Abstract Background Up to a third of patients with localized prostate cancer have unilateral disease that may be suitable for partial treatment with hemiablation. Objective To evaluate the ability of ...high intensity focused ultrasound (HIFU) to achieve local control of the tumor in patients with unilateral localized prostate cancer. Design, setting, and participants The French Urological Association initiated a prospective IDEAL multi-institutional study (2009–2015), to evaluate HIFU-hemiablation as a primary treatment. Intervention Multiparametric magnetic resonance imaging and biopsy were used for unilateral cancer diagnosis and control, and HIFU-hemiablation. Outcome measurements and statistical analysis Primary: absence of clinically significant cancer (CSC) on control biopsy at 1 yr (CSC: Gleason score ≥ 7 or cancer core length > 3 mm regardless of grade or > 2 positive cores). Secondary: presence of any cancer on biopsy, biochemical response, radical treatment free survival, adverse events, continence (no pad), erectile function (International Index of Erectile Function-5 ≥ 16), and quality of life (European Organization for Research and Treatment of Cancer QLQ-C28) questionnaires. Results and limitations One hundred and eleven patients were treated (mean age: 64.8 yr standard deviation 6.2; mean prostate-specific antigen: 6.2 ng/ml standard deviation 2.6; 68% low risk, 32% intermediate risk). Of the 101 patients with control biopsy, 96 (95%) and 94 (93%) had no CSC in the treated and contralateral lobes, respectively. Mean prostate-specific antigen at 2 yr was 2.3 ng/ml (standard deviation 1.7). The radical treatment-free survival rate at 2 years was 89% (radical treatments: six radical prostatectomies, three radiotherapies, and two HIFU). Adverse events were Grade 3 in 13%. At 12 mo continence and erectile functions were preserved in 97% and 78%. No significant decrease in quality of life score was observed at 12 mo. One limitation is the number of low-risk patients included in this study. Conclusions At 1 yr, HIFU-hemiablation was efficient with 95% absence of clinically significant cancer associated with low morbidity and preservation of quality of life. Radical treatment-free survival rate was 89% at 2 yr. Patient summary This report shows that high intensity focused ultrasound half-gland treatment of unilateral prostate cancer provides promising results with high cancer control and low morbidity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Abstract Background: The authors sought to determine the level of inspiratory pressure minimizing the risk of gastric insufflation while providing adequate pulmonary ventilation. The primary endpoint ...was the increase in incidence of gastric insufflation detected by ultrasonography of the antrum while inspiratory pressure for facemask pressure-controlled ventilation increased from 10 to 25 cm H2O. Methods: In this prospective, randomized, double-blind study, patients were allocated to one of the four groups (P10, P15, P20, and P25) defined by the inspiratory pressure applied during controlled-pressure ventilation: 10, 15, 20, and 25 cm H2O. Anesthesia was induced using propofol and remifentanil; no neuromuscular-blocking agent was administered. Once loss of eyelash reflex occurred, facemask ventilation was started for a 2-min period while gastric insufflation was detected by auscultation and by real-time ultrasonography of the antrum. The cross-sectional antral area was measured using ultrasonography before and after facemask ventilation. Respiratory parameters were recorded. Results: Sixty-seven patients were analyzed. The authors registered statistically significant increases in incidences of gastric insufflation with inspiratory pressure, from 0% (group P10) to 41% (group P25) according to auscultation, and from 19 to 59% according to ultrasonography. In groups P20 and P25, detection of gastric insufflation by ultrasonography was associated with a statistically significant increase in the antral area. Lung ventilation was insufficient for group P10. Conclusion: Inspiratory pressure of 15 cm H2O allowed for reduced occurrence of gastric insufflation with proper lung ventilation during induction of anesthesia with remifentanil and propofol in nonparalyzed and nonobese patients. (Anesthesiology 2014; 120:326-34)
Plasma-creatinine-based equations to estimate the glomerular filtration rate are recommended by several clinical guidelines. In 2009, Schwartz et al. adapted the traditional Schwartz equation to ...children and adolescents but did not find different k-coefficients between children and adolescents (k = 36.5 for all patients). We reevaluated the coefficient of the 2009-Schwartz formula according to sex and age in a pediatric population.
We used linear mixed-effects models to reestimate the 2009-Schwartz k-coefficient in 360 consecutive French subjects aged 1 to 18 years referred to a single centre between July 2003 and July 2010 (965 measurements). We assessed the agreement between the estimated glomerular filtration rate obtained with the new formula (called Schwartz-Lyon) and the rate measured by inulin clearance. We then compared this agreement to the one between the measured glomerular filtration rate and 2009-Schwartz formula, first in the French then in a Swedish cohort.
In Schwartz-Lyon formula, k was estimated at 32.5 in boys <13 years and all girls and at 36.5 in boys aged ≥13 years. The performance of this formula was higher than that of 2009-Schwartz formula in children <13 years. This was first supported by a statistically significant reduction of the overestimation of the measured glomerular filtration rate in both cohorts, by better 10% and 30% accuracies, and by a better concordance correlation coefficient.
