Showing papers by "Università Campus Bio-Medico published in 2017"

Mechanisms of diabetes mellitus-induced bone fragility

Abstract: The risk of fragility fractures is increased in patients with either type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM). Although BMD is decreased in T1DM, BMD in T2DM is often normal or even slightly elevated compared with an age-matched control population. However, in both T1DM and T2DM, bone turnover is decreased and the bone material properties and microstructure of bone are altered; the latter particularly so when microvascular complications are present. The pathophysiological mechanisms underlying bone fragility in diabetes mellitus are complex, and include hyperglycaemia, oxidative stress and the accumulation of advanced glycation endproducts that compromise collagen properties, increase marrow adiposity, release inflammatory factors and adipokines from visceral fat, and potentially alter the function of osteocytes. Additional factors including treatment-induced hypoglycaemia, certain antidiabetic medications with a direct effect on bone and mineral metabolism (such as thiazolidinediones), as well as an increased propensity for falls, all contribute to the increased fracture risk in patients with diabetes mellitus.

A European respiratory society technical standard : exhaled biomarkers in lung disease

Abstract: Breath tests cover the fraction of nitric oxide in expired gas (FENO), volatile organic compounds (VOCs), variables in exhaled breath condensate (EBC) and other measurements. For EBC and for FENO, official recommendations for standardised procedures are more than 10 years old and there is none for exhaled VOCs and particles. The aim of this document is to provide technical standards and recommendations for sample collection and analytic approaches and to highlight future research priorities in the field. For EBC and FENO, new developments and advances in technology have been evaluated in the current document. This report is not intended to provide clinical guidance on disease diagnosis and management. Clinicians and researchers with expertise in exhaled biomarkers were invited to participate. Published studies regarding methodology of breath tests were selected, discussed and evaluated in a consensus-based manner by the Task Force members. Recommendations for standardisation of sampling, analysing and reporting of data and suggestions for research to cover gaps in the evidence have been created and summarised. Application of breath biomarker measurement in a standardised manner will provide comparable results, thereby facilitating the potential use of these biomarkers in clinical practice.

Improved Outcomes With Retinoic Acid and Arsenic Trioxide Compared With Retinoic Acid and Chemotherapy in Non-High-Risk Acute Promyelocytic Leukemia: Final Results of the Randomized Italian-German APL0406 Trial.

Abstract: Purpose The initial results of the APL0406 trial showed that the combination of all- trans-retinoic acid (ATRA) and arsenic trioxide (ATO) is at least not inferior to standard ATRA and chemotherapy (CHT) in first-line therapy of low- or intermediate-risk acute promyelocytic leukemia (APL). We herein report the final analysis on the complete series of patients enrolled onto this trial. Patients and Methods The APL0406 study was a prospective, randomized, multicenter, open-label, phase III noninferiority trial. Eligible patients were adults between 18 and 71 years of age with newly diagnosed, low- or intermediate-risk APL (WBC at diagnosis ≤ 10 × 109/L). Overall, 276 patients were randomly assigned to receive ATRA-ATO or ATRA-CHT between October 2007 and January 2013. Results Of 263 patients evaluable for response to induction, 127 (100%) of 127 patients and 132 (97%) of 136 patients achieved complete remission (CR) in the ATRA-ATO and ATRA-CHT arms, respectively ( P = .12). After a median follow-up of 40.6 months, the event-free survival, cumulative incidence of relapse, and overall survival at 50 months for patients in the ATRA-ATO versus ATRA-CHT arms were 97.3% v 80%, 1.9% v 13.9%, and 99.2% v 92.6%, respectively ( P < .001, P = .0013, and P = .0073, respectively). Postinduction events included two relapses and one death in CR in the ATRA-ATO arm and two instances of molecular resistance after third consolidation, 15 relapses, and five deaths in CR in the ATRA-CHT arm. Two patients in the ATRA-CHT arm developed a therapy-related myeloid neoplasm. Conclusion These results show that the advantages of ATRA-ATO over ATRA-CHT increase over time and that there is significantly greater and more sustained antileukemic efficacy of ATO-ATRA compared with ATRA-CHT in low- and intermediate-risk APL.

