Search

Abstract Background Sagittal balance, commonly impaired in lumbar spinal stenosis (LSS) patients, is typically assessed using the sagittal vertical axis (SVA) with EOS imaging. However, to limit X-ray exposure and medical costs, it could be interesting to evaluate the capacity of quantified motion analysis to estimate the 3D modeling of SVA in patients with symptomatic LSS. Methods An estimation of the SVA in patients with LSS was performed with 3D motion analysis. SVA and “C7_PSI” (orthogonal horizontal distance between the vertical lines through the markers of the C7 vertebra and the middle of the posterosuperior iliac spine) were measured on 37 LSS patients using EOS radiography and postural and 3D motion analysis, respectively. Multiple stepwise linear regressions were performed with EOS SVA according to age, body mass index, C7_PSI and/or postural variables. Results A highly significant relationship was found between SVA and C7_PSI, mediolateral amplitude of CoP displacements and age (adjusted R²=0.69, p

Objective:. To evaluate the diagnostic accuracy of drain fluid lipase as an early predictor of postoperative pancreatic fistula and establish the most appropriate day for their measure. Background:. Clinically relevant postoperative pancreatic fistula remains a potentially life-threatening complication after pancreatic surgery. Early detection strategies remain key to reduce both the incidence and the burden of pancreatic fistula. Methods:. The LIPAse DRAIN (LIPADRAIN) study is a multicenter, prospective diagnostic study conducted in 7 tertiary university hospitals. Drain fluid values to detect clinically relevant postoperative pancreatic fistula from postoperative day 1 to postoperative day 6 were evaluated using receiver operating characteristic curve analysis. A biomarker was considered to be relevant for clinical use if its area under the curve (AUC) was greater than 0.75. Results:. Of the 625 patients included in the analysis, clinically relevant postoperative pancreatic fistula occurred in 203 (32%) patients. On postoperative days 3 and 4, drain fluid lipase was a reliable biomarker to detect clinically relevant postoperative pancreatic fistula (AUC: 0.761; 95% confidence interval [CI]: 0.761–0.799 and AUC: 0.784; 95% CI: 0.743–0.821, respectively). On postoperative day 3, with a threshold of 299 units/L, drain fluid lipase yielded a negative predictive value of 51%, sensitivity of 78%, and specificity of 63% for the detection of clinically relevant postoperative pancreatic fistula. Conclusions:. In this multicenter prospective study, drain fluid lipase is a reliable biomarker at postoperative days 3 and 4 for the diagnosis of clinically relevant postoperative pancreatic fistula after pancreatic surgery and should be systematically measured on postoperative day 3.

Abstract Background While not traditionally included in the conceptual understanding of circulation, the interstitium plays a critical role in maintaining fluid homeostasis. Fluid balance regulation is a critical aspect of septic shock, with a well-known association between fluid balance and outcome. The regulation of transcapillary flow is the first key to understand fluid homeostasis during sepsis. Main text Capillary permeability is increased during sepsis, and was classically considered to be necessary and sufficient to explain the increase of capillary filtration during inflammation. However, on the other side of the endothelial wall, the interstitium may play an even greater role to drive capillary leak. Indeed, the interstitial extracellular matrix forms a complex gel-like structure embedded in a collagen skeleton, and has the ability to directly attract intravascular fluid by decreasing its hydrostatic pressure. Thus, interstitium is not a mere passive reservoir, as was long thought, but is probably major determinant of fluid balance regulation during sepsis. Up to this date though, the role of the interstitium during sepsis and septic shock has been largely overlooked. A comprehensive vision of the interstitium may enlight our understanding of septic shock pathophysiology. Overall, we have identified five potential intersections between septic shock pathophysiology and the interstitium: 1. increase of oedema formation, interacting with organ function and metabolites diffusion; 2. interstitial pressure regulation, increasing transcapillary flow; 3. alteration of the extracellular matrix; 4. interstitial secretion of inflammatory mediators; 5. decrease of lymphatic outflow. Conclusions We aimed at reviewing the literature and summarizing the current knowledge along these specific axes, as well as methodological aspects related to interstitium exploration.

