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"Alexandre, Thomas"
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Milestones in the History of Esophagectomy: From Torek to Minimally Invasive Approaches
The history of esophagectomy reflects a journey of dedication, collaboration, and technical innovation, with ongoing endeavors aimed at optimizing outcomes and reducing complications. From its early attempts to modern minimally invasive approaches, the journey has been marked by perseverance and innovation. Franz J. A. Torek’s 1913 successful esophageal resection marked a milestone, demonstrating the feasibility of transthoracic esophagectomy and the potential for esophageal cancer cure. However, its high mortality rate posed challenges, and it took almost two decades for similar successes to emerge. Surgical techniques evolved with the left thoracotomy, right thoracotomy, and transhiatal approaches, expanding the indications for resection. Mechanical staplers introduced in the early 20th century transformed anastomosis, reducing complications. The advent of minimally invasive techniques in the 1990s aimed to minimize complications while maintaining oncological efficacy. Robot-assisted esophagectomy further pushed the boundaries of minimally invasive surgery. Collaborative efforts, particularly from the Worldwide Esophageal Cancer Collaboration and the Esophageal Complications Consensus Group, standardized reporting and advanced the understanding of outcomes. The introduction of risk prediction models aids in making informed decisions. Despite significant improvements in survival rates and postoperative mortality, anastomotic leaks remain a concern, with recent rates showing an increase. Prevention strategies include microvascular anastomosis and ischemic preconditioning, yet challenges persist.
Journal Article
New Model for Weather Stations Integrated to Intelligent Meteorological Forecasts in Brasilia
by
da Silva, Thomas Alexandre
,
Meneguette, Rodolfo I.
,
Serrano, Andre L. M.
in
Agricultural production
,
agro-meteorology
,
Air quality
2025
This paper presents a new model for low-cost solar-powered Automatic Weather Stations based on the ESP-32 microcontroller, modern sensors, and intelligent forecasts for Brasilia. The proposed system relies on compact, multifunctional sensors and features an open-source firmware project and open-circuit board design. It includes a BME688, AS7331, VEML7700, AS3935 for thermo-hygro-barometry (plus air quality), ultraviolet irradiance, luximetry, and fulminology, besides having a rainfall gauge and an anemometer. Powered by photovoltaic panels and batteries, it operates uninterruptedly under variable weather conditions, with data collected being sent via WiFi to a Web API that adapts the MZDN-HF (Meteorological Zone Delimited Neural Network–Hourly Forecaster) model compilation for Brasilia to produce accurate 24 h multivariate forecasts, which were evaluated through MAE, RMSE, and R2 metrics. Installed at the University of Brasilia, it demonstrates robust hardware performance and strong correlation with INMET’s A001 data, suitable for climate monitoring, precision agriculture, and environmental research.
Journal Article
Two Classes of Bacterial IMPDHs according to Their Quaternary Structures and Catalytic Properties
by
Alexandre, Thomas
,
Munier-Lehmann, Hélène
,
Rayna, Bertrand
in
Analysis
,
Bacillus thuringiensis
,
Bacteria
2015
Inosine-5'-monophosphate dehydrogenase (IMPDH) occupies a key position in purine nucleotide metabolism. In this study, we have performed the biochemical and physico-chemical characterization of eight bacterial IMPDHs, among which six were totally unexplored. This study led to a classification of bacterial IMPDHs according to the regulation of their catalytic properties and their quaternary structures. Class I IMPDHs are cooperative enzymes for IMP, which are activated by MgATP and are octameric in all tested conditions. On the other hand, class II IMPDHs behave as Michaelis-Menten enzymes for both substrates and are tetramers in their apo state or in the presence of IMP, which are shifted to octamers in the presence of NAD or MgATP. Our work provides new insights into the IMPDH functional regulation and a model for the quaternary structure modulation is proposed.
Journal Article
Medico-economic impact of thoracoscopy versus thoracotomy in lung cancer: multicentre randomised controlled trial (Lungsco01)
by
Magdaleinat, Pierre
,
Richard De Latour, Bertrand
,
Bernard, Alain
in
Adult
,
Cancer
,
Carcinoma, Non-Small-Cell Lung / surgery
2023
Background
Lungsco01 is the first study assessing the real benefits and the medico-economic impact of video-thoracoscopy versus open thoracotomy for non-small cell lung cancer in the French context.
