Beyond a Transmission Cable-New Technologies to Reveal the Richness in Axonal Electrophysiology.

The axon is a neuronal structure capable of processing, encoding, and transmitting information. This assessment contrasts with a limiting, but deeply rooted, perspective where the axon functions solely as a transmission cable of somatodendritic activity, sending signals in the form of stereotypical action potentials. This perspective arose, at least partially, because of the technical difficulties in probing axons: their extreme length-to-diameter ratio and intricate growth paths preclude the study of their dynamics through traditional techniques. Recent findings are challenging this view and revealing a much larger repertoire of axonal computations. Axons display complex signaling processes and structure-function relationships, which can be modulated via diverse activity-dependent mechanisms. Additionally, axons can exhibit patterns of activity that are dramatically different from those of their corresponding soma. Not surprisingly, many of these recent discoveries have been driven by novel technology developments, which allow for in vitro axon electrophysiology with unprecedented spatiotemporal resolution and signal-to-noise ratio. In this review, we outline the state-of-the-art in vitro toolset for axonal electrophysiology and summarize the recent discoveries in axon function it has enabled. We also review the increasing repertoire of microtechnologies for controlling axon guidance which, in combination with the available cutting-edge electrophysiology and imaging approaches, have the potential for more controlled and high-throughput in vitro studies. We anticipate that a larger adoption of these new technologies by the neuroscience community will drive a new era of experimental opportunities in the study of axon physiology and consequently, neuronal function.

Impact of sociodemographic and economic determinants of health on COVID-19 infection: incidence variation between reference periods.

OBJECTIVES: The COVID-19 pandemic hit Portugal in March 2020, causing widespread disruption to various aspects of society. While extensive research has been conducted on the significance of socio-economic disparities in infection risk, this study aims to enhance our understanding of their evolving relationship over time by analysing four distinct periods in 2020. STUDY DESIGN AND METHODS: This retrospective observational ecological study included individuals residing in the Primary Healthcare Cluster areas of Almada-Seixal and Western Lisbon and Oeiras, who tested positive for SARS-CoV-2 through a polymerase chain reaction (PCR) test between the 2nd of March and the 8th of November of 2020. Using incidence rates for each specific neighbourhood (n = 29) and period, we explored the relationship between neighbourhood-level socio-economic variables and the risk of infection using negative-binomial regression models. RESULTS: In the analysed period, a total of 8562 confirmed COVID-19 cases were identified. Overall incidence rates for each period were sequentially 2.74, 5.03, 3.99 and 14.29 COVID-19 cases per 100,000 person-days. Housing overcrowding, illiteracy rate and place of birth were associated with increased risk of infection, while age, congregate living, and employment in the secondary sector exhibited the opposite association. No association was consistent across all time periods. CONCLUSIONS: Our findings support the idea that the influence of socio-economic determinants of health is not immutable throughout time. In a pandemic context where information, knowledge, beliefs, and behaviours are ever-changing and evolving, a dynamic, inclusive, and adaptable approach to disease control can lead to a more equitable distribution of improved outcomes, benefiting all strata of society.

Standardising clinical outcomes measures for adult clinical trials in Fabry disease: A global Delphi consensus.

