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ImportanceBefore surgery, the best strategy for managing patients who are taking renin-angiotensin system inhibitors (RASIs) (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) is unknown. The lack of evidence leads to conflicting guidelines.ObjectiveTo evaluate whether a continuation strategy vs a discontinuation strategy of RASIs before major noncardiac surgery results in decreased complications at 28 days after surgery.Design, setting, and participantsRandomized clinical trial that included patients who were being treated with a RASI for at least 3 months and were scheduled to undergo a major noncardiac surgery between January 2018 and April 2023 at 40 hospitals in France.InterventionPatients were randomized to continue use of RASIs (n = 1107) until the day of surgery or to discontinue use of RASIs 48 hours prior to surgery (ie, they would take the last dose 3 days before surgery) (n = 1115).Main outcomes and measuresThe primary outcome was a composite of all-cause mortality and major postoperative complications within 28 days after surgery. The key secondary outcomes were episodes of hypotension during surgery, acute kidney injury, postoperative organ failure, and length of stay in the hospital and intensive care unit during the 28 days after surgery.ResultsOf the 2222 patients (mean age, 67 years [SD, 10 years]; 65% were male), 46% were being treated with angiotensin-converting enzyme inhibitors at baseline and 54% were being treated with angiotensin receptor blockers. The rate of all-cause mortality and major postoperative complications was 22% (245 of 1115 patients) in the RASI discontinuation group and 22% (247 of 1107 patients) in the RASI continuation group (risk ratio, 1.02 [95% CI, 0.87-1.19]; P = .85). Episodes of hypotension during surgery occurred in 41% of the patients in the RASI discontinuation group and in 54% of the patients in the RASI continuation group (risk ratio, 1.31 [95% CI, 1.19-1.44]). There were no other differences in the trial outcomes.Conclusions and relevanceAmong patients who underwent major noncardiac surgery, a continuation strategy of RASIs before surgery was not associated with a higher rate of postoperative complications than a discontinuation strategy.Trial registrationClinicalTrials.gov Identifier: NCT03374449.

Purpose To assess the performance of a local open-source large language model (LLM) in various information extraction tasks from real-life emergency brain MRI reports. Materials and Methods All consecutive emergency brain MRI reports written in 2022 from a French quaternary center were retrospectively reviewed. Two radiologists identified MRI scans that were performed in the emergency department for headaches. Four radiologists scored the reports conclusions as either normal or abnormal. Abnormalities were labeled as either headache-causing or incidental. Vicuna (LMSYS Org), an open-source LLM, performed the same tasks. Vicunas performance metrics were evaluated using the radiologists consensus as the reference standard. Results Among the 2398 reports during the study period, radiologists identified 595 that included headaches in the indication (median age of patients, 35 years [IQR, 26-51 years]; 68% [403 of 595] women). A positive finding was reported in 227 of 595 (38%) cases, 136 of which could explain the headache. The LLM had a sensitivity of 98.0% (95% CI: 96.5, 99.0) and specificity of 99.3% (95% CI: 98.8, 99.7) for detecting the presence of headache in the clinical context, a sensitivity of 99.4% (95% CI: 98.3, 99.9) and specificity of 98.6% (95% CI: 92.2, 100.0) for the use of contrast medium injection, a sensitivity of 96.0% (95% CI: 92.5, 98.2) and specificity of 98.9% (95% CI: 97.2, 99.7) for study categorization as either normal or abnormal, and a sensitivity of 88.2% (95% CI: 81.6, 93.1) and specificity of 73% (95% CI: 62, 81) for causal inference between MRI findings and headache. Conclusion An open-source LLM was able to extract information from free-text radiology reports with excellent accuracy without requiring further training. Keywords: Large Language Model (LLM), Generative Pretrained Transformers (GPT), Open Source, Information Extraction, Report, Brain, MRI Supplemental material is available for this article. Published under a CC BY 4.0 license. See also the commentary by Akinci DAntonoli and Bluethgen in this issue.

Car sharing systems emerged as a new answer to mobility challenges in smart and sustainable cities. Despite their apparent success, design and exploitation of such systems raise crucial strategic and operational challenges. To help planners and decision makers, simulation, analysis and optimization models are unavoidable. Based on the formal modelling and analysis power of stochastic Petri nets, this paper proposes a discrete event simulation model for electric car sharing systems for performance and analysis purposes, taking into account their complex dynamic behaviour, organization and parameters including capacities of the stations, battery and energy availability, locations of charging stations and also their car maintenance activities, not negligible compared to the case of bike-sharing systems.

