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1.
Clin Radiol ; 78(5): e425-e432, 2023 05.
Article de Anglais | MEDLINE | ID: mdl-36849278

RÉSUMÉ

AIM: To evaluate the Prostate Imaging Reporting and Data System, version 2.1 (PIRADS V2.1) criteria for seminal vesicle invasion (SVI) and examine whether the timing of last ejaculation influences the detection of SVI. MATERIALS AND METHODS: The study population consisted of 68 patients (34 with SVI, 34 without SVI, matching groups by age and prostate volume) who underwent PIRADS V2.1-compliant multiparametric magnetic resonance imaging (MRI; 34 at 1.5 T, 34 at 3 T). Before the examination, the time of last ejaculation (38/68 ≤ 5 days, 30/68 > 5 days) was collected via a questionnaire. The five PIRADS V2.1 criteria for SVI with subsequent overall assessment were evaluated retrospectively by two independent examiners (examiner 1 with >10 years of experience, examiner 2 with 6 months of experience) in a single-blinded fashion for all patients using a questionnaire and a six-point scale (0 = no, 1 = very likely not, 2 = probably not, 3 = possible, 4 = probable, 5 = certain). RESULTS: E1 achieved high specificity (100%) and positive predictive value (PPV; 100%) in the overall assessment, independent of the time of last ejaculation (sensitivity = 76.5%, negative predictive value [NPV] = 81%). The area under the curve (AUC) value was 0.882; for E2, it was 0.765. At ≤5 days, the AUC values of E1 and E2 differed significantly (0.867 versus 0.681, p=0.016), as did the diffusion restriction criterion (0.833 versus 0.681, p=0.028). E1 showed high AUC values independent of time. E2 had better values for all criteria at >5 days than at ≤5 days. There were no significant differences between the examiners in all observations at >5 days. CONCLUSION: The PIRADS V2.1 criteria are well suited for an experienced examiner to detect SVI independent of time point. An inexperienced examiner will benefit from patients being abstinent >5 days prior to MRI.


Sujet(s)
Prostate , Tumeurs de la prostate , Mâle , Humains , Prostate/imagerie diagnostique , Prostate/anatomopathologie , Vésicules séminales/imagerie diagnostique , Études rétrospectives , Éjaculation , Tumeurs de la prostate/anatomopathologie , Invasion tumorale/anatomopathologie , Imagerie par résonance magnétique/méthodes , Stadification tumorale
2.
Phys Rev Lett ; 129(3): 030603, 2022 Jul 15.
Article de Anglais | MEDLINE | ID: mdl-35905355

RÉSUMÉ

Modeling noisy oscillations of active systems is one of the current challenges in physics and biology. Because the physical mechanisms of such processes are often difficult to identify, we propose a linear stochastic model driven by a non-Markovian bistable noise that is capable of generating self-sustained periodic oscillation. We derive analytical predictions for most relevant dynamical and thermodynamic properties of the model. This minimal model turns out to describe accurately bistablelike oscillatory motion of hair bundles in bullfrog sacculus, extracted from experimental data. Based on and in agreement with these data, we estimate the power required to sustain such active oscillations to be of the order of 100 k_{B}T per oscillation cycle.


Sujet(s)
Cellules ciliées auditives , Physique , Animaux , Modèles linéaires , Rana catesbeiana
4.
Arch Toxicol ; 95(10): 3143-3159, 2021 10.
Article de Anglais | MEDLINE | ID: mdl-34091723

RÉSUMÉ

Several N-vinyl compounds are produced in high volumes and are widely employed in the production of copolymers and polymers used in chemical, pharmaceutical, cosmetic and food industry. Hence, information on their genotoxicity and carcinogenicity is requisite. This review presents hitherto available information on the carcinogenicity and genotoxicity of N-vinyl compounds as well as their metabolism potentially generating genotoxic and carcinogenic derivatives. The genotoxicity and carcinogenicity of the investigated N-vinyl compounds vary widely from no observed carcinogenicity tested in lifetime bioassays in two rodent species (up to very high doses) to carcinogenicity in rats at very low doses in the absence of apparent genotoxicity. Despite of the presence of the vinyl group potentially metabolized to an epoxide followed by covalent binding to DNA, genotoxicity was observed for only one of the considered N-vinyl compounds, N-vinyl carbazole. Carcinogenicity was investigated only for two, of which one, N-vinyl pyrrolidone was carcinogenic (but not genotoxic) and ranitidine was neither carcinogenic nor genotoxic. As far as investigated, neither a metabolically formed epoxide nor a therefrom derived diol has been reported for any of the considered N-vinyl compounds. It is concluded that the information collected in this review will further the understanding of the carcinogenic potentials of N-vinyl compounds and may eventually allow approaching their prediction and prevention. A suggestion how to prevent genotoxicity in designing of N-vinyl compounds is presented. However, the available information is scarce and further research especially on the metabolism of N-vinyl compounds is highly desirable.