BACKGROUND: Recent years have witnessed a considerable increase in clinical trials of new investigational agents for Fabry disease (FD). Several trials investigating different agents are currently in progress; however, lack of standardisation results in challenges to interpretation and comparison. To facilitate the standardisation of investigational programs, we have developed a common framework for future clinical trials in FD. METHODS AND FINDINGS: A broad consensus regarding clinical outcomes and ways to measure them was obtained via the Delphi methodology. 35 FD clinical experts from 4 continents, representing 3389 FD patients, participated in 3 rounds of Delphi procedure. The aim was to reach a consensus regarding clinical trial design, best treatment comparator, clinical outcomes, measurement of those clinical outcomes and inclusion and exclusion criteria. Consensus results of this initiative included: the selection of the adaptative clinical trial as the ideal study design and agalsidase beta as ideal comparator treatment due to its longstanding use in FD. Renal and cardiac outcomes, such as glomerular filtration rate, proteinuria and left ventricular mass index, were prioritised, whereas neurological outcomes including cerebrovascular and white matter lesions were dismissed as a primary or secondary outcome measure. Besides, there was a consensus regarding the importance of patient-related outcomes such as general quality of life, pain, and gastrointestinal symptoms. Also, unity about lysoGb3 and Gb3 tissue deposits as useful surrogate markers of the disease was obtained. The group recognised that cardiac T1 mapping still has potential but requires further development before its widespread introduction in clinical trials. Finally, patients with end-stage renal disease or renal transplant should be excluded unless a particular group for them is created inside the clinical trial. CONCLUSION: This consensus will help to shape the future of clinical trials in FD. We note that the FDA has, coincidentally, recently published draft guidelines on clinical trials in FD and welcome this contribution.

Rapid detection of biofilm-producing Candida species via MALDI-TOF mass spectrometry.

AIMS: The aim of this study was to evaluate the formation of biofilm by Candida spp. isolated from the bloodstream, using traditional spectrophotometric methodologies. In addition, the goal was to compare the results with those obtained through MALDI-TOF/MS, as well as to verify its use as a potential tool for the detection of biofilm-forming strains. METHODS AND RESULTS: Hundred and thirteen isolates of Candida spp. were studied: 41 were Candida albicans, 27 C. tropicalis, 18 C. glabrata, 17 C. parapsilosis and 10 C. krusei. Metabolic activity was determined through the tetrazolium salt (XTT) reduction assay and biomass by staining with Crystal Violet. All isolates were able to form biofilm, 94% of which were strong producers, with high biomass quantification (95%; 107/113) and high metabolic activity (99%; 112/113). Mass spectra of the biofilm-producing isolates showed differences in the intensity of mass peaks when compared with the spectra of the nonproducing strains. CONCLUSIONS: It was demonstrated that MALDI-TOF/MS was able to detect specific biofilm proteins, as the mass spectra of the isolates presented differences when compared with nonproducing strains. SIGNIFICANCE AND IMPACT OF THE STUDY: MALDI-TOF/MS can become a valuable tool for biofilm detection at the moment of the identification of the microorganism, thus contributing greatly to the management of patients with Candidemia.

Quality of Life and Characterization of Patients With Atopic Dermatitis in Portugal: The QUADEP Study.

BACKGROUND AND OBJECTIVE: To investigate the quality of life (QOL) of and to characterize patients with atopic dermatitis (AD) in Portugal. METHODS: This was a cross-sectional study of patients with AD and other eczemas. Skindex-29, Skindex-teen, and the Childhood Atopic Dermatitis Impact Scale (CADIS) were the instruments used to assess QOL in adults, teenagers, and children, respectively. The SF-12 was also used, and disease severity was evaluated using the Patient-Oriented SCORAD (PO-SCORAD) instrument. Associations with QOL were assessed based on the odds ratio (OR). P values <.05 and 95%CIs were considered statistically significant. RESULTS: The study population comprised 162 participants aged 0.5-74 years. We found that 37.3% of AD patients consider their disease disabling and that more than half of the patients feel stigmatized by society. The mean Skindex score for AD was 39.68, and the impact on QOL was severe in 44%. "Symptoms" was the most affected category in adults. AD was moderate to severe in 87% of the sample. One of the factors that most influenced poorer QOL in AD was age: with increasing age, the Skindex is likely to increase (OR, 1.03; 95%CI, 1.00-1.06). "Considering the disease a disability" was also associated (OR, 6.72; 95%CI, 2.56-17.63). QOL worsens with increasingly affected body area (OR, 1.07; 95%CI, 1.03-1.11) and the presence of edema (OR, 2.0; 95%CI, 1.23-3.40). CONCLUSIONS: This is the first study to provide data on QOL in patients with AD in Portugal. Our data show an expected negative impact. More awareness-raising activities are needed to increase knowledge, decrease stigmatization, and, consequently, address the factors involved in the QOL of patients with AD.

