Clinico-pathological factors associated with radioiodine refractory differentiated thyroid carcinoma status.

PURPOSE: Risk factors for developing radioiodine refractory thyroid cancer (RAIR-TC) have rarely been analyzed. The purpose of the present study was to find clinical and pathological features associated with the occurrence of RAIR-disease in differentiated thyroid cancers (DTC) and to establish an effective predictive risk score. METHODS: All cases of RAIR-DTC treated in our center from 1990 to 2020 were retrospectively reviewed. Each case was matched randomly with at least four RAI-avid DTC control patients based on histological and clinical criteria. Conditional logistic regression was used to examine the association between RAIR-disease and variables with univariate and multivariate analyses. A risk score was then developed from the multivariate conditional logistic regression model to predict the risk of refractory disease occurrence. The optimal cut-off value for predicting the occurrence of RAIR-TC was assessed by receiver operating characteristic (ROC) curves and Youden's statistic. RESULTS: We analyzed 159 RAIR-TC cases for a total of 759 controls and found 7 independent risk factors for predicting RAIR-TC occurrence: age at diagnosis ≥ 55, vascular invasion, synchronous cervical, pulmonary and bone metastases at initial work-up, cervical and pulmonary recurrence during follow-up. The predictive score of RAIR-disease showed a high discrimination power with a cut-off value of 8.9 out of 10 providing 86% sensitivity and 92% specificity with an area under the curve (AUC) of 0.95. CONCLUSION: Predicting the occurrence of RAIR-disease in DTC patients may allow clinicians to focus on systemic redifferentiating strategies and/or local treatments for metastatic lesions rather than pursuing with ineffective RAI-therapies.

Supraventricular cardiac conduction system exposure in breast cancer patients treated with radiotherapy and association with heart and cardiac chambers doses.

Purpose: To assess sinoatrial node (SAN) and atrioventricular node (AVN) doses for breast cancer (BC) patients treated with 3D-CRT and evaluate whether "large" cardiac structures (whole heart and four cardiac chambers) would be relevant surrogates. Material and methods: This single center study was based on 116 BCE patients (56 left-sided, 60 right-sided) treated with 3D-CRT without respiratory gating strategies and few IMN irradiations from 2009 to 2013. The heart, the left and right ventricles (LV, RV), the left and right atria (LA, RA) were contoured using multi-atlases for auto-segmentation. The SAN and the AVN were manually delineated using a specific atlas. Based on regression analysis, the coefficients of determination (R2) were estimated to evaluate whether "large" cardiac structures were relevant surrogates (R2 > 0.70) of SAN and AVN doses. Results: For left-sided BC, mean doses were: 3.60 ± 2.28 Gy for heart, 0.47 ± 0.24 Gy for SAN and 0.74 ± 0.29 Gy for AVN. For right-sided BC, mean heart dose was 0.60 ± 0.25 Gy, mean SAN dose was 1.57 ± 0.63 Gy (>85 % of patients with SAN doses > 1 Gy) and mean AVN dose was 0.51 ± 0.14 Gy. Among all "large" cardiac structures, RA appeared as the best surrogate for SAN doses (R2 > 0.80). Regarding AVN doses, the RA may also be an interesting surrogate for left-sided BC (R2 = 0.78), but none of "large" cardiac structures appeared as relevant surrogates among right-sided BC (all R2 < 0.70), except the LA for patients with IMN (R2 = 0.83). Conclusions: In BC patients treated 10 years ago with 3D-CRT, SAN and AVN exposure was moderate but could exceed 1 Gy to the SAN in many right-sided patients with no IMN-inclusion. The RA appeared as an interesting surrogate for SAN exposure. Specific conduction nodes delineation remains necessary by using modern radiotherapy techniques.

Risk of pacemaker implantation after radiotherapy for breast cancer: A study based on French nationwide health care database sample.

