., Resta, F., Moroni, L., Vezzoni, G., Scattaglia, L., Boscolo, E., Zattera, C., Fidel, T. M., Vincenzo, C., Bazzini, M., Lago, E., Bracchi, F., Sturniolo, G., Iotti, G., Mojoli, F., Belliato, M., Perotti, L., Mongodi, S., Tavazzi, G., Marseglia, G., Licari, A., Brambilla, I., Daniela, B., Antonella, B., Patrizia, C., Giulia, C., Giuditta, C., Marta, C., Rossana, D., Milena, F., Bianca, M., Roberta, M., Enza, M., Stefania, P., Maurizio, P., Elena, P., Antonio, P., Francesca, R., Antonella, S., Maurizio, Z., Guy, A., Laura, B., Ermanna, C., Giuliana, C., Luca, D., Gabriella, F., Gabriella, G., Alessia, G., Viviana, L., Claudia, L., Valentina, M., Simona, P., Marta, P., Alice, B., Giacomo, C., Irene, C., Alfonso, C., Raffella, D. M., Annapia, D. N., Alessandro, F., Guglielmo, F., Loretta, F., Federica, G., Alessandra, M., Novazzi, Federica, Giacomo, R., Beatrice, R., Maria, S. I., Monica, T., Edoardo, V. N., Cerino, A., Varchetta, S., Oliviero, B., Mantovani, S., Mele, D., Calvi, M., Tizzoni, M., Nicora, C., Triarico, A., Petronella, V., Lago, P., Rettani, M., Comandatore, F., Bissignandi, G., Gaiarsa, S., Bandi, C., Ferrari, A., and Pasi, F.
Subjects: Emergency Medical Services, Coronavirus disease 2019 (COVID-19), Pneumonia, Viral, Population, Disease, 030204 cardiovascular system & hematology, law.invention, Hospital, 03 medical and health sciences, Patient Admission, 0302 clinical medicine, law, Health care, Pandemic, Internal Medicine, medicine, Covid-19, Emergency department, Emergency medical system, Emergency medical system organization, SARS-CoV-2, COVID-19, Coronavirus Infections, Emergency Service, Hospital, Humans, Intensive Care Units, Italy, Pandemics, Viral, 030212 general & internal medicine, education, Emergency Service, education.field_of_study, business.industry, Outbreak, Pneumonia, medicine.disease, Intensive care unit, Im - Original, Emergency Medicine, Medical emergency, business
Abstract: Since December 2019, the world has been facing the life-threatening disease, named Coronavirus disease-19 (COVID-19), recognized as a pandemic by the World Health Organization. The response of the Emergency Medicine network, integrating "out-of-hospital" and "hospital" activation, is crucial whenever the health system has to face a medical emergency, being caused by natural or human-derived disasters as well as by a rapidly spreading epidemic outbreak. We here report the Pavia Emergency Medicine network response to the COVID-19 outbreak. The "out-of-hospital" response was analysed in terms of calls, rescues and missions, whereas the "hospital" response was detailed as number of admitted patients and subsequent hospitalisation or discharge. The data in the first 5 weeks of the Covid-19 outbreak (February 21-March 26, 2020) were compared with a reference time window referring to the previous 5 weeks (January 17-February 20, 2020) and with the corresponding historical average data from the previous 5 years (February 21-March 26). Since February 21, 2020, a sudden and sustained increase in the calls to the AREU 112 system was noted (+ 440%). After 5 weeks, the number of calls and missions was still higher as compared to both the reference pre-Covid-19 period (+ 48% and + 10%, respectively) and the historical control (+ 53% and + 22%, respectively). Owing to the overflow from the neighbouring hospitals, which rapidly became overwhelmed and had to temporarily close patient access, the population served by the Pavia system more than doubled (from 547.251 to 1.135.977 inhabitants, + 108%). To minimize the possibility of intra-hospital spreading of the infection, a separate "Emergency Department-Infective Disease" was created, which evaluated 1241 patients with suspected infection (38% of total ED admissions). Out of these 1241 patients, 58.0% (n = 720) were admitted in general wards (n = 629) or intensive care unit (n = 91). To allow this massive number of admissions, the hospital reshaped many general ward Units, which became Covid-19 Units (up to 270 beds) and increased the intensive care unit beds from 32 to 60. In the setting of a long-standing continuing emergency like the present Covid-19 outbreak, the integration, interaction and team work of the "out-of-hospital" and "in-hospital" systems have a pivotal role. The present study reports how the rapid and coordinated reorganization of both might help in facing such a disaster. AREU-112 and the Emergency Department should be ready to finely tune their usual cooperation to respond to a sudden and overwhelming increase in the healthcare needs brought about by a pandemia like the current one. This lesson should shape and reinforce the future.
Published: 2020
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34. Intermittent Hypoxia Augments Pulmonary Vasoconstrictor Reactivity through PKCβ/Mitochondrial Oxidant Signaling

Author: Benjimen R. Walker, Nancy L. Kanagy, Lindsay M. Herbert, Simin Yan, Michelle A. Sands, Charles E. Norton, Joshua R. Sheak, Laura V. Gonzalez Bosc, Thomas C. Resta, Jessica B. Snow, Nikki L. Jernigan, and Laura Weise-Cross
Subjects: Male, 0301 basic medicine, Indoles, Potassium Channels, Vascular smooth muscle, Clinical Biochemistry, Pharmacology, Maleimides, 0302 clinical medicine, Hypoxic pulmonary vasoconstriction, Protein Interaction Mapping, Hypoxia, Cells, Cultured, Original Research, Membrane Potential, Mitochondrial, Chemistry, Nuclear Proteins, Intermittent hypoxia, Free Radical Scavengers, Potassium channel, Mesenteric Arteries, Mitochondria, Tetradecanoylphorbol Acetate, medicine.symptom, Signal Transduction, Pulmonary and Respiratory Medicine, Hypertension, Pulmonary, Myocytes, Smooth Muscle, Pulmonary Artery, Cyclic N-Oxides, 03 medical and health sciences, Sleep Apnea Syndromes, Right ventricular hypertrophy, Protein Kinase C beta, medicine, Animals, Humans, Rats, Wistar, Molecular Biology, Protein kinase C, Cell Biology, medicine.disease, Pulmonary hypertension, Rats, Cytoskeletal Proteins, 030104 developmental biology, 030228 respiratory system, Vasoconstriction, Spin Labels, Carrier Proteins, Reactive Oxygen Species
Abstract: Pulmonary vasoconstriction resulting from intermittent hypoxia (IH) contributes to pulmonary hypertension (pHTN) in patients with sleep apnea (SA), although the mechanisms involved remain poorly understood. Based on prior studies in patients with SA and animal models of SA, the objective of this study was to evaluate the role of PKCβ and mitochondrial reactive oxygen species (mitoROS) in mediating enhanced pulmonary vasoconstrictor reactivity after IH. We hypothesized that PKCβ mediates vasoconstriction through interaction with the scaffolding protein PICK1 (protein interacting with C kinase 1), activation of mitochondrial ATP-sensitive potassium channels (mitoK(ATP)), and stimulated production of mitoROS. We further hypothesized that this signaling axis mediates enhanced vasoconstriction and pHTN after IH. Rats were exposed to IH or sham conditions (7 h/d, 4 wk). Chronic oral administration of the antioxidant Tempol or the PKCβ inhibitor LY-333531 abolished IH-induced increases in right ventricular systolic pressure and right ventricular hypertrophy. Furthermore, scavengers of O(2)(−) or mitoROS prevented enhanced PKCβ-dependent vasoconstrictor reactivity to endothelin-1 in pulmonary arteries from IH rats. In addition, this PKCβ/mitoROS signaling pathway could be stimulated by the PKC activator PMA in pulmonary arteries from control rats, and in both rat and human pulmonary arterial smooth muscle cells. These responses to PMA were attenuated by inhibition of mitoK(ATP) or PICK1. Subcellular fractionation and proximity ligation assays further demonstrated that PKCβ acutely translocates to mitochondria upon stimulation and associates with PICK1. We conclude that a PKCβ/mitoROS signaling axis contributes to enhanced vasoconstriction and pHTN after IH. Furthermore, PKCβ mediates pulmonary vasoconstriction through interaction with PICK1, activation of mitoK(ATP), and subsequent mitoROS generation.
Published: 2020
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35. A Smartphone-Aided Program to Support Video Calls, Leisure, and Occupational Activities in People with Moderate Intellectual Disability

Author: Jeff Sigafoos, Gloria Alberti, Mark F. O’Reilly, Giulio E. Lancioni, Emanuela Resta, and Valeria Chiariello
Subjects: Resource (project management), Social work, Intellectual disability, Applied psychology, medicine, Psychology (miscellaneous), Android (operating system), medicine.disease, Psychology, Social Sciences (miscellaneous), Session (web analytics)
Abstract: The study evaluated a new smartphone-aided program that added the possibility of making video calls to the leisure and activity options available in the previous version of the program. The participants were seven adults with moderate intellectual disability and sensory impairments who had been exposed to the original smartphone-aided program including leisure and activity options. The new version of the program (a) relied on the use of a Samsung Galaxy J4 Plus smartphone, which was fitted with Android 9.0 operating system and MacroDroid, and (b) alternated periods in which the participants could choose to engage in video calls and leisure with periods in which they were required to carry out occupational activities. Every session alternated four leisure and video call periods with three activity periods. During the baseline (i.e., with the original program), the participants engaged in leisure and activities, but did not manage to make video calls. During the post-intervention phase (i.e., with the new version of the program), the participants engaged in leisure and video calls and maintained their performance of occupational activities. Staff personnel rated the new version of the program more favorably than the previous version. The new version of the program can be a useful resource for people like the participants of this study.
Published: 2020
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36. Disease expression in juvenile polyposis syndrome: a retrospective survey on a cohort of 221 European patients and comparison with a literature-derived cohort of 473 SMAD4/BMPR1A pathogenic variant carriers

Author: Maurizio Genuardi, Robert Blatter, Benjamin Tschupp, Hans F. A. Vasen, Karl Heinimann, Fiona Lalloo, Gabriela Moeslein, D. Gareth Evans, Robert Hüneburg, Frederik J. Hes, Laura Renkonen-Sinisalo, Inge Bernstein, Stefan Aretz, Chrystelle Colas, Isabel Spier, Andrew Latchford, Nicoletta Resta, Heikki Järvinen, Dora Varvara, HUS Abdominal Center, II kirurgian klinikka, Department of Surgery, University of Helsinki, Helsinki University Hospital Area, Clinical sciences, Medical Genetics, University Hospital Basel [Basel], University of Basel (Unibas), University Hospital Bonn, Aalborg University [Denmark] (AAU), Unité fonctionnelle d'Oncogénétique et Angiogénétique Moléculaire [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU), Institut Curie [Paris], University of Manchester [Manchester], Fondazione 'Policlinico Universitario A. Gemelli' [Rome], Università cattolica del Sacro Cuore [Roma] (Unicatt), Leiden University Medical Center (LUMC), Universität Witten Herdecke, and University of Bari Aldo Moro (UNIBA)
Subjects: 0301 basic medicine, polyposis, 030105 genetics & heredity, PHENOTYPE, Settore MED/03 - GENETICA MEDICA, SMAD4, Surveys and Questionnaires, Genetics(clinical), Juvenile polyposis syndrome, Telangiectasia, Genetics (clinical), Smad4 Protein, Intestinal Polyposis, Stomach, 1184 Genetics, developmental biology, physiology, genotype–phenotype correlation, syndrome, PREVALENCE, GENOTYPE, 3. Good health, juvenile polyposis syndrome, medicine.anatomical_structure, Cohort, medicine.symptom, Adult, medicine.medical_specialty, Anemia, [SDV.CAN]Life Sciences [q-bio]/Cancer, colorectal cancer, genotype-phenotype correlation, Article, hereditary hemorrhagic telangiectasia, 03 medical and health sciences, Neoplastic Syndromes, Hereditary, Internal medicine, medicine, Humans, Bone Morphogenetic Protein Receptors, Type I, Germ-Line Mutation, BMPR1A, Retrospective Studies, MUTATIONS, business.industry, Cancer, Retrospective cohort study, medicine.disease, digestive system diseases, DELETIONS, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, 3111 Biomedicine, business
Abstract: International audience; Purpose: Juvenile polyposis syndrome (JPS) is a rare, autosomal-dominantly inherited cancer predisposition caused in approximately 50% of cases by pathogenic germline variants in SMAD4 and BMPR1A. We aimed to gather detailed clinical and molecular genetic information on JPS disease expression to provide a basis for management guidelines and establish open access variant databases.Methods: We performed a retrospective, questionnaire-based European multicenter survey on and established a cohort of SMAD4/BMPR1A pathogenic variant carriers from the medical literature.Results: We analyzed questionnaire-based data on 221 JPS patients (126 kindreds) from ten European centers and retrieved literature-based information on 473 patients. Compared with BMPR1A carriers, SMAD4 carriers displayed anemia twice as often (58% vs. 26%), and exclusively showed overlap symptoms with hemorrhagic telangiectasia (32%) and an increased prevalence (39% vs. 13%) of gastric juvenile polyps. Cancer, reported in 15% of JPS patients (median age 41 years), mainly occurred in the colorectum (overall: 62%, SMAD4: 58%, BMPR1A: 88%) and the stomach (overall: 21%; SMAD4: 27%, BMPR1A: 0%).Conclusion: This comprehensive retrospective study on genotype-phenotype correlations in 694 JPS patients corroborates previous observations on JPS in general and SMAD4 carriers in particular, facilitates recommendations for clinical management, and provides the basis for open access variant SMAD4 and BMPR1A databases.
Published: 2020
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37. Assessment of Induced Sputum Cellularity in COPD Patients Belonging to Two Different Classes of Air Pollution Exposure

Author: Onofrio Resta, Silvano Dragonieri, Giovanna Elisiana Carpagnano, Donato Lacedonia, Giulia Scioscia, Pierluigi Carratù, Grazia Pia Palladino, Maria Pia Foschino Barbaro, and Vitaliano Nicola Quaranta
Subjects: Pulmonary and Respiratory Medicine, Spirometry, medicine.medical_specialty, Exposed Population, Copd patients, Population, Induced sputum, Pilot Projects, Pulmonary Disease, Chronic Obstructive, Air Pollution, Internal medicine, medicine, Humans, education, education.field_of_study, COPD, medicine.diagnostic_test, business.industry, Sputum, General Medicine, medicine.disease, respiratory tract diseases, Rural area, medicine.symptom, business
Abstract: Introduction Several studies have previously demonstrated that long-term exposure to outdoor pollution present airway inflammation in term of an increase of sputum neutrophils. Aim and methods The aim of our study was to evaluate the level of airway inflammation by induced sputum in a group of 15 non-professionally exposed population of well-characterized COPD patients, residing in urban areas with high rate of outdoor pollution, compared to a control group of 13 individuals with COPD, living in rural areas with a low pollution rate. All participants underwent spirometry and sputum induction. Results A statistically significant increase in the percentage of neutrophil cell count was found among the residents in urban areas compared to those living in rural regions (89.1 vs 79.0, p Conclusions In conclusion, we showed that non-professionally exposed patients with COPD residing in highly-polluted urban areas had greater airway inflammation in terms of sputum neutrophils compared to a population with very similar characteristics, living in rural areas with lower outdoor pollution. The results of this pilot study may be relevant for the long term effect of environmental outdoor pollution in vulnerable patients like those with COPD.
Published: 2020
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38. Generation of a Triadin KnockOut Syndrome Zebrafish Model

Author: Marco Spreafico, Chiara Di Resta, Anna Santoni, Vanilla Martina Vecchi, Anna Marozzi, Alessia Brix, Anna Pistocchi, Simone Sala, Vecchi, V. M., Spreafico, M., Brix, A., Santoni, A., Sala, S., Pistocchi, A., Marozzi, A., and Di Resta, C.
Subjects: Morpholino, Muscle Fibers, Skeletal, Gene Expression, Muscle Proteins, Bioinformatics, Sudden cardiac death, Gene Knockout Techniques, Loss of Function Mutation, Medicine, Biology (General), Zebrafish, Spectroscopy, biology, Syndrome, General Medicine, Triadin KnockOut Syndrome, Phenotype, Computer Science Applications, Chemistry, heart defects, Heart defects, QH301-705.5, Danio, arrhythmic drugs, Article, Catalysis, Inorganic Chemistry, Animals, Humans, Genetic Predisposition to Disease, Physical and Theoretical Chemistry, Molecular Biology, Gene, QD1-999, Genetic Association Studies, business.industry, Mechanism (biology), Organic Chemistry, Arrhythmic drugs, Arrhythmias, Cardiac, biology.organism_classification, medicine.disease, zebrafish, Disease Models, Animal, Death, Sudden, Cardiac, Triadin, Carrier Proteins, business
Abstract: Different forms of sudden cardiac death have been described, including a recently identified form of genetic arrhythmogenic disorder, named “Triadin KnockOut Syndrome” (TKOS). TKOS is associated with recessive mutations in the TRDN gene, encoding for TRIADIN, but the pathogenic mechanism underlying the malignant phenotype has yet to be completely defined. Moreover, patients with TKOS are often refractory to conventional treatment, substantiating the need to identify new therapeutic strategies in order to prevent or treat cardiac events. The zebrafish (Danio rerio) heart is highly comparable to the human heart in terms of functions, signal pathways and ion channels, representing a good model to study cardiac disorders. In this work, we generated the first zebrafish model for trdn loss-of-function, by means of trdn morpholino injections, and characterized its phenotype. Although we did not observe any gross cardiac morphological defect between trdn loss-of-function embryos and controls, we found altered cardiac rhythm that was recovered by the administration of arrhythmic drugs. Our model will provide a suitable platform to study the effect of TRDN mutations and to perform drug screening to identify new pharmacological strategies for patients carrying TRDN mutations.
Published: 2021
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39. Fetal magnetic resonance imaging at 36 weeks predicts neonatal macrosomia

Author: Mieke Cannie, Vivien Dütemeyer, Caroline Kadji, Jacques Jani, Fouad Abi-Khalil, Elisa Bevilacqua, Eleonora Mazzone, Serge Benjou Etchoua, Serena Resta, Xin Kang, Andrew Carlin, Supporting clinical sciences, Radiology, and Clinical sciences
Subjects: Adult, medicine.medical_specialty, Percentile, Pregnancy Trimester, Third, Prenatal diagnosis, Fetal Macrosomia, Shoulder dystocia, Fetus, Fetus/diagnostic imaging, Prenatal Diagnosis, medicine, Humans, magnetic resonance imaging, Prospective Studies, Fetal Macrosomia/diagnostic imaging, medicine.diagnostic_test, Receiver operating characteristic, Obstetrics, business.industry, Ultrasound, Obstetrics and Gynecology, Gestational age, birth weight, Magnetic resonance imaging, Gold standard (test), medicine.disease, Radiology Nuclear Medicine and imaging, Female, pregnancy, business
Abstract: BACKGROUND: Large-for-gestational-age fetuses are at increased risk of perinatal morbidity and mortality. Magnetic resonance imaging seems to be more accurate than ultrasound in the prediction of macrosomia; however, there is no well-powered study comparing magnetic resonance imaging with ultrasound in routine pregnancies. OBJECTIVE: This study aimed to prospectively compare estimates of fetal weight based on 2-dimensional ultrasound and magnetic resonance imaging with actual birthweights in routine pregnancies. STUDY DESIGN: From May 2016 to February 2019, women received counseling at the 36-week clinic. Written informed consent was obtained for this Ethics Committee-approved study. In this prospective, single-center, blinded study, pregnant women with singleton pregnancies between 36 0/7 and 36 6/7 weeks' gestation underwent both standard evaluation of estimated fetal weight with ultrasound according to Hadlock et al and magnetic resonance imaging according to the formula developed by Baker et al, based on the measurement of the fetal body volume. Participants and clinicians were aware of the results of the ultrasound but blinded to the magnetic resonance imaging estimates. Birthweight percentile was considered as the gold standard for the ultrasound and magnetic resonance imaging-derived percentiles. The primary outcome was the area under the receiver operating characteristic curve for the prediction of large-for-gestation-age neonates with birthweights of ≥95th percentile. Secondary outcomes included the comparative prediction of large-for-gestation-age neonates with birthweights of ≥90th, 97th, and 99th percentiles and small-for-gestational-age neonates with birthweights of ≤10th, 5th, and 3rd percentiles for gestational age and maternal and perinatal complications. RESULTS: Of 2914 women who were initially approached, results from 2378 were available for analysis. Total fetal body volume measurements were possible for all fetuses, and the time required to perform the planimetric measurements by magnetic resonance imaging was 3.0 minutes (range, 1.3-5.6). The area under the receiver operating characteristic curve for the prediction of a birthweight of ≥95th percentile was 0.985 using prenatal magnetic resonance imaging and 0.900 using ultrasound (difference=0.085, P
Published: 2022
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40. MUM-1 immunohistochemistry has high accuracy and reliability in the diagnosis of chronic endometritis: a multi-centre comparative study with CD-138 immunostaining

