Whole-body tumour burden on [18F]DCFPyL PET/CT in biochemical recurrence of prostate cancer: association with tumour biology and PSA kinetics.

PURPOSE: The objective was to assess the association between molecular imaging (mi) variables on [18F]DCFPyL-PET/CT with clinical and disease characteristics and prostate specific antigen (PSA) related variables in patients with biochemical recurrence of prostate cancer (BRPC). MATERIAL AND METHODS: We analysed patients with BRPC after radical treatment. We obtained clinical and PSA variables: International Society of Urology Pathology (ISUP) grade group, European Association of Urology (EAU) risk classification, PSA (PSA≤1ng/ml, 12), PSA doubling time (PSAdt) and PSA velocity (PSAvel). All PET/CT scans were reviewed with the assistance of automated Prostate Molecular Imaging Standardized Evaluation (aPROMISE) software and lesions' segmentation in positive scans was performed using this platform. Standardized uptake value (SUV) derived variables; tumour burden variables [whole-body tumour volume (wbTV), whole-body tumour lesion activity (wbTLA) and whole-body mi PSMA (wbPSMA)] and miTNM staging were obtained. Cut-off of PSA and kinetics able to predict PET/CT results were obtained. Associations between disease and mi variables were analysed using ANOVA, Kruskal-Wallis and Spearman's correlation tests. Multivariate analysis was also performed. RESULTS: Two hundred and seventy-five patients were studied. [18F]DCFPyL-PET/CT were positive in 165/275 patients. In multivariate analysis, moment of biochemical recurrence, ISUP group, PSA level and PSAvel showed significant association with the detection rate. miTNM showed significant association with PSA level (p<0.001) and kinetics (p<0.001), being higher in patients with metastatic disease. Both PSA and PSAvel showed moderate correlation with wbTV, wbTLA and wbPSMA (p<0.001). A weak correlation with SUVs was found. Mean wbTV, wbTLA and wbPSMA values were significantly higher in PSA > 2ng/ml, PSAdt ≤ 6 months and PSAvel ≥ 0.2ng/ml/month groups. Also, wbTV (p=0.039) and wbPSMA (p=0.020) were significantly higher in patients with ISUP grade group 5. PSA and PSAvel cut-offs (1.15 ng/ml and 0.065 ng/ml/month) were significantly associated with a positive PET/CT. CONCLUSION: Higher PSA values, unfavourable PSA kinetics and ISUP grade group 5 were robust predictive variables of larger tumour burden variables on [18F]DCFPyL PET/CT assessed by aPROMISE platform.

Paclitaxel as HIPEC-Drug after Surgical Cytoreduction for Ovarian Peritoneal Metastases: A Randomized Phase III Clinical Trial (HIPECOVA).

Multidisciplinary strategies have transformed the management of advanced ovarian cancer. We aimed to evaluate the effectiveness of paclitaxel in hyperthermic intraperitoneal chemotherapy (HIPEC) following surgical cytoreduction for ovarian peritoneal metastases in a randomized phase III trial conducted between August 2012 and December 2019. Seventy-six patients were randomized to either the HIPEC or no HIPEC group. Although median values for the primary endpoints (recurrence-free survival (RFS) and overall survival (OS)) revealed superior outcomes for the HIPEC (RFS: 23 months, OS: 48 months) over the control group (RFS: 19 months, OS: 46 months), these differences were not statistically significant (p = 0.22 and p = 0.579). Notably, the HIPEC group demonstrated significantly higher 5-year OS and 3-year RFS rates (47.2% and 47.5%) compared to patients without HIPEC (34.5% and 21.3%). Stratification according to Peritoneal Surface Disease Severity Score (PSDSS) showed improved OS and RFS for patients with lower PSDSS (I-II) in the HIPEC-treated group (p = 0.033 and p = 0.042, respectively). The Clavien-Dindo classification of adverse event grades revealed no significant differences between HIPEC and controls (p = 0.482). While overall results were not statistically significant, our long-term follow-up emphasized the potential benefit of HIPEC-associated cytoreduction with paclitaxel, particularly in selected ovarian cancer patients with lower PSDSS indices.

Second radioiodine treatment in patients with differentiated thyroid carcinoma: Causes and effects.

