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Stereotactic body radiation therapy (SBRT) has become a new therapeutic option for primary renal cell carcinoma. However, treatment doses lack consistency in the literature. The primary objective of this study was to determine the maximum tolerated dose for renal cancer SBRT. This phase 1 multicentric dose-escalation study assessed 4 dose levels: 8 Gy × 4, 8 Gy × 5, 10 Gy × 4, and 12 Gy × 4. The primary objective of this study was to determine the maximal tolerated dose, defined by the occurrence of dose-limiting toxicity was defined as any acute side effect of grade ≥4 based on the Common Terminology Criteria for Averse Events, version 4.0. From October 2010 to September 2017, 13 patients were enrolled. The median follow-up was 23 months. There was no dose-limiting toxicity in our study, and the highest dose was reached successfully. No acute or late toxic effects above grade 2 were seen. There was no significant alteration of renal function after treatment. At 24 months, 2 patients had partial response and the others had stable disease. After 24 months of follow-up, no dose-limiting toxicity was seen at any of the prescribed dose levels in our study. The findings suggest that our last dose level of 48 Gy in 4 12-Gy fractions can be considered safe and can be used in further studies. [ABSTRACT FROM AUTHOR]

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Background and purpose The purpose of this study was to systematically determine the correlations between the post-thrombolytic changes of hemostasis parameters and the occurrence of early intracerebral hemorrhage (ICH). Methods In 72 consecutive patients with cerebral infarcts treated with rt-PA, plasma levels of fibrinogen, plasminogen, alpha2-antiplasmin, factor XIII, fibrin(ogen) degradation products (FDPs) and d -Dimers were measured at baseline, 2 and 24 h after thrombolysis. Correlations were studied between the hemostasis events and early (less than 24 h) hemorrhagic infarcts (HIs) or parenchymatous hematomas (PH). Results Of 72 patients, 6 patients (8.3%) had early PHs, 11 (15.3%) had early HIs, and 55 (76.4%) had no bleeding. Early HIs were not linked to any hemostasis parameter at any time. Univariate comparison of patients having early PHs with non-bleeding patients showed hemostasis abnormalities at 2 h: high FDP (p = 0.01), high Log FDP (p = 0.01), low fibrinogen (p = 0.01), and low Log fibrinogen (p = 0.01). Logistic regression adjusted for age, NIHSS and diabetes confirmed these 2 hour predictors: Log FDP (OR: 7.50; CI: 1.26 to 44.61, p = 0.03), and Log fibrinogen (OR: 19.32; CI: 1.81 to 205.98, p = 0.01). The decrease in fibrinogen less than 2 g/L multiplies the odds of early PH by a factor 12.82. Conclusion An early fibrinogen degradation coagulopathy involving an increase of FDP and a massive consumption of circulating fibrinogen is predictive of early parenchymal hematomas, indicating the occurrence of a particularly intense lysis of circulating fibrinogen. These results, if confirmed by future studies, suggest that early assays of fibrinogen and FDP may be useful in predicting the risk of post-thrombolytic intracerebral hematoma. [ABSTRACT FROM AUTHOR]