Sujet(s)
Cancérogènes/toxicité , Altération de l'ADN/effets des médicaments et des substances chimiques , Composés vinyliques/toxicité , Animaux , Tests de cancérogénicité , Cancérogènes/composition chimique , Humains , Souris , Tests de mutagénicité , Rats , Composés vinyliques/composition chimique
5.
J Cardiovasc Magn Reson ; 23(1): 15, 2021 03 01.
Article de Anglais | MEDLINE | ID: mdl-33641670

RÉSUMÉ

BACKGROUND: Circulatory efficiency reflects the ratio between total left ventricular work and the work required for maintaining cardiovascular circulation. The effect of severe aortic valve stenosis (AS) and aortic valve replacement (AVR) on left ventricular/circulatory mechanical power and efficiency is not yet fully understood. We aimed to quantify left ventricular (LV) efficiency in patients with severe AS before and after surgical AVR. METHODS: Circulatory efficiency was computed from cardiovascular magnetic resonance (CMR) imaging derived volumetric data, echocardiographic and clinical data in patients with severe AS (n = 41) before and 4 months after AVR and in age and sex-matched healthy subjects (n = 10). RESULTS: In patients with AS circulatory efficiency was significantly decreased compared to healthy subjects (9 ± 3% vs 12 ± 2%; p = 0.004). There were significant negative correlations between circulatory efficiency and LV myocardial mass (r = - 0.591, p < 0.001), myocardial fibrosis volume (r = - 0.427, p = 0.015), end systolic volume (r = - 0.609, p < 0.001) and NT-proBNP (r = - 0.444, p = 0.009) and significant positive correlation between circulatory efficiency and LV ejection fraction (r = 0.704, p < 0.001). After AVR, circulatory efficiency increased significantly in the total cohort (9 ± 3 vs 13 ± 5%; p < 0.001). However, in 10/41 (24%) patients, circulatory efficiency remained below 10% after AVR and, thus, did not restore to normal values. These patients also showed less reduction in myocardial fibrosis volume compared to patients with restored circulatory efficiency after AVR. CONCLUSION: In our cohort, circulatory efficiency is reduced in patients with severe AS. In 76% of cases, AVR leads to normalization of circulatory efficiency. However, in 24% of patients, circulatory efficiency remained below normal values even after successful AVR. In these patients also less regression of myocardial fibrosis volume was seen. Trial Registration clinicaltrials.gov NCT03172338, June 1, 2017, retrospectively registered.


Sujet(s)
Sténose aortique/chirurgie , Valve aortique/chirurgie , Implantation de valve prothétique cardiaque , Fonction ventriculaire gauche , Sujet âgé , Valve aortique/imagerie diagnostique , Valve aortique/physiopathologie , Sténose aortique/imagerie diagnostique , Sténose aortique/physiopathologie , Études cas-témoins , Échocardiographie-doppler , Femelle , Fibrose , Prothèse valvulaire cardiaque , Implantation de valve prothétique cardiaque/effets indésirables , Implantation de valve prothétique cardiaque/instrumentation , Humains , IRM dynamique , Mâle , Adulte d'âge moyen , Myocarde/anatomopathologie , Récupération fonctionnelle , Indice de gravité de la maladie , Facteurs temps , Résultat thérapeutique , Remodelage ventriculaire
6.
J Robot Surg ; 15(4): 571-577, 2021 Aug.
Article de Anglais | MEDLINE | ID: mdl-32885379

RÉSUMÉ

Partial nephrectomy (PN) for small renal masses is common, but outcomes are not reported in a standard manner. Traditionally, parameters such as 90-day mortality, blood loss, transfusion rates, length of stay, nephrometry scoring and complications are published but their collective impact on warm ischemia time (WIT) and post-surgery GFR is rarely determined. Thus, our aim was to assess if "Trifecta" and "Pentafecta" outcomes could be used as useful surgical outcome markers. A prospective database of 252 Robotic-Assisted PN (RAPN) cases (2008-2019) was analysed. "Pentafecta" was defined as achievement of "Trifecta" (negative surgical margin, no postoperative complications and WIT of < 25 min) plus over 90% estimated GFR preservation and no CKD stage upgrading at 1 year. Binary logistic regression analysis was conducted to predict factors which may prevent achieving a Trifecta/Pentafecta. Median tumour size was 3 cm and mean WIT was 15 min. Positive surgical margins (PSM) occurred in 2 cases. Overall, the intra-operative complication rate was 7%. One recurrence conferred 5-year cancer-free survival of 97%. Trifecta outcome was achieved in 169 (67%) and Pentafecta in 141 (56%) of cases. At logistic regression analysis, intraoperative blood loss was the only factor to affect Trifecta achievement (p = 0.018). Advanced patient age negatively impacted Pentafecta achievement (p = 0.010). The Trifecta and Pentafecta outcomes are easily applicable to PN data, and offer an internationally comparable PN outcome, quality measure. We recommend applying this standardization to national data collection to improve the quality of reporting and ease of interpretation of surgeon/centres' outcomes.