Author: Leonardo Resta, Ettore Cicinelli, Amerigo Vitagliano, Dana Ben-Tzur, V Cataldo, Marco Noventa, Alessandra Andrisani, Marco Balzani, Giovanni Buzzaccarini, Sergio Haimovich, Guido Ambrosini, Nico Picardi, Dominique de Ziegler, Carlo Saccardi, Loris Marin, Nili Raz, Rossana Cicinelli, and Pantaleo Greco
Subjects: Adult, Infertility, medicine.medical_specialty, Diagnostic accuracy, NO, CD138, Recurrent miscarriage, Genetics, medicine, Endometrial Polyp, Humans, Genetics (clinical), Retrospective Studies, Gynecology, Plasma cells, medicine.diagnostic_test, business.industry, Chronic endometritis, MUM-1, Reproducibility of Results, Obstetrics and Gynecology, General Medicine, Gold standard (test), medicine.disease, CD138, Plasma cells, Chronic endometritis, Diagnostic accuracy, MUM-1, Immunohistochemistry, Reproductive Physiology and Disease, Reproductive Medicine, Spain, Hysteroscopy, Interferon Regulatory Factors, Female, Syndecan-1, Endometritis, business, Chronic Endometritis, Biomarkers, Developmental Biology, Endometrial biopsy
Abstract: PURPOSE: The current gold standard for chronic endometritis (CE) diagnosis is immunohistochemistry (IHC) for CD-138. However, IHC for CD-138 is not exempt from diagnostic limitations. The aim of our study was to evaluate the reliability and accuracy of MUM-1 IHC, as compared with CD-138. METHODS: This is a multi-centre, retrospective, observational study, which included three tertiary hysteroscopic centres in university teaching hospitals. One hundred ninety-three consecutive women of reproductive age were referred to our hysteroscopy services due to infertility, recurrent miscarriage, abnormal uterine bleeding, endometrial polyps or myomas. All women underwent hysteroscopy plus endometrial biopsy. Endometrial samples were analysed through histology, CD138 and MUM-1 IHC. The primary outcome was to evaluate the diagnostic accuracy of MUM-1 IHC for CE, as compared with CD-138 IHC. RESULTS: Sensitivity and specificity of CD-138 and MUM-1 IHC were respectively 89.13%, 79.59% versus 93.48% and 85.03%. The overall diagnostic accuracy of MUM-1 and CD-138 IHC were similar (AUC = 0.893 vs AUC = 0.844). The intercorrelation coefficient for single measurements was high between the two techniques (ICC = 0.831, 0.761–0.881 95%CI). However, among CE positive women, MUM-1 allowed the identification of higher number of plasma cells/hpf than CD-138 (6.50 [SD 4.80] vs 5.05 [SD 3.37]; p = 0.017). Additionally, MUM-1 showed a higher inter-observer agreement as compared to CD-138. CONCLUSION: IHC for MUM-1 and CD-138 showed a similar accuracy for detecting endometrial stromal plasma cells. Notably, MUM-1 showed higher reliability in the paired comparison of the individual samples than CD-138. Thus, MUM-1 may represent a novel, promising add-on technique for the diagnosis of CE.
Published: 2022

41. Safety of hospital discharge before return of bowel function after elective colorectal surgery

Author: J Chapman, S, Blanco-Colino, R, Pérez-Ajates, S, O Anabitarte Bautista, Hodson, J, C Glasbey, J, Pata, F, Pellino, G, Sgrò, A, Soares, A, T van Elst, S Van Straten, Nepogodiev, D, Borakati, A, F Bath, M, H Yasin, I, Mclean, K, Arthur, T, Kovacevic, M, Delibegovic, S, Karamanliev, M, Swamad, M, Žebrák, R, Paramasivam, R, Martensen, A, M Larsen, H, Rädeker, L, E Frey, P, Kechagias, A, Venara, A, Duchalais, E, Ioannidis, A, Pasquali, S, Simioni, A, Farina, V, Podda, M, Lorenzon, L, Schaeff, V, Otto, A, Jakubauskas, M, R van Elst, T, Chu, M, Pvb, Fagan, I Wells, C, A Alagoa João, Juloski, J, Y El Kasmy El Kasmi, Espin-Basany, E, Clerc, D, Ciubotaru, C, Popescu, S, Yanishev, A, Lee, S, B Ozkan, B, A Yagız Sen, K Aktas, M, E Baki, B, Yüksek, B, Kamarajah, S, A Khaw, R, Mills, E, Goodson, R, Thakral, N, D Ablett, A, Adra, M, Kwek, I, M Khan, S, Quinn, P, R Manley, L, Badran, A, Ramjeeawon, A, Campbell, A, L Tan, H, S Rye, D, Rajaraman, N, G Norman, J, Vutipongsatorn, K, Solomou, G, Akhbari, M, Ali, A, Murray, V, M Baker, D, D Brandao, B, Stainer, B, Thavayogan, R, Jones, D, O Onafowokan, O, Gharooni, A, Dabab, N, Carlton-Carew, S, Kungwengwe, G, Gabriel, M, Sewart, E, C Shortland, T, Lawday, S, Pockney, P, Dawson, A, D Brumfitt, C, Stewart, P, B, Ng, K Luong, J, Ivanov, V, Borisova, A, Neykov, V, Kunčarová, K, Kološová, B, Antonova, T, Farkašová, M, L Harbjerg, J, Brandsborg, S, Brinck, S, D Kjaer, M, Mark-Christensen, A, P Unbehaun, K, Dalsgaard, P, D Lycke, K, Lenaoures, P, Brigand, C, Dumange, E, Gout, M, Moehwald, C, Prem, M, Alhalabi, O, Sliwinski, S, Krupp, J, Gablenz, E, Schmitzer, L, Kopp, A, Steinle, J, Gsenger, J, J Pohl, L, Riccardi, M, M Christodoulou, I, Konstantinidis, M, Machairas, N, Zoikas, A, Balalis, D, K Manatakis, D, L Aguilera, M, Marano, L, Fleres, F, Lovisetto, F, Sasia, D, Segalini, E, Pata, G, Lucchi, A, Sagnotta, A, Campagnaro, T, Petrelli, F, Gallo, G, Papandrea, M, Testa, V, Sinibaldi, G, F Di Candido, Colombo, F, Perrone, G, Aresu, S, Biancafarina, A, Canonico, G, Pagnanelli, M, Curletti, G, Bini, R, A de Manzoni Garberini, Impellizzeri, H, Cillara, N, Tutino, R, Picciariello, A, Coletta, D, Savino, G, Ferrara, F, Tamini, N, Talamo, G, Parini, D, Giamundo, P, A Lo Conte, Pagano, G, Ripetti, V, Pesce, A, Menduni, N, Giudicissi, R, Goldin, E, Rega, D, Belli, A, Andriola, V, Gordini, L, Foppa, C, Piccolo, G, Birindelli, A, Ferrari, C, Ballarini, Z, Tirelli, F, Milone, M, M De Rosa, S Pipitone Federico, N, Molteni, B, L Tilocca, P, Sancini, G, N Piozzi, G, Lauretta, A, Poillucci, G, Mulas, S, Simcikas, D, Portelli, L, Jwm van Wijnbergen, L Dinger, T, Sfh Ten Doesschate, Ashm van Dalen, D van den Bos, D, Hansmann, M, J Medina Feliz, Z Kuiper, S, Abdulrahman, Z, R Pruijssers, S, Farik, S, M Elliott, B, P Geneta, V, Wilton, S, Kandelaki, H, L Peng, S, Campbell, S, K Lim, Y, S Yassaie, S, Murray, M, Haran, C, Tan, J, Castro, J, Laranjeira, A, Catarino, S, Neves-Marques, C, G Correia, J, N Vieira, B, C Quintela, A, L Serra, M, Maciel, J, Cunha, M, J Aparício, D, Neves, J, Azevedo, J, Romano, M, Eiró, F, Romano, J, Monteiro, C, Claro, M, R Almeida, M, Peyroteo, M, D Machado, N, Capote, H, Ferreira, M, Sousa, X, Devesa, H, Cavadas, D, Guerreiro, I, Costa, M, Rosete, M, Salman, M, English, C, Mohammed, N, Litvin, A, V Ćuk, V, Mészárosová, K, Jaich, R, H De Lima, Brooks, S, Marx, M, M Nshalati Salvation, J García Cardo, Mora-Guzmán, I, J Sancho Muriel, U de Andres Olabarria, Muriel, P, C Jimenez Viñas, Alconchel, F, O Esteban Sinovas, C Fairén Oro, M López Otero, S Figueroa Jiménez, O Claramonte Bellmunt, J Martínez Caballero, Rubio-Pérez, I, M Aguilar-Martínez, M, J Segura-Sampedro, J, C Olmedo Moreno, D Negre Parra, M Estévez Diz, A, Martín-Balbuena, R, C Bustamante Recuenco, E Licardie Bolaños, R, Fernández, P, A Díaz Padillo, Forero-Torres, A, I Alberdi San Román, H Salvador Rosés, M Merayo Álvarez, P Villarejo Campos, C Lopes Moreira, C, P Uriol Peralta, M Serrano Navidad, Ripollés-Melchor, J, Garcea, A, H Gómez Facundo, P Troncoso Pereira, V Pérez Guarinos, C, Blaser, B, Piazza, G, Gagliardi, B, Serin, H, S Yurdaor, S, Arslan, E, Kopac, O, Uyanik, A, B Ozmen, B, Tiftik, E, Aksoy, B, Yalcinkaya, A, Ozoglu, F, D Kocer, M, Bilicen, G, N Cinar, E, Uslu, Ö, Kaya, Y, Demirci, K, Wong, J, Mmh, Farhan-Alanie, Suresh, G, Asif, A, J Finch, B, Bhahirathan, Y, Herron, J, Z Yi Tew, Obukofe, R, Russell, C, Suchett-Kay, I, Netke, T, Williams, L, Kisiel, A, Y Liu, F, Claireaux, H, James, P, Mondal, A, Kalderon, R, H Nadama, H, Al-Saraff, Z, Jph, Tam, Powell-Chandler, A, Wood, F, Rebecca, Gorgievska, Ragavoodoo, A, Thakrar, C, Rojoa, D, Palmer, C, Davidson, K, Giacci, L, Hale, J, W Gan, F, Makin-Taylor, R, Y Hey, C, Toh, C, M Findlay, J, Griffiths, N, Ganesananthan, S, Jasionowska, S, Poustie, M, Wong, C, Turner, T, Pyc, W, Sloper, W, Warner, C, Coey, J, Mason, D, Sait, S, Kowal, M, Owen, M, Saiyed, A, Ashworth, I, Akbari, K, Curran, M, Martin, P, Parker, D, Kwok, K, Lye, C, Ghaly, M, Sammour, T, Lewis, D, Mundasad, R, Wilkes, A, Ctercteko, G, Maslyankov, S, Dimov, R, Iliev, S, Dimitrov, D, Marek, F, Örhalmi, J, Skalický, P, Skalický, T, Chrz, K, Christensen, P, Worsøe, J, S Kristensen, E, J Emmertsen, K, S Loeve, U, L Mihaljevic, A, Herrle, F, M Konstantinidis, K, Korkolis, D, Karanikas, I, Vincenti, L, Anania, G, Borghi, F, Agresta, F, Maretto, I, Parisi, A, Bucci, L, G De Palma, Guglielmi, A, Cucinotta, E, F La Torre, Cianchi, F, Guerrieri, M, Trompetto, M, Persiani, R, Micheletto, G, Delrio, P, Cantafio, S, Ronconi, M, Pag, Bisagni, M De Prizio, Franceschi, A, Galleano, R, Cavallini, M, Brescia, A, D'Ambra, L, Benevento, A, Niolu, P, Calgaro, M, Colangelo, E, Grottola, T, F Altomare, D, Puleo, S, Salamone, G, Pietrabissa, A, Poggioli, G, Erdas, E, Ottonello, R, Tonini, V, Selvaggi, F, Sammarco, G, Ceccarelli, G, C De Nisco, Surgo, D, Taglietti, L, Ozolins, A, Sivinš, A, Poskus, T, Psaila, J, A Bemelman, W, J Graat, L, Langenhoff, B, Bpl, Wijnhoven, Ahw van de Ven, Poelman, M, Lps, Stassen, Slooter, G, Yiz, Acherman, Hoff, C, F Gerhards, M, Mwj, Stommel, J Hazebroek, E, Aaw van Geloven, A Schasfoort, R, L van Leeuwen, B, B Tuynman, J, Mwa van Tilburg, G Boerma, E, Sharma, P, Jenkins, B, P Bissett, I, Herd, A, Gordon, A, Vernon, D, Omundsen, M, J, Ly, Reddy, A, Bonnet, G, Harmston, C, Morales, M, Francisco, V, Costa, S, Manso, A, Amorim, E, Pereira, J, Cardoso, J, Ourô, S, Caratão, M, Nascimento, C, B Ribeiro da Silva, Taranu, V, Dias, R, Mendes, J, Allen, M, Silva, A, Carlos, S, Barbosa, E, Carneiro, C, Ramos, L, Lencastre, L, Martins, R, Silva-Vaz, P, F Ridgway, P, A McNamara, D, Cahill, R, Hogan, A, Larkin, J, R O'Connell, P, Negoi, I, Abelevich, A, M Ćuk, V, Vician, M, Ede, C, Sardiwalla, I, Mulira, S, Montwedi, D, Oyomno, M, Sabia, D, V Portugal Porras, Vigorita, V, G Sanz Ortega, García, J, A Espí Macías, F Blanco Antona, A Luján Mompeán, J, S Salvans Ruiz, Villarejo-Campos, P, M Romero Simó, Sánchez-Guillén, L, M Jiménez-Gómez, L, A 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V., Escovar, F. J., Fernandez, M. C., Martinez, A. P., Bergara, I. B., Olavarria, A. L., del Pozo Andres, E., Ortega, C., Arias-Camison, P. L., Arranz, J. M. N., Sexmero, M. J. M., Alonso, E. D., Moreno, A. I., Margarida, A., Pando, B., Marin, L. L., Calle, M. P., Cordero, M. J. R., Cuartango, A. S., Sanchez, E., Rodrigo, A. M., Diago, J. P., Lista, M. V., Terricabras, S. R., Sanz, L. B., Camprubi, E. A., Ferrandez, M. R., Lao, E. P., Miro, M. D. P., Alberca-Paramo, A., Verdejo, T. A., Canete-Manzanares, J., Molina-Florez, M., Hernandez, L. C. G., Nunez, S. O., Suarez-Sanchez, M., Martin-Fernandez, J., Liebana, M. M. S., Betancourth, C. F. C., Mico, S. S., Fernandez, A., Curtis, C., Bosch, M., Triguero, D., Ramirez, M. B., Diaz, N. R., Caraballo, I. G., Vicente, T. P., Orue-Echebarria, M. I., Sanchez-Calvo, L., Wang, D., Trueba-Collado, C., de Quiros, J. T. M. B., Jimenez, F. A. R., Ortega, A. P., Barbadillo, A. T., Pujana, E. R., Illera, M. V. F., Serralvo, A. D. L. 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J., Lam, S., Chipeta, C., Jain, C., Garofalidou, T., Novotny, S. A., Locke, S., Bowman, C., Begaj, A., Murphy, C., Radcliffe, K., Chong, J. T., Jeffrey, E., Chaudhury, N., Rajendran, K., Akbar, Z., Walters, B., Kulendrarajah, B., Tran, N., Shrestha, S., Parmar, S., Gallagher, C., Hennessy, L., Pentti, E., Badhrinarayanan, S., Fung, A., Mansoor, M., Kenny, R., Kan, P., Lee, D. E., Khosla, S., Samake, M., Shaban, F., Aftab, R., Gough, M., Woodburn, B., Vayalapra, S., Mcmurrugh, K., Jimulia, D., Deol, S., Pike, S., Embury-Young, Y., Patel, M., Kilgallon, E., Keating, R., Walsh, A., Khan, H., Logue, G., Orekoya, M., Alasmar, M., Charalambides, M., Llavall, A. C., Williamson, E., Bharwada, Y., Zearmal, S., Evans, H., Panikkar, M., de la Cruz, G., Caplan, J., Ruparelia, A., Tanvir, T., Soare, C., Pang, Y. 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B., Hoo, M., Gopaul, A., Scanlon, K., O'Dwyer, N., Jovanovic, M., Panyko, A., Van Vuuren, S., Centeno, A., Bernado, I. R., Senorans, M. P. G., Amor, L. G., Ramirez, A. C., Abrisqueta, J., Gomez, M. E., Arroyo, A., Cerdan, C., Romeu, N. G., Enriquez-Navascues, J. M., Collado-Roura, F., Curchod, P., Gaspar, S., Imadalou, L., Mutlu, D., Akyol, C., Uygur, F. A., Eray, I. C., Biyiklioglu, O., Cetin, M. F., Isik, A. E., Karip, B., Dogan, H., Sarigul, L., Tunc, E., Aydin, T., Bodur, S., Karabulut, K., Francis, A. A., Al-hadithi, A., Lau, I. S. F., Smith, E., Mahapatra, S., Mcauliffe, O., Imam, L., Akram, B., Hossaini, S., Davies, R., Ko, M., Collins, J., Pandya, A., Reilly, S., Archer, J., Livie, J., Chaudhry, F. A., Ntakomyti, E., Diallo, R., Bylinski, T., Wright, J., Masiha, E., Tung, J., Shirazi, B., Neilson, A., Epton, S., Patel, N., Trussell, S., Couldrey, A., and Donnelly, C.
Subjects: operative, Male, postoperative discharge, Postoperative Complications, 0302 clinical medicine, Colostomy, CRITERIA, Prospective Studies, Bowel function, Colectomy, IMAGINE, stoma, intestines, Proctectomy, Ileostomy, digestive, oral, and skin physiology, patient discharge, colorectal surgery, hospital discharge, bowel function, RECOVERY, Middle Aged, adult, colostomy, elective surgical procedures, female, follow-up studies, humans, ileostomy, ileus, male, middle aged, multivariate analysis, patient readmission, patient safety, postoperative complications, prospective studies, recovery of function, colectomy, proctectomy, Patient Discharge, Colorectal surgery, ileus - - discharge - bowel function - elective - colorectal surgery, Elective Surgical Procedures, 030220 oncology & carcinogenesis, Female, 030211 gastroenterology & hepatology, Patient Safety, Cohort study, safety, Adult, medicine.medical_specialty, Ileus, Patient Readmission, defecation, 03 medical and health sciences, medicine, Hospital discharge, Humans, colorectal surgery, colorectal resection, Colorectal resection, defecation, postoperative complications, colorectal surgery, intestines, patient discharge, patient readmission, safety, surgical procedures, operative, colorectal resection, ileus, business.industry, Recovery of Function, Odds ratio, medicine.disease, digestive system diseases, surgical procedures, Surgery, Multivariate Analysis, Defecation, business, Follow-Up Studies
Abstract: Ileus is common after colorectal surgery and is associated with an increased risk of postoperative complications. Identifying features of normal bowel recovery and the appropriateness for hospital discharge is challenging. This study explored the safety of hospital discharge before the return of bowel function.A prospective, multicentre cohort study was undertaken across an international collaborative network. Adult patients undergoing elective colorectal resection between January and April 2018 were included. The main outcome of interest was readmission to hospital within 30 days of surgery. The impact of discharge timing according to the return of bowel function was explored using multivariable regression analysis. Other outcomes were postoperative complications within 30 days of surgery, measured using the Clavien-Dindo classification system.A total of 3288 patients were included in the analysis, of whom 301 (9·2 per cent) were discharged before the return of bowel function. The median duration of hospital stay for patients discharged before and after return of bowel function was 5 (i.q.r. 4-7) and 7 (6-8) days respectively (P 0·001). There were no significant differences in rates of readmission between these groups (6·6 versus 8·0 per cent; P = 0·499), and this remained the case after multivariable adjustment for baseline differences (odds ratio 0·90, 95 per cent c.i. 0·55 to 1·46; P = 0·659). Rates of postoperative complications were also similar in those discharged before versus after return of bowel function (minor: 34·7 versus 39·5 per cent; major 3·3 versus 3·4 per cent; P = 0·110).Discharge before return of bowel function after elective colorectal surgery appears to be safe in appropriately selected patients.El íleo es frecuente tras la cirugía colorrectal y se asocia con un aumento del riesgo de las complicaciones postoperatorias. Identificar las características de una recuperación normal del tránsito y la idoneidad para el alta hospitalaria es una tarea difícil. Este estudio examinó la seguridad del alta hospitalaria antes del restablecimiento de la función intestinal. MÉTODOS: Se llevó a cabo un estudio de cohortes prospectivo y multicéntrico a través de una red de colaboración internacional. Se incluyeron pacientes adultos sometidos a resección electiva colorrectal entre enero y abril 2018. El objetivo principal fue el reingreso hospitalario durante los 30 primeros días tras la intervención. Se utilizó un análisis de regresión multivariable para evaluar el impacto del momento del alta en función del restablecimiento de la función intestinal. El objetivo secundario fue las complicaciones postoperatorias en los primeros 30 días después de la cirugía, valoradas mediante el sistema de clasificación de Clavien-Dindo.Se incluyeron en el análisis 3.288 pacientes, de los cuales 301 (9,2%) fueron dados de alta antes del restablecimiento de la función intestinal. La mediana de la estancia hospitalaria de los pacientes dados de alta antes y después del restablecimiento de la función intestinal fue 5 (rango intercuartílico: 4-7) y 7 (6-8) días, respectivamente (P 0,001). No hubo diferencias significativas en las tasas de reingreso entre estos grupos (6,6% versus 8,0%; P = 0,499), y este resultado se mantuvo en el análisis multivariable tras el ajuste por diferencias basales (razón de opotunidades, odds ratio, OR 0,90; i.c. del 95% 0,55-1,46, P = 0,659). Las tasas de complicaciones postoperarorias fueron similares en aquellos dados de alta antes o después del restablecimiento de la función intestinal (complicaciones menores: 34,7% versus 39,5%; complicaciones mayores 3,3% versus 3,4%; P = 0,110). CONCLUSIÓN: Dar de alta antes del restablecimiento de la función intestinal tras cirugía colorrectal electiva parece ser seguro en pacientes debidamente seleccionados.
Published: 2020
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42. Timing of nasogastric tube insertion and the risk of postoperative pneumonia: an international, prospective cohort study