Abstract Biofilm (BF) growth is believed to play a major role in the development of ventilator-associated pneumonia (VAP) in the intensive care unit. Despite concerted efforts to understand the potential implication of endotracheal tube (ETT)-BF dispersal, clinically relevant data are lacking to better characterize the impact of its mesostructure and microbiological singularity on the occurrence of VAP. We conducted a multicenter, retrospective observational study during the third wave of the COVID-19 pandemic, between March and May 2021. In total, 64 ETTs collected from 61 patients were included in the present BIOPAVIR study. Confocal microscopy acquisitions revealed two main morphological aspects of ETT-deposited BF: (1) a thin, continuous ribbon-shaped aspect, less likely monobacterial and predominantly associated with Enterobacter spp., Streptococcus pneumoniae or Viridans streptococci, and (2) a thicker, discontinuous, mushroom-shaped appearance, more likely characterized by the association of bacterial and fungal species in respiratory samples. The microbiological characterization of ETT-deposited BF found higher acquired resistance in more than 80% of analyzed BF phenotypes, compared to other colonization sites from the patient’s environment. These findings reveal BF as a singular microbiological compartment, and are of added clinical value, with a view to future ETT-deposited BF-based antimicrobial stewardship in critically ill patients. Trial registration NCT04926493. Retrospectively registered 15 June 2021.

Background The leading cause of acute bacterial meningitis in adults is Streptococcus pneumoniae. This infection is associated with high rates of mortality and morbidity related, among other factors, to the excessive host response to the pneumococcal lysis. Experimental in vitro and in vivo data show that the combination of corticosteroids/third-generation cephalosporins and the non-lytic antibiotic, daptomycin, has synergistic effects with (1) a rapid cerebrospinal fluid sterilisation, (2) less brain damages and (3) less loss of cognitive performances. Despite these encouraging results, daptomycin has never been evaluated in adult patients with pneumococcal meningitis.Methods and analysis The AddaMAP trial is a phase II, open-label, Simon’s two-stage, multicentre trial that has been designed to assess the efficacy and safety of adding daptomycin (10 mg/kg/d for 8 days) to the recommended treatment (corticosteroids+third generation cephalosporin) in adults with confirmed pneumococcal meningitis. The main endpoint is the disability-free survival (defined as modified Rankin Scale mRS≤2) at day 30. Secondary outcomes are overall mortality, disability at D30 and D90 (mRS, Glasgow Coma Scale and Glasgow Outcome Scales, mini-mental score), hearing loss (Hearing Handicap Inventory Test at D30 and D90, routine audiometric test and Hearing-it test at D30), and quality of life (12-item Short Form Survey and WHO QOL BREF). Seventy-two analysable patients are required.Ethics and dissemination The study protocol was approved by the Institutional Review Board of the IDF 1 of the ethics committee on 16 January 2018, and authorisation was obtained from the Agence Nationale de Securité des Médicaments et des Produits de Santé on 22 September 2017. The results will be submitted for publication in a peer-reviewed journal.Trial registration number NCT03480191.

Abstract Background The modulation of perioperative inflammation seems crucial to improve postoperative morbidity and cancer-related outcomes in patients undergoing oncological surgery. Data from the literature suggest that perioperative corticosteroids decrease inflammatory markers and might be associated with fewer complications in esophageal, liver, pancreatic and colorectal surgery. Their benefit on cancer-related outcomes has not been assessed. Methods The CORTIFRENCH trial is a phase III multicenter randomized double-blind placebo-controlled trial to assess the impact of a flash dose of preoperative corticosteroids versus placebo on postoperative morbidity and cancer-related outcomes after elective curative-intent surgery for digestive cancer. The primary endpoint is the frequency of patients with postoperative major complications occurring within 30 days after surgery (defined as all complications with Clavien-Dindo grade > 2). The secondary endpoints are the overall survival at 3 years, the disease-free survival at 3 years, the frequency of patients with intraabdominal infections and postoperative infections within 30 days after surgery and the hospital length of stay. We hypothesize a reduced risk of major complications and a better disease-survival at 3 years in the experimental group. Allowing for 5% of drop-out, 1 200 patients (600 per arm) should be included. Discussion This will be the first trial focusing on the impact of perioperative corticosteroids on cancer related outcomes. If significant, it might be a strong improvement on oncological outcomes for patients undergoing surgery for digestive cancers. Trial registration ClinicalTrials.gov, NCT03875690, Registered on March 15, 2019, URL: https://clinicaltrials.gov/ct2/show/NCT03875690 .