Effects of Sotagliflozin Added to Insulin in Patients with Type 1 Diabetes

Abstract: BackgroundIn most patients with type 1 diabetes, adequate glycemic control is not achieved with insulin therapy alone. We evaluated the safety and efficacy of sotagliflozin, an oral inhibitor of sodium–glucose cotransporters 1 and 2, in combination with insulin treatment in patients with type 1 diabetes. MethodsIn this phase 3, double-blind trial, which was conducted at 133 centers worldwide, we randomly assigned 1402 patients with type 1 diabetes who were receiving treatment with any insulin therapy (pump or injections) to receive sotagliflozin (400 mg per day) or placebo for 24 weeks. The primary end point was a glycated hemoglobin level lower than 7.0% at week 24, with no episodes of severe hypoglycemia or diabetic ketoacidosis after randomization. Secondary end points included the change from baseline in glycated hemoglobin level, weight, systolic blood pressure, and mean daily bolus dose of insulin. ResultsA significantly larger proportion of patients in the sotagliflozin group than in the placebo gr...

Cannabinoid CB2 receptor ligand profiling reveals biased signalling and off-target activity

Abstract: The cannabinoid CB2 receptor (CB2R) represents a promising therapeutic target for various forms of tissue injury and inflammatory diseases. Although numerous compounds have been developed and widely used to target CB2R, their selectivity, molecular mode of action and pharmacokinetic properties have been poorly characterized. Here we report the most extensive characterization of the molecular pharmacology of the most widely used CB2R ligands to date. In a collaborative effort between multiple academic and industry laboratories, we identify marked differences in the ability of certain agonists to activate distinct signalling pathways and to cause off-target effects. We reach a consensus that HU910, HU308 and JWH133 are the recommended selective CB2R agonists to study the role of CB2R in biological and disease processes. We believe that our unique approach would be highly suitable for the characterization of other therapeutic targets in drug discovery research.

Prevalence of malnutrition in patients at first medical oncology visit: the PreMiO study