Author: Glasbey J. C., Bibi S., Pata F., Ozkan B. B., Van Straten S., Hodson J., Chapman S. J., Blanco-Colino R., Pellino G., Sgro A., Soares A., van Elst T., Nepogodiev D., Borakati A., Bath M. F., Yasin I. H., Mclean K., Arthur T., Kovacevic M., Delibegovic S., Karamanliev M., Swamad M., Zebrak R., Paramasivam R., Martensen A., Larsen H. M., Radeker L., Frey P. E., Kechagias A., Venara A., Duchalais E., Ioannidis A., Pasquali S., Simioni A., Farina V., Podda M., Lorenzon L., ItSURG I., Schaeff V., Otto A., Jakubauskas M., van Elst T. R., Chu M., Fagan P. V. B., Wells C. I., Alagoa Joao A., Juloski J., Perez-Ajates S., Anabitarte Bautista O., El Kasmy Y., Espin-Basany E., Clerc D., Ciubotaru C., Popescu S., Yanishev A., Lee S., Yagiz Sen A., Aktas M. K., Baki B. E., Yuksek B., Kamarajah S., Khaw R. A., Mills E., Goodson R., Thakral N., Collaborative S., Ablett A. D., Adra M., Kwek I., Khan S. M., Quinn P., Manley L. R., Badran A., Ramjeeawon A., Campbell A., Tan H. L., Rye D. S., Rajaraman N., Norman J. G., Vutipongsatorn K., Solomou G., Akhbari M., Ali A., Murray V., Baker D. M., Brandao B. D., Stainer B., Thavayogan R., Jones D., Onafowokan O. O., Gharooni A., Dabab N., Carlton-Carew S., Kungwengwe G., Gabriel M., Sewart E., Shortland T. C., Lawday S., Pockney P., Dawson A., Brumfitt C. D., Stewart P., Ng B., Luong J. K., Ivanov V., Borisova A., Neykov V., Kuncarova K., Kolosova B., Antonova T., Farkasova M., Harbjerg J. L., Brandsborg S., Brinck S., Kjaer M. D., Mark-Christensen A., Unbehaun K. P., Dalsgaard P., Lycke K. D., LeNaoures P., Brigand C., Dumange E., Gout M., Moehwald C., Prem M., Alhalabi O., Sliwinski S., Krupp J., Gablenz E., Schmitzer L., Kopp A., Steinle J., Gsenger J., Pohl L. J., Riccardi M., Christodoulou I. M., Konstantinidis M., Machairas N., Zoikas A., Balalis D., Manatakis D. K., Aguilera M. L., Marano L., Fleres F., Lovisetto F., Sasia D., Segalini E., Pata G., Lucchi A., Sagnotta A., Campagnaro T., Petrelli F., Gallo G., Papandrea M., Testa V., Sinibaldi G., Di Candido F., Colombo F., Perrone G., Biancafarina A., Canonico G., Pagnanelli M., Curletti G., Bini R., de Manzoni Garberini A., Impellizzeri H., Cillara N., Tutino R., Picciariello A., Coletta D., Savino G., Ferrara F., Tamini N., Talamo G., Parini D., Giamundo P., lo Conte A., Pagano G., Ripetti V., Pesce A., Menduni N., Giudicissi R., Goldin E., Rega D., Belli A., Andriola V., Gordini L., Foppa C., Piccolo G., Birindelli A., Ferrari C., Ballarini Z., Tirelli F., Milone M., De Rosa M., Pipitone Federico N. S., Molteni B., Tilocca P. L., Sancini G., Piozzi G. N., Lauretta A., Poillucci G., Mulas S., Simcikas D., Portelli L., van Wijnbergen J. W. M., Dinger T. L., ten Doesschate S. F. H., van Dalen A. S. H. M., van den Bos D. D., Hansmann M., Medina Feliz J., Kuiper S. Z., Abdulrahman Z., Pruijssers S. R., Farik S., Elliott B. M., Geneta V. P., Wilton S., Kandelaki H., Peng S. L., Campbell S., Lim Y. K., Yassaie S. S., Murray M., Haran C., Tan J., Castro J., Laranjeira A., Catarino S., Neves-Marques C., Correia J. G., Vieira B. N., Quintela A. C., Serra M. L., Maciel J., Cunha M., Aparicio D. J., Neves J., Azevedo J., Romano M., Eiro F., Romano J., Monteiro C., Claro M., Almeida M. R., Peyroteo M., Machado N. D., Capote H., Ferreira M., Sousa X., Devesa H., Cavadas D., Guerreiro I., Costa M., Rosete M., Salman M., English C., Mohammed N., Litvin A., Cuk V. V., Meszarosova K., Jaich R., De Lima H., Brooks S., Marx M., Nshalati Salvation M., Garcia Cardo J., Mora-Guzman I., Sancho Muriel J., de Andres Olabarria U., Muriel P., Jimenez Vinas C., Alconchel F., Esteban Sinovas O., Gomez del Pulgar A., Fairen Oro C., Lopez Otero M., Figueroa Jimenez S., Claramonte Bellmunt O., Martinez Caballero J., Rubio-Perez I., Aguilar-Martinez M. M., Segura-Sampedro J. J., Olmedo Moreno C., Negre Parra D., Estevez Diz A. M., Martin-Balbuena R., Bustamante Recuenco C., Licardie Bolanos R. E., Fernandez P., Diaz Padillo A., Forero-Torres A., Alberdi San Roman I., Salvador Roses H., Merayo Alvarez M., Villarejo Campos P., Lopes Moreira C. C., Uriol Peralta P., Serrano Navidad M., Ripolles-Melchor J., Garcea A., Gomez Facundo H., Troncoso Pereira P., V Perez Guarinos C., Blaser B., Piazza G., Gagliardi B., Serin H., Yurdaor S. S., Arslan E., Kopac O., Uyanik A., Ozmen B. B., Tiftik E., Aksoy B., Yalcinkaya A., Ozoglu F., Kocer M. D., Bilicen G., Cinar E. N., Uslu O., Kaya Y., Demirci K., Wong J., Farhan-Alanie M. M. H., Suresh G., Asif A., Finch B. J., Bhahirathan Y., Herron J., Yi Tew Z., Obukofe R., Russell C., Suchett-Kay I., Netke T., Williams L., Kisiel A., Liu F. Y., Claireaux H., James P., Mondal A., Kalderon R., Nadama H. H., Al-Saraff Z., Tam J. P. H., Powell-Chandler A., Wood F., Gorgievska R., Ragavoodoo A., Thakrar C., Rojoa D., Palmer C., Davidson K., Giacci L., Hale J., Gan F. W., Makin-Taylor R., Hey C. Y., Toh C., Findlay J. M., Griffiths N., Ganesananthan S., Jasionowska S., Poustie M., Wong C., Turner T., Pyc W., Sloper W., Warner C., Coey J., Mason D., Sait S., Kowal M., Owen M., Saiyed A., Ashworth I., Akbari K., Curran M., Martin P., Parker D., Kwok K., Lye C., Ghaly M., Sammour T., Lewis D., Mundasad R., Wilkes A., Ctercteko G., Maslyankov S., Dimov R., Iliev S., Dimitrov D., Marek F., Orhalmi J., Skalicky P., Skalicky T., Chrz K., Christensen P., Worsoe J., Kristensen E. S., Emmertsen K. J., Loeve U. S., Mihaljevic A. L., Herrle F., Konstantinidis K. M., Korkolis D., Karanikas I., Vincenti L., Anania G., Borghi F., Agresta F., Maretto I., Parisi A., Bucci L., De Palma G., Guglielmi A., Cucinotta E., La Torre F., Cianchi F., Guerrieri M., Trompetto M., Persiani R., Micheletto G., Delrio P., Cantafio S., Ronconi M., Bisagni P. A. G., De Prizio M., Franceschi A., Galleano R., Cavallini M., Brescia A., D'Ambra L., Benevento A., Niolu P., Calgaro M., Colangelo E., Grottola T., Altomare D. F., Puleo S., Salamone G., Pietrabissa A., Poggioli G., Erdas E., Ottonello R., Tonini V., Selvaggi F., Sammarco G., Ceccarelli G., De Nisco C., Surgo D., Taglietti L., Ozolins A., Sivins A., Poskus T., Psaila J., Bemelman W. A., Graat L. J., Langenhoff B., Wijnhoven B. P. L., van de Ven A. H. W., Poelman M., Stassen L. P. S., Slooter G., Acherman Y. I. Z., Hoff C., Gerhards M. F., Stommel M. W. J., Hazebroek E. J., van Geloven A. A. W., Schasfoort R. A., van Leeuwen B. L., Tuynman J. B., van Tilburg M. W. A., Boerma E. G., Sharma P., Jenkins B., Bissett I. P., Herd A., Gordon A., Vernon D., Omundsen M., Ly J., Reddy A., Bonnet G., Harmston C., Morales M., Francisco V., Costa S., Manso A., Amorim E., Pereira J., Cardoso J., Ouro S., Caratao M., Nascimento C., Ribeiro da Silva B., Taranu V., Dias R., Mendes J., Allen M., Silva A., Carlos S., Barbosa E., Carneiro C., Ramos L., Lencastre L., Martins R., Silva-Vaz P., Ridgway P. F., McNamara D. A., Cahill R., Hogan A., Larkin J., O'Connell P. R., Negoi I., Abelevich A., Cuk V. M., Vician M., Ede C., Sardiwalla I., Mulira S., Montwedi D., Oyomno M., Sabia D., Portugal Porras V., Vigorita V., Sanz Ortega G., Garcia J., Espi Macias A., Blanco Antona F., Lujan Mompean J. A., Salvans Ruiz S., Villarejo-Campos P., Romero Simo M., Sanchez-Guillen L., Jimenez-Gomez L. M., Sanchez Lopez A., Golda T., Julia Bergkvist D., Nevado C., Noguera Aguilar J. F., cRicardo Felipe B., Septiem J., Rodriguez Sanchez A., Canete-Gomez J., Ruiz Montesinos I., Millan-Scheiding M., Prieto-Nieto I., Frasson M., Garcia Olmo D., Hubner M., Petermann D., Sauvain M. O., Ozben V., Gecim I. E., Disci E., Rencuzogullari A., Kurt A., Bisgin T., Pehlivan M., Isik A., Onur E., Leventoglu S., Haksal M. C., Erturk M. S., Keskin M., Guner A., Tutcu Sahin S., Ozbalci G. S., Pergel A., Albayrak D., Bruce D., Fearnhead N., Arthur J., Harron M., Beattie G., Titu L., Saunders M., Phillips J., Dindyal S., Cresswell B., Gercek Y., Lee J., Linn T., Faulkner G., Lockwood S., Rees J., Charalabopoulos A., Campbell B., Kontovounisios C., Amarnath T., Johnson M., Epanomeritakis E., Vigs S., Nastro P., Gilliam A., Smolarek S., Wilson T., Orbell J., McIntyre R., Agarwal T., Hainsworth P., Patel P., Vijay J., Liu B., Dhruva Rao P., Roxburgh C., Vipond M., Youssef H., Thorn C., Schizas A., Denley S., Bowley D., Das K., Cuming T., Saha A., Chung L., Pitt J., Davis P., Jones O., Taylor M., Bhargava A., Haji A., Watson N., Bloom I., Singh B., Norwood M., Gurjar S., Stylianides N., Mirza S., Evans M., Williams G., Patil P., Hernon J., Finch G., Green S., Chapple K., Fafemi O., Warusavitarne J., Samee A., Carden C., Ong L., Verma K., Joseph A., Rawat N., Pinkney T., Oke O., Glen P., Maxwell-Armstrong C., Oliphant R., Garner J., Moug S. J., Middleton S., Lund J. N., Smart N. J., Osborn G., Moore T., Raymond T., Knowles C. H., Hany T. S., Clarke R., Khera G., Brady R., Sellahewa C., Mason C., Torrance A., Lasithiotakis K., Knight J., Pullybank A., Ainsworth P., Reid F., Ramwell A., Maslekar S., George R., Skull A., Holtham S., Muhammad K., Lal R., Varcada M., Smith F. M., Howlader M., Defriend D., Kirk S., Richards T., Evans C., Borg C. M., Telford K., Sarfraz N., Busby K., Hollingshead J., Speake D., Pawa N., West D., Chadwick M., Komolafe O., Richardson S., Thornton M., Goede A., Osborne C., Bandyopadhyay D., Foong J., Lee Y. J., Liebenberg P., Mijalkov D., Wells A., Bull N., Ajmera A., Warburton T., Morgan S., Mahmoud A., Schachtel M., Mikhail B., Fomin I., Mekaeil B., Taylor N., Stevenson C., Drane A., Pahalawatta U., Lai L. T., Debiasio A., Jun H. J. S., Hengpoonthana R., Mendis D. M., Robb P. M., Lee H. J., Wyche A. A. B., Davis L. T., Chrimes A., Agarwal A., Zhao J., Williams S., Jayalath J. M. S. N., Khor S., Muddasani T., Childs S., Ridgway S., Blefari N. D. A., Tam H., Puchalski N., Ngai C., Mackenzie J., Johnson N., Holmes M., Zuzek R., Saluja T., Gould T., Goh Y. K., Selvaraj T., Beh Y. Z., Dudi-Venkata N. N., Horne D., Borrow J. L., Campbell C., Cousins G., Jackson L., Maheepala K., Zhao S., Holden E., Tutt L., Thompson B., Collins H., Louie F., Buckland B., Smith D., Chong C., Chua T. H., Nayak C., Redmond J., Tan R. R., Gramlick M., Teh J. S., Ng S. Y., Britten-Jones P., Mohd Rosli R., Pham H. D. V., Jegathees T., Coulter-Nile S. M. C. J., Gosselink M. P., Wang Y. L., Maciaszek M., Chrapko P. S., Nair A., Thirugnanasundralingam V., Muir K., Salibasic M., Pavlov V., Paycheva T., Lyulenina E., Kolev N., Nguen D., Mitkov Y., Mitkov E., Vladova P., Dimitrov V., Hussain M., Gabarski A., Ivanov T., Yotsov T., Ilieva I., Akisheva A., Shoshkova M., Nawaz E., Feradova H., Mladenov T., Jozaf V., Klail T., Pos M., Adel A., Sotona O., Bartos M., Amjad T., Maly O., Berec S., Hanusova M., Hurny M., Risko J., Ludvik M., Stercz M., Treskon R., Pospisil M., Hlavacova L., Tomanova D., Chodora S., Houdek O., Novicky R., Sobotkova K., Cha S., Suta Kimle K., Jirankova K., Bujda M., Paclik A., Trap A., Jurgens-Lahnstein J., Storm M., Damgaard I., Olawi F., Ehlern F., Raos M., Kristensen F. P., Bonnerup K., Amiri S., Enevoldsen M., Hojgaard Pedersen J., Jepsen B. N., Hillgaard T. K., Erichsen S. B., Nielsen C. V., Madsen C. P., Bjerke J., Skejo C. D., Aabling R. R., Sorensen J. S., Turunen A., Katunin J., Niskakangas M., Vignaud T., Frey S., Ricolleau C., Chanut F., Magnin J., Seiboldt T., Beck L., Zamzow K., Betge F., Poncelet A., Truant M., Hauschild H., Neugebauer N., Schoning L., CS Simon S., Galata C., Karampinis I., Thawel T., Seckler A. M., Kerem C., Durdevic S., Antonakopoulos F., Mathioulaki A., Chrysoheris P., Athanasopoulos P. G., Kalles V., Spyrou I., Barkolias C., Paspala A., Papaconstantinou D., Spartalis E., Arkadopoulos N., Prodromidou A., Garoufalia Z., Mendez D., Rosales J., Flores M., Garcia M., Garcia A., Noriega Z., Torselli D., Rodriguez J., Lafranceschina S., Artioli E., Giaccari S., Nevoso V., Schimera A., Marino S., Geretto P., Pellegrino L., Borghi B., Marano A., Corino C., Cannata G., Giuffrida M. C., Landra F., Ongaro D., Baronio G., Raimondo S., Casiraghi S., Salvadori R., Finotti E., Ciccioli E., Galgano A., Zuin M., Bettella A., Barina A., Vendramin E., Palano G., Schiavone D., Di Cintio A., Gemini A., Trastulli S., De Luca M., Desiderio J., Gubbiotti F., Cigognini M., Zaffaroni G., Maffioli A., Colombo S., Bondurri A., Sampietro G., Foschi D., Manigrasso M., Danzi M., Amato R., Anastasio L., Mastella F., Basile R., Peltrini R., Marra E., Luglio G., Giglio M., Anoldo P., Vertaldi S., Grimaldi L., Tammaro N., Pedrazzani C., Turri G., Lazzarini E., Conti C., Vulcano I., Bertilone E., Pintabona G., Viscosi F., Cerasari S., Galiffa G., Lapolla P., Del Basso C., Cirillo B., De Toma G., Fazzi K., Bini S., Coratti F., Montanelli P., Grandi S., Nelli T., Ben Khaled N., Cammelli F., Ferrini E., Billo M. E., Marrosu A. G., Scognamillo F., Pala C., Attene F., Carboni L., Ruggiu M. W., Gabbas G., Marziali I., Mazzocato S., Vergari R., Piazzai F., Kubolli I., Aggiusti A., Paolucci A., Ortenzi M., Olivieri M., Belluco C., Antona A. D., Basso S., Morino M., Mistrangelo M., Clerico G., De Santi G., Bitonti M. F., Frattalone M., Fico V., Santullo F., Belia F., Spinelli A., Marco M., Bevilacqua M., Tringali D., Bevilacqua E., Panizzo V., La Manna V., Migliore G., Aversano A., Fares Bucci A., Marino F., Carbone F., Incollingo P., Romano F. M., Zalla T., Baraghini M., Romoli L., Calussi M., Vellei S., Genzano C., Feroci F., Vita M., Barberis A., Serra D., Grassia M., Romelli M., Ruggiero S., Percassi A., Magri Piccinini A., Monti M., Magnoli M., Romano S., Gaetano P., Pilotta F., Baldassarre L., Bonati E., Aresu S., Saba A., Moretto G., Bacchion M., Casaril A., Inama M., Creciun M., Stella M., Gobatti D., Angelini M., Andolfi E., Miranda E., Scricciolo M., Provenza G., Cavallina G., Frezza B., Fontani A., Malatesti R., Pellicano G. A., Anania M., Pulighe F., Cruccu A., Murru M. L., Massaiu C., Balestra F., Pazzona M., Giannella A., Santangelo M., Frangella F., Magagnano D., Liberatore P., Brenna R., Giani A., Tirotta F., Famularo S., Angrisani M., Ceresoli M., Rondelli F., Angelucci G. P., Scaramuzzo R., Larcinese A., Fioriti C., Picone E., Nardi M., Castagnoli G., Bartoli A., Bellochi R., Spaziani A., Conti D., Poponesi V., Trippetti M., Amicucci S., Tazza G., Procacci P., Giovannini F., Basile E., Caristo G., De Nardi P., Rosati R., Marcocci G., Vignali A., Malerba M., Percivale A., Ghazouani O., Reggiani L., Spirito C., Moschetta G., Cosmi F., Romeo G., Gasparrini M., Sucameli F., Gennai A., Moggia E., Bianchi C., Bonfante P., Macina S., Feleppa C., Imperatore M., Tenconi S. M., Rausei S., Maioli D., Marchionini V., Sparta C., Mura F. A., Barmina M., Lorettu A., Rettaroli C., Mastino G., Ruggiu G. V., Mura G. A., Perrone B. A., De Angelis M., Mereu A., Adamo V., Bianco C., Ricciardiello M., Campanaro C., Panaccio P., Esposito L. M., D'Ascanio F., Pietroletti R., Chetta N., Aquilino F., Di Marco F., Amico A., Schembari E., Puglisi S., Licari L., Campanella S., Profita G., Falco N., Rotolo G., Venturelli P., De Marco P., Marciano M., Argenti F., Milani M. S., Malabarba S., Giambartolomei G., Vella I., Gronchi F., Ruggieri A., Roggiani A., Balsamo F., Gori A., Cuicchi D., D'Alessio R., Benvenuto D., Podda F., Cappellacci F., Salaris C., Sanna S., Marcialis J., Mosino L., Peddis M., Melis S., De Donno G., Aru A. C., Falsetti E., Lanari J., D'Errico U., Bianchini S., Figa F., Caiazzo A., Selvaggi L., Capozzolo A., Cerra C., Pirillo M., Cravano S., Libri I., Laquatra N., Isabello A., Truskovs A., Bartnick A., Malcevs E., Machatschek M. J., Alm J., Lapsa S., Delorme M., Zeynalov F., Larnovskis J., Sauka J., Bodrov D., Gailumsis R., Wiemann A. M., Muller N. 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C. H., Leow T. Y. S., Penningnieuwland G., de Ruiter A., Ribbers T., Aarts C. A. M., Tulek M. S., de Jonge J., Kocak S., Alqethami H. J., Constansia R., van Elst P. C., Tissink M. W., Gruter A., Vroom Y., Voeten D. M., Feenstra T., Azzahhafi J., Bofarid S., Kip M., Saleh W., Franssen S., Boon C. L., Franssen R. J. M., Romaen I., Jense M. T. F., D'Souza J., Pascoe R., Scott A., Stark E., Mulholland K., Lau W. K., Smith B., Adams S. I. B., Shah N., Ling E., Young J., Jacobson A., Macfater H., Chen S. Y., Kilpatrick K., Kim D. H., Dixon S., Yassaie S., Welman D., Coulter J., Morreau M., Li E., Rankin A., Winders J., Skipworth C., Stanfield B., Henderson N., Chuang A., Maskill L., Ker H., McLaughlin S. J. P., Kearney J., Sprosen H., Kerckhoffs P., Alsadat R., Cherry R., Chapman D. A., Singh N., Clucas A., Gatenby G., Kelly B., Ruppeldt P., McIntosh N. D., Koh S., Wilms H., Dalzell F., Tewhaiti-Smith J., Kader T., Yam S. 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J., Navarro Barrios A., Rodriguez Pedreno L., Garcia Moreno P., Garcia Gomez M., Rodrigues K., Platero Diago J., Veras Lista M., Rifa Terricabras S., Butler Sanz L., Alberch Camprubi E., Rico Ferrandez M., Puig Lao E., De Pablo Miro M., Alberca-Paramo A., Alia Verdejo T., Canete-Manzanares J., Molina-Florez M., Garcia Hernandez L. C., Orozco Nunez S., Suarez-Sanchez M., Martin-Fernandez J., Soriano Liebana M. M., Campo Betancourth C. F., Sevila Mico S., Fernandez A., Curtis C., Bosch M., Triguero D., Bosch Ramirez M., Ramayo Diaz N., Gonzalez Caraballo I., Pascual Vicente T., Orue-Echebarria M. I., Sanchez-Calvo L., Wang D., Trueba-Collado C., Morales Bernaldo de Quiros J. T., Lima Pinto F., Nunez OSullivan S., Ramos Jimenez F. A., Perez Ortega A., Trujillo Barbadillo A., Romero Pujana E., Fernandez Illera M. V., De La Llave Serralvo A., Mestres N., Cuello E., Merichal M., Sierra J. E., Escoll J., Rufas M., Pinillos A. I., Ortega J., Vivas Angeles P., Vives Figueras R., Baena Sanfeliu E., Campillo Alonso B., Alberich Prats M., Duran Arrocha J., Cornella Garceso N., Uribe Galeano C., Delisau Puig O., Castro A., Codony Bassols C., Fernandes N., Garcia Adamez J., Caula Freixa C., Sanchez M. J., Martin-Borregon P., Quevedo A., Martinez J., Marin J. M., Rodriguez P., Garcia Orozco J. J., Ferrusola Diaz D. A., Garcia Jimenez M. L., Castro Diez L., Mosquera Fernandez C., Alonso Batanero E., Cifrian Canales I., Calzada M. G., Recuenco C. B., Martin M. C., Esteban Avendano I., Jimenez Relimpio C., Lancho Lavilla P., Blanco Bartolome I., Gomez Cano I., Blasco Andres C., Alonso-Poza A., Dieguez B., Losada M., Gilsanz C., Garcia-Vico A., Roman-Rando A., Sanchez-Galvez M. A., Bersabe-Alonso I. M., Vadillo-Bohorquez A., Gutierrez Rios R. D., Eizaguirre Ubegun M., Novo Sukia I., Uribe Isado M., Ibanez Alda M., Pastor Idoate C., Abad-Motos A., Marinez-Hurtado E., Salvachua-Fernandez R., Padilla Zegarra E. D., Franco M., Martinez A., Ramos Martin P., Mate Mate P., Marcano Chavez C., Ayllon H., Jeri-McFarlane S., Soldevila-Verdeguer C., Pineno-Flores C., Ambrona-Zafra D., Fernandez-Vega L., Gil-Catalan A., Craus-Miguel A., Pujol-Cano N., Sena-Ruiz F., Gomez Jurado M. J., Alberti Delgado P., Bordanova Reverter A., Belzunce-Capo J. F., Verdaguer Tremolosa M., Lin Q., Muniesa C., Avelino L., Cholewa H., Sancho-Muriel J., Navasquillo M., Navio A., Abello D., De Jesus M., Alvarez E., Garcia J. M., Gil A., Giordano H. E., Mignon G., Vanoni A., Henkens A., Jarrar G., Odovic M., Willemin M., Milliet O., Hahnloser D., Demartines N., Teixeira H., Pittet O., Haller M. L., Huot A., Kefleyesus A., Bugmann A., Piotet L. M., Meijers L., Kurtoglu G. K., Sel E. K., Isler V. C., Yilmaz B. S., Adiyaman C., Kara M., Demirkaya H. C., Korkmaz H. K., Pektas A. M., Guner B., Islek E. C., Tombul H. B., Boztug C. Y., Tinaz A., Yilmaz M., Karaman Y., Akin F. A., Dansuk S., Bascavus M., Kaya M., Kutlu B., Seker M. 