The performance and simplicity of Schwartz formula are strong arguments for its routine use in children and adolescents. The specific coefficient for children aged <13 years further improves this performance.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
ObjectivesIntegrating malaria prediction models into malaria control strategies can help to anticipate the response to seasonal epidemics. This study aimed to explore the possibility of using routine ...malaria data and satellite-derived climate data to forecast malaria cases in Togo.MethodsGeneralised additive (mixed) models were developed to forecast the monthly number of malaria cases in 40 health districts and three target groups. Routinely collected malaria data from 2013 to 2016 and meteorological and vegetation data with a time lag of 1 or 2 months were used for model training, while the year 2017 was used for model testing. Two methods for selecting lagged meteorological and environmental variables were compared: a first method based on statistical approach (‘SA’) and a second method based on biological reasoning (‘BR’). Both methods were applied to obtain a model per target group and health district and a mixed model per target group and health region with the health district as a random effect. The predictive skills of the four models were compared for each health district and target group.ResultsThe most selected predictors in the models per district for the ‘SA’ method were the normalised difference vegetation index, minimum temperature and mean temperature. The ‘SA’ method provided the most accurate models for the training period, except for some health districts in children ≥5 years old and adults and in pregnant women. The most accurate models for the testing period varied by health district and target group, provided either by the ‘SA’ method or the ‘BR’ method. Despite the development of models with four different approaches, the number of malaria cases was inaccurately forecasted.ConclusionsThese models cannot be used as such in malaria control activities in Togo. The use of finer spatial and temporal scales and non-environmental data could improve malaria prediction.
The use of a quantitative treatment selection marker to choose between two treatment options requires the estimate of an optimal threshold above which one of these two treatments is preferred. ...Herein, the optimal threshold expression is based on the definition of a utility function which aims to quantify the expected utility of the population (e.g. life expectancy, quality of life) by taking into account both efficacy (success or failure) and toxicity of each treatment option. Therefore, the optimal threshold is the marker value that maximizes the expected utility of the population. A method modelling the marker distribution in patient subgroups defined by the received treatment and the outcome is proposed to calculate the parameters of the utility function so as to estimate the optimal threshold and its 95% credible interval using the Bayesian inference. The simulation study found that the method had low bias and coverage probability close to 95% in multiple settings, but also the need of large sample size to estimate the optimal threshold in some settings. The method is then applied to the PETACC-8 trial that compares the efficacy of chemotherapy with a combined chemotherapy + anti-epidermal growth factor receptor in stage III colorectal cancer.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Worldwide, COVID-19 outbreaks in nursing homes have often been sudden and massive. The study investigated the role SARS-CoV-2 virus spread in nearby population plays in introducing the disease in ...nursing homes.
This was carried out through modelling the occurrences of first cases in each of 943 nursing homes of Auvergne-Rhône-Alpes French Region over the first epidemic wave (March-July, 2020). The cumulative probabilities of COVID-19 outbreak in the nursing homes and those of hospitalization for the disease in the population were modelled in each of the twelve Départements of the Region over period March-July 2020. This allowed estimating the duration of the active outbreak period, the dates and heights of the peaks of outbreak probabilities in nursing homes, and the dates and heights of the peaks of hospitalization probabilities in the population. Spearman coefficient estimated the correlation between the two peak series.
The cumulative proportion of nursing homes with COVID-19 outbreaks was 52% (490/943; range: 22-70% acc. Département). The active outbreak period in the nursing homes lasted 11 to 21 days (acc. Département) and ended before lockdown end. Spearman correlation between outbreak probability peaks in nursing homes and hospitalization probability peaks in the population (surrogate of the incidence peaks) was estimated at 0.71 (95% CI: 0.66; 0.78).
The modelling highlighted a strong correlation between the outbreak in nursing homes and the external pressure of the disease. It indicated that avoiding disease outbreaks in nursing homes requires a tight control of virus spread in the surrounding populations.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective
To train and to test for prostate zonal segmentation an existing algorithm already trained for whole-gland segmentation.
Methods
The algorithm, combining model-based and deep learning–based ...approaches, was trained for zonal segmentation using the NCI-ISBI-2013 dataset and 70 T2-weighted datasets acquired at an academic centre. Test datasets were randomly selected among examinations performed at this centre on one of two scanners (General Electric, 1.5 T; Philips, 3 T) not used for training. Automated segmentations were corrected by two independent radiologists. When segmentation was initiated outside the prostate, images were cropped and segmentation repeated. Factors influencing the algorithm’s mean Dice similarity coefficient (DSC) and its precision were assessed using beta regression.
Results
Eighty-two test datasets were selected; one was excluded. In 13/81 datasets, segmentation started outside the prostate, but zonal segmentation was possible after image cropping. Depending on the radiologist chosen as reference, algorithm’s median DSCs were 96.4/97.4%, 91.8/93.0% and 79.9/89.6% for whole-gland, central gland and anterior fibromuscular stroma (AFMS) segmentations, respectively. DSCs comparing radiologists’ delineations were 95.8%, 93.6% and 81.7%, respectively. For all segmentation tasks, the scanner used for imaging significantly influenced the mean DSC and its precision, and the mean DSC was significantly lower in cases with initial segmentation outside the prostate. For central gland segmentation, the mean DSC was also significantly lower in larger prostates. The radiologist chosen as reference had no significant impact, except for AFMS segmentation.