BACKGROUND: Among cardiac complications of breast cancer radiotherapy (BC RT), there are very limited data on arrhythmia and conduction disorders, in particular severe cases requiring permanent pacemaker implantation (PPMI). Therefore, this exploratory study aimed to evaluate the risk of PPMI for BC patients treated with RT, compared with the general population and with BC patients not treated with RT. METHODS: The study was performed on a 1/97 representative sample of the French health care database (EGB database). Adult women with a first BC treated with or without RT between 2008 and 2016 were included, followed until 2018, and de novo PPMI were identified. We compared the PPMI incidence in BC cohort relative to the general population with standardized incidence ratio (SIR) and evaluated the risk of PPMI in RT patients compared to patients without RT with a competing risk survival analysis. RESULTS: A total of 3853 BCE patients were included. Among BC patients treated with RT, 28 PPMI cases were observed compared with 13 expected cases, corresponding to a SIR of 2.18 [95% CI: 1.45-3.06]. For BC patients not treated with RT, the SIR was 1.01 [95% CI: 0.40-1.90]. Patients treated with RT showed a borderline significant higher risk of PPMI compared with those not treated with RT (subdistribution Hazard Ratio = 2.08, 95% CI 0.87-4.97, p = 0.09). CONCLUSIONS: Our exploratory findings indicate that, over the last decade in France, BC patients treated with RT appeared to be at higher risk of PPMI than general population. Further studies are needed to expand on this topic.

Occupational low-dose irradiation and cancer risk among medical radiation workers.

BACKGROUND: Medical workers are the largest group of workers occupationally exposed to low doses of ionizing radiation (IR) worldwide. AIMS: This review presents all the cohorts of medical workers exposed in the world and summarizes cancer risks associated with radiation exposure in this population. METHODS: Epidemiological studies on health professionals exposed to IR published from 1975 to 2019 were reviewed. Strength of evidence was assessed according to the modified Royal College of General Practitioners three-star system. RESULTS: Among the 16 epidemiological studies focusing on cancers from 11 cohorts among medical staff exposed to radiation, higher risks of cancer were observed for pre-1950 exposure and for medical workers who performed fluoroscopically guided interventional procedures or radionuclides procedures compared to those who did not. However, strength of evidence supporting the associations remains moderate as several methodological limits including the lack of dosimetry data, lifestyle factors and recent updates may obscure the link between medical occupational exposure and cancer occurrence. CONCLUSIONS: Excess risk of cancer is suspected for high and former exposures. The more highly exposed professions, i.e. interventional physicians and nuclear medicine workers, should be monitored carefully. Collaborative projects aiming to increase the quantity and quality of information of the studied populations would be a key point.

Dose distribution of the brain tissue associated with cognitive functions in high-grade glioma patients.

PURPOSE: The purpose of this prospective dosimetric study was to assess the dose distribution regarding the brain areas implied in cognitive functions using two approaches: volumetric modulated arc therapy (VMAT) and helical tomotherapy (HT). PATIENTS AND METHODS: Thirty-seven patients were treated using a dual-arc VMAT approach for supratentorial glioblastoma between 2016 and 2018. The total dose of 60Gy in 30 daily fractions was administered to the planning target volume (PTV). The brain structures that play an important role in cognitive physiology, such as the hippocampi, corpus callosum, cerebellum, subventricular zones (SVZ), were delineated. For each patient, a new treatment plan in HT was determined by a second medical physicist in a blindly fashion according to the same dose constraints and priorities. Statistical analyses were performed using the Wilcoxon-signed rank test. RESULTS: Conformity indexes remained similar with both techniques. The mean values were 0.96 (0.19-1.00) for VMAT and 0.98 (range, 0.84-1.00) for HT, respectively (P=0.73). Significant D50% reductions were observed with VMAT compared to HT: 14.6Gy (3.8-28.0) versus 17.4Gy (12.1-25.0) for the normal brain (P=0.014); 32.5Gy (10.3-60.0) versus 35.6Gy (17.1-58.0) for the corpus callosum (P=0.038); 8.1Gy (0.4-34.0) versus 12.8Gy (0.8-27.0) for the cerebellum (P<0.001), respectively. CONCLUSION: The VMAT approach seemed to improve the sparing of the key brain areas implied in cognitive functions without jeopardizing PTV coverage.