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H., Alawattegama H., Seite E., Barrett A., Riordan E., Lam W., Dowdeswell M., Mulvenna C., Awokoya O., Gurowich L., Dhera K., Hayat S., Tincknell L., Spazzapan M., Teeling F., Sysum K., Latter J., Latter M., Khan S., Guruswamy M., Beedham W., Brazier E., Elghobashy M., Bajaj M., Mann H., Etel E., Woodmass M., Hayden H., Ali Y., Husain S., Arnold A., Pedersen A. C., Cunha P., Ahmed M., Al Zawawi S., Kudva V., Theodoropoulou K., Miscampbell M., Robinson A. V., Johnston J., Dharni A., Lamb S., Westerman T., Evans E., Campbell L., Gillespie M., Cheong C. M., Kulathevanayagam K., Varghese A., Ike S. I., Chu T. S. M., Baljer B., Mogg J. A. W., Rai P., Claireaux H. A., Williams M., Smillie R., Goetz J., Appleby E., Fadipe T., Vaughan-Burleigh S., Puri G., Hussain P., Flather R., Cutler A., Pathak S., Sheldon J., Collicott T., al-Ausi M., Jovaisaite A., Shah S. M., Khalid N., Gutmann D., Davison S., Alame Y. J., Syed L., Owen W. J., Ahsan S. D., Anthony-Uzoeto U., Macleod Hall C., Zheng S., Wynter K., James C., Sapre D., Ghosh R., Baird J., Cockburn L., Blackwood O., Simpson W., Jeong S., Bishop S., Bate R., Hobson C., Adam A. H., Redclift C., Do J., Adeleye O., Poli F., Batterham A., Brown S., Parekh J. N., Clay W., Pieri K., Jackson A., Saxena A., Gurung B., Oyebola T., O'Brien F., Djeugam B., Gardezi S., Ul-Hasan S., Martin-Hernandez M. P., Sisley M., Modi S., Antakia R., Elbayouk A., Soh Y. J., Mather J., Yusuf Z., Al-Sarraf Z., Naja M., Rassool S. B., Convill J., Nikookam Y., Warsame A., Pace C., Kiandee M., Ridwan R., Carey C., Hirri F., McMillan M. J. A., Ling J. J., Pendelbury L., Kerimzade K., Tang A., Howard E. O., Humayun S., Wadsworth O. J., Tan K., Abdelhameed F., Haglund C., Radnaeva I., Hu N., Rambhatla S., Waldron D., Madahar P., Malik S., Meney L. C., Ibrahim I., Kang C. K., Chiu J. Z. J., Livie V., Ibrahim B., Khalil M., Pooley G., Shishkin B., Docherty J., Southgate A., Coomes A., McGee F., Flanagan S., Tan Q. J., Anwar H., Clough R., Chrisp B., Cassels J., Cross G. W. V., Mercer L., Mercer C., Refalo A., Hadley R., McTighe A., Farrow F., Brodie A., Davis G., Shah D. R., Bowers C., Patel S., Morice O., Burzic A., Cheung J., Shashidhara A., Theodoraki G., Birk J., Ong A., Ng M. P. E., Wong R. T. W., Maese S., Yeap B., Iqbal Z., Rojoa D. M., Cabaleiro Barciela C., Ruddy C. M., Lindwe S., Qamar Y., Chuita S., Melaugh T., Hall J. D., Kouli O., Hassane A. S. I., Azhar A. W., Tan T. K., Perchard W., Scurr T., Campbell E., Kelk L., Ghosh A., Gibbins A., Mala D., Loizidou A., Hall O., Mecia L., Hew C., Varathan K., Tong L., Chandrasekar B., Buchanan E., O'Connell M., Kwak S. Y., Ong E. H., Gardner S., Lim J., Maden C., Illahi M., Xuan Tan Z., Stahl R., Stahl J., Hickman A., Collett D., Goolam-Mahomed Z., Allen B., Atiyah A., Ahmad H., Jones J., McGregor O., Ogundiya E., Boulbadaoui A., Kirnon-Jackman O., Lim Q. X., Peckham H., Yeoh T., Yong S. Q., Chen J. Y., Siva S., Sam Z. H., Gilani M., Goh Y. N., Muthukumar M. G., Phillips S., Tjoakarfa J., Giri A., Suresan S., Thomas P., Johnson T. A., Williams R. I., Rashid A., Kushairi A., Rais A., James A., Bugelli M., Chechelnitskaya Y., Sandhu N., Tandon R., Gray M., Kumar A., Ciurleo C., Nyamali I., Hiremath S., Sinha S., Chowdhary M., Bradley E., McTiernan M., Macdonald S., Sharkey S., McLaughlin N., Amey C., Kraria L., Skan O., Kind C., Tupper P., Van Rhee C., Honeyman S. I., Menon G., Jegatheeswaran L., Madhavan A., Warne M., Malcolm F. L., Lessware T., Wilkerson H. T., Chatterjee-Woolman S., Yoong A., Ahmed W. U. R., Longshaw A., Flannery O., Green R., Leaning M., Cragg J., Sharriff H., Doherty C., Kwan K. W. L., Sanders-Crook L., Bhatia S., Eames S., Lewis F., Kirupananthan P., Boh Z. Y., Dass S., Soma A., Newton A., Hill M., Shafiq Y., Brkljac M., Boyce L., English W. J., Lam S., Chipeta C., Jain C., Garofalidou T., Novotny S. A., Locke S., Bowman C., Begaj A., Murphy C., Radcliffe K., Chong J. T., Jeffrey E., Chaudhury N., Rajendran K., Akbar Z., Walters B., Kulendrarajah B., Tran N., Shrestha S., Parmar S., Gallagher C., Hennessy L., Pentti E., Badhrinarayanan S., Fung A., Mansoor M., Kenny R., Kan P., Lee D. E., Khosla S., Samake M., Shaban F., Aftab R., Gough M., Woodburn B., Vayalapra S., McMurrugh K., Jimulia D., Deol S., Pike S., Embury-Young Y., Patel M., Kilgallon E., Keating R., Walsh A., Khan H., Logue G., Orekoya M., Alasmar M., Charalambides M., Clave Llavall A., Williamson E., Bharwada Y., Zearmal S., Evans H., Panikkar M., de la Cruz G., Caplan J., Ruparelia A., Tanvir T., Soare C., Pang Y. L., Trotter J., Zaidi A., Thakrar V., Pulickal P., Ahmed H., Parnell J., Lennock S., Ford V., Brignall R., O'Neill D., Hanna R., Kane R., Nicola M., Rajput K., Xiao Y., Michael S., Wright E., Juniper S., Thompson E., Hoskyns L., Kanitkar A., Ross C., Unsworth A., Rshaidat H., Demarre K., Chiang A., Bareh A., van Dellen J., Faqihinejad C., Gadhvi A., Grant R., Lewsey J., Morris A., Martin H., McClarty C., Sanyal S., Alsaif A., Palkhi A., Bhopal S., Vishnu K S., Papanikolaou A., Mitra A., Nur A., Ali F., Burford C., Huq T., Irwin E., Matthews L., Ngu W. S., Hosfield T., Muneeb F., Page O., Zeb E., Al-Azzawi A., McIntosh J., Vucicevic A., Hughes M., Brooks L., Fanibi B., Dixon M., Njoku P., Morris D., Jobson J., Chowdhury H., Alawode D. O. T., Wynell-Mayow W., Udayachandran V., Alsoof D., Ekert J., Joseph N., Zulkefley N., Hunt G., Christodoulou T., Wright O., Soman S., Jamal M., Beqiri S., Borgas P., Christie S., Pereira F., Browne S., Yiu J., Dworkin A., Brayley J., Palmer A., Charalambos M., Jones C. S., Toner S., Cowden R., Lee L., Nicol P., Holman O., Imtiaz M., Albert V., Leung S. P., Erotocritou M., Stroud R., Wilkin R., Thomson W., Mackee L., G N., Bei Y., Mckenna Favier S., Ibrahim A., Kler A., Reynolds L., Mohamed S. H., Majeed Y., Fakim B., Jones A., Liversedge G., Carrington Z., Windebank J., Izzarina A., Akbani U., Craven J., Aldarragi A., Harding S., Millward A., Bedford M., Gopalan V., Midgen A., Khadka P., Cheng O., Taneja S., Manobharath N., Kok J. Y., Lim D. W. E., Buick T., Boland M., Piya S., Devlin R., Fairfield C. J., George R. J., Rahi M., Zaman S., Hajiev S., Ross T., Crisp E., Thompson C., Charalambous A., Hollywood J. L., Hammond R. F. 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A., Ntakomyti E., Diallo R., Bylinski T., Wright J., Masiha E., Tung J., Shirazi B., Neilson A., Epton S., Patel N., Trussell S., Couldrey A., Donnelly C., Eftychiou S., Glasbey J.C., Bibi S., Pata F., Ozkan B.B., Van Straten S., Hodson J., Chapman S.J., Blanco-Colino R., Pellino G., Sgro A., Soares A., van Elst T., Nepogodiev D., Borakati A., Bath M.F., Yasin I.H., Mclean K., Arthur T., Kovacevic M., Delibegovic S., Karamanliev M., Swamad M., Zebrak R., Paramasivam R., Martensen A., Larsen H.M., Radeker L., Frey P.E., Kechagias A., Venara A., Duchalais E., Ioannidis A., Pasquali S., Simioni A., Farina V., Podda M., Lorenzon L., ItSURG I., Schaeff V., Otto A., Jakubauskas M., van Elst T.R., Chu M., Fagan P.V.B., Wells C.I., Alagoa Joao A., Juloski J., Perez-Ajates S., Anabitarte Bautista O., El Kasmy Y., Espin-Basany E., Clerc D., Ciubotaru C., Popescu S., Yanishev A., Lee S., Yagiz Sen A., Aktas M.K., Baki B.E., Yuksek B., Kamarajah S., Khaw R.A., Mills E., Goodson R., Thakral N., 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Fleres F., Lovisetto F., Sasia D., Segalini E., Pata G., Lucchi A., Sagnotta A., Campagnaro T., Petrelli F., Gallo G., Papandrea M., Testa V., Sinibaldi G., Di Candido F., Colombo F., Perrone G., Biancafarina A., Canonico G., Pagnanelli M., Curletti G., Bini R., de Manzoni Garberini A., Impellizzeri H., Cillara N., Tutino R., Picciariello A., Coletta D., Savino G., Ferrara F., Tamini N., Talamo G., Parini D., Giamundo P., lo Conte A., Pagano G., Ripetti V., Pesce A., Menduni N., Giudicissi R., Goldin E., Rega D., Belli A., Andriola V., Gordini L., Foppa C., Piccolo G., Birindelli A., Ferrari C., Ballarini Z., Tirelli F., Milone M., De Rosa M., Pipitone Federico N.S., Molteni B., Tilocca P.L., Sancini G., Piozzi G.N., Lauretta A., Poillucci G., Mulas S., Simcikas D., Portelli L., van Wijnbergen J.W.M., Dinger T.L., ten Doesschate S.F.H., van Dalen A.S.H.M., van den Bos D.D., Hansmann M., Medina Feliz J., Kuiper S.Z., Abdulrahman Z., Pruijssers S.R., Farik S., Elliott B.M., Geneta V.P., Wilton S., Kandelaki H., Peng S.L., Campbell S., Lim Y.K., Yassaie S.S., Murray M., Haran C., Tan J., Castro J., Laranjeira A., Catarino S., Neves-Marques C., Correia J.G., Vieira B.N., Quintela A.C., Serra M.L., Maciel J., Cunha M., Aparicio D.J., Neves J., Azevedo J., Romano M., Eiro F., Romano J., Monteiro C., Claro M., Almeida M.R., Peyroteo M., Machado N.D., Capote H., Ferreira M., Sousa X., Devesa H., Cavadas D., Guerreiro I., Costa M., Rosete M., Salman M., English C., Mohammed N., Litvin A., Cuk V.V., Meszarosova K., Jaich R., De Lima H., Brooks S., Marx M., Nshalati Salvation M., Garcia Cardo J., Mora-Guzman I., Sancho Muriel J., de Andres Olabarria U., Muriel P., Jimenez Vinas C., Alconchel F., Esteban Sinovas O., Gomez del Pulgar A., Fairen Oro C., Lopez Otero M., Figueroa Jimenez S., Claramonte Bellmunt O., Martinez Caballero J., Rubio-Perez I., Aguilar-Martinez M.M., Segura-Sampedro J.J., Olmedo Moreno C., Negre Parra D., Estevez Diz A.M., Martin-Balbuena R., Bustamante Recuenco C., Licardie Bolanos R.E., Fernandez P., Diaz Padillo A., Forero-Torres A., Alberdi San Roman I., Salvador Roses H., Merayo Alvarez M., Villarejo Campos P., Lopes Moreira C.C., Uriol Peralta P., Serrano Navidad M., Ripolles-Melchor J., Garcea A., Gomez Facundo H., Troncoso Pereira P., V Perez Guarinos C., Blaser B., Piazza G., Gagliardi B., Serin H., Yurdaor S.S., Arslan E., Kopac O., Uyanik A., Ozmen B.B., Tiftik E., Aksoy B., Yalcinkaya A., Ozoglu F., Kocer M.D., Bilicen G., Cinar E.N., Uslu O., Kaya Y., Demirci K., Wong J., Farhan-Alanie M.M.H., Suresh G., Asif A., Finch B.J., Bhahirathan Y., Herron J., Yi Tew Z., Obukofe R., Russell C., Suchett-Kay I., Netke T., Williams L., Kisiel A., Liu F.Y., Claireaux H., James P., Mondal A., Kalderon R., Nadama H.H., Al-Saraff Z., Tam J.P.H., Powell-Chandler A., Wood F., Gorgievska R., Ragavoodoo A., Thakrar C., Rojoa D., Palmer C., Davidson K., Giacci L., Hale J., Gan F.W., Makin-Taylor R., Hey C.Y., Toh C., Findlay J.M., Griffiths N., Ganesananthan S., Jasionowska S., Poustie M., Wong C., Turner T., Pyc W., Sloper W., Warner C., Coey J., Mason D., Sait S., Kowal M., Owen M., Saiyed A., Ashworth I., Akbari K., Curran M., Martin P., Parker D., Kwok K., Lye C., Ghaly M., Sammour T., Lewis D., Mundasad R., Wilkes A., Ctercteko G., Maslyankov S., Dimov R., Iliev S., Dimitrov D., Marek F., Orhalmi J., Skalicky P., Skalicky T., Chrz K., Christensen P., Worsoe J., Kristensen E.S., Emmertsen K.J., Loeve U.S., Mihaljevic A.L., Herrle F., Konstantinidis K.M., Korkolis D., Karanikas I., Vincenti L., Anania G., Borghi F., Agresta F., Maretto I., Parisi A., Bucci L., De Palma G., Guglielmi A., Cucinotta E., La Torre F., Cianchi F., Guerrieri M., Trompetto M., Persiani R., Micheletto G., Delrio P., Cantafio S., Ronconi M., Bisagni P.A.G., De Prizio M., Franceschi A., Galleano R., Cavallini M., Brescia A., D'Ambra L., Benevento A., Niolu P., Calgaro M., Colangelo E., Grottola T., Altomare D.F., Puleo S., Salamone G., Pietrabissa A., Poggioli G., Erdas E., Ottonello R., Tonini V., Selvaggi F., Sammarco G., Ceccarelli G., De Nisco C., Surgo D., Taglietti L., Ozolins A., Sivins A., Poskus T., Psaila J., Bemelman W.A., Graat L.J., Langenhoff B., Wijnhoven B.P.L., van de Ven A.H.W., Poelman M., Stassen L.P.S., Slooter G., Acherman Y.I.Z., Hoff C., Gerhards M.F., Stommel M.W.J., Hazebroek E.J., van Geloven A.A.W., Schasfoort R.A., van Leeuwen B.L., Tuynman J.B., van Tilburg M.W.A., Boerma E.G., Sharma P., Jenkins B., Bissett I.P., Herd A., Gordon A., Vernon D., Omundsen M., Ly J., Reddy A., Bonnet G., Harmston C., Morales M., Francisco V., Costa S., Manso A., Amorim E., Pereira J., Cardoso J., Ouro S., Caratao M., Nascimento C., Ribeiro da Silva B., Taranu V., Dias R., Mendes J., Allen M., Silva A., Carlos S., Barbosa E., Carneiro C., Ramos L., Lencastre L., Martins R., Silva-Vaz P., Ridgway P.F., McNamara D.A., Cahill R., Hogan A., Larkin J., O'Connell P.R., Negoi I., Abelevich A., Cuk V.M., Vician M., Ede C., Sardiwalla I., Mulira S., Montwedi D., Oyomno M., Sabia D., Portugal Porras V., Vigorita V., Sanz Ortega G., Garcia J., Espi Macias A., Blanco Antona F., Lujan Mompean J.A., Salvans Ruiz S., Villarejo-Campos P., Romero Simo M., Sanchez-Guillen L., Jimenez-Gomez L.M., Sanchez Lopez A., Golda T., Julia Bergkvist D., Nevado C., Noguera Aguilar J.F., cRicardo Felipe B., Septiem J., Rodriguez Sanchez A., Canete-Gomez J., Ruiz Montesinos I., Millan-Scheiding M., Prieto-Nieto I., Frasson M., Garcia Olmo D., Hubner M., Petermann D., Sauvain M.O., Ozben V., Gecim I.E., Disci E., Rencuzogullari A., Kurt A., Bisgin T., Pehlivan M., Isik A., Onur E., Leventoglu S., Haksal M.C., Erturk M.S., Keskin M., Guner A., Tutcu Sahin S., Ozbalci G.S., Pergel A., Albayrak D., Bruce D., Fearnhead N., Arthur J., Harron M., Beattie G., Titu L., Saunders M., Phillips J., Dindyal S., Cresswell B., Gercek Y., Lee J., Linn T., Faulkner G., Lockwood S., Rees J., Charalabopoulos A., Campbell B., Kontovounisios 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Thompson B., Collins H., Louie F., Buckland B., Smith D., Chong C., Chua T.H., Nayak C., Redmond J., Tan R.R., Gramlick M., Teh J.S., Ng S.Y., Britten-Jones P., Mohd Rosli R., Pham H.D.V., Jegathees T., Coulter-Nile S.M.C.J., Gosselink M.P., Wang Y.L., Maciaszek M., Chrapko P.S., Nair A., Thirugnanasundralingam V., Muir K., Salibasic M., Pavlov V., Paycheva T., Lyulenina E., Kolev N., Nguen D., Mitkov Y., Mitkov E., Vladova P., Dimitrov V., Hussain M., Gabarski A., Ivanov T., Yotsov T., Ilieva I., Akisheva A., Shoshkova M., Nawaz E., Feradova H., Mladenov T., Jozaf V., Klail T., Pos M., Adel A., Sotona O., Bartos M., Amjad T., Maly O., Berec S., Hanusova M., Hurny M., Risko J., Ludvik M., Stercz M., Treskon R., Pospisil M., Hlavacova L., Tomanova D., Chodora S., Houdek O., Novicky R., Sobotkova K., Cha S., Suta Kimle K., Jirankova K., Bujda M., Paclik A., Trap A., Jurgens-Lahnstein J., Storm M., Damgaard I., Olawi F., Ehlern F., Raos M., Kristensen F.P., Bonnerup K., Amiri S., Enevoldsen M., Hojgaard Pedersen J., Jepsen B.N., Hillgaard T.K., Erichsen S.B., Nielsen C.V., Madsen C.P., Bjerke J., Skejo C.D., Aabling R.R., Sorensen J.S., Turunen A., Katunin J., Niskakangas M., Vignaud T., Frey S., Ricolleau C., Chanut F., Magnin J., Seiboldt T., Beck L., Zamzow K., Betge F., Poncelet A., Truant M., Hauschild H., Neugebauer N., Schoning L., CS Simon S., Galata C., Karampinis I., Thawel T., Seckler A.M., Kerem C., Durdevic S., Antonakopoulos F., Mathioulaki A., Chrysoheris P., Athanasopoulos P.G., Kalles V., Spyrou I., Barkolias C., Paspala A., Papaconstantinou D., Spartalis E., Arkadopoulos N., Prodromidou A., Garoufalia Z., Mendez D., Rosales J., Flores M., Garcia M., Garcia A., Noriega Z., Torselli D., Rodriguez J., Lafranceschina S., Artioli E., Giaccari S., Nevoso V., Schimera A., Marino S., Geretto P., Pellegrino L., Borghi B., Marano A., Corino C., Cannata G., Giuffrida M.C., Landra F., Ongaro D., Baronio G., Raimondo S., Casiraghi S., Salvadori R., Finotti 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Clerico G., De Santi G., Bitonti M.F., Frattalone M., Fico V., Santullo F., Belia F., Spinelli A., Marco M., Bevilacqua M., Tringali D., Bevilacqua E., Panizzo V., La Manna V., Migliore G., Aversano A., Fares Bucci A., Marino F., Carbone F., Incollingo P., Romano F.M., Zalla T., Baraghini M., Romoli L., Calussi M., Vellei S., Genzano C., Feroci F., Vita M., Barberis A., Serra D., Grassia M., Romelli M., Ruggiero S., Percassi A., Magri Piccinini A., Monti M., Magnoli M., Romano S., Gaetano P., Pilotta F., Baldassarre L., Bonati E., Aresu S., Saba A., Moretto G., Bacchion M., Casaril A., Inama M., Creciun M., Stella M., Gobatti D., Angelini M., Andolfi E., Miranda E., Scricciolo M., Provenza G., Cavallina G., Frezza B., Fontani A., Malatesti R., Pellicano G.A., Anania M., Pulighe F., Cruccu A., Murru M.L., Massaiu C., Balestra F., Pazzona M., Giannella A., Santangelo M., Frangella F., Magagnano D., Liberatore P., Brenna R., Giani A., Tirotta F., Famularo S., Angrisani M., Ceresoli M., Rondelli F., Angelucci G.P., Scaramuzzo R., Larcinese A., Fioriti C., Picone E., Nardi M., Castagnoli G., Bartoli A., Bellochi R., Spaziani A., Conti D., Poponesi V., Trippetti M., Amicucci S., Tazza G., Procacci P., Giovannini F., Basile E., Caristo G., De Nardi P., Rosati R., Marcocci G., Vignali A., Malerba M., Percivale A., Ghazouani O., Reggiani L., Spirito C., Moschetta G., Cosmi F., Romeo G., Gasparrini M., Sucameli F., Gennai A., Moggia E., Bianchi C., Bonfante P., Macina S., Feleppa C., Imperatore M., Tenconi S.M., Rausei S., Maioli D., Marchionini V., Sparta C., Mura F.A., Barmina M., Lorettu A., Rettaroli C., Mastino G., Ruggiu G.V., Mura G.A., Perrone B.A., De Angelis M., Mereu A., Adamo V., Bianco C., Ricciardiello M., Campanaro C., Panaccio P., Esposito L.M., D'Ascanio F., Pietroletti R., Chetta N., Aquilino F., Di Marco F., Amico A., Schembari E., Puglisi S., Licari L., Campanella S., Profita G., Falco N., Rotolo G., Venturelli P., De Marco P., Marciano M., Argenti F., Milani M.S., Malabarba S., Giambartolomei G., Vella I., Gronchi F., Ruggieri A., Roggiani A., Balsamo F., Gori A., Cuicchi D., D'Alessio R., Benvenuto D., Podda F., Cappellacci F., Salaris C., Sanna S., Marcialis J., Mosino L., Peddis M., Melis S., De Donno G., Aru A.C., Falsetti E., Lanari J., D'Errico U., Bianchini S., Figa F., Caiazzo A., Selvaggi L., Capozzolo A., Cerra C., Pirillo