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1. How syllabi relate to outcomes in higher education: A study of syllabi learner-centeredness and grade inequities in STEM.

Author

Eslami, Maryam, Sumarsono, Jacklyn, Dennin, Michael, Sato, Brian, Collins, Penelope, and Denaro, Kameryn

Subjects
Humans, Curriculum, Engineering, Technology, Students, Mathematics
Abstract

Fostering equity in undergraduate science, technology, engineering, and mathematics (STEM) programs can be accomplished by incorporating learner-centered pedagogies, resulting in the closing of opportunity gaps (defined here as the difference in grades earned by minoritized and non-minoritized students). We assessed STEM courses that exhibit small and large opportunity gaps at a minority-serving, research-intensive university, and evaluated the degree to which their syllabi are learner-centered, according to a previously validated rubric. We specifically chose syllabi as they are often the first interaction students have with a course, establish expectations for course policies and practices, and serve as a proxy for the course environment. We found STEM courses with more learner-centered syllabi had smaller opportunity gaps. The syllabus rubric factor that most correlated with smaller gaps was Power and Control, which reflects Students Role, Outside Resources, and Syllabus Focus. This work highlights the importance of course syllabi as a tool for instructors to create more inclusive classroom environments.

Published
2024

2. Moving the Needle: Evidence of an Effective Study Strategy Intervention in a Community College Biology Course

Author

Vemu, Sheela, Denaro, Kameryn, Sato, Brian K, and Williams, Adrienne E

Subjects
Stem Cell Research, Biology, Curriculum, Engineering, Female, Humans, Male, Students, United States, Universities, Curriculum and Pedagogy, Education
Abstract

Many science, technology, engineering, and math (STEM) community college students do not complete their degree, and these students are more likely to be women or in historically excluded racial or ethnic groups. In introductory courses, low grades can trigger this exodus. Implementation of high-impact study strategies could lead to increased academic performance and retention. The examination of study strategies rarely occurs at the community college level, even though community colleges educate approximately half of all STEM students in the United States who earn a bachelor's degree. To fill this research gap, we studied students in two biology courses at a Hispanic-serving community college. Students were asked their most commonly used study strategies at the start and end of the semester. They were given a presentation on study skills toward the beginning of the semester and asked to self-assess their study strategies for each exam. We observed a significantly higher course grade for students who reported spacing their studying and creating drawings when controlling for demographic factors, and usage of these strategies increased by the end of the semester. We conclude that high-impact study strategies can be taught to students in community college biology courses and result in higher course performance.

Published
2022

3. Identifying systemic inequity in higher education and opportunities for improvement.

Author

Denaro, Kameryn, Dennin, Kimberly, Dennin, Michael, and Sato, Brian

Subjects
Humans, Mathematics, Students, Universities, Engineering, Technology, Stem Cell Research, Quality Education, General Science & Technology
Abstract

It is well established that there is a national problem surrounding the equitable participation in and completion of science, technology, engineering, and mathematics (STEM) higher education programs. Persons excluded because of their ethnicity or race (PEERs) experience lower course performance, major retention, sense of belonging, and degree completion. It is unclear though how pervasive these issues are across an institution, from the individual instructor, course, and discipline perspectives. Examining over six years of institutional data from a large-enrollment, research-intensive, minority-serving university, we present an analysis of racial opportunity gaps between PEERs and non-PEERs to identify the consistency of these issues. From this analysis, we find that there is considerable variability as to whether a given course section taught by a single instructor does or does not exhibit opportunity gaps, although encouragingly we did identify exemplar instructors, course-instructor pairs, courses, and departments that consistently had no significant gaps observed. We also identified significant variation across course-instructor pairs within a department, and found that certain STEM disciplines were much more likely to have courses that exhibited opportunity gaps relative to others. Across nearly all disciplines though, it is clear that these gaps are more pervasive in the lower division curriculum. This work highlights a means to identify the extent of inequity in STEM success across a university by leveraging institutional data. These findings also lay the groundwork for future studies that will enable the intentional design of STEM education reform by leveraging beneficial practices used by instructors and departments assigning equitable grades.

Published
2022

4. Comparison of Cluster Analysis Methodologies for Characterization of Classroom Observation Protocol for Undergraduate STEM (COPUS) Data.

Author

Denaro, Kameryn, Sato, Brian, Harlow, Ashley, Aebersold, Andrea, and Verma, Mayank

Subjects
Humans, Data Collection, Cluster Analysis, Problem-Based Learning, Students, Education, Curriculum and Pedagogy
Abstract

The Classroom Observation Protocol for Undergraduate STEM (COPUS) provides descriptive feedback to instructors by capturing student and instructor behaviors occurring in the classroom. Due to the increasing prevalence of COPUS data collection, it is important to recognize how researchers determine whether groups of courses or instructors have unique classroom characteristics. One approach uses cluster analysis, highlighted by a recently developed tool, the COPUS Analyzer, that enables the characterization of COPUS data into one of seven clusters representing three groups of instructional styles (didactic, interactive, and student centered). Here, we examine a novel 250 course data set and present evidence that a predictive cluster analysis tool may not be appropriate for analyzing COPUS data. We perform a de novo cluster analysis and compare results with the COPUS Analyzer output and identify several contrasting outcomes regarding course characterizations. Additionally, we present two ensemble clustering algorithms: 1) k-means and 2) partitioning around medoids. Both ensemble algorithms categorize our classroom observation data into one of two clusters: traditional lecture or active learning. Finally, we discuss implications of these findings for education research studies that leverage COPUS data.

Published
2021

5. Use of the Test of Scientific Literacy Skills Reveals That Fundamental Literacy Is an Important Contributor to Scientific Literacy

Author

Shaffer, Justin F, Ferguson, Julie, and Denaro, Kameryn

Subjects
Curriculum and Pedagogy, Education, Behavioral and Social Science, Basic Behavioral and Social Science, Clinical Research, Pediatric, Quality Education, Aptitude, Aptitude Tests, Educational Measurement, Female, Humans, Linear Models, Literacy, Male, Science, Students, Test Taking Skills, Universities, Curriculum and pedagogy
Abstract

College science courses aim to teach students both disciplinary knowledge and scientific literacy skills. Several instruments have been developed to assess students' scientific literacy skills, but few studies have reported how demographic differences may play a role. The goal of this study was to determine whether demographic factors differentially impact students' scientific literacy skills. We assessed more than 700 students using the Test of Scientific Literacy Skills (TOSLS), a validated instrument developed to assess scientific literacy in college science courses. Interestingly, we found that Scholastic Aptitude Test (SAT) reading score was the strongest predictor of TOSLS performance, suggesting that fundamental literacy (reading comprehension) is a critical component of scientific literacy skills. Additionally, we found significant differences in raw scientific literacy skills on the basis of ethnicity (underrepresented minority [URM] vs. non-URM), major (science, technology, engineering, and mathematics [STEM] vs. non-STEM), year of college (e.g., senior vs. freshman), grade point average (GPA), and SAT math scores. However, when using multivariate regression models, we found no difference based on ethnicity. These data suggest that students' aptitude and level of training (based on GPA, SAT scores, STEM or non-STEM major, and year of college) are significantly correlated with scientific literacy skills and thus could be used as predictors for student success in courses that assess scientific literacy skills.

Published
2019

6. Assessment of total annual effective doses to representative person, for authorised and accidental releases from the Nuclear Medicine Department at Cattinara Hospital (Trieste, Italy)

Author

Michele Signoriello, Maria Rosa Fornasier, Mario de Denaro, Fulvia Arfelli, Benedetta Santoro, and Mara Severgnini

Subjects
Sewage, Biophysics, Humans, General Physics and Astronomy, Radiology, Nuclear Medicine and imaging, General Medicine, Nuclear Medicine, Radiation Dosage, Solid Waste, Hospitals
Abstract

Clinical procedures in a Nuclear Medicine Department produce radioactive liquid and solid waste. Regarding waste release into the environment from an authorised hospital, it is mandatory to verify the compliance with European Directive 2013/59/EURATOM, adopted by the Italian Government via the Legislative Decree 101/2020.Different activity release pathways into the environment from Trieste Nuclear Medicine Department have been analysed: liquid waste from patients' excreta discharged by sewage treatment system into the sea, and atmospheric releases following solid waste incineration. Reference models, provided by NCRP and IAEA guidelines, have been implemented to assess the impact of the discharged radioactivity for coastal waters and atmospheric transport conditions. Finally, an accidental fire event occurring in Radiopharmacy Laboratories has been simulated by HotSpot software.Advanced screening models give an effective dose to population of 5.3 · 10The total annual effective doses estimated to representative person, due to both Nuclear Medicine authorised clinical practices and in case of an accidental fire event, are in compliance with regulatory stipulations provided by Directives.

Published
2022

7. Harmonic ratio is the most responsive trunk-acceleration derived gait index to rehabilitation in people with Parkinson’s disease at moderate disease stages

Author

Stefano Filippo Castiglia, Dante Trabassi, Roberto De Icco, Antonella Tatarelli, Micol Avenali, Michele Corrado, Valentina Grillo, Gianluca Coppola, Alessandro Denaro, Cristina Tassorelli, and Mariano Serrao

Subjects
Acceleration, Rehabilitation, Biophysics, Humans, Parkinson Disease, Orthopedics and Sports Medicine, Walking, Gait, Walking Speed
Abstract

Harmonic ratios (HRs), recurrence quantification analysis in the antero-posterior direction (RQAThis study aimed to i) assess the internal and external responsiveness to rehabilitation of HR, RQAThe trunk acceleration patterns of 21 pwPD and 21 age- and speed-matched healthy subjects (HSmatched) were acquired during gait using an inertial measurement unit at baseline (T0). pwPD were also assessed after a 4-week rehabilitation period (T1). Each participant's HR in the antero-posterior (HRAt T1, HRWhen using inertial measurement units, HR

Published
2022

8. Selective contributions of executive function ability to the P3

Author

Catherine L, Reed, Audrey, Siqi-Liu, Kirsten, Lydic, Madison, Lodge, Aditi, Chitre, Chandlyr, Denaro, Astrid, Petropoulos, Jasmin, Joshi, Cindy M, Bukach, and Jane W, Couperus

Subjects
Executive Function, Memory, Short-Term, Neuropsychology and Physiological Psychology, Physiology (medical), General Neuroscience, Reaction Time, Humans, Attention
Abstract

The P3 component (P300, P3b) is considered to be an effective index of attention and categorization processes when elicited in a visual oddball task, specifically reflecting the selection of a rare target item among frequent non-targets. Researchers have proposed that target categorization is guided by representations of target features held in working memory (WM), thus guiding attention and categorization processes to distinguish targets from non-targets. Although WM is theorized to have visuospatial, verbal and executive function components, most studies do not investigate how these WM components contribute to the P3. This study uses an individual differences approach to determine whether correlations between WM capabilities and P3 amplitudes indicate a common underlying cognitive construct. Participants (n = 140) completed an 80/20 visual oddball task to elicit the P3 as well as independent visual working memory (VWM), spatial working memory (SPWM), and executive function (task switching (TS) and digit symbol substitution (DSS)) tests. Results indicated that measures of executive function, DSS and TS, but not VWM or SPWM ability, correlated with and predicted faster task response times and greater P3 amplitudes. RT and WM measures were not correlated with P3 fractional area latencies. These results support context updating theory. Executive function WM availability, whether as a property of the participant's processing system or based on task demands, plays a functional role in the P3 and an important role in efficient visual categorization and goal-directed learning.

Published
2022

9. Newly Diagnosed Multifocal GBM: A Monocentric Experience and Literature Review

Author

Valentina Baro, Giulia Cerretti, Michela Todoverto, Alessandro Della Puppa, Franco Chioffi, Francesco Volpin, Francesco Causin, Fabio Busato, Pasquale Fiduccia, Andrea Landi, Domenico d’Avella, Vittorina Zagonel, Luca Denaro, and Giuseppe Lombardi

Subjects
multifocal, glioblastoma, multicentric, oncology, surgery, survival, Antineoplastic Agents, Alkylating, Humans, Middle Aged, Retrospective Studies, Temozolomide, Brain Neoplasms, Dacarbazine, Antineoplastic Agents, Alkylating
Abstract

Glioblastomas with multiple foci at presentation (mGBMs) account for 2–35% of all GBMs. mGBMs have limited existing data and no standardized treatment. This study aims to determine their incidence, demographic and clinical features, outcome, and prognostic factors in terms of overall survival. We performed a monocentric retrospective study, reviewing patients treated at the Istituto Oncologico Veneto. Inclusion criteria were: new diagnosis of GBM and presence of multiple lesions on pre-treatment MRI. ECOG PS was used to evaluate clinical condition, RANO criteria for radiological assessment, and CTCAE v5.0 for treatment-related adverse events. The incidence of newly diagnosed mGBM was 7.2% and the study population consisted of 98 patients. Median age was 63 years, M:F ratio of 1.8:1, and a surgical approach was undertaken in 73 patients (mostly partial resection). MGMT was methylated in 47.5%, and 82 patients received active oncological treatment (65.9% radiotherapy plus temozolomide (RT + TMZ)). The disease control rate with RT + TMZ was 63%. Median OS of the entire study population was 10.2 months (95% CI 6.6–13.8), and median PFS was 4.2 months (95% CI 3.2–5.2). The ECOG PS, the extent of resection, and the RT + TMZ were significant prognostic factors in the univariate analysis for OS, but only the RT + TMZ was a significant independent OS predictor in the multivariate analysis (HR = 3.1, 95% IC 1.3–7.7, p = 0.014). The incidence of mGBM is not rare. RT + TMZ is confirmed to be an independent prognostic factor for survival and a safe and effective treatment. When feasible, RT + TMZ should be considered as a possible first-line treatment. The role of the extent of resection is still unclear.

Published
2022

10. The burden of percutaneous vertebroplasty: an epidemiological nationwide study in Italy from 2009 to 2015

Author

Laura Ruzzini, Sergio De Salvatore, Ilaria Piergentili, Rocco Papalia, Luca Denaro, Umile Giuseppe Longo, and Vincenzo Denaro

Subjects
medicine.medical_specialty, Epidemiology, medicine.medical_treatment, Population, Percutaneous vertebroplasty, medicine, Hospital discharge, Humans, Polymethyl Methacrylate, Effective treatment, Orthopedics and Sports Medicine, education, Vertebroplasty, education.field_of_study, business.industry, Incidence (epidemiology), Bone Cements, Italian population, Spine, Osteoporosis, Vertebral fracture, Female, Italy, Spinal Fractures, Emergency medicine, Surgery, Christian ministry, business
Abstract

Percutaneous vertebroplasty (PV) is a minimally invasive technique requiring the injection of polymethylmethacrylate cement into a collapsed or weakened vertebral body to stabilize the fracture. The present study aims to determine the trends in PV procedures over the recent years. The longitudinal analysis of national registers may help to understand the yearly trends and the economic burden of PV. The evaluation of the yearly national costs of this procedure is essential to surgeons, policymaker, hospital administrator and the healthcare system. Moreover, to observe possible variation in the trend of hospitalization between countries, the data of the present study were compared to the US population. Data of this study were collected from the National Hospital Discharge Reports reported at the Italian Ministry of Health regarding the years of this paper (2009–2015). The yearly number of hospital admission for PV, sex, age, days of hospitalization and primary diagnoses in the whole Italian population were calculated. 31,887 vertebroplasties were performed in Italy, with an incidence of 8.8 procedures for every 100,000 inhabitants. Females represented the majority of patients undergoing PV. The median length of hospital stay was 4.15 days. The mean hospital reimbursement was 4,629€ for each PV hospitalization. The burden of vertebral fracture is relevant in the Italian population, and PV constitutes a rapid and effective treatment. Compared to other countries, the costs of PV in Italy are relatively lower; however, it is important to define the incidence of this procedure to understand the economic trend of PV.

Published
2021

11. Lateral release associated with MPFL reconstruction in patients with acute patellar dislocation

Author

Nadim Kheir, Giuseppe Salvatore, Alessandra Berton, Alexander Orsi, Jonathan Egan, Amin Mohamadi, Joseph P. DeAngelis, Arun J. Ramappa, Umile Giuseppe Longo, Vincenzo Denaro, and Ara Nazarian

Subjects
Joint Instability, musculoskeletal diseases, Patellofemoral Joint, Rheumatology, RC925-935, Patellar Dislocation, Ligaments, Articular, Humans, Orthopedics and Sports Medicine, Patella, Diseases of the musculoskeletal system, musculoskeletal system
Abstract

Objective Medial patellofemoral ligament (MPFL) injury occurs in the majority of the cases of acute patellar dislocation. The role of concomitant lateral retinaculum release with MPFL reconstruction is not clearly understood. Even though the lateral retinaculum plays a role in both medial and lateral patellofemoral joint stability in MPFL intact knees, studies have shown mixed clinical outcomes following its release during MPFL reconstruction surgery. Better understanding of the biomechanical effects of the release of the lateral retinaculum during MPFL reconstruction is warranted. We hypothesize that performing a lateral release concurrent with MPFL reconstruction will disrupt the patellofemoral joint biomechanics and result in lateral patellar instability. Methods A previously developed and validated finite element (FE) model of the patellofemoral joint was used to understand the effect of lateral retinaculum release following MPFL reconstruction. Contact pressure (CP), contact area (CA) and lateral patellar displacement were recorded. abstract. Results FE modeling and analysis demonstrated that lateral retinacular release following MPFL reconstruction with tibial tuberosity-tibial groove distance (TT-TG) of 12 mm resulted in a 39% decrease in CP, 44% decrease in CA and a 20% increase in lateral patellar displacement when compared to a knee with an intact MPFL. In addition, there was a 45% decrease in CP, 44% decrease in CA and a 21% increase in lateral displacement when compared to a knee that only had an MPFL reconstruction. Conclusion This FE-based analysis exhibits that concomitant lateral retinaculum release with MPFL reconstruction results in decreased PF CA, CP and increased lateral patellar displacement with increased knee flexion, which may increase the risk of patellar instability.

