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Extended Reduced-Dose Apixaban for Cancer-Associated Venous Thromboembolism
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Tibial implant varus >3° does not adversely affect outcomes or revision rates in functionally aligned image‐based robotic total knee arthroplasty in a minimum of 2‐year follow‐up
No full textInternational audienceAbstract Purpose Functional alignment (FA) aims to restore knee kinematics by balancing laxities and adapting implant positioning. This study evaluates safety and outcomes of >3° varus tibial positioning in patients with varus deformity undergoing robotic‐assisted total knee arthroplasty (TKA). Methods This retrospective study included 337 patients with varus deformity undergoing robotic‐assisted TKA with FA principles with a minimum of 2‐year follow‐up. Patients were divided into two groups based on tibial varus positioning: ≤3° varus: Group A and >3° varus: Group B. Preoperative and postoperative coronal alignment, implant positioning, and outcomes were assessed using the Knee Society Score (KSS) and the Forgotten Joint Score (FJS) at final follow‐up. The primary outcome was implants' survivorship, and secondary outcomes included complication rates and functional scores. Statistical analyses included Mann–Whitney and Chi‐square tests for group comparisons, Kaplan–Meier survival analysis for implant survivorship, and multivariate regression for key covariates. Results Implant survivorship was 99.4% in Group B over a median follow‐up of 30 months, with one revision due to aseptic loosening and 100% in Group A ( p = 0.36). The overall complication rates were 12.7% in Group A and 10.2% in B ( p = 0.48). The median KSS‐knee and function scores were 94.5 and 90 in Group A and 94 and 90 in B ( p = 0.88 and 0.8, respectively). The final FJS was 82 in Group A and 84 in B ( p = 0.8). No significant differences were observed in postoperative knee range of motion between the two groups. Multivariate regression analysis showed that none of the included covariates were statistically significant predictors of implant failure. Conclusion FA in robotic‐assisted TKA with tibial positioning >3° varus seems to be safe and reliable in patients with varus deformity, demonstrating similar revision rates, implant survivorship, and outcomes compared to the ≤3° tibial varus group. Level of Evidence Level III
Molecular and cell phenotype programs in oral epithelial cells directed by co‐exposure to arsenic and smokeless tobacco
No full textInternational audienceAbstract Chronic exposure to arsenic can lead to various health issues, including cancer. Concerns have been mounting about the enhancement of arsenic toxicity through co‐exposure to various prevalent lifestyle habits. Smokeless tobacco (SLT) products are commonly consumed in South Asian countries, where their use frequently co‐occurs with exposure to arsenic from contaminated groundwater. To decipher the in vitro molecular and cellular responses to arsenic and/or smokeless tobacco, we performed temporal multi‐omics analysis of the transcriptome and DNA methylome remodeling in exposed hTERT‐immortalized human normal oral keratinocytes (NOK), as well as arsenic and/or smokeless tobacco genotoxicity and mutagenicity investigations in NOK cells and in human p53 knock‐in murine embryonic fibroblasts (Hupki MEF). RNAseq results from acute exposures of NOK cell to arsenic alone and in combination with smokeless tobacco extract revealed upregulation of genes with roles in cell cycle changes, apoptosis and inflammatory responses. This was in keeping with global DNA hypomethylation affecting genes involved in the same processes after chronic treatment. At the phenotypic level, we observed a dose‐dependent decrease in NOK cell viability, induction of DNA damage, cell cycle changes and increased apoptosis, with the most pronounced effects observed under arsenic and SLT co‐exposure conditions. Live‐cell imaging experiments indicated that the DNA damage likely resulted from induction of apoptosis, an observation validated by a lack of exome‐wide mutagenesis in response to chronic exposure to arsenic and/or smokeless tobacco. In sum, our integrative omics study provides novel insights into the acute and chronic responses to arsenic and smokeless tobacco (co‐)exposure, with both types of responses converging on several key mechanisms associated with cancer hallmark processes. The resulting rich catalogue of molecular programs in oral cells regulated by arsenic and smokeless tobacco (co‐)exposure may provide bases for future development of biomarkers for use in molecular cancer epidemiology studies of exposed populations at risk
Nighttime Treatment of Ruptured Intracranial Aneurysms Are Associated With Poor Outcomes