INTRODUCTION: Patients with incomplete response to initial therapy of thyroid cancer can be managed with ongoing observation or potentially additional therapies. Our aim was to assess the effect of a second radioactive iodine treatment (RAIT) and its relationship with causes and clinical variables. MATERIAL AND METHODS: Patients undergoing a second RAIT for biochemical or structural incomplete response to initial therapy of DTC were retrospectively included (n=120). They were categorised based on the American Thyroid Association (ATA) classification of response to initial therapy. Patients were reclassified in the following 6-18 months after second RAIT based on imaging findings and measurements of thyroglobulin and antithyroglobulin antibody levels. The associations of a downgrading of response category and progression-free survival (PFS), and the related variables, were evaluated. RESULTS: Sixty-six patients (55%) had a downgrading on ATA response category after second RAIT. A significant interdependence of causes for second RAIT and outcomes was found (χ2=29.400, p=0.001), with patients with neck reoperation showing a higher rate of indeterminate or excellent responses. A significant association between ATA response to second RAIT and absence of structural progression was found (χ2=44.914, p<0.001), with less structural progression in patients with downgrading on ATA response (χ2=30.914, p<0.001). There was also significant interdependence to some clinical variables, such as AJCC stage (χ2=8.460, p=0.015), ATA risk classification (χ2=10.694, p=0.005) and initial N stage (χ2=8.485, p=0.004). CONCLUSIONS: In selected cases, a second RAIT could lead to more robust responses with a potential improvement in prognosis in patients with incomplete response to initial DTC treatment.

Analytical performance validation of aPROMISE platform for prostate tumor burden, index and dominant tumor assessment with 18F-DCFPyL PET/CT. A pilot study.

To validate the performance of automated Prostate Cancer Molecular Imaging Standardized Evaluation (aPROMISE) in quantifying total prostate disease burden with 18F-DCFPyL PET/CT and to evaluate the interobserver and histopathologic concordance in the establishment of dominant and index tumor. Patients with a recent diagnosis of intermediate/high-risk prostate cancer underwent 18F-DCFPyL-PET/CT for staging purpose. In positive-18F-DCFPyL-PET/CT scans, automated prostate tumor segmentation was performed using aPROMISE software and compared to an in-house semiautomatic-manual guided segmentation procedure. SUV and volume related variables were obtained with two softwares. A blinded evaluation of dominant tumor (DT) and index tumor (IT) location was assessed by both groups of observers. In histopathological analysis, Gleason, International Society of Urological Pathology (ISUP) group, DT and IT location were obtained. We compared all the obtained variables by both software packages using intraclass correlation coefficient (ICC) and Cohen's kappa coefficient (k) for the concordance analysis. Fifty-four patients with a positive 18F-DCFPyL PET/CT were evaluated. The ICC for the SUVmax, SUVpeak, SUVmean, tumor volume (TV) and total lesion activity (TLA) was: 1, 0.833, 0.615, 0.494 and 0.950, respectively (p < 0.001 in all cases). For DT and IT detection, a high agreement was observed between both softwares (k = 0.733; p < 0.001 and k = 0.812; p < 0.001, respectively) although the concordances with histopathology were moderate (p < 0001). The analytical validation of aPROMISE showed a good performance for the SUVmax, TLA, DT and IT definition in comparison to our in-house method, although the concordance was moderate with histopathology for DT and IT.

Diagnostic and therapeutic impact of PET/CT with 18F-DCFPyL versus 18F-Fluorocholine in initial staging of intermediate-/high-risk prostate cancer: a pilot study.

AIM: To assess the diagnostic and therapeutic impact of PET/CT with 18F-DCFPyL with respect to 18F-Fluorocholine in initial staging of intermediate-/high-risk prostate cancer (PCa). MATERIAL AND METHODS: Patients with recent diagnosis of intermediate-/high-risk PCa without androgen deprivation therapy and previous 18F-Fluorocholine-PET/CT (negative for extraprostatic disease or with oligometastatic disease) were referred to 18F-DCFPyL-PET/CT. Patients' disease characteristic as grade group, D'Amico risk category (intermediate/high), prostate-specific antigen (PSA) closest to PET/CTs and its kinetics were obtained. The overall detection rate (DR) and molecular imaging TNM (miTNM) stage according to the prostate cancer molecular imaging standardized evaluation (PROMISE) criteria were assessed for both radiotracers, and their concordance (Kappa coefficient) was analyzed. The diagnostic and therapeutic impact of 18F-DCFPyL with respect to 18F-Fluorocholine was evaluated. RESULTS: Fifty-eight patients were analyzed (84.5% high-risk). 18F-Fluorocholine showed a higher DR than 18F-DCFPyL of prostate gland involvement (100% versus 93.1%) and pelvic node disease (37.9% versus 31%; k = 0.436, p = 0.001). On the other hand, 18F-DCFPyL-PET/CT showed a higher DR of metastatic disease than 18F-Fluorocholine-PET/CT, 9/58 patients (15.5%): 3 M1a, 5 M1b and 1 M1c) versus 5/58 (8.6%) patients: 1 M1a and 4 M1b), k = 0.426; p = 0.001. No significant association was found between clinical characteristics (grade group, risk category, PSA level and kinetic) and 18F-Fluorocholine or 18F-DCFPyL results. The results of 18F-DCFPyL-PET/CT modified the previously planned treatment compared to 18F-Fluorocholine-PET/CT in 13 patients (22.4%). CONCLUSIONS: 18F-Fluorocholine and 18F-DCFPyL PET/CT showed a similar DR of prostate gland and lymph node involvement, although with moderate concordance for the latter. 18F-DCFPyL was superior to 18F-Fluorocholine in detecting regional and distant metastasis with a therapeutic impact in one of every five patients.