Rationale & Objective: Blood pressure (BP) control is essential for preventing cardiorenal complications in chronic kidney disease (CKD), but most patients fail to reach BP target. We assessed longitudinal patterns of antihypertensive drug prescription and systolic BP. Study Design: Prospective observational cohort study. Setting & Population: In total, 2,755 hypertensive patients with CKD stages 3-4, receiving care from a nephrologist, from the French CKD–Renal Epidemiology and Information Network (CKD-REIN cohort study). Exposure: Patient factors, including sociodemographic characteristics, medical history, and laboratory data, and provider factors, including number of primary care physician and specialist encounters. Outcomes: Changes in antihypertensive drug-class prescription during follow-up: add-on or withdrawal. Analytical Approach: Hierarchical shared-frailty models to estimate hazard ratios (HR) to deal with clustering at the nephrologist level and linear mixed models to describe systolic BP trajectory. Results: At baseline, median age was 69 years, and mean estimated glomerular filtration rate was 33 mL/min/1.73 m². In total, 66% of patients were men, 81% had BP ≥ 130/80 mm Hg, and 75% were prescribed ≥2 antihypertensive drugs. During a median 5-year follow-up, the rate of changes of antihypertensive prescription was 50 per 100 person-years, 23 per 100 for add-ons, and 25 per 100 for withdrawals. After adjusting for risk factors, systolic BP, and the number of antihypertensive drugs, poor medication adherence was associated with increased HR for add-on (1.35, 95% confidence interval [CI], 1.01-1.80), whereas a lower education level was associated with increased HR for withdrawal (1.23, 95% CI, 1.02-1.49) for 9-11 years versus ≥12 years. More frequent nephrologist visits (≥4 vs none) were associated with higher HRs of add-on and withdrawal (1.52, 95% CI, 1.06-2.18; 1.57, 95% CI, 1.12-2.19, respectively), whereas associations with visit frequency to other physicians varied with their specialty. Mean systolic BP decreased by 4 mm Hg following drug add-on but tended to increase thereafter. Limitations: Lack of information on prescriber and drug dosing. Conclusions: In patients with CKD and poor BP control, changes in antihypertensive drug prescriptions are common and relate to clinician preferences and patients’ tolerability. Sustainable reduction in systolic BP after add-on of a drug class is infrequently achieved. Plain-Language Summary: Blood pressure (BP) control remains unattained in most patients with chronic kidney disease (CKD), raising questions about how antihypertensive treatment is managed. Our study highlights dynamic, yet heterogeneous patterns of antihypertensive drug prescriptions in patients with CKD stages 3-4 receiving care from a nephrologist over 5 years of follow-up. Modifiable factors such as high body mass index and poor medication adherence were associated with higher hazard of adding-on an antihypertensive drug class, independently of baseline BP and antihypertensive treatment. Similarly, lower education level was associated with antihypertensive drug withdrawn, as was more frequent visits to primary care physicians, underlining the importance of coordinated care. Sustainable reduction in systolic BP after add-on of a drug class is infrequently achieved and may be related to drug withdrawal and poor treatment adherence.

BackgroundLittle is known about the effect of combined exposure to different air pollutants on mortality in dialysis patients. This study aimed to investigate the association of multiple exposures to air pollutants with all-cause and cause-specific death in dialysis patients.Materials and methodsThis registry-based nationwide cohort study included 90,373 adult kidney failure patients initiating maintenance dialysis between 2012 and 2020 identified from the French REIN registry. Estimated mean annual municipality levels of PM2.5, PM10, and NO2 between 2009 and 2020 were combined in different composite air pollution scores to estimate each participant’s exposure at the residential place one to 3 years before dialysis initiation. Adjusted cause-specific Cox proportional hazard models were used to estimate hazard ratios (HRs) per interquartile range (IQR) greater air pollution score. Effect measure modification was assessed for age, sex, dialysis care model, and baseline comorbidities.ResultsHigher levels of the main air pollution score were associated with a greater rate of all-cause deaths (HR, 1.082 [95% confidence interval (CI), 1.057–1.104] per IQR increase), regardless of the exposure lag. This association was also confirmed in cause-specific analyses, most markedly for infectious mortality (HR, 1.686 [95% CI, 1.470–1.933]). Sensitivity analyses with alternative composite air pollution scores showed consistent findings. Subgroup analyses revealed a significantly stronger association among women and fewer comorbid patients.DiscussionLong-term multiple air pollutant exposure is associated with all-cause and cause-specific mortality among patients receiving maintenance dialysis, suggesting that air pollution may be a significant contributor to the increasing trend of CKD-attributable mortality worldwide.