No full textInternational audienceBACKGROUND AND OBJECTIVES: Rebleeding of ruptured intracranial aneurysms (RIA) is associated with poor outcomes. Although immediate treatment of RIAs is preferred, optimal treatment timing is multifactorial and may be a complicating factor for achieving the best outcomes. The objective of this study was to compare outcomes for patients with RIAs as a function of treatment time of day. To the best of our knowledge, this is the first study that examines how treatment time of day influences treatment outcomes. METHODS: This retrospective single-center study included all patients who were treated, either surgically or endovascularly, for RIAs within 24 hours after admission. Exclusion criteria were blister, mycotic or giant aneurysms, or incomplete records. The modified Rankin Scale was used to evaluate treatment outcomes using multivariate analysis. Nighttime treatment was defined when greater than 50% of the procedure was performed between 10 pm and 7 am , with other times classified as daytime treatment. Off-hours treatment was defined when more than 50% of the procedure was performed between 7 pm and 7 am , with other times classified as on-hours. RESULTS: This study included 493 patients, with 84.2% (415) treated during the daytime, 15.8% (78) during the nighttime, 67.5% (333) during on-hours, and 32.5% (160) during off-hours. These groups did not differ according to age, sex, World Federation of Neurosurgical Societies and Fisher scales, aneurysm size, location, and surgical or endovascular treatment. Outcomes were favorable (modified Rankin Scale 0-2) for 72.0% (299) of patients treated during the daytime and 60.0% (46) of patients treated during the nighttime. Aneurysm treatment during the nighttime (OR: 0.50 [95% CI: 0.28-0.91], P = .023) but not during off-hours (OR: 0.76 [0.50-1.14], P = .18) was independently associated with unfavorable outcomes. CONCLUSION: Nighttime treatment was associated with poorer outcomes. Further studies are needed to evaluate outcomes if treatment is postponed to daytime hours
CDK4 inactivation inhibits apoptosis via mitochondria-ER contact remodeling in triple-negative breast cancer
No full textInternational audienceAbstract The energetic demands of proliferating cells during tumorigenesis require close coordination between the cell cycle and metabolism. While CDK4 is known for its role in cell proliferation, its metabolic function in cancer, particularly in triple-negative breast cancer (TNBC), remains unclear. Our study, using genetic and pharmacological approaches, reveals that CDK4 inactivation only modestly impacts TNBC cell proliferation and tumor formation. Notably, CDK4 depletion or long-term CDK4/6 inhibition confers resistance to apoptosis in TNBC cells. Mechanistically, CDK4 enhances mitochondria-endoplasmic reticulum contact (MERCs) formation, promoting mitochondrial fission and ER-mitochondrial calcium signaling, which are crucial for TNBC metabolic flexibility. Phosphoproteomic analysis identified CDK4’s role in regulating PKA activity at MERCs. In this work, we highlight CDK4’s role in mitochondrial apoptosis inhibition and suggest that targeting MERCs-associated metabolic shifts could enhance TNBC therapy
Improving hydroacoustic methods for monitoring suspended‐sand flux and grain size in sediment‐laden rivers
No full textInternational audienceAbstract Suspended‐sand concentration and grain‐size data in rivers provide valuable information on the catchment's dynamics for scientists and river managers. Producing continuous measurements of suspended‐sand concentrations remains a scientific challenge due to their high spatial and temporal variability. Traditional methods such as sediment‐rating curves may be highly uncertain, and optical turbidity is insensitive to coarse particles when there are many fine particles. Surrogate hydroacoustic methods aim to improve sand concentration measurements. These single‐ or dual‐frequency acoustic methods use acoustic attenuation and/or backscatter to estimate fine‐sediment (i.e., silt and clay) and/or sand concentration and possibly grain size. New methods have recently been developed and applied in rivers exhibiting a wide range of sediment conditions in North America but not independently tested elsewhere by other researchers. In this article, we apply, adapt and evaluate hydroacoustic methods to continuously estimate suspended‐sand concentration and grain size in an Alpine river with high suspended‐sediment concentrations. From the example of the River Isère at Grenoble Campus, France, we show that the hydroacoustic methods adapted to local conditions may yield valuable sand concentration estimates consistent with traditional measurements. Compared with prior knowledge, limited additional information on the grain size can be obtained due to high uncertainties. Hydroacoustic concentration estimates are more sensitive to real changes in concentration at the event scale than traditional rating‐curve methods that relate concentration to discharge only. These findings open the perspective for facilitated sand concentration monitoring at a higher temporal resolution with decreased field work
Virtual surgical planning in orthognathic surgery: A prospective evaluation of postoperative accuracy
No full textInternational audienceObjectives: The development of 3D computer-assisted technologies over the past years has led to vast improvements in orthognathic surgery. The aim of the present study was to evaluate differences in maxillary position between 3D virtual surgical planning (VSP) and surgical results.Materials and methods: We assessed data from 25 patients who underwent bimaxillary non-segmented orthognathic surgery with 3D VSP. Each patient underwent a postoperative CT scan within 40 days after surgery. We compared the STL (Standard Triangulation Language) file from the VSP with that obtained from the postoperative CT.Results: According to our comparative analysis, the postoperative and VSP 3D models did not statistically differ. The Lin concordance correlation coefficient was always >0.95 for each landmark, but in 21 patients (84 % of the sample) we identified at least one point with a difference of more than 1.5 mm between the postoperative and VSP 3D model on at least one axis. The most frequently observed differences corresponded to sagittal translation and pitch rotation.Conclusions: An intraoperative clinical and aesthetic evaluation of the consequences of bone movements on patient face is strongly recommended, also when we use VSP because we may have clinically significant differences from the planning