The effect of PD-L1 testing on the cost-effectiveness and economic impact of immune checkpoint inhibitors for the second-line treatment of NSCLC.

BACKGROUND: Immune checkpoint inhibitors improve outcomes compared with chemotherapy in lung cancer. Tumor PD-L1 receptor expression is being studied as a predictive biomarker. The objective of this study was to assess the cost-effectiveness and economic impact of second-line treatment with nivolumab, pembrolizumab, and atezolizumab with and without the use of PD-L1 testing for patient selection. DESIGN: We developed a decision-analytic model to determine the cost-effectiveness of PD-L1 assessment and second-line immunotherapy versus docetaxel. The model used outcomes data from randomized clinical trials (RCTs) and drug acquisition costs from the United States. Thereafter, we used epidemiologic data to estimate the economic impact of the treatment. RESULTS: We included four RCTs (2 with nivolumab, 1 with pembrolizumab, and 1 with atezolizumab). The incremental quality-adjusted life year (QALY) for nivolumab was 0.417 among squamous tumors and 0.287 among non-squamous tumors and the incremental cost-effectiveness ratio (ICER) were $155 605 and $187 685, respectively. The QALY gain in the base case for atezolizumab was 0.354 and the ICER was $215 802. Compared with treating all patients, the selection of patients by PD-L1 expression improved incremental QALY by up to 183% and decreased the ICER by up to 65%. Pembrolizumab was studied only in patients whose tumors expressed PD-L1. The QALY gain was 0.346 and the ICER was $98 421. Patient selection also reduced the budget impact of immunotherapy. CONCLUSION: The use of PD-L1 expression as a biomarker increases cost-effectiveness of immunotherapy but also diminishes the number of potential life-years saved.

The effects of pharmacist interventions on adult outpatients with cancer: A systematic review.

WHAT IS KNOWN AND OBJECTIVES: Most antineoplastic drugs are highly toxic and have low therapeutic indexes, which can result in drug-related problems. In this context, pharmacist interventions may play an important role in the success of the treatment. The objective of this study was to examine the effects of pharmacist interventions on adult outpatients with cancer using antineoplastic drugs. METHODS: A literature search was performed using PubMed, ISI Web of Science and LILACS databases from January 1990 to April 2016, using MeSH terms or text words related to pharmacist interventions, cancer and outpatient care. Studies published in English, Portuguese or Spanish on the effects of pharmacist interventions in outcome measures in adult outpatients with cancer were included. Two independent authors performed study selection and data extraction with a consensus process. The articles were analysed according to previously established criteria, such as country, study design, setting, population, type of cancer, description of the intervention and control groups, outcomes, main conclusions and study limitations. RESULTS AND DISCUSSION: A total of 874 records were identified, of which 11 satisfied the inclusion criteria. The studies were conducted mainly in the United States and included patients aged >50 years. Most studies had a before-after design. Pharmacist interventions primarily included educating and counselling patients on the management of adverse events. Rates of nausea and vomiting control, medication adherence and patient satisfaction were the most common outcome measures; a significant benefit in these parameters as a result of pharmacist interventions was noted in most studies. WHAT IS NEW AND CONCLUSION: The findings from this systematic review indicate that pharmacist interventions can improve outcome measures in outpatients with cancer. However, the collective quality of the studies was poor and gaps identified indicate that further research is needed to provide more robust results.

A diabetic foot ulcer treated with hydrogel and hyperbaric oxygen therapy: a case study.