Sujet(s)
Tumeurs du rein , Interventions chirurgicales robotisées , Humains , Tumeurs du rein/chirurgie , Récidive tumorale locale , Néphrectomie , Normes de référence , Études rétrospectives , Interventions chirurgicales robotisées/méthodes , Résultat thérapeutique
7.
Pediatr Cardiol ; 42(1): 78-88, 2021 Jan.
Article de Anglais | MEDLINE | ID: mdl-33009919

RÉSUMÉ

Interventional closure of congenital ventricular septal defects (VSD) is recording a continuous rise in acceptance. Complete atrioventricular block (cAVB) and residual shunting are major concerns during follow-up, but long-term data for both are still limited. We retrospectively evaluated the outcome of patients with interventional VSD closure and focused on long-term results (> 1 year follow-up). Transcatheter VSD closures were performed between 1993 and 2015, in 149 patients requiring 155 procedures (104 perimembranous, 29 muscular, 19 residual post-surgical VSDs, and 3 with multiple defects). The following devices were used: 65 × Amplatzer™ Membranous VSD Occluder, 33 × Duct Occluder II, 27 × Muscular VSD Occluder, 3 × Duct Occluder I, 24 × PFM-Nit-Occlud®, and 3 × Rashkind-Occluder. The median age at time of implantation was 6.2 (0.01-66.1) years, median height 117 (49-188) cm, and median weight 20.9 (3.2-117) kg. Median follow-up time was 6.2 (1.1-21.3) years and closure rate was 86.2% at last follow-up. Complications resulting in device explantation include one case of cAVB with a Membranous VSD occluder 7 days after implantation and four cases due to residual shunt/malposition. Six (4%) deaths occurred during follow-up with only one procedural related death from a hybrid VSD closure. Overall, our reported results of interventional VSD closure show favorable outcomes with only one (0.7%) episode of cAVB. Interventional closure offers a good alternative to surgical closure and shows improved performance by using softer devices. However, prospective long-term data in the current era with different devices are still mandatory to assess the effectiveness and safety of this procedure.


Sujet(s)
Procédures de chirurgie cardiaque/méthodes , Communications interventriculaires/chirurgie , Adolescent , Adulte , Sujet âgé , Troubles du rythme cardiaque/épidémiologie , Bloc atrioventriculaire/épidémiologie , Cathétérisme cardiaque/méthodes , Enfant , Enfant d'âge préscolaire , Femelle , Études de suivi , Communications interventriculaires/mortalité , Implantation de valve prothétique cardiaque/méthodes , Humains , Nourrisson , Mâle , Adulte d'âge moyen , Complications postopératoires/épidémiologie , Études rétrospectives , Résultat thérapeutique , Jeune adulte
8.
Rev. Hosp. Clin. Univ. Chile ; 32(3): 244-255, 2021. graf
Article de Espagnol | LILACS | ID: biblio-1348528

RÉSUMÉ

Acute pancreatitis is a prevalent disease, with variable clinical course: several patients recover quickly and uneventfully, while others require treatment in critical care units with long hospital stay and even with a considerable mortality. The patient's symptoms, laboratory tests and radiological images allow diagnosis without major difficulties. However, early identification of more severe cases can be difficult, and it determines the adequate selection of the hospitalization unit and the quick initiation of the appropriate therapy. In this paper we give some practical treatment guidelines for the everyday clinical practice: immediate severity stratification, fluid replacement and pain control. Early enteral nutrition, monitorization of severe cases in critical care units, adequate therapeutic but no prophylactic use of antibiotics assures the best treatment results. (AU)


Sujet(s)
Humains , Mâle , Femelle , Adulte , Adulte d'âge moyen , Pancréatite/diagnostic , Pancréatite/thérapie , Pancréatite/classification , Pancréatite/complications
9.
Neth Heart J ; 28(7-8): 418-423, 2020 Jul.
Article de Anglais | MEDLINE | ID: mdl-32648153

RÉSUMÉ

BACKGROUND: Chloroquine, a quinolone antimalarial drug, is known to potentially inhibit pH-dependent viral replication of the SARS-CoV­2 infection. Therefore, chloroquine is considered as a treatment option for coronavirus disease 2019 (COVID-19). Chloroquine is known for prolonging the QT interval, but limited data are available on the extent of this QT-prolonging effect. OBJECTIVE: To assess the QTc-prolonging potential of chloroquine in COVID-19 patients and to evaluate whether this prolongation increases with the cumulative dose of chloroquine and is associated with the peak plasma concentration of chloroquine. Furthermore, the number of patients who prematurely discontinued treatment or had an adjustment in dose due to QTc-interval prolongation was established. METHODS: A retrospective, observational study was performed in patients aged over 18 years, hospitalised for a suspected or proven infection with COVID-19, and therefore treated with chloroquine, with a baseline electrocardiogram (ECG) performed prior to the start of treatment and at least one ECG after starting the treatment. RESULTS: In total, 397 patients were included. The mean increase in QTc interval throughout the treatment with chloroquine was 33 ms. Nineteen out of 344 patients unnecessarily had their treatment prematurely discontinued or adjusted due to a prolonged QTc interval based on the computerised interpretation of the ECG. CONCLUSION: Chloroquine treatment in COVID-19 patients gradually increased the QTc interval. Due to a significant number of overestimated QTc intervals by computer analysis, it is advisable to measure the QTc interval manually before adjusting the dose or withdrawing this potentially beneficial medication.

