Publications by authors named "Alberto Costa"

169 Publications

Medical vulnerability of individuals with Down syndrome to severe COVID-19-data from the Trisomy 21 Research Society and the UK ISARIC4C survey.

EClinicalMedicine 2021 Feb 22:100769. Epub 2021 Feb 22.

Institute of Psychiatry, Psychology, and Neuroscience, Department of Forensic and Neurodevelopmental Sciences, King's College London, London, United Kingdom.

Background: Health conditions, immune dysfunction, and premature aging associated with trisomy 21 (Down syndrome, DS) may impact the clinical course of COVID-19.

Methods: The T21RS COVID-19 Initiative launched an international survey for clinicians or caregivers on patients with COVID-19 and DS. Data collected between April and October 2020 (N=1046) were analysed and compared with the UK ISARIC4C survey of hospitalized COVID-19 patients with and without DS.

Findings: The mean age of COVID-19 patients with DS in the T21RS survey was 29 years (SD = 18). Similar to the general population, the most frequent signs and symptoms of COVID-19 were fever, cough, and shortness of breath. Joint/muscle pain and vomiting or nausea were less frequent ( < 0.01), whereas altered consciousness/confusion were more frequent ( < 0.01). Risk factors for hospitalization and mortality were similar to the general population with the addition of congenital heart defects as a risk factor for hospitalization. Mortality rates showed a rapid increase from age 40 and were higher in patients with DS (T21RS DS versus non-DS patients: risk ratio (RR) = 3.5 (95%-CI=2.6;4.4), ISARIC4C DS versus non-DS patients: RR = 2.9 (95%-CI=2.1;3.8)) even after adjusting for known risk factors for COVID-19 mortality.

Interpretation: Leading signs/symptoms of COVID-19 and risk factors for severe disease course are similar to the general population. However, individuals with DS present significantly higher rates of medical complications and mortality, especially from age 40.

Funding: Down Syndrome Affiliates in Action, DSMIG-USA, GiGi's Playhouse, Jerome Lejeune Foundation, LuMind IDSC Foundation, The Matthew Foundation, NDSS, National Task Group on Intellectual Disabilities and Dementia Practices.
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http://dx.doi.org/10.1016/j.eclinm.2021.100769DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897934PMC
February 2021

Cognitive and mental health changes and their vulnerability factors related to COVID-19 lockdown in Italy.

PLoS One 2021 27;16(1):e0246204. Epub 2021 Jan 27.

Department of General Psychology, University of Padua, Padua, Italy.

The COVID-19 pandemic and government imposed social restrictions like lockdown exposed most individuals to an unprecedented stress, increasing mental health disorders worldwide. We explored subjective cognitive functioning and mental health changes and their possible interplay related to COVID-19-lockdown. We also investigated potential risk factors to identify more vulnerable groups. Across Italy, 1215 respondents completed our Qualtrics-based online-survey during the end of a seven to 10-week imposed lockdown and home confinement (from April 29 to May 17, 2020). We found subjective cognitive functioning and mental health severely changed in association with the lockdown. Under government regulations, cognitive complaints were mostly perceived in routine tasks involving attention, temporal orientation and executive functions-with no changes in language abilities. A paradoxical effect was observed for memory, with reduced forgetfulness compared to pre-lockdown. We found higher severity and prevalence of depression, anxiety disorders, abnormal sleep, appetite changes, reduced libido and health anxiety: with mild-to-severe depression and anxiety prevalence climbing to 32 and 36 percent, respectively, under restrictions. Being female, under 45 years, working from home or being underemployed were all identified as relevant risk factors for worsening cognition and mental health. Frequent consumers of COVID-19 mass media information or residents in highly infected communities reported higher depression and anxiety symptoms, particularly hypochondria in the latter. If similar restrictions are reimposed, governments must carefully consider these more vulnerable groups in their decisions, whilst developing effective global and long-term responses to the cognitive and mental health challenges of this type of pandemic; as well as implementing appropriate psychological interventions with specific guidelines: particularly regarding exposure to COVID-19 mass-media reports.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246204PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840042PMC
February 2021

Profiling Persistent Asthma Phenotypes in Adolescents: A Longitudinal Diagnostic Evaluation from the INSPIRERS Studies.

Int J Environ Res Public Health 2021 Jan 24;18(3). Epub 2021 Jan 24.

Center for Health Technology and Services Research (CINTESIS), Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal.

We aimed to identify persistent asthma phenotypes among adolescents and to evaluate longitudinally asthma-related outcomes across phenotypes. Adolescents (13-17 years) from the prospective, observational, and multicenter INSPIRERS studies, conducted in Portugal and Spain, were included ( = 162). Latent class analysis was applied to demographic, environmental, and clinical variables, collected at a baseline medical visit. Longitudinal differences in clinical variables were assessed at a 4-month follow-up telephone contact ( = 128). Three classes/phenotypes of persistent asthma were identified. Adolescents in class 1 ( = 87) were highly symptomatic at baseline and presented the highest number of unscheduled healthcare visits per month and exacerbations per month, both at baseline and follow-up. Class 2 ( = 32) was characterized by female predominance, more frequent obesity, and uncontrolled upper/lower airways symptoms at baseline. At follow-up, there was a significant increase in the proportion of controlled lower airway symptoms ( < 0.001). Class 3 ( = 43) included mostly males with controlled lower airways symptoms; at follow-up, while keeping symptom control, there was a significant increase in exacerbations/month ( = 0.015). We have identified distinct phenotypes of persistent asthma in adolescents with different patterns in longitudinal asthma-related outcomes, supporting the importance of profiling asthma phenotypes in predicting disease outcomes that might inform targeted interventions and reduce future risk.
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http://dx.doi.org/10.3390/ijerph18031015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7908090PMC
January 2021

ESO-ESSO-ESTRO Multidisciplinary Course in Oncology for Medical Students: 4 Years of Experience (2016-2019).

