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Tumor mutation burden (TMB) is often used as a biomarker for immunogenicity and prerequisite for immune checkpoint inhibitor (ICI) therapy. However, it is becoming increasingly evident that not all tumors with high TMB respond to ICIs as expected. It has been shown that the ability of T-cells to infiltrate the tumor microenvironment and elicit a specific immune response is dependent not only on the TMB, but also on intra-tumor heterogeneity and the fraction of low-frequency subclonal mutations that make up the tumor. High intra-tumor heterogeneity leads to inefficient recognition of tumor neoantigens by T-cells due to their diluted frequency and spatial heterogeneity. Clinical studies have shown that tumors with a high degree of intra-tumor heterogeneity respond poorly to ICI therapy, and previous cytotoxic treatment may increase the intra-tumor heterogeneity and render second-line ICI therapy less effective. This paper reviews the role of ICI therapy when following chemotherapy or radiation to determine if they may be better suited as first-line therapy in patients with high TMB, low intra-tumor heterogeneity, and high PD-1, PD-L1, or CTLA-4 expression.

Herein, we report the optimization of Pb(II) ions removal from soil by electrokinetic remediation, using the response surface methodology (RSM) based on central composite design (CCD) describing individual and interactive effects of three chosen variables: the current intensity (I), electrolyte concentration (C) and remediation time (t). Sulfuric acid was selected as the electrolyte medium. The physicochemical properties of the soil were well characterized. The electrokinetic remediation (EKR) experiments were performed in galvanostatic mode, at constant current intensity. The lead Pb(II) content was measured using the atomic absorption spectrophotometer (AAS). Designing and modeling of the experimental runs were done using the Design Expert software. The results establish that the quadratic polynomial model matches the experimental data between the removal efficiency (η %) and the influencing factors. The obtained p-values (<0.05) through ANOVA analysis reveal a significant term, suggesting that the model was satisfactory. The significance of influencing factors increases is in that order: I < C (H2SO4) < t; increasing the remediation time translates into higher removal efficiencies. The statistical optimization strategy used in this study was successful in attaining the maximal lead removal of 86.79% using current intensity of 0.05 A, H2SO4 concentration of 0.05 M, and remediation time of 24 h 38 min. Ultimately, besides the great potential of the electrokinetic remediation for efficient removal of Pb(II) species, the RSM-based CCD is a promising and valuable tool for modeling and optimizing their elimination from contaminated soils. [ABSTRACT FROM AUTHOR]

The study undertaken in this work indicates that it is possible to exploit the industrial by products such as fly ash and bottom ash from the combustion of coal in Jorf lasfar thermal power and valorize them as additive in the construction materials. Because in addition to their poozolanic activity, these ashes have technical, economical and ecological compelling interests. In this work we have studied the effects of substitution of limestone in the CPJ45 cement by fly ash or bottom ash on the mechanical properties of prepared mortars, on the grinding time and on the hydration of the new cements. Different analysis techniques were undertaken to determine the physico-chemical characteristics of the starting materials. X-ray fluorescence (XRF) had permitted the classification of fly ash and bottom ash in the class F from their levels on major oxides. Rietveld quantitative phase analysis (RQPA) allowed us to compare the percentages of clinker phases with that calculated with bogue formulas. The result showed that the values found by RQPA of C3S and C3A were much higher than those calculated, while for the C2S the values given by RQPA were much lower. The isothermal conduction micro calorimeter was used to measure the heat evolution during the hydration of the cements prepared. We noticed that the additions of fly ash or bottom ash have accelerated the hydration of C3A and have delayed that of C3S. The tests performed by substituting limestone in CPJ45 by different proportions of fly ash or bottom ash have shown that the effect of these ashes on the mechanical properties of cement CPJ45. We have observed that the 28days mechanical strengths of the mortar went for a maximum with the substitution of lime stone by 6% of fly ash and 7% of bottom ash; We have also observed that increasing the amount of substitution of lime stone by fly ash had decreased the grinding time and had eliminated the clogging of the cement on the mill balls.

Purpose: Net ultrafiltration (UF NET ) during continuous renal replacement therapy (CRRT) can control fluid balance (FB), but is usually 0 ml·h -1 in patients with vasopressors due to the risk of hemodynamic instability associated with CRRT (HIRRT). We evaluated a UF NET strategy adjusted by functional hemodynamics to control the FB of patients with vasopressors, compared to the standard of care., Methods: In this randomized, controlled, open-label, parallel-group, multicenter, proof-of-concept trial, adults receiving vasopressors, CRRT since ≤ 24 h and cardiac output monitoring were randomized (ratio 1:1) to receive during 72 h a UF NET  ≥ 100 ml·h -1 , adjusted using a functional hemodynamic protocol (intervention), or a UF NET  ≤ 25 ml·h -1 (control). The primary outcome was the cumulative FB at 72 h and was analyzed in patients alive at 72 h and in whom monitoring and CRRT were continuously provided (modified intention-to-treat population [mITT]). Secondary outcomes were analyzed in the intention-to-treat (ITT) population., Results: Between June 2021 and April 2023, 55 patients (age 69 [interquartile range, IQR: 62; 74], 35% female, Sequential Organ Failure Assessment (SOFA) 13 [11; 15]) were randomized (25 interventions, 30 controls). In the mITT population, (21 interventions, 24 controls), the 72 h FB was -2650 [-4574; -309] ml in the intervention arm, and 1841 [821; 5327] ml in controls (difference: 4942 [95% confidence interval: 2736-6902] ml, P < 0.01). Hemodynamics, oxygenation and the number of HIRRT at 72 h, and day-90 mortality did not statistically differ between arms., Conclusion: In patients with vasopressors, a UF NET fluid removal strategy secured by a hemodynamic protocol allowed active fluid balance control, compared to the standard of care., (© 2024. The Author(s).)

