Publications by authors named "Catherine Daniel"

61 Publications

Adherent-Invasive and Non-Invasive Isolates Differ in Their Effects on Lifespan.

Microorganisms 2021 Aug 27;9(9). Epub 2021 Aug 27.

Univ. Lille, Inserm, CHU Lille, U1286-INFINITE-Institute for Translational Research in Inflammation, F-59000 Lille, France.

The adherent-invasive (AIEC) pathotype has been implicated in the pathogenesis of inflammatory bowel diseases in general and in Crohn's disease (CD) in particular. AIEC strains are primarily characterized by their ability to adhere to and invade intestinal epithelial cells. However, the genetic and phenotypic features of AIEC isolates vary greatly as a function of the strain's clonality, host factors, and the gut microenvironment. It is thus essential to identify the determinants of AIEC pathogenicity and understand their role in intestinal epithelial barrier dysfunction and inflammation. We reasoned that soil nematode (a simple but powerful model of host-bacterium interactions) could be used to study the virulence of AIEC vs. non- AIEC strains. Indeed, we found that the colonization of (strain N2) by impacted survival in a strain-specific manner. Moreover, the AIEC strains' ability to invade cells in vitro was linked to the median lifespan in (strain PX627). However, neither the intrinsic invasiveness (i.e., the fact for an individual strain to be characterized as invasive or not) nor AIEC's virulence levels (i.e., the intensity of invasion, established in % from the infectious inoculum) in intestinal epithelial cells was correlated with ' lifespan in the killing assay. Nevertheless, AIEC longevity of might be a relevant model for screening anti-adhesion drugs and anti-invasive probiotics.
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http://dx.doi.org/10.3390/microorganisms9091823DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8465672PMC
August 2021

Screening major trauma patients for prevalence of illicit drugs.

Drug Alcohol Rev 2021 Jul 15. Epub 2021 Jul 15.

Department of Medicine, Royal Melbourne Hospital, Melbourne, Australia.

Introduction: Australasian emergency departments (ED) routinely test patient alcohol levels following major trauma, but assessment for illicit drugs is uncommon.

Methods: A prospective cross-sectional study of major motor-vehicle-related trauma patients attending both adult major trauma centres in Victoria, Australia. All eligible patients had point-of-care saliva testing to determine the prevalence of common illicit drugs.

Results: Over 12 months, 1411 patients were screened, 36 refused (2.6%) and 63 were excluded. Of the final 1312 cases included, 173 (13.2%; 95% confidence interval 11.5, 15.1) tested positive to at least one illicit substance, with 133 (76.9%; 69.7, 82.8) positive for meth/amphetamines. One in five had more than one illicit substance detected. Patients testing positive were most frequently in motor vehicles (91.9% vs. 85.6%) and least frequently cyclists (2.3% vs. 4.2%) or pedestrians (5.2% vs. 10.3%), compared to those testing negative. They were younger (mean age 35.4 vs. 43.1 years), more likely to arrive overnight (27.2% vs. 12.1%) or after single vehicle crashes (54.3% vs. 42.3%). Although the initial disposition from ED did not differ, those testing positive were more likely to re-present within 28 days (13.9% vs. 5.4%).

Discussion And Conclusions: A high prevalence of potentially illicit substances among patients presenting with suspected major trauma supports the need for urgent preventive strategies. The low rate of patient refusal and large numbers screened by ED staff suggests that point-of care testing for illicit substances in major trauma is acceptable and feasible. This study and ongoing surveillance may be used to inform driver education strategies.
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http://dx.doi.org/10.1111/dar.13355DOI Listing
July 2021

Impact of COVID-19 on the management of patients with thoracic cancers in a tertiary referral center.

Lung Cancer 2021 07 8;157:79-84. Epub 2021 May 8.

Institut Curie, Paris, France; Université Paris Saclay, Université Versailles Saint Quentin, Unité de Formation et de Recherche Simone Veil - Santé, Montigny le Bretonneux, France. Electronic address:

Introduction: Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 has spread worldwide in 2020 leading the World Health Organization to declare a pandemic. Patients with thoracic cancers have been reported at higher risk to develop severe disease, and die from COVID-19. In this setting, clinical practice recommendations for the management of patients were published. We report here how these guidelines were implemented in a routine practice setting.

Methods: We retrospectively collected the characteristics, treatment regimen and modification, as well as COVID-19 status and death for all patients with thoracic malignancies scheduled for an appointment at Institute Curie from March 23 to April 17 2020.

Results: A total of 339 patients were included. Treatment strategy was modified for a total of 110 (32 %) patients because of COVID-19; these modifications were in accordance with guidelines for 92 % of patients. The majority of dose modifications were related to immune checkpoint inhibitors, for which switch to flat dosing every 4-6 weeks was made. A total of 5 (1.5 %) patients were diagnosed with COVID-19 disease, 1 of whom died from disease complication.

Conclusion: Our study provides a unique insight in the decision making for patients with thoracic malignancies in the setting of COVID-19 outbreak, showing how guidelines were implemented in the clinic, and what may be optimized in the clinical practice of thoracic oncology in the future.
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http://dx.doi.org/10.1016/j.lungcan.2021.05.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105127PMC
July 2021

High and synergistic activity between mTORC1 and PLK1 inhibition in adenocarcinoma NSCLC.

Oncotarget 2021 Apr 13;12(8):859-872. Epub 2021 Apr 13.

Laboratory of Preclinical Investigation, Department of Translational Research, Institut Curie, PSL University, Paris, France.