10.
Regul Toxicol Pharmacol ; 108: 104442, 2019 Nov.
Article de Anglais | MEDLINE | ID: mdl-31421187

RÉSUMÉ

Read-across and grouping is one of the most commonly used alternative approaches for data gap filling in registrations submitted under the REACH Regulation as defined by the European Chemicals Agency (ECHA) in their 'Read-Across Assessment Framework' (RAAF, 2017). At the same time, the application of read-across is rejected by ECHA frequently due to various reasons. As a major reason hereof, applicants fail to reduce the level of 'remaining uncertainty' intrinsical to every read-across approach compared to testing a substance experimentally. Recently, the use of metabolomics to support read-across cases with biological information has been reported in a case study with phenoxy herbicides (Ravenzwaay et al., 2016). In the present case-study a 'weight-of-evidence' read-across approach from 2-aminoethanol (MEA = 'source') to 3-aminopropanol (3AP = 'target') with metabolomics as 'supporting evidence' reducing the remaining uncertainties is reported. We demonstrate the high structural similarity of the two analogous substances based on the available data and we report how metabolome data add confidence concerning mechanistic similarity in this read-across approach. Finally, the herein described read-across case supported by metabolomics is used to cover the data gaps in repeated dose and reproductive toxicity endpoint of 3AP via weight of evidence for the REACH-registration.


Sujet(s)
Éthanolamine/toxicité , Métabolome/effets des médicaments et des substances chimiques , Propanolamines/toxicité , Animaux , Femelle , Mâle , Métabolomique , Rat Wistar , Appréciation des risques , Tests de toxicité
11.
Oncoimmunology ; 8(9): e1624130, 2019.
Article de Anglais | MEDLINE | ID: mdl-31428522

RÉSUMÉ

A diversity of T helper (Th) subsets (Th1, Th2, Th17) has been identified in the human tumor microenvironment. In breast cancer, the role of Th subsets remains controversial, and a systematic study integrating Th subset diversity, T cell inflammation, breast cancer molecular subtypes, and patient prognosis, is lacking. In primary untreated breast cancer samples, we analyzed 19 Th cytokines at the protein level. Eight were T cell-specific, and subsequently measured in 106 prospectively-collected untreated samples. The dominant Th cytokines across all breast cancer samples were IFN-γ and IL-2. Th2 cytokines (IL-4, IL-5, IL-13) were expressed at low levels and not associated with any breast cancer subtype. Th17 cytokines (IL-17A and IL-17F) were up-regulated in triple negative breast cancer (TNBC), specifically in T cell non-inflamed tumors. In order to get insight into prognosis, we exploited the METABRIC transcriptomic dataset. We derived Th1, Th2, and Th17 metagenes based on manually curated Th signatures, and found that a high Th17 metagene was of good prognosis in T cell non-inflamed TNBC. Multivariate Cox modeling selected the Nottingham Prognostic Index (NPI), Th2 and Th17 metagenes as additive predictors of breast cancer-specific survival, which defined novel and highly distinct prognostic groups within TNBC. Our results reveal that Th17 is a novel prognostic composite biomarker in T cell non-inflamed TNBC. Integrating immune cell and tumor molecular diversity is an efficient strategy for prognostic stratification of cancer patients.

12.
Sci Rep ; 9(1): 3327, 2019 Feb 26.
Article de Anglais | MEDLINE | ID: mdl-30804387

RÉSUMÉ

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

13.
Curr Microbiol ; 76(4): 520-526, 2019 Apr.
Article de Anglais | MEDLINE | ID: mdl-30805700

RÉSUMÉ

Clostridium (Clostridioides) difficile ribotype 027 (RT027) was detected in Germany for the first time in 2007 during an outbreak in the region of Trier, Rhineland-Palatinate and is today the most prevalent ribotype (RT) in Europe. We aimed to determine the changes in RT distribution and corresponding antimicrobial resistance in clinical C. difficile isolates between two time points (2007 and 2017) in one tertiary care hospital in Germany. C. difficile isolates recovered in 2007 and in 2017 (80 isolates per year, respectively) from patients at a Tertiary Care University Hospital in North-Rhine Westphalia were analyzed. Isolates were characterized by ribotyping and susceptibility testing using gradient tests (metronidazole, vancomycin) and the disk diffusion method (moxifloxacin). Between 2007 and 2017, a clear switch from RT001 [18.75% (n = 15) in 2007 versus 3.75% (n = 3) in 2017 P = 0.003] to RT027 [0% in 2007 versus 21.25% (n = 17) in 2017] was evident. While minimal inhibitory concentrations (MICs) of vancomycin were stable, a significant metronidazole MIC creep was determined (MIC50 = 0.047 in 2007 versus MIC50 = 0.094 in 2017, P < 0.0001 using the Man-Whitney test). We detected one metronidazole-resistant isolate (0.6%). Interestingly, in total we encountered more isolates resistant to moxifloxacin in 2007 (42 (52.25%) than in 2017 [(30 (37.5%), P = 0.06)]). We could demonstrate that RT027 replaced RT001 in the last 10 years in our hospital. Furthermore, our data show a metronidazole MIC creep in C. difficile isolates over the last 10 years and an unexpected decrease of isolates resistant to moxifloxacin.