Published
2022

12. Trends in hospitalisation of Subtalar Joint Arthroereisis in Italy from 2009 to 2016

Author

Vincenzo Denaro, Ilaria Piergentili, Umile Giuseppe Longo, Leonardo Oggiano, Pier Francesco Costici, Laura Ruzzini, Sergio De Salvatore, and Rocco Papalia

Subjects
Male, 030222 orthopedics, Pediatrics, medicine.medical_specialty, business.industry, Incidence (epidemiology), Subtalar joint arthroereisis, Subtalar Joint, 030229 sport sciences, Flatfoot, Hospitalization, 03 medical and health sciences, 0302 clinical medicine, Italy, Hospital discharge, Humans, Medicine, Orthopedics and Sports Medicine, Christian ministry, In patient, business, Flexible Flatfoot
Abstract

Subtalar Joint Arthroereisis (SJA) is the most used technique for the treatment of flexible flatfoot. Limited data are reported to trends of hospitalisation for SJA. This study aimed to estimate annual admissions and the geographical distribution of SJA in young Italian patients from 2009 to 2016.Data of this study were collected from the National Hospital Discharge Reports reported at the Italian Ministry of Health. The yearly number of SJA, sex, age and days of hospitalisation were calculated. Public and Private hospitalisations have been analysed individually.1.6762 hospitalisations for SJA were performed in Italy during the study period, and the incidence increased from 8.22 to 117.08 (cases/100,000 inhabitants). Men represented the majority of young patients treated by SJA. The mean length of stay was 1.55 ± 0.818 days.The prevalence of admissions of young patients for SJA increases from 2009 to 2016. The majority of the procedure was performed in public hospitals, but a shorter length of stay was reported in patients treated in private hospitals (p 0.001). This study highlighted the limits of ICD-9; in fact, difficulties in procedure codification and heterogeneity in diagnosis and procedures performed were reported.

Published
2022

13. Psychological Approaches for the Integrative Care of Chronic Low Back Pain: A Systematic Review and Metanalysis

Author

Giorgia Petrucci, Giuseppe Francesco Papalia, Fabrizio Russo, Gianluca Vadalà, Michela Piredda, Maria Grazia De Marinis, Rocco Papalia, and Vincenzo Denaro

Subjects
Adult, mindfulness-based stress reduction, Health, Toxicology and Mutagenesis, Public Health, Environmental and Occupational Health, Review, cognitive behavioral therapy, fear-avoidance beliefs, disability, depression, Quality of Life, Humans, Medicine, Chronic Pain, Mindfulness, low back pain
Abstract

Chronic low back pain (CLBP) is the most common cause of disability worldwide, affecting about 12% to 30% of the adult population. Psychological factors play an important role in the experience of pain, and may be predictive of pain persistence, disability, and long-term sick leave. The aim of this meta-analysis was to identify and to describe the most common psychological approaches used to treat patients who suffer from CLBP. A systematic search was performed on PubMed/MEDLINE and Cochrane Central. Overall, 16 studies with a total of 1058 patients were included in the analysis. Our results suggest that cognitive behavioral therapy (CBT) and mindfulness-based stress reduction (MBSR) interventions are both associated with an improvement in terms of pain intensity and quality of life when singularly compared to usual care. Disability also improved in both groups when compared to usual care. Significant differences in fear-avoidance beliefs were noted in the CBT group compared to usual care. Therefore, psychological factors are related to and influence CLBP. It is crucial to develop curative approaches that take these variables into account. Our findings suggest that CBT and MBSR modify pain-related outcomes and that they could be implemented in clinical practice.

Published
2022

14. Retear rates after rotator cuff surgery: a systematic review and meta-analysis

Author

Arianna Carnevale, Vincenzo Denaro, Emiliano Schena, Alessandra Berton, Vincenzo Candela, Umile Giuseppe Longo, and Ilaria Piergentili

Subjects
Rotator cuff, medicine.medical_specialty, Sports medicine, medicine.medical_treatment, Rotator cuff tear, Diseases of the musculoskeletal system, Cochrane Library, Arthroplasty, Rotator Cuff Injuries, Timing of retear, Arthroscopy, Rheumatology, Medicine, Humans, Orthopedics and Sports Medicine, Rehabilitation, business.industry, Odds ratio, Magnetic Resonance Imaging, Confidence interval, Rotator cuff retear, Surgery, medicine.anatomical_structure, Treatment Outcome, Risk factors, RC925-935, Meta-analysis, Orthopedic surgery, business, Research Article
Abstract

BackgroundRotator cuff retear (RCR) is one of the main postoperative drawbacks. RCR can be considered a multifactorial issue, which causes are related either to biological than biomechanical factors. The aim of this study was to define the incidence of RCR after surgical treatment at different time points and to identify the main factors influencing the postoperative rotator cuff (RC) healing.MethodsA systematic review and meta-analysis were performed following the PRISMA guidelines. A comprehensive search of the literature was carried out in July 2020, using PubMed and Cochrane Library databases. Only level 1 and 2 clinical evidence studies were included. Studies were included if patients with preoperative repairable full-thickness RC tears were treated surgically, and if studies reported postoperative RCR confirmed by imaging diagnostic. The association between timing of retear and follow-up time points were investigated using an inverse-variance method of pooling data. A subgroup meta-analysis was performed using the DerSimonian and Laird method for the estimation of the between-study variance, i.e., τ2. The association between retear rate after surgery and patients’ age, preoperative tear size, fatty infiltration, postoperative rehabilitation protocol, surgical techniques, and RC repairs was determined by expressing the effect measure in terms of odds ratio (OR) with 95% confidence interval (CI). The Mantel-Haenszel method with 95% CIs was used.ResultsThirty-one articles were included in this study. The percentage of RCR after surgery was 15% at 3 months follow-up, 21% at 3–6 months follow-up, 16% at 6–12 months follow-up, 21% at 12–24 months follow-up, 16% at follow-up longer than 24 months. The main factors influencing RC healing are both patient-related (i.e., age, larger tear size, fatty infiltration) and not patient-related (i.e., postoperative rehabilitation protocol, surgical techniques, and procedures).ConclusionsPostoperative RC healing is influenced by patient-related and non-patient-related factors. Further high-level clinical studies are needed to provide highly relevant clinical results.

Published
2021

15. Management of intracranial hypertension following traumatic brain injury: a best clinical practice adoption proposal for intracranial pressure monitoring and decompressive craniectomy. Joint statements by the Traumatic Brain Injury Section of the Italian Society of Neurosurgery (SINch) and the Neuroanesthesia and Neurocritical Care Study Group of the Italian Society of Anesthesia, Analgesia, Resuscitation and Intensive Care (SIAARTI)

Author

Iaccarino C., Lippa L., Munari M., Castioni C. A., Robba C., Caricato A., Pompucci A., Signoretti S., Zona G., Rasulo F. A., Aimar E., Amato S., Angileri F. F., Anile C., Assietti R., Baratto V., Barbanera A., Basile L., Battaglia R., Bellocchi S., Bertuccio A., Blanco S., Bolognini A., Boniferro B., Bordi L., Bortolotti C., Brandini V., Broger M., Brollo M., Caffarella D. D., Caggiano C., Cantisani P. L., Capone C., Cappelletto B., Capuano C., Carangelo B., Caruselli G., Chessa M. A., Chiara M., Chibbaro S., Cioffi V., Ciprianocecchi P., Colistra D., Conti C., Contratti F., Costella G. B., Cuoci A., D'Avella D., D'Ercole M., Deangelis M., Defalco R., de Luca G., de Marinis P., Del Vecchio C., Delfinis C., Denaro L., Deodato F., Desogus N., Disomma A., Domenicucci M., Dones F., Fina M., Fiori L., Fricia M., Gaetani P., Gazzeri R., Gentile M., Germano A., Ghadirpour R., Gianfreda C. D., Gigante N., Gigli R., Giorgetti J., Giusa M., Gravina U. G., Grippi L., Guida F., Guizzardi G., Iannuzzo G., Kropp M., Lattanzi L., Lucantoni D., Maffei L., Magliulo M., Marconi F., Marruzzo D., Martellotta N., Marton E., Maugeri R., Mauro G., Meli F., Menniti A., Merciadri P., Milanese L., Nardacci B., Nasi D., Orvieto P., Pacca P., Pansini G., Panzarasa G., Passanisi M., Pavesi G., Pizzoni C., Pulera F., Rapana A., Ricci A., Rispoli R., Rotondo M., Russo N., Santilli S., Scarano E., Schwarz A., Servadei F., Simonetti G., Stefini R., Talamonti G., Turrisi A., Valente V. M., Villa A., Vindigni M., Visocchi M., Vitali M., Wierzbicki V., Zambon G., Zanotti B., Zenga F., Alampi D., Alessandri F., Aloj F., Amigoni A., Aspide R., Bertuetti R., Betti V., Bilotta F., Bonato V., Bosco E., Brita M., Buscema G., Cafiero T., Cappuccio D., Caradonna M., Caria C. G., Casartelliliviero M., Ciritella P., Cirrincione S., Citerio G., Colelli S., Coletta F., Concordia L., Congedo E., Covotta M., Crimella F., Dall'Acqua G., De Cassai A., Defulviis S., Deperi E., Deana C., Delgaudio A., Denittis N., Dicolandrea S., Divezza F., Ferri F., Flocco R., Fontana C., Forastierimolinari A., Frangiosa A., Fumagalli P., Fuselli E., Garbarino M. M., Gelormini D., Geraci C., Geraldini F., Giacomucci A., Giampaoli V., Giorgetti D., Gritti P., Gualdani S., Iacovazzo C., Iermano C., Latronico N., Lugari S., Lusenti F., Maglione C., Magnoni S., Maiarota F., Malla M., Marchesi M., Martino C., Matteotti I., Mazzeo A. T., Morello G., Nardiello I., Paticchio F., Pegoli M., Perotti V., Piazzolla M., Picciafuochi F., Rachedi N., Radolovich D. K., Recchia A., Riccardi S., Romagnoli S., Sala S., Scafuro M. A., Sgarlata P., Soragni A., Stefani F., Stival E., Stofella G., Terranova F., Tinturini R., Togni T., Toto R., Trapani D., Tringali E., Tullo L., Valente A., Valeo T., Varelli G., Villani R., Zamacavicchi F., Zanello M., Zarrillo N., Zugni N., Iaccarino, C, Lippa, L, Munari, M, Castioni, C, Robba, C, Caricato, A, Pompucci, A, Signoretti, S, Zona, G, Rasulo, F, Aimar, E, Amato, S, Angileri, F, Anile, C, Assietti, R, Baratto, V, Barbanera, A, Basile, L, Battaglia, R, Bellocchi, S, Bertuccio, A, Blanco, S, Bolognini, A, Boniferro, B, Bordi, L, Bortolotti, C, Brandini, V, Broger, M, Brollo, M, Caffarella, D, Caggiano, C, Cantisani, P, Capone, C, Cappelletto, B, Capuano, C, Carangelo, B, Caruselli, G, Chessa, M, Chiara, M, Chibbaro, S, Cioffi, V, Ciprianocecchi, P, Colistra, D, Conti, C, Contratti, F, Costella, G, Cuoci, A, D'Avella, D, D'Ercole, M, Deangelis, M, Defalco, R, de Luca, G, de Marinis, P, Del Vecchio, C, Delfinis, C, Denaro, L, Deodato, F, Desogus, N, Disomma, A, Domenicucci, M, Dones, F, Fina, M, Fiori, L, Fricia, M, Gaetani, P, Gazzeri, R, Gentile, M, Germano, A, Ghadirpour, R, Gianfreda, C, Gigante, N, Gigli, R, Giorgetti, J, Giusa, M, Gravina, U, Grippi, L, Guida, F, Guizzardi, G, Iannuzzo, G, Kropp, M, Lattanzi, L, Lucantoni, D, Maffei, L, Magliulo, M, Marconi, F, Marruzzo, D, Martellotta, N, Marton, E, Maugeri, R, Mauro, G, Meli, F, Menniti, A, Merciadri, P, Milanese, L, Nardacci, B, Nasi, D, Orvieto, P, Pacca, P, Pansini, G, Panzarasa, G, Passanisi, M, Pavesi, G, Pizzoni, C, Pulera, F, Rapana, A, Ricci, A, Rispoli, R, Rotondo, M, Russo, N, Santilli, S, Scarano, E, Schwarz, A, Servadei, F, Simonetti, G, Stefini, R, Talamonti, G, Turrisi, A, Valente, V, Villa, A, Vindigni, M, Visocchi, M, Vitali, M, Wierzbicki, V, Zambon, G, Zanotti, B, Zenga, F, Alampi, D, Alessandri, F, Aloj, F, Amigoni, A, Aspide, R, Bertuetti, R, Betti, V, Bilotta, F, Bonato, V, Bosco, E, Brita, M, Buscema, G, Cafiero, T, Cappuccio, D, Caradonna, M, Caria, C, Casartelliliviero, M, Ciritella, P, Cirrincione, S, Citerio, G, Colelli, S, Coletta, F, Concordia, L, Congedo, E, Covotta, M, Crimella, F, Dall'Acqua, G, De Cassai, A, Defulviis, S, Deperi, E, Deana, C, Delgaudio, A, Denittis, N, Dicolandrea, S, Divezza, F, Ferri, F, Flocco, R, Fontana, C, Forastierimolinari, A, Frangiosa, A, Fumagalli, P, Fuselli, E, Garbarino, M, Gelormini, D, Geraci, C, Geraldini, F, Giacomucci, A, Giampaoli, V, Giorgetti, D, Gritti, P, Gualdani, S, Iacovazzo, C, Iermano, C, Latronico, N, Lugari, S, Lusenti, F, Maglione, C, Magnoni, S, Maiarota, F, Malla, M, Marchesi, M, Martino, C, Matteotti, I, Mazzeo, A, Morello, G, Nardiello, I, Paticchio, F, Pegoli, M, Perotti, V, Piazzolla, M, Picciafuochi, F, Rachedi, N, Radolovich, D, Recchia, A, Riccardi, S, Romagnoli, S, Sala, S, Scafuro, M, Sgarlata, P, Soragni, A, Stefani, F, Stival, E, Stofella, G, Terranova, F, Tinturini, R, Togni, T, Toto, R, Trapani, D, Tringali, E, Tullo, L, Valente, A, Valeo, T, Varelli, G, Villani, R, Zamacavicchi, F, Zanello, M, Zarrillo, N, Zugni, N, Iaccarino, C., Lippa, L., Munari, M., Castioni, C. A., Robba, C., Caricato, A., Pompucci, A., Signoretti, S., Zona, G., Rasulo, F. A., Aimar, E., Amato, S., Angileri, F. F., Anile, C., Assietti, R., Baratto, V., Barbanera, A., Basile, L., Battaglia, R., Bellocchi, S., Bertuccio, A., Blanco, S., Bolognini, A., Boniferro, B., Bordi, L., Bortolotti, C., Brandini, V., Broger, M., Brollo, M., Caffarella, D. D., Caggiano, C., Cantisani, P. L., Capone, C., Cappelletto, B., Capuano, C., Carangelo, B., Caruselli, G., Chessa, M. A., Chiara, M., Chibbaro, S., Cioffi, V., Ciprianocecchi, P., Colistra, D., Conti, C., Contratti, F., Costella, G. B., Cuoci, A., D'Avella, D., D'Ercole, M., Deangelis, M., Defalco, R., de Luca, G., de Marinis, P., Del Vecchio, C., Delfinis, C., Denaro, L., Deodato, F., Desogus, N., Disomma, A., Domenicucci, M., Dones, F., Fina, M., Fiori, L., Fricia, M., Gaetani, P., Gazzeri, R., Gentile, M., Germano, A., Ghadirpour, R., Gianfreda, C. D., Gigante, N., Gigli, R., Giorgetti, J., Giusa, M., Gravina, U. G., Grippi, L., Guida, F., Guizzardi, G., Iannuzzo, G., Kropp, M., Lattanzi, L., Lucantoni, D., Maffei, L., Magliulo, M., Marconi, F., Marruzzo, D., Martellotta, N., Marton, E., Maugeri, R., Mauro, G., Meli, F., Menniti, A., Merciadri, P., Milanese, L., Nardacci, B., Nasi, D., Orvieto, P., Pacca, P., Pansini, G., Panzarasa, G., Passanisi, M., Pavesi, G., Pizzoni, C., Pulera, F., Rapana, A., Ricci, A., Rispoli, R., Rotondo, M., Russo, N., Santilli, S., Scarano, E., Schwarz, A., Servadei, F., Simonetti, G., Stefini, R., Talamonti, G., Turrisi, A., Valente, V. M., Villa, A., Vindigni, M., Visocchi, M., Vitali, M., Wierzbicki, V., Zambon, G., Zanotti, B., Zenga, F., Alampi, D., Alessandri, F., Aloj, F., Amigoni, A., Aspide, R., Bertuetti, R., Betti, V., Bilotta, F., Bonato, V., Bosco, E., Brita, M., Buscema, G., Cafiero, T., Cappuccio, D., Caradonna, M., Caria, C. G., Casartelliliviero, M., Ciritella, P., Cirrincione, S., Citerio, G., Colelli, S., Coletta, F., Concordia, L., Congedo, E., Covotta, M., Crimella, F., Dall'Acqua, G., De Cassai, A., Defulviis, S., Deperi, E., Deana, C., Delgaudio, A., Denittis, N., Dicolandrea, S., Divezza, F., Ferri, F., Flocco, R., Fontana, C., Forastierimolinari, A., Frangiosa, A., Fumagalli, P., Fuselli, E., Garbarino, M. M., Gelormini, D., Geraci, C., Geraldini, F., Giacomucci, A., Giampaoli, V., Giorgetti, D., Gritti, P., Gualdani, S., Iacovazzo, C., Iermano, C., Latronico, N., Lugari, S., Lusenti, F., Maglione, C., Magnoni, S., Maiarota, F., Malla, M., Marchesi, M., Martino, C., Matteotti, I., Mazzeo, A. T., Morello, G., Nardiello, I., Paticchio, F., Pegoli, M., Perotti, V., Piazzolla, M., Picciafuochi, F., Rachedi, N., Radolovich, D. K., Recchia, A., Riccardi, S., Romagnoli, S., Sala, S., Scafuro, M. A., Sgarlata, P., Soragni, A., Stefani, F., Stival, E., Stofella, G., Terranova, F., Tinturini, R., Togni, T., Toto, R., Trapani, D., Tringali, E., Tullo, L., Valente, A., Valeo, T., Varelli, G., Villani, R., Zamacavicchi, F., Zanello, M., Zarrillo, N., and Zugni, N.