Abstract: // Maurizio Muscaritoli 1 , Simone Lucia 1 , Alessio Farcomeni 2 , Vito Lorusso 3 , Valeria Saracino 3 , Carlo Barone 4 , Francesca Plastino 4 , Stefania Gori 5 , Roberto Magarotto 5 , Giacomo Carteni 6 , Bruno Chiurazzi 6 , Ida Pavese 7 , Luca Marchetti 7 , Vittorina Zagonel 8 , Eleonora Bergo 8 , Giuseppe Tonini 9 , Marco Imperatori 9 , Carmelo Iacono 10 , Luigi Maiorana 10 , Carmine Pinto 11 , Daniela Rubino 11 , Luigi Cavanna 12 , Roberto Di Cicilia 12 , Teresa Gamucci 13 , Silvia Quadrini 13 , Salvatore Palazzo 14 , Stefano Minardi 14 , Marco Merlano 15 , Giuseppe Colucci 16 and Paolo Marchetti 17, 18 , on behalf of the PreMiO Study Group 19 1 Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy 2 Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy 3 Department of Medical Oncology, National Cancer Research Centre Giovanni Paolo II, Bari, Italy 4 Department of Medical Oncology, Catholic University of Sacred Heart, Largo A. Gemelli, Rome, Italy 5 Medical Oncology Unit, Ospedale Sacro Cuore Don Calabria, Verona, Italy 6 Oncology Unit, Antonio Cardarelli Hospital, Naples, Italy 7 Oncology Unit, San Pietro Fatebenefratelli Hospital, Rome, Italy 8 Department of Clinical and Experimental Oncology, Medical Oncology 1, Veneto Institute of Oncology IOV - IRCCS, Padua, Italy 9 Department of Oncology, University Campus Bio-Medico of Rome, Rome, Italy 10 Department of Medical Oncology, Azienda Ospedaliera Civile - Maria Paterno Arezzo, Ragusa, Italy 11 Medical Oncology, Clinical Cancer Centre, IRCCS-Arcispedale S. Maria Nuova, Reggio Emilia, Italy 12 Department of Oncology-Hematology, Guglielmo da Saliceto Hospital, Piacenza, Italy 13 Medical Oncology Unit, S.S. Trinita Hospital, Sora, Italy 14 Division of Medical Oncology, Mariano Santo Hospital, Azienda Ospedaliera, Cosenza, Italy 15 Medical Oncology, Oncology Department, S. Croce & Carle Teaching Hospital, Cuneo, Italy 16 Medical Oncology Department, National Cancer Research Centre Giovanni Paolo II, Bari, Italy 17 Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology Sapienza, St. Andrea Hospital, Rome, Italy 18 IDI-IRCCS, Rome, Italy 19 The PreMiO Study group also included investigators who contributed to patients’ enrollment Correspondence to: Maurizio Muscaritoli, email: maurizio.muscaritoli@uniroma1.it Keywords: malnutrition, cancer, cachexia, sarcopenia, oncology Received: April 27, 2017 Accepted: June 20, 2017 Published: August 10, 2017 ABSTRACT Background: In cancer patients, malnutrition is associated with treatment toxicity, complications, reduced physical functioning, and decreased survival. The Prevalence of Malnutrition in Oncology (PreMiO) study identified malnutrition or its risk among cancer patients making their first medical oncology visit. Innovatively, oncologists, not nutritionists, evaluated the nutritional status of the patients in this study. Methods: PreMiO was a prospective, observational study conducted at 22 medical oncology centers across Italy. For inclusion, adult patients (>18 years) had a solid tumor diagnosis, were treatment-naive, and had a life expectancy >3 months. Malnutrition was identified by the Mini Nutritional Assessment (MNA), appetite status with a visual analog scale (VAS), and appetite loss with a modified version of Anorexia-Cachexia Subscale (AC/S-12) of the Functional Assessment of Anorexia-Cachexia Therapy (FAACT). Findings: Of patients enrolled ( N= 1,952), 51% had nutritional impairment; 9% were overtly malnourished, and 43% were at risk for malnutrition. Severity of malnutrition was positively correlated with the stage of cancer. Over 40% of patients were experiencing anorexia, as reported in the VAS and FAACT questionnaire. During the prior six months, 64% of patients lost weight (1–10 kg). Interpretation: Malnutrition, anorexia, and weight loss are common in cancer patients, even at their first visit to a medical oncology center.

Activity-based protein profiling reveals off-target proteins of the FAAH inhibitor BIA 10-2474

Abstract: A recent phase 1 trial of the fatty acid amide hydrolase (FAAH) inhibitor BIA 10-2474 led to the death of one volunteer and produced mild-to-severe neurological symptoms in four others. Although the cause of the clinical neurotoxicity is unknown, it has been postulated, given the clinical safety profile of other tested FAAH inhibitors, that off-target activities of BIA 10-2474 may have played a role. Here we use activity-based proteomic methods to determine the protein interaction landscape of BIA 10-2474 in human cells and tissues. This analysis revealed that the drug inhibits several lipases that are not targeted by PF04457845, a highly selective and clinically tested FAAH inhibitor. BIA 10-2474, but not PF04457845, produced substantial alterations in lipid networks in human cortical neurons, suggesting that promiscuous lipase inhibitors have the potential to cause metabolic dysregulation in the nervous system.

Auxin minimum triggers the developmental switch from cell division to cell differentiation in the Arabidopsis root.

Abstract: In multicellular organisms, a stringent control of the transition between cell division and differentiation is crucial for correct tissue and organ development. In the Arabidopsis root, the boundary between dividing and differentiating cells is positioned by the antagonistic interaction of the hormones auxin and cytokinin. Cytokinin affects polar auxin transport, but how this impacts the positional information required to establish this tissue boundary, is still unknown. By combining computational modeling with molecular genetics, we show that boundary formation is dependent on cytokinin’s control on auxin polar transport and degradation. The regulation of both processes shapes the auxin profile in a well-defined auxin minimum. This auxin minimum positions the boundary between dividing and differentiating cells, acting as a trigger for this developmental transition, thus controlling meristem size.