M., Cravano S., Libri I., Laquatra N., Isabello A., Truskovs A., Bartnick A., Malcevs E., Machatschek M.J., Alm J., Lapsa S., Delorme M., Zeynalov F., Larnovskis J., Sauka J., Bodrov D., Gailumsis R., Wiemann A.M., Muller N.L., Jelovskis I., Deksnis D., Bauermeister Potts O., Slimbajevs T., Samalavicius N.E., Nutautiene V., Zeromskas P., Jurgaitis J., Aliosin O., Slepavicius A., Eismontas V., Kybransiene M., Dulskas A., Kuliavas J., Kavaliauskas P., Kavaliauskaite R., Poskus E., Danys D., Kryzauskas M., Mikalauskas S., Rackauskas R., Drungilas M., Jotautas V., Strupas K., Cachia C., Cefai C., Youssef Y., Degaetano D., Debono S., Sammut M., Cassar J., Sammut K., Looijen R.C., Becker M.A.J., Comert D., te Molder L., Tromp J., Matthee E., Tissen Y.M., Brinkhuis E., de Vries H.S., 't Hart E., Beckers K., Bekker Y., Kakar S., van Smaalen T.C., Veen O.C., Dingemans S.A., van den Brink L.C., Vijgen G.H.E.J., van de Voort E.M.F., van der Pool A., van Rest K.L.C., Haak T., Sluijpers N.R.F., Molenaar C.J.L., Gordinou de Gouberville M.C., Saleh S., Mens M.A., Hoeks E.M., Nieuwenhuizen S., van Praag E.M., Westerduin E., Smit M.P.C.M., van der Lely S.J., Nasimi B., Gerdsen M., Stijns R.C.H., Leow T.Y.S., Penningnieuwland G., de Ruiter A., Ribbers T., Aarts C.A.M., Tulek M.S., de Jonge J., Kocak S., Alqethami H.J., Constansia R., van Elst P.C., Tissink M.W., Gruter A., Vroom Y., Voeten D.M., Feenstra T., Azzahhafi J., Bofarid S., Kip M., Saleh W., Franssen S., Boon C.L., Franssen R.J.M., Romaen I., Jense M.T.F., D'Souza J., Pascoe R., Scott A., Stark E., Mulholland K., Lau W.K., Smith B., Adams S.I.B., Shah N., Ling E., Young J., Jacobson A., Macfater H., Chen S.Y., Kilpatrick K., Kim D.H., Dixon S., Yassaie S., Welman D., Coulter J., Morreau M., Li E., Rankin A., Winders J., Skipworth C., Stanfield B., Henderson N., Chuang A., Maskill L., Ker H., McLaughlin S.J.P., Kearney J., Sprosen H., Kerckhoffs P., Alsadat R., Cherry R., Chapman D.A., Singh N., Clucas A., Gatenby G., Kelly B., Ruppeldt P., McIntosh N.D., Koh S., Wilms H., Dalzell F., Tewhaiti-Smith J., Kader T., Yam S.T., Dahya D., Hardie Boys M., Fleischl W., Skavysh A., Mouldey K., Hu R., Edwards S., Matthews C., Aitken E., Walker M., Tome M., Patrocinio S., Amado F., Batista A., Seabra J., Praxedes V., Monteiro N., Martins I., Santos T.C., Lages R.R., Pimentel A., Sa T., Bernardes F.M., Saraiva P., Almeida J., Mendes M., Fernandes V., Ribeiro A., Soares D., Martins T., Miguel I., Martins J., Cunha M.F., Melo J., Veiga D.N., Rachadell J., Vareda R., Roseira J., Aveiro D., Couto M., Loureiro A.R., Louro H., Queiros T., Castro B., Fonseca S., Carvalho L., Torre A.P., Amado A., Leite M., Miranda P., Cunha C., Silva R., Pina S., Paixao I., Orelhas L., Santos J., Pacheco A., Rocha A.F., Jervis M.J., Pedro V., Paixao V., Guerreiro A., Melo D., Correia D., Capella V., Moinhos T., Silva M., Silva A.G., Galvao D., Mora A., Bettencourt R., Costa F., Gil I., Morgado J., Monica I., Oliveira S., Ribeiro H., Guimaraes N., Duarte M., Miranda J., Martins S.F., Parreira R., Faustino A., Medeiros N., Castro R., Soares B., Resendes M., Almeida P., Cruz A., Vaz Pinto G., Sousa D., Costa Santos D., Silva F., Fialho G., Reia M., Pratas N., Costa C., Costa J., Morais S., Machado A., Horta V., Rocha-Melo M., Patricio J., Pereira M., Lima R., Cinza A.M., Oliveira J., Velez C., Borges F., Simoes J., Botelho P., Cismasiu B., Alves D., Dias B., Goncalves J.P., Valente P., Freire L., Saraiva R., Moreira M., Fragoso M., Guimaraes J., Cruz G., Ribeiro J., Borges da Ponte I., Almeida S., Martins A.R., Louro T., Morgado M., Ferreira A.S., Alves M., Oliveira N., Lerias R., Estalagem I., Botelho C., Bartolo J., Fidalgo Antunes C., Cabral F., Brito Silva F., Dias Matos A., Santos M., Cunha R., Sousa M., Canotilho R., Correia A.M., Martins P.C., Jardim J.A.M., Domingos S.P., Baiao J.M., Rocha B.S., Lopes N.M.R.O., Jordao D.M., Angelo M.D., Caroco T., Gomes J.R., Monteiro R.G., Varghese S., Boyle E., Aljohmani L., Alexander J., Graziadei V., McCaughey C., Jain A., Ramanayake H., Sabnani R., Colon L.F., Bansal N., Stephens I., Tan R., Sharma S., Doherty G., Fenn S., Mulhare E., Walsh M., Leavey C., Costigan O., Griffin S., Dockry E., Khogali E., Aly A.K., McPhedran R., O'Gorman D., Vermeulen D., Dervan L., Kang S.J., Dixon O., Morrissey E., Compton M., Pentony A.R., Piong C.L., Nossier R., Hanna J., Sabir K., Eow S.Y., Ladak N., Boersma D., Kamath P.J., Soh T.B.W., Dyer A.H., Chee S.Y., Tan I.X.H., Kelliher A., Adeusi L., Howarth N., McCawley N., O'Neill A., Jones M.R., Saleh R., Singh A., Senaratne R., Kakodkar P., Balasubramanian I., Al-Salihi A., Vyas V., Vedadi A., Popescu S.S., Piras K., Ciubotaru C.I., Romanova E., Ponomarev N., Savchenko A., Luzan R., Lutovinova E., Gavrilina A., Barkovskaya A., Kudelkina N., Topchubaev D., Radulovic R., Milosevic K., Bojicic J., Gencic M., Jankovic U., Zubowicz M., Suchan P.K., Gerstmeier J., Brazitikou E., Fytrou E., Celik M., Dubovsky M., Schmalenbeck J., Sautter S.C., Ceyran H., Fitchat N., Mathebula S., Chauke J., Mculu W., Ngwenya Z., Withey K., Piperidis A., Toyi Y., Nicolaides A., Jaffer T., Sparke A., Van Staden N., McDuling C.R., Claassen L., Kruger C., Weyers J., Lecler J., Yebes A., Mana O.C., Gomez H., Riba L., Perez J., Casaval Cornejo L., Vicente Rodriguez I., Jimenez Escovar F., Calvo Fernandez M., Portugal Martinez A., Badiola Bergara I., Landaluce Olavarria A., del Pozo Andres E., Samartin Toimil C., Primo Alvarez J.C., Rodriguez Fernandez L., Ortega C., Ossola M.E., Camarero E., Martinez Illan M., Aranda Garcia L., Lazaro 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Nunez OSullivan S., Ramos Jimenez F.A., Perez Ortega A., Trujillo Barbadillo A., Romero Pujana E., Fernandez Illera M.V., De La Llave Serralvo A., Mestres N., Cuello E., Merichal M., Sierra J.E., Escoll J., Rufas M., Pinillos A.I., Ortega J., Vivas Angeles P., Vives Figueras R., Baena Sanfeliu E., Campillo Alonso B., Alberich Prats M., Duran Arrocha J., Cornella Garceso N., Uribe Galeano C., Delisau Puig O., Castro A., Codony Bassols C., Fernandes N., Garcia Adamez J., Caula Freixa C., Sanchez M.J., Martin-Borregon P., Quevedo A., Martinez J., Marin J.M., Rodriguez P., Garcia Orozco J.J., Ferrusola Diaz D.A., Garcia Jimenez M.L., Castro Diez L., Mosquera Fernandez C., Alonso Batanero E., Cifrian Canales I., Calzada M.G., Recuenco C.B., Martin M.C., Esteban Avendano I., Jimenez Relimpio C., Lancho Lavilla P., Blanco Bartolome I., Gomez Cano I., Blasco Andres C., Alonso-Poza A., Dieguez B., Losada M., Gilsanz C., Garcia-Vico A., Roman-Rando A., Sanchez-Galvez M.A., Bersabe-Alonso I.M., 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Karabulut A., Yilmaz D., Kuyumcu O.F., Kutluk F., Emiroglu B., Mollavelioglu B., Gereklioglu D., Guler M., Toprak S., Afsar H.B., Guler S.E., Alizade E., Alemdag G., Ulusahin M., Gul E.B., Yildirim R., Semiz A., Bektur G., Tomas K., Yarenci E., Demiroglu Y., Sunal A., Baykan B., Abbasguliyev H., Mutlu V., Mahmoudi Y., Dossa S.A.A., Mizan S.R., Demirtas B., Cavus T., Yuksek A., Mazlum S.S., Yelkenci C., Baran T., Satilmisoglu M., Sahin A.Z., Kilinc A., Isik K., Yumurtaci O., Emin A., Girit C., Yildirak M.K., Senyigit E., Guldag A., Soyleyici B., Aytin Y.E., Akay F.E., Iskan N.G., Mutlu B., Sunay A.O., Tie-Gill T., Ramsay G., De Paola L., McGuckin S., Alshakhs A., Ahmeidat A., Goergen N., Ali Z., Mullarkey L., Walshe R., Lewis E., Berry B., Moneim J., Mookerjee S., Christy S., Ojofeitimi O., Carroll L., Hylands A., Delaugere L.P., Reveendran D., Coulter C., Ralston C., Laverty L., Gallagher P., Ahmed A., Yeo Y.Q., Elliott D., Bennett J., Mcnamara M., Sivarajah S., Dunmore C., Aitken G., Nair M., Aly M.H., Buari M., Ahmed K., Sheikh Z., Monks M., Lehmann J., Rotimi O., Bell T., Limnatitou D., Gormley S., Taleongpong P., Patel V., Macgregor L., Amini S., Turner C., Dwyer-Hemmings L., Busuttil A., Powell J., Hensher C., Vivian F., Wcislo K., Millar Z., Hirosue S., Ogunmwonyi I., Nakakande D., Gaze H., Nirmalanantha A., Bin Amran M.A., Foulkes A., Jones N., Pillai S., Khoury G., Powell T., Maleyko I., Sangheli A., Ransome M., Isse M., Aromolaran O., Bholah H., Anbarasan J., Rehman S., Hu E., Timms S., Reynolds W., Hotchkies A., Misra V., Theocharidou L., Malik T., Janmohamed I., Carhart B., Khan A., Hullait R., Rylance A., Butt S., Leathes J., Philip Rajathasan T., Jeddy H., Kyaw H.A., Wong N., Karelia S., Clements J.M., Rainey M., Joshi N., Rahman A., Gallagher M., Rebuffa N., Abdelgalil R., Siaw Yen Lai R., Laurence N., Thomas S., Green C., Frostick R., Khera R., Povey M., Wong H.L., McCusker C., Hlukha L., Pike G., Kamel F., Thakkar R., Donaldson C., Sequeira Campos 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F., Sysum K., Latter J., Latter M., Khan S., Guruswamy M., Beedham W., Brazier E., Elghobashy M., Bajaj M., Mann H., Etel E., Woodmass M., Hayden H., Ali Y., Husain S., Arnold A., Pedersen A.C., Cunha P., Ahmed M., Al Zawawi S., Kudva V., Theodoropoulou K., Miscampbell M., Robinson A.V., Johnston J., Dharni A., Lamb S., Westerman T., Evans E., Campbell L., Gillespie M., Cheong C.M., Kulathevanayagam K., Varghese A., Ike S.I., Chu T.S.M., Baljer B., Mogg J.A.W., Rai P., Claireaux H.A., Williams M., Smillie R., Goetz J., Appleby E., Fadipe T., Vaughan-Burleigh S., Puri G., Hussain P., Flather R., Cutler A., Pathak S., Sheldon J., Collicott T., al-Ausi M., Jovaisaite A., Shah S.M., Khalid N., Gutmann D., Davison S., Alame Y.J., Syed L., Owen W.J., Ahsan S.D., Anthony-Uzoeto U., Macleod Hall C., Zheng S., Wynter K., James C., Sapre D., Ghosh R., Baird J., Cockburn L., Blackwood O., Simpson W., Jeong S., Bishop S., Bate R., Hobson C., Adam A.H., Redclift C., Do J., Adeleye O., Poli F., Batterham A., Brown S., Parekh J.N., Clay W., Pieri K., Jackson A., Saxena A., Gurung B., Oyebola T., O'Brien F., Djeugam B., Gardezi S., Ul-Hasan S., Martin-Hernandez M.P., Sisley M., Modi S., Antakia R., Elbayouk A., Soh Y.J., Mather J., Yusuf Z., Al-Sarraf Z., Naja M., Rassool S.B., Convill J., Nikookam Y., Warsame A., Pace C., Kiandee M., Ridwan R., Carey C., Hirri F., McMillan M.J.A., Ling J.J., Pendelbury L., Kerimzade K., Tang A., Howard E.O., Humayun S., Wadsworth O.J., Tan K., Abdelhameed F., Haglund C., Radnaeva I., Hu N., Rambhatla S., Waldron D., Madahar P., Malik S., Meney L.C., Ibrahim I., Kang C.K., Chiu J.Z.J., Livie V., Ibrahim B., Khalil M., Pooley G., Shishkin B., Docherty J., Southgate A., Coomes A., McGee F., Flanagan S., Tan Q.J., Anwar H., Clough R., Chrisp B., Cassels J., Cross G.W.V., Mercer L., Mercer C., Refalo A., Hadley R., McTighe A., Farrow F., Brodie A., Davis G., Shah D.R., Bowers C., Patel S., Morice O., Burzic A., Cheung J., Shashidhara A., Theodoraki 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McMurrugh K., Jimulia D., Deol S., Pike S., Embury-Young Y., Patel M., Kilgallon E., Keating R., Walsh A., Khan H., Logue G., Orekoya M., Alasmar M., Charalambides M., Clave Llavall A., Williamson E., Bharwada Y., Zearmal S., Evans H., Panikkar M., de la Cruz G., Caplan J., Ruparelia A., Tanvir T., Soare C., Pang Y.L., Trotter J., Zaidi A., Thakrar V., Pulickal P., Ahmed H., Parnell J., Lennock S., Ford V., Brignall R., O'Neill D., Hanna R., Kane R., Nicola M., Rajput K., Xiao Y., Michael S., Wright E., Juniper S., Thompson E., Hoskyns L., Kanitkar A., Ross C., Unsworth A., Rshaidat H., Demarre K., Chiang A., Bareh A., van Dellen J., Faqihinejad C., Gadhvi A., Grant R., Lewsey J., Morris A., Martin H., McClarty C., Sanyal S., Alsaif A., Palkhi A., Bhopal S., Vishnu K S., Papanikolaou A., Mitra A., Nur A., Ali F., Burford C., Huq T., Irwin E., Matthews L., Ngu W.S., Hosfield T., Muneeb F., Page O., Zeb E., Al-Azzawi A., McIntosh J., Vucicevic A., Hughes M., Brooks L., Fanibi B., Dixon M., Njoku P., Morris D., Jobson J., Chowdhury H., Alawode D.O.T., Wynell-Mayow W., Udayachandran V., Alsoof D., Ekert J., Joseph N., Zulkefley N., Hunt G., Christodoulou T., Wright O., Soman S., Jamal M., Beqiri S., Borgas P., Christie S., Pereira F., Browne S., Yiu J., Dworkin A., Brayley J., Palmer A., Charalambos M., Jones C.S., Toner S., Cowden R., Lee L., Nicol P., Holman O., Imtiaz M., Albert V., Leung S.P., Erotocritou M., Stroud R., Wilkin R., Thomson W., Mackee L., G N., Bei Y., Mckenna Favier S., Ibrahim A., Kler A., Reynolds L., Mohamed S.H., Majeed Y., Fakim B., Jones A., Liversedge G., Carrington Z., Windebank J., Izzarina A., Akbani U., Craven J., Aldarragi A., Harding S., Millward A., Bedford M., Gopalan V., Midgen A., Khadka P., Cheng O., Taneja S., Manobharath N., Kok J.Y., Lim D.W.E., Buick T., Boland M., Piya S., Devlin R., Fairfield C.J., George R.J., Rahi M., Zaman S., Hajiev S., Ross T., Crisp E., Thompson C., Charalambous A., Hollywood J.L., Hammond R.F.L., 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J., Shirazi B., Neilson A., Epton S., Patel N., Trussell S., Couldrey A., Donnelly C., Eftychiou S., Glasbey, J. C., Bibi, S., Pata, F., Ozkan, B. B., Van Straten, S., Hodson, J., Chapman, S. J., Blanco-Colino, R., Pellino, G., Sgro, A., Soares, A., van Elst, T., Nepogodiev, D., Borakati, A., Bath, M. F., Yasin, I. H., Mclean, K., Arthur, T., Kovacevic, M., Delibegovic, S., Karamanliev, M., Swamad, M., Zebrak, R., Paramasivam, R., Martensen, A., Larsen, H. M., Radeker, L., Frey, P. E., Kechagias, A., Venara, A., Duchalais, E., Ioannidis, A., Pasquali, S., Simioni, A., Farina, V., Podda, M., Lorenzon, L., Itsurg, I., Schaeff, V., Otto, A., Jakubauskas, M., van Elst, T. R., Chu, M., Fagan, P. V. B., Wells, C. I., Alagoa Joao, A., Juloski, J., Perez-Ajates, S., Anabitarte Bautista, O., El Kasmy, Y., Espin-Basany, E., Clerc, D., Ciubotaru, C., Popescu, S., Yanishev, A., Lee, S., Yagiz Sen, A., Aktas, M. K., Baki, B. E., Yuksek, B., Kamarajah, S., Khaw, R. A., Mills, E., Goodson, R., Thakral, N., Collaborative, S., Ablett, A. D., Adra, M., Kwek, I., Khan, S. M., Quinn, P., Manley, L. 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D., Hansmann, M., Medina Feliz, J., Kuiper, S. Z., Abdulrahman, Z., Pruijssers, S. R., Farik, S., Elliott, B. M., Geneta, V. P., Wilton, S., Kandelaki, H., Peng, S. L., Campbell, S., Lim, Y. K., Yassaie, S. S., Murray, M., Haran, C., Tan, J., Castro, J., Laranjeira, A., Catarino, S., Neves-Marques, C., Correia, J. G., Vieira, B. N., Quintela, A. C., Serra, M. L., Maciel, J., Cunha, M., Aparicio, D. J., Neves, J., Azevedo, J., Romano, M., Eiro, F., Romano, J., Monteiro, C., Claro, M., Almeida, M. R., Peyroteo, M., Machado, N. D., Capote, H., Ferreira, M., Sousa, X., Devesa, H., Cavadas, D., Guerreiro, I., Costa, M., Rosete, M., Salman, M., English, C., Mohammed, N., Litvin, A., Cuk, V. V., Meszarosova, K., Jaich, R., De Lima, H., Brooks, S., Marx, M., Nshalati Salvation, M., Garcia Cardo, J., Mora-Guzman, I., Sancho Muriel, J., de Andres Olabarria, U., Muriel, P., Jimenez Vinas, C., Alconchel, F., Esteban Sinovas, O., Gomez del Pulgar, A., Fairen Oro, C., Lopez Otero, M., Figueroa Jimenez, S., Claramonte Bellmunt, O., Martinez Caballero, J., Rubio-Perez, I., Aguilar-Martinez, M. M., Segura-Sampedro, J. J., Olmedo Moreno, C., Negre Parra, D., Estevez Diz, A. M., Martin-Balbuena, R., Bustamante Recuenco, C., Licardie Bolanos, R. E., Fernandez, P., Diaz Padillo, A., Forero-Torres, A., Alberdi San Roman, I., Salvador Roses, H., Merayo Alvarez, M., Villarejo Campos, P., Lopes Moreira, C. C., Uriol Peralta, P., Serrano Navidad, M., Ripolles-Melchor, J., Garcea, A., Gomez Facundo, H., Troncoso Pereira, P., V Perez Guarinos, C., Blaser, B., Piazza, G., Gagliardi, B., Serin, H., Yurdaor, S. S., Arslan, E., Kopac, O., Uyanik, A., Ozmen, B. B., Tiftik, E., Aksoy, B., Yalcinkaya, A., Ozoglu, F., Kocer, M. D., Bilicen, G., Cinar, E. N., Uslu, O., Kaya, Y., Demirci, K., Wong, J., Farhan-Alanie, M. M. H., Suresh, G., Asif, A., Finch, B. J., Bhahirathan, Y., Herron, J., Yi Tew, Z., Obukofe, R., Russell, C., Suchett-Kay, I., Netke, T., Williams, L., Kisiel, A., Liu, F. Y., Claireaux, H., James, P., Mondal, A., Kalderon, R., Nadama, H. H., Al-Saraff, Z., Tam, J. P. H., Powell-Chandler, A., Wood, F., Gorgievska, R., Ragavoodoo, A., Thakrar, C., Rojoa, D., Palmer, C., Davidson, K., Giacci, L., Hale, J., Gan, F. W., Makin-Taylor, R., Hey, C. Y., Toh, C., Findlay, J. M., Griffiths, N., Ganesananthan, S., Jasionowska, S., Poustie, M., Wong, C., Turner, T., Pyc, W., Sloper, W., Warner, C., Coey, J., Mason, D., Sait, S., Kowal, M., Owen, M., Saiyed, A., Ashworth, I., Akbari, K., Curran, M., Martin, P., Parker, D., Kwok, K., Lye, C., Ghaly, M., Sammour, T., Lewis, D., Mundasad, R., Wilkes, A., Ctercteko, G., Maslyankov, S., Dimov, R., Iliev, S., Dimitrov, D., Marek, F., Orhalmi, J., Skalicky, P., Skalicky, T., Chrz, K., Christensen, P., Worsoe, J., Kristensen, E. S., Emmertsen, K. J., Loeve, U. S., Mihaljevic, A. L., Herrle, F., Konstantinidis, K. M., Korkolis, D., Karanikas, I., Vincenti, L., Anania, G., Borghi, F., Agresta, F., Maretto, I., Parisi, A., Bucci, L., De Palma, G., Guglielmi, A., Cucinotta, E., La Torre, F., Cianchi, F., Guerrieri, M., Trompetto, M., Persiani, R., Micheletto, G., Delrio, P., Cantafio, S., Ronconi, M., Bisagni, P. A. 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F., cRicardo Felipe, B., Septiem, J., Rodriguez Sanchez, A., Canete-Gomez, J., Ruiz Montesinos, I., Millan-Scheiding, M., Prieto-Nieto, I., Frasson, M., Garcia Olmo, D., Hubner, M., Petermann, D., Sauvain, M. O., Ozben, V., Gecim, I. E., Disci, E., Rencuzogullari, A., Kurt, A., Bisgin, T., Pehlivan, M., Isik, A., Onur, E., Leventoglu, S., Haksal, M. C., Erturk, M. S., Keskin, M., Guner, A., Tutcu Sahin, S., Ozbalci, G. 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T., Chrimes, A., Agarwal, A., Zhao, J., Williams, S., Jayalath, J. M. S. N., Khor, S., Muddasani, T., Childs, S., Ridgway, S., Blefari, N. D. A., Tam, H., Puchalski, N., Ngai, C., Mackenzie, J., Johnson, N., Holmes, M., Zuzek, R., Saluja, T., Gould, T., Goh, Y. K., Selvaraj, T., Beh, Y. Z., Dudi-Venkata, N. N., Horne, D., Borrow, J. L., Campbell, C., Cousins, G., Jackson, L., Maheepala, K., Zhao, S., Holden, E., Tutt, L., Thompson, B., Collins, H., Louie, F., Buckland, B., Smith, D., Chong, C., Chua, T. H., Nayak, C., Redmond, J., Tan, R. R., Gramlick, M., Teh, J. S., Ng, S. Y., Britten-Jones, P., Mohd Rosli, R., Pham, H. D. V., Jegathees, T., Coulter-Nile, S. M. C. J., Gosselink, M. P., Wang, Y. L., Maciaszek, M., Chrapko, P. 