Subjects
medicine.medical_specialty, Decompressive Craniectomy, Consensus development conference, Decompressive craniectomy, Guideline, Traumatic brain injuries, Critical Care, Intracranial Pressure, medicine.medical_treatment, MEDLINE, Neurosurgery, Traumatic brain injurie, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Intensive care, Settore MED/41 - ANESTESIOLOGIA, Brain Injuries, Traumatic, medicine, Humans, Anesthesia, Intensive care medicine, Randomized Controlled Trials as Topic, business.industry, Neurointensive care, Evidence-based medicine, Italy, 030220 oncology & carcinogenesis, Intracranial pressure monitoring, Surgery, Neurology (clinical), Analgesia, Intracranial Hypertension, business, 030217 neurology & neurosurgery, Human
Abstract

No robust evidence is provided by literature regarding the management of intracranial hypertension following severe traumatic brain injury (TBI). This is mostly due to the lack of prospective randomized controlled trials (RCTs), the presence of studies containing extreme heterogeneously collected populations and controversial considerations about chosen outcome. A scientific society should provide guidelines for care management and scientific support for those areas for which evidence-based medicine has not been identified. However, RCTs in severe TBI have failed to establish intervention effectiveness, arising the need to make greater use of tools such as Consensus Conferences between experts, which have the advantage of providing recommendations based on experience, on the analysis of updated literature data and on the direct comparison of different logistic realities. The Italian scientific societies should provide guidelines following the national laws ruling the best medical practice. However, many limitations do not allow the collection of data supporting high levels of evidence for intracranial pressure (ICP) monitoring and decompressive craniectomy (DC) in patients with severe TBI. This intersociety document proposes best practice guidelines for this subsetting of patients to be adopted on a national Italian level, along with joint statements from "TBI Section" of the Italian Society of Neurosurgery (SINch) endorsed by the Neuroanesthesia and Neurocritical Care Study Group of the Italian Society of Anesthesia, Analgesia, Resuscitation and Intensive Care (SIAARTI). Presented here is a recap of recommendations on management of ICP and DC supported a high level of available evidence and rate of agreement expressed by the assemblies during the more recent consensus conferences, where members of both groups have had a role of active participants and supporters. The listed recommendations have been sent to a panel of experts consisting of the 107 members of the "TBI Section" of the SINch and the 111 members of the Neuroanesthesia and Neurocritical Care Study Group of the SIAARTI. The aim of the survey was to test a preliminary evaluation of the grade of predictable future adherence of the recommendations following this intersociety proposal. The following recommendations are suggested as representing best clinical practice, nevertheless, adoption of local multidisciplinary protocols regarding thresholds of ICP values, drug therapies, hemostasis management and perioperative care of decompressed patients is strongly recommended to improve treatment efficiency, to increase the quality of data collection and to provide more powerful evidence with future studies. Thus, for this future perspective a rapid overview of the role of the multimodal neuromonitoring in the optimal severe TBI management is also provided in this document. It is reasonable to assume that the recommendations reported in this paper will in future be updated by new observations arising from future trials. They are not binding, and this document should be offered as a guidance for clinical practice through an intersociety agreement, taking in consideration the low level of evidence.

Published
2021

16. Early surgery and definitive cure in small sporadic vestibular schwannoma

Author

Elisabetta Zanoletti, Stefano Concheri, Giulia Tealdo, Diego Cazzador, Luca Denaro, Domenico d’Avella, and Antonio Mazzoni

Subjects
General Energy, Postoperative Complications, Treatment Outcome, Otorhinolaryngology, Hearing, Hearing Loss, Sensorineural, Hearing Tests, Humans, Neuroma, Acoustic, Retrospective Studies
Abstract

To report surgical outcomes of a cohort of small sporadic vestibular schwannoma and discuss the role of early surgery.Retrospective descriptive analysis of 234 consecutive patients with small vestibular schwannoma operated on with translabyrinthine or hearing preservation surgical approaches. Outcome measures were control of disease, postoperative facial nerve function, complications and hearing outcome.A translabyrinthine approach was performed in 59% of cases, hearing preservation surgery in 40% and transmeatal approach in 1%, respectively. Complete resection was achieved in 100% of cases. Overall, postoperative major and minor complications were 8.5% in the series, with complete recovery and no sequalae. Facial nerve function at one year postoperatively was House-Brackmann scale (HB) 1-2 in 95% of cases. The rate of hearing preservation was 70% A-B-C classes of Tokyo classification and 77% AB classes of AAOHNS classification.Early surgery in small vestibular schwannoma is a valid option, due to good functional outcomes, low morbidity and definitive cure. Early surgery is associated with better outcomes when considered in relation to non-surgical treatments reported in the literature.Chirurgia precoce e guarigione definitiva nel piccolo schwannoma vestibolare sporadico.Presentare i risultati chirurgici di una serie di piccoli neurinomi sporadici e discutere il ruolo della chirurgia precoce nel trattamento.Analisi retrospettiva e descrittiva di 234 pazienti affetti da piccolo schwannoma vestibolare operato con approccio translabirintico o chirurgia di preservazione dell’udito (HPS). I risultati sono discussi alla luce del controllo di malattia, della funzione postoperatoria del nervo facciale, dell’insorgenza di complicanze e della preservazione uditiva.L’approccio translabirintico è stato eseguito nel 59% dei casi, HPS nel 40% e quello transmeatale nell’1%. La resezione completa è stata ottenuta nel 100% dei casi. Si sono osservate complicanze postoperatorie nell’8,5% dei casi, risoltesi con completa guarigione e assenza di sequele. La funzione del nervo facciale a 1 anno dall’intervento è stata I-II HB nel 95% dei casi; il tasso di conservazione dell’udito del 70% in classe A-B-C secondo la classificazione di Tokyo e del 77% in classe A-B secondo la classificazione AAO-HNS.La chirurgia precoce nel piccolo schwannoma vestibolare si è rivelata essere un’opzione conveniente in alternativa alle terapie non chirurgiche, considerate nell’intero corso della terapia, in ragione dei risultati, della bassa morbidità e della guarigione definitiva.

Published
2022

17. An Inflammatory Signature to Predict the Clinical Benefit of First-Line Cetuximab Plus Platinum-Based Chemotherapy in Recurrent/Metastatic Head and Neck Cancer

Author

Stefano Cavalieri, Mara Serena Serafini, Andrea Carenzo, Silvana Canevari, Deborah Lenoci, Federico Pistore, Rosalba Miceli, Stefania Vecchio, Daris Ferrari, Cecilia Moro, Andrea Sponghini, Alessia Caldara, Maria Cossu Rocca, Simona Secondino, Gabriella Moretti, Nerina Denaro, Francesco Caponigro, Emanuela Vaccher, Gaetana Rinaldi, Francesco Ferraù, Paolo Bossi, Lisa Licitra, and Loris De Cecco

Subjects
Inflammation, inflammatory signature, Squamous Cell Carcinoma of Head and Neck, Settore MED/06 - Oncologia Medica, General Medicine, targeted therapy, HNSCC, gene-expression, ErbB Receptors, Neoplasm Recurrence, Local, cetuximab, immune biomarkers, Antineoplastic Combined Chemotherapy Protocols, Cetuximab, Humans, Neoplasm Recurrence, Local, Head and Neck Neoplasms, Platinum
Abstract

Epidermal growth factor receptor (EGFR) pathway has been shown to play a crucial role in several inflammatory conditions and host immune-inflammation status is related to tumor prognosis. This study aims to evaluate the prognostic significance of a four-gene inflammatory signature in recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients treated with the EGFR inhibitor cetuximab plus chemotherapy. The inflammatory signature was assessed on 123 R/M HNSCC patients, enrolled in the multicenter trial B490 receiving first-line cetuximab plus platinum-based chemotherapy. The primary endpoint of the study was progression free survival (PFS), while secondary endpoints were overall survival (OS) and objective response rate (ORR). The patient population was subdivided into 3 groups according to the signature score groups. The four-genes-signature proved a significant prognostic value, resulting in a median PFS of 9.2 months in patients with high vs. 6.2 months for intermediate vs. 3.9 months for low values (p = 0.0016). The same findings were confirmed for OS, with median time of 18.4, 13.4, and 7.5 months for high, intermediate, and low values of the score, respectively (p = 0.0001). When ORR was considered, the signature was significantly higher in responders than in non-responders (p = 0.0092), reaching an area under the curve (AUC) of 0.65 (95% CI: 0.55–0.75). Our findings highlight the role of inflammation in the response to cetuximab and chemotherapy in R/M-HNSCC and may have translational implications for improving treatment selection.

Published
2022

18. Shoulder replacement: an epidemiological nationwide study from 2009 to 2019

Author

Umile Giuseppe, Longo, Rocco, Papalia, Alessandro, Castagna, Sergio, De Salvatore, Enrico, Guerra, Ilaria, Piergentili, and Vincenzo, Denaro

Subjects
Adult, Reoperation, Treatment Outcome, Rheumatology, Arthroplasty, Replacement, Shoulder, Shoulder Joint, Humans, Female, Orthopedics and Sports Medicine, Hemiarthroplasty, Prospective Studies, Arthroplasty, Replacement, State Medicine
Abstract

Background Shoulder replacement (SR) constitutes the gold standard treatment for severe shoulder diseases, including osteoarthritis, rheumatoid arthritis, complex fractures, avascular necrosis and rotator cuff arthropathy. Although several countries have national registries, there is a lack of epidemiological data on SR. Sharing national statistics and correlating those to other countries could be helpful to compare outcomes and costs internationally. This paper aims to evaluate the trend of hospitalizations for SR (both first implants and revisions of anatomical and reverse prosthesis) in Italy from 2009 to 2019, based on the National Hospital Discharge Reports (S.D.O) provided by the Italian National Health Service (INHS). Moreover, the economic impact on the healthcare system of SR and SR revisions was assessed, providing a statistical prediction for the next ten years. Methods The data used in this paper were about patients who underwent Total Shoulder Replacement (TSR), Shoulder Hemiarthroplasty (SH) or Revision of shoulder joint replacement (RSR) from 2009 to 2019 in Italy. Information about patients was anonymous and included age, sex, days of hospitalization, procedures and diagnoses codes. Results From 2009 to 2019, 73,046 TSR and SH were performed in adult Italian residents, with a cumulative incidence of 13.6 cases per 100,000 adult Italian residents. While, 2,129 revisions of shoulder replacement were performed, with a cumulative incidence of 0.4 cases per 100,000 residents. Overall, females represented the majority of the cases (72.4% of patients who underwent TSR or SH and 59.1% of patients who underwent RSR). From 2009 to 2019, has been assessed an overall cost of 625,638,990€ for TSR or SH procedures in Italy. While, an overall cost of 9,855,141€ for RSR procedures in Italy was calculated. Conclusions The incidence of SR and RSR is expected to increase in the following years, constituting a burden for the healthcare systems. Overall, in Italy, the females represented the majority of patients. Further prospective studies on this topic in different countries can be con-ducted to make comparisons.

Published
2022

19. COVID-19 and neurodegeneration: The mitochondrial connection

Author

Christopher A. Denaro, Yara I. Haloush, Samuel Y. Hsiao, John J. Orgera, Teresa Osorio, Lindsey M. Riggs, Joshua W. Sassaman, Sarah A. Williams, Anthony R. Monte Carlo, Renata T. Da Costa, Andrey Grigoriev, and Maria E. Solesio

Subjects
Central Nervous System, Aging, SARS-CoV-2, Blood-Brain Barrier, Humans, COVID-19, Cell Biology, Mitochondria
Abstract

There is still a significant lack of knowledge regarding many aspects of the etiopathology and consequences of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in humans. For example, the variety of molecular mechanisms mediating this infection, and the long-term consequences of the disease remain poorly understood. It first seemed like the SARS-CoV-2 infection primarily caused a serious respiratory syndrome. However, over the last years, an increasing number of studies also pointed towards the damaging effects of this infection has on the central nervous system (CNS). In fact, evidence suggests a possible disruption of the blood-brain barrier and deleterious effects on the CNS, especially in patients who already suffer from other pathologies, such as neurodegenerative disorders. The molecular mechanisms behind these effects on the CNS could involve the dysregulation of mitochondrial physiology, a well-known early marker of neurodegeneration and a hallmark of aging. Moreover, mitochondria are involved in the activation of the inflammatory response, which has also been broadly described in the CNS in COVID-19. Here, we critically review the current bibliography regarding the presence of neurodegenerative symptoms in COVID-19 patients, with a special emphasis on the mitochondrial mechanisms of these disorders.

