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Abstract Background Concomitant chemo-radiotherapy is the reference treatment for non-resectable locally-advanced Non-Small Cell Lung Cancer (NSCLC). Increasing radiotherapy total dose in the whole tumour volume has been shown to be deleterious. Functional imaging with positron emission tomography (PET/CT) offers the potential to identify smaller and biologically meaningful target volumes that could be irradiated with larger doses without compromising Organs At Risk (OAR) tolerance. This study investigated four scenarios, based on 18FDG and 18F-miso PET/CT, to delineate the target volumes and derive radiotherapy plans delivering up to 74Gy. Method Twenty-one NSCLC patients, selected from a prospective phase II trial, had 18FDG- and 18F-miso PET/CT before the start of radiotherapy and 18FDG PET/CT during the radiotherapy (42Gy). The plans were based planned on a standard plan delivering 66 Gy (plan 1) and on three different boost strategies to deliver 74Gy total dose in pre-treatment 18FDG hotspot (70% of SUVmax) (plan 2), pre-treatment 18F-miso target (SUVmax > 1.4) (plan 3) and per-treatment 18FDG residual (40% of SUVmax). (plan 4). Results The mean target volumes were 4.8 cc (± 1.1) for 18FDG hotspot, 38.9 cc (± 14.5) for 18F-miso and 36.0 cc (± 10.1) for per-treatment 18FDG. In standard plan (66 Gy), the mean dose covering 95% of the PTV (D95%) were 66.5 (± 0.33), 66.1 (± 0.32) and 66.1 (± 0.32) Gy for 18FDG hotspot, 18F-miso and per-treatment 18FDG. In scenario 2, the mean D95% was 72.5 (± 0.25) Gy in 18FDG hotspot versus 67.9 (± 0.49) and 67.9 Gy (± 0.52) in 18F-miso and per-treatment 18FDG, respectively. In scenario 3, the mean D95% was 72.2 (± 0.27) Gy to 18F-miso versus 70.4 (± 0.74) and 69.5Gy (± 0.74) for 18FDG hotspot and per-treatment 18FDG, respectively. In scenario 4, the mean D95% was 73.1 (± 0.3) Gy to 18FDG per-treatment versus 71.9 (± 0.61) and 69.8 (± 0.61) Gy for 18FDG hotspot and 18F-miso, respectively. The dose/volume constraints to OARs were matched in all scenarios. Conclusion Escalated doses can be selectively planned in NSCLC target volumes delineated on 18FDG and 18F-miso PET/CT functional images. The most relevant strategy should be investigated in clinical trials. Trial registration (RTEP5, NCT01576796, registered 15 june 2012)

L'optimisation de l'exploitation des gisements d'hydrocarbures est devenue aujourd'hui,avec la grave crise énergétique que nous traversons, le problème numéro un du mondepétrolier. Afin d'améliorer la production on est obligé de mettre en ceuvre des techniques derécupération assistée qui coûtent très cher et dont le choix est basé sur les propriétés physiques du pétrole, de la roche réservoir et l'état d'exploitation même du gisement.Nous avons donc étudié le comportement volumétrique et viscosimétrique de la fraction lourde d'hydrocarbures ainsi que la mise au point d'une technique d'analyse de cette fraction. Nos mesures ont porté essentiellement sur les corps purs suivants : nCe, nC, nC, nC9, nClo, nC12, nC14, nCls, cyclo Ce, cyclo C" cyclo Cs, méthyl cyclo Cg, benzène, toluène, xylène et triméthylbenzène dans un domaine de température et de pression s'étendant de 20 à 120 °C et de la pression atmosphérique à 400 bars.A partir de ces données expérimentales nous avons développé deux modèles prévisionnels : l'un pour la masse volumique des mélanges basé sur l'équation d'état de Redlich-Kwong et l'introduction de coefficients d'interaction binaire, l'autre sur les viscosités des mélanges à partir d'une équation d'Andrade modi-fiée et de la loi de mélange d'Arrhénius. The principal problem facing the petroleum industry during the present severe energy crisis is ta optimise production from hydrocarbon fields. In order to improve production, enhanced recovery techniques must be used. These are extremely expensive and are chosen on the basis of physical properties of the ail, the réservoir rocks and working conditions of the field. The volumetric and viscometric behovior of the heavy hydrocarbon fraction was therefore studied. A technique for analyzing this fraction was also developed. M~asurements essentially concerned the following pure substances : nC, nC, nC, nC, nC1e,nC,,, nC14,nC18, cyclo C,,cycloC,, cyclo Ce, methyl cycIo Cs, benzène, toluene, xylene and trimethylbenzene in temoerature and pressure range from 20 ta 120' C and from on aimospheric pressure to 440 bars. of state and the introduction of binary interaction coefficients, and the other concerned the viscosities of the mixtures on the basis of a modified Andrade equation and the Arrhenius mixing rule.