Significant rational is available for specific targeting of PI3K/AKT/mTOR pathway in the treatment of non-small cell lung cancer (NSCLC). However, almost all clinical trials that have evaluated Pi3K pathway-based monotherapies/combinations did not observe an improvement of patient's outcome. The aim of our study was therefore to define combination of treatment based on the determination of predictive markers of resistance to the mTORC1 inhibitor RAD001/Everolimus. An study showed high efficacy of RAD001 in NSCLC Patient-Derived Xenografts (PDXs). When looking at biomarkers of resistance by RT-PCR study, three genes were found to be highly expressed in resistant tumors, i.e., , , and . We have then focused our study on the combination of RAD001 + Volasertib, a PLK1 inhibitor, and observed a high antitumor activity of the combination in comparison to each monotherapy; similarly, a clear synergistic effect between the two compounds was found in an study. Pharmacodynamics study demonstrated that this synergy was due to (1) tumor vascularization decrease, increase of the HIF1 protein expression and decrease of the intracellular pH, and (2) decrease of the Carbonic Anhydrase 9 (CAIX) protein that could not correct intracellular acidosis. In conclusion, all these preclinical data strongly suggest that the inhibition of mTORC1 and PLK1 proteins may be a promising therapeutic approach for NSCLC patients.
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http://dx.doi.org/10.18632/oncotarget.27930DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057272PMC
April 2021

Persistence and dynamics of fluorescent in the healthy inflamed gut.

Gut Microbes 2021 Jan-Dec;13(1):1-16

Univ. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - Center for Infection and Immunity of Lille, F-59000 Lill, France.

The gastrointestinal tract is the main ecological niche in which strains may provide health benefits in mammals. There is currently a need to characterize host-microbe interactions in space and time by tracking these bacteria . We combined noninvasive whole-body imaging with fluorescence confocal microscopy imaging to monitor the impact of intestinal inflammation on the persistence of orally administered NCIMB8826 in healthy and inflamed mouse colons. We developed fluorescent strains and demonstrated that mCherry is the best system for imaging and fluorescence confocal microscopy of these bacteria. We also used whole-body imaging to show that this anti-inflammatory, orally administered strain persists for longer and at higher counts in the inflamed colon than in the healthy colon. We confirmed these results by the confocal imaging of colons from mice with experimental colitis for 3 days after induction. Moreover, extended orthogonal view projections enabled us to localize individual in sites that differed for healthy inflamed guts. In healthy colons, orally administered bacteria were localized in the lumen (in close contact with commensal bacteria) and sometimes in the crypts (albeit very rarely in contact with intestinal cells). The bacteria were observed within and outside the mucus layer. In contrast, bacteria in the inflamed colon were mostly located in the lumen and (in less inflamed areas) within the mucus layer. In more intensely inflamed areas (i.e., where the colon had undergone structural damage), the were in direct contact with damaged epithelial cells. Taken as a whole, our results show that fluorescently labeled can be used to study the persistence of these bacteria in inflamed guts using both noninvasive whole-body imaging and fluorescence confocal microscopy.
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http://dx.doi.org/10.1080/19490976.2021.1897374DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009120PMC
March 2021

Assessment of Pb(II), Cd(II), and Al(III) Removal Capacity of Bacteria from Food and Gut Ecological Niches: Insights into Biodiversity to Limit Intestinal Biodisponibility of Toxic Metals.

Microorganisms 2021 Feb 22;9(2). Epub 2021 Feb 22.

ULR 4483-IMPECS-IMPact de l'Environnement Chimique sur la Santé humaine, Institut Pasteur de Lille, CHU Lille, Université de Lille, F-59000 Lille, France.

Toxic metals (such as lead, cadmium, and, to a lesser extent, aluminum) are detrimental to health when ingested in food or water or when inhaled. By interacting with heavy metals, gut and food-derived microbes can actively and/or passively modulate (by adsorption and/or sequestration) the bioavailability of these toxins inside the gut. This "intestinal bioremediation" involves the selection of safe microbes specifically able to immobilize metals. We used inductively coupled plasma mass spectrometry to investigate the in vitro ability of 225 bacteria to remove the potentially harmful trace elements lead, cadmium, and aluminum. Interspecies and intraspecies comparisons were performed among the Firmicutes (mostly lactic acid bacteria, including spp., with some , , and representatives), Actinobacteria, and Proteobacteria. The removal of a mixture of lead and cadmium was also investigated. Although the objective of the study was not to elucidate the mechanisms of heavy metal removal for each strain and each metal, we nevertheless identified promising candidate bacteria as probiotics for the intestinal bioremediation of Pb(II) and Cd(II).
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http://dx.doi.org/10.3390/microorganisms9020456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7926695PMC
February 2021

Use of the Safewards Model in healthcare services: a mixed-method scoping review protocol.

BMJ Open 2020 12 7;10(12):e039109. Epub 2020 Dec 7.

Nursing, The University of Melbourne, Melbourne, Victoria, Australia.

Introduction: Safewards is an organisational approach to delivering inpatient mental health services. The aim of Safewards is to minimise the number of situations in which conflict arises between healthcare workers and patients that lead to the use of coercive interventions (restriction and/or containment).The Safewards Model has been developed, implemented and evaluated for its impact on all forms of containment. Safewards has been adopted as the recommended approach to preventing patient agitation and clinical aggression in some jurisdictions. Notwithstanding these recommendations, the outcomes of Safewards for staff and patients have not been comprehensively described.The aim of the scoping review is to describe (1) Safewards interventions; (2) how Safewards interventions have been implemented in healthcare settings; (3) outcome measures used to evaluate the effectiveness of Safewards; (4) barriers and enablers to the uptake and sustainability of Safewards. This review will provide a foundation for further research and/or systematic review of the effectiveness of Safewards.