Background Little is known, in man, in the post-thrombolytic molecular dynamics of haemostasis, particularly the effect of rt-PA on antifibrinolytic components such as alpha2 anti-plasmin and Factor XIII. Aims and hypothesis The purpose of this study was to systematically determine changes in coagulation and fibrinolytic parameters after thrombolysis with rt-PA during 24 h. We also aimed to correlate these parameters with different acute ischemic stroke subtypes and global outcome. Methods Eighty consecutive patients with cerebral infarcts treated with rt-PA had their plasma levels of fibrinogen, plasminogen, alpha2-antiplasmin, Factor XIII, fibrin(ogen) degradation products (FDP) and D-Dimers measured at baseline (h0), 2 (h2) and 24 h (h24) after initiation of thrombolysis. Correlations between the variations of these components were statistically studied, using the Spearman rank test or the Pearson test. These haemostatic parameters were also compared with cardioembolic and non cardioembolic patients, as well as between poor and favourable outcome patients. Results Between h0 and h2, a decrease in fibrinogen, plasminogen, alpha2-antiplasmin, and factor XIII was observed, while an increase in FDP and D-Dimers took place. These values returned to the initial levels at h24. At 2 h, the decrease in fibrinogen was significantly correlated with that of plasminogen (0.48, p = 0.01), alpha2-antiplasmin (0.48, p = 0.004), and factor XIII (0.44, p = 0.01); the decrease in plasminogen was significantly correlated with those of antifibrinolytic components, factor XIII (0.47, p = 0.02) and alpha2-antiplasmin (r = 0.77, p < 0.001). These variations were independent of NIHSS. Cardioembolic infarcts showed a statistically significant greater h0–h2 decrease in plasminogen (p = 0.04) and an h0–h2 increase in FDP (p = 0.02). Poor outcome was linked to low plasminogen values at 2 and 24 h. Conclusions Supposed to be fibrin-specific, rt-PA induces a decrease in circulating fibrinogen, significantly linked to a decrease in plasminogen. A collateral increase in antifibrinolytic agents such as factor XIII and alpha2-antiplasmin is also observed. At 2 h, a significant decrease in plasminogen and a significant increase in fibrin(ogen) degradation products (FDP) are observed in cardioembolic infarcts, and appear as early independent predictors of this aetiology. A low plasminogen value at 2 h is potentially predictive of poor prognosis at 3 months. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Androgens have a positive effect on penile growth in children, but they may also have a repressive effect on the healing process. The aim of this prospective study was to compare the outcomes of onlay urethroplasty with and without preoperative androgen stimulation in patients with severe hypospadias. Patients and method: Of 300 severe hypospadias cases treated at a single institution, 126 operated on by the same surgeon had complete follow-up data, and 30 of these received preoperative androgen treatment (human chorionic gonadotrophin and/or systemic testosterone) 1–24 months before surgery. Results: Thirty-five patients presented with a complication (27.7%) of whom 26 (20.6%) had a fistula or dehiscence. Among patients on androgen stimulation there was a 30% healing complication rate (9/30) whereas for those without this was 17.7% (17/96). When androgenic treatment was given > 3 months prior to surgery the healing complication rate was 21.7% (5/23), and when < 3 months prior to surgery the rate reached 57% (4/7). Mean follow up was 41 months (10–97). Conclusion: Although the numbers were too small in this series to reach statistical significance, the tissular interactions of androgens in the healing process reported by dermatologists should alert the hypospadiologists and lead to a further prospective study to define the optimal protocol for stimulation of the penis in specific cases without affecting outcome. [Copyright &y& Elsevier]

Background The prognosis of poorly differentiated thyroid carcinomas (PDTC) is heterogeneous though generally poor. The objectives of this study were to identify clinical and molecular factors of poor prognosis. Methods One hundred four consecutive patients treated for a PDTC between 01/01/2000 and 31/12/2010 were included in this study. A pathological review was done for all cases (blinded to clinical data and outcome). Results All patients underwent thyroidectomy. Adjuvant radioactive-iodine was administered in 95.2% of them. Tumours were pT3 or pT4 in 68.3% of cases and metastatic in 38.5% of patients. Extrathyroidal extension (ETE) was observed in 40% of patients. At the end of the initial treatment, only 37% of patients were considered in remission. Fifty-two patients (50%) became refractory to radioiodine during follow-up. The 5-year overall survival was 72.8% and the 5-year recurrence-free survival (RFS) was 45.3%. Remission after initial treatment was an independent factor of RFS (HR = 0.22; [0.10–0.49]). ETE was the only significant parameter influencing the overall survival in multivariate analysis. TERT promoter mutations at positions −124 (C228T) and −146 (C250T) were present in 38.1% of analysed patients and significantly associated with radioiodine resistance but not with overall survival. Half of TERT promoter mutant tumours harboured also RAS or BRAF mutations. Conclusion PDTC form a heterogeneous group of patients with usual late-stage diagnosis, low radioactive iodine avidity and frequent metastatic spread. TERT promoter mutations could help to identify patients with high risk of radio-iodine refractoriness. [ABSTRACT FROM AUTHOR]