J Cancer Educ 2021 Jan 2. Epub 2021 Jan 2.

Oncology, Antwerp University Hospital, Edegem, Belgium.

The ESO-ESSO-ESTRO Multidisciplinary Course in Oncology is intended to fill the gap of the undergraduate fragmented oncology education, to provide insight into all theoretical and practical aspects of oncology, and to encourage future professional choices towards an oncology discipline. Students are exposed to (a) preclinical cancer topics; (b) natural history of the disease; (c) laboratory diagnostic tests; (d) medical, radiation, surgical, and palliative treatment; and (e) direct or through multidisciplinary patients' approach. Students are obliged to attend (i) all theoretical lectures, (ii) clinical case presentations, (iii) laboratories and ward visits, and (iv) to prepare and present a specific project under supervision. Participation is limited to 24 medical students who are selected through a competitive application process. Between 2016 and 2019, 96 students from 29 countries have attended. Data analysis derived from a given questionnaire demonstrates that most of the participants have declared that (1) they have achieved their expectations and objectives, (2) they have highly rated both clinical and non-clinical teaching oncological topics, and (3) they have been stimulated in developing a professional career in the field of oncology.
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http://dx.doi.org/10.1007/s13187-020-01947-3DOI Listing
January 2021

European Cancer Organisation Essential Requirements for Quality Cancer Care (ERQCC): Lung cancer.

Lung Cancer 2020 12 4;150:221-239. Epub 2020 Sep 4.

European Cancer Organisation; Iridium Kankernetwerk and University of Antwerp, Wilrijk-Antwerp, Belgium.

European Cancer Organisation Essential Requirements for Quality Cancer Care (ERQCC) are written by experts representing all disciplines involved in cancer care in Europe. They give patients, health professionals, managers and policymakers a guide to essential care throughout the patient journey. Lung cancer is the leading cause of cancer mortality and has a wide variation in treatment and outcomes in Europe. It is a major healthcare burden and has complex diagnosis and treatment challenges. Care must only be carried out in lung cancer units or centres that have a core multidisciplinary team (MDT) and an extended team of health professionals detailed here. Such units are far from universal in European countries. To meet European aspirations for comprehensive cancer control, healthcare organisations must consider the requirements in this paper, paying particular attention to multidisciplinarity and patient-centred pathways from diagnosis, to treatment, to survivorship.
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http://dx.doi.org/10.1016/j.lungcan.2020.08.017DOI Listing
December 2020

An international survey on the impact of COVID-19 in individuals with Down syndrome.

medRxiv 2020 Nov 5. Epub 2020 Nov 5.

Background: Health conditions and immune dysfunction associated with trisomy 21 (Down syndrome, DS) may impact the clinical course of COVID-19 once infected by SARS-CoV-2.

Methods: The T21RS COVID-19 Initiative launched an international survey for clinicians or caregivers/family members on patients with COVID-19 and DS (N=1046). De-identified survey data collected between April and October 2020 were analysed and compared with the UK ISARIC4C survey of hospitalized COVID-19 patients with and without DS. COVID-19 patients with DS from the ISARIC4C survey (ISARIC4C DS cases=100) were matched to a random set of patients without DS (ISARIC4C controls=400) and hospitalized DS cases in the T21RS survey (T21RS DS cases=100) based on age, gender, and ethnicity.

Finding: The mean age in the T21RS survey was 29 years (SD=18), 73% lived with their family. Similar to the general population, the most frequent signs and symptoms of COVID-19 were fever, cough, and shortness of breath. Pain and nausea were reported less frequently (p<0.01), whereas altered consciousness/confusion were reported more frequently (p<0.01). Risk factors for hospitalization and mortality were similar to the general population (age, male gender, diabetes, obesity, dementia) with the addition of congenital heart defects as a risk factor for hospitalization. Mortality rates showed a rapid increase from age 40 and were higher than for controls (T21RS DS versus controls: risk ratio (RR)=3.5 (95%-CI=2.6;4.4), ISARIC4C DS versus controls: RR=2.9 (95%-CI=2.1;3.8)) even after adjusting for known risk factors for COVID-19 mortality.

Interpretation: Leading signs/symptoms of COVID-19 and risk factors for severe disease course are similar to the general population. However, individuals with DS present significantly higher rates of mortality, especially from age 40.

Funding: Down Syndrome Affiliates in Action, Down Syndrome Medical Interest Group-USA, GiGi's Playhouse, Jerome Lejeune Foundation, LuMind IDSC Foundation, Matthews Foundation, National Down Syndrome Society, National Task Group on Intellectual Disabilities and Dementia Practices.
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http://dx.doi.org/10.1101/2020.11.03.20225359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7654903PMC
November 2020

Does Cue Focality Modulate Age-related Performance in Prospective Memory? An fMRI Investigation.