Methods And Analysis: Peer-reviewed manuscripts of quantitative, qualitative and mixed-method research in English with be included for the period 01 January 2013- December 31st 2020. Electronic databases including Cumulative Index to Nursing and Allied Health Literature, Cochrane, Embase, Emcare, Joanna Briggs Institute, Medline, Global Health, PsycINFO and Scopus will be searched. Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for Scoping Reviews checklist and explanation and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocol will be followed. Publications will be excluded if they do not include the required participants, concept or context. Two reviewers will independently screen all titles and abstracts and full-text studies for inclusion.

Ethics And Dissemination: Ethical approval for this review is not required as the information to be collected is publicly available. There are no participants or safety considerations in this review of published literature. Key findings for future research and clinical practice will be disseminated though peer-reviewed publication, stakeholder reporting and conference presentations.
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http://dx.doi.org/10.1136/bmjopen-2020-039109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7722816PMC
December 2020

Characteristics and clinical outcomes for mental health patients admitted to a behavioural assessment unit: Implications for model of care and practice.

Int J Ment Health Nurs 2021 Feb 14;30(1):249-260. Epub 2020 Sep 14.

Department of Nursing, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Victoria, Australia.

Behavioural assessment units (BAU) have been established in emergency departments (EDs) to provide short-term observation, treatment, and care to people experiencing acute behavioural disturbance. A prospective observational study was conducted in a cohort of adult patients admitted to one BAU located within an ED (July-December 2017) to compare clinical characteristics, treatment outcomes, and use of restrictive interventions for those who received a specialist mental health (MH) assessment with those who did not. Of the 457 patients, 61.5% received a specialist MH assessment. This group had a lower acuity (Australasian Triage Score 10.4%; CI 0.2-2.0% vs 13.6%; CI 9.3-19.5%); more arrived with police (28.8%; CI 23.8-34.3 vs 5.1%; CI 2.7-9.4%); and were subjected to restrictive interventions while in the BAU. Security responses for unarmed threat (code grey) were higher (10.9%; CI 7.8-15.0% vs 4.4%; CI 2.3-8.5%), as was the use of chemical restraint (4.2%; CI 2.4-7.2 vs 0.0% CI 0.0 - 2.1%). Those requiring specialist MH assessment had a longer length of stay (12.7 vs 5.2 hours). Further development of the BAU model of care must include targeted, evidence-based strategies to minimize the use of restrictive interventions and ensure timely access to acute mental health services.
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http://dx.doi.org/10.1111/inm.12779DOI Listing
February 2021

Congenital Diaphragmatic Hernia in an Adult Patient.

Am J Med 2021 01 14;134(1):e4-e5. Epub 2020 Aug 14.

Department of Medicine, Baylor College of Medicine, Houston, Tex.

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http://dx.doi.org/10.1016/j.amjmed.2020.06.043DOI Listing
January 2021

High-dose dietary supplementation with zinc prevents gut inflammation: Investigation of the role of metallothioneins and beyond by transcriptomic and metagenomic studies.

FASEB J 2020 09 30;34(9):12615-12633. Epub 2020 Jul 30.

Univ. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, Lille, France.

Although it is known that zinc has several beneficial roles in the context of gut inflammation, the underlying mechanisms have not been extensively characterized. Zinc (Zn) is known to be the primary physiological inducer of the expression of the metallothionein (MT) superfamily of small stress-responsive proteins. The expression of MTs in various tissues is induced or enhanced (including the gastrointestinal tract (GIT)) by a variety of stimuli, including infection and inflammation. However, the MTs' exact role in inflammation is still subject to debate. In order to establish whether or not MTs are the sole vectors in the Zn-based modulation of intestinal inflammation, we used transcriptomic and metagenomic approaches to assess the potential effect of dietary Zn, the mechanisms underlying the MTs' beneficial effects, and the induction of previously unidentified mediators. We found that the expression of endogenous MTs in the mouse GIT was stimulated by an optimized dietary supplementation with Zn. The protective effects of dietary supplementation with Zn were then evaluated in mouse models of chemically induced colitis. The potential contribution of MTs and other pathways was explored via transcriptomic analyses of the ileum and colon in Zn-treated mice. The microbiota's role was also assessed via fecal 16S rRNA sequencing. We found that high-dose dietary supplementation with Zn induced the expression of MT-encoding genes in the colon of healthy mice. We next demonstrated that the Zn diet significantly protected mice in the two models of induced colitis. When comparing Zn-treated and control mice, various genes were found to be differentially expressed in the colon and the ileum. Finally, we found that Zn supplementation did not modify the overall structure of the fecal microbiota, with the exception of (i) a significant increase in endogenous Clostridiaceae, and (ii) some subtle but specific changes at the family and genus levels. Our results emphasize the beneficial effects of excess dietary Zn on the prevention of colitis and inflammatory events in mouse models. The main underlying mechanisms were driven by the multifaceted roles of MTs and the other potential molecular mediators highlighted by our transcriptomic analyses although we cannot rule out contributions by other factors from the host and/or the microbiota.
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http://dx.doi.org/10.1096/fj.202000562RRDOI Listing
September 2020

Physical comorbidities in private psychiatric inpatients: Prevalence and its association with quality of life and functional impairment.

Int J Ment Health Nurs 2020 Dec 16;29(6):1253-1261. Epub 2020 Jul 16.

Department of Nursing, The University of Melbourne, Melbourne, Victoria, Australia.