Usefulness of High-Frequency Ultrasound in the Classification of Histologic Subtypes of Primary Basal Cell Carcinoma. / Utilidad de la ecografía cutánea en la clasificación de subtipos de los carcinomas basocelulares primarios.

INTRODUCTION: Incisional biopsy may not always provide a correct classification of histologic subtypes of basal cell carcinoma (BCC). High-frequency ultrasound (HFUS) imaging of the skin is useful for the diagnosis and management of this tumor. OBJECTIVES: The main aim of this study was to compare the diagnostic value of HFUS compared with punch biopsy for the correct classification of histologic subtypes of primary BCC. We also analyzed the influence of tumor size and histologic subtype (single subtype vs. mixed) on the diagnostic yield of HFUS and punch biopsy. METHODS: Retrospective observational study of primary BCCs treated by the Dermatology Department of Hospital Costa del Sol in Marbella, Spain, between october 2013 and may 2014. Surgical excision was preceded by HFUS imaging (Dermascan C©, 20-MHz linear probe) and a punch biopsy in all cases. We compared the overall diagnostic yield and accuracy (sensitivity, specificity, positive predictive value [PPV], and negative predictive value [NPV]) of HFUS and punch biopsy against the gold standard (excisional biopsy with serial sections) for overall and subgroup results. RESULTS: We studied 156 cases. The overall diagnostic yield was 73.7% for HFUS (sensitivity, 74.5%; specificity, 73%) and 79.9% for punch biopsy (sensitivity, 76%; specificity, 82%). In the subgroup analyses, HFUS had a PPV of 93.3% for superficial BCC (vs. 92% for punch biopsy). In the analysis by tumor size, HFUS achieved an overall diagnostic yield of 70.4% for tumors measuring 40mm2 or less and 77.3% for larger tumors; the NPV was 82% in both size groups. Punch biopsy performed better in the diagnosis of small lesions (overall diagnostic yield of 86.4% for lesions ≤40mm2 vs. 72.6% for lesions >40mm2). CONCLUSIONS: HFUS imaging was particularly useful for ruling out infiltrating BCCs, diagnosing simple, superficial BCCs, and correctly classifying BCCs larger than 40mm2.

Patient radiation doses in paediatric interventional cardiology procedures: a review.

A large number of investigations into the radiation doses from x-ray guided interventional cardiology procedures in children have been carried out in recent years. A review was conducted of these studies, gathering data on kerma area product (P KA), fluoroscopic screening time (FT), air kerma, and estimates of effective dose and organ doses. The majority of studies focus on P KA and FT with no estimation of dose to the patient. A greater than ten-fold variation in average P KA was found between different studies, even where data were stratified by patient age or weight. Typical values of P KA were 0.6-10 Gy · cm2 (<1 year/10 kg), 1.5-30 Gy · cm2 (1-5 years), 2-40 Gy · cm2 (5-10 years), 5-100 Gy · cm2 (10-16 years) and 10-200 Gy · cm2 (>16 years). P KA was lowest for heart biopsy (0.3-10 Gy · cm2 for all ages combined) and atrial septostomy (0.4-4.0 Gy · cm2), and highest for pulmonary artery angioplasty (1.5-35 Gy · cm2) and right ventricular outflow tract dilatation (139 Gy · cm2). Most estimates of patient dose were in the form of effective dose (typically 3-15 mSv) which is of limited usefulness in individualised risk assessment. Few studies estimated organ doses. Despite advances in radiation protection, recent publications have reported surprisingly large doses, as represented by P KA and air kerma. There is little indication of a fall in these dose indicators over the last 15 years. Nor is there much suggestion of a fall in doses associated with the use of flat panel detectors, as opposed to image intensifiers. An assessment of the impact of radiation dose in the context of overall patient outcome is required.

Responsiveness of the Spanish Version of the "Skin Cancer Index".