Exp Aging Res 2021 Jan-Feb;47(1):1-20. Epub 2020 Oct 27.

Laboratory of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation , Rome, Italy.

How prospective memory (PM) weakens with increasing age has been largely debated. We hypothesized that automatic and strategic PM processes, respectively mediated by focal and non-focal cues, are differently affected by aging, even starting from 50-60 years of age. We investigated this issue using a 2 × 2 design in which focal and non-focal experimental conditions were created by varying the conjoint nature of the ongoing task (lexical decision vs. syllable matching tasks) and the PM cue (words vs. syllables). In the whole-brain analysis we found that the left inferior frontal gyrus and the middle cingulate cortex were more activated when young compared to older individuals performed a PM task; moreover, the anterior cingulate cortex was selectively activated during non-focal PM when the cues were words. In a region-of-interest analysis we observed that the medial and the lateral portions of the rostral prefrontal cortex were associated with the focal and non-focal conditions respectively, more in young than in older adults. Our findings provide evidence in support of early age-related differences in automatic/strategic PM functioning.
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http://dx.doi.org/10.1080/0361073X.2020.1839310DOI Listing
October 2020

Breast cancer in the oldest old (≥ 89 years): Tumor characteristics, treatment choices, clinical outcomes and literature review.

Eur J Surg Oncol 2020 Oct 13. Epub 2020 Oct 13.

CSSI, Centro di Senologia Della Svizzera Italiana, Ente Ospedaliero Cantonale - EOC, Switzerland; Gynecology and Obstetric Department, Ente Ospedaliero Cantonale - EOC, Lugano, Switzerland.

Introduction: Risk of breast cancer increases with age and very few data are available in patients older than 89.

Methods: A retrospective analysis on patients aged 89 and older treated between 2008 and 2019 at our certified breast center. The aim was to analyze clinical characteristics, decision-making, treatment, outcomes and open questions regarding this subpopulation for which there is a lack of guidelines.

Results: 58 patients included. Tumor characteristics were analyzed, 85% patients underwent surgery of which 44% had a mastectomy. The median follow-up and overall survival were 20 and 76 months, respectively.The median survival of metastatic and non-metastatic patients were 14 and 50 months, respectively. Most patients did not receive any adjuvant treatment and among these 14% had a relapse.

Conclusions: Elderly patients should not be under or over-treated because of their age; they represent a large heterogeneous group deserving a sub-stratification for a better tailored treatment.
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http://dx.doi.org/10.1016/j.ejso.2020.10.008DOI Listing
October 2020

The Self-Awareness Multilevel Assessment Scale, a New Tool for the Assessment of Self-Awareness After Severe Acquired Brain Injury: Preliminary Findings.

Front Psychol 2020 24;11:1732. Epub 2020 Jul 24.

Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Santa Lucia Foundation, Rome, Italy.

Self-awareness (SA) is frequently impaired after severe acquired brain injury (sABI) and may lead to reduced subject's compliance to treatment, worse functional outcome, and high caregiver distress. Considering the multifaceted nature of SA, a specific and effective assessment is crucial to address treatment of impairment of SA (ISA). Many tools can currently assess ISA; however, they have some important limits. In the present study, we proposed the Self-Awareness Multilevel Assessment Scale (SAMAS), a new scale for assessment of SA at different levels (i.e., , , and ) across all domains of functioning. The SAMAS has been designed to be administered by the cognitive/behavioral therapist with the involvement of a patient's relative. Findings showed that the SAMAS allowed specifically assessing SA at a level and on all possible functional domains. More interestingly, it seems also able to assess both and SA, thus overcoming some important limits of other current assessment methods. Our findings are consistent with a holistic perspective of the patient with sABI because thanks to the combined use of assessing tools, the SAMAS can provide an accurate diagnosis of ISA, thus better addressing the neurorehabilitation treatment and, accordingly, reducing the possible occurrence of its primary and secondary implications.
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http://dx.doi.org/10.3389/fpsyg.2020.01732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7393213PMC
July 2020

The clinical training centers fellowships: a European School of Oncology career development program (2013-2019).

Future Oncol 2020 Sep 21;16(26):1969-1976. Epub 2020 Jun 21.

European School of Oncology, Milan, Italy.

This article refers to the European School of Oncology Clinical Training Centers (CTCs) program, which is a granted Fellowships program dedicated to young oncologists in training. A total of 74 fellowships were offered by several CTCs during the last 7 years. Candidates were enrolled for 3-6 months of training rotations as fellows or observers in more than 30 training programs in well known Cancer Centers around Europe. Fellowships were covering medical, surgical, radiation and pediatric oncology specialties, laboratory diagnostic training and experimental, translational and clinical research. Fellows originated from Europe, Latin America and Mediterranean Africa. Analysis of the questionnaire assessment showed that 95.5% of the fellows evaluated CTC programs with an 'excellent' or 'very good' score, while 100% declare that they had reached their objectives. The European School of Oncology CTC program designed for an additional practical education abroad meets the needs of young oncologists.
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http://dx.doi.org/10.2217/fon-2020-0193DOI Listing
September 2020

Noninvasive assessment of autonomic modulation of heart rate variability in the Ts65Dn mouse model of Down syndrome: A proof of principle study.