Head-to-Head Comparison of [18F]F-choline and Imaging of Prostate-Specific Membrane Antigen, Using [18F]DCFPyL PET/CT, in Patients with Biochemical Recurrence of Prostate Cancer.

PURPOSE: To analyse diagnostic and therapeutic impact of molecular imaging TNM (miTNM) stage obtained with [18F]DCFPyL versus [18F]F-choline in head-to-head comparison in biochemical recurrence (BCR) of prostate cancer (PCa). MATERIAL AND METHODS: Patients with BCR of PCa after radical treatment with previous [18F]F-choline-PET/CT (negative or oligometastatic disease) were recruited to [18F]DCFPyL-PET/CT. Patients were classified according to: grade group, European Association of Urology classification, PSA, PSA doubling time (PSAdt) and PSA velocity (PSAvel). The overall detection rate (DR) and miTNM stage according to PROMISE criteria were assessed for both radiotracers and also correlated (Kappa). The influence of PSA and kinetics on both PET/CT (DR and miTNM) and predictive value of unfavourable kinetics on miTNM were determined. Cut-off PSA, PSAdt and PSAvel values able to predict PET/CT results were determined. Change in miTNM and treatment derived from [18F]DCFPyL information compared with [18F]F-choline were also evaluated. RESULTS: We studied 138 patients. [18F]DCFPyL showed a higher DR than [18F]F-choline (64.5% versus 33.3%) with a fair agreement. [18F]DCFPyL and [18F]F-choline detected T in 33.3% versus 19.6%, N in 27.5% versus 13.8%, and M in 30.4% versus 8.7%. Both tracers' DR showed significant associations with PSA and PSAvel. Significant association was only found between miTNM and PSA on [18F]F-choline-PET/CT (p = 0.033). For [18F]F-choline and [18F]DCFPyL-PET/CT, a PSAdt cut-off of 4.09 and 5.59 months, respectively, were able to predict M stage. [18F]DCFPyL changed therapeutic management in 40/138 patients. CONCLUSIONS: [18F]DCFPyL provides a higher DR and superior miTNM staging than [18F]F-choline in restaging BCR, especially with high PSA and unfavourable PSA kinetics, showing a fair agreement to [18F]F-choline.

Correlation of Global and Regional Amyloid Burden by 18 F-Florbetaben PET/CT With Cognitive Impairment Profile and Severity.

PURPOSE: To assess the correlation between profile and severity deterioration in the neuropsychological assessment and the most affected regions in amyloid PET semiquantification. The influence of vascular risk and other potential confounding factors was also evaluated. METHODS: A retrospective, observational, and multicenter study including all patients referred for amyloid PET in daily practice was conducted. Patients underwent neuropsychological assessment, and cognitive decline severity and domain(s) affected were recorded. The patients were grouped according to cognitive impairment (CI) profile and severity: (A) no CI, single-domain amnestic CI, multiple-domain amnestic CI, and nonamnestic CI; and (B) mild CI, moderate and severe dementia. An adapted Framingham Stroke Risk Profile was calculated for each individual. Depression and parkinsonism were also recorded. Standardized quantitative analysis software was used to obtain standardized uptake value ratio (SUVR) values from PET/CT images. The corresponding associations were assessed with the most appropriate statistical tests. RESULTS: One hundred twenty-nine patients were included (62 men, 67 women; 64.67 ± 7.47 years old). Significant differences in global and regional amyloid load were exclusively found in women between non-CI and moderate dementia ( P = 0.006, for total-cerebellum SUVR). Posterior and anterior cingulates and prefrontal cortex best represented CI severity ( P = 0.003, 0.006, and 0.006, respectively). No relationship between the CI profile and the regional amyloid load was shown. A significantly high positive correlation was found between age and vascular risk and between these variables and amyloid load in nearly all regions, especially in women with moderate dementia. CONCLUSION: Semiquantitative analysis of amyloid PET by SUVR values revealed a significant correlation between amyloid burden and CI severity, although only in women.

A Head-to-Head Comparison of 18F-Fluorocholine PET/CT and Conventional MRI as Predictors of Outcome in IDH Wild-Type High-Grade Gliomas.