The aim of this study was to examine the association between physical health conditions and quality of life and functioning in private psychiatric inpatients. We sought to determine whether quality of life and functioning was poorer in individuals with physical comorbidity compared to those without. A quantitative correlational descriptive design was utilized. Seventy patients were included in sequential order within a week of admission to hospital. Participants completed the SF-36 survey, and the corresponding hospital records were audited. The STROBE guidelines were followed in the reporting of this research. The study found that 64.3% (45/70) of participants had one or more comorbid physical health conditions, primarily cardiovascular, respiratory, musculoskeletal, endocrine and medically unexplained conditions or syndromes. Chronic pain was experienced by 40% (28/70) of participants, and 47.6% (33/70) were found to be overweight or obese. Tobacco smoking and obesity were risk factors associated with physical comorbidity (P = 0.02 and P < 0.001, respectively). Quality of life and functioning were poorer in those with physical health conditions, particularly in the SF-36 domains of bodily pain, physical functioning and general health (P < 0.001, P = 0.003 and P = 0.005, respectively). Physical health conditions were largely prevalent, and quality of life and functioning were poorer in those with physical comorbidities. The implementation of clinical guidelines for the monitoring of physical health has been proposed as well as a dedicated physical health nursing role. Continuation of integrative programmes focusing on both physical and mental health may also benefit patients in this setting.
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http://dx.doi.org/10.1111/inm.12764DOI Listing
December 2020

Immune Checkpoint Inhibitors Rechallenge Efficacy in Non-Small-Cell Lung Cancer Patients.

Clin Lung Cancer 2020 09 8;21(5):e497-e510. Epub 2020 May 8.

Thoracic Oncology Unit SHUPP, CHU Grenoble-Alpes, Grenoble, France.

Background: Immune checkpoint inhibitor (ICPi) rechallenge could represent an attractive option in non-small-cell lung cancer (NSCLC), yet no sufficient data supporting this strategy are available. This retrospective observational multicenter national study explored the efficacy of anti-programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) rechallenge in advanced NSCLC patients, looking for potential clinical features associated with greater outcomes.

Patients And Methods: We retrospectively collected data from 144 advanced NSCLC patients whose disease was rechallenged with ICPis after ≥ 12 weeks of discontinuation. The progression-free survival (PFS) and overall survival (OS) were calculated from first or second ICPi initiation to disease progression (PFS1 and PFSR, respectively), death, or last follow-up (OS1, OSR), respectively.

Results: The median (interquartile range) age was 63 (58-70) years. Most patients were male (67%) and smokers (87%). Most had adenocarcinomas (62%) and/or stage IV disease at diagnosis (66%). The best response at rechallenge was not associated with that under the first ICPi (P = 1.10). The median (95% confidence interval) PFS1 and PFSR were 13 (10-16.5) and 4.4 (3-6.5) months, respectively. The median (95% confidence interval) OS1 and OSR were 3.3 (2.9-3.9) and 1.5 (1.0-2.1) years, respectively. Longer PFSR and OSR were found in patients discontinuing first ICPi because of toxicity or clinical decision, those not receiving systemic treatment between the two ICPis, and those with good Eastern Cooperative Oncology Group performance status at rechallenge. Only performance status proved to affect outcomes at multivariate analysis.

Conclusion: Patients discontinuing first ICPi because of toxicity or clinical decision, those able to maintain a treatment-free period, and those with good performance status may be potential candidates for rechallenge.
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http://dx.doi.org/10.1016/j.cllc.2020.04.013DOI Listing
September 2020

Lamotrigine-induced DRESS Syndrome Manifesting as 'Eosinophilic Colitis': An Uncommon Presentation of a Very Uncommon Condition.

Cureus 2020 Apr 7;12(4):e7570. Epub 2020 Apr 7.

Internal Medicine, Baylor College of Medicine, Houston, USA.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare drug-induced hypersensitivity reaction that manifests with a variety of signs and symptoms. It is an important condition that must be recognized by all physicians because if untreated, it can be fatal. There are a variety of medications that are responsible for this condition. The liver, lungs, and kidneys are commonly affected, with the involvement of the gastrointestinal tract being very rare; only a few cases are reported worldwide. We are presenting a case of lamotrigine-induced DRESS syndrome manifesting as colitis. A 32-year-old female presented with diarrhea, two weeks after the initiation of lamotrigine. Her condition worsened with the development of a generalized rash and bloody diarrhea. Further investigations revealed that she likely had a drug reaction secondary to lamotrigine. Fortunately, prompt initiation of systemic steroids led to the resolution of her symptoms.
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http://dx.doi.org/10.7759/cureus.7570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7205376PMC
April 2020

Amphetamine-type stimulant use among patients admitted to the emergency department behavioural assessment unit: Screening and referral outcomes.

Int J Ment Health Nurs 2020 Oct 6;29(5):796-807. Epub 2020 Mar 6.

Quality and Improvement, Melbourne Health, Parkville, Victoria, Australia.

Amphetamine-type stimulant use, including methamphetamine, amphetamine, and 3,4-methylenedioxymethamphetamine, is associated with a range of behavioural symptoms. Screening for amphetamine-type stimulant use among people presenting to the emergency department with behavioural disturbance and referral to treatment has not been evaluated. The objective of this study was to determine the prevalence of amphetamine-type stimulant use among patients admitted to a behavioural assessment unit and report referral outcomes. A prospective observational design was used. Individuals who tested positive or self-reported amphetamine-type stimulant use were referred to the alcohol and other drug clinician. We measured the prevalence of amphetamine-type stimulant use in saliva and by self-report along with rates of referral. The setting was a behavioural assessment unit located within an Australian emergency department. Admitted adults were enrolled from July to December 2017. Those who tested positive or self-reported amphetamine-type stimulant use were provided with harm reduction advice and offered referral. Four hundred and seventy-two tests were performed. Fifteen were excluded due to invalid results or redundant enrolment. Of the 457 individuals, 59% were male, with a mean age of 35 years (SD 13). Fifty-three (11.6%, 95% CI: 8.9-15.0) tested positive for amphetamine-type stimulants. Of those with a negative test, 44 (9.6%, 95% CI: 7.3-12.7) self-reported amphetamine-type stimulant use in the previous 24 hours. The prevalence of amphetamine-type stimulant use was 21.2% (95% CI: 17.7-25.2). Most accepted referral to the alcohol and other drug clinician (85.6%, 95% CI 77.2-91.2). The emergency visit represents a window of opportunity for screening for amphetamine-type stimulant use and initiating referrals.
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http://dx.doi.org/10.1111/inm.12710DOI Listing
October 2020

Restrictive interventions in Victorian emergency departments: A study of current clinical practice.