This study introduces an optimized hybrid deep learning approach that leverages meteorological data to improve short-term wind energy forecasting in desert regions. Over a year, various machine learning and deep learning models have been tested across different wind speed categories, with multiple performance metrics used for evaluation. Hyperparameter optimization for the LSTM and Conv-Dual Attention Long Short-Term Memory (Conv-DA-LSTM) architectures was performed. A comparison of the techniques indicates that the deep learning methods consistently outperform the classical techniques, with Conv-DA-LSTM yielding the best overall performance with a clear margin. This method obtained the lowest error rates (RMSE: 71.866) and the highest level of accuracy (R 2 : 0.93). The optimization clearly works for higher wind speeds, achieving a remarkable improvement of 22.9%. When we look at the monthly performance, all the months presented at least some level of consistent enhancement (RRMSE reductions from 1.6 to 10.2%). These findings highlight the potential of advanced deep learning techniques in enhancing wind energy forecasting accuracy, particularly in challenging desert environments. The hybrid method developed in this study presents a promising direction for improving renewable energy management. This allows for more efficient resource allocation and improves wind resource predictability., (© 2024. The Author(s).)

Rapid, simultaneous detection of organic chemical pollutants in water is an important issue to solve for protecting human health. This study investigated the possibility of developing an in situ reusable optical sensor capable of selective measurements utilizing a chalcogenide transducer supplemented by a hydrophobic polymer membrane with detection based on evanescent waves in the mid-infrared spectrum. In order to optimise a polyisobutylene hydrophobic film deposited on a chalcogenide waveguide, a zinc selenide prism was utilized as a testbed for performing attenuated total reflection with Fourier-transform infrared spectroscopy. To comply with the levels mentioned in health guidelines, the target detection range in this study was kept rather low, with the concentration range extended from 50 ppb to 100 ppm to cover accidental pollution problems, while targeted hydrocarbons (benzene, toluene, and xylene) were still detected at a concentration of 100 ppb. Infrared measurements in the selected range showed a linear behaviour, with the exception of two constantly reproducible plateau phases around 25 and 80 ppm, which were observable for two polymer film thicknesses of 5 and 10 μm. The polymer was also found to be reusable by regenerating it with water between individual measurements by increasing the water temperature and flow to facilitate reverse exchange kinetics. Given the good conformability of the hydrophobic polymer when coated on chalcogenide photonic circuits and its demonstrated ability to detect organic pollutants in water and to be regenerated afterwards, a microfluidic channel utilising water flow over an evanescent wave optical transducer based on a chalcogenide waveguide and a polyisobutylene (PIB) hydrophobic layer deposited on its surface was successfully fabricated from polydimethylsiloxane by filling a mold prepared via CAD and 3D printing techniques.

Aim: To investigate the performance of the 2021 ERC/ESICM-recommended algorithm for predicting poor outcome after cardiac arrest (CA) and potential tools for predicting neurological recovery in patients with indeterminate outcome., Methods: Prospective, multicenter study on out-of-hospital CA survivors from 28 ICUs of the AfterROSC network. In patients comatose with a Glasgow Coma Scale motor score ≤3 at ≥72 h after resuscitation, we measured: (1) the accuracy of neurological examination, biomarkers (neuron-specific enolase, NSE), electrophysiology (EEG and SSEP) and neuroimaging (brain CT and MRI) for predicting poor outcome (modified Rankin scale score ≥4 at 90 days), and (2) the ability of low or decreasing NSE levels and benign EEG to predict good outcome in patients whose prognosis remained indeterminate., Results: Among 337 included patients, the ERC-ESICM algorithm predicted poor neurological outcome in 175 patients, and the positive predictive value for an unfavourable outcome was 100% [98-100]%. The specificity of individual predictors ranged from 90% for EEG to 100% for clinical examination and SSEP. Among the remaining 162 patients with indeterminate outcome, a combination of 2 favourable signs predicted good outcome with 99[96-100]% specificity and 23[11-38]% sensitivity., Conclusion: All comatose resuscitated patients who fulfilled the ERC-ESICM criteria for poor outcome after CA had poor outcome at three months, even if a self-fulfilling prophecy cannot be completely excluded. In patients with indeterminate outcome (half of the population), favourable signs predicted neurological recovery, reducing prognostic uncertainty., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: “Jean Baptiste Lascarrou reports financial support was provided by BD. Jean Baptiste Lascarrou reports financial support was provided by Masimo Corporation. Guillaume Geri reports financial support was provided by BD. Guillaume Geri reports financial support was provided by Bard. Claudio Sandroni and Alain Cariou are Associate Editor of Resuscitation If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper”., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: Tuberculosis remains a major global health challenge, with delayed diagnosis contributing to increased transmission and disease burden. While microbiological tests are the gold standard for confirming active tuberculosis, many cases lack microbiological evidence, necessitating additional clinical and laboratory data for diagnosis. The complete blood count (CBC), an inexpensive and widely available test, could provide a valuable tool for tuberculosis diagnosis by analyzing disturbances in blood parameters. This study aimed to develop and evaluate a machine learning (ML)-based web application, TubIAgnosis, for diagnosing active tuberculosis using CBC data., Methods: We conducted a retrospective case-control study using data from 449 tuberculosis patients and 1200 healthy controls in Oran, Algeria, from January 2016 to April 2023. Eight ML algorithms were trained on 18 CBC parameters and demographic data. Model performance was evaluated using balanced accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve (AUC)., Results: The best-performing model, Extreme Gradient Boosting (XGB), achieved a balanced accuracy of 83.3%, AUC of 89.4%, sensitivity of 83.3%, and specificity of 83.3% on the testing dataset. Platelet-to-lymphocyte ratio was the most influential parameter in this ML predictive model. The best performing model (XGB) was made available online as a web application called TubIAgnosis, which is available free of charge at https://yh5f0z-ghermi-mohamed.shinyapps.io/TubIAgnosis/., Conclusions: TubIAgnosis, a ML-based web application utilizing CBC data, demonstrated promising performance for diagnosing active tuberculosis. This accessible and cost-effective tool could complement existing diagnostic methods, particularly in resource-limited settings. Prospective studies are warranted to further validate and refine this approach., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background: The severity and course of sepsis-associated acute kidney injury (SA-AKI) are correlated with the mortality rate. Early detection of SA-AKI subphenotypes might facilitate the rapid provision of individualized care., Patients and Methods: In this post-hoc analysis of a multicenter prospective study, we combined conventional kidney function variables with serial measurements of urine (tissue inhibitor of metalloproteinase-2 [TIMP-2])* (insulin-like growth factor-binding protein [IGFBP7]) at 0, 6, 12, and 24 h) and then using an unsupervised hierarchical clustering of principal components (HCPC) approach to identify different phenotypes of SA-AKI. We then compared the subphenotypes with regard to a composite outcome of in-hospital death or the initiation of renal replacement therapy (RRT)., Results: We included 184 patients presenting SA-AKI within 6 h of the initiation of catecholamines. Three distinct subphenotypes were identified: subphenotype A (99 patients) was characterized by a normal urine output (UO), a low SCr and a low [TIMP-2]*[IGFBP7] level; subphenotype B (74 patients) was characterized by existing chronic kidney disease (CKD), a higher SCr, a low UO, and an intermediate [TIMP-2]*[IGFBP7] level; and subphenotype C was characterized by very low UO, a very high [TIMP-2]*[IGFBP7] level, and an intermediate SCr level. With subphenotype A as the reference, the adjusted hazard ratio (aHR) [95%CI] for the composite outcome was 3.77 [1.92-7.42] ( p  < 0.001) for subphenotype B and 4.80 [1.67-13.82] ( p  = 0.004) for subphenotype C., Conclusions: Combining conventional kidney function variables with urine measurements of [TIMP-2]*[IGFBP7] might help to identify distinct SA-AKI subphenotypes with different short-term courses and survival rates.