The EU-AIMS Longitudinal European Autism Project (LEAP): design and methodologies to identify and validate stratification biomarkers for autism spectrum disorders

Abstract: The tremendous clinical and aetiological diversity among individuals with autism spectrum disorder (ASD) has been a major obstacle to the development of new treatments, as many may only be effective in particular subgroups. Precision medicine approaches aim to overcome this challenge by combining pathophysiologically based treatments with stratification biomarkers that predict which treatment may be most beneficial for particular individuals. However, so far, we have no single validated stratification biomarker for ASD. This may be due to the fact that most research studies primarily have focused on the identification of mean case-control differences, rather than within-group variability, and included small samples that were underpowered for stratification approaches. The EU-AIMS Longitudinal European Autism Project (LEAP) is to date the largest multi-centre, multi-disciplinary observational study worldwide that aims to identify and validate stratification biomarkers for ASD. LEAP includes 437 children and adults with ASD and 300 individuals with typical development or mild intellectual disability. Using an accelerated longitudinal design, each participant is comprehensively characterised in terms of clinical symptoms, comorbidities, functional outcomes, neurocognitive profile, brain structure and function, biochemical markers and genomics. In addition, 51 twin-pairs (of which 36 had one sibling with ASD) are included to identify genetic and environmental factors in phenotypic variability. Here, we describe the demographic characteristics of the cohort, planned analytic stratification approaches, criteria and steps to validate candidate stratification markers, pre-registration procedures to increase transparency, standardisation and data robustness across all analyses, and share some ‘lessons learnt’. A clinical characterisation of the cohort is given in the companion paper (Charman et al., accepted). We expect that LEAP will enable us to confirm, reject and refine current hypotheses of neurocognitive/neurobiological abnormalities, identify biologically and clinically meaningful ASD subgroups, and help us map phenotypic heterogeneity to different aetiologies.

Adult-onset autoimmune diabetes: current knowledge and implications for management

Abstract: Adult-onset autoimmune diabetes is a heterogeneous disease that is characterized by a reduced genetic load, a less intensive autoimmune process and a mild metabolic decompensation at onset compared with young-onset type 1 diabetes mellitus (T1DM). The majority of patients with adult-onset autoimmune diabetes do not require insulin treatment for at least 6 months after diagnosis. Such patients are defined as having latent autoimmune diabetes in adults (LADA), which is distinct from classic adult-onset T1DM. The extensive heterogeneity of adult-onset autoimmune diabetes is apparent beyond the distinction between classic adult-onset T1DM and LADA. LADA is characterized by genetic, phenotypic and humoral heterogeneity, encompassing different degrees of insulin resistance and autoimmunity; this heterogeneity is probably a result of different pathological mechanisms, which have implications for treatment. The existence of heterogeneous phenotypes in LADA makes it difficult to establish an a priori treatment algorithm, and therefore, a personalized medicine approach is required. In this Review, we discuss the current understanding and gaps in knowledge regarding the pathophysiology and clinical features of adult-onset autoimmune diabetes and highlight the similarities and differences with classic T1DM and type 2 diabetes mellitus.

TRPV1 channels are critical brain inflammation detectors and neuropathic pain biomarkers in mice

Abstract: The capsaicin receptor TRPV1 has been widely characterized in the sensory system as a key component of pain and inflammation. A large amount of evidence shows that TRPV1 is also functional in the brain although its role is still debated. Here we report that TRPV1 is highly expressed in microglial cells rather than neurons of the anterior cingulate cortex and other brain areas. We found that stimulation of microglial TRPV1 controls cortical microglia activation per se and indirectly enhances glutamatergic transmission in neurons by promoting extracellular microglial microvesicles shedding. Conversely, in the cortex of mice suffering from neuropathic pain, TRPV1 is also present in neurons affecting their intrinsic electrical properties and synaptic strength. Altogether, these findings identify brain TRPV1 as potential detector of harmful stimuli and a key player of microglia to neuron communication.

Strongly bound excitons in anatase TiO2 single crystals and nanoparticles.