Methods
Two hundred and fifty nine adult patients from 10 French centres were randomised in this prospective multicentre randomised controlled trial, between July 29, 2016, and November 24, 2020. Survival from surgical intervention to day 30 and later was compared with the log-rank test. Total quality-adjusted-life-years (QALYs) were calculated using the EQ-5D-3L®. For medico-economic analyses at 30 days and at 3 months after surgery, resources consumed were valorised (€ 2018) from a hospital perspective. First, since mortality was infrequent and not different between the two arms, cost-minimisation analyses were performed considering only the cost differential. Second, based on complete cases on QALYs, cost-utility analyses were performed taking into account cost and QALY differential. Acceptability curves and the 95% confidence intervals for the incremental ratios were then obtained using the non-parametric bootstrap method (10,000 replications). Sensitivity analyses were performed using multiple imputations with the chained equation method.
Results
The average cumulative costs of thoracotomy were lower than those of video-thoracoscopy at 30 days (€9,730 (SD = 3,597)
vs.
€11,290 (SD = 4,729)) and at 3 months (€9,863 (SD = 3,508)
vs.
€11,912 (SD = 5,159)). In the cost-utility analyses, the incremental cost-utility ratio was €19,162 per additional QALY gained at 30 days (€36,733 at 3 months). The acceptability curve revealed a 64% probability of efficiency at 30 days for video-thoracoscopy, at a widely-accepted willingness-to-pay threshold of €25,000 (34% at 3 months). Ratios increased after multiple imputations, implying a higher cost for video-thoracoscopy for an additional QALY gain (ratios: €26,015 at 30 days, €42,779 at 3 months).
Conclusions
Given our results, the economic efficiency of video-thoracoscopy at 30 days remains fragile at a willingness-to-pay threshold of €25,000/QALY. The economic efficiency is not established beyond that time horizon. The acceptability curves given will allow decision-makers to judge the probability of efficiency of this technology at other willingness-to-pay thresholds.
Trial registration
NCT02502318.
Journal Article
Beyond Body Mass Index: The Impact of Height and Height‐Normalised Weight on Overall Survival of Lung Cancer Undergoing Surgery
by
Prieto, Mathilde
,
Barthes, Françoise Le Pimpec
,
Alifano, Marco
in
Aged
,
Body Height
,
Body Mass Index
2025
Introduction Unlike most malignancies, increased adiposity, as expressed by a higher body mass index (BMI), is associated with improved prognosis after lung cancer surgery at the population level. Height, one of the determinants of BMI, is associated with better survival, independent of other confounders, even though BMI is calculated as weight divided by height squared. The association of weight with survival is difficult to assess because, at the individual level, weight is closely linked to height and does not directly reflect adiposity. In this study, we examined the impact of height and weight on overall survival in a large population of patients undergoing upfront surgery for lung cancer. Methods We extracted data on all consecutive patients with stage I–IIIA non‐small cell lung cancer included in a surgical nationwide dataset over a 16‐year period. For each sex, height was categorised in sex‐specific quartiles (sH). Sex‐specific height‐normalised weight (sHNW) was defined as the ratio of an individual's weight to the mean weight of individuals of the same sex and height, and it was categorised into quartiles. Finally, the sum of the category membership (ranging from 1 to 4 according to quartiles) of sH and sHNW was calculated, and the results were categorised into four groups of sH/sHNW. Overall survival (OS) was assessed by Kaplan–Meier, and differences evaluated by log‐rank. Cox models were built. Results The study included 50 653 patients. Mean age was 65.61 ± 9.45 and 31.99% were women. sH predicted OS, taller height being protective [crude HRs of second, third, and fourth quartiles vs. first quartile: 0.94 (95% CI 0.91–0.98), 0.89 (0.86–0.92), 0.77 (0.74–0.81); p < 0.0001]. sHNW was also associated with OS, with lower sHNW category being associated with worse outcome and higher sHNW categories being protective [crude HRs of second, third and fourth quartiles vs. first quartile: 0.88 (0.85–0.92), 0.82 (0.79–0.85), 0.85 (0.81–0.88); p < 0.0001]. The four classes of sH/sHNW showed higher differences in prognosis with respective crude HRs of 0.88 (0.84–0.93), 0.76 (0.73–0.80) and 0.70 (0.66–0.74) in the intermediate lower, intermediate higher and higher class as compared with the lower class. Five‐year overall survival rates were 58.65% (56.89–60.45), 62.96% (62.15–63.78), 67.71% (67.02–68.41) and 70.12% (68.98–71.26), in the lower, intermediate lower, intermediate higher and higher class, respectively. All Cox models showed that sHNW and sH/sHNW predicted survival independently from common confounders. Conclusions Our study demonstrated that sHNW and sH/sHNW are strong prognostic factors of resectable lung cancer. This finding could have both epidemiologic and biological relevance.