Conclusions
The algorithm performance fell within the range of inter-reader variability but remained significantly impacted by the scanner used for imaging.
Key Points
•
Median Dice similarity coefficients obtained by the algorithm fell within human inter-reader variability for the three segmentation tasks (whole gland, central gland, anterior fibromuscular stroma)
.
•
The scanner used for imaging significantly impacted the performance of the automated segmentation for the three segmentation tasks
.
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The performance of the automated segmentation of the anterior fibromuscular stroma was highly variable across patients and showed also high variability across the two radiologists
.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
In both observational and randomized studies, associations with overall survival are by and large assessed on a multiplicative scale using the Cox model. However, clinicians and clinical researchers ...have an ardent interest in assessing absolute benefit associated with treatments. In older patients, some studies have reported lower relative treatment effect, which might translate into similar or even greater absolute treatment effect given their high baseline hazard for clinical events.
The effect of treatment and the effect modification of treatment were respectively assessed using a multiplicative and an additive hazard model in an analysis adjusted for propensity score in the context of coronary surgery.
The multiplicative model yielded a lower relative hazard reduction with bilateral internal thoracic artery grafting in older patients (Hazard ratio for interaction/year = 1.03, 95%CI: 1.00 to 1.06, p = 0.05) whereas the additive model reported a similar absolute hazard reduction with increasing age (Delta for interaction/year = 0.10, 95%CI: -0.27 to 0.46, p = 0.61). The number needed to treat derived from the propensity score-adjusted multiplicative model was remarkably similar at the end of the follow-up in patients aged < = 60 and in patients >70.
The present example demonstrates that a lower treatment effect in older patients on a relative scale can conversely translate into a similar treatment effect on an additive scale due to large baseline hazard differences. Importantly, absolute risk reduction, either crude or adjusted, can be calculated from multiplicative survival models. We advocate for a wider use of the absolute scale, especially using additive hazard models, to assess treatment effect and treatment effect modification.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Purpose
The management of pituitary apoplexy, a rare emergency neuroendocrine condition, is controversial. The aim of the present study is to compare the outcomes of patients with pituitary apoplexy ...managed either by a conservative or surgical approach.
Methods
A retrospective cohort study including patients diagnosed between 2007 and 2018 in a tertiary French university hospital. Pituitary Apoplexy Score (PAS) was retrospectively applied in the perspective of therapeutic decision support.
Results
Forty-six patients were treated for pituitary apoplexy either with conservative management (
n
= 27) or surgery (
n
= 19). At initial evaluation, visual field defects (VFD) and visual acuity impairment were more frequent in patients from the surgery group. At 1 year there were no statistical differences in the rates of complete/near-complete resolution of VFD (100 vs. 91.7%), visual acuity impairment (100 vs. 87.5%), and cranial nerve palsies (83.3 vs. 100%), between conservative and surgical treatment groups. There were more endocrine deficits at 1 year in the surgical group (
p
= 0.029). PAS (
n
= 41) was 3.4 on average in the early surgery group and 1.3 in the conservative treatment/delayed surgery group. Among patients with a score < 4, 31.3% were operated at first line and did not present better outcomes than patients managed conservatively. In all, 88.9% of patients with a score ≥ 4 underwent surgery.
Conclusions
PAS may be a reliable parameter for defining therapeutic strategy. Patients with non-severe and nonprogressive neuro-ophthalmological deficits can be managed conservatively without negative impact on outcomes, thus surgery should be reserved only for those patients with a PAS ≥ 4.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Familial Mediterranean fever (FMF) is the most frequent hereditary autoinflammatory disease. Its diagnosis relies on a set of clinical criteria and a genetic confirmation on identification of ...biallelic pathogenic
variants.
encodes pyrin, an inflammasome sensor. Using a kinase inhibitor, UCN-01, we recently identified that dephosphorylation of FMF-associated pyrin mutants leads to inflammasome activation. The aim of this study was to assess whether quantifying UCN-01-mediated inflammasome activation could discriminate FMF patients from healthy donors (HD) and from patients with other inflammatory disorders (OID).
Real-time pyroptosis and IL-1β secretion were monitored in response to UCN-01 in monocytes from FMF patients (n=67), HD (n=71) and OID patients (n=40). Sensitivity and specificity of the resulting diagnostic tests were determined by receiver operating characteristic curve analyses.
Inflammasome monitoring in response to UCN-01 discriminates FMF patients from other individuals. Pyroptosis assessment leads to a fast FMF diagnosis while combining pyroptosis and IL-1β dosage renders UCN-01-based assays highly sensitive and specific. UCN-01-triggered monocytes responses were influenced by
gene dosage and
mutations in a similar way as clinical phenotypes are.
UCN-01-based inflammasome assays could be used to rapidly diagnose FMF, with high sensitivity and specificity.
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