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P., Scaramuzzo, R., Larcinese, A., Fioriti, C., Picone, E., Nardi, M., Castagnoli, G., Bartoli, A., Bellochi, R., Spaziani, A., Conti, D., Poponesi, V., Trippetti, M., Amicucci, S., Tazza, G., Procacci, P., Giovannini, F., Basile, E., Caristo, G., De Nardi, P., Rosati, R., Marcocci, G., Vignali, A., Malerba, M., Percivale, A., Ghazouani, O., Reggiani, L., Spirito, C., Moschetta, G., Cosmi, F., Romeo, G., Gasparrini, M., Sucameli, F., Gennai, A., Moggia, E., Bianchi, C., Bonfante, P., Macina, S., Feleppa, C., Imperatore, M., Tenconi, S. M., Rausei, S., Maioli, D., Marchionini, V., Sparta, C., Mura, F. A., Barmina, M., Lorettu, A., Rettaroli, C., Mastino, G., Ruggiu, G. V., Mura, G. A., Perrone, B. A., De Angelis, M., Mereu, A., Adamo, V., Bianco, C., Ricciardiello, M., Campanaro, C., Panaccio, P., Esposito, L. 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E., Nutautiene, V., Zeromskas, P., Jurgaitis, J., Aliosin, O., Slepavicius, A., Eismontas, V., Kybransiene, M., Dulskas, A., Kuliavas, J., Kavaliauskas, P., Kavaliauskaite, R., Poskus, E., Danys, D., Kryzauskas, M., Mikalauskas, S., Rackauskas, R., Drungilas, M., Jotautas, V., Strupas, K., Cachia, C., Cefai, C., Youssef, Y., Degaetano, D., Debono, S., Sammut, M., Cassar, J., Sammut, K., Looijen, R. C., Becker, M. A. J., Comert, D., te Molder, L., Tromp, J., Matthee, E., Tissen, Y. M., Brinkhuis, E., de Vries, H. S., 't Hart, E., Beckers, K., Bekker, Y., Kakar, S., van Smaalen, T. C., Veen, O. C., Dingemans, S. A., van den Brink, L. C., Vijgen, G. H. E. J., van de Voort, E. M. F., van der Pool, A., van Rest, K. L. C., Haak, T., Sluijpers, N. R. F., Molenaar, C. J. L., Gordinou de Gouberville, M. C., Saleh, S., Mens, M. A., Hoeks, E. M., Nieuwenhuizen, S., van Praag, E. M., Westerduin, E., Smit, M. P. C. M., van der Lely, S. J., Nasimi, B., Gerdsen, M., Stijns, R. C. H., Leow, T. Y. 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G., Galvao, D., Mora, A., Bettencourt, R., Costa, F., Gil, I., Morgado, J., Monica, I., Oliveira, S., Ribeiro, H., Guimaraes, N., Duarte, M., Miranda, J., Martins, S. F., Parreira, R., Faustino, A., Medeiros, N., Castro, R., Soares, B., Resendes, M., Almeida, P., Cruz, A., Vaz Pinto, G., Sousa, D., Costa Santos, D., Silva, F., Fialho, G., Reia, M., Pratas, N., Costa, C., Costa, J., Morais, S., Machado, A., Horta, V., Rocha-Melo, M., Patricio, J., Pereira, M., Lima, R., Cinza, A. M., Oliveira, J., Velez, C., Borges, F., Simoes, J., Botelho, P., Cismasiu, B., Alves, D., Dias, B., Goncalves, J. P., Valente, P., Freire, L., Saraiva, R., Moreira, M., Fragoso, M., Guimaraes, J., Cruz, G., Ribeiro, J., Borges da Ponte, I., Almeida, S., Martins, A. R., Louro, T., Morgado, M., Ferreira, A. S., Alves, M., Oliveira, N., Lerias, R., Estalagem, I., Botelho, C., Bartolo, J., Fidalgo Antunes, C., Cabral, F., Brito Silva, F., Dias Matos, A., Santos, M., Cunha, R., Sousa, M., Canotilho, R., Correia, A. M., Martins, P. C., Jardim, J. A. M., Domingos, S. P., Baiao, J. M., Rocha, B. S., Lopes, N. M. R. O., Jordao, D. M., Angelo, M. D., Caroco, T., Gomes, J. R., Monteiro, R. G., Varghese, S., Boyle, E., Aljohmani, L., Alexander, J., Graziadei, V., Mccaughey, C., Jain, A., Ramanayake, H., Sabnani, R., Colon, L. F., Bansal, N., Stephens, I., Tan, R., Sharma, S., Doherty, G., Fenn, S., Mulhare, E., Walsh, M., Leavey, C., Costigan, O., Griffin, S., Dockry, E., Khogali, E., Aly, A. K., Mcphedran, R., O'Gorman, D., Vermeulen, D., Dervan, L., Kang, S. J., Dixon, O., Morrissey, E., Compton, M., Pentony, A. R., Piong, C. L., Nossier, R., Hanna, J., Sabir, K., Eow, S. Y., Ladak, N., Boersma, D., Kamath, P. J., Soh, T. B. W., Dyer, A. H., Chee, S. Y., Tan, I. X. 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I., Ortega, J., Vivas Angeles, P., Vives Figueras, R., Baena Sanfeliu, E., Campillo Alonso, B., Alberich Prats, M., Duran Arrocha, J., Cornella Garceso, N., Uribe Galeano, C., Delisau Puig, O., Castro, A., Codony Bassols, C., Fernandes, N., Garcia Adamez, J., Caula Freixa, C., Sanchez, M. J., Martin-Borregon, P., Quevedo, A., Martinez, J., Marin, J. M., Rodriguez, P., Garcia Orozco, J. J., Ferrusola Diaz, D. A., Garcia Jimenez, M. L., Castro Diez, L., Mosquera Fernandez, C., Alonso Batanero, E., Cifrian Canales, I., Calzada, M. G., Recuenco, C. B., Martin, M. C., Esteban Avendano, I., Jimenez Relimpio, C., Lancho Lavilla, P., Blanco Bartolome, I., Gomez Cano, I., Blasco Andres, C., Alonso-Poza, A., Dieguez, B., Losada, M., Gilsanz, C., Garcia-Vico, A., Roman-Rando, A., Sanchez-Galvez, M. A., Bersabe-Alonso, I. M., Vadillo-Bohorquez, A., Gutierrez Rios, R. D., Eizaguirre Ubegun, M., Novo Sukia, I., Uribe Isado, M., Ibanez Alda, M., Pastor Idoate, C., Abad-Motos, A., Marinez-Hurtado, E., Salvachua-Fernandez, R., Padilla Zegarra, E. D., Franco, M., Martinez, A., Ramos Martin, P., Mate Mate, P., Marcano Chavez, C., Ayllon, H., Jeri-McFarlane, S., Soldevila-Verdeguer, C., Pineno-Flores, C., Ambrona-Zafra, D., Fernandez-Vega, L., Gil-Catalan, A., Craus-Miguel, A., Pujol-Cano, N., Sena-Ruiz, F., Gomez Jurado, M. J., Alberti Delgado, P., Bordanova Reverter, A., Belzunce-Capo, J. F., Verdaguer Tremolosa, M., Lin, Q., Muniesa, C., Avelino, L., Cholewa, H., Sancho-Muriel, J., Navasquillo, M., Navio, A., Abello, D., De Jesus, M., Alvarez, E., Garcia, J. M., Gil, A., Giordano, H. E., Mignon, G., Vanoni, A., Henkens, A., Jarrar, G., Odovic, M., Willemin, M., Milliet, O., Hahnloser, D., Demartines, N., Teixeira, H., Pittet, O., Haller, M. L., Huot, A., Kefleyesus, A., Bugmann, A., Piotet, L. M., Meijers, L., Kurtoglu, G. K., Sel, E. K., Isler, V. 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O., Tie-Gill, T., Ramsay, G., De Paola, L., Mcguckin, S., Alshakhs, A., Ahmeidat, A., Goergen, N., Ali, Z., Mullarkey, L., Walshe, R., Lewis, E., Berry, B., Moneim, J., Mookerjee, S., Christy, S., Ojofeitimi, O., Carroll, L., Hylands, A., Delaugere, L. P., Reveendran, D., Coulter, C., Ralston, C., Laverty, L., Gallagher, P., Ahmed, A., Yeo, Y. Q., Elliott, D., Bennett, J., Mcnamara, M., Sivarajah, S., Dunmore, C., Aitken, G., Nair, M., Aly, M. H., Buari, M., Ahmed, K., Sheikh, Z., Monks, M., Lehmann, J., Rotimi, O., Bell, T., Limnatitou, D., Gormley, S., Taleongpong, P., Patel, V., Macgregor, L., Amini, S., Turner, C., Dwyer-Hemmings, L., Busuttil, A., Powell, J., Hensher, C., Vivian, F., Wcislo, K., Millar, Z., Hirosue, S., Ogunmwonyi, I., Nakakande, D., Gaze, H., Nirmalanantha, A., Bin Amran, M. A., Foulkes, A., Jones, N., Pillai, S., Khoury, G., Powell, T., Maleyko, I., Sangheli, A., Ransome, M., Isse, M., Aromolaran, O., Bholah, H., Anbarasan, J., Rehman, S., Hu, E., Timms, S., Reynolds, W., Hotchkies, A., Misra, V., Theocharidou, L., Malik, T., Janmohamed, I., Carhart, B., Khan, A., Hullait, R., Rylance, A., Butt, S., Leathes, J., Philip Rajathasan, T., Jeddy, H., Kyaw, H. A., Wong, N., Karelia, S., Clements, J. M., Rainey, M., Joshi, N., Rahman, A., Gallagher, M., Rebuffa, N., Abdelgalil, R., Siaw Yen Lai, R., Laurence, N., Thomas, S., Green, C., Frostick, R., Khera, R., Povey, M., Wong, H. L., Mccusker, C., Hlukha, L., Pike, G., Kamel, F., Thakkar, R., Donaldson, C., Sequeira Campos, M., Armitage, M. N., Hussain, A. S., Hardy, B., Hassan Serry, M. Y., Bradbury, M., Osunronbi, T., Tam, L. Y. C., Khanan Kaabneh, A., Lawther, J., Fisher, P., Tribedi, T., Moosa, A., Ramdin, A., Goble, M., Downs, E., Wheldon, L., Baggus, E., Mandal, A., Nayeem, A., Ahmed, S., Fradley, W., Wilson, C., Gallagher, S., Criswell, T., Ward, J., Mukkavilli, A., Stubbs, B., Fordyce, W., Suchdev, N., Wei Lim, S., Sookramanien, S. R., Chan, A., Bointas, G., Paul, M., Ward, K. L., Bagnall, M., Pherwani, S. A., Wang, K., Mitchell, L., Heyworth, J., Ayyar, S., Polson, R., Mackenzie, E., Doyle, N., Habib, Z., Zardab, M., Sartaj, F., Farooq, H., Tabibi, M., Drury, D. J., James, S. J., Barnett, R., Teasdale, A. B., Richardson, E. T. J., Thomas, D. A., Williams, R. L., Najabat-Lattif, H. F., Cahya, E., Lou, G., Coyle, M., Homyer, K., Zhu, L. Y., Woods, M., Chang, J., O'Callaghan, H., Suchett-Kaye, I., Mihailidis, T. 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Leeuwen, B.L., Tuynman, J.B., van Tilburg, M., Boerma, E.G., Bissett, I.P., Ourô, S., Caratão, M., Ridgway, P.F., McNamara, D.A., O'Connell, P.R., Ćuk, V.M., García, J., Espí Macías, A., Luján Mompeán, J.A., Romero Simó, M., Sánchez-Guillén, L., Jiménez-Gómez, L.M., Sánchez López, A., Julià Bergkvist, D., Noguera Aguilar, J.F., Rodríguez Sánchez, A., Cañete-Gómez, J., Millán-Scheiding, M., García Olmo, D., Hübner, M., Sauvain, M.O., Geçim, I.E., Disçi, E., Haksal, M.C., Erturk, M.S., Ozbalci, G.S., McIntyre, R., Moug, S.J., Lund, J.N., Smart, N.J., Knowles, C.H., Hany, T.S., Smith, F.M., Borg, C.M., Lee, Y.J., Lai, L.T., Jun, H., Mendis, D.M., Robb, P.M., Lee, H.J., Wyche, A., Davis, L.T., Jayalath, J., Blefari, N., Goh, Y.K., Beh, Y.Z., Dudi-Venkata, N.N., Borrow, J.L., Chua, T.H., Tan, R.R., Teh, J.S., Ng, S.Y., Pham, H., Coulter-Nile, S., Gosselink, M.P., Wang, Y.L., Chrapko, P.S., Pös, M., Bartoš, M., Malý, O., Hanušová, M., Hurný, M., Riško, J., Treskoň, R., Pospíšil, M., Hlaváčová, L., Tomanová, D., Novický, R., Sobotková, K., Šuta Kimle, K., Paclík, A., Jürgens-Lahnstein, J., Kristensen, F.P., Bønnerup, K., Højgaard Pedersen, J., Jepsen, B.N., Hillgaard, T.K., Erichsen, S.B., Nielsen, C.V., Madsen, C.P., Skejø, C.D., Aabling, R.R., Sørensen, J.S., Schöning, L., Cs Simon, S., Thäwel, T., Seckler, A.M., Athanasopoulos, P.G., Giuffrida, M.C., Billo, M.E., Marrosu, A.G., Ruggiu, M.W., Antona, A.D., Bitonti, M.F., Romano, F.M., Pellicanò, G.A., Murru, M.L., Angelucci, G.P., Tenconi, S.M., Mura, F.A., Ruggiu, G.V., Mura, G.A., Perrone, B.A., Esposito, L.M., Marcianò, M., Milani, M.S., Aru, A.C., Figà, F., Truškovs, A., Machatschek, M.J., Wiemann, A.M., Müller, N.L., Samalavicius, N.E., Poškus, E., Kryžauskas, M., Poškus, T., Looijen, R.C., Becker, M., Te Molder, L., Tissen, Y.M., de Vries, H.S., van Smaalen, T.C., Veen, O.C., Dingemans, S.A., van den Brink, L.C., Vijgen, G., van de Voort, E., van Rest, K., Sluijpers, N., Molenaar, C., Gordinou de Gouberville, M.C., Mens, M.A., Hoeks, E.M., van Praag, E.M., Smit, M., van der Lely, S.J., Stijns, R., Leow, T., Aarts, C., Tulek, M.S., Alqethami, H.J., van Elst, P.C., Tissink, M.W., Grüter, A., Voeten, D.M., Boon, C.L., Franssen, R., Jense, M., Lau, W.K., Adams, S., Chen, S.Y., Kim, D.H., McLaughlin, S., Chapman, D.A., McIntosh, N.D., Yam, S.T., Tomé, M., Santos, T.C., Lages, R.R., Sá, T.C., Bernardes, F.M., Cunha, M.F., Veiga, D.N., Loureiro, A.R., Torre, A.P., Paixão, I., Rocha, A.F., Jervis, M.J., Paixão, V., Silva, A.G., Galvão, D., Mónica, I., Guimarães, N., Martins, S.F., Patrício, J., Cinza, A.M., Simões, J., Gonçalves, J.P., Guimarães, J., Martins, A.R., Ferreira, A.S., Lérias, R., Bártolo, J., Correia, A.M., Martins, P.C., Jardim, J., Domingos, S.P., Baião, J.M., Rocha, B.S., Lopes, N., Jordão, D.M., Ângelo, M.D., Caroço, T., Gomes, J.R., Monteiro, R.G., McCaughey, C., Colon, L.F., Dockry, É., Aly, A.K., McPhedran, R., Kang, S.J., Pentony, A.R., Piong, C.L., Eow, S.Y., Kamath, P.J., Soh, T., Dyer, A.H., Chee, S.Y., Tan, I., McCawley, N., Jones, M.R., Popescu, S.S., Ciubotaru, C.I., Radulović, R., Miloševic, K., Bojičić, J., Genčić, M., Janković, U., Sucháň, P.K., Dubovský, M., Sautter, S.C., McDuling, C.R., Mana, O.C., Vicente Rodríguez, I., Jiménez Escovar, F., Calvo Fernández, M., Portugal Martínez, A., Del Pozo Andrés, E., Samartín Toimil, C., Primo Álvarez, J.C., Ossola, M.E., Martínez Illán, M., Aranda García, L., Lázaro Cardona, M., Livianos Arias-Camisón, P., Nieto Arranz, J.M., Mateos Sexmero, M.J., Liquete Marín, L., Pérez Calle, M., Ramos Cordero, M.J., Sánchez, E., Martínez Díaz, J.M., Ruiz Manzanera, J.J., Navarro Barrios, Á., Rodríguez Pedreño, L., García Moreno, P., García Gómez, M., Rifà Terricabras, S., Alberch Camprubí, E., Rico Ferrández, M., De Pablo Miró, M., Cañete-Manzanares, J., García Hernández, L.C., Orozco Nuñez, S., Soriano Liébana, M.M., Campo Betancourth, C.F., Bosch Ramírez, M., Ramayo Díaz, N., González Caraballo, I., Orue-Echebarria, M.I., Sánchez-Calvo, L., Morales Bernaldo de Quirós, J.T., Núñez O Sullivan, S., Ramos Jiménez, F.A., Pérez Ortega, A., Fernandez Illera, M.V., Sierra, J.E., Pinillos, A.I., Cornellà Garceso, N., García Ádamez, J., Sánchez, M.J., Martín-Borregón, P., Martínez, J., Marín, J.M., Rodríguez, P., Garcia Orozco, J.J., Ferrusola Diaz, D.A., Garcia Jimenez, M.L., Cifrián Canales, I., Calzada, M.G., Recuenco, C.B., Martin, M.C., Esteban Avendaño, I., Jiménez Relimpio, C., Blanco Bartolomé, I., Gómez Cano, I., Blasco Andrés, C., García-Vico, A., Sánchez-Gálvez, M.Á., Bersabe-Alonso, I.M., Gutierrez Rios, R.D., Ibañez Alda, M., Marínez-Hurtado, E., Salvachua-Fernández, R., Padilla Zegarra, E.D., Jerí-McFarlane, S., Pineño-Flores, C., Fernández-Vega, L., Gil-Catalán, A., Gómez Jurado, M.J., Belzunce-Capó, J.F., Navío, A., Abelló, D., Garcia, J.M., Giordano, H.E., Haller, M.L., Piotet, L.M., Kurtoglu, G.K., Sel, E.K., Isler, V.C., Yilmaz, B.S., Demirkaya, H.C., Korkmaz, H.K., Pektas, A.M., Güner, B., İşlek, E.C., Tombul, H.B., Boztuğ, C.Y., Tınaz, A., Yılmaz, M., Akın, F.A., Başçavuş, M., Seker, M.C., Koçak, Z.B., Karapinar, Y.E., Köseoglu, E., Agca, M.H., Alim, Y.E., Kürklü, Ö., Çalar, S.N., Kavar, R.C., Cevlik, A.D., Turk, E.G., Erdönmez, H., Gürsoy, F., Önsal, U., Özbek, M., Kasar, P.A., Özen, D., Ölmez, M., Sariçiçek, T., Tipi, O.U., Benli, G.E., Bilgili, A.C., Kiraz, I.N., Demirci, Z.S., Aksoy, A.B., Karagöz, E., Tümer, S.S., Abdulrahman, S., Kuyumcu, O.F., Afsar, H.B., Guler, S.E., Gul, E.B., Dossa, S., Mizan, S.R., Mazlum, S.S., Sahin, A.Z., Kilinç, A., Yumurtaci, Ö., Girit, Ç., Yildirak, M.K., Güldag, A., Söyleyici, B., Aytin, Y.E., Akay, F.E., Iskan, N.G., Sunay, A.O., McGuckin, S., Delaugere, L.P., Yeo, Y.Q., Aly, M.H., Bin Amran, M.A., Kyaw, H.A., Clements, J.M., Wong, H.L., McCusker, C., Armitage, M.N., Hussain, A.S., Hassan Serry, M.Y., Tam, L., Sookramanien, S.R., Ward, K.L., Pherwani, S.A., Drury, D.J., James, S.J., Teasdale, A.B., Richardson, E., Thomas, D.A., Williams, R.L., Najabat-Lattif, H.F., Zhu, L.Y., Mihailidis, T.H., Pedersen, A.C., Robinson, A.V., Cheong, C.M., Ike, S.I., Chu, T., Mogg, J., Claireaux, H.A., Al-Ausi, M., Shah, S.M., Alame, Y.J., Owen, W.J., Ahsan, S.D., Adam, A.H., Parekh, J.N., Martin-Hernandez, M.P., Soh, Y.J., Rassool, S.B., McMillan, M., Ling, J.J., Howard, E.O., Wadsworth, O.J., Meney, L.C., Kang, C.K., Chiu, J., McGee, F., Tan, Q.J., Cross, G., McTighe, A., Shah, D.R., Ng, M., Wong, R., Rojoa, D.M., Ruddy, C.M., Hall, J.D., Hassane, A., Azhar, A.W., Tan, T.K., Kwak, S.Y., Ong, E.H., McGregor, O., Lim, Q.X., Yong, S.Q., Chen, J.Y., Sam, Z.H., Goh, Y.N., Muthukumar, M.G., Johnson, T.A., Williams, R.I., McTiernan, M., McLaughlin, N., Honeyman, S.I., Malcolm, F.L., Wilkerson, H.T., Ahmed, W., Kwan, K., Boh, Z.Y., English, W.J., Novotny, S.A., Chong, J.T., Lee, D.E., McMurrugh, K., Clavé Llavall, A., Pang, Y.L., McClarty, C., Ngu, W.S., McIntosh, J., Alawode, D., Jones, C.S., Leung, S.P., Mohamed, S.H., Kok, J.Y., Lim, D., Fairfield, C.J., George, R.J., Hollywood, J.L., Hammond, R., Flint, E.J., Lee, Y.D., Skalický, A., Ojakäär, A., Dörr-Harim, C., Cufari, M.E., Gusai, G.P., Di Mola Ospedale Ss Annunziata, F.F., Loche, G.A., Stellingwerf, M.E., van de Pas, K., Brandsma, A.M., Rottier, S.J., Ong, H.I., O'Connor, D.B., Jovanović, M., Bernado, I.R., Paniagua Garcia Señorans, M., González Amor, L., Cuenca Ramírez, A., Cerdán, C., Gómez Romeu, N., Enriquez-Navascues, J.M., Uygur, F.A., Eray, I.C., Çetin, M.F., Isik, A.E., Sarıgül, L., Francis, A.A., Al-Hadithi, A., Lau, I., McAuliffe, O., Roche, C.D., Chaudhry, F.A., Amsterdam Gastroenterology Endocrinology Metabolism, Other Research, Graduate School, Surgery, Oncology, AII - Infectious diseases, and ACS - Microcirculation
Subjects: medicine.medical_specialty, endocrine system, general surgery, Gastrointestinal, endocrine system diseases, Settore MED/18 - CHIRURGIA GENERALE, pulmonary complications, 03 medical and health sciences, 0302 clinical medicine, Ileus, Nasogastric tube insertion, Medicine, pulmonary complication, pneumonia, EPIDEMIOLOGY, Humans, Prospective Studies, colorectal surgery, nasogastric tube, Prospective cohort study, Intubation, Gastrointestinal, OUTCOMES, VENTILATOR-ASSOCIATED PNEUMONIA, business.industry, Elective Surgical Procedures, Pneumonia, Confounding, Gastroenterology, nutritional and metabolic diseases, Odds ratio, Postoperative pneumonia, medicine.disease, Colorectal surgery, Surgery, body regions, Intubation, Gastrointestinal/adverse effects, Pneumonia/epidemiology, Pneumonia/etiology, Pneumonia/prevention & control, 030220 oncology & carcinogenesis, Vomiting, 030211 gastroenterology & hepatology, medicine.symptom, business, Intubation, hormones, hormone substitutes, and hormone antagonists
Abstract: © 2020 The Association of Coloproctology of Great Britain and IrelandAim: Aspiration is a common cause of pneumonia in patients with postoperative ileus. Insertion of a nasogastric tube (NGT) is often performed, but this can be distressing. The aim of this study was to determine whether the timing of NGT insertion after surgery (before versus after vomiting) was associated with reduced rates of pneumonia in patients undergoing elective colorectal surgery. Method: This was a preplanned secondary analysis of a multicentre, prospective cohort study. Patients undergoing elective colorectal surgery between January 2018 and April 2018 were eligible. Those receiving a NGT were divided into three groups, based on the timing of the insertion: routine NGT (inserted at the time of surgery), prophylactic NGT (inserted after surgery but before vomiting) and reactive NGT (inserted after surgery and after vomiting). The primary outcome was the development of pneumonia within 30 days of surgery, which was compared between the prophylactic and reactive NGT groups using multivariable regression analysis. Results: A total of 4715 patients were included in the analysis and 1536 (32.6%) received a NGT. These were classified as routine in 926 (60.3%), reactive in 461 (30.0%) and prophylactic in 149 (9.7%). Two hundred patients (4.2%) developed pneumonia (no NGT 2.7%; routine NGT 5.2%; reactive NGT 10.6%; prophylactic NGT 11.4%). After adjustment for confounding factors, no significant difference in pneumonia rates was detected between the prophylactic and reactive NGT groups (odds ratio 1.03, 95% CI 0.56–1.87, P = 0.932). Conclusion: In patients who required the insertion of a NGT after surgery, prophylactic insertion was not associated with fewer cases of pneumonia within 30 days of surgery compared with reactive insertion.
Published: 2020
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43. Impact of the COVID-19 pandemic on surgery for thyroid cancer in Italy: nationwide retrospective study

