An ordinal CNN approach for the assessment of neurological damage in Parkinson’s disease patients

3D image scans are an assessment tool for neurological damage in Parkinson’s disease (PD) patients. This diagnosis process can be automatized to help medical staff through Decision Support Systems (DSSs), and Convolutional Neural Networks (CNNs) are good candidates, because they are effective when applied to spatial data. This paper proposes a 3D CNN ordinal model for assessing the level or neurological damage in PD patients. Given that CNNs need large datasets to achieve acceptable performance, a data augmentation method is adapted to work with spatial data. We consider the Ordinal Graph-based Oversampling via Shortest Paths (OGO-SP) method, which applies a gamma probability distribution for inter-class data generation. A modification of OGO-SP is proposed, the OGO-SP- algorithm, which applies the beta distribution for generating synthetic samples in the inter-class region, a better suited distribution when compared to gamma. The evaluation of the different methods is based on a novel 3D image dataset provided by the Hospital Universitario ‘Reina Sofía’ (Córdoba, Spain). We show how the ordinal methodology improves the performance with respect to the nominal one, and how OGO-SP- yields better performance than OGO-SP

Initial clinical and treatment patterns of advanced differentiated thyroid cancer: ERUDIT study

Advanced differentiated thyroid cancer; Epidemiological study; Survival prognostic factorsCáncer de tiroides diferenciado avanzado; Estudio epidemiológico; Factores pronósticos de supervivenciaCàncer de tiroide diferenciat avançat; Estudi epidemiològic; Factors pronòstics de supervivènciaBackground Up to 30% of differentiated thyroid cancer (DTC) will develop advanced-stage disease (aDTC) with reduced overall survival (OS). Objective The aim of this study is to characterize initial diagnosis of aDTC, its therapeutic management, and prognosis in Spain and Portugal. Methods A multicentre, longitudinal, retrospective study of adult patients diagnosed with aDTC in the Iberian Peninsula was conducted between January 2007 and December 2012. Analyses of baseline characteristics and results of initial treatments, relapse- or progression-free survival ((RP)FS) from first DTC diagnosis, OS, and prognostic factors impacting the evolution of advanced disease were evaluated. Results Two hundred and thirteen patients (median age: 63 years; 57% female) were eligible from 23 hospitals. Advanced disease presented at first diagnosis (de novo aDTC) included 54% of patients, while 46% had relapsed from early disease (recurrent/progressive eDTC). At initial stage, most patients received surgery (98%) and/or radioiodine (RAI) (89%), with no differences seen between median OS (95% CI) (10.4 (7.3–15.3) years) and median disease-specific-survival (95% CI) (11.1 (8.7–16.2) years; log-rank test P = 0.4737). Age at diagnosis being <55 years was associated with a lower risk of death (Wald chi-square (Wc-s) P < 0.0001), while a poor response to RAI to a higher risk of death ((Wc-s) P < 0.05). In the eDTC cohort, median (RP)FS (95% CI) was of 1.7 (1.0–2.0) years after RAI, with R0/R1 surgeries being the only common significant favourable factor for longer (RP)FS and time to aDTC ((Wc-s) P < 0.05). Conclusion Identification of early treatment-dependent prognostic factors for an unfavourable course of advanced disease is possible. An intensified therapeutic attitude may reverse this trend and should be considered in poor-performing patients. Prospective studies are required to confirm these findings.ERUDIT study was sponsored and funded by Eisai Farmacéutica S.A. (Madrid, Spain)

How clinical imaging can assess cancer biology.

Human cancers represent complex structures, which display substantial inter- and intratumor heterogeneity in their genetic expression and phenotypic features. However, cancers usually exhibit characteristic structural, physiologic, and molecular features and display specific biological capabilities named hallmarks. Many of these tumor traits are imageable through different imaging techniques. Imaging is able to spatially map key cancer features and tumor heterogeneity improving tumor diagnosis, characterization, and management. This paper aims to summarize the current and emerging applications of imaging in tumor biology assessment

Ordinal classification of the affectation level of 3D-images in Parkinson diseases