(1) Aim: To study the associations between imaging parameters derived from contrast-enhanced MRI (CE-MRI) and 18F-fluorocholine PET/CT and their performance as prognostic predictors in isocitrate dehydrogenase wild-type (IDH-wt) high-grade gliomas. (2) Methods: A prospective, multicenter study (FuMeGA: Functional and Metabolic Glioma Analysis) including patients with baseline CE-MRI and 18F-fluorocholine PET/CT and IDH wild-type high-grade gliomas. Clinical variables such as performance status, extent of surgery and adjuvant treatments (Stupp protocol vs others) were obtained and used to discriminate overall survival (OS) and progression-free survival (PFS) as end points. Multilesionality was assessed on the visual analysis of PET/CT and CE-MRI images. After tumor segmentation, standardized uptake value (SUV)-based variables for PET/CT and volume-based and geometrical variables for PET/CT and CE-MRI were calculated. The relationships among imaging techniques variables and their association with prognosis were evaluated using Pearson's chi-square test and the t-test. Receiver operator characteristic, Kaplan−Meier and Cox regression were used for the survival analysis. (3) Results: 54 patients were assessed. The median PFS and OS were 5 and 11 months, respectively. Significant strong relationships between volume-dependent variables obtained from PET/CT and CE-MRI were found (r > 0.750, p < 0.05). For OS, significant associations were found with SUVmax, SUVpeak, SUVmean and sphericity (HR: 1.17, p = 0.035; HR: 1.24, p = 0.042; HR: 1.62, p = 0.040 and HR: 0.8, p = 0.022, respectively). Among clinical variables, only Stupp protocol and age showed significant associations with OS and PFS. No CE-MRI derived variables showed significant association with prognosis. In multivariate analysis, age (HR: 1.04, p = 0.002), Stupp protocol (HR: 2.81, p = 0.001), multilesionality (HR: 2.20, p = 0.013) and sphericity (HR: 0.79, p = 0.027) derived from PET/CT showed independent associations with OS. For PFS, only age (HR: 1.03, p = 0.021) and treatment protocol (HR: 2.20, p = 0.008) were significant predictors. (4) Conclusions: 18F-fluorocholine PET/CT metabolic and radiomic variables were robust prognostic predictors in patients with IDH-wt high-grade gliomas, outperforming CE-MRI derived variables.

Early Recurrence Detection of Glioma Using 18 F-Fluorocholine PET/CT : GliReDe Pilot Study.

OBJECTIVE: The aim of this study was to analyze the usefulness of 18 F-fluorocholine PET/CT in the early diagnosis of tumor recurrence, increasing the diagnosis confidence of MRI. METHODS: Patients with a previous gross total resection of glioma and the first suspicious or doubtful for recurrence MRI were prospectively included and subjected to 18 F-fluorocholine PET/CT. An independent and combined assessment of 18 F-fluorocholine PET/CT and multimodal MRI was performed classifying the studies as positive or negative for tumor recurrence. Final diagnosis (recurrence or not) was obtained by histological confirmation or clinical and imaging follow-up. The relation of SUV max and tumor-to-background ratio with progression, the diagnostic performance of imaging techniques, and their concordance (κ Cohen) were analyzed. RESULTS: Twenty-four studies on 21 patients were assessed. Recurrence was diagnosed in 20 cases. PET/CT was positive in 23 cases (3 false positive), whereas MRI was positive in 15 cases (1 false positive). MRI was false negative in 6 cases. There was no false negative on 18 F-fluorocholine PET/CT. Accuracy of PET/CT versus MRI was 87.5% and 70.8%, respectively. The combined evaluation of both techniques did not show any advantage with respect to PET/CT results alone. The concordance between both imaging techniques was low (κ = 0.135; P = 0.375). SUV max and tumor-to-background ratio were related to recurrence (areas under the curve of 0.844 [ P = 0.033] and 0.869 [ P = 0.022], respectively). CONCLUSIONS: 18 F-fluorocholine PET/CT was helpful for increasing the diagnostic confidence in the cases of MRI doubtful for recurrence in order to avoid a delayed diagnosis.

Increasing the confidence of 18F-Florbetaben PET interpretations: Machine learning quantitative approximation.

AIM: To assess the added value of semiquantitative parameters on the visual assessment and to study the patterns of 18F-Florbetaben brain deposition. MATERIALS AND METHODS: Retrospective analysis of multicenter study performed in patients with mild cognitive impairment or dementia of uncertain origin. 18F-Florbetaben PET scans were visually interpreted by two experienced observers, analyzing target regions in order to calculate the interobserver agreement. Semiquantification of all cortical regions with respect to three reference regions was performed to obtain standardized uptake value ratios (SUVRs). The ability of SUVRs to predict the visual evaluation, the possibility of preferential radiotracer deposition in some target regions and interhemisphere differences were analyzed. RESULTS: 135 patients were evaluated. In the visual assessment, 72 were classified as positive. Interobserver agreement was excellent. All SUVRs were significantly higher in positive PET scans than in negative ones. Prefrontal area and posterior cingulate were the cortical regions with the best correlations with the visual evaluation, followed by the composite region. Using ROC analysis, the SUVRs obtained in same target locations showed the best diagnostic performance. CONCLUSIONS: The derived information from target regions seems to help the visual classification, based on a preferential amyloid ß deposit, allowing machine learning. The amyloid ß deposit, although diffuse in all cortical regions, seems not to be uniform and symmetric.