Multiple myeloma (MM) frequently causes vertebral fractures (VF). Some are lytic lesions and others have the aspect of benign osteoporotic fractures not requiring anti-myeloma treatment. We explored outcome of these patients with smoldering myeloma (SM) and osteoporotic VF.In this retrospective bi-centric study, patients were identified using a systematic keyword search on electronic medical records. Patients with SM and isolated VF of osteoporotic aspect without indications for myeloma-specific therapy were included.Overall, 13 (7 %) of the 184 identified patients had SM and VF confirmed to be osteoporotic (median number of VF was 3). During follow-up, 12 (92 %) patients evolved to symptomatic MM, 7 (54 %) of them within 18 months (early progressors). Myeloma defining events were new lytic bone lesions in 7 patients (53.8 %). The serum calcium level was significantly higher in the early progressor group (median 2.35 IQR [2.31–2.38] and 2.28 IQR [2.21–2.29] respectively, p = 0.003). Early progressors had a higher number of VF at diagnosis (3.0 [2.0–5.5] vs 1.0 [1.0–2.5], p = 0.18) and more frequently evolved to symptomatic MM because of lytic bone lesions (5 [71 %] vs 2 [33 %], p = 0.13) compared to late progressors.VF of osteoporotic appearance in the context of SM is a rare situation but at high risk of rapid progression to symptomatic MM, suggesting that they may represent bone fragility linked to MM infiltration rather than solely osteoporotic fractures. Further studies are needed to assess if earlier treatment might be beneficial in this population.

In chronic myeloid leukemia, the identification of early molecular predictors of stable treatment-free remission (TFR) after tyrosine kinase inhibitor (TKI) discontinuation is challenging. The predictive values of residual disease (BCR::ABL1 quantification) at months 3 and 6 and more recently, BCR::ABL1 transcript halving time (HT) have been described, but no study compared the predictive value of different early parameters. Using a real-world cohort of 408 patients, we compared the performance of the ELTS score, BCR::ABL1 HT, and residual disease at month 3 and 6 to predict the molecular response, achievement of the TKI discontinuation criteria, and TFR maintenance. The performances of BCR::ABL1 HT and residual disease at month 3 were similar. Residual disease at month 6 displayed the best performance for predicting the optimal response (area under the ROC curve between 0.81 and 0.92; cut-off values: 0.11% for MR4 at month 24 and 0.12% for MR4.5 at month 48). Conversely, no early parameter predicted reaching the TKI discontinuation criteria and TFR maintenance. We obtained similar results when patients were divided in subgroups by first-line treatment (imatinib vs second generation TKI, 2G-TKI). We identified a relationship between ELTS score, earlier milestones and TFR maintenance only in the 2G-TKI group. In conclusion, this first comparative study of early therapeutic response parameters showed that they are excellent indicators of TKI efficacy (BCR::ABL1 transcript reduction) and best responders. Conversely, they did not predict the achievement of the TKI discontinuation criteria and TFR maintenance, suggesting that other parameters are involved in TFR maintenance.

Introduction Chronic wound care remains a critical public health challenge in terms of prevalence, quality of life and healthcare costs on a global scale. Currently used methods to assess the size and content of wounds include direct contact techniques based on double-layer film, ruler measurements, digital photography and visual examination. Nowadays, despite these evaluations, close monitoring and tracking of these chronic wounds remain a great challenge. The use of telemonitoring through digital measurement tools may offer a potential means of improving healing management processes. Many studies have evaluated the size and content of the wound through digital devices such as mobile phones and computers. However, the clinical accuracy of these tools remains to be clarified. The objective of this systematic review is to assess and consolidate the current state-of-the-art digital devices for both quantitative (length, width, surface area, perimeter, volume and depth) and qualitative (granulation, fibrin, necrosis and slough) indicators of wound care.Methods and analysis We will include studies using digital measurement methods from databases such as EBSCO, Cochrane Library, MEDLINE, Web of Science and EMBASE, limited to French and English publications until November 15, 2023. Following the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines, selection involves two independent reviewers conducting title and abstract screenings, study selections, data extractions and risk-of-bias assessments using QUADAS-2. Discrepancies will be resolved through discussion or a third reviewer.Ethics and dissemination Primary data will not be collected in this study; thus, ethical approval will not be required. The study’s findings will be published in a peer-reviewed journal.PROSPERO registration number CRD42023396642.