Background: Outcomes in patients with relatively high His-bundle (HB) capture thresholds at implantation are unknown. This study aimed to compare changes in the HB capture threshold and prognosis between patients with a relatively high threshold and those with a low threshold., Methods and Results: Forty-nine patients who underwent permanent HB pacing (HBP) were divided into two groups: low (<1.25 V at 1.0 ms; n=35) and high (1.25-2.49 V; n=14) baseline HB capture threshold groups. The HB capture threshold was evaluated at implantation, and after 1 week, 1, 3, and 6 months, and every 6 months thereafter. HB capture threshold rise was defined as threshold rise ≥1.0 V at 1.0 ms compared with implantation measures. We compared outcomes between the groups. During a mean follow-up period of 34.6 months, the high-threshold group showed a trend toward a higher incidence of HB capture threshold of ≥2.5 V (50% vs. 14%; P=0.023), HBP abandonment (29% vs. 8.6%; P=0.091), lead revision (21% vs. 2.9%; P=0.065), and clinical events (all-cause death, heart failure hospitalization, and new-onset or progression of atrial fibrillation; 50% vs. 23%; P=0.089) than the low-threshold group. A baseline HB capture threshold of ≥1.25V was an independent predictor of clinical events., Conclusions: A relatively high HB capture threshold is associated with increased risk of HBP abandonment, lead revision, and poor clinical outcomes., Competing Interests: S.Y. and R.S. are affiliated with a department sponsored by Medtronic Japan. T.M. is a member of Circulation Reports’ Editorial Team. The other authors have no conflicts of interest to disclose., (Copyright © 2024, THE JAPANESE CIRCULATION SOCIETY.)

Introduction: In Algeria, the number of patients treated by dialysis is estimated at 23,798 in 2019. Kidney transplantation is the best therapeutic option for patients suffering from end stage kidney Disease (ESKD). However, this procedure is costly and requires complex management. The aim of this study is to assess the costs associated with kidney transplantation at the University Hospital Establishment of Oran, Algeria (UHEO)., Materials and Methods: A retrospective, descriptive, monocentric study was carried out on 31 patients who underwent kidney transplantation at the UHEO. Estimated costs included drugs, consumables, imaging and laboratory tests for pre-transplant examinations, immediate post-transplant hospitalization, post-transplant follow-up and management of any complications., Results: The average cost of graft preparation was 485,438.31 Algerian Dinar (DZD). Immediate post-transplant hospitalization represented an average cost of 375,484.70 DZD. The first year post-transplantation was the most costly with an average cost of 1,305,197.40 DZD mainly attributed to treatment, hospitalization, clinical and paraclinical examinations., Conclusion: This study estimated the cost of kidney transplantation at the UHEO and revealed that the cost of the first year is the most important due to many factors. It also showed that costs tend to decrease with the age of the transplant and the clinical stability of the recipient.

Background: The TactiFlex SE catheter (TFSE, Abbott) with a contact force (CF) sensor and a laser-cut irrigated-tip has recently become available but lacks a lesion quality marker. This study aimed to explore distinctions in lesion characteristics between the TFSE and the ThermoCool SmartTouch SurroundFlow catheter (STSF, Biosense Webster), which utilizes a porous irrigated tip, and to assess the most effective application settings for the TFSE., Methods: Lesions were generated using varying settings of radiofrequency power (30-50 W), CF (10-20 g), application duration (10-40 s), and catheter orientation (perpendicular or parallel) in an ex vivo porcine model. Comparative analysis between the TFSE and STSF was conducted for lesion characteristics and incidence of steam pops using predictive models in regression analyses., Results: Among 720 applications, the TFSE exhibited a significantly lower incidence of steam pops compared to the STSF (0.6% vs. 36.8%, P < 0.001). Moreover, coefficients of determination (R 2 ) for the TFSE were higher than those for the STSF concerning lesion depth (0.710 vs. 0.541) and volume (0.723 vs. 0.618). The lesion size generated with the TFSE was notably smaller than that with the STSF under identical application settings. Additionally, to achieve a lesion depth ≥ 4.0 mm, the TFSE required an application duration 8-12 s longer than the STSF under similar settings., Conclusions: The TFSE demonstrated a lower incidence of steam pops and superior predictability in lesion size compared to the STSF. However, the TFSE necessitated a longer application duration than the STSF to achieve an adequate lesion size., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