Abstract: Anatase TiO2 is among the most studied materials for light-energy conversion applications, but the nature of its fundamental charge excitations is still unknown. Yet it is crucial to establish whether light absorption creates uncorrelated electron-hole pairs or bound excitons and, in the latter case, to determine their character. Here, by combining steady-state angle-resolved photoemission spectroscopy and spectroscopic ellipsometry with state-of-the-art ab initio calculations, we demonstrate that the direct optical gap of single crystals is dominated by a strongly bound exciton rising over the continuum of indirect interband transitions. This exciton possesses an intermediate character between the Wannier-Mott and Frenkel regimes and displays a peculiar two-dimensional wavefunction in the three-dimensional lattice. The nature of the higher-energy excitations is also identified. The universal validity of our results is confirmed up to room temperature by observing the same elementary excitations in defect-rich samples (doped single crystals and nanoparticles) via ultrafast two-dimensional deep-ultraviolet spectroscopy.Here the authors combine steady-state angle-resolved photoemission spectroscopy, ellipsometry and ultrafast two-dimensional ultraviolet spectroscopy to examine the role of many-body correlations in anatase TiO2, revealing the existence of strongly bound excitons in single crystals and nanoparticles.

Classification of M1/M2-polarized human macrophages by label-free hyperspectral reflectance confocal microscopy and multivariate analysis.

Abstract: The possibility of detecting and classifying living cells in a label-free and non-invasive manner holds significant theranostic potential. In this work, Hyperspectral Imaging (HSI) has been successfully applied to the analysis of macrophagic polarization, given its central role in several pathological settings, including the regulation of tumour microenvironment. Human monocyte derived macrophages have been investigated using hyperspectral reflectance confocal microscopy, and hyperspectral datasets have been analysed in terms of M1 vs. M2 polarization by Principal Components Analysis (PCA). Following PCA, Linear Discriminant Analysis has been implemented for semi-automatic classification of macrophagic polarization from HSI data. Our results confirm the possibility to perform single-cell-level in vitro classification of M1 vs. M2 macrophages in a non-invasive and label-free manner with a high accuracy (above 98% for cells deriving from the same donor), supporting the idea of applying the technique to the study of complex interacting cellular systems, such in the case of tumour-immunity in vitro models.

Thromboembolic Risk, Bleeding Outcomes and Effect of Different Antithrombotic Strategies in Very Elderly Patients With Atrial Fibrillation: A Sub-Analysis From the PREFER in AF ( PRE vention o F Thromboembolic Events- E uropean R egistry in A trial F ibrillation).

Abstract: BackgroundIncreasing age predisposes to both thromboembolic and bleeding events in patients with atrial fibrillation; therefore, balancing risks and benefits of antithrombotic strategies in older p...

Visual loss and other cranial ischaemic complications in giant cell arteritis.

Abstract: Giant cell arteritis (GCA) is the most common form of vasculitis in individuals aged 50 years and over. GCA typically affects large and medium-sized arteries, with a predilection for the extracranial branches of the carotid artery. Patients with GCA usually present with symptoms and signs that are directly related to the artery that is affected, with or without constitutional manifestations. The most dreaded complication of GCA is visual loss, which affects about one in six patients and is typically caused by arteritis of the ophthalmic branches of the internal carotid artery. Before the advent of glucocorticoid treatment, the prevalence of visual complications was high. Increasing awareness by physicians of the symptoms of GCA and advances in diagnostic techniques over the past twenty years have also contributed to a substantial decline in the frequency of permanent visual loss. Ischaemic brain lesions are less common than visual lesions, and mostly result from vasculitis of the extradural vertebral or carotid arteries. In the case of both the eye and the brain, ischaemic damage is thought to result from arterial stenosis or occlusion that occurs secondary to the inflammatory process. The inflammatory response at the onset of arteritis, its role as a predictor of complications and the role of traditional cardiovascular risk factors have been extensively investigated in the past decade. In this Review, the epidemiology, risk factors, clinical presentation and current therapeutic approach of GCA-related ischaemic events are discussed, with a particular emphasis on visual loss.

Respiratory Frequency during Exercise: The Neglected Physiological Measure.