Prognostic Potential of Postoperative 18F-Fluorocholine PET/CT in Patients With High-Grade Glioma. Clinical Validation of FuMeGA Postoperative PET Criteria.

OBJECTIVE: The aim of this study was to assess the prognostic performance of postoperative 18F-fluorocholine PET/CT in patients with high-grade glioma (HGG). METHODS: Patients with HGG who underwent preoperative and postoperative 18F-fluorocholine PET/CT were prospectively enrolled in the study. Postoperative MRI was classified as complete versus incomplete resection. Postoperative 18F-fluorocholine PET/CT was classified as negative (complete) or positive for metabolic residual tumor (incomplete resection) using a 5-point score system. The correlation of positive locations on PET/CT with the sites of subsequent tumor recurrence was evaluated. The concordance of postoperative imaging techniques (Cohen κ) and their relation with progression-free survival and overall survival were assessed using Kaplan-Meier method and Cox regression analysis. RESULTS: Fifty-one studies, belonging to 47 patients, were assessed. Four patients underwent 2 postoperative 18F-fluorocholine PET/CT scans as they needed a second tumor resection for recurrence. In the follow-up, 42 patients progressed, and 37 died. Concordance between postoperative PET/CT and MRI assessment was poor. Resection grade on MRI did not show any significant association with prognosis. In multivariate analysis, only age and postoperative PET/CT showed significant association with progression-free survival (hazard ratio [HR], 1.03 [1.01-1.06, P = 0.006] and 1.88 [0.96-3.71, P = 0.067], respectively) and overall survival (HR, 1.04 [1.01-1.07, P = 0.004] and 2.63 [1.22-5.68, P = 0.014], respectively). Postoperative positive 18F-fluorocholine PET/CT locations correlated with the sites of subsequent tumor recurrence in 81.82% of cases. CONCLUSION: Postoperative 18F-fluorocholine PET/CT seems superior to postoperative MRI in the outcome prediction of patients with HGG, outperforming it in the identification of the most probable location of tumor recurrence.

SUVmax to tumor perimeter distance: a robust radiomics prognostic biomarker in resectable non-small cell lung cancer patients.

OBJECTIVE: The purpose of this study was to evaluate the prognostic value of novel geometric variables obtained from pre-treatment [18F]FDG PET/CT with respect to classical ones in patients with non-small cell lung cancer (NSCLC). METHODS: Retrospective study including stage I-III NSCLC patients with baseline [18F]FDG PET/CT. Clinical, histopathologic, and metabolic parameters were obtained. After tumor segmentation, SUV and volume-based variables, global texture, sphericity, and two novel parameters, normalized SUVpeak to centroid distance (nSCD) and normalized SUVmax to perimeter distance (nSPD), were obtained. Early recurrence (ER) and short-term mortality (STM) were used as end points. Univariate logistic regression and multivariate logistic regression with respect to ER and STM were performed. RESULTS: A cohort of 173 patients was selected. ER was detected in 49/104 of patients with recurrent disease. Additionally, 100 patients died and 53 had STM. Age, pathologic lymphovascular invasion, lymph nodal infiltration, TNM stage, nSCD, and nSPD were associated with ER, although only age (aOR = 1.06, p = 0.002), pathologic lymphovascular invasion (aOR = 3.40, p = 0.022), and nSPD (aOR = 0.02, p = 0.018) were significant independent predictors of ER in multivariate analysis. Age, lymph nodal infiltration, TNM stage, nSCD, and nSPD were predictors of STM. Age (aOR = 1.05, p = 0.006), lymph nodal infiltration (aOR = 2.72, p = 0.005), and nSPD (aOR = 0.03, p = 0.022) were significantly associated with STM in multivariate analysis. Coefficient of variation (COV) and SUVmean/SUVmax ratio did not show significant predictive value with respect to ER or STM. CONCLUSION: The geometric variables, nSCD and nSPD, are robust biomarkers of the poorest outcome prediction of patients with NSCLC with respect to classical PET variables. KEY POINTS: • In NSCLC patients, it is crucial to find prognostic parameters since TNM system alone cannot explain the variation in lung cancer survival. • Age, lymphovascular invasion, lymph nodal infiltration, and metabolic geometrical parameters were useful as prognostic parameters. • The displacement grade of the highest point of metabolic activity towards the periphery assessed by geometric variables obtained from [18F]FDG PET/CT was a robust biomarker of the poorest outcome prediction of patients with NSCLC.