There is a strong interest in monitoring copper in environmental waters, but its direct analysis suffers from strong matrix interferences. This is why, a sample pretreatment based on solid-phase extraction (SPE) is often used but conventional sorbents usually lack specificity. It is overcome with ion-imprinted polymers (IIPs). This work evaluates for the first time the use of the dummy approach for the synthesis of Cu(II)-targeting IIPs. Two analog ions Ni(II) and Zn(II) were tested as templates and the resulting IIPs were packed in SPE cartridges. The SPE procedure was designed by optimizing a washing step following the sample percolation, to eliminate the interfering ions retained on the IIP by non-specific interactions. To optimize the washing step, solutions at different pH or containing tris(hydroxymethyl)aminomethane as a complexing agent at different concentrations were tested and combined. Zn-IIP appeared more promising than Ni-IIP, showing excellent specificity and a high selectivity. Its retention capacity was determined to be 100 µg/g, and different isotherm models were evaluated to fit with the adsorption data. Finally, applications to mineral and sea waters were successfully completed and led to high and repeatable extraction recoveries for Cu(II) (88 ± 1% and 83 ± 3%, respectively)., (© 2024 Wiley‐VCH GmbH.)

Purpose: The effect of renal replacement therapy (RRT) in comatose patients with acute kidney injury (AKI) remains unclear. We compared two RRT initiation strategies on the probability of awakening in comatose patients with severe AKI., Methods: We conducted a post hoc analysis of a trial comparing two delayed RRT initiation strategies in patients with severe AKI. Patients were monitored until they had oliguria for more than 72 h and/or blood urea nitrogen higher than 112 mg/dL and then randomized to a delayed strategy (RRT initiated after randomization) or a more-delayed one (RRT initiated if complication occurred or when blood urea nitrogen exceeded 140 mg/dL). We included only comatose patients (Richmond Agitation-Sedation scale [RASS] < - 3), irrespective of sedation, at randomization. A multi-state model was built, defining five mutually exclusive states: death, coma (RASS < - 3), incomplete awakening (RASS [- 3; - 2]), awakening (RASS [- 1; + 1] two consecutive days), and agitation (RASS >  + 1). Primary outcome was the transition from coma to awakening during 28 days after randomization., Results: A total of 168 comatose patients (90 delayed and 78 more-delayed) underwent randomization. The transition intensity from coma to awakening was lower in the more-delayed group (hazard ratio [HR] = 0.36 [0.17-0.78]; p = 0.010). Time spent awake was 10.11 days [8.11-12.15] and 7.63 days [5.57-9.64] in the delayed and the more-delayed groups, respectively. Two sensitivity analyses were performed based on sedation status and sedation practices across centers, yielding comparable results., Conclusion: In comatose patients with severe AKI, a more-delayed RRT initiation strategy resulted in a lower chance of transitioning from coma to awakening., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Rationale: Psychological resilience (the ability to thrive in adversity) may protect against mental-health symptoms in healthcare professionals during coronavirus disease (COVID-19) waves. Objectives: To identify determinants of resilience in ICU staff members. Methods: In this cross-sectional survey in 21 French ICUs, staff members completed the 10-item Connor-Davidson Resilience Scale, Hospital Anxiety and Depression Scale, and Impact of Event Scale-Revised (for post-traumatic stress disorder [PTSD]). Factors independently associated with resilience were identified. Measurements and Main Results: The response rate was 73.1% (950 of 1,300). The median 10-item Connor-Davidson Resilience Scale score was 29 (interquartile range, 25-32). Symptoms of anxiety, depression, and PTSD were present in 61%, 39%, and 36% of staff members, respectively. Distress associated with the COVID-19 infodemic was correlated with symptoms of depression and PTSD. More resilient respondents less often had symptoms of anxiety, depression, and PTSD. Greater resilience was independently associated with male sex, having provided intensive care during the early waves, having managed more than 50 patients with COVID-19, and, compared with earlier waves, working longer hours, having greater motivation, and more often involving families in end-of-life decisions. Independent risk factors for lower resilience were having managed more than 10 patients who died of COVID-19, having felt frightened or isolated, and greater distress from the COVID-19 infodemic. Conclusions: This study identifies modifiable determinants of resilience among ICU staff members. Longitudinal studies are needed to determine whether prior resilience decreases the risk of mental ill health during subsequent challenges. Hospital and ICU managers, for whom preserving mental well-being among staff members is a key duty, should pay careful attention to resilience.

Around 10% of critically ill patients suffer acute kidney injury (AKI) requiring kidney replacement therapy (KRT), with a mortality rate approaching 50%. Although most survivors achieve sufficient renal recovery to be weaned from KRT, there are no recognized guidelines on the optimal period for weaning from KRT. A systematic review was conducted using a peer-reviewed strategy, combining themes of KRT (intermittent hemodialysis, CKRT: continuous veno-venous hemo/dialysis/filtration/diafiltration, sustained low-efficiency dialysis/filtration), factors predictive of successful weaning (defined as a prolonged period without new KRT) and patient outcomes. Our research resulted in studies, all observational, describing clinical and biological parameters predictive of successful weaning from KRT. Urine output prior to KRT cessation is the most studied variable and the most widely used in practice. Other predictive factors, such as urinary urea and creatinine and new urinary and serum renal biomarkers, including cystatin C and neutrophil gelatinase-associated lipocalin (NGAL), were also analyzed in the light of recent studies. This review presents the rationale for early weaning from KRT, the parameters that can guide it, and its practical modalities. Once the patient's clinical condition has stabilized and volume status optimized, a diuresis greater than 500 mL/day should prompt the intensivist to consider weaning. Urinary parameters could be useful in predicting weaning success but have yet to be validated.