Abstract: The use of wearable sensor technology for athlete training monitoring is growing exponentially, but some important measures and related wearable devices have received little attention so far. Respiratory frequency (fR), for example, is emerging as a valuable measurement for training monitoring. Despite the availability of unobtrusive wearable devices measuring fR with relatively good accuracy, fR is not commonly monitored during training. Yet fR is currently measured as a vital sign by multiparameter wearable devices in the military field, clinical settings, and occupational activities. When these devices have been used during exercise, fR was used for limited applications like the estimation of the ventilatory threshold. However, more information can be gained from fR. Unlike heart rate, [Formula: see text]O2, and blood lactate, fR is strongly associated with perceived exertion during a variety of exercise paradigms, and under several experimental interventions affecting performance like muscle fatigue, glycogen depletion, heat exposure and hypoxia. This suggests that fR is a strong marker of physical effort. Furthermore, unlike other physiological variables, fR responds rapidly to variations in workload during high-intensity interval training (HIIT), with potential important implications for many sporting activities. This Perspective article aims to (i) present scientific evidence supporting the relevance of fR for training monitoring; (ii) critically revise possible methodologies to measure fR and the accuracy of currently available respiratory wearables; (iii) provide preliminary indication on how to analyze fR data. This viewpoint is expected to advance the field of training monitoring and stimulate directions for future development of sports wearables.

The EU-AIMS Longitudinal European Autism Project (LEAP): Clinical characterisation

Abstract: The EU-AIMS Longitudinal European Autism Project (LEAP) is to date the largest multi-centre, multi-disciplinary observational study on biomarkers for autism spectrum disorder (ASD) The current paper describes the clinical characteristics of the LEAP cohort and examines age, sex and IQ differences in ASD core symptoms and common co-occurring psychiatric symptoms A companion paper describes the overall design and experimental protocol and outlines the strategy to identify stratification biomarkers From six research centres in four European countries, we recruited 437 children and adults with ASD and 300 controls between the ages of 6 and 30 years with IQs varying between 50 and 148 We conducted in-depth clinical characterisation including a wide range of observational, interview and questionnaire measures of the ASD phenotype, as well as co-occurring psychiatric symptoms The cohort showed heterogeneity in ASD symptom presentation, with only minimal to moderate site differences on core clinical and cognitive measures On both parent-report interview and questionnaire measures, ASD symptom severity was lower in adults compared to children and adolescents The precise pattern of differences varied across measures, but there was some evidence of both lower social symptoms and lower repetitive behaviour severity in adults Males had higher ASD symptom scores than females on clinician-rated and parent interview diagnostic measures but not on parent-reported dimensional measures of ASD symptoms In contrast, self-reported ASD symptom severity was higher in adults compared to adolescents, and in adult females compared to males Higher scores on ASD symptom measures were moderately associated with lower IQ Both inattentive and hyperactive/impulsive ADHD symptoms were lower in adults than in children and adolescents, and males with ASD had higher levels of inattentive and hyperactive/impulsive ADHD symptoms than females The established phenotypic heterogeneity in ASD is well captured in the LEAP cohort Variation both in core ASD symptom severity and in commonly co-occurring psychiatric symptoms were systematically associated with sex, age and IQ The pattern of ASD symptom differences with age and sex also varied by whether these were clinician ratings or parent- or self-reported which has important implications for establishing stratification biomarkers and for their potential use as outcome measures in clinical trials

Performance Evaluation of Bluetooth Low Energy: A Systematic Review

Abstract: Small, compact and embedded sensors are a pervasive technology in everyday life for a wide number of applications (e.g., wearable devices, domotics, e-health systems, etc.). In this context, wireless transmission plays a key role, and among available solutions, Bluetooth Low Energy (BLE) is gaining more and more popularity. BLE merges together good performance, low-energy consumption and widespread diffusion. The aim of this work is to review the main methodologies adopted to investigate BLE performance. The first part of this review is an in-depth description of the protocol, highlighting the main characteristics and implementation details. The second part reviews the state of the art on BLE characteristics and performance. In particular, we analyze throughput, maximum number of connectable sensors, power consumption, latency and maximum reachable range, with the aim to identify what are the current limits of BLE technology. The main results can be resumed as follows: throughput may theoretically reach the limit of ~230 kbps, but actual applications analyzed in this review show throughputs limited to ~100 kbps; the maximum reachable range is strictly dependent on the radio power, and it goes up to a few tens of meters; the maximum number of nodes in the network depends on connection parameters, on the network architecture and specific device characteristics, but it is usually lower than 10; power consumption and latency are largely modeled and analyzed and are strictly dependent on a huge number of parameters. Most of these characteristics are based on analytical models, but there is a need for rigorous experimental evaluations to understand the actual limits.