This study reports on the case of an elderly patient, with diabetes, and a bullous wound on the left big toe that led to an amputation of the first and second left toes. The amputation was because of deep injury as it was not able to heal with a conventional treatment. After completing the normal treatment and the removal of a bacterial infection in the lesion, the patient underwent a treatment that was based on a hydrogel gel (0.9% saline solution) and hyperbaric oxygen therapy (HBOT). After 60 sessions of the therapy, almost complete closure of the wound was observed. There were no reports of discomfort or infection during the treatment. After seven months of treatment almost complete healing was observed with no infection. This treatment appears to be effective and should be recommended for the treatment of DFUs.

The blood-tendon barrier: identification and characterisation of a novel tissue barrier in tendon blood vessels.

In the last decade, nanobiotechnology research has emerged as a revolutionising new approach to the 21st century pharmaceutical challenges, offering valuable gains in a vast set of biomedical applications. In the field of bone tissue engineering, a broad range of nanotechnology-based delivery systems have been researched and the most recent developments in high-throughput technology and in silico approaches are creating very high expectations. This review presents a comprehensive overview of the emergent nanotechnology-based materials, processing techniques and research strategies for the delivery of pharmaceutics to bone including the materials general characteristics and the available drug delivery systems to distribute agents systemically or locally. Complementary to what was stated above, it also reviews the latest high-throughput processing techniques and the existent in silico tools (mathematical and computational models) used to help on the design of delivery systems.

Systematic review of the economic evaluations of novel therapeutic agents in multiple myeloma: what is the reporting quality?

WHAT IS KNOWN AND OBJECTIVE: Given the increasing healthcare costs and the recent introduction of novel agents in the treatment for multiple myeloma (MM), an incurable haematologic malignancy, more efficient use of existing resources is fundamental. The objective of this study was to systematically review economic evaluations of the use of novel agents in MM and assess their reporting quality. METHODS: A literature search was performed in PubMed/Medline, Latin American and Caribbean Health Sciences Literature, Cost-Effectiveness Analysis Registry and the National Health Services Economic Evaluation Database for economic evaluations up to June 2015. The search strategy included Medical Subject Headings terms or text words related to MM, economic evaluations and drugs. Full economic evaluations of bortezomib, thalidomide or lenalidomide in patients with MM that were published in English, Portuguese or Spanish were included. Two independent authors performed study selection, data extraction and quality assessment using 24 items from the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement. RESULTS AND DISCUSSION: Of the 132 potentially relevant records identified, eight satisfied the inclusion criteria. Most studies were cost-effectiveness analyses combined with cost-utility analyses (n = 6) from the public payer perspective (n = 4) and were performed in Europe (n = 6) on patients with refractory or relapsed MM (n = 5). All studies were based on economic models, with four of them using discrete event simulation. We found bortezomib-based therapies to be one of the more commonly selected treatment strategies for comparison (n = 7). Overall, the intervention was more effective and costlier than the alternative strategy (average of $54 630 per life year; $68 261 per quality-adjusted life year-QALY). The CHEERS' total score was 14·6 (SD = 2·6) with the most frequent problems being the lack of precision measures for all model parameters, no evaluation of heterogeneity of the results by subgroup analyses and no description of the role the funder in the identification, design, conduct and reporting of the analysis. WHAT IS NEW AND CONCLUSION: Most analyses of the novel therapeutic agents determined that they were cost-effective in MM at a threshold of up to $100 000/QALY. Nevertheless, the poor reporting quality of the economic studies requires improvement to ensure greater transparency.

Lung cancer survival and sex-specific patterns in Portugal: A population-based analysis.