Assess the changes in anxiety, depression, and stress levels over time and identify risk factors among healthcare workers in French emergency departments (EDs) during the first COVID-19 outbreak. A prospective, multicenter study was conducted in 4 EDs and an emergency medical service (SAMU). During 3 months, participants completed fortnightly questionnaires to assess anxiety, depression, and stress using the Hospital Anxiety and Depression and the Chamoux-Simard scale. The changes in anxiety, depression, and stress levels over time were modelled by a linear mixed model including a period effect and a continuous time effect within periods. A total of 211 respondents (43.5 %) completed the survey at inclusion. There was a decrease in mean anxiety (from 7.33 to 5.05, p < 0.001), mean depression (from 4.16 to 3.05, p = 0.009), mean stress at work (from 41.2 to 30.2, p = 0.008), and mean stress at home (from 33.0 to 26.0, p = 0.031) at the beginning of each period. The mean anxiety level was higher for administrative staff (+0.53) and lower for paramedics (−0.61, p = 0.047) compared to physicians. The anxiety level increased with the number of day and night shifts (0.13/day, p < 0.001, 0.12/night, p = 0.025) as did stress at work (1.6/day, p < 0.001, 1.1/night, p = 0.007). Reassigned healthcare workers were at higher risk of stress particularly compared to SAMU workers (stress at work: p = 0.015, at home: p = 0.021, in life in general: p = 0.018). Although anxiety, depression, and stress decreased over time, anxiety was higher among physicians and administrative staff. Reassignment and working hours were identified as potential risk factors for mental health distress in EDs. • During the first COVID-19 outbreak, levels of anxiety, depression, and stress decreased over time among healthcare workers. • The levels of anxiety, remained higher for physicians and administrative staff than for paramedics. • Reassignment and working hours were identified as potential risk factors for mental health distress in EDs. [ABSTRACT FROM AUTHOR]

Résumé But et objectif La dénutrition hospitalière, à l’origine de morbidités pour le patient, soulève la question du bon usage de la nutrition artificielle. L’objectif de ce travail était d’effectuer un état des lieux de la pratique de nutrition parentérale « à la carte » en population pédiatrique. Matériel et méthodes La qualité de la prise en charge nutritionnelle a été évaluée sur 3 paramètres : la pertinence de l’indication, la qualité de la prescription et la rigueur de la surveillance. L’ensemble des patients ayant bénéficié d’une nutrition parentérale « à la carte » au cours de l’année 2012 a été examiné. Parallèlement, un questionnaire d’évaluation des connaissances des prescripteurs a été réalisé et diffusé. Résultats Quarante-deux patients ont été inclus (308 prescriptions). L’indication était pertinente dans 88 % des cas. La prescription était conforme dans 36 % des cas (110/308). L’évaluation de la rigueur de la surveillance a mis en évidence un suivi plus rigoureux une fois la nutrition parentérale instaurée et un défaut de suivi de certains paramètres biologiques. L’analyse du questionnaire a permis la mise en évidence de certaines lacunes dans les connaissances pratiques de la nutrition parentérale chez les prescripteurs. Conclusions Au terme de ce travail, il apparaît qu’un suivi satisfaisant des recommandations est réalisé concernant l’indication de la nutrition parentérale. En revanche, les résultats démontrent aussi une insuffisance du suivi des recommandations portant sur la prescription et la surveillance. Les résultats du questionnaire seront mis à profit pour la réalisation d’action de formation ciblée. Background and aims Malnutrition is correlated to a worsen outcome in children, and often requires nutritional support which prescription is challenging. This study assessed the prescription quality level of individualized compounded parenteral nutrition (PN). Methods Children admitted in 2012 to France pediatric university hospital and who received individualized compounded PN were retrospectively included. Newborns were not included. PN prescription was assessed according to its indication accuracy, its composition adequacy, and its tolerance monitoring. Simultaneously, prescribers’ knowledge about individualized compounding was surveyed. Results Forty-two children were included, and their 308 related PN prescriptions analyzed. PN indication was relevant in 88%, but PN nutrient composition matched with standards in 110 (36%) of the prescriptions only. PN tolerance monitoring assessment highlighted some insufficiencies in biological parameters follow up. Finally, the survey showed insufficient theoretical knowledge of PN prescribers. Conclusion PN indication accuracy was satisfying whereas progress was needed to improve nutrient compounding prescription and tolerance monitoring. Teaching programs are required to achieve these goals and will be started according to our results. [ABSTRACT FROM AUTHOR]

Background: Haemodynamically unstable patients often require arterial and venous catheter insertion urgently. We hypothesised that ultrasound-guided arterial and venous catheterisation would reduce mechanical complications.Methods: We performed a prospective RCT, where patients requiring both urgent arterial and venous femoral catheterisation were randomised to either ultrasound-guided or landmark-guided catheterisation. Complications and characteristics of catheter insertion (procedure duration, number of punctures, and procedure success) were recorded at the time of insertion (immediate complications). Late complications were investigated by ultrasound examination performed between the third and seventh days after randomisation. Primary outcome was the proportion of patients with at least one mechanical complication (immediate or late), by intention-to-treat analysis. Secondary outcomes included success rate, procedure time, and number of punctures.Results: We analysed 136 subjects (102 [75%] male; age range: 27-62 yr) by intention to treat. The proportion of subjects with one or more complications was lower in 22/67 (33%) subjects undergoing ultrasound-guided catheterisation compared with landmark-guided catheterisation (40/69 [58%]; odds ratio: 0.35 [95% confidence interval: 0.18-0.71]; P=0.003). Ultrasound-guided catheterisation reduced both immediate (27%, compared with 51% in the landmark approach group; P=0.004) and late (10%, compared with 23% in the landmark approach group; P=0.047) complications. Ultrasound guidance also reduced the proportion of patients who developed deep vein thrombosis (4%, compared with 22% following landmark approach; P=0.012), and achieved a higher procedural success rate (96% vs 78%; P=0.004).Conclusions: An ultrasound-guided approach reduced mechanical complications after urgent femoral arterial and venous catheterisation, while increasing procedural success.Clinical Trial Registration: NCT02820909. [ABSTRACT FROM AUTHOR]