Author: Medas, F., Ansaldo, G. L., Avenia, N., Basili, G., Bononi, M., Bove, A., Carcoforo, P., Casaril, A., Cavallaro, G., Conzo, G., De Pasquale, L., Del Rio, P., Dionigi, G., Dobrinja, C., Docimo, G., Graceffa, G., Iacobone, M., Innaro, N., Lombardi, C. P., Novelli, G., Palestini, N., Pedicini, F., Perigli, G., Pezzolla, A., Pezzullo, L., Scerrino, G., Spiezia, S., Testini, M., Calo, P. G., Anedda, G., Antonelli, G., Arrigoni, G., Badii, B., Bonati, E., Boniardi, M., Bulfamante, A. M., Candalise, V., Cangiano, A., Canu, G. L., Cappellacci, F., Caracciolo, A., Caruso, E., Casal Ide, E., Chiappini, A., Chiofalo, M. G., Cipolla, C., Costigliola, L., Cozzani, F., Crocco, A., Crocetti, D., De Manzini, N., DI Gioia, A., DI Resta, V., Eramo, R., Erdas, E., Ferriolo, S., Filardo, M., Filograna Pignatelli, M., Gervasi, R., Giudici, F., Gordini, L., Gurrado, A., Impellizzeri, H., Inama, M., Koleva Radica, M., Laforgia, R., Lattarulo, S., Loderer, T., Lucchini, R., Mascioli, F., Marcellinaro, R., Menditto, R., Melfa, G., Minuto, M., Misso, C., Offi, C., Orlando, G., Ossola, P., Pagetta, C., Pasculli, A., Patrone, R., Pauna, I., Pennetti Pennella, F., Pietrasanta, D., Pino, A., Pinto, V. L., Piras, S., Polistena, A., Portinari, M., Reina, S., Rotolo, G., Russo, G., Scalise, E., Sgaramella, L. I., Sibilla, M. G., Spinelli, S., Spoletini, D., Curto, L. S., Tascone, M., Torresan, F., Varaldo, E., Viviani, E., Zucca, A., Medas, F, Ansaldo, G L, Avenia, N, Basili, G, Bononi, M, Bove, A, Carcoforo, P, Casaril, A, Cavallaro, G, Conzo, G, De Pasquale, L, Del Rio, P, Dionigi, G, Dobrinja, C, Docimo, G, Graceffa, G, Iacobone, M, Innaro, N, Lombardi, C P, Novelli, G, Palestini, N, Pedicini, F, Perigli, G, Pezzolla, A, Pezzullo, L, Scerrino, G, Spiezia, S, Testini, M, Calò, P G, Cipolla C, Medas, F., Ansaldo, G. L., Avenia, N., Basili, G., Bononi, M., Bove, A., Carcoforo, P., Casaril, A., Cavallaro, G., Conzo, G., De Pasquale, L., Del Rio, P., Dionigi, G., Dobrinja, C., Docimo, G., Graceffa, G., Iacobone, M., Innaro, N., Lombardi, C. P., Novelli, G., Palestini, N., Pedicini, F., Perigli, G., Pezzolla, A., Pezzullo, L., Scerrino, G., Spiezia, S., Testini, M., Calo, P. G., Anedda, G., Antonelli, G., Arrigoni, G., Badii, B., Bonati, E., Boniardi, M., Bulfamante, A. M., Candalise, V., Cangiano, A., Canu, G. L., Cappellacci, F., Caracciolo, A., Caruso, E., Casal Ide, E., Chiappini, A., Chiofalo, M. G., Cipolla, C., Costigliola, L., Cozzani, F., Crocco, A., Crocetti, D., De Manzini, N., DI Gioia, A., DI Resta, V., Eramo, R., Erdas, E., Ferriolo, S., Filardo, M., Filograna Pignatelli, M., Gervasi, R., Giudici, F., Gordini, L., Gurrado, A., Impellizzeri, H., Inama, M., Koleva Radica, M., Laforgia, R., Lattarulo, S., Loderer, T., Lucchini, R., Mascioli, F., Marcellinaro, R., Menditto, R., Melfa, G., Minuto, M., Misso, C., Offi, C., Orlando, G., Ossola, P., Pagetta, C., Pasculli, A., Patrone, R., Pauna, I., Pennetti Pennella, F., Pietrasanta, D., Pino, A., Pinto, V. L., Piras, S., Polistena, A., Portinari, M., Reina, S., Rotolo, G., Russo, G., Scalise, E., Sgaramella, L. I., Sibilla, M. G., Spinelli, S., Spoletini, D., Curto, L. S., Tascone, M., Torresan, F., Varaldo, E., Viviani, E., and Zucca, A.
Subjects: 2019-20 coronavirus outbreak, medicine.medical_specialty, AcademicSubjects/MED00910, Coronavirus disease 2019 (COVID-19), medicine.medical_treatment, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), pandemics, NO, Pandemic, Research Letter, medicine, humans, Thyroid cancer, Thyroid Neoplasm, LS7_4, Thyroid Neoplasms, Thyroidectomy, SARS-CoV-2, COVID-19, Pandemics, Italy, business.industry, thyroid neoplasms, Retrospective cohort study, medicine.disease, Comorbidity, comorbidity, retrospective studies, thyroidectomy, Settore MED/18 - Chirurgia Generale, Emergency medicine, Surgery, AcademicSubjects/MED00010, business
Abstract: N/A
Published: 2021