Published
2022

20. Initial Invasive or Conservative Strategy for Stable Coronary Disease

Author

Maron D. J., Hochman J. S., Reynolds H. R., Bangalore S., O'Brien S. M., Boden W. E., Chaitman B. R., Senior R., Lopez-Sendon J., Alexander K. P., Lopes R. D., Shaw L. J., Berger J. S., Newman J. D., Sidhu M. S., Goodman S. G., Ruzyllo W., Gosselin G., Maggioni A. P., White H. D., Bhargava B., Min J. K., John Mancini G. B., Berman D. S., Picard M. H., Kwong R. Y., Ali Z. A., Mark D. B., Spertus J. A., Krishnan M. N., Elghamaz A., Moorthy N., Hueb W. A., Demkow M., Mavromatis K., Bockeria O., Peteiro J., Miller T. D., Szwed H., Doerr R., Keltai M., Selvanayagam J. B., Gabriel Steg P., Held C., Kohsaka S., Mavromichalis S., Kirby R., Jeffries N. O., Harrell F. E., Rockhold F. W., Broderick S., Bruce Ferguson T., Williams D. O., Harrington R. A., Stone G. W., Rosenberg Y, ISCHEMIA Research Group: Joseph Ricci, A Tello Montoliu, A I Robero Aniorte, Abbey Mulder, Abhay A Laddu, Abhinav Goyal, Abhishek Dubey, Abhishek Goyal, Abigail Knighton, Abraham Oomman, Adam J Jaskowiak, Adam Kolodziej, Adam Witkowski, Adnan Hameed, Adriana Anesini, Afshan Hussain, Agne Juceviciene, Agne Urboniene, Agnes Jakal, Agnieszka Szramowska, Ahmad Khairuddin, Ahmed Abdel-Latif, Ahmed Adel, Ahmed Aljzeeri, Ahmed Kamal, Ahmed Talaat, Aimee Mann, Aira Contreras, Ajit Kumar, V K Kumar, Akemi Furukawa, Akshay Bagai, Akvile Smigelskaite, Alain Furber, Alain Rheault, Alaine Melanie Loehr, Alan Rosen, Albert Varga, Albertina Qelaj, Alberto Barioli, Aldo Russo, Alec Moorman, Alejandro Gisbert, Aleksandra Fratczak, Aleksandras Laucevicius, Alena Kuleshova, Alessandro Sionis, Alexander A Sirker, Alexander M Chernyavskiy, Alexandra Craft, Alexandra Vazquez, Alexandre Ciappina Hueb, Alexandre S Colafranseschi, Alexandre Schaan de Quadros, Alexandre Tognon, Ali Alghamdi, Alice Manica Muller, Aline Nogueira Rabaça, Aline Peixoto Deiro, Alison Hallam, Allegra Stone, Allison Schley, Almudena Castro, Alvaro Rabelo Ales, Amanda Germann, Amanda O'Malley, Amar Uxa, Amarachi Ojajuni, Amarino C Oliveira Jr, Amber B Hull, Ambuj Roy, Amer Zarka, Amir Janmohamed, Ammani Brown, Ammy Malinay, Amparo Martinez Monzonis, Amy J Richards, Amy Iskandrian, Amy Ollinger, Ana D Djordjevic-Dikic, Ana Fernández Martínez, Ana Gomes Almeida, Ana Paula Batista, Ana Rita Francisco, Ana S Mladenovic, Ana Santana, Anam Siddiqui, Anastasia M Kuzmina-Krutetskaya, Andras Vertes, Andre S Sousa, Andre Gabriel, André Schmidt, Andrea M Lundeen, Andrea Bartykowszki, Andrea Lorimer, Andrea Mortara, Andrea Pascual, Andreia Coelho, Andreia Rocha, Andrés García-Rincón, Andrew G Howarth, Andrew J Moriarty, Andrew Docherty, Andrew Starovoytov, Andrew Zurick, Andrzej Łabyk, Andrzej Swiatkowski, Andy Lam, Anelise Kawakami, Angela Hoye, Angela Kim, Angelique Smit, Angelo Nobre, Anil V Shah, Anja Ljubez, Anjali Anand, Ankush Sachdeva, Ann Greenberg, Ann Luyten, Ann Ostrander, Anna Di Donato, Anna Cichocka-Radwan, Anna Fojt, Anna Plachcinska, Anna Proietti, Anna Teresinska, Anne Marie Webb, Anne Cartwright, Anne Heath, Anne Mackin, Anong Amaritakomol, Anong Chaiyasri, Anoop Chauhan, Anoop Mathew, Anthony Gemignani, Anto Luigi Andres, Antonia Vega, Antonietta Hansen, Antonino Ginel Iglesias, Antonio Carlos Carvalho, Antonio Di Chiara, Antonio Serra Peñaranda, Antonio Carvalho, Antonio Colombo, Antonio Fiarresga, Anupama Rao, Aquiles Valdespino-Estrada, Araceli Boan, Areef Ishani, Ariel Diaz, Arijit Ghosh, Arintaya Prommintikul, Arline Roberts, Arnold H Seto, Arnold P Good, Arshed Quyyumi, Arthur J Labovitz, Arthur Kerner, Arturo S Campos-Santaolalla, Arunima Misra, Ashok Mukherjee, Ashok Seth, Ashraf Seedhom, Asim N Cheema, Asker Ahmed, Atul Mathur, Atul Verma, Audrey W Leong, Axel Åkerblom, Axelle Fuentes, Aynun Naher, Badhma Valaiyapathi, Baljeet Kaur, Bandula Guruge, Barbara 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Euathrongchit, Jyotsna Garg, K Manjula Rani, K Preethi, Kaatje Goetschalckx, Kai Eggers, Kamalakar Surineni, Kanae Hirase, T R Kapilamoorthy, Karen Calfas, Karen Gratrix, Karen Hallett, Karen Hultberg, Karen Nugent, Karen Petrosyan, Karen Swan, Karolina Kryczka, Karolina Wojtczak-Soska, Karolina Wojtera, Karsten Lenk, Karthik Ramasamy, Katarzyna Łuczak, Katarzyna Malinowska, Kate Pointon, Kate Robb, Katherine Martin, Kathleen Claes, Kathryn Carruthers, Kathy E Siegel, Katia Drouin, Katie Fowler-Lehman, Kavita Rawat, Kay Rowe, Keiichi Fukuda, Keith A A Fox, Ken Mahaffey, Kendra Unterbrink, Kenneth Giedd, Kerrie Van Loo, Kerry Lee, Kerstin Bonin, Kevin R Bainey, Kevin T Harley, Kevin Anstrom, Kevin Chan, Kevin Croce, Kevin Landolfo, Kevin Marzo, Keyur Patel, Khaled Abdul-Nour, Khaled Alfakih, Khaled Dajani, Khaled Ziada, Khaula Baloch, Khrystyna Kushniriuk, Kian-Keong Poh, Kim F Ireland, Kim Holland, Kimberly Ann Byrne, Kimberly E Halverson, Kimberly Elmore, Kimberly Miller-Cox, Kiran Reddy, Kirsten J Quiles, Kirsty Abercrombie, Klaus Matschke, Konrad Szymczyk, Koo Hui Chan, Kotiboinna Preethi, Kozhaya Sokhon, Krissada Meemuk, Kristian Thygesen, Kristin M Salmi, Kristin Newby, Kristina Wippler, Kristine Arges, Kristine Teoh, Krystal Etherington, Krystyna Łoboz-Grudzień, Krzysztof W Reczuch, Krzysztof Bury, Krzysztof Drzymalski, Krzysztof Kukuła, Kuo-Tzu Sung, Kurt Huber, Ladda Douangvila, Lance Sullenberger, Larissa Miranda Trama, Laszlone Matics, Laura Drew, Laura Flint, Laura Keinaite, Laura Sarti, Laurel Kolakaluri, Lawrence M Phillips, Lawrence Friedman, Lawrence Phillips, Lazar Velicki, Leah Howell, Leandro C Maranan, Leanne Cox, Ledjalem Daba, Lei Zhang, Lekshmi Dharmarajan, Leo Bockeria, Leonardo Pizzol Caetano, Leonardo Bridi, Leonid L Bershtein, Leszek Sokalski, Li Hai Yan, Li Li, Lia Nijmeijer, Lidia Sousa, Lihong Xu, Lihua Zhang, Lili Zhang, Lilia Schiavi, Lilian Mazza Barbosa, Lillian L Khor, Lina Felix-Stern, Linda L Hall, Linda M Hollenweger, Linda Arcand, Linda Davidson-Ray, Linda Schwarz, Lindsey N Sikora, Lingping Chi, Lino Patricio, Liping Zhang, Lisa Chaytor, Lisa Hatch, Lisa McCloy, Lisa Wong, Liselotte Persson, Lixin Jiang, Liz Low, Ljiljana Pupic, Loïc Bière, Lorenzo Monti, Lori Christensen, Lori Pritchard, Loriane Black, Lori-Ann Desimone, Lori-Ann Larmand, Lorraine McGregor, Louise Morby, Louise Thomson, Luc Harvey, Luciana de Pádua Baptista, Lucilla Garcia, Ludivine Eliahou, Ludmila Helmer, Luis F Smidt, Luis Bernanrdes, Luis Guzman, Luiz A Carvalho, Luyang Xiong, Lynette L Teo, Lynn M Neeson, Lynne Winstanley, M Barbara Srichai-Parsia, M Quintana Giner, M Sowjanya Reddy, M Valdés Chávarri, M Grazia Rossi, Maarten Simoons, Maayan Konigstein, Maciej Lesiak, Maciej Olsowka, Mafalda Selas, Magalie Corfias, Magdalena Madero Rovalo, Magdalena Łanocha, Magdalena Miller, Magdalena Misztal-Teodorczyk, Magdalena Rantinella, Magdy Abdelhamid, Magnolia Jimenez, Mahboob Alam, Mahevamma Mylarappa, Mahfouz El Shahawy, Mahmoud Mohamed, Mahmud Al-Bustami, Majo X Joseph, Malgorzata Frach, Małgorzta Celińska-Spodar, Malte Helm, Manas Chacko, Mandy Murphy, Manitha Vinod, Manjula Rani, Manu Dhawan, Manuela Mombelli, Marcel Weber, Marcello Galvani, Marcelo Jamus Rodrigues, Marcia F Dubin, Marcia F Werner Bayer, Marcin Szkopiak, Marco Antonio Monsalve, Marco Bizzaro Santos, Marco Magnoni, Marco Marini, Marco Sicuro, Marco Zenati, Marcos Valério Coimbra Resende, Marek Roik, Margalit Bentzvi, Margaret Gilsenan, Margaret Iraola, Margot C Quinn, Maria A Alfonso, Maria Antonieta Pereira Moraes, María Dolores Martínez-Ruíz, María Fernanda Canales, Maria Inês Caetano, Maria P Corral, Maria Pérez García, Maria Victoria Actis, Maria Aguirre, Maria Andreasson, Maria Aprile, Maria Colton, Maria Eugenia Martin, Maria Lasala, Maria Lorenzo, Maria Posada, Maria Shier, Maria Thottam, Mariana V Furtado, Mariana Yumi Okada, Marianna D A Dracoulakis, Marianne De Andrade, Mariano Rubio, Marie Essermark, Marielle Scherrer-Crosbie, Marija T Petrovic, Marija Zdravkovic, Marilyn Black, Marina Garcia, Mario J Garcia, Mariola Szulik, Marisa Orgera, Mark A de Belder, Mark Harbinson, Mark Hyun, Mark Peterson, Mark Xavier, Marlowe Mosley, Marta Capinha, Marta Marcinkiewicz-Siemion, Marta Swiderek, Martha Meyer, Martina Ceseri, Martina Tricoli, Marvin Kronenberg, Mary Williams, Mary Ann Champagne, Mary Colleen Rogge, Mary R Soltau, Mary Streif, Massimo Villella, Massoud Leesar, Matei Claudia, Mateusz Solecki, Matías Nicolás Mungo, Matthew Wall Jr, Matthew Budoff, Matthew Jezior, Matthew Luckie, Matthias Friedrich, Mauren P Haeffner, Maximilian Tscharre, Max-Paul Winter, Mayana Almeida, Mayil S Krishnam, Mayuri Patel, Meenakshi Mishra, Megan Manocchia, Meghana Kakade, Melanie J Munro, Melissa D Chaplin, Melissa LeFevre, Mervyn Andiapen, Michael A Gibson, Michael B Rubens, Michael C Turner, Michael D Shapiro, Michael W Lee, Michael Berlowitz, Michael Davidson, Michael Mack, Michael McDaniel, Michael Mumma, Michal Wlodarczyk, Michel G Khouri, Michel S Slama, Michele Rawlins, Michelle M Bonner, Michelle M Seib, Michelle Chang, Michelle Crowder, Michelle Dixon, Michelle Mayon, Michelle McEvoy, Michelle Yee, Miguel M Fernandes, Miguel Nobre Menezes, Miguel Souto Bayarri, Miguel Barrero, Mikhail T Torosoff, Milan R Dobric, Milan Dobric, Milica Nikola Dekleva, Milind Avdhoot Gadkari, Millie Gomez, Min Tun Kyaw, Miriam Brooks, Miroslav Stevo Martinovic, Mitchel B Lustre, Mohammad Tariq Vakani, Mohammad El-Hajjar, Mohammed Al-Amoodi, Mohammed Hussain, Mohammed Saleem, Moisés Blanco-Calvo, Moisés Jiménez-Santos, Mona Bhatia, Monica Rosca, Monika Laukyte, Montserrat Gracida Blanca, Montserrat Vila Perales, Mouaz H Al-Mallah, Moysés de Oliveira Filho, Mpiko Ntsekhe, Muhamed Saric, Mulei Chen, Myriam Brousseau, Myrthes Emy Takiuti, Nada Cemerlic-Adjic, Nadia Asif, Nadia Gakou, Nafisa Hussain, Nana O Katamadze, Nancy L Clapp, Nancy Aedy, Nandita Nataraj, Nanette K Wenger, Naomi Uchida, Nasrul Ismail, Natalia S Oliveira, Natalia de Carvalho Maffei, Natalie Spitzer, Natasha C Putnam, Naved Aslam, Neamat Mowafy, Neeraj Pandit, Neeraj Parakh, Nevena Garcevic, Ngaire Meadows, Nhi N Tran, Nicholas Danchin, Nicki Lakeman, Nicola Johnston, Nicolas W Shammas, Nicole Saint Vrestil, Nicole Deming, Nier Zhong, Niket Patel, Nikola N Boskovic, Nikolaos Karogiannis, Nikos Werner, Nina Johnston, Ning Zhang, Ning Zhou, Niree Hindoyan, Nirmal Kumar, Nitika Chadha, Nitish Naik, Nodira Aripova, Noloyiso Mtana, Nona A Eskelson, Noor Syamira Mokhtar, Noppon Taksaudom, Nor Asiah Basri, Nora Marchelletta, Norma Hogg, Nungshi Jungla, Nuno Ferreira, Oksana A Lubyanaya, Olga B Nikolaeva, Olga Cañavate, Olga Sobrino, Olga Walesiak, Olga Walter, Olga Zdończyk, Olivia J Lim, Olivia Anaya, Olivia Mancilla, Olivier Dubourg, Olugbenga Bello, Omar Almousalli, Omar Thompson, Oni Olurinde, Or Harel, Osama Raheem, Oscar Méndiz, Óscar Prada-Delgado, Oz Shapira, P Christian Schulze, Pachara Panpunuan, Pal Maurovich-Horvat, Pallav Garg, Paloma Moraga, Pam Singh, Pamela Julian, Pamela Ouyang, Pamela Sigel, Pamela Woodard, Panpan Zhou, Paola Emanuela Poggio, Paola Smanio, Paolo Calabro, Paramjit Jeetley, Pascal Goube, Patricia K Nguyen, Patricia Alarie, Patricia Arakelian, Patricia Arsenault, Patricia Blaise, Patricia Brito, Patricia Cowper, Patricia Endsley, Patricia Mieses, Patrick B Alexander, Patrick Donnelly, Patrick Wilmot, Patrycja Lebioda, Paul C Gordon, Paul Der Mesropian, Paul Galiwango, Paul Hauptman, Paul Kennedy, Paula Beardsley, Paula García-González, Paulo Cury Rezende, Paulo Ricardo Caramori, Pavel S Kozlov, Pedro Canas Silva, Pedro Gabriel Melo Barros E Silva, Pedro Píccaro de Oliveira, Pedro Carvalho, Pedro Modas, Pedro Rio, Peeyush Jain, Peiyu He, Peter A McCullough, Peter H Stone, Peter M Pollak, Peter Douglass, Peter Henriksen, Peter OKane, Peter Ong, Philip Jones, Philip Rogal, Philippe Généreux, Philippe Menasche, Philippe Rheault, Phoebe Goold, Pierre Gervais, Pierre Michaud, Pilar Calvillo, Ping Chai, Piotr Jakubowski, Piotr Pruszczyk, Piotr Slomka, Piyamitr Sritara, Poay-Huan Loh, Poonam Sonawane, Pouneh Samadi, Pragnesh P Parikh, Prakash Deedwania, Pranav M Patel, Praneeth Polamuri, Pratiksha Sharma, Precilia Vasquez, Preeti Kamath, Prince Thomas, Priyadarshani Arambam, Puja K Mehta, Purvez Grant, Pushpa Naik, Qi Zhong, Qian Zhao, Qiang Zhou, Qianqian Yuan, Qin Yu, Qingxian Li, Qiulan Xie, Qiutang Zeng, R J Vindhya, R James Gerlach, Rachel King, Rada Vučić, Radmila Lyubarova, Radoslaw Pracon, Raewyn Fisher, Rafael Beyar, Rafael Diaz, Rafael Selgas, Raffaele Bugiardini, Raffaele Fanelli, Raisa Kavalakkat, V S Rajalekshmi, Rajat S Barua, Rajeev Menon, Rajesh Gopalan Nair, Rajesh Francis, Rajiv Narang, Rakesh Yadav, Ralph Alan Huston, T Ramakrishnan, Ramesh de Silva, Rami El Mahmoud, Ramiro Carvalho, Ramon de Jesús-Pérez, Ramona Stevens, Ran Leng, Ranjan Kachru, Ranjit Kumar Nath, Raquel Sanchez, Raven R Dwyer, Raven Lee, Ray Wyman, Raymond C Wong, Raymond W Little, Raymundo Ocaranza Sanchez, Rebecca J Wimmer, Rebecca Bariciano, Rebecca Otis, Rebekah R Herrmann, Reem Yunis, Reinette Hampson, Renato Abdala Karam, Renee C Hessian, Renee Kaneshiro, Reshma Ravindran, Reto Andreas Gamma, Reyna Bhandari, Reza Arsanjani, Ricardo L Lopes, Ricardo Mendes Oliveira, Ricardo Costa, Richa Bhatt, Richard F Davies, Richard H J Trimlett, Richard Goldweit, Rik Hermanides, Rine Nakanishi, Rinu R Sidh, Risha Patel, Rita Coram, Rizwan A Siddiqui, Rob S Beanlands, Robert J Hamburger, Robert K Riezebos, Robert M Donnino, Robert Bojar, Robert Chilton, Robert Guyton, Robert Henderson, Robert Kornberg, Robert Leber, Robert Mao, Robert Stenberg, Roberta P Santos, Roberto René Favaloro, Roberto Amati, Rodolfo G S D Lima, Rodrigo J Cerci, Rogerio Tumelero, Rohit Tandon, Roma Tewari, Romalisa Miranda-Peats, Ron Wald, Ronald A Mastouri, Ronald G Morford, Ronald G Schwartz, Ronald P Pedalino, Rongrong Hu, Ronnell A Hansen, Ronny A Cohen, Rory Hachamovitch, Rosa Homem, Rosa Sandonato, Rosane Laimer, Rosann Gans, Roxanne Yost, Roy Mathew, Rubén Baleón-Espinosa, Ruben Ramos, Rubine Gevorgyan, Rui Ferreira, Rui Jing, Ruth Pérez-Fernández, S K Dwivedi, S Ramakrishnan, Saadat Khan, Sabahat Bokhari, Sabu Thomas, Sadath Lubna, Sajeeda Parveen Khan, Sajeev Chakanalil Govindan, Saket Girotra, Saleem Kassam, Sallie Canada, Salvador Cruz-Flores, Samaa Mohamed, Samantha Ly, Sameh El Kaffas, Samia Massalha, Sampoornima Setty, Samuel Nwosu, Sandeep Seth, Sandeep Singh, Sander R Niehe, Sandra M Rivest, Sandra S Zier, Sandra Ahoud, Sandy Carr, Sanjay Ganapathi, Sanjay Shetty, Sanjeev Sharma, Santa Jimenez, Santhosh Satheesh, Santiago A Garcia, Sara Fernandez, Sara Karlsson, Sara Salkind, Sara Temiyasathit, Sarah Medina Rodriguez, Sarah Beaudry, Sarah Hadjih, Sarah Williams, Sarah Zahrani, Sarju Ralhan, Sasa Hinic, Sasko Kedev, Satinder Singh, Satoshi Yasuda, Satvic Cholenahally Manjunath, Sau Lee, Scott M Kaczkowski, Scott Kinlay, Sean W Hayes, Sebastian Sobczak, Senait Asier, Sergey A Sayganov, Seth I Sokol, Shaheen Pandie, Shaiful Azmi Yahaya, Shamir Mehta, Shao-Ping Nie, Sharad Chandra, Sharder Islam, Sharon Tai, Sheetal Rupesh Karwa, Sheri Ussery, Sheromani Bajaj, Sherron C Crook, Shigeyuki Nishimura, Shintaro Nakano, Shirin Heydari, Shiv Kumar Choudhary, Shivali Patel, Shobana Ganesan, Shruti Pandey, Shuyang Zhang, Shweta Hande, Siddharth Gadage, Sik-Yin V Tan, Silvia Zottis Poletti, Silvia Riera, Silvia Valbuena, Simon Walsh, Simona Maspoli, Simone Savaris, Si-Ting Feng, So Yang Cho, Solomon Yakubov, Songlin Zhu, Songtao Wang, Sonia Guerrero, Sonika Gupta, Sonja Salinger Martinovic, Sonya Brons, Sorin Brener, Sothinathan Gurunathan, Souheil Saba, Soundarya Nayak, Sowjanya Reddy, Srinivasa Potluri, Sriram Sudarshan, Srun Kuanprasert, Stacie Van Oosterhout, Stamatios Lerakis, Stanley E Cobos, Stefan C Bertog, Stefan M Simović, Stefan Weikl, Stefano Di Marco, Stefano Provasoli, Stephanie A Tirado, Stephanie C Boer, Stephanie M Lane, Stephanie Ferket, Stephanie Kelly, Stephanie Wasmiller, Stephen H McKellar, Stephen P Hoole, Stephen Fremes, Stephen Preston, Steve Leung, Steven A Fein, Steven J Lindsay, Steven P Sedlis, Steven Giovannone, Steven Michael, Steven Weitz, Stijn van Vugt, Subhash Banerjee, Sudhir Naik, Suellen Hosino, Sukie Desire, Sukit Yamwong, Suku T Thambar, Sulagna Mookherjee, Suman Singh, Sundeep Mishra, Sunil Kumar Verma, Supap Kulthawong, Supatchara Khwakhong, Surendra Naik, Suresh Babu, Surin Woragidpoonpol, Suryaprakash Narayanappa, Susan Derbyshire, Susan Gent, Susan Mathus, Susan Milbrandt, Susan Moore, Susan Regan, Susan Stinson, Susan Webber, Susana Silva, Susanna Stevens, Susanne Gruensfelder, Suthara Aramcharoen, Suvarna Kolhe, Suzana Tavares, Suzanne Arnold, Suzanne Welsh, Svetlana Apostolovic, Swapna Kunhunny, Ta-Chuan Hung, Taissa Zappernick, Tali Sharir, Talita Silva, Tamara Colaiácovo Soares, Tapan Umesh Pillay, Tarun K Mittal, Tatiana Trifonova, Tauane Bello Duarte, Tauqir Huk, Téodora Dutoiu, Terrance Chua, Terry Weyand, Thabitha Charles, Theodoros Kofidis, Theresa McCreary, Thierry Lefevre, Thippeekaa Arumairajah, Thitipong Tepsuwan, Thomas J Mulhearn, Thomas M Meyer, Thomas P Rocco, Thomas R Downes, Thomas Crain, Thomas Haldis, Thomas Mathew, Thomas Redick, Thounaojam Indira Devi, Thuraia Nageh, Tia Cauthren, Tiago Silva, Tiffany Little, Tijana Andric, Tina Harding, Titus Lau, Tiziana Formisano, Tiziano Moccetti, Tomasz Ciurus, Tomasz Mazurek, Tomasz Tarchalski, Toshiyuki Nagai, Tri Tran, Tricia Youn, Trish Tucker, Trudie Milner, Tuhina Bose, Tushar Kotecha, Udo Sechtem, Uma S Valeti, Umberto Cucchini, Umesh Badami, Upendra Kaul, V K Bahl, V S Narain, Valentina Casali, Valeria Godoy, Valerie Robesyn, Vamshi P Priya, Vandana Yadav, Vera McKinney, Veronica De Lenges, Veronica Tinnirello, Vicente Miro, Victor Navarro, Victoria Gumerova, Victoria Hernandez, Vidya Seeratan, Vijay Kumar, Vikentiy Y Kozulin, Viktoria Bulkley, Vilmar Veiga Jr, Vincent Setang, C P Vineeth, Virginai Pubull Nuñez, Virginia Fernández-Figares, Vitor Gomes, Viviana Gabriel, Viviane Dos Santos, Viviane Almeida, Vlad A Iliescu, Vladan Mudrenovic, Vladimir Dzavik, Vojislav L Giga, Walter Enrique Mogrovejo, Wan Xian Chan, Wanda C Marfori, Wanda Parker, Warangkana Mekara, Wassim Nona, Wayne Old, Wayne Pennachi, Weerachai Nawarawong, Wei Chen, Wei Su, Weibing Xing, Wei-Ren Lan, Wenda Crawford, Wendy L Stewart, Wendy Drewes, Wenhua Lin, William B Abernethy, William D Salerno, William F Fearon, William Vergoni, William Weintraub, Winnie C Sia, Wlodzimierz J Musial, Xacobe Flores-Ríos, Xavier Garcia-Moll Marimon, Xi Su, Xiang Ma, Xiangqiong Gu, Xiao Wang, Xiaomei Li, Xiaowei Yao, Xin Fu, Xin Su, Xin Zeng, Xinchun Yang, Xiuhong Li, Xuehua Fang, Xutong Wang, Yaming Geng, Yan Yan, Yanek Pépin-Dubois, Yanfu Wang, Yang Wang, Yanmeng Tian, Yaping Huang, Yechen Han, Yesenia Zambrano, Yi-Hsuan Yang, Ying Tung Sia, Yining Yang, Yitong Ma, Yolayfi Peralta, Yongjian Wu, Yu Kunwu, Yu Zhao, Yudong Peng, Yueh-Hung Lin, Yulan Zhao, Yumei Dong, Yunhai Zhao, Yutthaphan Wannasopha, Yvonne Taul, Zakir Sahul, Zalina Kudzoeva, Zbigniew Kalarus, Zeljko Z Markovic, Zhen Huang, Zheng Ji, Zhenyu Liu, Zhou Yue, Zhulin Zhang, Zhuxi Li, Zile Singh Meharwal, Ziliang Bai, Zixiang Yu, Zohra Huda, Zoltan Davidovits