BackgroundPerioperative anaphylaxis is a rare and acute systemic manifestation of drug-induced hypersensitivity reactions that occurs following anesthesia induction; the two main classes of drugs responsible for these reactions being neuromuscular blocking agents (NMBA) and antibiotics. The sensitization mechanisms to the drugs are not precisely known, and few risk factors have been described. A growing body of evidence underlines a link between occurrence of allergy and microbiota composition. However, no data exist on microbiota in perioperative anaphylaxis. The aim of this study was to compare circulating microbiota richness and composition between perioperative anaphylaxis patients and matched controls.MethodsCirculating 16s rDNA was quantified and sequenced in serum samples from 20 individuals with fully characterized IgE-mediated NMBA-related anaphylaxis and 20 controls matched on sex, age, NMBA received, type of surgery and infectious status. Microbiota composition was analyzed with a published bioinformatic pipeline and links with patients clinical and biological data investigated.ResultsAnalysis of microbiota diversity showed that anaphylaxis patients seem to have a richer circulating microbiota than controls, but no major differences of composition could be detected with global diversity indexes. Pairwise comparison showed a difference in relative abundance between patients and controls for Saprospiraceae, Enterobacteriaceae, Veillonellaceae, Escherichia-Shigella, Pseudarcicella, Rhodoferax, and Lewinella. Some taxa were associated with concentrations of mast cell tryptase and specific IgE.ConclusionWe did not find a global difference in terms of microbiota composition between anaphylaxis patient and controls. However, several taxa were associated with anaphylaxis patients and with their biological data. These findings must be further confirmed in different settings to broaden our understanding of drug anaphylaxis pathophysiology and identify predisposition markers.

Abstract The evaluation of tumor follow-up according to RECIST 1.1 has become essential in clinical practice given its role in therapeutic decision making. At the same time, radiologists are facing an increase in activity while facing a shortage. Radiographic technologists could contribute to the follow-up of these measures, but no studies have evaluated their ability to perform them. Ninety breast cancer patients were performed three CT follow-ups between September 2017 and August 2021. 270 follow-up treatment CT scans were analyzed including 445 target lesions. The rate of agreement of classifications RECIST 1.1 between five technologists and radiologists yielded moderate (k value between 0.47 and 0.52) and substantial (k value = 0.62 and k = 0.67) agreement values. 112 CT were classified as progressive disease (PD) by the radiologists, and 414 new lesions were identified. The analysis showed a percentage of strict agreement of progressive disease classification between reader-technologists and radiologists ranging from substantial to almost perfect agreement (range 73–97%). Analysis of intra-observer agreement was strong at almost perfect (k > 0.78) for 3 technologists. These results are encouraging regarding the ability of selected technologists to perform measurements according to RECIST 1.1 criteria by CT scan with good identification of disease progression.