Physiol Rep 2020 06;8(12):e14486

Division of Pediatric Neurology, Department of Pediatrics, Case Western Reserve University, Cleveland, OH, USA.

Introduction: The Ts65Dn mouse is the most widely used animal model of Down syndrome (DS). Differences in autonomic regulation of heart rate variability (HRV) in individuals with DS have been hypothesized. Pharmacological studies in animal models may help us understand mechanisms underlying observed changes in HRV in people with DS.

Objective: To investigate the use a new, noninvasive technique to assess cardiac autonomic modulation in Ts65Dn mice under the effect of adrenergic and cholinergic agonists.

Method: We recorded electrocardiograms (ECGs) from 12 Ts65Dn and 12 euploid control mice. A 30-min baseline recording was followed by the injection of an adrenergic (isoproterenol [Iso]) or cholinergic (carbachol [CCh]) agonist. Heart rate and HRV were analyzed using a series of methods customized for mice.

Results And Discussion: The ECG apparatus described here allowed us to detect noninvasively long series of heartbeats in freely-moving animals. During baseline conditions, the yield of detectable heartbeats was 3%-27% of the estimated total number of events, which increased to 35%-70% during the 15-min period after either Iso or CCh injections. Ts65Dn mice displayed a robust enhanced Iso-induced negative chronotropic rebound response compared with euploid control mice. We observed a significantly smaller CCh response in Ts65Dn versus control euploid mice in the 6- to 10-min-interval postcarbachol injection.

Conclusion: This work showed that the techniques described here are sufficient for this type of study. However, future studies involving the use of more selective pharmacological agents and/or genetic manipulations will be key to advance a mechanistic understanding of cardiac autonomic regulation in DS.
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http://dx.doi.org/10.14814/phy2.14486DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7305244PMC
June 2020

Quantitative Analysis of Retinal Structure and Function in Two Chromosomally Altered Mouse Models of Down Syndrome.

Invest Ophthalmol Vis Sci 2020 05;61(5):25

,.

Purpose: Ophthalmic disorders are among the most prevalent Down syndrome (DS) comorbidities. Therefore, when studying mouse models of DS, ignoring how vision is affected can lead to misinterpretation of results from assessments dependent on the integrity of the visual system. Here, we used imaging and electroretinography (ERG) to study eye structure and function in two important mouse models of DS: Ts65Dn and Dp(16)1Yey/+.

Methods: Cornea and anterior segment were examined with a slit-lamp. Thickness of retinal layers was quantified by optical coherence tomography (OCT). Eye and lens dimensions were measured by magnetic resonance imaging (MRI). Retinal vasculature parameters were assessed by bright field and fluorescent imaging, and by retinal flat-mount preparations. Ganzfeld ERG responses to flash stimuli were used to assess retinal function in adult mice.

Results: Total retinal thickness is significantly increased in Ts65Dn and Dp(16)1Yey/+ compared with control mice, because of increased thickness of inner retinal layers, including the inner nuclear layer (INL). Increased retinal vessel caliber was found in both chromosomally altered mice when compared with controls. ERG responses in Ts65Dn and Dp(16)1Yey/+ mice showed subtle alterations compared with controls. These, however, seemed to be unrelated to the thickness of the INL, but instead dependent on the anesthetic agent used (ketamine, tribromoethanol, or urethane).

Conclusions: We provide evidence of retinal alterations in Ts65Dn and Dp(16)1Yey/+ mice that are similar to those reported in persons with DS. Our ERG results are also a reminder that consideration should be given to the choice of anesthetic agents in such experiments.
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http://dx.doi.org/10.1167/iovs.61.5.25DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7405684PMC
May 2020

The impact of the European School of Oncology masterclass in clinical oncology on self-professional development.

Crit Rev Oncol Hematol 2020 Jul 28;151:102976. Epub 2020 Apr 28.

European School of Oncology, Milan, Italy.

We investigated the impact of the European School of Oncology's (ESO) Masterclass (MCO) in Clinical Oncology on the career development of young participants. MCO represents the flagship educational activity of ESO and is organized annually, mostly in collaboration with the European Society for Medical Oncology (ESMO) in five different geographical regions. A questionnaire consisting of 21 questions was sent to all doctors who attended the ESO MCOs from 2009 to 2016. The 228 responders were mostly from European countries and hold the specialty of Medical Oncology. Ninety-five percent of them evaluated ESO MCOs as "extremely useful" or "useful" for their professional career. Around 60% were trained at University Hospitals or Cancer Institutes and currently, one-third of them are employed in Academic Centers. Eighty percent have performed translational or clinical research and 77.5% were able to publish in pertinent international journals. The contribution of ESO MCOs to trainees' career development in different oncology disciplines around the world is discussed.
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http://dx.doi.org/10.1016/j.critrevonc.2020.102976DOI Listing
July 2020

Clinical Case Presentation and Discussion During ESO-ESMO Masterclass: a 10-Year Interactive Educational Experience.

J Cancer Educ 2020 Apr 17. Epub 2020 Apr 17.

European School of Oncology, Milan, Italy.