Sujet(s)
Antibactériens/pharmacologie , Clostridioides difficile/effets des médicaments et des substances chimiques , Clostridioides difficile/génétique , Infections à Clostridium/microbiologie , Résistance bactérienne aux médicaments , Ribotypage/statistiques et données numériques , Clostridioides difficile/classification , Clostridioides difficile/isolement et purification , Infections à Clostridium/épidémiologie , Surveillance épidémiologique , Fèces/microbiologie , Allemagne/épidémiologie , Humains , Métronidazole/pharmacologie , Tests de sensibilité microbienne , Moxifloxacine/pharmacologie , Ribotypage/tendances , Centres de soins tertiaires , Vancomycine/pharmacologie
14.
Clin Res Cardiol ; 108(6): 683-690, 2019 Jun.
Article de Anglais | MEDLINE | ID: mdl-30519781

RÉSUMÉ

BACKGROUND: As there are limited data about the clinical practice of catheter ablation in asymptomatic children and adolescents with ventricular preexcitation on ECG, we performed the multicenter "CASPED" (Catheter ablation in ASymptomatic PEDiatric patients with Ventricular Preexcitation) study. METHODS AND RESULTS: In 182 consecutive children and adolescents aged between 8 and 18 years (mean age 12.9 ± 2.6 years; 65% male) with asymptomatic ventricular preexcitation, a total of 196 accessory pathways (APs) were targeted. APs were right sided (62%) or left sided (38%). The most common right-sided AP location was the posteroseptal region (38%). Ablation was performed using radiofrequency (RF) energy (93%), cryoablation (4%) or both (3%). Mean procedure time was 137.6 ± 62.0 min with a mean fluoroscopy time of 15.6 ± 13.8 min. A 3D mapping or catheter localization system was used in 32% of patients. Catheter ablation was acutely successful in 166/182 patients (91.2%). Mortality was 0% and there were no major periprocedural complications. AP recurrence was observed in 14/166 patients (8.4%) during a mean follow-up time of 19.7 ± 8.5 months. A second ablation attempt was performed in 20 patients and was successful in 16/20 patients (80%). Overall, long-term success rate was 92.3%. CONCLUSION: In this retrospective multicenter study, the outcome of catheter ablation for asymptomatic preexcitation in children and adolescents irrespective of antegrade AP conduction properties is summarized. The complication rate was low and success rate was high, the latter mainly depending on pathway location. The promising results of the study may have future impact on the ongoing risk-benefit discussion regarding catheter ablation in the setting of asymptomatic preexcitation in children and adolescents.


Sujet(s)
Faisceau accessoire atrioventriculaire , Ablation par cathéter , Cryochirurgie , Syndrome de Wolff-Parkinson-White/chirurgie , Potentiels d'action , Adolescent , Facteurs âges , Maladies asymptomatiques , Ablation par cathéter/effets indésirables , Ablation par cathéter/mortalité , Enfant , Cryochirurgie/effets indésirables , Cryochirurgie/mortalité , Femelle , Allemagne , Rythme cardiaque , Humains , Mâle , Récidive , Études rétrospectives , Facteurs de risque , Suisse , Facteurs temps , Résultat thérapeutique , Syndrome de Wolff-Parkinson-White/diagnostic , Syndrome de Wolff-Parkinson-White/mortalité , Syndrome de Wolff-Parkinson-White/physiopathologie
15.
Can Assoc Radiol J ; 69(1): 38-50, 2018 Feb.
Article de Anglais | MEDLINE | ID: mdl-29458954

RÉSUMÉ

Hepatopancreaticobiliary tumours are often diagnosed at an advanced disease stage, in which encasement or invasion of local biliary or vascular structures has already occurred. Irreversible electroporation (IRE) is an image-guided tumour ablation technique that induces cell death by exposing the tumour to high-voltage electrical pulses. The cellular membrane is disrupted, while sparing the extracellular matrix of critical tubular structures. The preservation of tissue integrity makes IRE an attractive treatment option for tumours in the vicinity of vital structures such as splanchnic blood vessels and major bile ducts. This article reviews current data and discusses future trends of IRE for hepatopancreaticobiliary tumours.