Parkinson's disease is characterised by a decrease in the density of presynaptic dopamine transporters in the striatum. Frequently, the corresponding diagnosis is performed using a qualitative analysis of the 3D-images obtained after the administration of [Formula: see text]I-ioflupane, considering a binary classification problem (absence or existence of Parkinson's disease). In this work, we propose a new methodology for classifying this kind of images in three classes depending on the level of severity of the disease in the image. To tackle this problem, we use an ordinal classifier given the natural order of the class labels. A novel strategy to perform feature selection is developed because of the large number of voxels in the image, and a method for generating synthetic images is proposed to improve the quality of the classifier. The methodology is tested on 434 studies conducted between September 2015 and January 2019, divided into three groups: 271 without alteration of the presynaptic nigrostriatal pathway, 73 with a slight alteration and 90 with severe alteration. Results confirm that the methodology improves the state-of-the-art algorithms, and that it is able to find informative voxels outside the standard regions of interest used for this problem. The differences are assessed by statistical tests which show that the proposed image ordinal classification could be considered as a decision support system in medicine.This research has been partially supported by the “Ministerio de Economía, Industria y Competitividad” of Spain (Ref. TIN2017-85887-C2-1-P) and the “Fondo Europeo de Desarrollo Regional (FEDER) y de la Consejería de Economía, Conocimiento, Empresas y Universidad” of the “Junta de Andalucía” (Spain) (Ref. UCO-1261651).Ye

How clinical imaging can assess cancer biology

Abstract Human cancers represent complex structures, which display substantial inter- and intratumor heterogeneity in their genetic expression and phenotypic features. However, cancers usually exhibit characteristic structural, physiologic, and molecular features and display specific biological capabilities named hallmarks. Many of these tumor traits are imageable through different imaging techniques. Imaging is able to spatially map key cancer features and tumor heterogeneity improving tumor diagnosis, characterization, and management. This paper aims to summarize the current and emerging applications of imaging in tumor biology assessment

[18F]DCFPyL PET/CT versus [18F]fluoromethylcholine PET/CT in Biochemical Recurrence of Prostate Cancer (PYTHON): a prospective, open label, cross-over, comparative study

Abstract Purpose Primary objective was to compare the per-patient detection rates (DR) of [ 18 F]DCFPyL versus [ 18 F]fluoromethylcholine positron emission tomography/computed tomography (PET/CT), in patients with first prostate cancer (PCa) biochemical recurrence (BCR). Secondary endpoints included safety and impact on patient management (PM). Methods This was a prospective, open label, cross-over, comparative study with randomized treatment administration of [ 18 F]DCFPyL (investigational medicinal product) or [ 18 F]fluoromethylcholine (comparator). Men with rising prostate-specific antigen (PSA) after initial curative therapy were enrolled. [ 18 F]DCFPyL and [ 18 F]fluoromethylcholine PET/CTs were performed within a maximum time interval of 12 days. DR was defined as the percentage of positive PET/CT scans identified by 3 central imaging readers. PM was assessed by comparing the proposed pre-PET/CT treatment with the local treatment", defined after considering both PET/CTs. Results A total of 205 patients with first BCR after radical prostatectomy (73%; median PSA = 0.46 ng/ml [CI 0.16;27.0]) or radiation therapy (27%; median PSA = 4.23 ng/ml [CI 1.4;98.6]) underwent [ 18 F]DCFPyL- and/or [ 18 F]fluoromethylcholine -PET/CTs, between July and December 2020, at 22 European sites. 201 patients completed the study. The per-patient DR was significantly higher for [ 18 F]DCFPyL- compared to [ 18 F]fluoromethylcholine -PET/CTs (58% (117/201 patients) vs. 40% (81/201 patients), p  2.0: 50/57 (88%) vs. 39/57 (68%) for [ 18 F]DCFPyL- and [ 18 F]fluoromethylcholine -PET/CT, respectively). [ 18 F]DCFPyL PET/CT had an impact on PM in 44% (90/204) of patients versus 29% (58/202) for [ 18 F]fluoromethylcholine. Overall, no drug-related nor serious adverse events were observed. Conclusions The primary endpoint of this study was achieved, confirming a significantly higher detection rate for [ 18 F]DCFPyL compared to [ 18 F]fluoromethylcholine, in men with first BCR of PCa, across a wide PSA range. [ 18 F]DCFPyL was safe and well tolerated

Data_Sheet_1_Effect of the Mediterranean diet and probiotic supplementation in the management of mild cognitive impairment: Rationale, methods, and baseline characteristics.docx