Metabolism of the Endocannabinoid Anandamide: Open Questions after 25 Years.

Abstract: Cannabis extracts have been used for centuries, but its main active principle Δ9-tetrahydrocannabinol was identified about 50 years ago Yet, it is only 25 years ago that the first endogenous ligand of the same receptors engaged by the cannabis agents was discovered This “en-docannabinoid” was identified as N-arachidonoylethanolamine (or anandamide), and was shown to have several receptors, metabolic enzymes and transporters that altogether drive its biological activi-ty Here I report on the latest advances about anandamide metabolism, with the aim of focusing open questions still awaiting an answer for a deeper understanding of anandamide activity, and for translating anandamide-based drugs into novel therapeutics for human diseases

Efficacy of stereotactic body radiotherapy in oligorecurrent and in oligoprogressive prostate cancer: new evidence from a multicentric study.

Abstract: The aim of the present study is to evaluate the impact of metastases-directed stereotactic body radiotherapy in two groups of oligometastatic prostate cancer (PC) patients: oligorecurrent PC and oligoprogressive castration-resistant PC (oligo-CRPC). Inclusion criteria of the present multicentre retrospective analysis were: (1) oligorecurrent PC, defined as the presence of 1–3 lesions (bone or nodes) detected with choline positron emission tomography or CT plus bone scan following biochemical recurrence; (2) oligo-CRPC, defined as metastases (bone or nodes) detected after a prostatic-specific antigen rise during androgen deprivation therapy (ADT). Primary end points were: distant progression-free survival (DPFS) and ADT-free survival in oligorecurrent PC patients; DPFS and second-line systemic treatment-free survival in oligo-CRPC patients. About 100 patients with oligorecurrent PC (139 lesions) and 41 with oligo-CRPC (70 lesions), treated between March 2010 and April 2016, were analysed. After a median follow-up of 20.4 months, in the oligorecurrent group 1- and 2-year DPFS were 64.4 and 43%. The rate of LC was 92.8% at 2 years. At a median follow-up of 23.4 months, in the oligo-CRPC group 1- and 2-year DPFS were 43.2 and 21.6%. Limitations include the retrospective design. Stereotactic body radiotherapy seems to be a useful treatment both for oligorecurrent and oligo-CRPC.

Laser Ablation for Cancer: Past, Present and Future

Abstract: Laser ablation (LA) is gaining acceptance for the treatment of tumors as an alternative to surgical resection. This paper reviews the use of lasers for ablative and surgical applications. Also reviewed are solutions aimed at improving LA outcomes: hyperthermal treatment planning tools and thermometric techniques during LA, used to guide the surgeon in the choice and adjustment of the optimal laser settings, and the potential use of nanoparticles to allow biologic selectivity of ablative treatments. Promising technical solutions and a better knowledge of laser-tissue interaction should allow LA to be used in a safe and effective manner as a cancer treatment.

Reverse shoulder arthroplasty for massive irreparable rotator cuff tears and cuff tear arthropathy: a systematic review