CD39 is the rate-limiting enzyme for the molecular signal cascade leading to the generation of ADP and adenosine monophosphate (AMP). In conjunction with CD73, CD39 converts adenosine triphosphate (ATP) to ADP and AMP, which leads to the accumulation of immunosuppressive adenosine in the tumor microenvironment. This review focuses on the role of CD39 and CD73 in immune response and malignant progression, including the expression of CD39 within the tumor microenvironment and its relationship to immune effector cells, and its role in antigen presentation. The role of CD39- and CD73-targeting therapeutics and cancer-directed clinical trials investigating CD39 modulation are also explored.

Background: In immunocompromised patients with acute respiratory failure (ARF), the clinical significance of respiratory virus detection in the nasopharynx remains uncertain., Research Question: Is viral detection in nasopharyngeal swabs associated with causes and outcomes of ARF in immunocompromised patients?, Study Design and Methods: This preplanned post hoc analysis of a randomized controlled trial enrolled immunocompromised patients admitted to 32 ICUs for ARF between May 2016 and December 2017. Nasopharyngeal swabs sampled at inclusion were assessed for 23 respiratory pathogens using multiplex polymerase chain reaction (PCR) assay. Causes of ARF were established by managing physicians and were reviewed by three expert investigators masked to the multiplex PCR assay results. Associations between virus detection in nasopharyngeal swabs, causes of ARF, and composite outcome of day 28 mortality, invasive mechanical ventilation (IMV), or both were assessed., Results: Among the 510 sampled patients, the multiplex PCR assay results were positive in 103 patients (20.2%), and a virus was detected in 102 samples: rhinoviruses or enteroviruses in 35.5%, coronaviruses in 10.9%, and flu-like viruses (influenza virus, parainfluenza virus, respiratory syncytial virus, human metapneumovirus) in 52.7%. The cause of ARF varied significantly according to the results of the multiplex PCR assay, especially the proportion of viral pneumonia: 50.0% with flu-like viruses, 14.0% with other viruses, and 3.6% when no virus was detected (P < .001). No difference was found in the composite outcome of day 28 mortality, IMV, or both according to positive assay findings (54.9% vs 54.7%; P = .965). In a pre-established subgroup analysis, flu-like virus detection was associated with a higher rate of day 28 mortality, IMV, or both among recipients of allogeneic hematopoietic stem cell transplantation compared with those without detected virus., Interpretation: In immunocompromised patients with ARF, the results of nasopharyngeal multiplex PCR assays are not associated with IMV or mortality. A final diagnosis of viral pneumonia is retained in one-third of patients with positive assay results and in one-half of the patients with a flu-like virus., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: J. L. reports receiving personal fees from Qiagen and Abbott Rapid Diagnostics SAS. V. L. received support for article research from Assistance Publique - Hôpitaux de Paris and is treasurer of the GRRR-OH research group, which has received fees from Pfizer, Fisher-Paykel, Gilead, Astellas, Sanofi, and Alexion. F. B. reports personal fees from Merck Sharp and Dohme and BioMérieux outside the submitted work. A. D. reports grants from the French Ministry of Health; grants and personal fees from Philips, Fisher & Paykel, Respinor, and Lungpacer; personal fees from Baxter, Getinge, Gilead, and Lowenstein; and nonfinancial support from Fisher & Paykel outside the submitted work. E. A. has received fees for lectures from MSD, Pfizer, and Alexion; his institution and research group have received support from Baxter, Jazz Pharmaceuticals, Fisher & Paykel, Gilead, Alexion, and Ablynx; and he received support for article research from Assistance Publique - Hôpitaux de Paris. None declared (A. M., M. B., S. M.-D., L. F., S. J., K. K., A. K., L. A., N. B., A.-S. M., E. C., F. P., M. S., D. M.)., (Copyright © 2023 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

This study aims to determine the chemical composition of essential oil (EO) extracted from the aerial parts of Schinus molle L., as well as its phytotoxicity on germination and seedling growth against some invasive weed species of cereal crops and wheat ( Triticum durum , cultivar Chen'S). Gas chromatography/mass spectrometry (GC-MS) identified 51 components (representing 95.26% of the total EO composition). Shyobunone (10.14%), 1-phellandrene (9.63%), α-cadinol (7.46%), δ-cadinene (7.45%), and germacrene D (7.09%) were the most abundant compounds. The effect of EO on weed species germination, root and shoot growth was moderate to strong. When 0.02% and 0.03% of the oil were applied, EO had a strong phytotoxic effect, resulting in 100% failure of Bromus rigidus germination. In addition to determining the responsible compound, the observed phytotoxicity suggestedthat S. molle essential oil could be used as an environmentally friendly biopesticide.