Background. Skin Cancer Index (SCI) is a specific questionnaire measuring health related quality of life (HRQL) in patients with cervicofacial non-melanoma skin cancer (CFNMSC). The original scale has recently been adapted and validated into Spanish. Objectives. Evaluate the responsiveness of the Spanish version of SCI. Methods. Patients with CFNMSC candidate for surgical treatment were administered the questionnaire at time of diagnostic (t0), 7 days after surgery (t1), and 5 months after surgery (t2). The scale and subscales scores (C1: social/appearance, C2: emotional) were then evaluated. Differences between t0-t1, t1-t2, and t0-t2 were determined and a gender-and-age segmented analysis was performed. Results. 88 patients, 54.8% male, mean age 62.5 years, completed the study. Differences between t0-t1 and t1-t2 scores were statistically significant (p < 0.05). The lowest values were found at time of diagnosis and postsurgery. Women and patients under 65 years showed the lowest values at the three times. Limitations. Concrete geographic and cultural area. Clinical and histological variables are not analysed. Conclusions. Our results confirm responsiveness of the Spanish version of the SCI. Further development of the instrument in Spanish-speaking countries and populations will make it possible to extend worldwide research and knowledge horizons on skin cancer.

Childhood CT scans and cancer risk: impact of predisposing factors for cancer on the risk estimates.

To investigate the role of cancer predisposing factors (PFs) on the associations between paediatric computed tomography (CT) scan exposures and subsequent risk of central nervous system (CNS) tumours and leukaemia. A cohort of children who underwent a CT scan in 2000-2010 in 23 French radiology departments was linked with the national childhood cancers registry and national vital status registry; information on PFs was retrieved through hospital discharge databases. In children without PF, hazard ratios of 1.07 (95% CI 0.99-1.10) for CNS tumours (15 cases) and 1.16 (95% CI 0.77-1.27) for leukaemia (12 cases) were estimated for each 10 mGy increment in CT x-rays organ doses. These estimates were similar to those obtained in the whole cohort. In children with PFs, no positive dose-risk association was observed, possibly related to earlier non-cancer mortality in this group. Our results suggest a modifying effect of PFs on CT-related cancer risks, but need to be confirmed by longer follow-up and other studies.

[Vaccination before and during pregnancy]. / La vaccination de la femme avant la grossesse et pendant la grossesse.

Vaccination of pregnant women is designed to protect the mother and the fetus from preventable diseases through vaccination. Authorized vaccines contain inactivated viruses, otherwise (l ive virus), they cannot be made during pregnancy. Vaccines offered in all circumstances are those against influenza, at any point in pregnancy, and diphtheria-tetanus-pertussis, in the 3rd trimester. Hepatitis A and/or B, meningitis, pneumococcal, rabies, anthrax vaccines must be considered in post exposure. There is not enough data on vaccines against typhoid fever, Japanese encephalitis, cholera during the pregnancy. Vaccines to be done at distance of pregnancy are those against chickenpox, rubella, measles and mumps for unprotected women, as well as the vaccine against HPV, BCG, yellow fever and smallpox. In conclusion, only influenza vaccines and diphtheria-tetanus-pertussis showed a safe profile during pregnancy. Other vaccines should be considered in the event of exposure to risk of illness with the help of an infectious disease specialist.

La vaccination de la femme enceinte vise à protéger la mère et le foetus de maladies évitables par cette démarche. Les vaccins autorisés contiennent des virus inactivés, dans le cas contraire (virus vivants), ils sont contre indiqués pendant la grossesse. Les vaccins à proposer en toutes circonstances sont ceux de la grippe à n'importe quel moment de la grossesse et de la diphtérie-tétanos-coqueluche, au 3e trimestre. En cas d'exposition à risque, on peut envisager la vaccination contre l'hépatite A et/ou B, la méningite, le pneumocoque, la rage, l'anthrax. Les données sont insuffisantes concernant les vaccins de la fièvre typhoïde, de l'encéphalite japonaise et du choléra. Les vaccins proposés en dehors de la grossesse sont ceux de la varicelle, la rubéole, la rougeole et les oreillons pour les femmes non protégées, ainsi que le vaccin de l'HPV, la fièvre jaune et le BCG. En conclusion, seuls les vaccins antigrippaux et anti diphtérie-tétanos-coqueluche ont montré un profil d'innocuité sûr pendant la grossesse. Les autres vaccins doivent s'envisager en cas d'exposition à risque après avis d'un infectiologue.