Introduction Conflicts between relatives and physicians may arise when decisions are being made about limiting life-sustaining therapies (LST). The aim of this study was to describe the motives for, and management of team-family conflicts surrounding LST limitation decisions in French adult ICUs. Methods Between June and October 2021, French ICU physicians were invited to answer a questionnaire. The development of the questionnaire followed a validated methodology with the collaboration of consultants in clinical ethics, a sociologist, a statistician and ICU clinicians. Results Among 186 physicians contacted, 160 (86%) answered all the questions. Conflicts over LST limitation decisions were mainly related to requests by relatives to continue treatments considered to be unreasonably obstinate by ICU physicians. The absence of advance directives, a lack of communication, a multitude of relatives, and religious or cultural issues were frequently mentioned as factors contributing to conflicts. Iterative interviews with relatives and proposal of psychological support were the most widely used tools in attempting to resolve conflict, while the intervention of a palliative care team, a local ethics resource or the hospital mediator were rarely solicited. In most cases, the decision was suspended at least temporarily. Possible consequences include stress and psychological exhaustion among caregivers. Improving communication and anticipation by knowing the patient’s wishes would help avoid these conflicts. Conclusion Team-family conflicts during LST limitation decisions are mainly related to requests from relatives to continue treatments deemed unreasonable by physicians. Reflection on the role of relatives in the decision-making process seems essential for the future.

IntroductionIn a nationwide survey of practices, we sought to define the criteria, circumstances and consequences of non-beneficial admissions to the intensive care unit (ICU), with a view to proposing measures to avoid such situations.MethodsICU physicians from a French research in ethics network participated in an online survey. The first part recorded age, sex, and years' experience of the participants. In the second part, there were 8 to 12 proposals on each of 4 main domains: (1) What criteria could be used to qualify an ICU stay as non-beneficial? (2) What circumstances result in the admission of a patient whose ICU stay may later be deemed non-beneficial? (3) What are the consequences of a non-beneficial stay in the ICU? (4) What measures could be implemented to avoid admissions that later come to be considered as non-beneficial? Responses were on a 5-point Likert scale ranging from "Strongly disagree" to "Strongly agree".ResultsAmong 164 physicians contacted, 154 (94%) responded. The majority cited several criteria used to qualify a stay as non-beneficial. Similarly, >80% cited several possible circumstances that could result in non-beneficial admissions, including lack of knowledge of the case and the patient's history, and failure to anticipate acute deterioration. Possible consequences of non-beneficial stays included stress and anxiety for the patient/family, misunderstandings and conflict. Discussing the utility of possible ICU admission in the framework of the patient's overall healthcare goals was hailed as a means to prevent non-beneficial admissions.ConclusionThe results of this survey suggest that joint discussions should take place during the patient's healthcare trajectory, before the acute need for ICU arises, with a view to limiting or avoiding ICU stays that may later come to be deemed "non-beneficial".

IntroductionRefractory septic shock (RSS) is characterized by high vasopressor requirements, as a consequence of vasopressor resistance, which may be caused or enhanced by sympathetic hyperactivation. Experimental models and clinical trials show a reduction in vasopressor requirements and improved microcirculation compared to conventional sedation. Dexmedetomidine did not reduce mortality in clinical trials, but few septic shock patients were enrolled. This pilot trial aims to evaluate vasopressor re-sensitization with dexmedetomidine and assess the effect size, in order to design a larger trial.MethodsThis is an investigator-initiated, multicenter, randomized, double-blind, placebo-controlled trial, comparing dexmedetomidine versus placebo in RSS patients with norepinephrine dose ≥0.5μg/kg/min. The primary outcome is blood pressure response to phenylephrine challenge, 6 hours after completion of a first challenge, after study treatment initiation. Secondary outcomes include feasibility and safety outcomes (bradycardia), mortality, vasopressor requirements, heart rate variability, plasma and urine catecholamines levels. The sample size is estimated at 32 patients to show a 20% improvement in blood pressure response to phenylephrine. Randomization (1:1) will be stratified by center, sedation type and presence of liver cirrhosis. Blood pressure and ECG will be continuously recorded for the first 24 h, enabling high-quality data collection for the primary and secondary endpoints. The study was approved by the ethics committee “Sud-Est VI” (2019-000726-22) and patients will be included after informed consent.DiscussionThe present study will be the first randomized trial to specifically address the hemodynamic effects of dexmedetomidine in patients with septic shock. We implement a high-quality process for data acquisition and recording in the first 24 h, ensuring maximal quality for the evaluation of both efficacy and safety outcomes, as well as transparency of results. The results of the study will be used to elaborate a full-scale randomized controlled trial with mortality as primary outcome in RSS patients.Trial registrationRegistered with ClinicalTrials.gov (NCT03953677). Registered 16 May 2019, https://clinicaltrials.gov/ct2/show/NCT03953677.