Summary: Background: Preoperative COVID-19 has been associated with excess postoperative morbi-mortality. Consequently, guidelines were developed that recommended the postponement of surgery for at least 7 weeks after the infection. We hypothesised that vaccination against the SARS-CoV-2 and the large predominance of the Omicron variant attenuated the effect of a preoperative COVID-19 on the occurrence of postoperative respiratory morbidity. Methods: We conducted a prospective cohort study in 41 French centres between 15 March and 30 May 2022 (ClinicalTrials NCT05336110), aimed at comparing the postoperative respiratory morbidity between patients with and without preoperative COVID-19 within 8 weeks prior to surgery. The primary outcome was a composite outcome combining the occurrence of pneumonia, acute respiratory failure, unexpected mechanical ventilation, and pulmonary embolism within the first 30 postoperative days. Secondary outcomes were 30-day mortality, hospital length-of-stay, readmissions, and non-respiratory infections. The sample size was determined to have 90% power to identify a doubling of the primary outcome rate. Adjusted analyses were performed using propensity score modelling and inverse probability weighting. Findings: Of the 4928 patients assessed for the primary outcome, of whom 92.4% were vaccinated against the SARS-CoV-2, 705 had preoperative COVID-19. The primary outcome was reported in 140 (2.8%) patients. An 8-week preoperative COVID-19 was not associated with increased postoperative respiratory morbidity (odds ratio 1.08 [95% CI 0.48–2.13]; p = 0.83). None of the secondary outcomes differed between the two groups. Sensitivity analyses concerning the timing between COVID-19 and surgery, and the clinical presentations of preoperative COVID-19 did not show any association with the primary outcome, except for COVID-19 patients with ongoing symptoms the day of surgery (OR 4.29 [1.02–15.8]; p = 0.04). Interpretation: In our Omicron-predominant, highly immunised population undergoing general surgery, a preoperative COVID-19 was not associated with increased postoperative respiratory morbidity. Funding: The study was fully funded by the French Society of Anaesthesiology and Intensive Care Medicine (SFAR).

Tumor hypoxia is a complex and evolving phenomenon both in time and space. Molecular imaging allows to approach these variations, but the tracers used have their own limitations. PET imaging has the disadvantage of low resolution and must take into account molecular biodistribution, but has the advantage of high targeting accuracy. The relationship between the signal in MRI imaging and oxygen is complex but hopefully it would lead to the detection of truly oxygen-depleted tissue. Different ways of imaging hypoxia are discussed in this review, with nuclear medicine tracers such as [18F]-FMISO, [18F]-FAZA, or [64Cu]-ATSM but also with MRI techniques such as perfusion imaging, diffusion MRI or oxygen-enhanced MRI. Hypoxia is a pejorative factor regarding aggressiveness, tumor dissemination and resistance to treatments. Therefore, having accurate tools is particularly important.

Allergies and atopy have emerged as significant public health concerns, with a progressively increasing incidence over the last two decades. Anaphylaxis is the most severe form of allergic reactions, characterized by a rapid onset and potentially fatal outcome, even in healthy individuals. Due to the unpredictable nature and potential lethality of anaphylaxis and the wide range of allergens involved, clinical studies in human patients have proven to be challenging. Diagnosis is further complicated by the lack of reliable laboratory biomarkers to confirm clinical suspicion. Thus, animal models have been developed to replicate human anaphylaxis and explore its pathophysiology. Whereas results obtained from animal models may not always be directly translatable to humans, they serve as a foundation for understanding the underlying mechanisms. Animal models are an essential tool for investigating new biomarkers that could be incorporated into the allergy workup for patients, as well as for the development of novel treatments. Two primary pathways have been described in animals and humans: classic, predominantly involving IgE and histamine, and alternative, reliant on IgG and the platelet-activating factor. This review will focus essentially on the former and aims to describe the most utilized IgE-mediated anaphylaxis animal models, including their respective advantages and limitations.

Abstract Purpose To determine the impact of the Bayesian penalized likelihood (BPL) reconstruction algorithm in comparison to OSEM on hypoxia PET/CT images of NSCLC using 18F-MIZO and 18F-FAZA. Materials and methods Images of low-contrasted (SBR = 3) micro-spheres of Jaszczak phantom were acquired. Twenty patients with lung neoplasia were included. Each patient benefitted from 18F-MISO and/or 18F-FAZA PET/CT exams, reconstructed with OSEM and BPL. Lesion was considered as hypoxic if the lesion SUVmax > 1.4. A blind evaluation of lesion detectability and image quality was performed on a set of 78 randomized BPL and OSEM images by 10 nuclear physicians. SUVmax, SUVmean, and hypoxic volumes using 3 thresholding approaches were measured and compared for each reconstruction. Results The phantom and patient datasets showed a significant increase of quantitative parameters using BPL compared to OSEM but had no impact on detectability. The optimal beta parameter determined by the phantom analysis was β350. Regarding patient data, there was no clear trend of image quality improvement using BPL. There was no correlation between SUVmax increase with BPL and either SUV or hypoxic volume from the initial OSEM reconstruction. Hypoxic volume obtained by a SUV > 1.4 thresholding was not impacted by the BPL reconstruction parameter. Conclusion BPL allows a significant increase in quantitative parameters and contrast without significantly improving the lesion detectability or image quality. The variation in hypoxic volume by BPL depends on the method used but SUV > 1.4 thresholding seems to be the more robust method, not impacted by the reconstruction method (BPL or OSEM). Trial registration ClinicalTrials.gov , NCT02490696 . Registered 1 June 2015