In this study, we successfully synthesized Ce3+-activated gadolinium aluminum garnet phosphors using the sol–gel method, incorporating various Gd3+ substitution levels denoted by the chemical formula (Y0.98−xGdx)3Al5O12:Ce: 0.06 (x = 0, 0.2, 0.4, 0.6). This study allowed us to discern the impact of Gd3+ substitution on garnet phase stability, crystallographic parameters, morphology, and luminescence properties. X-ray diffraction analysis revealed the pronounced sensitivity of the garnet phase to variations in Gd3+ content. Notably, discernible alterations were observed in both the reduction and shift of diffraction peaks, directly correlating with the percentage of Gd3+ doping. X-ray photoelectron spectroscopy revealed distinct core-level photoelectron and Auger transition peaks for yttrium, oxygen, aluminum, and gadolinium (Gd 3d, Gd 4d). Trace amounts of cerium were confirmed by the Ce 3d photoelectron peaks in both spectra, indicating the successful incorporation of the Ce dopant in the materials. Atomic force microscopy revealed that the incorporation of Gd resulted in significant changes, especially in granular formation. Field-emission scanning electron microscopy (FE-SEM) micrographs demonstrated the formation of agglomerated particles alongside a broad and asymmetrical particle size distribution. The particles exhibited an irregular morphology devoid of pores. Photoluminescence analysis revealed the distinctive yellow emission of Ce3+-doped YAG phosphors, attributed to the 5d–4f transition of the Ce3+ ion. Notably, an observed decrease in emission intensity was associated with an increase in Gd3+ content. [ABSTRACT FROM AUTHOR]

Background and Hypothesis Cardiovascular diseases are a leading cause of morbidity and mortality in patients with chronic kidney disease (CKD). Acute kidney injury (AKI) has been increasingly recognized as a potential exacerbating factor for cardiovascular events in these patients. The CKD-REIN study aims to explore the relationship between AKI and the risk of major adverse cardiovascular events (MACE) in a cohort of CKD patients. We hypothesize that AKI is a significant and independent predictor of MACE in patients with CKD, and that the severity of AKI correlates with the risk of subsequent cardiovascular events. Methods This prospective cohort study included 3033 adult CKD patients from 40 outpatient nephrology clinics in France. Patients were followed for a median of 5.2 years. AKI episodes were identified and staged based on the KDIGO-AKI criteria. Cardiovascular events, including myocardial infarction, stroke, heart failure hospitalization, and cardiovascular death, were systematically recorded. The association between AKI and MACE was analyzed using a multivariable Cox model, adjusting for confounders such as demographic characteristics, medical history, and baseline kidney function. Results During the follow-up, 530 patients experienced at least one episode of AKI. The cumulative incidence of MACE at 1 year post-AKI was 8.1%. Patients with AKI had a significantly increased risk of MACE, with an adjusted hazard ratio (HR) of 5.78 (P  < .001). The risk was consistent across different MACE components and was independent of age, sex, CKD stage, or comorbidities. The risk of MACE was higher for more severe AKI stages and for AKI events requiring hospitalization or associated with incomplete renal recovery. Conclusion The findings of this study confirm that AKI is a significant independent predictor of MACE in CKD patients, demonstrating a strong severity–response relationship. These results underscore the importance of vigilant cardiovascular monitoring and preventive strategies in CKD patients following AKI episodes. Understanding the mechanisms linking AKI to cardiovascular outcomes is crucial for developing targeted interventions to mitigate these risks. [ABSTRACT FROM AUTHOR]

Background Although hepatic production of FGF23 has been suggested in chronic settings, there are no data indicating hypophosphatemia resulting from acute hepatic FGF23 production. Based on two clinical observations of profound hypophosphatemia in the setting of acute hepatitis, our study investigates the hypothesis of acute FGF23 liver expression. Methods Retrospective analyses were conducted to estimate FGF23 liver expression both qualitatively (in situ hybridization) and quantitatively (relative FGF23 gene expression and protein production) on histological specimens of human and murine acute hepatitis livers, compared with controls of hepatic fibrosis or healthy liver. Results The index clinical case involves acute alcoholic hepatitis complicated by profound hypophosphatemia due to phosphate diabetes, revealing a major production of both FGF23 C-terminal fraction (cFGF23) and bio-intact form (iFGF23, 39 751 RU/mL, N: 21–91; and 228.6 pg/mL, N: 22.7–93.1, respectively). A second case of acute hepatitis related to erythrocytic protoporphyria also exhibited comparable abnormalities. In both cases, no other cause of renal phosphate wasting was identified, and the hydroelectrolytic disorders disappeared in parallel with normalization of the liver balance and FGF23 levels. Histological data of acute hepatitis compared with cirrhosis and healthy liver confirmed our hypothesis of hepatic FGF23 overproduction. Furthermore, mouse models showed a significant increase in FGF23 mRNA relative liver expression in acute hepatitis and a moderate increase in cirrhosis, compared with healthy liver (respectively 60.55 ± 16.75 and 3.70 ± 0.87 vs 1.00 ± 0.65, both P  < .05). These findings were also confirmed at the protein level. Conclusion This translational study raises the hypothesis of renal phosphate wasting induced by excessive hepatic production of FGF23 in case of acute hepatitis. [ABSTRACT FROM AUTHOR]