Journal Article
Comprehensive bile acid pool analysis during ex-vivo liver perfusion in a porcine model of ischemia-reperfusion injury
by
Rossignol, Guillaume
,
Mohkam, Kayvan
,
Bidault, Valeska
in
692/308/1426
,
692/4020/4021/288
,
Animal models
2024
Bile acids (BA) are key for liver regeneration and injury. This study aims at analyzing the changes in the BA pool induced by ischemia-reperfusion (IRI) and investigates the impact of hypothermic oxygenated perfusion (HOPE) on the BA pool compared to static cold storage (SCS). In a porcine model of IRI, liver grafts underwent 30 min of asystolic warm ischemia followed by 6 h of SCS (n = 6) ± 2 h of HOPE (n = 6) and 2 h of ex-situ warm reperfusion. The BA pool in bile samples was analyzed with liquid chromatography coupled with tandem mass spectrometry. We identified 16 BA and observed significant changes in response to ischemia-reperfusion, which were associated with both protective and injury mechanisms. Second, HOPE-treated liver grafts exhibited a more protective BA phenotype, characterized by a more hydrophilic BA pool compared to SCS. Key BA, such as GlycoCholic Acid, were identified and were associated with a decreased transaminase release and improved lactate clearance during reperfusion. Partial Least Square-Discriminant Analysis revealed a distinct injury profile for the HOPE group. In conclusion, the BA pool changes with liver graft IRI, and preservation with HOPE results in a protective BA phenotype compared to SCS.
Journal Article
Rapid Diagnosis of Lung Tumors, a Feasability Study Using Maldi-Tof Mass Spectrometry
by
D’journo, Xavier-Benoit
,
Flaudrops, Christophe
,
Brégeon, Fabienne
in
Aged
,
Analysis
,
Biology and Life Sciences
2016
Despite recent advances in imaging and core or endoscopic biopsies, a percentage of patients have a major lung resection without diagnosis. We aimed to assess the feasibility of a rapid tissue preparation/analysis to discriminate cancerous from non-cancerous lung tissue.
Fresh sample preparations were analyzed with the Microflex LTTM MALDI-TOF analyzer. Each main reference spectra (MSP) was consecutively included in a database. After definitive pathological diagnosis, each MSP was labeled as either cancerous or non-cancerous (normal, inflammatory, infectious nodules). A strategy was constructed based on the number of concordant responses of a mass spectrometry scoring algorithm. A 3-step evaluation included an internal and blind validation of a preliminary database (n = 182 reference spectra from the 100 first patients), followed by validation on a whole cohort database (n = 300 reference spectra from 159 patients). Diagnostic performance indicators were calculated.
127 cancerous and 173 non-cancerous samples (144 peripheral biopsies and 29 inflammatory or infectious lesions) were processed within 30 minutes after biopsy sampling. At the most discriminatory level, the samples were correctly classified with a sensitivity, specificity and global accuracy of 92.1%, 97.1% and 95%, respectively.
The feasibility of rapid MALDI-TOF analysis, coupled with a very simple lung preparation procedure, appears promising and should be tested in several surgical settings where rapid on-site evaluation of abnormal tissue is required. In the operating room, it appears promising in case of tumors with an uncertain preoperative diagnosis and should be tested as a complementary approach to frozen-biopsy analysis.
Journal Article