Subjects
Male, Cardiac Catheterization, Computed Tomography Angiography, medicine.medical_treatment, Myocardial Ischemia, Coronary Disease, Coronary Artery Disease, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Coronary Angiography, ISCHEMIA Research Group, law.invention, Angina, Coronary artery disease, 0302 clinical medicine, Randomized controlled trial, law, Cardiovascular Disease, Myocardial Revascularization, 030212 general & internal medicine, Coronary Artery Bypass, 11 Medical and Health Sciences, Cardiac catheterization, General Medicine, Middle Aged, humanities, Cardiovascular Diseases, Cardiology, Female, Human, medicine.medical_specialty, Ischemia, Article, 03 medical and health sciences, Geriatric cardiology, Percutaneous Coronary Intervention, General & Internal Medicine, Internal medicine, medicine, Humans, Angina, Unstable, Aged, business.industry, Coronary Artery Bypa, Percutaneous coronary intervention, Bayes Theorem, medicine.disease, Heart failure, Quality of Life, business
Abstract

BACKGROUND: Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS: We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS: Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, -1.8 percentage points; 95% CI, -4.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS: Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA ClinicalTrials.gov number, NCT01471522.).

Published
2020

21. VITOM®-3D: preliminary experience with intradural extramedullary spinal tumors

Author

Domenico D'Avella, Teresa Somma, Oreste de Divitiis, Luca Denaro, Elena d'Avella, Matteo Sacco, DE Divitiis, Oreste, D'Avella, Elena, Denaro, Luca, Somma, Teresa, Sacco, Matteo, and D'Avella, Domenico

Subjects
Microsurgery, medicine.medical_specialty, Population, Neurosurgical Procedures, Central Nervous System Neoplasms, Learning experience, 03 medical and health sciences, 0302 clinical medicine, Intradural Extramedullary Spinal Tumors, medicine, Brain Stem Neoplasms, Humans, education, Surgical treatment, Microscopy, education.field_of_study, Spinal Neoplasms, business.industry, General surgery, 030220 oncology & carcinogenesis, High definition, Surgery, Neurology (clinical), Neurosurgery, business, 030217 neurology & neurosurgery, Working environment
Abstract

Background: In the last decade, application of the high-definition exoscope to different neurosurgical procedures has been reported in the literature. We described the first experience with the VITOM®-3D (Video Telescope Operating Microscope, Karl Storz Endoscopy, Tuttlingen, Germany) for the surgical treatment of intradural extra-medullary tumors. Methods: Five neurosurgical procedures for the removal of intradural extra-medullary tumors were performed with the VITOM®-3D. Patients' population, feasibility of surgery under the exoscope visualization, VITOM®-3D's technical and optical characteristics, and surgical outcome were analyzed. Results: All surgeries were performed following the common steps of spinal neurosurgical intradural procedures. The exoscope offered excellent, magnified, and brilliantly illuminated high-definition images of the surgical field in all the described cases. All the reported surgical operations were successfully completed under exoscope magnification from both the technical as well as the clinical points of view. No complications potentially related to the use of the exoscope occurred. Working environment ergonomics and trainees learning experience were the most relevant benefits associated with the use of exoscope. Conclusions: VITOM®-3D may represent a valid visualization tool in spinal procedure for intradural extra-medullary tumors. Our preliminary experience can be useful in better define the role of VITOM®-3D in neurosurgery.

Published
2022

22. Impaired cognitive control in patients with brain tumors

Author

Vincenza Tarantino, Antonino Visalli, Silvia Facchini, Chiara Rossato, Alessandra Bertoldo, Erica Silvestri, Diego Cecchin, Mariagrazia Capizzi, Mariagiulia Anglani, Valentina Baro, Luca Denaro, Alessandro Della Puppa, Domenico D'Avella, Maurizio Corbetta, Antonino Vallesi, Tarantino, Vincenza, Visalli, Antonino, Facchini, Silvia, Rossato, Chiara, Bertoldo, Alessandra, Silvestri, Erica, Cecchin, Diego, Capizzi, Mariagrazia, Anglani, Mariagiulia, Baro, Valentina, Denaro, Luca, Della Puppa, Alessandro, D'Avella, Domenico, Corbetta, Maurizio, and Vallesi, Antonino

Subjects
Brain Mapping, Brain Neoplasms, Cognitive Neuroscience, Reactive control, Prefrontal Cortex, Experimental and Cognitive Psychology, Lesion-symptom mapping, Brain tumor, Behavioral Neuroscience, Cognition, Proactive control, AX-CPT, Reaction Time, Humans, Brain tumor, AX-CPT, Stroop, Lesion-symptom mapping, Proactive control, Reactive control, Cognitive Dysfunction, Stroop
Abstract

Though the assessment of cognitive functions is proven to be a reliable prognostic indicator in patients with brain tumors, some of these functions, such as cognitive control, are still rarely investigated. The objective of this study was to examine proactive and reactive control functions in patients with focal brain tumors and to identify lesioned brain areas more at "risk" for developing impairment of these functions. To this end, a group of twenty-two patients, candidate to surgery, were tested with an AX-CPT task and a Stroop task, along with a clinical neuropsychological assessment, and their performance was compared to that of a well-matched healthy control group. Although overall accuracy and response times were similar for patients and control groups, the patient group failed more on the BX trials of the AX-CPT task and on the incongruent trials of the Stroop task, specifically. Behavioral results were associated with the damaged brain areas, mostly distributed in right frontal regions, by means of a lesion-symptom mapping multivariate approach. This analysis showed that a white matter cluster in the right prefrontal area was associated with lower d'-context values on the AX-CPT, which reflected the fact that these patients rely more on later information (reactive processes) to respond to unexpected and conflicting stimuli, than on earlier contextual cues (proactive processes). Taken together, these results suggest that patients with brain tumors present an imbalance between proactive and reactive control strategies in high interfering conditions, in association with right prefrontal white matter lesions.

Published
2022

23. Complete response to immunotherapy in sinonasal undifferentiated carcinoma

Author

Ornella Garrone, Nerina Denaro, Paolo Bossi, Gianmauro Numico, and Marco Merlano

Subjects
Male, 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Maxillary Sinus Neoplasms, medicine.medical_treatment, Young Adult, 03 medical and health sciences, Sinonasal undifferentiated carcinoma, 0302 clinical medicine, Internal medicine, medicine, Humans, Neoplasm Metastasis, Complete response, Neoplasm Staging, business.industry, Carcinoma, Disease Management, General Medicine, Immunotherapy, medicine.disease, Combined Modality Therapy, Treatment Outcome, 030104 developmental biology, 030220 oncology & carcinogenesis, Locally advanced disease, Disease Susceptibility, Neoplasm Grading, Presentation (obstetrics), Tomography, X-Ray Computed, business, Biomarkers
Abstract

Sinonasal undifferentiated carcinoma (SNUC) is an uncommon aggressive tumor. Locally advanced disease is usually diagnosed at presentation. Multidisciplinary approach is essential and aims to ensure optimal trimodal strategy. Induction chemotherapy is preferred in order to select patients who will benefit from chemoradiotherapy or surgery. Immunotherapy is not indicated in patients with recurrent SNUC. We describe an impressive response in a young man previously treated with radiotherapy and chemotherapy and demolitive surgery who had metastatic bone and lung disease. We also report data on PD-L1, next-generation sequencing, and neutrophil/platelets ratio.

Published
2021

24. Sellar and parasellar lesions: multidisciplinary management

Author

Enzo Emanuelli, Claudia Zanotti, Luca Denaro, Gloria Schiavo, Maria Baldovin, and Sara Munari

Subjects
medicine.medical_specialty, Endoscope, Pituitary Abscess, pituitary adenoma, Tuberculum Sellae Meningioma, 03 medical and health sciences, Craniopharyngioma, 0302 clinical medicine, Aneurysm, Pituitary adenoma, medicine.artery, medicine, Meningeal Neoplasms, Humans, Pituitary Neoplasms, 030223 otorhinolaryngology, regione sellare e parasellare, base cranica, Retrospective Studies, business.industry, sellar and parasellar region, skull base, endoscopic endonasal approach, approccio endoscopico endonasale, medicine.disease, General Energy, Otorhinolaryngology, 030220 oncology & carcinogenesis, adenoma ipofisario, Radiology, Internal carotid artery, Chondrosarcoma, Neoplasm Recurrence, Local, Clivus Chordoma, business, Meningioma, Research Article
Abstract

The endoscopic endonasal transsphenoidal approach to the sella and parasellar regions is now increasingly used for removal of a variety of lesions localized in the ventral skull base. The advantage of the endoscope is enhanced visualization and improved panoramic view that can result in more complete removal of the tumor. An extensive knowledge of the anatomy is mandatory to approach this region.From February 2009 to March 2020, the endoscopic endonasal approach was used in 153 patients with sellar and parasellar lesions, at our Institution: 136 pituitary adenomas, 7 craniopharyngiomas, 3 Rathke's cysts, a tuberculum sellae meningioma, an aneurysm of the internal carotid artery (ICA), a clivus chordoma, a papillary glioneuronal tumor, an histiocytosis, a pituitary metastasis from breast cancer and a chondrosarcoma.The most common surgical complications were cerebral spinal fluid leak (9), bleeding (2), pituitary abscess (2). Among endocrinological complications, the most important were diabete insipidus (23) and panhypopituitarism (3). Two patients complicated with meningitis. There were no visual worsening and no operative mortality. We had persistence of disease in 20 cases. Twelve patients underwent surgical revision for recurrence of the disease.Pre-operative planning and collaboration with several specialists are necessary in order to offer the patient the best treatment, minimizing complications.Lesioni della regione sellare e parasellare: gestione multidisciplinare.Introduzione: L’approccio endoscopico endonasale trans-naso-sfenoidale alla sella e alla regione parasellare è a oggi l’approccio più utilizzato per lesioni localizzate nella parte ventrale della base cranica. Il vantaggio di questa tecnica consiste in una miglior visualizzazione panoramica del sito chirurgico che consente una rimozione quanto più completa del tumore. Un’approfondita conoscenza dell’anatomia è d’obbligo per iniziare ad approcciare questa regione.Da febbraio 2009 a marzo 2020, abbiamo trattato nel nostro Istituto 153 pazienti con lesioni sellari e parassellari mediante approccio endoscopico endonasale; di questi 136 erano adenomi dell’ipofisi, 7 craniofaringiomi, 3 cisti di Rathke, un meningioma del tubercolo sellae, un aneurisma dell’arteria carotide interna, un cordoma del clivus, un tumore glioneuronale papillare, un’istiocitosi, una metastasi pituitaria da cancro al seno e un condrosarcoma.Le complicanze chirurgiche più comuni sono state la rinoliquorrea (9), il sanguinamento (2), l’ascesso pituitarico (2). Tra le complicanze endocrinologiche, le più importanti sono state il diabete insipido (23) e il panipopituitarismo (3). Due pazienti si sono complicati con meningite. Non ci sono stati deficit visivi né mortalità intraoperatoria. Abbiamo avuto persistenza di malattia in 20 casi. Dodici pazienti sono stati sottoposti a reintervento per recidiva.Un’adeguata pianificazione preoperatoria e la collaborazione tra diversi specialisti sono necessarie per offrire al paziente il miglior trattamento possibile, riducendo al minimo le complicanze.

Published
2021

25. Moving the Needle: Evidence of an Effective Study Strategy Intervention in a Community College Biology Course

Author

Sheela Vemu, Kameryn Denaro, Brian K. Sato, Adrienne E. Williams, and McFarland, Jenny

Subjects
Male, Universities, Stem Cell Research, General Biochemistry, Genetics and Molecular Biology, United States, Education, Quality Education, Engineering, Humans, Female, Curriculum, Students, Biology, Curriculum and Pedagogy
Abstract

Many science, technology, engineering, and math (STEM) community college students do not complete their degree, and these students are more likely to be women or in historically excluded racial or ethnic groups. In introductory courses, low grades can trigger this exodus. Implementation of high-impact study strategies could lead to increased academic performance and retention. The examination of study strategies rarely occurs at the community college level, even though community colleges educate approximately half of all STEM students in the United States who earn a bachelor's degree. To fill this research gap, we studied students in two biology courses at a Hispanic-serving community college. Students were asked their most commonly used study strategies at the start and end of the semester. They were given a presentation on study skills toward the beginning of the semester and asked to self-assess their study strategies for each exam. We observed a significantly higher course grade for students who reported spacing their studying and creating drawings when controlling for demographic factors, and usage of these strategies increased by the end of the semester. We conclude that high-impact study strategies can be taught to students in community college biology courses and result in higher course performance.

Published
2022

26. Defining current practice patterns of vestibular schwannoma management in Italy: results of a nationwide survey

Author

Elisabetta Zanoletti, Nicola Quaranta, Francesco Signorelli, Domenico D'Avella, Marco Pontrelli, Luca Denaro, Sabino Ciprelli, Giovanni Danesi, and Diego Cazzador

Subjects
medicine.medical_specialty, acoustic neuroma, chirurgia del basicranio, neurinoma dell’acustico, medicine.medical_treatment, Acoustic neuroma, Schwannoma, Radiosurgery, Nationwide survey, Neurosurgical Procedures, Vestibology, 03 medical and health sciences, 0302 clinical medicine, vestibular schwannoma, Multidisciplinary approach, skull base surgery, Surveys and Questionnaires, microchirurgia, medicine, Humans, schwannoma vestibolare, 030223 otorhinolaryngology, business.industry, microsurgery, Neuroma, Acoustic, Microsurgery, medicine.disease, General Energy, Italy, Otorhinolaryngology, Current practice, 030220 oncology & carcinogenesis, Family medicine, stereotactic radiotherapy, Neurosurgery, business, radioterapia stereotassica
Abstract

Despite the increasing incidence rate of vestibular schwannomas (VS), controversies in their management are still present.A 35-item multiple-choice survey investigating the current practice patterns of VS care was sent to the members of the Italian Society of Otolaryngology, Head and Neck Surgery (SIO) and of the Italian Society of Neurosurgery (SINCH).Among 66 respondents, 37 (56.0%) claimed to be actively involved in VS management. Most interviewees (35.1%) declared20 years of experience and 59.5% claimed to work in an academic practice. The number of cases evaluated in each centre per year varied widely, with 54.0% evaluating25 cases/year and only 13.6%100 cases/year. Multidisciplinary care for VS evaluation was confirmed by 50.0% of respondents, and multidisciplinary surgical care by 62.2%. Observation and surgery were the most common management options proposed. Further details regarding VS care are presented.The present study provides the first overview on the current practice patterns of VS care in Italy. Although integrated in most centres, a multidisciplinary model of care needs to be encouraged. Wide heterogeneity in experience and practices is mostly influenced by the surgeon's different specialties and by the lack of shared guidelines.L’attuale gestione dello schwannoma vestibolare in Italia: risultati di una survey nazionale.Nonostante il costante incremento di incidenza dello schwannoma vestibolare (VS), non vi è ancora uniformità nella gestione di tale patologia.Un questionario di 35 domande sulle strategie di trattamento del VS è stato sottoposto ai membri della SIO e della SINCH.Tra i 66 intervistati che hanno risposto al questionario, il 56,0% ha confermato di prendere parte attivamente nel trattamento dello VS. La maggioranza dei partecipanti (35,1%) dichiarava20 anni di esperienza nel settore, e il 59,5% di lavorare in un contesto accademico. Il 54,0% degli intervistati ha affermato di valutare25 casi/anno, mentre solo il 13,6%100 casi/anno. Il 50,0% ha dichiarato di valutare lo VS nell’ambito di un gruppo multidisciplinare, mentre il 62,2% di operare in un contesto multidisciplinare. L’approccio conservativo e la chirurgia si confermavano le strategie terapeutiche più frequentemente proposte.Lo studio presenta una prima panoramica sulle strategie di trattamento dello VS in Italia. Nonostante un modello multidisciplinare di gestione dello VS sia già diffuso in molti centri, è necessario incrementarne ulteriormente lo sviluppo. Le diverse specializzazioni del chirurgo e la mancanza di linee guida condivise contribuiscono a determinare la vasta eterogeneità osservata nella gestione del VS nel nostro Paese.