Sujet(s)
Techniques d'ablation/méthodes , Électroporation/méthodes , Tumeurs du foie/chirurgie , Tumeurs du pancréas/chirurgie , Humains , Foie/chirurgie , Pancréas/chirurgie
16.
Eur J Cancer ; 91: 47-55, 2018 03.
Article de Anglais | MEDLINE | ID: mdl-29331751

RÉSUMÉ

BACKGROUND: We aimed at identifying deleterious genomic alterations from untreated head and neck squamous cell carcinoma (HNSCC) patients, and assessing their prognostic value. PATIENTS AND METHODS: We retrieved 122 HNSCC patients who underwent primary surgery. Targeted NGS was used to analyse a panel of 100 genes selected among the most frequently altered genes in HNSCC and potential therapeutic targets. We selected only deleterious (activating or inactivating) single nucleotide variations, and copy number variations for analysis. Univariate and multivariate analyses were performed to assess the prognostic value of altered genes. RESULTS: A median of 2 (range: 0-10) genomic alterations per sample was observed. Most frequently altered genes involved the cell cycle pathway (TP53 [60%], CCND1 [30%], CDKN2A [25%]), the PI3K/AKT/MTOR pathway (PIK3CA [12%]), tyrosine kinase receptors (EGFR [9%], FGFR1 [5%]) and cell differentiation (FAT1 [7%], NOTCH1 [4%]). TP53 mutations (p = 0.003), CCND1 amplifications (p = 0.04), CDKN2A alterations (p = 0.02) and FGFR1 amplifications (p = 0.003), correlated with shorter overall survival (OS). The number of genomic alterations was significantly higher in the HPV-negative population (p = 0.029) and correlated with a shorter OS (p < 0.0001). Only TP53 mutation and FGFR1 amplification status remained statistically significant in the multivariate analysis. CONCLUSION: These results suggest that genomic alterations involving the cell cycle (TP53, CCND1, CDKN2A), as well as FGFR1 amplifications and tumour genomic alterations burden are prognostic biomarkers and might be therapeutic targets for patients with HNSCC.


Sujet(s)
Marqueurs biologiques tumoraux/génétique , Carcinome épidermoïde/génétique , Amplification de gène , Analyse de profil d'expression de gènes/méthodes , Tumeurs de la tête et du cou/génétique , Récepteur FGFR1/génétique , Transcriptome , Adulte , Sujet âgé , Carcinome épidermoïde/mortalité , Carcinome épidermoïde/anatomopathologie , Carcinome épidermoïde/chirurgie , Loi du khi-deux , Cycline D1/génétique , Inhibiteur p16 de kinase cycline-dépendante , Inhibiteur p18 de kinase cycline-dépendante/génétique , Variations de nombre de copies de segment d'ADN , Femelle , Prédisposition génétique à une maladie , Tumeurs de la tête et du cou/mortalité , Tumeurs de la tête et du cou/anatomopathologie , Tumeurs de la tête et du cou/chirurgie , Séquençage nucléotidique à haut débit , Humains , Estimation de Kaplan-Meier , Mâle , Adulte d'âge moyen , Analyse multifactorielle , Phénotype , Polymorphisme de nucléotide simple , Valeur prédictive des tests , Modèles des risques proportionnels , Études rétrospectives , Facteurs de risque , Carcinome épidermoïde de la tête et du cou , Facteurs temps , Résultat thérapeutique , Protéine p53 suppresseur de tumeur/génétique , Jeune adulte
17.
Appl Clin Inform ; 9(1): 54-61, 2018 01.
Article de Anglais | MEDLINE | ID: mdl-29365340

RÉSUMÉ

BACKGROUND: In 2015, the German Federal Ministry of Education and Research initiated a large data integration and data sharing research initiative to improve the reuse of data from patient care and translational research. The Observational Medical Outcomes Partnership (OMOP) common data model and the Observational Health Data Sciences and Informatics (OHDSI) tools could be used as a core element in this initiative for harmonizing the terminologies used as well as facilitating the federation of research analyses across institutions. OBJECTIVE: To realize an OMOP/OHDSI-based pilot implementation within a consortium of eight German university hospitals, evaluate the applicability to support data harmonization and sharing among them, and identify potential enhancement requirements. METHODS: The vocabularies and terminological mapping required for importing the fact data were prepared, and the process for importing the data from the source files was designed. For eight German university hospitals, a virtual machine preconfigured with the OMOP database and the OHDSI tools as well as the jobs to import the data and conduct the analysis was provided. Last, a federated/distributed query to test the approach was executed. RESULTS: While the mapping of ICD-10 German Modification succeeded with a rate of 98.8% of all terms for diagnoses, the procedures could not be mapped and hence an extension to the OMOP standard terminologies had to be made.Overall, the data of 3 million inpatients with approximately 26 million conditions, 21 million procedures, and 23 million observations have been imported.A federated query to identify a cohort of colorectal cancer patients was successfully executed and yielded 16,701 patient cases visualized in a Sunburst plot. CONCLUSION: OMOP/OHDSI is a viable open source solution for data integration in a German research consortium. Once the terminology problems can be solved, researchers can build on an active community for further development.