In this article, we report on the clinical case presentations that have been delivered during the ESO or ESO-ESMO Masterclasses in Clinical Oncology in the last 10 years. Masterclasses have been held in three different geographical continents including Europe, Middle East, and Latin America, in which participants had to submit a clinical case and present it either in front of a tumor board (multidisciplinary-like sessions) or in small groups. Clinical case presentation is a unique part of the educational program preparing young oncologists to present and discuss their own patients with distinguished experts. In each Masterclass, between 40 and 55 clinical cases-depending on the number of participants-are presented. All presentations are assessed and evaluated by faculty members as well as by the rest of the participants.
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http://dx.doi.org/10.1007/s13187-020-01744-yDOI Listing
April 2020

The requirements of a specialist breast centre.

Breast 2020 Jun 26;51:65-84. Epub 2020 Feb 26.

Iridium Kankernetwerk, University of Antwerp, Faculty of Medicine and Health Sciences, Campus Drie Eiken, Wilrijk-Antwerp, Belgium.

This article is an update of the requirements of a specialist breast centre, produced by EUSOMA and endorsed by ECCO as part of Essential Requirements for Quality Cancer Care (ERQCC) programme, and ESMO. To meet aspirations for comprehensive cancer control, healthcare organisations must consider the requirements in this article, paying particular attention to multidisciplinarity and patient-centred pathways from diagnosis, to treatment, to survivorship.
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http://dx.doi.org/10.1016/j.breast.2020.02.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7375681PMC
June 2020

ECCO Essential Requirements for Quality Cancer Care: Prostate cancer.

Crit Rev Oncol Hematol 2020 Apr 7;148:102861. Epub 2020 Jan 7.

European Cancer Organisation (ECCO).

Background: ECCO Essential Requirements for Quality Cancer Care (ERQCC) are written by experts representing all disciplines involved in cancer care in Europe. They give oncology teams, patients, policymakers and managers an overview of essential care throughout the patient journey.

Prostate Cancer: Prostate cancer is the second most common male cancer and has a wide variation in outcomes in Europe. It has complex diagnosis and treatment challenges, and is a major healthcare burden. Care must only be a carried out in prostate/urology cancer units or centres that have a core multidisciplinary team (MDT) and an extended team of health professionals. Such units are far from universal in European countries. To meet European aspirations for comprehensive cancer control, healthcare organisations must consider the requirements in this paper, paying particular attention to multidisciplinarity and patient-centred pathways from diagnosis, to treatment, to survivorship.
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http://dx.doi.org/10.1016/j.critrevonc.2019.102861DOI Listing
April 2020

Metabolomics Approach Expands the Classification of Propolis Samples from Midwest Brazil.

J Nat Prod 2020 02 7;83(2):333-343. Epub 2020 Feb 7.

Institute of Chemistry , Universidade Federal de Mato Grosso do Sul , Campo Grande , MS 79074-460 , Brazil.

Propolis samples collected from five areas in Mato Grosso do Sul state, Midwest Brazil, comprising portions of the Cerrado, Pantanal, and Atlantic Forest ecosystems, were investigated for metabolomic profiles and evaluated for antioxidant and antitumor potential. Chemical profiles were determined by HPLC-DAD-MS/MS data and evaluated using principal component analysis and hierarchical clustering analysis to discern chemical composition patterns. Based on phytogeographical origin and chemical composition, 20 potential markers were identified and five groups were distinguished: (I) Cerrado/Central, (II) Atlantic Forest/South, (III) Cerrado-Pantanal transition area/Northwest, (IV) Cerrado/North, and (V) Pantanal/West. Drawing on HPLC-DAD-MS/MS and NMR data, 47 compounds were successfully or tentatively identified, including prenylated phenylpropanoids, flavonoids, isoflavonoids, and di- and triterpenoids, among other constituents. Isoflavonoids, typically found in red propolis from Northeast Brazil, are being reported for the first time in a propolis sample from the Midwest. A new prenylated aromatic compound, ()-3-[4-hydroxy-3-(2-hydroxy-3-methylbut-3-en-1-yl)-5-(3-methylbut-2-en-1-yl)phenyl]propenoic acid, was obtained. Samples in group II exhibited promising antitumor potential against prostate and breast carcinoma cells, as did samples in groups III and IV against the latter cell line. The sample in group I, despite containing the highest amount of total phenolic compounds and being the only sample to exhibit scavenging activity against DPPH, was not the most cytotoxic against the cell lines tested.
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http://dx.doi.org/10.1021/acs.jnatprod.9b00783DOI Listing
February 2020

Changing the education paradigm in oncology: ESO masterclass, 17 years of continuous success.

Crit Rev Oncol Hematol 2020 Feb 1;146:102798. Epub 2019 Aug 1.

European School of Oncology, Milan, Italy.