Published
2021

27. Mu and Delta Opioid Receptor Targeting Reduces Connexin 43-Based Heterocellular Coupling during Neuropathic Pain

Author

Nunzio Vicario, Simona Denaro, Rita Turnaturi, Lucia Longhitano, Federica Maria Spitale, Salvatore Spoto, Agostino Marrazzo, Agata Zappalà, Daniele Tibullo, Giovanni Li Volti, Santina Chiechio, Lorella Pasquinucci, Rosalba Parenti, and Carmela Parenti

Subjects
Receptors, Opioid, mu, microglia, Opioid, Catalysis, Inorganic Chemistry, delta, astrocyte, chronic constriction injury, MOR, DOR, inflammation, Receptors, Opioid, delta, Receptors, Humans, Physical and Theoretical Chemistry, Molecular Biology, Spectroscopy, Analgesics, Organic Chemistry, General Medicine, Computer Science Applications, Analgesics, Opioid, Spinal Cord, mu, Hyperalgesia, Connexin 43, Receptors, Opioid, Neuralgia
Abstract

Chronic neuropathic pain emerges from either central or peripheral lesions inducing spontaneous or amplified responses to non-noxious stimuli. Despite different pharmacological approaches to treat such a chronic disease, neuropathic pain still represents an unmet clinical need, due to long-term therapeutic regimens and severe side effects that limit application of currently available drugs. A critical phenomenon involved in central sensitization is the exchange of signalling molecules and cytokines, between glia and neurons, driving the chronicization process. Herein, using a chronic constriction injury (CCI) model of neuropathic pain, we evaluated the efficacy of the mu (M-) and delta (D-) opioid receptor (-OR) targeting agent LP2 in modulating connexin-based heterocellular coupling and cytokine levels. We found that long-term efficacy of LP2 is consequent to MOR-DOR targeting resulting in the reduction of CCI-induced astrocyte-to-microglia heterocellular coupling mediated by connexin 43. We also found that single targeting of DOR reduces TNF and IL-6 levels in the chronic phase of the disease, but the peripheral and central discharge as the primary source of excitotoxic stimulation in the spinal cord requires a simultaneous MOR-DOR targeting to reduce CCI-induced neuropathic pain.

Published
2022

28. Trends in hospitalization for pediatric hip arthroplasty: an epidemiological Nationwide study in Italy from 2001 to 2015

Author

Umile Giuseppe Longo, Rocco Papalia, Sergio De Salvatore, Laura Ruzzini, Ilaria Piergentili, Giuseppe Salvatore, Vincenzo Candela, and Vincenzo Denaro

Subjects
Adult, Hospitalization, Male, Epidemiologic Studies, Young Adult, Adolescent, Italy, Arthroplasty, Replacement, Hip, Pediatrics, Perinatology and Child Health, Humans, Female, Child, Patient Discharge
Abstract

Background The epidemiology of Pediatric Hip Arthroplasty (PHA) is unclear. Prevalence of PHA in Europe was reported in Scandinavian registries, but data on this procedure are not described in other countries. Therefore, it is challenging to redact a complete and valid epidemiological report on PHA in Europe. Nevertheless, national health statistics for PHA are helpful for an international audience, as different treatments are reported between countries. Moreover, sharing national statistics and correlating those to other countries’ protocols could be helpful to compare outcomes for different procedures internationally. The principal purpose is to evaluate the yearly hospital admission for PHA in Italy. Methods Data of this study were collected from the National Hospital Discharge Reports (SDO) reported at the Italian Ministry of Health. Results From 2001 to 2015, 770 PHA hospitalizations were performed in Italy, with an incidence of 0.5 procedures for every 100,000 pediatric Italian inhabitants. The average age of patients was 15.2 ± 4.6 years. The mean length of days of hospitalization was 10.9 ± 8.6 days. The majority of patients were male of 15–19 years old age group. A progressive decrease in days of hospitalizations was found during the years of the study. Conclusions In Europe, the incidence of hospital admission for PHA is not fully described. There is a lack of consensus on the best type of surgery to perform on young patients. Epidemiological studies are helpful to understand the national variation of a specific surgical procedure and compare them with other countries.

Published
2022

29. Effect of Eribulin on Angiogenesis and the Expression of Endothelial Adhesion Molecules

Author

ANDREA ABBONA, MATTEO PACCAGNELLA, SIMONETTA ASTIGIANO, STEFANIA MARTINI, NERINA DENARO, FIORELLA RUATTA, OTTAVIA BARBIERI, MARCO MERLANO, and ORNELLA GARRONE

Subjects
Cancer Research, Oncology, Paclitaxel, Transforming Growth Factor beta, Neoplasms, Tumor Microenvironment, Humans, Vinorelbine, General Medicine, Ketones, Furans, Intercellular Adhesion Molecule-1
Abstract

Tumor vasculature is an important component of the tumor microenvironment and deeply affects anticancer immune response. Eribulin is a non-taxane inhibitor of the mitotic spindle. However, off-target effects interfering with the tumor vasculature have been reported. The mechanisms responsible of this effect are still unclear.We designed an in vitro study to investigate the effect of eribulin, with or without TGF-β, on neo-angiogenesis, and on the expression of the adhesion molecules ICAM-1 and VCAM-1. We also investigated the effects of paclitaxel and vinorelbine under the same experimental conditions.Eribulin up-regulated the epithelial markers VE-cadherin and CD-31 in HUVEC and inhibited tube formation in HUVEC cells cultured in Matrigel. The drug effectively arrested tube formation even in the presence of TGF-β and counteracted the TGF-β-induced change in cell shape from the endothelial cobblestone-like morphology to an elongated spindle-shaped morphology. We also observed that eribulin was able to upregulate ICAM-1 and to counteract its down-regulation induced by TGF-β.Eribulin exerts different off-label effects: increases vascular remodeling, counteracts the endothelial-to-mesenchymal transition (EndMT) mediated by TGF-β and promotes tumor infiltration by immune cells via increasing the expression of ICAM-1 and transcription of CD31 and VE-cadherin. Moreover, eribulin was able to inhibit vasculature remodeling and the induction of EndMT mediated by TGF-β better than vinorelbine and paclitaxel. The effects observed in this study might have important therapeutic consequence if the drug is combined with immunotherapy.

Published
2022

30. Artificial Intelligence and Computer Aided Diagnosis in Chronic Low Back Pain: A Systematic Review

Author

Federico D’Antoni, Fabrizio Russo, Luca Ambrosio, Luca Bacco, Luca Vollero, Gianluca Vadalà, Mario Merone, Rocco Papalia, and Vincenzo Denaro

Subjects
Artificial Intelligence, Computers, Health, Toxicology and Mutagenesis, Public Health, Environmental and Occupational Health, Humans, Diagnosis, Computer-Assisted, Intervertebral Disc Degeneration, Low Back Pain
Abstract

Low Back Pain (LBP) is currently the first cause of disability in the world, with a significant socioeconomic burden. Diagnosis and treatment of LBP often involve a multidisciplinary, individualized approach consisting of several outcome measures and imaging data along with emerging technologies. The increased amount of data generated in this process has led to the development of methods related to artificial intelligence (AI), and to computer-aided diagnosis (CAD) in particular, which aim to assist and improve the diagnosis and treatment of LBP. In this manuscript, we have systematically reviewed the available literature on the use of CAD in the diagnosis and treatment of chronic LBP. A systematic research of PubMed, Scopus, and Web of Science electronic databases was performed. The search strategy was set as the combinations of the following keywords: “Artificial Intelligence”, “Machine Learning”, “Deep Learning”, “Neural Network”, “Computer Aided Diagnosis”, “Low Back Pain”, “Lumbar”, “Intervertebral Disc Degeneration”, “Spine Surgery”, etc. The search returned a total of 1536 articles. After duplication removal and evaluation of the abstracts, 1386 were excluded, whereas 93 papers were excluded after full-text examination, taking the number of eligible articles to 57. The main applications of CAD in LBP included classification and regression. Classification is used to identify or categorize a disease, whereas regression is used to produce a numerical output as a quantitative evaluation of some measure. The best performing systems were developed to diagnose degenerative changes of the spine from imaging data, with average accuracy rates >80%. However, notable outcomes were also reported for CAD tools executing different tasks including analysis of clinical, biomechanical, electrophysiological, and functional imaging data. Further studies are needed to better define the role of CAD in LBP care.

Published
2022

31. The prevalence of Fabry disease in a statewide chronic kidney disease cohort - Outcomes of the aCQuiRE (Ckd.Qld fabRy Epidemiology) study

Author

Andrew Mallett, Phoebe Jane Kearey, Anne Cameron, Helen G. Healy, Charles Denaro, Mark Thomas, Vincent W. Lee, Samantha Louise Stark, Maria Fuller, Zaimin Wang, and Wendy E. Hoy

Subjects
Adult, Male, Cross-Sectional Studies, Nephrology, Renal Dialysis, Prevalence, Fabry Disease, Humans, Female, Middle Aged, Renal Insufficiency, Chronic
Abstract

Background Prevalence of Fabry disease amongst Chronic Kidney Disease (CKD) patients on haemodialysis has been shown to be approximately 0.2%. Methods We undertook a cross-sectional study employing a cascade screening strategy for Fabry Disease amongst 3000 adult, male and female patients affected by CKD stage 1-5D/T at public, specialty renal practices within participating Queensland Hospital and Health Services from October 2017 to August 2019. A multi-tiered FD screening strategy, utilising a combination of dried blood spot (DBS) enzymatic testing, and if low, then lyso-GB3 testing and DNA sequencing, was used. Results Mean (SD) age was 64.0 (15.8) years (n = 2992), and 57.9% were male. Eight participants withrew out of the 3000 who consented. Of 2992 screened, 6 (0.20%) received a diagnosis of FD, 2902 (96.99%) did not have FD, and 84 (2.81%) received inconclusive results. Of the patients diagnosed with FD, mean age was 48.5 years; 5 were male (0.29%) and 1 was female (0.08%); 4 were on kidney replacement therapy (2 dialysis and 2 transplant); 3 were new diagnoses. Conclusions Estimated overall FD prevalence was 0.20%. Screening of the broader CKD population may be beneficial in identifying cases of FD. Trial registration The aCQuiRE Study has been prospectively registered with the Queensland Health Database of Research Activity (DORA, https://dora.health.qld.gov.au) as pj09946 (Registered 3rd July 2017).

Published
2022

32. COVID-19 Pandemic Increases the Impact of Low Back Pain: A Systematic Review and Metanalysis

Author

Giuseppe Francesco Papalia, Giorgia Petrucci, Fabrizio Russo, Luca Ambrosio, Gianluca Vadalà, Sergio Iavicoli, Rocco Papalia, and Vincenzo Denaro

Subjects
Health, Toxicology and Mutagenesis, Communicable Disease Control, Public Health, Environmental and Occupational Health, Prevalence, COVID-19, Humans, Low Back Pain, Pandemics
Abstract

In March 2019, the World Health Organization (WHO) recognized the COVID-19 pandemic as a global issue. To reduce the spread of this disease, health safety pathways were implemented worldwide. These extraordinary measures changed people’s lifestyles, e.g., by being forced to isolate, and in many cases, to work remotely from home. Low back pain (LBP), the most common cause of disability worldwide, is often a symptom of COVID-19. Moreover, it is often associated with different lifestyle features (type of job, physical activity, body weight). Therefore, the purpose of this systematic review and meta-analysis was to estimate the effect of the COVID-19 lockdown on LBP intensity and prevalence compared with LBP rates before the pandemic. A systematic search was performed on Scopus, PubMed, and Cochrane Central. Overall, eight studies with 2365 patients were included in the analysis. We used the Joanna Briggs Institute (JBI) critical appraisal tool to evaluate the risk of bias: six studies (75%) were at moderate risk of bias and two studies (25%) were at low risk of bias. These studies showed an increase in both the prevalence and intensity of LBP during the COVID-19 lockdown.

Published
2022

33. Does Workers’ Compensation Status Affect Outcomes after Lumbar Spine Surgery? A Systematic Review and Meta-Analysis

Author

Gianluca Vadalà, Sergio Iavicoli, Luca Fontana, Jorma Rantanen, Sergio De Salvatore, Rocco Papalia, Luca Ambrosio, Fabrizio Russo, Vincenzo Denaro, Russo, Fabrizio, De Salvatore, Sergio, Ambrosio, Luca, Vadalà, Gianluca, Fontana, Luca, Papalia, Rocco, Rantanen, Jorma, Iavicoli, Sergio, and Denaro, Vincenzo

Subjects
medicine.medical_specialty, Health, Toxicology and Mutagenesis, lumbar decompression, MEDLINE, Workers' compensation, CINAHL, Review, Occupational safety and health, Neurosurgical Procedures, 03 medical and health sciences, 0302 clinical medicine, Muscu-loskeletal disorder, Back pain, Medicine, Humans, pain, 030212 general & internal medicine, low back pain, Lumbar Vertebrae, business.industry, Public Health, Environmental and Occupational Health, satisfaction, return to work, Low back pain, 3. Good health, Review article, lumbar fusion, Spinal Fusion, Treatment Outcome, disability, Meta-analysis, occupational health, Physical therapy, Workers' Compensation, medicine.symptom, musculoskeletal disorders, business, 030217 neurology & neurosurgery, insurance
Abstract

Low back pain (LBP) is currently the leading cause of disability worldwide and the most common reason for workers’ compensation (WC) claims. Studies have demonstrated that receiving WC is associated with a negative prognosis following treatment for a vast range of health conditions. However, the impact of WC on outcomes after spine surgery is still controversial. The aim of this meta-analysis was to systematically review the literature and analyze the impact of compensation status on outcomes after lumbar spine surgery. A systematic search was performed on Medline, Scopus, CINAHL, EMBASE and CENTRAL databases. The review included studies of patients undergoing lumbar spine surgery in which compensation status was reported. Methodological quality was assessed through ROBINS-I and quality of evidence was estimated using the GRADE rating. A total of 26 studies with a total of 2668 patients were included in the analysis. WC patients had higher post-operative pain and disability, as well as lower satisfaction after surgery when compared to those without WC. Furthermore, WC patients demonstrated to have a delayed return to work. According to our results, compensation status is associated with poor outcomes after lumbar spine surgery. Contextualizing post-operative outcomes in clinical and work-related domains helps understand the multifactorial nature of the phenomenon.

Published
2021

34. Infection after spinal surgery and procedures

Author

A, Di Martino, R, Papalia, E, Albo, L, Diaz, L, Denaro, V, Denaro, Di Martino, A, Papalia, R, Albo, E, Diaz, L, Denaro, L, and Denaro, V

Subjects
Humans, Surgical Wound Infection, Spinal Diseases, spine, infection
Abstract

Postoperative infections after spinal surgery are a challenging issue, difficult to diagnose and treat, that requires prolonged medical therapy and even surgery. In this paper, we aim to review the current standards in the diagnosis and treatment of post-procedural Spondylodiscitis (SD). We performed a review of the available literature focusing on diagnostic and therapeutic standards of post-procedural SD, both after minimally invasive procedures and open surgery. Spinal infections can occur in less invasive procedures with an incidence ranging from 0.26% to 2.75%. Post-surgical spinal infections range from 2.1% to 8.5% for instrumented surgery, whereas these are less than 1% in open surgery without instrumentation. MRI is currently the most sensitive and specific technique to diagnose postoperative SD. CT guided aspiration culture should be performed in all patients with deep-seated infections with negative blood cultures. Early infections start with wound healing problems within a few weeks from surgery, and the occurrence of fever and an increase in serum markers of inflammation. Late infections often cause chronic pain, implant failure, non-union or wound dehiscence even a long time after surgery. The onset of the infection differentiates the specific treatment. Indeed, in the early postoperative period spinal fusion is not appropriate yet, and the stability of the fusion site only relies on the instrumentation. Therefore, even when suitable, implant removal may lead to undesirable consequences. In chronic infections, on the other hand, implant removal is unlikely to determine instability since the fusion has already been accomplished.

Published
2019

35. Should evoked potential monitoring be used in degenerative cervical spine surgery? A systematic review

Author

Luca Denaro, Rocco Papalia, Vincenzo Denaro, Alberto Di Martino, Antonio Caldaria, Guglielmo Torre, Di Martino, Alberto, Papalia, Rocco, Caldaria, Antonio, Torre, Guglielmo, Denaro, Luca, and Denaro, Vincenzo

Subjects
medicine.medical_specialty, Intraoperative Neurophysiological Monitoring, Sports medicine, Decompression, Spinal stenosis, Evoked potential, MEDLINE, Neurosurgical Procedures, 03 medical and health sciences, Spinal Stenosis, 0302 clinical medicine, Cervical spine surgery, Evoked Potentials, Somatosensory, Humans, Medicine, Orthopedics and Sports Medicine, IONM, Retrospective Studies, Orthopedic surgery, 030222 orthopedics, business.industry, 030229 sport sciences, Middle Aged, Evoked potentials, MEP, medicine.disease, SSEP, Stenosis, Somatosensory evoked potential, Anesthesia, Surgery, Systematic Review, business, RD701-811
Abstract

Background Intraoperative somatosensory evoked potential (SSEP) and transcranial motor evoked potential (tcMEP) monitoring are frequently used in spinal as well as spinal cord surgery for so-called intraoperative neuromonitoring (IONM), while the combination of these techniques is known as concomitant multimodal intraoperative monitoring (MIOM). The aim of this review is to collect available evidence concerning use of IONM and MIOM in cervical decompression surgery in the degenerative setting and attempt to identify the best practice to be advocated. Materials and methods A review of the PubMed and MEDLINE databases and Cochrane Central Registry of Controlled Trials was performed. Studies were included if they involved patients who underwent cervical spine decompression surgery for degenerative stenosis with use of IONM or MIOM and where sensitivity/specificity was reported. Results In the identified studies, the sensitivity of SSEP was estimated to be between 22 and 100% with constant specificity of 100%. In the included studies, the sensitivity of MEP was estimated to be between 78 and 100% with specificity ranging from 83.2 to 100%. Conclusions On the basis of available evidence, MIOM could be a helpful tool in decompression cervical spine surgery in patients affected by degenerative spinal stenosis, since it is associated with high specificity and sensitivity for detection of intraoperative neural damage. However, evidence is still lacking regarding patient selection to identify individuals in whom monitoring is indicated. Level of evidence IV (systematic review of studies with LOE II to IV).