Purpose: Studies have suggested benefits from magnesium sulphate in thrombotic thrombocytopenic purpura (TTP). We aimed to measure the effects of magnesium sulphate supplementation on TTP recovery., Methods: In this multicenter, randomised, double-blind, controlled, superiority study, we enrolled adults with a clinical diagnosis of TTP. Patients were randomly allocated to receive magnesium sulphate (6 g intravenously followed by a continuous infusion of 6 g/24 h for 3 days) or placebo, in addition to the standard treatment. The primary outcome was the median time to platelet normalisation (defined as a platelet count ≥ 150 G/L). Efficacy and safety were assessed by intention-to-treat., Results: Overall, we enrolled 74 participants, including one who withdrew his/her consent. Seventy-three patients were further analyzed, 35 (48%) allocated to magnesium sulphate and 38 (52%) to placebo. The median time to platelet normalisation was 4 days (95% confidence interval [CI], 3-4) in the magnesium sulphate group and 4 days (95% CI 3-5) in the placebo group. The cause-specific hazard ratio of response was 0.93 (95% CI 0.58-1.48, p = 0.75). The number of patients with ≥ 1 serious adverse reactions was similar in the two groups. By day 90, four patients in the magnesium sulphate group and two patients in the placebo group had died (p = 0.42). The most frequent adverse event was low blood pressure occurring in 34% in the magnesium sulphate group and 29% in the placebo group (p = 0.80)., Conclusion: Among patients with TTP, the addition of magnesium sulphate to the standard of care did not result in a significant improvement in time to platelet normalisation., (© 2023. Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: The aim of this study was to determine, in critically ill patients treated with therapeutic plasma exchange (TPE), the incidence of adverse events as well as the incidence of secondary infections and its predictive factors., Design: A multicenter retrospective cohort study of an intensive care population treated with TPE to collect adverse events and infectious complications. The characteristics of patients who developed an infection after plasma exchange were compared with those of patients who did not., Setting: Four ICUs of French university hospitals., Patients: All adults admitted between January 1, 2015, and December 31, 2019, who received at least one plasma exchange session were included., Interventions: None., Measurements and Main Results: A total of 711 TPE sessions were performed on 124 patients. The most frequent TPE indications were thrombotic microangiopathies ( n = 32, 26%), myasthenia gravis ( n = 25, 20%), and acute polyradiculoneuropathy ( n = 12, 10%). Among the 124 patients, 22 (21%) developed arterial hypotension, 12 (12%) fever, and 9 (9%) electrolyte disturbance during TPE. Moreover, 60 (48%) presented at least one infectious complication: ventilator-associated pneumonia 42, pneumonia 13, bacteremia 18 (of which 6 catheter-related infections) viral reactivation 14. Independent risk factors for ICU-acquired infection were the ICU length of stay (24 vs. 7 d; hazard ratio [HR]: 1.09 [1.04-1.15], p < 0.001) and invasive mechanical ventilation (92% vs. 35%; HR: 16.2 [5.0-53.0], p < 0.001)., Conclusions: In critically ill patients treated with TPE, adverse events occurring during the procedure remain moderately frequent and are mostly not life-threatening. Infectious complications, mainly ventilation-associated pneumonia, are frequent in this population. The need of mechanical ventilation and longer ICU stay is associated with an increased risk of infection., Competing Interests: The authors disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Background: Acute respiratory failure (ARF) is the leading cause of ICU admission. Viruses are increasingly recognized as a cause of pneumonia in immunocompromised patients, but epidemiologic data are scarce. We used the Groupe de Recherche en Réanimation Respiratoire en Onco-Hématologie's database (2003-2017, 72 intensive care units) to describe the spectrum of critically ill immunocompromised patients with virus-detected ARF and to report their outcomes. Then, patients with virus-detected ARF were matched based on clinical characteristics and severity (1:3 ratio) with patients with ARF from other origins., Results: Of the 4038 immunocompromised patients in the whole cohort, 370 (9.2%) had a diagnosis of virus-detected ARF and were included in the study. Influenza was the most common virus (59%), followed by respiratory syncytial virus (14%), with significant seasonal variation. An associated bacterial infection was identified in 79 patients (21%) and an invasive pulmonary aspergillosis in 23 patients (6%). The crude in-hospital mortality rate was 37.8%. Factors associated with mortality were: neutropenia (OR = 1.74, 95% confidence interval, CI [1.05-2.89]), poor performance status (OR = 1.84, CI [1.12-3.03]), and the need for invasive mechanical ventilation on the day of admission (OR = 1.97, CI [1.14-3.40]). The type of virus was not associated with mortality. After matching, patients with virus-detected ARF had lower mortality (OR = 0.77, CI [0.60-0.98]) than patients with ARF from other causes. This result was mostly driven by influenza-like viruses, namely, respiratory syncytial virus, parainfluenza virus, and human metapneumovirus (OR = 0.54, CI [0.33-0.88])., Conclusions: In immunocompromised patients with virus-detected ARF, mortality is high, whatever the species, mainly influenced by clinical severity and poor general status. However, compared to non-viral ARF, in-hospital mortality was lower, especially for patients with detected viruses other than influenza., (© 2023. La Société de Réanimation de Langue Francaise = The French Society of Intensive Care (SRLF).)

Background: Out-of-hospital cardiac arrest (OHCA) is a heterogeneous entity with multiple origins and prognoses. An early, reliable assessment of the prognosis is useful to adapt therapeutic strategy, tailor intensity of care, and inform relatives. We aimed primarily to undertake a prospective multicentric study to evaluate predictive performance of the Cardiac Arrest Prognosis (CAHP) Score as compare to historical dataset systematically collected after OHCA (Utstein style criteria). Our secondary aim was to evaluate other dedicated scores for predicting outcome after OHCA and to compare them to Utstein style criteria., Methods: We prospectively collected data from 24 French and Belgium Intensive Care Units (ICUs) between August 2020 and June 2022. All cases of non-traumatic OHCA (cardiac and non-cardiac causes) patients with stable return of spontaneous circulation (ROSC) and comatose at ICU admission (defined by Glasgow coma score ≤ 8) on ICU admission were included. The primary outcome was the modified Rankin scale (mRS) at day 90 after cardiac arrest, assessed by phone interviews. A wide range of developed scores (CAHP, OHCA, CREST, C-Graph, TTM, CAST, NULL-PLEASE, and MIRACLE2) were included, and their accuracies in predicting poor outcome at 90 days after OHCA (defined as mRS ≥ 4) were determined using the area under the receiving operating characteristic curve (AUROC) and the calibration belt., Results: During the study period, 907 patients were screened, and 658 were included in the study. Patients were predominantly male (72%), with a mean age of 61 ± 15, most having collapsed from a supposed cardiac cause (64%). The mortality rate at day 90 was 63% and unfavorable neurological outcomes were observed in 66%. The performance (AUROC) of Utstein criteria for poor outcome prediction was moderate at 0.79 [0.76-0.83], whereas AUROCs from other scores varied from 0.79 [0.75-0.83] to 0.88 [0.86-0.91]. For each score, the proportion of patients for whom individual values could not be calculated varied from 1.4% to 17.4%., Conclusions: In patients admitted to ICUs after a successfully resuscitated OHCA, most of the scores available for the evaluation of the subsequent prognosis are more efficient than the usual Utstein criteria but calibration is unacceptable for some of them. Our results show that some scores (CAHP, sCAHP, mCAHP, OHCA, rCAST) have superior performance, and that their ease and speed of determination should encourage their use. Trial registration https://clinicaltrials.gov/ct2/show/NCT04167891., (© 2023. La Société de Réanimation de Langue Francaise = The French Society of Intensive Care (SRLF).)