Abstract Background In FDG-PET, SUV images are hampered by large potential biases. Our aim was to develop an alternative method (ParaPET) to generate 3D kinetic parametric FDG-PET images easy to perform in clinical oncology. Methods The key points of our method are the use of a new error model of PET measurement extracted from a late dynamic PET acquisition of 15 min, centered over the lesion and an image-derived input function (IDIF). The 15-min acquisition is reconstructed to obtain five images of FDG mean activity concentration and images of its variance to model errors of PET measurement. Our approach is carried out on each voxel to derive 3D kinetic parameter images. ParaPET was evaluated and compared to Patlak analysis as a reference. Hunter and Barbolosi methods (Barbolosi-Bl: with blood samples or Barbolosi-Im: with IDIF) were also investigated and compared to Patlak. Our evaluation was carried on K i index, the net influx rate and its maximum value in the lesion (K i,max). Results This parameter was obtained from 41 non-small cell lung cancer lesions associated with 4 to 5 blood samples per patient, required for the Patlak analysis. Compare to Patlak, the median relative difference and associated range (median; [min;max]) in K i,max estimates were not statistically significant (Wilcoxon test) for ParaPET (− 3.0%; [− 31.9%; 47.3%]; p = 0.08) but statistically significant for Barbolosi-Bl (− 8.0%; [− 30.8%; 53.7%]; p = 0.001), Barbolosi-Im (− 7.9%; [− 38.4%; 30.6%]; p = 0.007) or Hunter (32.8%; [− 14.6%; 132.2%]; p

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that typically results in death within 3–5 years after diagnosis. To date, there is no curative treatment and therefore an urgent unmet need of neuroprotective and/or neurorestorative treatments. Due to their spectrum of capacities in the central nervous system—e.g., development, plasticity, maintenance, neurogenesis—neurotrophic growth factors (NTF) have been exploited for therapeutic strategies in ALS for decades. In this review we present the initial strategy of using single NTF by different routes of administration to the use of stem cells transplantation to express a multiple NTFs-rich secretome to finally focus on a new biotherapy based on the human platelet lysates, the natural healing system containing a mix of pleitropic NTF and having immunomodulatory function. This review highlights that this latter treatment may be crucial to power the neuroprotection and/or neurorestoration therapy requested in this devastating disease.

In oncology, texture features extracted from positron emission tomography with 18-fluorodeoxyglucose images (FDG-PET) are of increasing interest for predictive and prognostic studies, leading to several tens of features per tumor. To select the best features, the use of a random forest (RF) classifier was investigated.Sixty-five patients with an esophageal cancer treated with a combined chemo-radiation therapy were retrospectively included. All patients underwent a pretreatment whole-body FDG-PET. The patients were followed for 3 years after the end of the treatment. The response assessment was performed 1 month after the end of the therapy. Patients were classified as complete responders and non-complete responders. Sixty-one features were extracted from medical records and PET images. First, Spearman's analysis was performed to eliminate correlated features. Then, the best predictive and prognostic subsets of features were selected using a RF algorithm. These results were compared to those obtained by a Mann-Whitney U test (predictive study) and a univariate Kaplan-Meier analysis (prognostic study).Among the 61 initial features, 28 were not correlated. From these 28 features, the best subset of complementary features found using the RF classifier to predict response was composed of 2 features: metabolic tumor volume (MTV) and homogeneity from the co-occurrence matrix. The corresponding predictive value (AUC = 0.836 ± 0.105, Se = 82 ± 9%, Sp = 91 ± 12%) was higher than the best predictive results found using the Mann-Whitney test: busyness from the gray level difference matrix (P < 0.0001, AUC = 0.810, Se = 66%, Sp = 88%). The best prognostic subset found using RF was composed of 3 features: MTV and 2 clinical features (WHO status and nutritional risk index) (AUC = 0.822 ± 0.059, Se = 79 ± 9%, Sp = 95 ± 6%), while no feature was significantly prognostic according to the Kaplan-Meier analysis.The RF classifier can improve predictive and prognostic values compared to the Mann-Whitney U test and the univariate Kaplan-Meier survival analysis when applied to several tens of features in a limited patient database.