In this review, we summarize the history of the 41 Masterclasses in Clinical Oncology (MCO) organized by ESO or ESO-ESMO during the last 17 years. MCOs have been held in five different geographical regions including: a) Central Europe, b) Eastern Europe and Balkans, c) Baltic and Euroasia, d) Arab World and Southern European Countries and e) Latin America. More than 2.000 young oncologists have attended and more than 250 distinguished faculty members have actively participated. The program exposes students to sessions covering all major tumors ("big killers") and to spotlights updating information on various important cancers and related topics. Participants are able to present their own clinical case in front of a tumor board or in parallel group sessions and are evaluated by a Learning Assessment Test (LAT) at the end of the event. They are asked to discuss the programme, using a questionnaire on the goals, quality and organization of the MCOs, which has been very highly scored by most of the participants. The Masterclass in Clinical Oncology has become the major educational event of ESO, intending to educate young oncologists from various countries within or outside Europe, providing an up-to-date interactive program based on solid evidence for all presented topics.
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http://dx.doi.org/10.1016/j.critrevonc.2019.07.022DOI Listing
February 2020

ESO-ESMO Masterclass in Clinical Oncology: Analysis and Evaluation of the Learning Self-Assessment Test.

J Cancer Educ 2019 Dec 16. Epub 2019 Dec 16.

European School of Oncology, Milan, Italy.

Masterclass in Clinical Oncology (MCO) represents the "key educational event" of European School of Oncology's (ESO) teaching program. MCO in collaboration with European Society for Medical Oncology (ESMO) is a multidisciplinary and clinical oriented educational event offered mainly to young oncologists worldwide. It provides full immersion in oncology with clinical case presentations and a Learning Self-Assessment Test (LSAT).LSAT is consisting of 45 multiple choice questions on an electronic platform referring to the material taught during the MCO. Three questions related to their topics are requested in advance from each faculty member. The major intentions of LSAT are the following: (a) the learning reflection of the massive information given during 4-5 days of intensive teaching and (b) to offer the opportunity to the participants to prepare themselves for their National Boards or for ESMO examination.In this article, we are analyzing and evaluating the results of LSAT from the ESO-ESMO Central European MCOs. We used the information of Central European MCOs for analysis due to the homogeneity of the available data. We assessed the level of participants' knowledge in relation to their oncology specialty or to their country of origin and the level of the quality of faculty teaching.
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http://dx.doi.org/10.1007/s13187-019-01664-6DOI Listing
December 2019

Estimating dyskinesia severity in Parkinson's disease by using a waist-worn sensor: concurrent validity study.

Sci Rep 2019 09 17;9(1):13434. Epub 2019 Sep 17.

Technical Research Centre for Dependency Care and Autonomous Living(CETpD), Universitat Politècnica de Catalunya, Vilanova i la Geltru, Spain.

Our research team previously developed an accelerometry-based device, which can be worn on the waist during daily life activities and detects the occurrence of dyskinesia in patients with Parkinson's disease. The goal of this study was to analyze the magnitude of correlation between the numeric output of the device algorithm and the results of the Unified Dyskinesia Rating Scale (UDysRS), administered by a physician. In this study, 13 Parkinson's patients, who were symptomatic with dyskinesias, were monitored with the device at home, for an average period of 30 minutes, while performing normal daily life activities. Each patient's activity was simultaneously video-recorded. A physician was in charge of reviewing the recorded videos and determining the severity of dyskinesia through the UDysRS for every patient. The sensor device yielded only one value for dyskinesia severity, which was calculated by averaging the recorded device readings. Correlation between the results of physician's assessment and the sensor output was analyzed with the Spearman's correlation coefficient. The correlation coefficient between the sensor output and UDysRS result was 0.70 (CI 95%: 0.33-0.88; p = 0.01). Since the sensor was located on the waist, the correlation between the sensor output and the results of the trunk and legs scale sub-items was calculated: 0.91 (CI 95% 0.76-0.97: p < 0.001). The conclusion is that the magnitude of dyskinesia, as measured by the tested device, presented good correlation with that observed by a physician.
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http://dx.doi.org/10.1038/s41598-019-49798-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6748910PMC
September 2019

The Value and Future Developments of Multidisciplinary Team Cancer Care.

Am Soc Clin Oncol Educ Book 2019 Jan 17;39:332-340. Epub 2019 May 17.

5 European School of Oncology, Milan, Italy.

Multidisciplinary teams (MDTs) have been recommended as a key part of best cancer care for 25 years. Here, we set out the functions and approaches of MDTs and review their impact. Although the literature is patchy in quality, MDTs contribute to improving cancer care and outcomes. They must be well organized, efficient, and well led; work with sound and timely information; and communicate well within the team and with their patients. Patients need carefully prepared information to help them share in the decision-making process. MDTs will be improved by a series of ongoing innovative developments. Increasing information from molecular pathology will increase the precision of their decisions, although the technologies remain expensive and may not be accessible in all countries for some time. New point-of-care testing technologies will improve the quality and timeliness of testing. Good informatics is essential to deliver the information to patients and the MDT. MDTs should be research active, delivering clinical trials, and this should improve outcomes for all of their patients. Patient engagement and empowerment in MDTs should improve patient satisfaction and outcomes. Patient-reported outcome measures will improve MDTs' insights into their patients' problems and symptoms and can improve patient outcomes.
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http://dx.doi.org/10.1200/EDBK_236857DOI Listing
January 2019

Medio-lateral functional dissociation of the rostral prefrontal cortex with focal/non-focal cues during a prospective memory task.

Brain Imaging Behav 2020 Aug;14(4):1175-1186

Laboratory of Clinical and Behavioral Neurology, Santa Lucia Foundation, via Ardeatina 306, 00179, Rome, Italy.