Objectives: The use of extended intermittent infusion (EII) or continuous infusion (CI) of meropenem is recommended in intensive care unit (ICU) patients, but few data comparing these two options are available. This retrospective cohort study was conducted between 1 January 2019 and 31 March 2020 in a teaching hospital ICU. It aimed to determine the meropenem plasma concentrations achieved with CI and EII., Methods: The study included septic patients treated with meropenem who had one or more meropenem plasma trough (Cmin) or steady-state concentration (Css) measurement(s), as appropriate. It then assessed the factors independently associated with attainment of the target concentration (Cmin or Css ≥ 10 mg/L) and the toxicity threshold (Cmin or Css ≥ 50 mg/L) using logistic regression models., Results: Among the 70 patients analysed, the characteristics of those treated with EII (n = 33) and CI (n = 37) were balanced with the exception of estimates glomerular filtration rate (eGFR): median 30 mL/min/m 2 (IQR 30, 84) vs. 79 mL/min/m 2 (IQR 30, 124). Of the patients treated with EII, 21 (64%) achieved the target concentration, whereas 31 (97%) of those treated with CI achieved it (P < 0.001). Factors associated with target attainment were: CI (OR 16.28, 95% CI 2.05-407.5), daily dose ≥ 40 mg/kg (OR 12.23, 95% CI 1.76-197.0; P = 0.03) and eGFR (OR 0.98, 95% CI 0.97-0.99; P = 0.02). Attainment of toxicity threshold was associated with daily dose > 70 mg/kg (OR 35.5, 95% CI 5.61-410.3; P < 0.001)., Conclusion: The results suggest the use of meropenem CI at 40-70 mg/kg/day, particularly in septic ICU patients with normal or augmented renal clearance., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: A higher sodium (Na) dialysate concentration is recommended during renal replacement therapy (RRT) of acute kidney injury (AKI) to improve intradialytic hemodynamic tolerance, but it may lead to Na loading to the patient. We aimed to evaluate Na flux according to Na dialysate and infusate concentrations at 140 and 145 mmol/L during hemodialysis (HD) and hemodiafiltration (HDF)., Methods: Fourteen AKI patients that underwent consecutive HD or HDF sessions with Na dialysate/infusate at 140 and 145 mmol/L were included. Per-dialytic flux of Na was estimated using mean sodium logarithmic concentration including diffusive and convective influx. We compared the flux of sodium between HD140 and 145, and between HDF140 and 145., Results: Nine HD140, ten HDF140, nine HD145, and 11 HDF145 sessions were analyzed. A Na gradient from the dialysate/replacement fluid to the patient was observed with dialysate/infusate Na at 145 mmol/L in both HD and HDF (p = 0.01). The comparison of HD145 to HD140 showed that higher Na dialysate induced a diffusive Na gradient to the patient (163 mmol vs. -25 mmol, p = 0.004) and that of HDF145 to -140 (211 vs. 36 mmol, p = 0.03) as well. Intradialytic hemodynamic tolerance was similar across all RRT sessions., Conclusions: During both HD and HDF, a substantial Na loading occurred with a Na dialysate and infusate at 145 mmol/L. This Na loading is smaller in HDF with Na dialysate and infusate concentration at 140 mmol/L and inversed with HD140. Clinical and intradialytic hemodynamic tolerance was fair regardless of Na dialysate and infusate., (© 2022 The Authors. Artificial Organs published by International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Objectives: We aimed at assessing the efficacy and safety on antibiotic exposure of a strategy combining a respiratory multiplex PCR (mPCR) with enlarged panel and daily procalcitonin (PCT) measurements, as compared with a conventional strategy, in adult patients who were critically ill with laboratory-confirmed SARS-CoV-2 pneumonia., Methods: This multicentre, parallel-group, open-label, randomized controlled trial enrolled patients admitted to 13 intensive care units (ICUs) in France. Patients were assigned (1:1) to the control strategy, in which antibiotic streamlining remained at the discretion of the physicians, or interventional strategy, consisting of using mPCR and daily PCT measurements within the first 7 days of randomization to streamline initial antibiotic therapy, with antibiotic continuation encouraged when PCT was >1 ng/mL and discouraged if < 1 ng/mL or decreased by 80% from baseline. All patients underwent conventional microbiological tests and cultures. The primary end point was antibiotic-free days at day 28., Results: Between April 20th and November 23rd 2020, 194 patients were randomized, of whom 191 were retained in the intention-to-treat analysis. Respiratory bacterial co-infection was detected in 48.4% (45/93) and 21.4% (21/98) in the interventional and control group, respectively. The number of antibiotic-free days was 12.0 (0.0; 25.0) and 14.0 (0.0; 24.0) days, respectively (difference, -2.0, (95% CI, -10.6 to 6.6), p=0.89). Superinfection rates were high (51.6% and 48.5%, respectively). Mortality rates and ICU lengths of stay did not differ between groups., Discussion: In severe SARS-CoV-2 pneumonia, the mPCR/PCT algorithm strategy did not affect 28-day antibiotics exposure nor the major clinical outcomes, as compared with routine practice., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Several ion-imprinted polymers (IIPs) were synthesized via bulk polymerization with Cu(II) as template ion, methacrylic acid as functional monomer, ethylene glycol dimethacrylate as crosslinking agent, and azobisisobutyronitrile as initiator in acetonitrile or methanol as porogen solvent. Non-imprinted polymers (NIPs) were similarly synthesized but without Cu(II). After grounding and sieving, the template ions were removed from IIPs particles through several cycles of elimination in 3 M HCl. All NIPs were equally subjected to this acid treatment with the exception of one NIP, called unwashed NIP. The resulting IIP/NIP particles were packed in solid phase extraction (SPE) cartridges for characterization. The SPE protocol was