Abstract: To report the outcomes and complications of reverse shoulder arthroplasty (RSA) in massive irreparable rotator cuff tears (MIRCT) and cuff tear arthropathy (CTA). A systematic review of the literature contained in Medline, Cochrane, EMBASE, Google Scholar and Ovid databases was conducted on May 1, 2016, according to PRISMA guidelines. The key words “reverse total shoulder arthroplasty” or “reverse total shoulder prostheses” with “rotator cuff tears”; “failed rotator cuff surgery”; “massive rotator cuff tears”; “irreparable rotator cuff tears”; “cuff tear arthropathy”; “outcomes”; “complications” were matched. All articles reporting outcomes and complications of RSA for the management of MIRCT or CTA were included. The comparison between preoperative and postoperative clinical scores, as well as range of motion (ROM), was performed using the Wilcoxon–Mann–Whitney test. P values lower than 0.05 were considered statistically significant. Seven articles were included in our qualitative synthesis. A statistically significant improvement in all clinical scores and ROM was found comparing the preoperative value with the postoperative value. The degrees of retroversion of the humeral stem of the RSA do not influence the functional outcomes in a statistically significant fashion. There were 17.4% of complications. The most frequent was heterotopic ossification, occurring in 6.6% of patients. Revision surgery was necessary in 7.3% of patients. RSA restores pain-free ROM and improves function of the shoulder in patients with MIRCT or CTA. However, complications occur in a high percentage of patients. The lack of level I studies limits the real understanding of the potentials and limitations of RSA for the management of MIRCT and CTA.

Electronic Nose Technology in Respiratory Diseases.

Abstract: Electronic noses (e-noses) are based on arrays of different sensor types that respond to specific features of an odorant molecule, mostly volatile organic compounds (VOCs). Differently from gas chromatography and mass spectrometry, e-noses can distinguish VOCs spectrum by pattern recognition. E-nose technology has successfully been used in commercial applications, including military, environmental, and food industry. Human-exhaled breath contains a mixture of over 3000 VOCs, which offers the postulate that e-nose technology can have medical applications. Based on the above hypothesis, an increasing number of studies have shown that breath profiling by e-nose could play a role in the diagnosis and/or screening of various respiratory and systemic diseases. The aim of the present study was to review the principal literature on the application of e-nose technology in respiratory diseases.

The role of novel biomarker HE4 in the diagnosis, prognosis and follow-up of ovarian cancer: a systematic review

Abstract: Ovarian cancer is the leading cause of death from gynecologic cancers, in fact, >80% of cases are diagnosed as advanced-stage disease associated with a high mortality rate (<40% of women cured). A systematic review was performed to estimate the role of HE4 in the diagnosis, prognosis and follow-up of ovarian tumors. Areas covered: A comprehensive search of the literature from January 1952 to August 2016 was conducted using the terms 'ovarian tumor' and 'ovarian cancer' combined with 'HE4' and 'human epididymis protein 4'. The search identified a total of 259 citations, of which 141 were potentially relevant after initial evaluation. Of these studies, 75 primary studies met the inclusion criteria and were analyzed, with a total of 14,773 patients. Expert commentary: Serum HE4 dosage is a useful preoperative test for predicting the benign or malignant nature of pelvic masses. It seems to have a promising role in the prediction of clinical and surgical outcomes. Moreover, HE4 seems to better predict recurrence in comparison to CA-125.

European Thyroid Association Guidelines regarding Thyroid Nodule Molecular Fine-Needle Aspiration Cytology Diagnostics.

Abstract: Molecular fine-needle aspiration (FNA) cytology diagnostics has the potential to address the inherent limitation of FNA cytology which is an indeterminate (atypia of undetermined significance/follicular lesion of undetermined significance follicular neoplasm) cytology Because of the emerging role of molecular FNA cytology diagnostics, the European Thyroid Association convened a panel of international experts to review methodological aspects, indications, results, and limitations of molecular FNA cytology diagnostics The panel reviewed the evidence for the diagnostic value of mutation panel assessment (including at least BRAF, NRAS, HRAS, KRAS, PAX8/PPARG, RET/PTC) of targeted next generation sequencing and of a microarray gene expression classifier (GEC) test in the diagnostic assessment of an indeterminate cytology thyroid nodule Moreover, possible surgical consequences of molecular FNA diagnostic results of thyroid nodules and the evidence that analysis of a molecular FNA diagnostic panel of somatic mutations or a microarray GEC test can alter the follow-up were reviewed Molecular tests may help clinicians to drive patient care and the surgical decision if the analysis is performed in specialized laboratories These molecular tests require standardization of performance characteristics and appropriate calibration as well as analytic validation before clinical interpretation