Emerg Med Australas 2020 06 26;32(3):393-400. Epub 2019 Nov 26.

Emergency Department, Ballarat Hospital, Ballarat, Victoria, Australia.

Objective: To determine current clinical practices for managing behavioural emergencies within Victorian public hospital EDs.

Methods: A multi-centre retrospective study involving all patients who attended ED in 2016 at the Alfred, Ballarat, Dandenong, Geelong and Royal Melbourne Hospitals. The primary outcome was the rate of patient presentations with at least one restrictive intervention. Secondary outcomes included the rate of security calls for unarmed threats (Code Grey), legal status under the Mental Health Act at both the time of ED arrival and the restrictive intervention, and intervention details. For each site, data on 100 patients who had a restrictive intervention were randomly extracted for indication and methods of restraint.

Results: In 2016, 327 454 patients presented to the five EDs; the Code Grey rate was 1.49% (95% CI 1.45-1.54). Within the Code Grey population, 942 had at least one restrictive intervention (24.3%, 95% CI 23.0-25.7). Details were extracted on 494 patients. The majority (62.8%, 95% CI 58.4-67.1) were restrained under a Duty of Care. Physical restraint was used for 165 (33.4%, 95% CI 29.3-37.8) patients, 296 were mechanically restrained (59.9%, 95% CI 55.4-64.3), median mechanical restraint time 180 min (IQR 75-360), and 388 chemically restrained (78.5%, 95% CI 74.6-82.0).

Conclusions: Restrictive interventions in the ED largely occurred under a Duty of Care. Care of patients managed under legislation that covers assessment and treatment of mental illness has a strong clinical governance framework and focus on minimising restrictive interventions. However, this is not applied to the majority of patients who experience restraint in Victorian EDs.
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http://dx.doi.org/10.1111/1742-6723.13412DOI Listing
June 2020

Polymorphism in the LcrV Antigen Enables Immune Escape From the Protection Conferred by an LcrV-Secreting in a Pseudotuberculosis Mouse Model.

Front Immunol 2019 2;10:1830. Epub 2019 Aug 2.

Université de Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - Center for Infection and Immunity of Lille, Lille, France.

Yersinioses caused by , and are significant concerns in human and veterinary health. The link between virulence and the potent LcrV antigen has prompted the latter's selection as a major component of anti- vaccines. Here, we report that (i) the group of species encompassing and produces at least five different clades of LcrV and (ii) vaccination of mice with an LcrV-secreting only protected against strains producing the same LcrV clade as that of used for vaccination. By vaccinating with engineered LcrVs and challenging mice with strains producing either type of LcrV or a LcrV mutated for regions of interest, we highlight key polymorphic residues responsible for the absence of cross-protection. Our results show that an anti-LcrV-based vaccine should contain multiple LcrV clades if protection against the widest possible array of strains is sought.
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http://dx.doi.org/10.3389/fimmu.2019.01830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6688116PMC
October 2020

Contribution of the Gut Microbiota in P28GST-Mediated Anti-Inflammatory Effects: Experimental and Clinical Insights.

Cells 2019 06 12;8(6). Epub 2019 Jun 12.

Univ. Lille, Inserm, CHU Lille, U995 - LIRIC - Lille Inflammation Research International Center, F-59000 Lille, France.

An original immuno-regulatory strategy against inflammatory bowel diseases based on the use of 28 kDa glutathione S-transferase (P28GST), a unique schistosome protein, was recently proposed. Improvement of intestinal inflammation occurs through restoration of the immunological balance between pro-inflammatory T-helper 1 (Th1) responses and both T-helper 2 (Th2) and regulatory responses. However, detailed mechanisms explaining how P28GST prevents colitis and promotes gut homeostasis remain unknown. Considering the complex interplay between the adaptive and innate immune system and the intestinal microbiota, we raised the question of the possible role of the microbial ecosystem in the anti-inflammatory effects mediated by the helminth-derived P28GST protein. We first analyzed, by 16S rRNA sequencing, the bacterial profiles of mice fecal microbiota at several time points of the P28GST-immunomodulation period prior to trinitrobenzene sulfonic acid (TNBS)-colitis. The influence of gut microbiota in the P28GST-mediated anti-inflammatory effects was then assessed by fecal microbiota transplantation experiments from P28GST-immunized mice to either conventional or microbiota depleted naïve recipient mice. Finally, the experimental data were supplemented by the temporal fecal microbiota compositions of P28GST-treated Crohn's disease patients from a pilot clinical study (NCT02281916). The P28GST administration slightly modulated the diversity and composition of mouse fecal microbiota while it significantly reduced experimental colitis in mice. Fecal microbiota transplantation experiments failed to restore the P28GST-induced anti-inflammatory effects. In Crohn's disease patients, P28GST also induced slight changes in their overall fecal bacterial composition. Collectively, these results provide key elements in both the anti-inflammatory mechanisms and the safe therapeutic use of immunomodulation with such promising helminth-derived molecules.
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http://dx.doi.org/10.3390/cells8060577DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6627314PMC
June 2019

Real-life efficacy of osimertinib in pretreated patients with advanced non-small cell lung cancer harboring EGFR T790M mutation.