INTRODUCTION: In Portugal, lung cancer (LC) is the first cause of cancer-related death and of death and disability combined. This study aims to analyze the overall survival (OS) and relative survival (RS) of patients diagnosed with LC in 2009-2011 by socio-demographic and tumor characteristics, and analyze sex-specific patterns. METHODS: We estimated 5-year OS using the Kaplan-Meier method and 5-year net survival through the RS framework. Cox regression modeling was used to determine the hazard ratio (HR) of death associated with each independent variable. FINDINGS: For the 11,523 cases analyzed, median 5-year OS was 264 days (95% confidence interval [CI]: 254.8-273.2), the cumulative OS was 13.6% and RS was 15.1%. Males had a lower median survival (237 days; 95% CI: 228.2-245.7) compared to females (416 days; 95% CI: 384.4-447.6) (p < 0.0001) and lower 5-year RS proportions (12.1% vs. 24.9%). RS progressively decreased with age (41.7% for age-group <40 to 7.2% for ≥80) and stage (66.6% for stage I to 2.4% for stage IV). As predictors of decreased survival, we identified male gender, increasing age >50, histologic types (squamous cell carcinoma, non-small cell lung cancer not otherwise specified, other unspecified and small cell lung cancer), and increasing stage. Compared to women, the risk of death in men was 37.7% higher (HR = 1.386; 95% CI: 1.295-1.484). CONCLUSIONS: The differences between OS and RS were small, reflecting the high lethality of LC. Male gender and older age are factors related to poor prognosis. Histology also plays a role in survival prognosis and varies with gender, but the factor related to the worst survival is stage. Although the study reflects data from a decade ago, and major changes occurred in diagnosis, staging and treatment, particularly for advanced disease, as LC mortality is strongly correlated with late stage diagnosis, all efforts should be made to secure early diagnosis and improve survival prospects.

Paternal deprivation prior to adolescence and vulnerability to pituitary adenomas.

It has been reported that women with prolactinoma were exposed, early in life, to an environment characterized by an absent or violent father. The present study was designed to evaluate whether paternal absence or violent paternal behavior were more prevalent in patients with pituitary adenomas (prolactinoma, acromegaly, non-secreting adenoma and Cushing's disease) compared to a control population. We conducted an observational case-control multicenter study. We interviewed 395 patients with prolactinoma (296 females and 99 males), 130 with acromegaly (87 females and 43 males), 237 with non-secreting adenoma (144 females and 93 males) and 68 with Cushing's disease (61 females and 7 males) and 365 patients from the same clinics with nodular thyroid disease or lymphocytic thyroiditis with euthyroidism as controls. Violent or absent fathers were significantly more prevalent in patients with prolactinoma or acromegaly than in controls (P = 0.001 and P = 0.002, respectively) but not in patients with non-secreting adenoma or corticotrophinoma. Absent fathers in prolactinoma and acromegaly versus controls: P = 0.001 and P = 0.119. Violent fathers in prolactinoma and acromegaly versus controls: P = 0.069 and P = 0.001. The prevalence of absent or violent fathers was also significantly higher in prolactinoma and acromegaly when compared to non-secreting adenoma (P = 0.039 and P = 0.033, respectively). Paternal deprivation before adolescence may be a risk factor for prolactinoma and acromegaly but not for non-secreting pituitary adenomas or Cushing's disease.

Prognostic factors during outpatient treatment for alcohol dependence: cohort study with 6 months of treatment follow-up.