Published
2019

36. Virtual Reality for Shoulder Rehabilitation: Accuracy Evaluation of Oculus Quest 2

Author

Arianna Carnevale, Ilaria Mannocchi, Mohamed Saifeddine Hadj Sassi, Marco Carli, Giovanna De De Luca, Umile Giuseppe Longo, Vincenzo Denaro, Emiliano Schena, Carnevale, Arianna, Mannocchi, Ilaria, Sassi Mohamed Saifeddine, Hadj, Carli, Marco, De Luca, Giovanna, Longo Umile, Giuseppe, Denaro, Vincenzo, and Schena, Emiliano

Subjects
Male, Shoulder, Movement, Virtual Reality, Biochemistry, Atomic and Molecular Physics, and Optics, virtual reality, Oculus Quest 2, upper limb, rehabilitation, shoulder, Biomechanical Phenomena, Analytical Chemistry, Upper Extremity, Humans, Female, Electrical and Electronic Engineering, Instrumentation
Abstract

Virtual reality (VR) systems are becoming increasingly attractive as joint kinematics monitoring systems during rehabilitation. This study aimed to evaluate the accuracy of the Oculus Quest 2 in measuring translational and rotational displacements. As the Oculus Quest 2 was chosen for future applications in shoulder rehabilitation, the translation range (minimum: ~200 mm, maximum: ~700 mm) corresponded to the forearm length of the 5th percentile female and the upper limb length of the 95th percentile male. The controller was moved on two structures designed to allow different translational displacements and rotations in the range 0–180°, to cover the range of motion of the upper limb. The controller measures were compared with those of a Qualisys optical capture system. The results showed a mean absolute error of 13.52 ± 6.57 mm at a distance of 500 mm from the head-mounted display along the x-direction. The maximum mean absolute error for rotational displacements was found to be 1.11 ± 0.37° for a rotation of 40° around the z-axis. Oculus Quest 2 is a promising VR tool for monitoring shoulder kinematics during rehabilitation. The inside-out movement tracking makes Oculus Quest 2 a viable alternative to traditional motion analysis systems.

Published
2022

37. Deep deltoid ligament injury is related to rotational instability of the ankle joint: a biomechanical study

Author

Mattia Loppini, Vincenzo Denaro, Ugo Trovato, Christopher W. DiGiovanni, Angela Lanotte, Laura Risi Ambrogioni, Vincenzo Candela, Caterina Fumo, Umile Giuseppe Longo, and Francisco Forriol

Subjects
Adult, Joint Instability, Male, Syndesmosis, Rotation, Joint stability, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Deltoid ligament, Cadaver, medicine, Humans, Orthopedics and Sports Medicine, Ankle Injuries, 030222 orthopedics, business.industry, 030229 sport sciences, Anatomy, musculoskeletal system, medicine.disease, Sagittal plane, Biomechanical Phenomena, medicine.anatomical_structure, Coronal plane, Ligaments, Articular, Ligament, Diastasis, Surgery, Ankle, business, human activities
Abstract

In the athletic population, the prevalence of isolated syndesmotic lesions is high. To detect potential instability of the ankle is crucial to define those lesions in need of surgical management. The aim was to define how the extent of tibio-fibular syndesmotic ligament injury influences the overall stability of the ankle joint in a cadaver model. Twenty fresh-frozen through knee cadaveric leg specimens were subjected to different simulated syndesmotic ligament lesions. In Group 1 (n = 10), the order of ligament sectioning was: anterior tibio-fibular ligament (ATFL), superficial deltoid ligament (SDL), deep deltoid ligament (DDL), posterior tibio-fibular ligament (PTFL), and progressive sectioning at 10, 50 and 100 mm of the distal interosseous membrane (IOM). In Group 2 (n = 10), the sequence was: ATFL, PITFL, 10 and then 50 mm of the distal IOM, SDL, DDL, and 100 mm of the distal IOM. Diastasis of 4 mm in the coronal or sagittal plane and external rotation of the ankle greater than 20° were considered indicative of instability. Both coronal and sagittal diastasis exceeded 4 mm with injury patterns characterized by IOM lesions extending beyond 5 cm. External rotation of the ankle exceeded 20° with injury patterns characterized by a DDL lesion. Coronal and sagittal plane diastases of the tibio-fibular syndesmosis are particularly affected by sequential lesions involving the IOM, whereas increased external rotation of the ankle most depends on DDL. The identification of the specific syndesmotic and deltoid ligament injuries is crucial to understanding which lesions need operative management. The knowledge of which pattern of tibio-fibular syndesmotic ligament injury influences the ankle joint stability is crucial in defining which lesions need for surgical management.

Published
2020

38. Multishell Diffusion MRI–Based Tractography of the Facial Nerve in Vestibular Schwannoma

Author

Luca Denaro, Andrea Landi, Domenico D'Avella, Valentina Baro, Alessandra Bertoldo, Sabrina Brigadoi, Maria Giulia Anglani, Marco Castellaro, Francesco Causin, Roberto Dell'Acqua, Elisabetta Zanoletti, and Manuela Moretto

Subjects
Male, Partial volume, Schwannoma, Neurosurgical Procedures, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Image Interpretation, Computer-Assisted, Humans, Medicine, Radiology, Nuclear Medicine and imaging, Head & Neck, Vestibular system, business.industry, Neuroma, Acoustic, Middle Aged, medicine.disease, Neuroma, Cerebellopontine angle, Facial nerve, Facial Nerve, Diffusion Tensor Imaging, Surgery, Computer-Assisted, Female, Neurology (clinical), business, Nuclear medicine, Algorithms, 030217 neurology & neurosurgery, Diffusion MRI, Tractography
Abstract

BACKGROUND AND PURPOSE: Tractography of the facial nerve based on single-shell diffusion MR imaging is thought to be helpful before surgery for resection of vestibular schwannoma. However, this paradigm can be vitiated by the isotropic diffusion of the CSF, the convoluted path of the facial nerve, and its crossing with other bundles. Here we propose a multishell diffusion MR imaging acquisition scheme combined with probabilistic tractography that has the potential to provide a presurgical facial nerve reconstruction uncontaminated by such effects. MATERIALS AND METHODS: Five patients scheduled for vestibular schwannoma resection underwent multishell diffusion MR imaging (b-values = 0, 300, 1000, 2000 s/mm2). Facial nerve tractography was performed with a probabilistic algorithm and anatomic seeds located in the brain stem, cerebellopontine cistern, and internal auditory canal. A single-shell diffusion MR imaging (b-value = 0, 1000 s/mm2) subset was extrapolated from the multishell diffusion MR imaging data. The quality of the facial nerve reconstruction based on both multishell diffusion MR imaging and single-shell diffusion MR imaging sequences was assessed against intraoperative videos recorded during the operation. RESULTS: Single-shell diffusion MR imaging–based tractography was characterized by failures in facial nerve tracking (2/5 cases) and inaccurate facial nerve reconstructions displaying false-positives and partial volume effects. In contrast, multishell diffusion MR imaging–based tractography provided accurate facial nerve reconstructions (4/5 cases), even in the presence of ostensibly complex patterns. CONCLUSIONS: In comparison with single-shell diffusion MR imaging, the combination of multishell diffusion MR imaging–based tractography and probabilistic algorithms is a more valuable aid for surgeons before vestibular schwannoma resection, providing more accurate facial nerve reconstructions, which may ultimately improve the postsurgical patient’s outcome.

Published
2020

39. Direct thrombectomy for stroke in the presence of absolute exclusion criteria for thrombolysis

Author

Paolo Invernizzi, Roberto Menozzi, Federico Carimati, Cristina Dell’Aera, Maria Ruggiero, Mauro Gentile, Bruno Bonetti, Giuseppe Ganci, Stefano Barbero, Patrizia Nencini, Rossana Tassi, Marina Mannino, Simona Sacco, Umberto Scoditti, Ilaria Casetta, Davide Castellano, Luigi Simonetti, Maria Pia Prontera, Luigi Chiumarulo, Lucio Castellan, Stefano Forlivesi, Mauro Magoni, Valentina Saia, Francesco Causin, Alfredo Petrone, Giovanni Orlandi, Nicola Limbucci, Sandra Bracco, Alfonsina Casalena, Ettore Nicolini, Elisa Francesca Maria Ciceri, Nicola Cavasin, Manuel Corato, Guido Squassina, Manuel Cappellari, Annalisa Sugo, Cinzia Finocchi, Federica Schirru, Sergio Vinci, Fabrizio Sallustio, Nunzio Paolo Nuzzi, Wiliam Auteri, Roberto Gasparotti, Valerio Da Ros, Marco Petruzzelli, Pietro Amistà, Pietro Filauri, Guido Bigliardi, Mauro Bergui, Domenico Inzitari, Giuseppe Carità, Alessandro Sgreccia, Cristiano Azzini, Andrea Naldi, Edoardo Puglielli, Giuseppe Craparo, Stefano Vallone, Nicola Burdi, Giulio Guidetti, G Lazzarotti, R. Cavallo, Samuele Cioni, Sara Biguzzi, Salvatore Mangiafico, Federica Viaro, Danilo Toni, Adriana Critelli, Giovanni Pracucci, Maria Federica Denaro, Andrea Zini, and Carlo Pellegrino

Subjects
medicine.medical_specialty, medicine.medical_treatment, Brain Ischemia/drug therapy, Brain Ischemia, NO, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Hematoma, Fibrinolytic Agents, Outcome, Stroke, Thrombectomy, Thrombolysis, Humans, Thrombolytic Therapy, Treatment Outcome, Modified Rankin Scale, Internal medicine, Occlusion, Medicine, 030212 general & internal medicine, Neuroradiology, Intracerebral hemorrhage, business.industry, medicine.disease, Neurology, Cohort, Cardiology, Neurology (clinical), business, 030217 neurology & neurosurgery, Cohort study
Abstract

Intravenous thrombolysis (IVT)-ineligible patients undergoing direct thrombectomy tended to have poorer functional outcome as compared with IVT-eligible patients undergoing bridging therapy. We aimed to assess radiological and functional outcomes in large vessel occlusion-related stroke patients receiving direct thrombectomy in the presence of absolute exclusion criteria for IVT vs relative exclusion criteria for IVT and vs non-exclusion criteria for IVT. A cohort study on prospectively collected data from 2282 patients enrolled in the Italian Registry of Endovascular Treatment in Acute Stroke cohort for treatment with direct thrombectomy (n = 486, absolute exclusion criteria for IVT alone; n = 384, absolute in combination with relative exclusion criteria for IVT; n = 777, relative exclusion criteria for IVT alone; n = 635, non-exclusion criteria for IVT). After adjustment for unbalanced variables (model 1), ORs for 3-month death was higher in the presence of absolute exclusion criteria for IVT alone (vs relative exclusion criteria for IVT alone) (1.595, 95% CI 1.042–2.440) and in the presence of absolute exclusion criteria for IVT alone (vs non-exclusion criteria for IVT) (1.235, 95% CI 1.014–1.504). After adjustment for predefined variables (model 2: age, sex, pre-stroke mRS ≤ 1, NIHSS, occlusion in the anterior circulation, onset-to-groin time, and procedure time), ORs for 3-month death was higher in the presence of absolute exclusion criteria for IVT alone (vs relative exclusion criteria for IVT alone) (1.235, 95% CI 1.014–1.504) and in the presence of absolute exclusion criteria for IVT alone (vs non-exclusion criteria for IVT) (1.246, 95% CI 1.039–1.495). No significant difference was found between the groups as regards any type of intracerebral hemorrhage and parenchymal hematoma within 24 h, successful and complete recanalization after procedure, and modified Rankin Scale score 0–2 at 3 months. After adjustment for predefined variables of model 2, ORs for death were higher in the presence of recent administration of IV heparin (OR: 2.077), platelet count

Published
2020

40. Treating patients with cancer amidst the COVID-19 pandemic: experience of a regional hospital in the Piedmont region in northern Italy

Author

Nerina Denaro, Cristina Granetto, Ornella Garrone, Vincenzo Ricci, Paola Vanella, Ida Colantonio, Nicola Crosetto, Anna Maria Vandone, Marcella Occelli, Fiorella Ruatta, Marco Merlano, Carolina Cauchi, Gianna Di Costanzo, and Elena Fea

Subjects
Adult, Male, China, Cancer Research, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Pneumonia, Viral, Medical Oncology, 030218 nuclear medicine & medical imaging, Betacoronavirus, 03 medical and health sciences, 0302 clinical medicine, Neoplasms, Pandemic, Humans, Socioeconomics, Pandemics, Aged, Aged, 80 and over, Oncologists, SARS-CoV-2, COVID-19, Neoplasms therapy, General Medicine, Middle Aged, Hospitals, Northern italy, Dilemma, Regional hospital, Geography, Italy, Oncology, 030220 oncology & carcinogenesis, Female, Coronavirus Infections
Abstract

Background:The coronavirus disease 2019 (COVID-19) pandemic is posing an unprecedented dilemma to oncologists worldwide, forcing them to decide whether to continue or suspend treatments in order to protect their most vulnerable patients from infection. After the first report from China, the outbreak spread rapidly worldwide. To, date no clear indications on how to treat patients with cancer with COVID-19 infection are available.Methods:We report data on 21 patients with cancer referred to a single medical oncology unit of a general hospital from mid-March to April 23, 2020.Results:Nine patients were on active cancer therapy during the infection and all stopped medical treatments. Overall 8 patients developed pneumonia and 6 patients died of COVID-19.Conclusion:The management of patients with cancer during the pandemic should be carefully balanced and discussed among oncologists and other key professionals involved in the treatment of this vulnerable group of patients, in order to balance the risk of treatment and the risk of infection.

Published
2020

41. A new mini-open technique of arthroscopically assisted Latarjet

Author

Ettore, Taverna, Umile Giuseppe, Longo, Vincenzo, Guarrella, Guido, Garavaglia, Carlo, Perfetti, Luca Maria, Sconfienza, Laura, Broffoni, and Vincenzo, Denaro

Subjects
Adult, Joint Instability, Male, Complications, lcsh:Diseases of the musculoskeletal system, Adolescent, Arthroplasty, Young Adult, Arthroscopy, Endobutton, Humans, Range of Motion, Articular, Mini-open, Retrospective Studies, Postoperative Care, Bone Transplantation, Shoulder Joint, Shoulder Dislocation, Arthroscopic Latarjet, Osteotomy, Treatment Outcome, Technical Advance, Latarjet, Female, lcsh:RC925-935, Tomography, X-Ray Computed, Follow-Up Studies
Abstract

Background The aim is to describe a new arthroscopically assisted Latarjet technique. Methods We evaluated the clinical and radiological findings of 60 patients with chronic recurrent anterior gleno-humeral instability who underwent, between September 2013 and November 2014, an arthroscopically-assisted Latarjet procedure with double round endobutton fixation. Inclusion criteria were: chronic anterior recurrent instability, Instability Severity Index Score (ISIS) greater than three points, a glenoid bone defect > 15% or a Hill Sachs lesion with concomitant glenoid bone defect > 10%. During surgery the joint capsule and the anterior glenoid labrum were detached. Two drill tunnels perpendicular to the neck of the glenoid were made through a guide. An accessible pilot hole through the glenoid was created to allows the passage of guidewires for coracoid guidance and final fixation onto the anterior glenoid. Through a restricted deltopectoral access a coracoid osteotomy was made. Finally, the graft was prepared, inserted and secured using half-stitches. Results The mean follow-up was 32.5 months (range 24–32 months). At a mean follow-up, 56 of the 60 subjects claimed a stable shoulder without postoperative complaints, two (3.3%) had an anterior dislocation after new traumatic injury, and two (3.3%) complained of subjective instability. At the latest follow-up, four subjects complained of painful recurrent anterior instability during abduction-external rotation with apprehension. At 1 year, the graft had migrated in one patient (1.7%) and judged not healed and high positioned in another patient (1.7%). Moreover, a glenoid bony gain of 26.3% was recorded. At the latest follow-up, three patients had grade 1 according to Samilson and Prieto classification asymptomatic degenerative changes. Nerve injuries and infections were not detected. None of the 60 patients underwent revision surgery. Healing rate of the graft was 96.7%. Conclusions This technique of arthroscopically assisted Latarjet combines mini-open and arthroscopic approach for improving the precision of the bony tunnels in the glenoid and coracoid placement, minimizing any potential risk of neurologic complications. It can be an option in subjects with anterior gleno-humeral instability and glenoid bone defect. Further studies should be performed to confirm our preliminary results. Trial registration Trial registration number 61/int/2017 Name of registry: ORS Date of registration 11.5.2017 Date of enrolment of the first participant to the trial: September 2013 ‘retrospectively registered’ Level of evidence IV

Published
2020

42. Antibiotic prophylaxis in primary and revision shoulder replacement: a systematic review

Author

Laura Risi Ambrogioni, Umile Giuseppe Longo, Silvia Dsoke, Maria Grazia De Marinis, Anna Marchetti, Gabriella Facchinetti, Claudia Mazzella, Vincenzo Denaro, and Vincenzo Candela

Subjects
Adult, Male, medicine.medical_specialty, Prosthesis-Related Infections, lcsh:Diseases of the musculoskeletal system, Adolescent, medicine.drug_class, medicine.medical_treatment, Antibiotics, Periprosthetic, Total shoulder replacement, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Sex Factors, Rheumatology, medicine, Humans, Orthopedics and Sports Medicine, 030212 general & internal medicine, Propionibacterium acnes, Antibiotic prophylaxis, Intensive care medicine, Child, Gram-Positive Bacterial Infections, Aged, 030222 orthopedics, business.industry, Shoulder Joint, Perioperative, Middle Aged, Antimicrobial, Arthroplasty, Anti-Bacterial Agents, Regimen, Treatment Outcome, Arthroplasty, Replacement, Shoulder, Female, Shoulder arthroplasty, lcsh:RC925-935, business, Infection, Shoulder replacement, Follow-Up Studies, Research Article
Abstract

Background One of the most common bacteria responsible for most Periprosthetic joint infection (PJI) is Propionibacterium acnes. Even though the rate of infections in patients undergoing total shoulder arthroplasty is increasing, effective diagnostic tests and the precautions taken during the surgery are not yet adequate. This systematic review aims to evaluate the effectiveness of antimicrobial prophylaxis in PJI in shoulder replacement and to provide health workers with the best approach to the use of antimicrobial agents based on currently available clinical evidence. Methods a systematic review of the literature was carried out in accordance with the PRISMA Statement. Studies concerning the effectiveness of antimicrobial prophylaxis in the prevention of PJI in patients undergoing shoulder replacement were included. Results Seven studies were included in the final analysis because they were considered valid. A total of 3272 patients underwent a surgical procedure, most of which were males. The male population has a greater presence of hair, therefore a greater risk of P. acnes. in surface cultures. Patients were assessed at an average follow-up period of 20 months ranging from 9 weeks to 53 months. Conclusion The optimal perioperative antimicrobial regimen is controversial. The clinical guidelines recommend the use of only one antibiotic as prophylaxis but considering the increase in the rates of antibiotic-resistant infections, the question arises whether antibiotic prophylaxis should be extended for adequate coverage. Shoulder arthroplasty performed on the male population must be carefully checked after surgery for the possible presence of P. Acnes.