Lung Cancer 2019 01 27;127:96-102. Epub 2018 Nov 27.

CHI de Créteil, France.

Objectives The efficacy of osimertinib in pretreated patients with advanced non-small cell lung cancer (NSCLC) harboring EGFR T790 M resistance mutation was demonstrated in clinical trials. However, data on efficacy of osimertinib in real world remain rare. Materials and methods This retrospective multicentric study analyzed T790M-positive advanced NSCLC patients enrolled in French early access program for osimertinib. Patients were pretreated with first- or second-generation EGFR tyrosine-kinase inhibitor and for a majority with chemotherapy. Primary endpoints were progression-free survival (PFS) and overall survival (OS) from osimertinib initiation. Results 205 patients (mean age, 69.5 years; female, 68.8%; adenocarcinoma, 97.5%, never-smokers, 71.5%) were analyzed. Osimertinib was used in second and third line in 18.0% and 82.0% of patients, respectively. Median PFS was 12.4 (95% CI, 10.1-15.1) months. In patients with and without cerebral metastasis, PFS was 9.7 (7.7-13.5) and 15.1 (12.0-17.1) months (p = 0.21), respectively. PFS in second and third line or more was 12.6 (6.7-17.5) and 12.4 (9.7-15.3) months, respectively. Median PFS in patients with EGFR exon 19 deletion and exon 21 mutation was 13.5 (10.1-16.0) and 9.7 (7.4-13.2) months, respectively (p = 0.049). Median OS since osimertinib initiation was 20.5 (16.9-24.3) months: 23.1 (18.6-27.8) and 18.0 (12.2-22.2) months in patients without and with cerebral metastasis (p = 0.11); 17.5 (11.6-27.8) and 21.7 (17.3-24.3) months as second or third line of treatment or more (p = 0.46), respectively. Median OS in patients with EGFR exon 19 deletion and exon 21 mutation was 23.1 (18.6-25.7) and 15.3 (11.6-21.7) months, respectively (p = 0.03). Osimertinib dosage was modified in 8.0% of patients and definitively discontinued for adverse events in 5.9%. Fifty patients benefited from rebiopsy (persistence of T790 M mutation, 44.7%; C797S mutation, 21.1%; cMET amplification, 8.0%). Conclusion In pretreated patients with T790M-mutated advanced NSCLC, the efficacy of osimertinib appears similar in real-world setting to that of clinical trials.
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http://dx.doi.org/10.1016/j.lungcan.2018.11.037DOI Listing
January 2019

Occurrence and Dynamism of Lactic Acid Bacteria in Distinct Ecological Niches: A Multifaceted Functional Health Perspective.

Front Microbiol 2018 27;9:2899. Epub 2018 Nov 27.

Université de Lille, Inserm, CHU Lille, U995 - LIRIC - Lille Inflammation Research International Center, Lille, France.

Lactic acid bacteria (LAB) are representative members of multiple ecosystems on earth, displaying dynamic interactions within animal and plant kingdoms in respect with other microbes. This highly heterogeneous phylogenetic group has coevolved with plants, invertebrates, and vertebrates, establishing either mutualism, symbiosis, commensalism, or even parasitism-like behavior with their hosts. Depending on their location and environment conditions, LAB can be dominant or sometimes in minority within ecosystems. Whatever their origins and relative abundance in specific anatomic sites, LAB exhibit multifaceted ecological and functional properties. While some resident LAB permanently inhabit distinct animal mucosal cavities, others are provided by food and may transiently occupy the gastrointestinal tract. It is admitted that the overall gut microbiome has a deep impact on health and diseases. Here, we examined the presence and the physiological role of LAB in the healthy human and several animal microbiome. Moreover, we also highlighted some dysbiotic states and related consequences for health, considering both the resident and the so-called "transionts" microorganisms. Whether LAB-related health effects act collectively or follow a strain-specificity dogma is also addressed. Besides the highly suggested contribution of LAB to interplay with immune, metabolic, and even brain-axis regulation, the possible involvement of LAB in xenobiotic detoxification processes and metal equilibrium is also tackled. Recent technological developments such as functional metagenomics, metabolomics, high-content screening and design and experimental models now open new horizons for LAB as markers applied for disease diagnosis, susceptibility, and follow-up. Moreover, identification of general and more specific molecular mechanisms based on antioxidant, antimicrobial, anti-inflammatory, and detoxifying properties of LAB currently extends their selection and promising use, either as probiotics, in traditional and functional foods, for dedicated treatments and mostly for maintenance of normobiosis and homeostasis.
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http://dx.doi.org/10.3389/fmicb.2018.02899DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6277688PMC
November 2018

Cost-effectiveness of , and testing for decision making in advanced nonsmall cell lung carcinoma: the French IFCT-PREDICT.amm study.

Eur Respir J 2018 03 15;51(3). Epub 2018 Mar 15.