44. Cost-effectiveness of switching from omalizumab to mepolizumab in uncontrolled severe eosinophilic asthma

Author: Girolamo Pelaia, Nicola Scichilone, Emanuela Resta, Cecilia Calabrese, Maria D'Amato, Nunzio Crimi, Maria Pia Foschino Barbaro, Corrado Pelaia, Onofrio Resta, Giulia Scioscia, and Giovanna Elisiana Carpagnano
Subjects: medicine.medical_specialty, Exacerbation, Cost effectiveness, business.industry, Omalizumab, medicine.disease, Discontinuation, Pulmonary function testing, Internal medicine, Exhaled nitric oxide, medicine, business, Mepolizumab, medicine.drug, Asthma
Abstract: Background: Severe asthma is burdened by frequent exacerbations and use of oral corticosteroids (OCS) which worsen patients’ quality of life and increased healthcare spending. Objectives: To assess the clinical and economic impact of switching from omalizumab (OMA) to mepolizumab (MEP) in patients eligible for both biologics but not optimally controlled with OMA. Methods: Uncontrolled patients referred to 6 asthma clinics in south of Italy switched from OMA to MEP, were enrolled and followed-up to Jan 2020. Clinical information included blood eosinophil count, asthma control test (ACT), pulmonary function, IgE, exhaled nitric oxide (FeNO), OCS intake, drugs, exacerbations/hospitalizations, visits and exams. A 12-months standardized total cost per patient pre and post MEP was calculated in the perspective of Italian National Health System. Results: 33 patients were enrolled: 5 male, median age 59 years, disease onset 24 years. At OMA discontinuation, 89% were OCS-dependent with annual mean rate of 3.1 exacerbations. The switch to MEP reduced both exacerbation (-2.8) and OCS-dependent patients (-76%). Pulmonary function improved and both IgE, FENO and eosinophils serum decreased. Annual cost was €11,277 with OMA and €12,498 with MEP (p=0.2041), the increment due to biologic (+€1,673) was partially offset by the saving due to all other cost items (-€452). Conclusions: Patients with severe eosinophilic asthma not controlled by OMA experienced a clinically benefit in asthma control switching to MEP with a slight economic impact.
Published: 2020
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45. Novel SCN5A p.V1429M Variant Segregation in a Family with Brugada Syndrome

Author: Carlo Pappone, Emanuela T Locati, Luigi Anastasia, Giorgio Casari, Giuseppe Ciconte, Chiara Di Resta, Sara Benedetti, Gabriele Vicedomini, Emanuele Micaglio, Andrea Ghiroldi, Luigi Giannelli, Michelle M. Monasky, Valeria Borrelli, Monasky, M. M., Micaglio, E., Ciconte, G., Borrelli, V., Giannelli, L., Vicedomini, G., Ghiroldi, A., Anastasia, L., Locati, E. T., Benedetti, S., Di Resta, C., Casari, G., and Pappone, C.
Subjects: 0301 basic medicine, Genetic testing, family, Case Report, 030204 cardiovascular system & hematology, medicine.disease_cause, Sudden cardiac death, lcsh:Chemistry, 0302 clinical medicine, Channelopathy, Variant, lcsh:QH301-705.5, Spectroscopy, SCN5A, Brugada syndrome, Genetics, Mutation, medicine.diagnostic_test, Sodium channel, General Medicine, Computer Science Applications, Medical genetics, Arrhythmia, Human, sodium channel, medicine.medical_specialty, Disease Association, Biology, arrhythmia, Catalysis, sudden cardiac death, genetic testing, Inorganic Chemistry, 03 medical and health sciences, channelopathy, medicine, Family, human, Physical and Theoretical Chemistry, Molecular Biology, Gene, Organic Chemistry, fungi, medicine.disease, 030104 developmental biology, lcsh:Biology (General), lcsh:QD1-999, variant, mutation
Abstract: Brugada syndrome (BrS) is diagnosed by the presence of an elevated ST-segment and can result in sudden cardiac death. The most commonly found mutated gene is SCN5A, which some argue is the only gene that has been definitively confirmed to cause BrS, while the potential causative effect of other genes is still under debate. While the issue of BrS genetics is currently a hot topic, current knowledge is not able to result in molecular confirmation of over half of BrS cases. Therefore, it is difficult to develop research models with wide potential. Instead, the clinical genetics first need to be better understood. In this study, we provide crucial human data on the novel heterozygous variant NM_198056.2:c.4285G>A (p.Val1429Met) in the SCN5A gene, and demonstrate its segregation with BrS, suggesting a pathogenic effect. These results provide the first disease association with this variant and are crucial clinical data to communicate to basic scientists, who could perform functional studies to better understand the molecular effects of this clinically-relevant variant in BrS.
Published: 2020

46. Updated clinical overview on cardiac laminopathies: an electrical and mechanical disease

Author: Sara Benedetti, Maurizio Ferrari, Simone Sala, Lorenzo Gigli, Giovanni Peretto, C. Di Resta, P. Della Bella, Peretto, G., Sala, S., Benedetti, S., Di Resta, C., Gigli, L., Ferrari, M., and Della Bella, P.
Subjects: medicine.medical_specialty, Heart disease, Heart Diseases, Cardiomyopathy, LMNA, heart failure, Disease, 030204 cardiovascular system & hematology, arrhythmia, Asymptomatic, sudden cardiac death, Sudden cardiac death, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, lamin, genetics, 030212 general & internal medicine, Musculoskeletal Diseases, Special Issue on Laminopathies, business.industry, Dilated cardiomyopathy, Cell Biology, medicine.disease, Lamin Type A, Heart failure, Cardiology, genetic, medicine.symptom, business, arrhythmias, cardiomyopathy
Abstract: Cardiac laminopathies, associated with mutations in the LMNA gene, encompass a wide spectrum of clinical manifestations, involving electrical and mechanical alterations of cardiomyocytes. Thus, dilated cardiomyopathy, bradyarrhythmias and atrial or ventricular tachyarrhythmias may occur in a number of combined phenotypes. Nowadays, some attempt has been made to identify clinical predictors for the most life-threatening complications of LMNA-associated heart disease, i.e. sudden cardiac death and end-stage heart failure. The goal of this manuscript is to combine the most recent evidences in an updated review to show the state-of-the-art of such a complex disease group. This is supposed to be the starting point to collect more data and design new ad hoc studies to identify clinically useful predictors to stratify risk in mutation carriers, including probands and their asymptomatic relatives.
Published: 2018

47. A short-term treatment with BKI-1294 does not protect foetuses from sheep experimentally infected with Neospora caninum tachyzoites during pregnancy

Author: Wesley C. Van Voorhis, Matthew A. Hulverson, Victor Herrero García, Manuel Pizarro Díaz, Grant R. Whitman, Darío Cleofé-Resta, Roberto Sánchez-Sánchez, Michela Re, Luis Miguel Ferrer, Luis Miguel Ortega-Mora, Raquel Vallejo-García, Julio Benavides, Ignacio Ferre, Bárbara Pérez-Arroyo, Andrew Hemphill, Ryan Choi, Héctor Ruiz, Universidad Complutense de Madrid, Universidad de Zaragoza, Swiss National Science Foundation, National Institutes of Health (US), National Institute of Food and Agriculture (US), Comunidad de Madrid, Benavides, Julio, and Benavides, Julio [0000-0001-9706-100X]
Subjects: Regular article, Transplacental transmission, Placenta, BKI-1294, Neospora caninum, Stimulation, 610 Medicine & health, Infectious and parasitic diseases, RC109-216, Parasite load, Andrology, Mice, Fetus, Antigen, Pregnancy, medicine, Animals, Pharmacology (medical), reproductive and urinary physiology, Pharmacology, Sheep, biology, 630 Agriculture, Coccidiosis, business.industry, Neospora, Abortion, 500 Science, biology.organism_classification, medicine.disease, Toxoplasmosis, Infectious Diseases, Experimental chemotherapy, Ganado ovino, Vertical transmission, 570 Life sciences, 590 Animals (Zoology), Female, Parasitology, Veterinaria, business
Abstract: The Neospora caninum Calcium-dependent protein kinase 1 (NcCDPK1) inhibitor BKI-1294 had demonstrated excellent efficacy in a pregnant mouse model of neosporosis, and was also highly efficacious in a pregnant sheep model of toxoplasmosis. In this work, we present the efficacy of BKI-1294 treatment (dosed 5 times orally every 48 h) starting 48 h after intravenous infection of sheep with 105 Nc-Spain7 tachyzoites at mid-pregnancy. In the dams, BKI-1294 plasma concentrations were above the IC50 for N. caninum for 12–15 days. In treated sheep, when they were compared to untreated ones, we observed a minor increase in rectal temperature, higher IFNγ levels after blood stimulation in vitro, and a minor increase of IgG levels against N. caninum soluble antigens through day 28 post-infection. Additionally, the anti-NcSAG1 and anti-NcSAG4 IgGs were lower in treated dams on days 21 and 42 post-infection. However, BKI-1294 did not protect against abortion (87% foetal mortality in both infected groups, treated and untreated) and did not reduce transplacental transmission, parasite load or lesions in placentomes and foetal brain. The lack of foetal protection was likely caused by short systemic exposure in the dams and suboptimal foetal exposure to this parasitostatic drug, which was unable to reduce replication of the likely established N. caninum tachyzoites in the foetus at the moment of treatment. New BKIs with a very low plasma clearance and good ability to cross the blood-brain and placental barriers need to be developed., Graphical abstract Image 1, Highlights • BKI-1294 triggers a transiently decrease in anti-N. caninum IgG levels in sheep. • BKI-1294 does not protect against abortion and vertical transmission of N. caninum. • The efficacy of BKI-1294 is different in pregnant mice and sheep models of neosporosis.
Published: 2021
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48. Spitz Nevus with Features of Clark Nevus, So-Called SPARK Nevus: Case Series Presentation with Emphasis on Cytological and Histological Features

Author: Eugenio Maiorano, Antonietta Cimmino, Gerardo Cazzato, Leonardo Resta, Lucia Lospalluti, Anna Colagrande, and Giuseppe Ingravallo
Subjects: Clark Nevus, medicine.medical_specialty, Series (stratigraphy), skin, business.industry, Dermatology, medicine.disease, Spitz nevus, SPARK nevus, Article, dysplastic nevus, Clark, dermatopathology, SPARK (programming language), RL1-803, medicine, Dysplastic nevus, Nevus, Dermatopathology, Presentation (obstetrics), business, computer, computer.programming_language
Abstract: Background: SPARK nevus represents a little-known and characterized entity, with few case series available in the literature. Methods and results: we present a case series of 12 patients (6 F and 6 M) between January 2005 and December 2020 and conduct a review of the current literature. Ten articles were selected on the basis of the adopted inclusion criteria and the PRISMA guidelines. Conclusions: The definition of histopathological and dermoscopic criteria are important to allow for an agreement to be reached among dermopathologists, and for the development of a consensus on higher case studies. To our knowledge, there are not many case series in the literature, and ours is part of the attempt to increase the knowledge of an entity that remains little-known and characterized.
Published: 2021
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49. GLUT1, GLUT3 Expression and 18FDG-PET/CT in Human Malignant Melanoma: What Relationship Exists? New Insights and Perspectives

Author: Gerardo Cazzato, Vera Loizzi, Teresa Lettini, Francesca Arezzo, Giuseppe Ingravallo, Leonardo Resta, Roberta Rossi, Sara Sablone, Emilio Bellitti, Paolo Romita, Lucia Lospalluti, Caterina Abbatepaolo, Gennaro Cormio, Caterina Foti, Anna Colagrande, and Antonietta Cimmino
Subjects: Oncology, medicine.medical_specialty, Skin Neoplasms, QH301-705.5, malignant melanoma, Review, Breslow Thickness, Fluorodeoxyglucose F18, perspectives, Positron Emission Tomography Computed Tomography, Internal medicine, medicine, Humans, Biology (General), Melanoma, Glucose Transporter Type 1, Glucose Transporter Type 3, biology, Mechanism (biology), business.industry, Publications, Glucose transporter, Cancer, General Medicine, medicine.disease, Systematic review, immunohistochemistry, biology.protein, GLUT1, business, GLUT3
Abstract: Background: Malignant melanoma is the most aggressive of skin cancers and the 19th most common cancer worldwide, with an estimated age-standardized incidence rate of 2.8–3.1 per 100,000; although there have been clear advances in therapeutic treatment, the prognosis of MM patients with Breslow thickness greater than 1 mm is still quite poor today. The study of how melanoma cells manage to survive and proliferate by consuming glucose has been partially addressed in the literature, but some rather interesting results are starting to be present. Methods: A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and a search of PubMed and Web of Sciences (WoS) databases was performed until 27 September 2021 using the terms: glucose transporter 1 and 3 and GLUT1/3 in combination with each of the following: melanoma, neoplasm and immunohistochemistry. Results: In total, 46 records were initially identified in the literature search, of which six were duplicates. After screening for eligibility and inclusion criteria, 16 publications were ultimately included. Conclusions: the results discussed regarding the role and expression of GLUT are still far from definitive, but further steps toward understanding and stopping this mechanism have, at least in part, been taken. New studies and new discoveries should lead to further clarification of some aspects since the various mechanisms of glucose uptake by neoplastic cells are not limited to the transporters of the GLUT family alone.
Published: 2021

50. EPV204/#454 Inguinal metastases as presenting sign of ovarian cancer

Author: Vera Loizzi, Gennaro Cormio, V Cataldo, Gerardo Cazzato, C Putino, M Mongelli, Francesca Arezzo, Leonardo Resta, and G Serio
Subjects: medicine.medical_specialty, business.industry, medicine, Radiology, Ovarian cancer, medicine.disease, business, Sign (mathematics)
Published: 2021
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