designed by optimizing a washing step following the sample percolation to eliminate potential interfering ions prior to the elution of Cu(II), all fractions analyzed by inductively coupled plasma mass spectrometry. The best IIP showed a high specificity (recovery of Cu(II) vs. interfering ions) and a good selectivity (retention on IIP vs. NIP). Its adsorption capacity was determined to be 63 μg g -1 . Then, a volume of 50 mL was percolated with 30 mg of IIP, thus giving rise to an enrichment factor of 24. Finally, applications to real samples (mineral and sea waters) were successfully performed. In addition, Brunauer-Emmett-Teller analyses showed that the surface area of the washed NIP was almost double that of the unwashed one (140.70 vs. 74.49 m 2  g -1 ), demonstrating for the first time that the post-treatment of a NIP after its synthesis may have a significant impact on its porous structure, and thus need to be more precisely detailed by authors in the future papers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Background: Immune checkpoint inhibitors (ICI) have transformed cancer treatment over the last decade. Alongside this therapeutic improvement, a new variety of side effects has emerged, called immune-related adverse events (irAEs), potentially affecting any organ. Among these irAEs, myocarditis is rare but life-threatening., Methods: We conducted a multicenter cross-sectional retrospective study with the aim of better characterizing ICI-related myocarditis. Myocarditis diagnosis was based on the recent consensus statement of the International Cardio-Oncology Society., Results: Twenty-nine patients were identified, from six different referral centers. Most patients (55%) were treated using anti-programmed-death 1, rather than ICI combination (35%) or anti-programmed-death-ligand 1 (10%). Transthoracic echocardiography was abnormal in 52% of them, and cardiac magnetic resonance showed abnormal features in 14/24 patients (58%). Eleven patients (38%) were classified as severe. Compared with other patients, they had more frequently pre-existing systemic autoimmune disease (45% vs 6%, p=0.018), higher troponin level on admission (42-fold the upper limit vs 3.55-fold, p=0.001), and exhibited anti-acetylcholine receptor autoantibodies (p=0.001). Seven patients (24%) had myocarditis-related death, and eight more patients died from cancer progression during follow-up. Twenty-eight patients received glucocorticoids, 10 underwent plasma exchanges, 8 received intravenous immunoglobulins, and 5 other immunosuppressants. ICI rechallenge was performed in six patients, with only one myocarditis relapse., Discussion: The management of ICI-related myocarditis may be challenging and requires a multidisciplinary approach. Prognostic features are herein described and may help to allow ICI rechallenge for some patients with smoldering presentation, after an accurate evaluation of benefit-risk balance., Competing Interests: Competing interests: AM has received fees from AbbVie, Actelion, CSL Behring, Experf, Novartis, and Shire and declares speaking fees from AstraZeneca, Sanofi-Aventis and BMS in the last 5 years. PG is a medical expert for LFB (Laboratoire Français du Biofractionnement) and has received fees from AbbVie, Actelion, Boehringer Ingelheim France, Bouchara-Recordati, Novartis, Pfizer, and Roche in the last 5 years. Other authors declare that they have no conflicts of interest., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: We aimed to characterize the outcomes of patients with severe meningoencephalitis requiring intensive care., Methods: We conducted a prospective multicenter international cohort study (2017-2020) in 68 centers across 7 countries. Eligible patients were adults admitted to the intensive care unit (ICU) with meningoencephalitis, defined by an acute onset of encephalopathy (Glasgow coma scale (GCS) score [Formula: see text] 13), a cerebrospinal fluid pleocytosis [Formula: see text] 5 cells/mm 3 , and at least two of the following criteria: fever, seizures, focal neurological deficit, abnormal neuroimaging, and/or electroencephalogram. The primary endpoint was poor functional outcome at 3 months, defined by a score of three to six on the modified Rankin scale. Multivariable analyses stratified on centers investigated ICU admission variables associated with the primary endpoint., Results: Among 599 patients enrolled, 589 (98.3%) completed the 3-month follow-up and were included. Overall, 591 etiologies were identified in those patients which were categorized into five groups: acute bacterial meningitis (n = 247, 41.9%); infectious encephalitis of viral, subacute bacterial, or fungal/parasitic origin (n = 140, 23.7%); autoimmune encephalitis (n = 38, 6.4%); neoplastic/toxic encephalitis (n = 11, 1.9%); and encephalitis of unknown origin (n = 155, 26.2%). Overall, 298 patients (50.5%, 95% CI 46.6-54.6%) had a poor functional outcome, including 152 deaths (25.8%). Variables independently associated with a poor functional outcome were age > 60 years (OR 1.75, 95% CI 1.22-2.51), immunodepression (OR 1.98, 95% CI 1.27-3.08), time between hospital and ICU admission > 1 day (OR 2.02, 95% CI 1.44-2.99), a motor component on the GCS [Formula: see text] 3 (OR 2.23, 95% CI 1.49-3.45), hemiparesis/hemiplegia (OR 2.48, 95% CI 1.47-4.18), respiratory failure (OR 1.76, 95% CI 1.05-2.94), and cardiovascular failure (OR 1.72, 95% CI 1.07-2.75). In contrast, administration of a third-generation cephalosporin (OR 0.54, 95% CI 0.37-0.78) and acyclovir (OR 0.55, 95% CI 0.38-0.80) on ICU admission were protective., Conclusion: Meningoencephalitis is a severe neurologic syndrome associated with high mortality and disability rates at 3 months. Actionable factors for which improvement could be made include time from hospital to ICU admission, early antimicrobial therapy, and detection of respiratory and cardiovascular complications at admission., (© 2023. Springer-Verlag GmbH Germany, part of Springer Nature.)