Follow-up of children exposed to ionising radiation from cardiac catheterisation: the Coccinelle study.

Cardiac catheterisation has become an essential tool in the diagnosis and treatment of children with a wide variety of congenital and acquired forms of cardiovascular disease. Despite the clear clinical benefit to the patient, radiation exposure from paediatric cardiac catheterisation procedures (CCPs) may be substantial. Given children's greater sensitivity to radiation and the longer life span during which radiation health effects can develop, an epidemiological cohort study, named Coccinelle or 'Ladybird' (French acronym for 'Cohorte sur le risque de cancer après cardiologie interventionnelle pédiatrique'), is carried out in France to evaluate the risks of leukaemia and solid cancers in this population. A total number of 8000 included children are expected. Individual CCP-related doses will be assessed for each child included in the cohort. For each CCP performed, dosimetric parameters (dose-area product, fluoroscopy time and total number of cine frames) are retrieved retrospectively. Organ doses, especially to the lung, the oesophagus and the thyroid, are calculated with PCXMC software. The cohort will be followed up through linkage with French paediatric cancer registries.

[Ultrasound in the management of non-melanoma skin cancer]. / Ecografía aplicada al manejo del cáncer cutáneo no melanoma.

Cutaneous ultrasound plays an important role in the study and management of non-melanoma skin cancer. Among other factors, this technique contributes to the diagnosis and differential diagnosis of these tumours, the establishment of their size and relation to neighbouring structures, the delimitation of surgical margins, and the detection of subclinical and recurrent lesions. The present article analyses the role of cutaneous ultrasound in the field of non-melanoma skin cancer (basal and squamous cell carcinomas, lymphomas and dermatofibrosarcoma) through a literature review.

Skin cancer prevention and detection campaign at golf courses on Spain's Costa del Sol.

BACKGROUND AND OBJECTIVES: Skin cancer prevention and detection campaigns targeting specific groups are necessary and have proven to be more effective than those aimed at the general population. Interventions in outdoor tourist spots have proven successful, although none have specifically targeted golf courses. The aims of this study were to describe the risk profile of golfers and golf course workers and evaluate the impact of a skin cancer prevention and early detection intervention. MATERIAL AND METHODS: This was a cross-sectional descriptive study conducted at 6 golf courses. The intervention included a skin examination and completion of a questionnaire about demographic details, risk factors, and sun exposure and sun protection habits. Participants were also given advice on sun protection measures, self-examination, and use of sunscreens, and were asked about their satisfaction with the intervention and their intention to change their current behaviors. The effect was measured in terms of the diagnoses made, satisfaction with the intervention, reported intention to change, and potential effect in terms of existing risk factors. RESULTS: Of the 351 participants (57% golfers and 43% golf course workers), 70.4% had fair skin, 11.7% had a family history of skin cancer, and 8.5% had a personal history of skin cancer. Skin cancer and actinic keratoses were diagnosed in 10.7% and 40% of the golfers, respectively. The session was rated positively by 99.4% of the participants; 93.9% stated that they intended to improve their sun exposure habits and 93.4% said that they planned to examine their skin more frequently. CONCLUSIONS: Our findings confirm that golf course workers and, in particular, golfers are an important target for skin cancer prevention campaigns. This is the first intervention to specifically target golf courses, and it proved to be both feasible and useful. Its success appears to be attributable to numerous factors: it was conducted at golf courses, had multiple components, and was preceded by a motivational campaign.

Are the studies on cancer risk from CT scans biased by indication? Elements of answer from a large-scale cohort study in France.