The rostral prefrontal cortex (rPFC) is crucial in prospective memory (PM) behavior. Several functional magnetic resonance imaging studies showed that its medial (mrPFC) and lateral (lrPFC) portions dissociate during PM tasks. In light of the Multiprocess theory (McDaniel and Einstein 2000), here we tested whether the two portions of the rPFC are dissociable by modulating strategic vs. spontaneous processes during a PM task. We investigated these two processes by means of a 2 × 2 experimental design in which focal vs. non-focal conditions were modulated by varying the conjoint nature of the ongoing task (i.e., lexical decision vs. syllable matching) and the PM cue (words vs. syllables). Using the two portions of the rPFC as regions of interest, we found an effect of the non-focal condition in the lrPFC and, conversely, an effect of the focal condition in the mrPFC. In the whole-brain analysis we found an effect of the non-focal condition in the bilateral intraparietal sulcus, the bilateral middle frontal gyrus, the supplementary motor areas and the vermis of the cerebellum, whereas we found an effect of the focal condition in the ventromedial PFC. Overall, our results show that different brain regions are involved when multiple processes underlying PM behavior are modulated.
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http://dx.doi.org/10.1007/s11682-019-00063-1DOI Listing
August 2020

On the Design of Broad-Based Neuropsychological Test Batteries to Assess the Cognitive Abilities of Individuals with Down Syndrome in the Context of Clinical Trials.

Brain Sci 2018 Nov 26;8(12). Epub 2018 Nov 26.

Division of Neurology and Epilepsy, Department of Pediatrics, Case Western Reserve University, Cleveland, OH 44106, USA.

Down syndrome (DS) is the most common genetically-defined cause of intellectual disability. Neurodevelopmental deficits displayed by individuals with DS are generally global, however, disproportionate deficits in cognitive processes that depend heavily on the hippocampus and prefrontal cortex are also well documented. Additionally, DS is associated with relative strengths in visual processing and visuospatial short-term memory, and weaknesses in the verbal domain. Although reports of pharmacological rescuing of learning and memory deficits in mouse models of DS abound in the literature, proving the principle that cognitive ability of persons with DS can be boosted through pharmacological means is still an elusive goal. The design of customized batteries of neuropsychological efficacy outcome measures is essential for the successful implementation of clinical trials of potential cognitive enhancing strategies. Here, we review the neurocognitive phenotype of individuals with DS and major broad-based test batteries designed to quantify specific cognitive domains in these individuals, including the one used in a pilot trial of the drug memantine. The main goal is to illustrate the essential considerations in planning trials to enhance cognitive functions in individuals with DS, which should also have implications for the design of similar studies in individuals with other forms of intellectual disability.
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http://dx.doi.org/10.3390/brainsci8120205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6315396PMC
November 2018

The contribution of neuropsychological and neuroimaging research to the definition of the neurocognitive correlates of apathy.

Neuropsychologia 2018 09 17;118(Pt B):1-3. Epub 2018 Aug 17.

Department of Clinical and Behavioral Neurology, Santa Lucia Foundation, Rome, Italy; Department of Psychology, Niccolò Cusano University, Rome, Italy. Electronic address:

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http://dx.doi.org/10.1016/j.neuropsychologia.2018.08.013DOI Listing
September 2018

Pharmacological Modulation of Three Modalities of CA1 Hippocampal Long-Term Potentiation in the Ts65Dn Mouse Model of Down Syndrome.

Neural Plast 2018 10;2018:9235796. Epub 2018 Apr 10.

Division of Pediatric Neurology, Department of Pediatrics, Case Western Reserve University, Cleveland, OH 44106, USA.

The Ts65Dn mouse is the most studied animal model of Down syndrome. Past research has shown a significant reduction in CA1 hippocampal long-term potentiation (LTP) induced by theta-burst stimulation (TBS), but not in LTP induced by high-frequency stimulation (HFS), in slices from Ts65Dn mice compared with euploid mouse-derived slices. Additionally, therapeutically relevant doses of the drug memantine were shown to rescue learning and memory deficits in Ts65Dn mice. Here, we observed that 1 M memantine had no detectable effect on HFS-induced LTP in either Ts65Dn- or control-derived slices, but it rescued TBS-induced LTP in Ts65Dn-derived slices to control euploid levels. Then, we assessed LTP induced by four HFS (4xHFS) and found that this form of LTP was significantly depressed in Ts65Dn slices when compared with LTP in euploid control slices. Memantine, however, did not rescue this phenotype. Because 4xHFS-induced LTP had not yet been characterized in Ts65Dn mice, we also investigated the effects of picrotoxin, amyloid beta oligomers, and soluble recombinant human prion protein (rPrP) on this form of LTP. Whereas ≥10 M picrotoxin increased LTP to control levels, it also caused seizure-like oscillations. Neither amyloid beta oligomers nor rPrP had any effect on 4xHFS-induced LTP in Ts65Dn-derived slices.
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http://dx.doi.org/10.1155/2018/9235796DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5914153PMC
November 2018

Apathy in individuals with Parkinson's disease associated with mild cognitive impairment. A neuropsychological investigation.

Neuropsychologia 2018 09 19;118(Pt B):4-11. Epub 2018 May 19.

IRCCS Fondazione Santa Lucia, Rome, Italy; Tor Vergata University, Rome, Italy.