Abstract Background TERT promoter mutations are associated with adverse clinicopathological characteristics in thyroid carcinomas and considered as a major indicator of poor outcomes. Nevertheless, most studies have pooled heterogeneous types of thyroid carcinomas and have been conducted retrospectively. We investigated the association between TERT promoter mutations and recurrence in a prospective series of 173 intermediate- to high-risk patients with thyroid cancer. Patients Patients referred for radioiodine treatment after thyroidectomy for intermediate- to high-risk differentiated thyroid carcinoma were included in a prospective observational study and tested for TERT promoter, BRAF, and RAS mutations of their primary tumours. We analysed the relationship between TERT promoter mutations and outcomes. Results The prevalence of TERT promoter mutations was 20.2% (35/173) in the total population. It was significantly higher in tumours harbouring aggressive histological features (poorly differentiated carcinoma, tall cell variant of papillary cancer or widely invasive follicular cancer) than in non-aggressive tumours: 32.7% (16/49) versus 15.3% (19/124; p = 0.020). TERT promoter mutations were also strongly associated with age ≥45 years (p = 0.005), pT4 stage (p = 0.015), metastatic disease (p = 0.014), and extrathyroidal extension (p = 0.002). TERT promoter mutations were associated with poor outcomes in the total population (p < 0.001) but not in the subgroup of non-metastatic patients (p = 0.051). However, they were associated with a worse outcome in patients both free of metastases and devoid of aggressive histological features. Neither BRAF nor RAS mutations were associated with event-free survival in non-metastatic patients. Conclusion Although their prognostic value does not seem to overcome that of histology, TERT promoter mutations may help to better define the prognosis of localized thyroid cancer patients without aggressive histology. Highlights • TERT mutations are associated with clinicopathological adverse features, even in intermediate- to high-risk thyroid cancer. • In intermediate- to high-risk thyroid cancer, TERT mutations do not overcome the prognostic value of histological features. • TERT mutations may be useful to identify high-risk patients among those without adverse histological features. [ABSTRACT FROM AUTHOR]

Objective Aneurysm wall biomechanics are not yet an integral part of aneurysm rupture risk evaluation. We aimed to develop a new technique describing the biomechanical properties of aneurysm wall and correlating them to rupture status. Methods Aneurysm wall samples collected during surgery were submitted before and after freezing to tensile tests or as fresh samples to indentation tests. The lateral stiffness or the Young's modulus of the different samples was determined as a function of the mechanical test used. The impact of freezing on biomechanical properties was evaluated. The correlation of clinical and radiologic data with the biomechanical profile of the aneurysm samples was investigated. Two-photon microscopy was used to study collagen fiber organization. Results Sixteen aneurysm samples (11 unruptured and 5 ruptured) were included. Freezing decreased tissue stiffness. No significant difference was found between ruptured and unruptured aneurysm wall samples regarding demographic characteristics, ethnicity, smoking status, arterial hypertension, site, size and shape of the aneurysm, PHASES score, mechanical profile, or overall Young's modulus. Indentation tests found that the rupture occurred in a restricted area of increased elastic capacity and unruptured areas had increased stiffness. Two-photon microscopy found disruption of the collagen fiber network in rupture zones. Conclusions The indentation test of fresh aneurysm wall samples described the heterogeneity of biomechanical properties of the tissue and found increased elastic capacity in the rupture zone and increased stiffness in the remainder of the aneurysm. This study could be a basis for further research aimed at building a biomechanical-based model of aneurysm rupture risk. Highlights • Indentation test of fresh aneurysm wall samples is feasible. • It reliably describes the heterogeneity of biomechanical properties of the tissue. • Rupture occurs in a restricted area of increased elastic capacity. [ABSTRACT FROM AUTHOR]