Sujet(s)
Comportement coopératif , Mise en oeuvre des programmes de santé , Hôpitaux universitaires , , Allemagne , Humains , Enquêtes et questionnaires , Vocabulaire
18.
Gastroenterol. latinoam ; 29(1): 9-15, 2018. tab, graf
Article de Espagnol | LILACS | ID: biblio-1116687

RÉSUMÉ

Background: Atrophic gastritis (AG) and intestinal metaplasia (IM) are stages that appear in the process of gastric carcinogenesis. Their presence requires programmed endoscopic vigilance. Objectives: To determine the frequency of AG and IM in gastric biopsies (GB) taken according to Sydney Protocol and to correlate them with endoscopic findings. Methods: Retrospective descriptive analysis of 233 upper gastrointestinal endoscopies with GB per Sydney Protocol. OLGA (Operative Link for Gastritis Assessment) and OLGIM (Operative Link for Gastric Intestinal Metaplasia Assessment) scores were calculated based on the GB description. Endoscopic findings were analyzed for atypical findings and compared to the GB report. Statistic analysis for Kappa and ANOVA was performed via Stata 12. Results: Mean age of patients was 58 ± 12 years. 69% were women. The frequency of AG and IM was 44% and 33% in the antrum, 31% and 20% in the angular incisure and 14% and 9% in the body, respectively. AG and IM were more frequent in the antrum (p < 0.05). AG and IM were more severe in the angular incisure and body (p < 0.05). We were unable to calculate OLGA and OLGIM in 6% and 9% of cases, respectively, due to absence of severity description in GB. 53% were OLGA 0, 42% OLGA I-II and 5% OLGA III-IV. 70% were OLGIM 0, 25% OLGIM I-II and 5% OLGIM III-IV. Agreement between endoscopic and histological findings was best for IM in the antrum (75.5%, Kappa 0.4). Sensitivity and specificity of endoscopic findings were 39% and 70% for AG, and 30% and 85% for IM, respectively. Conclusion: AG and IM are frequent findings in our patients. Due to the low endoscopic sensitivity for AG and IM, we suggest a systematic GB sampling using Sydney Protocol in patients over 40 years old.


Introducción: La gastritis crónica atrófica (GCA) y la metaplasia intestinal (MI) son etapas en el proceso de carcinogénesis gástrica, su presencia requiere control endoscópico programado. Objetivos: Determinar la frecuencia de GCA y MI en biopsias gástricas (BG) por protocolo de Sydney y relacionarlas con el hallazgo endoscópico. Métodos: Estudio descriptivo mediante revisión de 233 endoscopias digestivas altas con BG por Protocolo Sydney. Se graduó puntaje OLGA (Operative Link for Gastritis Assessment) y OLGIM (Operative Link for Gastric Intestinal Metaplasia Assessment) según la descripción de la BG. Se definió el hallazgo endoscópico según su informe y se comparó con BG como patrón de referencia. Estadística: Stata 12 para Kappa y ANOVA. Resultados: Edad promedio 58 ± 12 años, 69% mujeres. La frecuencia de GCA y MI en antro fue de 44 y 33%, en ángulo 31 y 20% y en cuerpo 14 y 9%, respectivamente. Hubo mayor frecuencia de GCA y MI en antro (p < 0,05). La graduación de GCA y MI fue mayor en ángulo y cuerpo (p < 0,05). No se obtuvo OLGA en 6% y OLGIM en 9% por ausencia de graduación. La frecuencia de OLGA 0 fue de 53%, OLGA I-II 42%, OLGA III-IV 5%, OLGIM O 70%, OLGIM I-II 25% y OLGIM III-IV 5%. La mejor correlación se observó entre la MI antral endoscópica con la histológica (75,5%, Kappa 0,4). La sensibilidad y especificidad endoscópica fue de 39 y 70% para GCA y 30 y 85% para MI. Conclusión: GCA y MI son hallazgos frecuentes en nuestros pacientes. Por la baja sensibilidad endoscópica en la identificación de GCA y MI sugerimos la toma sistemática de BG por protocolo de Sydney en pacientes mayores de 40 años.


Sujet(s)
Humains , Mâle , Femelle , Adolescent , Adulte , Adulte d'âge moyen , Sujet âgé , Sujet âgé de 80 ans ou plus , Jeune adulte , États précancéreux/diagnostic , États précancéreux/épidémiologie , Gastrite atrophique/diagnostic , Gastrite atrophique/épidémiologie , Métaplasie/diagnostic , Métaplasie/épidémiologie , États précancéreux/anatomopathologie , Biopsie/méthodes , Chili/épidémiologie , Protocoles cliniques , Dépistage de masse/méthodes , Épidémiologie Descriptive , Prévalence , Études rétrospectives , Analyse de variance , Endoscopie gastrointestinale , Sensibilité et spécificité , Muqueuse gastrique/anatomopathologie , Gastrite atrophique/anatomopathologie , Métaplasie/anatomopathologie
19.
Gastroenterol. latinoam ; 29(1): 21-26, 2018. ilus
Article de Espagnol | LILACS | ID: biblio-1116763

RÉSUMÉ

Pancreas divisum (PD) is the most common congenital anatomical variant of the pancreas. Its etiological implication in recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP) has been recurrently questioned. Normal anatomy and variants: 80-90% of the population has normal anatomy, with excretion of exocrine pancreatic secretion to the duodenum by the major papilla. Three anatomical variants of PD have been described: classic PD with visible ventral duct, but total absence of fusion; PD with absence of ventral duct; and incomplete PD, with a rudimentary connection between the ventral and dorsal ducts. Clinical implication: This anatomical variant is symptomatic in less than 5% of the carriers, being associated to higher prevalence in patients with RAP However, the relationship between PD and RAP is considered probable, only in cases of association with mutation of the CFTR gene. Obstructive CP can develop in the segment drained by the dorsal duct. Diagnosis: Magnetic resonance cholangiopancreatography (MRCP) is the most sensitive diagnostic method. Other non-invasive diagnostic methods are endosonography and computed tomography (CT), the latter with lower performance. Treatment: The current trend in acute pancreatitis (AP) where PD is assumed as an etiological factor, is endoscopic resolution, with papillotomy with or without a pancreatic stent.