Apathy is frequently reported in individuals with Parkinson's disease (PD) and is hypothesized to be associated with frontal-striatal related cognitive functions. Available data, however, do not provide univocal results. Moreover, this relationship has been poorly investigated in PD patients with mild cognitive impairment (MCI). This study was aimed at investigating the association between severity of apathy of PD patients and their performance on neuropsychological tests investigating executive abilities. Individuals with PD (i.e., with and without MCI) and healthy controls (HCs) were administered a neuropsychological test battery that investigated episodic memory, language, short-term memory and attention, visual-spatial abilities and executive functions. Subjects were also administered additional neuropsychological tests to evaluate the different executive subcomponents (i.e., planning/abstract reasoning, self-monitoring/response inhibition, working memory, shifting and fluency). The Apathy Evaluation Scale (AES) was administered to assess apathy severity. Linear regression analyses were applied to the data; results showed that in the PD group with MCI, the best cognitive factor associated to the AES score was patients' scores on the executive tests and, in particular, their scores on tests examining planning/abstract reasoning. By contrast, in the PD group without MCI, the cognitive performance was not significantly associated to apathy severity. Findings of the study document a specific association between reduced efficiency of the executive system and apathy severity in individuals with PD and MCI. This association indirectly supports the hypothesis of a relationship between motivational disorders and dysregulation of the activity of the frontal-striatal networks in PD patients.
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http://dx.doi.org/10.1016/j.neuropsychologia.2018.05.016DOI Listing
September 2018

ECCO essential requirements for quality cancer care: Oesophageal and gastric cancer.

Crit Rev Oncol Hematol 2018 Feb 2;122:179-193. Epub 2018 Jan 2.

European CanCer Organisation (ECCO); Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. Electronic address:

Background: ECCO essential requirements for quality cancer care (ERQCC) are checklists and explanations of organisation and actions that are necessary to give high-quality care to patients who have a specific type of cancer. They are written by European experts representing all disciplines involved in cancer care. ERQCC papers give oncology teams, patients, policymakers and managers an overview of the elements needed in any healthcare system to provide high quality of care throughout the patient journey. References are made to clinical guidelines and other resources where appropriate, and the focus is on care in Europe.

Oesophageal And Gastric: ESSENTIAL REQUIREMENTS FOR QUALITY CARE: CONCLUSION: Taken together, the information presented in this paper provides a comprehensive description of the essential requirements for establishing a high-quality OG cancer service. The ERQCC expert group is aware that it is not possible to propose a 'one size fits all' system for all countries, but urges that access to multidisciplinary units or centres must be guaranteed for all those with OG cancer.
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http://dx.doi.org/10.1016/j.critrevonc.2017.12.019DOI Listing
February 2018

ECCO essential requirements for quality cancer care: Melanoma.

Crit Rev Oncol Hematol 2018 Feb 2;122:164-178. Epub 2018 Jan 2.

European CanCer Organisation (ECCO); Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. Electronic address:

Background: ECCO essential requirements for quality cancer care (ERQCC) are explanations and descriptions of challenges, organisation and actions that are necessary to give high-quality care to patients who have a specific type of cancer. They are written by European experts representing all disciplines involved in cancer care. ERQCC papers give oncology teams, patients, policymakers and managers an overview of the elements needed in any healthcare system to provide high quality of care throughout the patient journey. References are made to clinical guidelines and other resources where appropriate, and the focus is on care in Europe.

Melanoma: ESSENTIAL REQUIREMENTS FOR QUALITY CARE: CONCLUSION: Taken together, the information presented in this paper provides a comprehensive description of the essential requirements for establishing a high-quality service for melanoma. The ERQCC expert group is aware that it is not possible to propose a 'one size fits all' system for all countries, but urges that access to multidisciplinary teams and specialised treatments is guaranteed to all patients with melanoma.
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http://dx.doi.org/10.1016/j.critrevonc.2017.12.020DOI Listing
February 2018

Risk Factors for Shoulder Stiffness: Current Concepts.

Joints 2017 Dec 11;5(4):217-223. Epub 2017 Dec 11.

Laboratorio di Biotecnologie applicate all'Ortopedia, IRCCS Istituto Ortopedico Galeazzi, Milan, Italy.

Shoulder stiffness is a condition of painful restriction of the glenohumeral range of motion. Numerous risk factors for primary and postoperative shoulder stiffness have been described. This article summarizes the known aspects of the pathophysiology of shoulder stiffness, with special attention to elements of molecular biology and genetics, which could influence the risk of developing shoulder stiffness. Furthermore, the role of hormonal and metabolic factors, medical disorders, drugs, and of other published risk factors for primary and postoperative shoulder stiffness is reviewed and discussed. Finally, aspects related to shoulder surgery and postoperative rehabilitation protocols, which could influence the development of postoperative stiffness are presented.
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http://dx.doi.org/10.1055/s-0037-1608951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5738468PMC
December 2017

Targeting gait and life quality in persons with Parkinson's disease: Potential benefits of Equine-Assisted Interventions.

Parkinsonism Relat Disord 2018 02 11;47:94-95. Epub 2017 Dec 11.

Center for Behavioral Sciences and Mental Health, Istituto Superiore di Sanità, Rome, Italy.

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http://dx.doi.org/10.1016/j.parkreldis.2017.12.003DOI Listing
February 2018