Diagnostic methodology in labelled leukocyte scan for prosthetic / non-prosthetic osteoarticular infection: Visual or semi-quantitative analysis? One- or two-day protocol?

OBJECTIVE: as scarce literature on the topic is available, we aimed to compare diagnostic utility of semi-quantitative versus visual analysis in labelled white blood cell scintigraphy (WBCS) for osteoarticular infection. One-day and two-day protocols were assessed, particularly in orthopaedic devices. MATERIAL AND METHODS: prospective study of 79 consecutive patients with suspected osteoarticular infection. In all patients, WBCS were performed at 30min, 4h, 8h and 24h. Images were analysed by grouping in two protocols: one-day-protocol (experts evaluated 30min, 4h and 8h planar images) and two-day-protocol (experts evaluated 30min, 4h and 24h planar images). Planar images were interpreted qualitative and semiquantitatively and also were compared grouping patients with and without orthopaedic devices. To find which cut-off value of the percentage variation could predict of osteoarticular infection, multiple cut-off values were calculated in both protocols from the Youden index. Three blinded readers analysed the images. RESULTS: Comparing final diagnosis visual analysis of the one-day-protocol provided better results with sensitivity of 95.5%, specificity of 93% and diagnostic accuracy of 93.7% (p<001) than the two-day-protocol with values of 86.4%, 94.7% and 92.4%, respectively (p<001). For semi-quantitative analysis, the one-day-protocol also obtained better results with sensitivity of 72.7%, specificity of 78.9% and accuracy of 77.2% (p<001) than two-day-protocol (no significant results; p=0.14), especially in the group of patients with orthopaedic devices (sensitivity of 100%, specificity of 79.5% and accuracy of 82.7%; p<001). CONCLUSIONS: most accurate approach in the diagnosis of osteoarticular infection corresponded to visual analysis in one-day-protocol that showed greater sensitivity and specificity than semi-quantitative analysis. Semi-quantitative analysis only could be useful when visual analysis is doubtful. In patients with joint prostheses, an increase in percentage variation above 9% obtained maximum sensitivity and negative predictive value.

Clinical impact and immunological alterations in asthmatic patients allergic to grass pollen subjected to high urban pollution in Madrid.

BACKGROUND: The prevalence of asthma has increased in recent decades. Among the reasons for this increase is environmental pollution. Pollutants cause bronchial inflammation and introduce modifications in the pollen, making it more allergenic. OBJECTIVE: Assess symptoms and medication requirements of asthmatic patients with grass allergies in Madrid (high urban pollution) and Ciudad Real (low pollution), and simultaneously evaluate the in vitro effects that pollen collected in both areas has on the immune cells of patients. METHODS: During two pollen seasons, patients from both cities were included. The patients recorded their symptoms and the asthma medication they took daily. In both cities, pollen data, pollutants and meteorological variables were evaluated. The response to different cell populations from patients in both areas were analysed after "in vitro" stimulation with pollen from both cities. RESULTS: The symptoms and medication use of the patients in Madrid was 29.94% higher. The NO2 concentration in Madrid was triple that of Ciudad Real (33.4 vs. 9.1 µg/m3 of air). All other pollutants had very similar concentrations during the study period. Pollen from the high pollution area caused a significant enhancement of T-CD8+ and NK cells proliferation compared with pollen of low pollution area, independently of the patient's origin. CONCLUSION: Asthmatic patients from Madrid have a worse clinical evolution than those from Ciudad Real because of higher levels of urban pollution, and this could be driven by the higher capacity of pollen of Madrid to activate T-CD8+ and NK cells.

Formaldehyde, acrolein and other carbonyls in dwellings of university students. Levels and source characterization.