AIMS: To identify prognostic factors to outpatient alcohol treatment on admission as well as during the treatment period. METHODS: A cohort study of n = 209 alcoholic patients (DSM-IV) during 6 months of outpatient treatment. Eight medical doctors from two hospitals were involved. Co-responsible participation in treatment was a necessary condition. At admission, we documented socio demographic factors, use of other drugs and severity of alcohol consumption. During the 6 months, we observed medication for prevention of alcohol relapse [disulfiram (DIS), acamprosate], number of sessions with the doctor, number of phases of the consultation and medication for depression. Primary outcome variables were time to first heavy relapse and abstinence of heavy alcohol consumption. These were measured with Timeline Followback. Five or more alcohol units of 10 g in one relapse day were considered heavy relapse. RESULTS: The patients were 84% males, with 41 years median age; the median alcohol consumption was 192 g per day with a median duration of 13 years of heavy consumption. The median education was 6 years with 61% of the patients from lower socio-economic levels. The Kaplan-Meier heavy relapse rate at 6 months was 23%. On admission to treatment, female gender, lower socio-economic levels, cocaine use, >20 years of consumption, gamma glutamyl transferase values above normal and five or more alcohol-related problems on the Alcohol-Related Problem Questionnaire predicted worse outcomes. Having a full-time job and shorter abstinence time before treatment (until 7 days) predicted better outcomes. During the 6 months, we found that DIS for <120 days was a prognostic factor of worse outcomes. DIS for at least 120 days, >50% of adherence to consultations and more than two phases on each consultation predicted better outcomes. The combined sensitivity and specificity for DIS for at least 120 days, >50% of adherence to consultations and more than two phases on consultation regarding abstinence from heavy relapse were respectively 100 and 71%. CONCLUSIONS: During 6 months of outpatient treatment, longer adherence to DIS and consultations as well as more phases in a consultation involving necessarily a co-responsible predict a good outcome independently of the patient features at admission.

National trends in the use of oral chemotherapy over 13 years.

Background: Systemic cancer therapy has traditionally been administered using an intravenous (IV) route, implying patients' frequent visits to hospitals to access to their therapy. If we consider the actual pipeline in oncology, oral chemotherapy will be the main component of cancer treatment in the next few years. This shift in the administration route requires different care models in order to guarantee treatment efficacy and safety. Objective: To analyze time trends in oral chemotherapy consumption in Portugal. Method: Oral chemotherapy consumption over a 13-year period (2008-2020) was analyzed, considering dispensed units by the administration route with respective costs, resorting to the drug regulatory agency (INFARMED I.P.) database. Oral consumption patterns were further explored using common daily doses (CDD) for three conditions, including chronic myeloid leukemia (CML), non-small-cell lung cancer (NSCLC), and breast cancer (BC), to adjust for the effect of varying doses. Data were analyzed descriptively resorting to Microsoft Office Excel 2010. Results: Overall chemotherapy consumption increased +Δ54.7%, with the highest contribution in units observed in oral forms (+Δ58.8%). The total expenditure increased +Δ96.5%, and despite the increase in oral forms (+Δ221.6%), intravenous forms continued to be the major cost driver, with an important contribution from immunotherapy. Much of the increase was led by the approval of 40 new IV and 48 new oral cancer medications with higher costs introduced in the market. Using CDD as an alternative metric to units had varying impacts by indication. The observed increases seemed to focus on specific cancer sites with varying effect; in CML, there was a 2.39-fold increase, compared to 4.41 for NSCLC and 1.86 for BC. However, for BC, two distinct sub-patterns were observed for hormone therapy (increasing 1.83) and for the novel tyrosine kinase inhibitors (increasing 40.8). Conclusion: The growing use of oral chemotherapy is obvious and calls for investments in supporting patients in managing medication adherence and adverse events. The shifts in the healthcare system are complex and need to be prioritized. Our data suggest that priority could be attributed to cancer sites driving innovation, namely, advanced breast cancer.

Bidirectional flow of action potentials in axons drives activity dynamics in neuronal cultures.

Objective. Recent technological advances are revealing the complex physiology of the axon and challenging long-standing assumptions. Namely, while most action potential (AP) initiation occurs at the axon initial segment in central nervous system neurons, initiation in distal parts of the axon has been reported to occur in both physiological and pathological conditions. The functional role of these ectopic APs, if exists, is still not clear, nor its impact on network activity dynamics.Approach. Using an electrophysiology platform specifically designed for assessing axonal conduction we show here for the first time regular and effective bidirectional axonal conduction in hippocampal and dorsal root ganglia cultures. We investigate and characterize this bidirectional propagation both in physiological conditions and after distal axotomy.Main results.A significant fraction of APs are not coming from the canonical synapse-dendrite-soma signal flow, but instead from signals originating at the distal axon. Importantly, antidromic APs may carry information and can have a functional impact on the neuron, as they consistently depolarize the soma. Thus, plasticity or gene transduction mechanisms triggered by soma depolarization can also be affected by these antidromic APs. Conduction velocity is asymmetrical, with antidromic conduction being slower than orthodromic.Significance.Altogether these findings have important implications for the study of neuronal functionin vitro, reshaping our understanding on how information flows in neuronal cultures.