Comparable outcomes between cruciate‐substituting and posterior‐stabilized inserts in robotic total knee arthroplasty under the functional alignment principles
No full textInternational audienceAbstract Purpose Functional alignment (FA) has emerged as a personalized strategy in total knee arthroplasty (TKA) to optimize outcomes by accounting for patient‐specific anatomical and soft tissue characteristics. Limited evidence exists on how polyethylene insert type, specifically cruciate‐substituting (CS) versus posterior‐stabilized (PS), impacts clinical outcomes and complications in this context. Methods This retrospective comparative study included 329 patients who underwent robotic‐assisted TKA with FA principles with a minimum 2‐year follow‐up. Patients were divided into two groups: CS or PS implants. CS inserts were selected for patients with an intact posterior cruciate ligament (PCL), while PS inserts were used in cases of PCL insufficiency or significant flexion contractures. Preoperative and post‐operative outcomes, including Knee Society Scores (KSS), Forgotten Joint Scores (FJS), range of motion (ROM) and complications, were assessed. Implant survivorship was analyzed using the Kaplan–Meier method. Results At a median follow‐up of 36 months, no significant differences were observed between CS and PS groups in KSS (knee: p = 0.45; function: p = 0.4), FJS ( p = 0.7) or ROM (median flexion: 130° in both groups, p = 0.52). Specific complications included intraoperative lateral condyle fractures in the PS group and femoral component revisions due to instability in the CS group. The overall complication rates and implant survivorship were comparable ( p = 0.55 and p = 0.85, respectively). Conclusion This study is the first to evaluate polyethylene insert type in FA and demonstrates that both CS and PS inserts provide comparable outcomes and safety profiles in robotic‐assisted TKA. These findings underscore the importance of patient‐specific implant selection, with further research needed to assess long‐term results. Level of Evidence Level III
Cold snaring vs. standard forceps biopsy in sampling colorectal cancer: a comparative case report
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Early bacterial co-infections and ventilator-associated lower respiratory tract infections among intubated patients during the first and second COVID-19 waves: a European comparative cohort study
No full textInternational audienceBackground: The management of severe SARS-CoV-2 pneumonia, alongside logistical constraints, evolved between the first and subsequent COVID-19 waves. This study aimed to compare the prevalence of early bacterial pulmonary co-infections and the incidence of ventilator-associated lower respiratory tract infections (VA-LRTI) across the first and second waves of the pandemic, and to characterize their microbiology.Methods: Latter part of a multicenter retrospective European cohort analysis conducted in 35 ICUs. Adult patients admitted for SARS-CoV-2 pneumonia and requiring invasive mechanical ventilation ≥ 48 h were consecutively included from both waves (February-May 2020 for period 1, October 2020-April 2021 for period 2). Co-infections were defined by bacterial isolation in respiratory secretions or blood cultures, or a positive pneumococcal urinary antigen test, within 48 h after intubation. VA-LRTI, including ventilator-associated tracheobronchitis (VAT) and ventilator-associated pneumonia (VAP), were diagnosed using clinical, radiological and quantitative microbiological criteria. The 28-day cumulative incidence of first VA-LRTI episodes was estimated using the Kalbfleisch and Prentice method, with co-infection prevalence and VA-LRTI incidence compared using multivariable logistic regression and Fine-and-Gray models, respectively.Results: The study included 1,154 patients (558 in period 1 and 596 in period 2). Co-infection prevalence significantly rose from 9.7% in period 1 to 14.9% in period 2 (adjusted odds ratio (95% confidence interval) 1.52 (1.04-2.22), p = 0.03). Gram-positive cocci dropped from 59 to 48% of co-infections between periods 1 and 2. The overall incidence of VA-LRTI was similar across periods (50.4% and 53.9%, adjusted sub distribution hazard ratio (sHR) 1.14 (0.96-1.35), p = 0.11), with a significant increase in VAP incidence in period 2 (36% to 44.8%, adjusted sHR 1.37 (1.12-1.66), p = 0.001), predominantly occurring within the initial 14 days after intubation, and a concurrent significant decrease in VAT incidence (14.3% to 9.1%, adjusted sHR 0.61 (0.42-0.88), p = 0.007). Gram-negative bacilli, led by Pseudomonas aeruginosa, Enterobacter spp., and Klebsiella spp., were responsible for 89% and 84% of VA-LRTI in periods 1 and 2, respectively.Conclusions: Between the first and second COVID-19 waves, the prevalence of early bacterial pulmonary co-infections significantly increased among intubated patients. Although the overall incidence of VA-LRTI remained stable, there was a significant shift from VAT to VAP episodes