Fifteen carbonyl compounds were investigated in the living rooms and bedrooms of 25 university student flats in the urban area of Ciudad Real (Central Southern Spain) in wintertime. Carbonyls were sampled using Radiello ® passive samplers refilled in the laboratory according to the method described in ISO 16000-3 Standard. The most abundant carbonyls in the living rooms and bedrooms were formaldehyde, acetone, acetaldehyde, hexaldehyde and butyraldehyde. The median concentration levels in the living rooms and bedrooms were: 28.6 and 34.2 µg m-3 for formaldehyde, 18.3 and 23.1 µg m-3 for acetone, 14.3 and 15.8 µg m-3 for acetaldehyde, 11.4 and 14.1 µg m-3 for hexaldehyde and 10.8 and 12.4 µg m-3 for butyraldehyde. The median concentration of formaldehyde, benzaldehyde, valeraldehyde and hexaldehyde was significantly higher in the bedrooms than in the living rooms. Indoor concentrations were significantly higher than outdoor concentrations for all carbonyl measured, indicating that sources in the indoor environment are prevailing in all flats. Principal component analysis, multiple linear regressions and Spearman correlation coefficients were used to investigate the origin, the indoor pollutants determinants and to establish common sources between carbonyls. Eight components were extracted from the application of PCA to the indoor and outdoor measurements accounting for 97.7% of the total variance. Formaldehyde, acetone, acetaldehyde and acrolein presented different indoor sources. In the multiple linear regression analysis, higher formaldehyde concentrations were found in those living rooms with wood floor and smoking was positively associated to acetone, propionaldehyde, benzaldehyde and isovaleraldehyde. Formaldehyde, acetaldehyde, acrolein, acetone, propionaldehyde and benzaldehyde concentrations were compared with relevant international guidelines, being their concentrations below recommended values except acrolein, where all measured flats exceeded the reference levels; it would be important to focus on the characterization of emission sources of acrolein in indoor air in order to minimise the exposure and health risk.

Interim and end-treatment 18F-Fluorocholine PET/CT and bone scan in prostate cancer patients treated with Radium 223 dichloride.

To assess the predictive and prognostic aim of interim and end-treatment 18F-fluorocholine PET/CT (FCH-PET/CT) and 99mTc-methilen diphosphonate bone scintigraphy (BS) in patients with castration-resistant prostate cancer and bone metastases (CRPC-BM) treated with Radium 223 dichloride (223Ra). Prospective and multicentre ChoPET-Rad study including 82 patients with CRPC-BM. Baseline, after 3 (interim) and 6 doses (end-treatment) BS and FCH PET/CT were performed in patients who meet the study criteria. Clinical variables, imaging and clinical progression were obtained and their association with progression free survival (PFS), and overall survival (OS) was studied. Agreement between BS and FCH PET/CT response was assessed using Kappa (K) analysis. Median of PFS and OS was 3 and 16 months, respectively. Agreement between interim BS and FCH PET/CT was weak (K: 0.28; p = 0.004). No agreement was observed between end-treatment diagnostic studies. Interim and end-treatment FCH PET/CT were related to PFS (p = 0.011 and p < 0.001, respectively). Therapeutic failure and interim BS and FCH PET/CT showed association with OS (p < 0.001, p = 0.037 and p = 0.008, respectively). Interim and end-treatment FCH PET/CT were good predictors of biochemical progression in patients treated with 223Ra. Therapeutic failure and progression in interim BS or FCH PET/CT were adverse factors for OS.

Ubiquinol Supplementation Improves Gender-Dependent Cerebral Vasoreactivity and Ameliorates Chronic Inflammation and Endothelial Dysfunction in Patients with Mild Cognitive Impairment.

Ubiquinol can protect endothelial cells from multiple mechanisms that cause endothelial damage and vascular dysfunction, thus contributing to dementia. A total of 69 participants diagnosed with mild cognitive impairment (MCI) received either 200 mg/day ubiquinol (Ub) or placebo for 1 year. Cognitive assessment of patients was performed at baseline and after 1 year of follow-up. Patients' cerebral vasoreactivity was examined using transcranial Doppler sonography, and levels of Ub and lipopolysaccharide (LPS) in plasma samples were quantified. Cell viability and necrotic cell death were determined using the microvascular endothelial cell line bEnd3. Coenzyme Q10 (CoQ) levels increased in patients supplemented for 1 year with ubiquinol versus baseline and the placebo group, although higher levels were observed in male patients. The higher cCoQ concentration in male patients improved cerebral vasoreactivity CRV and reduced inflammation, although the effect of Ub supplementation on neurological improvement was negligible in this study. Furthermore, plasma from Ub-supplemented patients improved the viability of endothelial cells, although only in T2DM and hypertensive patients. This suggests that ubiquinol supplementation could be recommended to reach a concentration of 5 µg/mL in plasma in MCI patients as a complement to conventional treatment.

Exogenous Melatonin Improves the Reproductive Outcomes of Yearling Iberian Red Deer (Cervus elaphus hispanicus) Hinds.