OBJECTIVE: Major trauma is characterized by a pro-inflammatory response, followed by an immunosuppression. Recently, in trauma patients, the lack of recovery of monocyte Human Leukocyte Antigen DR (mHLA-DR, a biomarker of ICU-acquired immunosuppression) between days 1-2 and days 3-4 has been demonstrated to be independently associated with sepsis development. The main objective of this study was to determine whether early measurements of IL-6 (interleukin-6) and IL-10 plasma concentrations (as markers of initial severity) could improve, in association with mHLA-DR recovery, the prediction of sepsis occurrence in severe trauma patients. DESIGN: Prospective observational study over 24 months in a Trauma ICU at university hospital. PATIENTS: Trauma patients with an ISS over 25 and age over 18 were included. MEASUREMENTS AND MAIN RESULTS: mHLA-DR was assessed by flow cytometry, IL-6 and IL-10 concentrations by ELISA. 100 consecutive severely injured patients were monitored (mean ISS 37±10). 37 patients developed sepsis. IL-6 concentrations and slope of mHLA-DR expression between days 1-2 and days 3-4 were significantly different between septic and non-septic patients. IL-10 was not detectable in most patients. After adjustment for usual clinical confounders, when assessed as a pair, multivariate logistic regression analysis revealed that a slope of mHLA-DR expression (days 3-4/days 1-2)≤1.1 and a IL-6 concentration ≥ 67.1 pg/ml remained highly associated with the development of sepsis (adjusted OR 18.4, 95% CI 4.9; 69.4, p = .00002). CONCLUSIONS: After multivariate regression logistic analysis, when assessed as a pair, a high IL-6 concentration and a persistent mHLA-DR decreased expression were found to be in relation with the development of sepsis with the best predictive value. This study underlines the usefulness of daily monitoring of immune function to identify trauma patients at a high risk of infection.

Abstract A female patient, with normal familial history, developed at the age of 30 months an episode of diarrhoea, vomiting and lethargy which resolved spontaneously. At the age of 3 years, the patient re-iterated vomiting, was sub-febrile and hypoglycemic, fell into coma, developed seizures and sequels involving right hemi-body. Urinary excretion of hexanoylglycine and suberylglycine was low during this metabolic decompensation. A study of pre- and post-prandial blood glucose and ketones over a period of 24 hours showed a normal glycaemic cycle but a failure to form ketones after 12 hours fasting, suggesting a mitochondrial β-oxidation defect. Total blood carnitine was lowered with unesterified carnitine being half of the lowest control value. A diagnosis of mild MCAD deficiency (MCADD) was based on rates of 1-14C-octanoate and 9, 10-3H-myristate oxidation and of octanoyl-CoA dehydrogenase being reduced to 25% of control values. Other mitochondrial fatty acid oxidation proteins were functionally normal. De novo acylcarnitine synthesis in whole blood samples incubated with deuterated palmitate was also typical of MCADD. Genetic studies showed that the patient was compound heterozygous with a sequence variation in both of the two ACADM alleles; one had the common c.985A>G mutation and the other had a novel c.145C>G mutation. This is the first report for the ACADM gene c.145C>G mutation: it is located in exon 3 and causes a replacement of glutamine to glutamate at position 24 of the mature protein (Q24E). Associated with heterozygosity for c.985A>G mutation, this mutation is responsible for a mild MCADD phenotype along with a clinical story corroborating the emerging literature view that patients with genotypes representing mild MCADD (high residual enzyme activity and low urinary levels of glycine conjugates), similar to some of the mild MCADDs detected by MS/MS newborn screening, may be at risk for disease presentation.