BACKGROUND: Recent epidemiological results suggested an increase of cancer risk after receiving computed tomography (CT) scans in childhood or adolescence. Their interpretation is questioned due to the lack of information about the reasons for examination. Our objective was to estimate the cancer risk related to childhood CT scans, and examine how cancer-predisposing factors (PFs) affect assessment of the radiation-related risk. METHODS: The cohort included 67,274 children who had a first scan before the age of 10 years from 2000 to 2010 in 23 French departments. Cumulative X-rays doses were estimated from radiology protocols. Cancer incidence was retrieved through the national registry of childhood cancers; PF from discharge diagnoses. RESULTS: During a mean follow-up of 4 years, 27 cases of tumours of the central nervous system, 25 of leukaemia and 21 of lymphoma were diagnosed; 32% of them among children with PF. Specific patterns of CT exposures were observed according to PFs. Adjustment for PF reduced the excess risk estimates related to cumulative doses from CT scans. No significant excess risk was observed in relation to CT exposures. CONCLUSIONS: This study suggests that the indication for examinations, whether suspected cancer or PF management, should be considered to avoid overestimation of the cancer risks associated with CT scans.

A Spanish version of the Skin Cancer Index: a questionnaire for measuring quality of life in patients with cervicofacial nonmelanoma skin cancer.

INTRODUCTION: The Skin Cancer Index (SCI) is the first specific patient-reported outcome measure for patients with cervicofacial nonmelanoma skin cancer. To date, only the original English version has been published. OBJECTIVES: To develop a Spanish version of the SCI that is semantically and linguistically equivalent to the original, and to evaluate its measurement properties in this different cultural environment. MATERIAL AND METHODS: A cross-sectional study was conducted of the cultural adaptation and empirical validation of the questionnaire, analysing the psychometric properties of the new index at different stages. RESULTS: Of 440 patients recruited to the study, 431 (95%) completed the Spanish version of the SCI questionnaire, in a mean time of 6·3 min (SD 2·9). Factor analysis of the scale revealed commonality and loading values of < 0·5 for three of the 15 items. The remaining 12 items converged into two components: appearance/social aspects (seven items) and emotional aspects (five items). Both domains presented a high level of internal consistency, with Cronbach's alpha values above 0·8. The convergent-discriminant validity analysis produced correlations higher than 0·3 for the mental component of the Short Form Health Survey-12v2 Health Questionnaire (correlation coefficient 0·39) and the Dermatology Quality of Life Index (correlation coefficient -0·30). In the test-retest, nine of the 12 items produced a weighted kappa value exceeding 0·4, and for the remaining three items, the absolute agreement percentage exceeded 60%. CONCLUSIONS: The Spanish version of the SCI quality of life scale has been satisfactorily adapted and validated for use in Spanish-speaking countries and populations.

The usefulness of high-resolution ultrasound in detecting invasive disease in recurrent basal cell carcinoma after nonsurgical treatment.

INTRODUCTION AND OBJECTIVES: Accurate subtyping of basal cell carcinoma (BCC) is crucial for the effective management of this disease and it is particularly important to distinguish between aggressive and nonaggressive histologic variants. Histologic subtype is not always accurately identified by biopsy and this can have serious implications. High-resolution ultrasound (HRUS) is a recent technique that has proven to be of value in differentiating between variants of BCC. The aim of this study was to investigate the potential usefulness of HRUS for detecting invasive disease in recurrent BCC treated nonsurgically following an initial diagnosis of noninvasive BCC by biopsy. MATERIAL AND METHODS: This was a prospective observational study of consecutive cases of BCC with clinical suspicion of recurrence following nonsurgical treatment and a pretreatment diagnosis of superficial BCC by punch biopsy. Before surgical excision, the recurrent lesions were evaluated by HRUS followed by a punch biopsy of the site of suspected recurrence. The diagnostic agreement between HRUS, punch biopsy, and excisional biopsy was then evaluated. RESULTS: Eight lesions were studied. HRUS identified invasive disease in 3 of the 4 cases that were incorrectly classified as superficial subtypes by punch biopsy. CONCLUSION: HRUS could be useful for detecting persistent tumor after nonsurgical treatment and for choosing the site most likely to harbor invasive disease for punch biopsy.