El páncreas divisum (PD) es la variante anatómica congénita más frecuente del páncreas. Su implicancia etiológica en pancreatitis aguda recurrente (PAR) y pancreatitis crónica (PC) ha sido frecuentemente cuestionada. Anatomía normal y variantes: 80-90% de la población presenta anatomía normal, con salida de secreción pancreática exocrina al duodeno por la papila mayor. Se han descrito 3 variantes anatómicas: PD clásico con conducto ventral visible, pero ausencia total de fusión; PD con ausencia de conducto ventral; y PD incompleto, con conexión rudimentaria entre los conductos ventral y dorsal. Implicancia clínica: Esta variante anatómica da síntomas en menos de 5% de los portadores, asociándose a mayor prevalencia en pacientes con PAR. Sin embargo, se considera probable la relación entre PD y PAR, solo en casos de asociación con mutación del gen CFTR. Pancreatitis crónica (PC) obstructiva se puede desarrollar en el segmento drenado por el conducto dorsal. Diagnóstico: La colangiopancreatografía por resonancia magnética (CPRM) es el método diagnóstico más sensible. Otros métodos diagnósticos no invasivos son la endosonografía y tomografía computada (TC), este último de menor rendimiento. Tratamiento: La tendencia actual en PA donde se asume PD como factor etiológico, es la resolución endoscópica, con papilotomía con o sin stent.


Sujet(s)
Humains , Pancréas/malformations , Maladies du pancréas/physiopathologie , Pancréatite/physiopathologie , Maladies du pancréas/chirurgie , Maladies du pancréas/diagnostic , Pancréatite/chirurgie , Pancréatite/diagnostic , Récidive , Maladie aigüe , Cholangiopancréatographie par résonance magnétique , Variation anatomique
20.
GMS J Med Educ ; 34(5): Doc61, 2017.
Article de Anglais | MEDLINE | ID: mdl-29226229

RÉSUMÉ

Introduction: Radiology plays a crucial role in the emergency care setting by delivering early and precise diagnoses under pressure of time, right at the beginning of patient treatment. Although there is a need for postgraduate education in emergency radiology, most of the national bodies responsible do not offer it in a uniform fashion and a general proof of qualification is missing in Europe. Therefore, the European Society of Radiology (ESR) has founded the (Sub-)Society of Emergency Radiology (ESER), prompting them to develop a European curriculum. This trend, which is currently also encouraged in many other non-radiological specialties which demand the highest professional qualifications, often lacks expertise in medical education. Goals: The goal of this article is the general description of the curricular planning process for a European postgraduate subspecialisation programme, using the example of Emergency Radiology (European Diploma in Emergency Radiology, EDER), including the utilisation of TOOLS and recommendations derived from comparable projects. Project description: The project was divided into partial steps: the timeline displayed in a GANTT chart, and tasks and responsibilities assigned in a RASCI matrix. The curriculum was iteratively developed using the KERN approach and steps were prioritised using the PARETO principle. Furthermore, the following TOOLS were used: limitations and needs assessment, SWOT analysis, formulating learning objectives and categorising them after MILLER and SCLO, and using BLOOM's taxonomy for cognitive learning objectives and operationalising them according to MAGER. Psychomotoric and affective learning objectives were assigned to CANMEDS roles, grouped by topic using CLUSTERING, and then mapped by MATRIX analysis to appropriate learning and evaluation methods. Striving for continuous improvement, the curriculum was finally embedded in curricular quality management. Results: The standardisation of the EDER access, considering the different national conditions, the minimisation of European learners' attendance phases, restricting expenses by best possible use of existing structures, respecting the requirements and retaining the support of the European umbrella society ESR, finishing the project by a specific deadline and the demands of continuous improvement were particular challenges. A curriculum with the eligibility of five years' speciality training in general radiology has evolved on schedule. The subspeciality training lasts at least one year and is divided into webinars, workshops during congresses (e.g. the annual ESR and ESER congresses) and one year practical training at the individual learner's corresponding local hospitals, which adhere to a catalogue of requirements, comparable to national educational policies. The curriculum is completed by passing a written and oral exam (diploma) and re-accreditation every five years. Conclusions: Despite complex requirements, the TOOLS utilised allowed an almost seamless, resource-minimised, professional, location-independent distributed development of a European subspeciality curriculum within one year. The definitive implementation is still due. If any deviations from the draft presented should become necessary in the future, the embedment in the curricular quality management will lead to a redirection in the right way and, furthermore, secure a continuous improvement in the best way possible.


Sujet(s)
Programme d'études , Radiologie/enseignement et éducation , Enseignement médical , Europe , Allemagne
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