Service de Pneumologie, Assistance Publique Hôpitaux de Paris, Hôpital Tenon, Sorbonne Universités, UPMC Université Paris 06, GRC 04, Theranoscan, Paris, France.

rearrangement and / mutations constitute the primary biomarkers tested to provide targeted or nontargeted therapies in advanced nonsmall cell lung cancer (NSCLC) patients. Our objective was to assess the cost-effectiveness of biomarker testing for NSCLC.Between 2013 and 2014, 843 treatment-naive patients were prospectively recruited at 19 French hospitals into a longitudinal observational cohort study. Two testing strategies were compared, with "at least one biomarker status known" and "at least status known", in addition to "no biomarker testing" as the reference strategy. The Kaplan-Meier approach was employed to assess restricted mean survival time. Direct medical costs incurred by hospitals were estimated with regard to treatment, inpatient care and biomarker testing.Compared with "no biomarker testing", the "at least one biomarker status known" strategy yielded an incremental cost-effectiveness ratio of EUR13 230 per life-year saved, which decreased to EUR7444 per life-year saved with the "at least status known" testing strategy. In sensitivity analyses, biomarker testing strategies were less costly and more effective in 41% of iterations.In summary, molecular testing prior to treatment initiation proves to be cost-effective in advanced NSCLC management and may assist decision makers in defining conditions for further implementation of these innovations in general practice.
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http://dx.doi.org/10.1183/13993003.01467-2017DOI Listing
March 2018

L. plantarum WCFS1 enhances Treg frequencies by activating DCs even in absence of sampling of bacteria in the Peyer Patches.

Sci Rep 2018 01 29;8(1):1785. Epub 2018 Jan 29.

Top Institute Food and Nutrition, Wageningen, The Netherlands.

Probiotics such as L. plantarum WCFS1 can modulate immune responses in healthy subjects but how this occurs is still largely unknown. Immune-sampling in the Peyer Patches has been suggested to be one of the mechanisms. Here we studied the systemic and intestinal immune effects in combination with a trafficking study through the intestine of a well-established immunomodulating probiotic, i.e. L. plantarum WCFS1. We demonstrate that not more than 2-3 bacteria were sampled and in many animals not any bacterium could be found in the PP. Despite this, L. plantarum was associated with a strong increase in infiltration of regulatory CD103 DCs and generation of regulatory T cells in the spleen. Also, a reduced splenic T helper cell cytokine response was observed after ex vivo restimulation. L. plantarum enhanced Treg cells and attenuated the T helper 2 response in healthy mice. We demonstrate that, in healthy mice, immune sampling is a rare phenomenon and not required for immunomodulation. Also in absence of any sampling immune activation was found illustrating that host-microbe interaction on the Peyer Patches was enough to induce immunomodulation of DCs and T-cells.
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http://dx.doi.org/10.1038/s41598-018-20243-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5788989PMC
January 2018

Drosophila Perpetuates Nutritional Mutualism by Promoting the Fitness of Its Intestinal Symbiont Lactobacillus plantarum.

Cell Metab 2018 02 28;27(2):362-377.e8. Epub 2017 Dec 28.

Institut de Génomique Fonctionnelle de Lyon (IGFL), Université de Lyon, Ecole Normale Supérieure de Lyon, CNRS UMR 5242, Université Claude Bernard Lyon 1, 69364 Lyon Cedex 07, France. Electronic address:

Facultative animal-bacteria symbioses, which are critical determinants of animal fitness, are largely assumed to be mutualistic. However, whether commensal bacteria benefit from the association has not been rigorously assessed. Using a simple and tractable gnotobiotic model- Drosophila mono-associated with one of its dominant commensals, Lactobacillus plantarum-we reveal that in addition to benefiting animal growth, this facultative symbiosis has a positive impact on commensal bacteria fitness. We find that bacteria encounter a strong cost during gut transit, yet larvae-derived maintenance factors override this cost and increase bacterial population fitness, thus perpetuating symbiosis. In addition, we demonstrate that the maintenance of the association is required for achieving maximum animal growth benefits upon chronic undernutrition. Taken together, our study establishes a prototypical case of facultative nutritional mutualism, whereby a farming mechanism perpetuates animal-bacteria symbiosis, which bolsters fitness gains for both partners upon poor nutritional conditions.
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http://dx.doi.org/10.1016/j.cmet.2017.11.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5807057PMC
February 2018

BCL-2 as a therapeutic target in chronic lymphocytic leukemia.

Clin Adv Hematol Oncol 2017 Mar;15(3):210-218

Center for Chronic Lymphocytic Leukemia, Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania.

Venetoclax (formerly ABT-199) was recently approved in the United States for the treatment of patients who have relapsed or refractory chronic lymphocytic leukemia (CLL) with the 17p deletion. Venetoclax has demonstrated marked activity as monotherapy as well as in combination with cytotoxic chemotherapies, B-cell receptor inhibitors, and anti-CD20 monoclonal antibodies across the spectrum of CLL. The potency of venetoclax has been associated with a unique ability to induce deep (minimal residual disease-negative) complete remissions that appear to be durable. Its toxicity profile includes manageable hematologic toxicities, as well as the potential for tumor lysis syndrome. Here, we review the BCL-2 pathway and the mechanism of action of BCL-2 inhibitors, the activity and safety profile of venetoclax, and the practical application of venetoclax in the management of patients with CLL.
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March 2017

Characterization of the protective immune response to Yersinia pseudotuberculosis infection in mice vaccinated with an LcrV-secreting strain of Lactococcus lactis.

Vaccine 2016 11 11;34(47):5762-5767. Epub 2016 Oct 11.

Univ. Lille, Inserm, CNRS, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - CIIL - Center for Infection and Immunity of Lille, F-59000 Lille, France. Electronic address:

Background: Pseudotuberculosis is an infection caused by the bacterial enteropathogen Yersinia pseudotuberculosis and is considered to be a significant problem in veterinary medicine. We previously found that intranasal administration of a recombinant Lactococcus lactis strain that secretes the low-calcium response V (LcrV) antigen from Y. pseudotuberculosis (Ll-LcrV) confers protection against a lethal Y. pseudotuberculosis infection. Here, we aimed at characterizing the immunological basis of this LcrV-elicited protective response and at determining the duration of vaccine-induced immunity.