The aim of this study was to assess the effect of melatonin implants on the reproductive performance of yearling Iberian red deer (Cervus elaphus hispanicus) hinds. It also explored exogenous melatonin administration as a tool to minimize the negative effect of a low yearling hind's liveweight on their reproductive efficiency. In addition, the effect of melatonin-treated yearling hinds on non-treated hinds was studied in order to provide a practical and economical protocol to improve farms' productivity. A total of 4520 Iberian red deer hinds belonging to the same farm were included in this study. Melatonin (108 mg/hind) implants were administered three-fold every 30 days before the breeding season. Fertility rates, calves' weights and calving dates were registered for each hind. The results showed that exogenous melatonin increased significantly (p < 0.05) the calves' weight (32.39 ± 1.07 kg vs. 27.65 ± 1.11 kg for Weight 1calf (July) and 46.59 ± 1.50 kg vs. 41.79 ± 1.54 kg for Weight 2calf (August, at weaning)) and advanced the calving date by 15 days in yearling hinds compared to the non-treated group. In addition, the administration of melatonin implants before the breeding season was able to minimize the negative effect of low yearling hinds' liveweight (Weight 1hind) on their future reproductive outcomes, as the fertility rates increased by 46% and the calves' weight increased by 7 kg after the melatonin treatment, regardless of the yearlings' weight. Finally, when both experimental groups (melatonin and non-treated) were kept separate, higher fertility rates (76.73 ± 7.18% vs. 66.94 ± 7.41%) were observed for the melatonin-treated hinds compared to the non-treated hinds. However, when both groups of yearling hinds were maintained together, no significant differences were observed in their fertility outcomes (78.13 ± 21.26% vs. 78.12 ± 23.32%). Therefore, melatonin implants may be used in yearling Iberian red deer hinds as a management tool to improve their reproductive productivity.

18F-choline PET/computed tomography and clinical parameters in the detection of significant prostate cancer in patients with increased prostate-specific antigen levels and previous negative biopsies.

OBJECTIVES: The aim of this study is to assess the value of the F-choline PET/computed tomography (CT) in predicting significant prostate cancer (sPCa) in patients with persistently increased prostate-specific antigen (PSA) levels and previous negative biopsies. To study the possible predictive added value of F-choline PET/CT to clinical variables and biomarkers derived from PSA in detecting sPCa. METHODS: We evaluated patients who underwent F-choline PET/CT because of ongoing suspicion of prostate cancer (PCa) due to elevated PSA levels (4-20 ng/mL) and at least one previous negative or no conclusive prostate biopsy for PCa. Age, PSA, free PSA, free/total PSA ratio, PSA velocity, PSA doubling time, PSA density and score risk were obtained. F-choline PET/CT was classified as negative/positive (PET-categorical). Additionally, we subclassified F-choline PET/CT according to the radiotracer uptake patterns (PET-pattern). The reference standard was the histological confirmation. Accuracy of PET/CT was evaluated. Univariate and multivariate logistic regression analyses were performed for metabolic and clinical variables. RESULTS: A total of 78 patients were included in our study, 23 had PCa (15 with sPCa). The PET pattern showed the highest accuracy and was the most powerful predictor of sPCa. In this research, the prediction of sPCa was improved combining PET pattern and score risk. CONCLUSION: F-choline PET/CT is a potential tool for predicting sPCa in patients with persistently increased PSA levels and previous negative biopsies, and also it could improve the performance of score risk in predicting sPCa.

18F-Fluorocholine PET/CT in the Prediction of Molecular Subtypes and Prognosis for Gliomas.

AIM: To study the association of metabolic features of F-fluorocholine in gliomas with histopathological and molecular parameters, progression-free survival (PFS) and overall survival (OS). METHODS: Prospective multicenter and nonrandomized study (Functional and Metabolic Glioma Analysis). Patients underwent a basal F-fluorocholine PET/CT and were included after histological confirmation of glioma. Histological and molecular profile was assessed: grade, Ki-67, isocitrate dehydrogenase status and 1p/19q codeletion. Patients underwent standard treatment after surgery or biopsy, depending on their clinical situation. Overall survival and PFS were obtained after follow-up. After tumor segmentation of PET images, SUV and volume-based variables, sphericity, surface, coefficient of variation, and multilesionality were obtained. Relations of metabolic variables with histological, molecular profile and prognosis were evaluated using Pearson χ and t test. Receiver operator caracteristic curves were used to obtain the cutoff of PET variables. Survival analysis was performed using Kaplan-Meier and Cox regression analysis. RESULTS: Forty-five patients were assessed; 38 were diagnosed as having high-grade gliomas. Significant differences of SUV-based variables with isocitrate dehydrogenase status, tumor grade, and Ki-67 were found. Tumor grade, Ki-67, SUVmax, and SUVmean were related to progression. Kaplan-Meier analysis revealed significant associations of SUVmax, SUVmean, and multilesionaly with OS and PFS. SUVmean, sphericity, and multilesionality were independent predictors of OS and PFS in Cox regression analysis. CONCLUSIONS: Metabolic information obtained from F-fluorocholine PET of patients with glioma may be useful in the prediction of tumor biology and patient prognosis.