Published
2020

43. Genetic factors in rotator cuff pathology: potential influence of col 5A1 polymorphism in outcomes of rotator cuff repair

Author

Vincenzo Denaro, Caterina Fusilli, Vincenzo Candela, Giacomo Rizzello, Alessandro De Luca, Stefano Petrillo, Umile Giuseppe Longo, and Katia Margiotti

Subjects
Adult, Male, Shoulder, lcsh:Internal medicine, Genotype, lcsh:QH426-470, Single-nucleotide polymorphism, Outcomes, Bioinformatics, Achilles Tendon, Polymorphism, Single Nucleotide, COL5A1 polymorphism, Rotator Cuff Injuries, Rotator Cuff, 03 medical and health sciences, Arthroscopy, 0302 clinical medicine, Genetics, Humans, Medicine, Rotator cuff, lcsh:RC31-1245, Genetics (clinical), Aged, Genetic association, 030222 orthopedics, medicine.diagnostic_test, business.industry, Rotator cuff, genetic, 030229 sport sciences, Middle Aged, medicine.disease, Tendon, lcsh:Genetics, medicine.anatomical_structure, Tendinopathy, Female, business, Range of motion, Collagen Type V, Research Article
Abstract

BackgroundInvestigations in genetics have provided valuable information about the correlation between gene variants and tendinopathy. Single Nucleotide Polymorphisms of COL5A1 gene are reported to be involved in Achilles tendinopathy, chronic degenerative tendon changes at the elbow, and other tendinopathies. The influence of Single Nucleotide Polymorphisms of COL5A1 was previously analyzed in rotator cuff disease with confounding results. Moreover, the rs12722 polymorphism in COL5A1 gene has been implicated in the aetiology of musculoskeletal soft tissue injuries in several association studies. This study aims to analyse the possible influence of rs12722 polymorphism in COL5A1 in the outcomes of rotator cuff repair.MethodsSeventy-nine patients were included in the study. DNA was extracted from 1.2 ml of venous blood and genotyped for COL5A1 SNPs rs12722. Rotator cuff muscle strength and range of motion (ROM) in anterior elevation, external and internal rotation of the shoulder were evaluated.ResultsPatients presenting COL5A1 SNP rs12722 CC showed a ROM of passive external rotation statistically significantly higher compared to patients with CT genotype and TT genotype.ConclusionsCOL5A1 SNP rs12722 may influence the functional outcomes of RCRs, even though further studies are required to confirm these preliminary results.

Published
2020

44. Rapid disease progression in patient with mismatch-repair deficiency pituitary ACTH-secreting adenoma treated with checkpoint inhibitor pembrolizumab

Author

Mario Caccese, Carla Scaroni, Enzo Emanuelli, Luca Denaro, Mattia Barbot, Matteo Fassan, Filippo Ceccato, Giuseppe Lombardi, Domenico D'Avella, Vittorina Zagonel, Marta Padovan, and Marina Paola Gardiman

Subjects
Male, 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Adenoma, medicine.medical_treatment, Pembrolizumab, Adrenocorticotropic hormone, Antibodies, Monoclonal, Humanized, DNA Mismatch Repair, 03 medical and health sciences, Antineoplastic Agents, Immunological, 0302 clinical medicine, Neoplastic Syndromes, Hereditary, Pituitary adenoma, Internal medicine, medicine, PMS2, Humans, Pharmacology (medical), Pharmacology, Temozolomide, Brain Neoplasms, business.industry, Immunotherapy, Middle Aged, Prognosis, medicine.disease, digestive system diseases, ACTH-Secreting Pituitary Adenoma, 030104 developmental biology, MSH2, 030220 oncology & carcinogenesis, Disease Progression, Colorectal Neoplasms, business, medicine.drug
Abstract

Secreting pituitary adenomas are tumors for which few treatment options are available, including surgical treatment and management of hormonal imbalance due to altered pituitary secretion. In case of inoperable relapse, radiotherapy or chemotherapeutic treatment can be considered; the effectiveness of these treatments, however, remains limited. In the immunotherapy era, it is necessary to select patients who can benefit from immunotherapeutic treatment. Mismatch repair deficiency is strongly associated with responsiveness to anti-PD-1 in other cancers and can be detected using immunohistochemistry for MLH1, MSH2, MHS6, and PMS2. In this case report, we report a case of rapid disease progression to pembrolizumab in a patient with a MMRd pituitary adrenocorticotropic hormone (ACTH)-secreting adenoma. For the best of our knowledge, we described for the first time, a poor efficacy of pembrolizumab in a patient with ACTH-secreting pituitary adenoma having mismatch repair deficiency probably caused by high levels of cortisol in this patient. Prospective study should be performed to assess the activity of immune checkpoint inhibitor alone or in association with temozolomide in this subsetting of pituitary adenomas.

Published
2020

45. The Ckd. Qld fabRy Epidemiology (aCQuiRE) study protocol: identifying the prevalence of Fabry disease amongst patients with kidney disease in Queensland, Australia

Author

P. Kearey, Helen Healy, Mark Thomas, Wendy E. Hoy, Vincent W. Lee, Samantha Stark, A. Cameron, Andrew Mallett, Maria Fuller, and Charles Denaro

Subjects
Adult, Male, Nephrology, medicine.medical_specialty, Delayed Diagnosis, Genetic testing, Lysosomal storage disorder, medicine.medical_treatment, Population, 030232 urology & nephrology, Globotriaosylceramide, 030204 cardiovascular system & hematology, lcsh:RC870-923, Study Protocol, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Clinical Protocols, Renal Dialysis, Internal medicine, Epidemiology, Prevalence, medicine, Humans, Prospective Studies, Renal Insufficiency, Chronic, education, Dialysis, Sphingolipids, education.field_of_study, Fabry disease, Alpha-galactosidase, medicine.diagnostic_test, business.industry, medicine.disease, lcsh:Diseases of the genitourinary system. Urology, chemistry, Female, Queensland, Glycolipids, business, Kidney disease
Abstract

Background Fabry disease (FD) is a rare, lysosomal storage disorder caused by the absence or deficiency of the enzyme alpha-galactosidase A (α-Gal A) that leads to the abnormal accumulation of the lipid globotriaosylceramide (GB3) in a variety of cell types and tissues throughout the body. FD has an x-linked inheritance pattern. Previously thought to be only carriers, females can also experience FD symptomatology. Symptoms vary in type and severity from patient to patient and tend to increase in severity with age. FD symptoms are non-specific and may be shared with those of other diseases. Misdiagnoses and diagnostic delays are common, often resulting in progressive, irreversible tissue damage. The estimated prevalence of FD in the general population is 1:40,000 to 1:117,000 individuals. However, it is estimated that the prevalence of FD in the dialysis population is 0.12 to 0.7%. Little is known about the prevalence of FD in the broader Chronic Kidney Disease (CKD) population. Methods This is an epidemiological study of the prevalence of FD in CKD patents identified from the public renal speciality practices in Queensland, Australia. A cascade approach to screening is being employed with dried blood spot testing for blood levels of alpha-galactosidase A (Alpha-Gal), with follow-up testing for patients with abnormal results by plasma levels of globotriaosylsphingosine (Lyso-GB3) for females and non-definitive cases in males. A diagnosis of FD is confirmed through genetic testing of the GLA gene in cases suspected of having FD based upon Alpha-Gal and Lyso-GB3 testing. Discussion Expected outcomes of this study include more information about the prevalence of FD at all stages of CKD, including for both males and females. The study may also provide information about common characteristics of FD to assist with diagnosis and optimal management/treatment. Screening is also available for family members of diagnosed patients, with potential for early diagnosis of FD and intervention for those individuals. Trial registration Queensland Health Database of Research Activity (DORA, https://dora.health.qld.gov.au) pj09946 (Registered 3rd July 2017).

Published
2020

46. Exploring the association between specific genes and the onset of idiopathic scoliosis: a systematic review

Author

Sergio De Salvatore, Laura Ruzzini, Umile Giuseppe Longo, Martina Marino, Alessandra Greco, Ilaria Piergentili, Pier Francesco Costici, and Vincenzo Denaro

Subjects
Adolescent, Scoliosis, Genetics, Humans, Polymorphism, Single Nucleotide, Genetics (clinical), Adaptor Proteins, Signal Transducing
Abstract

Background Idiopathic Scoliosis (IS) is the most common spinal deformity in adolescents, accounting for 80% of all spinal deformities. However, the etiology remains uncertain in most cases, being identified as Adolescent Idiopathic Scoliosis (AIS). IS treatments range from observation and sport to bracing or surgery. Several risk factors including sex and familiarity, have been linked with IS. Although there are still many uncertainties regarding the cause of this pathology, several studies report a greater incidence of the defect in families in which at least one other first degree relative is affected. This study systematically reviews the available literature to identify the most significant genes or variants related to the development and onset of IS. Methods The research question was formulated using a PIOS approach on the following databases: Medline, Embase, Cinahl, Scopus, Web of Science and Google Scholar. The search was performed from July to August 2021, and articles from the inception of the database to August 2021 were searched. Results 24 of the 919 initially identified studies were included in the present review. The 24 included studies observed a total of 16,316 cases and 81,567 controls. All the considered studies stated either the affected gene and/or specific SNPs. CHD7, SH2B1, ESR, CALM1, LBX1, MATN1, CHL1, FBN1 and FBN2 genes were associated with IS development. Conclusions Although association can be found in some candidate genes the field of research regarding genetic association with the onset of IS still requires more information.

Published
2022

47. Identifying systemic inequity in higher education and opportunities for improvement

Author

Kameryn Denaro, Kimberly Dennin, Michael Dennin, Brian Sato, and Amaral, Luís A Nunes

Subjects
Quality Education, Technology, Multidisciplinary, Engineering, Universities, General Science & Technology, ComputingMilieux_COMPUTERSANDEDUCATION, Humans, Students, Stem Cell Research, Mathematics
Abstract

It is well established that there is a national problem surrounding the equitable participation in and completion of science, technology, engineering, and mathematics (STEM) higher education programs. Persons excluded because of their ethnicity or race (PEERs) experience lower course performance, major retention, sense of belonging, and degree completion. It is unclear though how pervasive these issues are across an institution, from the individual instructor, course, and discipline perspectives. Examining over six years of institutional data from a large-enrollment, research-intensive, minority-serving university, we present an analysis of racial opportunity gaps between PEERs and non-PEERs to identify the consistency of these issues. From this analysis, we find that there is considerable variability as to whether a given course section taught by a single instructor does or does not exhibit opportunity gaps, although encouragingly we did identify exemplar instructors, course-instructor pairs, courses, and departments that consistently had no significant gaps observed. We also identified significant variation across course-instructor pairs within a department, and found that certain STEM disciplines were much more likely to have courses that exhibited opportunity gaps relative to others. Across nearly all disciplines though, it is clear that these gaps are more pervasive in the lower division curriculum. This work highlights a means to identify the extent of inequity in STEM success across a university by leveraging institutional data. These findings also lay the groundwork for future studies that will enable the intentional design of STEM education reform by leveraging beneficial practices used by instructors and departments assigning equitable grades.

Published
2022

48. Cochlear implant in vestibular schwannomas: long-term outcomes and critical analysis of indications

Author

Flavia Sorrentino, Giulia Tealdo, Diego Cazzador, Niccolò Favaretto, Davide Brotto, Silvia Montino, Ezio Caserta, Roberto Bovo, Luca Denaro, Valentina Baro, Domenico D’Avella, Alessandro Martini, Antonio Mazzoni, Gino Marioni, and Elisabetta Zanoletti

Subjects
Neurofibromatosis 2, Neuroma, Acoustic, General Medicine, Cochlear implant, Hearing rehabilitation, Neurofibromatosis type 2, Sporadic, Vestibular schwannoma, Cochlear Implantation, Cochlear Implants, Treatment Outcome, Otorhinolaryngology, Humans, Hearing Loss, Retrospective Studies
Abstract

To describe our institutional experience in cochlear implantation after vestibular schwannoma (VS) resection, and compare the audiological outcomes between sporadic and neurofibromatosis type 2 (NF2) VS sub-cohorts of patients, and in relation to preoperative contralateral hearing.Seventeen patients (8 sporadic and 9 NF2-associated VSs) who had undergone VS resection and cochlear implant (CI) were analyzed retrospectively. Audiological outcomes at 24 months were correlated with preoperative clinical variables. The results according to VS type (sporadic vs. NF2-associated) and contralateral hearing (impaired vs. normal) were compared.Fourteen CIs were actively used by the patients (77.8%). Twenty-four months after CI activation, the median postoperative PTA (pure tone average) was 45.6 dB nHL and a measurable WRS (Word Recognition Score) was achieved by 44.4% of patients (median WRS = 40%). The median postoperative PTA in the implanted ear resulted better in the group with an impaired contralateral hearing (36.3 dB nHL vs. 78.8 dB nHL, p = 0.019). Good preoperative contralateral hearing status (A-B classes of AAO-HNS) was a negative prognostic factor for CI performance on open-set discrimination (OR = 28.0, 95% CI 2.07-379.25, p = 0.012).CI is a viable rehabilitative option for patients with sporadic or NF2-associated VS. A good contralateral hearing adversely affects CI outcome and should be taken into consideration for patients' selection and rehabilitation programs.

Published
2022

49. Immunotherapy in nonendemic nasopharyngeal carcinoma: Real-world data from two nonendemic regions

Author

Panagiota Economopoulou, Anastasios Pantazopoulos, Aris Spathis, Ioannis Kotsantis, Anastasios Kyriazoglou, George Kavourakis, Roubini Zakopoulou, Ioannis Chatzidakis, Maria Anastasiou, Maria Prevezanou, Carlo Resteghini, Lisa Licitra, Cristiana Bergamini, Elena Colombo, Francesca Caspani, Nerina Denaro, Stefania Vecchio, Pierluigi Bonomo, Maria Cossu Rocca, Federica Bertolini, Daris Ferrari, Amanda Psyrri, and Paolo Bossi

Subjects
Male, Nasopharyngeal Carcinoma, Greece, QH301-705.5, Nonendemic region, Nasopharyngeal cancer, immunotherapy, nasopharyngeal cancer, EBV DNA, nonendemic region, General Medicine, Immunotherapy, Aged, Female, Humans, Immune Checkpoint Inhibitors, Italy, Neoplasm Metastasis, Progression-Free Survival, Survival Analysis, Article, Biology (General)
Abstract

Background: nasopharyngeal carcinoma (NPC) is a complex disease entity that mainly predominates in endemic regions. Real-world data with immunotherapy from nonendemic regions are limited. Methods: we collected data from patients with recurrent/metastatic (R/M) NPC treated at a center in Greece and 8 centers in Italy. Between 2016 and 2021, 46 patients who were treated with at least one cycle of immune checkpoint inhibitors (ICI) were identified. Herein, we present our results and a review of the literature. Results: assessment of response was available in 42 patients. Overall, 11 patients responded to immunotherapy (Overall Response Rate-ORR 26.2%). Three patients had complete response (CR), and 8 patients had partial response (PR). Disease control rate (DCR) was 61.9%. Median Progression Free Survival (PFS) was 5.6 months and median Overall Survival (OS) was 19.1 months. Responders to ICI improved PFS and OS as compared to that of nonresponders. A lower probability of responding to ICI was shown in patients with more than three metastatic sites (p = 0.073), metastatic disease at initial diagnosis, (p = 0.039) or EBV DNA positive before ICI initiation, (p = 0.074). Decline in EBV DNA levels was found to be statistically significant associated with best response to ICI (p = 0.049). Safety was manageable. Conclusions: among 46 patients with R/M NPC treated with immunotherapy in two nonendemic regions, ORR was 26.2% and durable responses were observed. Low disease burden could serve as a biomarker for response to ICI.

Published
2022

50. Pharmacognostic approach to evaluate the micromorphological, phytochemical and biological features of Citrus lumia seeds

Author

Smeriglio, Antonella, Denaro, Marcella, Di Gristina, Emilio, Mastracci, Luca, Grillo, Federica, Cornara, Laura, and Trombetta, Domenico

Subjects
Citrus, Erythrocytes, Plant Extracts, Antioxidant properties, Mononuclear, Phytochemicals, Phytochemical profile, Seed extract, General Medicine, Anti-inflammatory activity, Citrus lumia Risso, Micro-morphological features, Antioxidants, Humans, Leukocytes, Mononuclear, Seeds, Analytical Chemistry, Anti-inflammatory activity, Antioxidant properties, Citrus lumia Risso, Micro-morphological features, Phytochemical profile, Seed extract, Antioxidants, Citrus, Erythrocytes, Humans, Leukocytes, Mononuclear, Phytochemicals, Plant Extracts, Seeds, Leukocytes, Food Science
Abstract

This study evaluated the micro-morphology as well as the chemical and biological features of Citrus lumia seeds. The cream-colored pyriform seed showed a woody coat covered by a thick layer of mucilage and an embryo with two large cotyledons rich in oil bodies. Hydroxycinnamic acid glycosides and flavonoids are the most abundant compounds in methanol and ethyl acetate extracts (ME and EAE), respectively. Conversely, fatty acids and α-tocopherol represent the main bioactive compounds in the hexane extract (HE). ME showed the most promising antioxidant and anti-inflammatory activities already in cell-free assays. These results were confirmed by experiments carried out on human primary cells. Indeed, ME showed the best inhibitory activity against heat-induced haemolysis and ROS formation in erythrocytes. Moreover, the same order of potency (ME EAE HE) was observed also on peripheral blood mononuclear cells, in which the seed extracts were able to decrease TNF-α and IL-6 release after LPS-induced inflammation.

Published
2022

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