IntroductionMild cognitive impairment (MCI) can progress to Alzheimer’s disease (AD). When MCI is not properly controlled, the speed of deterioration can dramatically increase. Reduction of oxidative stress/inflammation and the modulation of the gut-brain axis could be new potential therapeutic targets for the prevention and treatment of AD. Consumption of specific nutrients, diets and probiotic supplementation have been evaluated for neurodegenerative disorders. We focus on a detailed description of the study methods and baseline characteristics of a clinical trial aiming to evaluate the efficacy of a combined nutritional intervention, i.e., a Mediterranean diet with probiotics, on cognitive capacity in a population with MCI.MethodsIn this randomized, latin-square crossover, double-blind, and controlled dietary intervention trial (clinicaltrials.gov NCT05029765), 47 MCI patients were randomized to consume three dietary interventions for 24-weeks each: (1) A Mediterranean diet supplemented with probiotics (109 colony-forming units of Lactobacillus rhamnosus and Bifidobacterium longum); (2) A Mediterranean diet + placebo; and (3) A Healthy diet according to the World Health Organization (WHO) recommendations. Participants will be evaluated before and after each of the three intervention periods (each 24-weeks, with a total of 72-weeks) for adherence to the assigned diet, blood tests, cognitive performance, gut microbiota analysis and functional neuroimaging studies.ResultsFifty patients, ≥60 years-old and diagnosed with MCI, underwent randomization. A total of 47 patients completed follow-up dietary interventions (57.4% males), with a good glycemic control (HbA1c 5.8 ± 0.1%, fasting glucose and insulin 99.7 ± 3.3 mg/dL and 10.4 ± 0.9 mU/L, respectively), elevated systolic blood pressure (136.9 ± 2.1 mmHg) and increased degree of inflammation (high-sensitivity C-reactive protein, 8.8 ± 0.9 mg/dL). Baseline adherence to the Mediterranean diet was medium (7.5 ± 0.3 points on the score that ranged from 0 to 14 points).ConclusionThe results of this clinical study would provide more evidence on the need for dietary therapeutic strategies, for clinical and individual practice, in the management of MCI patients to reduce the risk of AD development. Targeting lifestyle modifications in high-risk populations could prevent substantial cases of cognitive decline.Clinical trial registration[ClinicalTrials.gov], identifier [NCT05029765].</p

Initial clinical and treatment patterns of advanced differentiated thyroid cancer: ERUDIT study

Background: Up to 30% of differentiated thyroid cancer (DTC) will develop advanced-stage disease (aDTC) with reduced overall survival (OS). Objective: The aim of this study is to characterize initial diagnosis of aDTC, its therapeutic management, and prognosis in Spain and Portugal. Methods: A multicentre, longitudinal, retrospective study of adult patients diagnosed with aDTC in the Iberian Peninsula was conducted between January 2007 and December 2012. Analyses of baseline characteristics and results of initial treatments, relapse- or progression-free survival ((RP)FS) from first DTC diagnosis, OS, and prognostic factors impacting the evolution of advanced disease were evaluated. Results: Two hundred and thirteen patients (median age: 63 years; 57% female) were eligible from 23 hospitals. Advanced disease presented at first diagnosis (de novo aDTC) included 54% of patients, while 46% had relapsed from early disease (recurrent/progressive eDTC). At initial stage, most patients received surgery (98%) and/or radioiodine (RAI) (89%), with no differences seen between median OS (95% CI) (10.4 (7.3-15.3) years) and median disease-specific-survival (95% CI) (11.1 (8.7-16.2) years; log-rank test P = 0.4737). Age at diagnosis being <55 years was associated with a lower risk of death (Wald chi-square (Wc-s) P < 0.0001), while a poor response to RAI to a higher risk of death ((Wc-s) P < 0.05). In the eDTC cohort, median (RP)FS (95% CI) was of 1.7 (1.0-2.0) years after RAI, with R0/R1 surgeries being the only common significant favourable factor for longer (RP)FS and time to aDTC ((Wc-s) P < 0.05). Conclusion: Identification of early treatment-dependent prognostic factors for an unfavourable course of advanced disease is possible. An intensified therapeutic attitude may reverse this trend and should be considered in poor-performing patients. Prospective studies are required to confirm these findings.Advanced differentiated thyroid cancerEpidemiological studyRadioiodine-refractory differentiated thyroid cancerRelapsing differentiated thyroid cancerRelapsing prognostic factorsSurvival prognostic factor