Methods: Splenocytes from BALB/c mice intranasally immunized with Ll-LcrV or Ll as control were immunostained then analyzed by flow cytometry. Protection against a lethal intravenous injection of Y. pseudotuberculosis was also determined (i) in immunized BALB/c mice depleted or not of CD4, CD8 or CD25 cells and (ii) in naïve BALB/c mice receiving serum from immunized mice by counting the number of bacteria in liver and spleen. Lastly, survival rate of immunized BALB/c mice following a lethal intravenous injection of Y. pseudotuberculosis was followed up to 9-months.

Results: We found that T and B lymphocytes but not non-conventional lymphoid cells were affected by Ll-LcrV immunization. We also observed that depletion of CD4 and CD25 but not CD8 cells in immunized mice eradicated protection against a lethal systemic Y. pseudotuberculosis infection, suggesting that activated CD4 T lymphocytes are required for vaccine-induced protection. Adoptive transfer of LcrV-specific antibodies from Ll-LcrV-immunized animals significantly reduced the bacterial counts in the liver compared to non-vaccinated mice. Lastly, the protective immunity conferred by Ll-LcrV decreased slightly over time; nevertheless almost 60% of the mice survived a lethal bacterial challenge at 9months post-vaccination.

Conclusion: Mucosal vaccination of mice with Ll-LcrV induced cell- and antibody-mediated protective immunity against Y. pseudotuberculosis infection in the mouse and the protection is long-lasting.
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http://dx.doi.org/10.1016/j.vaccine.2016.09.060DOI Listing
November 2016

Corrigendum to "Snapshot on a Pilot Metagenomic Study for the Appraisal of Gut Microbial Diversity in Mice, Cat, and Man".

Gastroenterol Res Pract 2016 28;2016:3053727. Epub 2016 Jul 28.

Université Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019, UMR 8204, Centre d'Infection et d'Immunité de Lille, 59000 Lille, France.

[This corrects the article DOI: 10.1155/2016/6587825.].
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http://dx.doi.org/10.1155/2016/3053727DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4980530PMC
August 2016

Snapshot on a Pilot Metagenomic Study for the Appraisal of Gut Microbial Diversity in Mice, Cat, and Man.

Gastroenterol Res Pract 2016 24;2016:6587825. Epub 2016 Apr 24.

Université Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019, UMR 8204, Centre d'Infection et d'Immunité de Lille, 59000 Lille, France.

Gut microbiota plays a key role in the maintenance of homeostasis and host physiology, comprising development, metabolism, and immunity. Profiling the composition and the gastrointestinal microbiome with a reliable methodology is of substantial interest to yield new insights into the pathogenesis of many diseases as well as defining new prophylactic and therapeutic interventions. Here, we briefly present our methodology applied to fecal samples from mice and then further extended to the samples from a cat and a single human subject at 4 different time points as examples to illustrate the methodological strengths. Both interindividual and time-related variations are demonstrated and discussed.
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http://dx.doi.org/10.1155/2016/6587825DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4860491PMC
May 2016

Does oral exposure to cadmium and lead mediate susceptibility to colitis? The dark-and-bright sides of heavy metals in gut ecology.

Sci Rep 2016 Jan 11;6:19200. Epub 2016 Jan 11.

Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - CIIL - Centre d'Infection et d'Immunité de Lille, F-59000 Lille, France.

Although the heavy metals cadmium (Cd) and lead (Pb) are known environmental health concerns, their long-term impacts on gut ecology and susceptibility to gastrointestinal autoimmune diseases have not been extensively investigated. We sought to determine whether subchronic oral exposure to Cd or Pb is a risk factor for the development and progression of inflammatory bowel disease (IBD). Mice were exposed to various doses of CdCl2 or PbCl2 in drinking water for 1, 4 or 6 weeks prior to infection with Salmonella, the induction of colitis with dextran sodium sulfate (DSS) or trinitrobenzene sulfonic acid (TNBS). In human cell-based models, exposure to Cd and Pb is associated with reduced transepithelial electric resistance and changes in bacteria-induced cytokine responses. Although 1- and 6-week exposures did not have clear effects on the response to Salmonella infectious challenges, 1-week short-term treatments with CdCl2 tended to enhance intestinal inflammation in mice. Unexpectedly, subchronic exposure to Cd and (to a lesser extent) Pb significantly mitigated some of the symptoms of DSS-induced colitis and reduced the severity of TNBS colitis in a dose-dependent manner. The possible adaptive and immunosuppressive mechanisms by which heavy metals might reduce intestinal inflammation are explored and discussed.
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http://dx.doi.org/10.1038/srep19200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4707487PMC
January 2016

Deficiencies in the Management of Iron Deficiency Anemia During Childhood.

Pediatr Blood Cancer 2016 Apr 5;63(4):743-5. Epub 2016 Jan 5.

Department of Pediatrics, The University of Texas Southwestern Medical Center, Dallas, Texas.

Limited high-quality evidence supports the management of iron deficiency anemia (IDA). To assess our institutional performance in this area, we retrospectively reviewed IDA treatment practices in 195 consecutive children referred to our center from 2006 to mid-2010. The majority of children were ≤4 years old (64%) and had nutritional IDA (74%). In 11- to 18-year-old patients (31%), the primary etiology was menorrhagia (42%). Many were referred directly to the emergency department and/or prescribed iron doses outside the recommended range. Poor medication adherence and being lost-to-follow-up were common. Substantial improvements are required in the management of IDA.
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http://dx.doi.org/10.1002/pbc.25861DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4755821PMC
April 2016
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