NMDA channels together with L-type calcium currents and calcium-activated nonspecific cationic currents are sufficient to generate windup in WDR neurons.

Windup is characterized as a frequency-dependent increase in the number of evoked action potentials in dorsal horn neurons in response to electrical stimulation of afferent C-fibers. This phenomenon was first described in the mid-60s, but the core mechanisms behind it still remain elusive. Several factors affecting its dynamics have been identified, but the distinction between modulating mechanisms from generating mechanisms is not always clear. Several mechanisms contribute to the excitation of dorsal horn neurons exhibiting windup, and one of our main aims was to help making this distinction. The approach presented here relies on mathematical and computational analysis to study the mechanism(s) underlying windup. From experimentally obtained windup profiles, we extract the time scale of the facilitation mechanisms that may support the characteristics of windup. Guided by these values and using simulations of a biologically realistic compartmental model of a wide dynamic range (WDR) neuron, we are able to assess the contribution of each mechanism for the generation of action potentials windup. We show that the key mechanisms giving rise to windup is the temporal summation of N-methyl-d-aspartate (NMDA) long-lasting postsynaptic responses taking place on top of a membrane potential cumulative depolarization. Calcium-activated nonspecific cationic currents driven by calcium influx from L-type calcium channels and synaptic currents support this cumulative depolarization and plateau formation in WDR neuron membrane potential. The effects of different nonhomogeneous stimulation protocols are explored, and their important role in clarifying many aspects of the windup generation is shown. The models are used to produce several predictions that can be tested experimentally.

Relevance of quantification in brain PET studies with 18F-FDG. / Relevancia de la cuantificación en los estudios PET cerebrales con 18F-FDG.

The inclusion of 18F-FDG PET as a biomarker in the diagnostic criteria of neurodegenerative diseases and its indication in the presurgical assessment for drug-resistant epilepsies allow to improve specificity of these diagnosis. The traditional interpretation of neurological PET studies has been performed qualitatively, although in the last decade, several quantitative evaluation methods have emerged. This technical development has become relevant in clinical practice, improving specificity, reproducibility and reducing the interrater reliability derived from visual analysis. In this article we update/review the main imaging processing techniques currently used. This may allow the Nuclear Medicine physician to know their advantages and disadvantages when including these procedures in daily clinical practice.

Comprehensive analysis of meningioma in the first two decades of life: A systematic review.

PURPOSE: To evaluate the relationship between meningioma histological subtype and tumor site in under-20 year-olds. METHODS: A review of the literature on meningioma during the first 2 decades of life was carried out through a Medline search up to February 2019. To evaluate the adult population, a cross-sectional study was conducted on patients operated on between 2000 and 2014 in a single institution. Exclusion criteria comprised: series reports and papers that lacked detailed description of clinical findings, neuroimaging confirmation of tumor location, and/or at least 5 years' follow-up. RESULTS: One hundred and seven manuscripts were included, for 365 under-20 year-old patients: 200 male, and 164 female. Histopathology found 197 cases (53.9%) of WHO grade I meningioma, with predominance of meningothelial (41.1%) and transitional (30.9%) subtypes; 123 (33.7%) grade II, and 45 (12.3%) grade III. For 65 (18.25%) of the 356 cases, recurrence was documented, with only 24 deaths (6.7%). CONCLUSION: Meningioma in this population presented 2 differences compared to the adult population: male predominance, and high incidence of atypical meningioma. Surgery was the primary treatment. Adjuvant radiotherapy is controversial in the literature.