[Orbital neurenteric cyst. A case report and review of the literature]. / Kystes neurentériques de l'orbite. À propos d'un cas et revue de la littérature.

INTRODUCTION: Neurenteric cysts defined as a cyst lined by endodermal-type epithelium are extremely rare. We report a rare case of an orbital neurenteric cyst. CASE REPORT: A 19-year-old female presented with an orbital cyst tumor that had cosmetic consequences. The signal of the cyst was not enhanced after administration of gadolinium on MRI examination. The patient underwent surgery due to the increase in size of the tumor. A complete cyst removal including the cyst wall through the inferior palpebral fold was performed. The histological examination confirmed the diagnostic of neurenteric cyst. The patient was discharged home in excellent condition. CONCLUSION: This report discusses the clinical presentation, neuroradiological aspect, pathological findings and therapeutic consideration of the neurenteric cyst. We described a rare case of orbital neurenteric cyst. Due to the local recurrence rate observed after partial resection, the goal of the surgery should be a total resection of the cyst with the cyst wall.

Resveratrol and its metabolites bind to PPARs.

Resveratrol, a modulator of several signaling proteins, can exert off-target effects involving the peroxisome proliferator-activated receptor (PPAR) transcription factors. However, evidence for the direct interaction between this polyphenol and PPARs is lacking. Here, we addressed the hypothesis that resveratrol and its metabolites control aspects of PPAR transcriptional activity through direct interaction with PPARs. Bioaffinity chromatographic studies with the immobilized ligand-binding domains (LBDs) of PPARγ and PPARα and isothermal titration calorimetry allowed the binding affinities of resveratrol, resveratrol 3-O-glucuronide, resveratrol 4-O-glucuronide, and resveratrol 3-O-sulfate to both PPAR-LBDs to be determined. Interaction of resveratrol, resveratrol 3-O-glucuronide, and resveratrol 4-O-glucuronide with PPARγ-LBD occurred with binding affinities of 1.4, 1.1, and 0.8 µM, respectively, although only resveratrol bound to the PPARα-LBD with a binding affinity of 2.7 µM. Subsequently, X-ray crystallographic studies were carried out to characterize resveratrol binding to the PPARγ-LBD at the molecular level. The electron density map from the crystal structure of the complex between PPARγ-LBD and resveratrol revealed the presence of one molecule of resveratrol bound to the LBD of PPARγ, with the ligand occupying a position close to that of other known PPARγ ligands. Transactivation assays were also performed in HepG2 cells, with the results showing that resveratrol was not a PPAR agonist but instead was able to displace rosiglitazone from PPARγ and Wy-14643 from PPARα with IC50 values of (27.4±1.8) µM and (31.7±2.5) µM, respectively. We propose that resveratrol acts as a PPAR antagonist through its direct interaction with PPARγ and PPARα.

Local reference levels and organ doses from pediatric cardiac interventional procedures.

Interventional cardiology (IC) procedures can be responsible for relatively high radiation doses compared to conventional radiology especially for young patients. The aim of this study was to assess current exposure levels in a French reference centre of pediatric IC. Dosimetric data including dose area product (DAP), fluoroscopy time (FT) and number of cine frame (NF) were analysed taking into account patient weight. Doses to the lungs, esophagus, breast and thyroid were evaluated using anthropomorphic phantoms and thermoluminescent dosimeters. Finally, effective doses (E) were calculated using DAP and conversion factors calculated with PCXMC 2.0 software. 801 IC procedures performed between 2010 and 2011 were analysed. Large variations were observed for DAP, FT and NF values for a given procedure and a given weight group. The assessment of organ doses showed high levels of dose to the lungs and esophagus especially in new-born babies. For diagnostic procedures, E varied from 0.3 to 23 mSv with a mean value of 4.8 mSv and for therapeutic procedures, values ranged from 0.1 to 48.4 mSv with a mean value of 7.3 mSv. The highest values were recorded for angioplasty procedures (mean 13 mSv, range 0.6-48.4 mSv). The increasing use of IC in pediatric population stresses the need of setting up reference levels and keeping doses to children as low as possible.