Lipopolysaccharide (LPS) is a key player for innate immunity activation. It is therefore a prime target for sepsis treatment, as antibiotics are not sufficient to improve outcome during septic shock. An extracorporeal removal method by polymyxin (PMX) B direct hemoperfusion (PMX-DHP) is used in Japan, but recent trials failed to show a significant lowering of circulating LPS levels after PMX-DHP therapy. PMX-DHP has a direct effect on LPS molecules. However, LPS is not present in a free form in the circulation, as it is mainly carried by lipoproteins, including LDLs. Lipoproteins are critical for physiological LPS clearance, as LPSs are carried by LDLs to the liver for elimination. We hypothesized that LDL apheresis could be an alternate method for LPS removal. First, we demonstrated in vitro that LDL apheresis microbeads are almost as efficient as PMX beads to reduce LPS concentration in LPS-spiked human plasma, whereas it is not active in PBS. We found that PMX was also adsorbing lipoproteins, although less specifically. Then, we found that endogenous LPS of patients treated by LDL apheresis for familial hypercholesterolemia is also removed during their LDL apheresis sessions, with both electrostatic-based devices and filtration devices. Finally, LPS circulating in the plasma of septic shock and severe sepsis patients with gram-negative bacteremia was also removed in vitro by LDL adsorption. Overall, these results underline the importance of lipoproteins for LPS clearance, making them a prime target to study and treat endotoxemia-related conditions.

BackgroundIn French Guiana poverty is widespread and specialized care is lacking. We aimed to compare strokes between precarious and non-precarious patients within French Guiana and to compare the epidemiology of ischemic strokes and their outcomes between French Guiana and mainland France.MethodsA multicenter prospective cohort examined the influence of social inequalities on stroke characteristics. Consecutive patients aged > 18 years admitted for an acute ischemic stroke, confirmed by neuroimaging were eligible. Exclusion criteria were a history of symptomatic stroke, presence of other short-term life-threatening diseases and inability to contact patients by telephone during follow-up. Social deprivation was measured using the EPICES score, which is based on a multidimensional questionnaire.ResultsOverall, 652 patients with ischemic stroke were included. The patients in French Guiana were 7 years younger, were more frequently male, of sub-Saharan ancestry, they had a low level of education, and were more often precarious (67.7%) than the patients included in Dijon (39.2%). The origin of the ischemic stroke was predominantly lacunar for patients included in French Guiana and cardioembolic for patients included in Dijon, with greater severity for patients included in Dijon. The proportion of patients with known pre-stroke hypertension, diabetes, or a history of Transient Ischemic Accident was greater in French Guiana than in Dijon. In contrast, hypercholesterolemia, atrial fibrillation, and history of Myocardial Infarction were more frequently found in patients included in Dijon than in patients included in French Guiana. Fibrinolysis was less frequent in French Guiana than in Dijon, 24% of patients arriving early enough receiving thrombolysis in French Guiana vs. 45% in Dijon, P < 0.0001. However, after adjustment for patient characteristics, the effect of the center on the use of fibrinolysis disappeared. When comparing precarious and non-precarious patients within French Guiana, the main difference was the younger age and the lower mortality of precarious patients—notably immigrants.ConclusionPrecariousness was widespread in French Guiana. Within French Guiana, despite a younger age among foreigners than French patients, the risk factors, mechanisms, and outcomes were homogenous across socioeconomic strata. The observed differences between the two contrasted French territories suggested that, beyond health inequalities, the epidemiology of cardiovascular risk factors may differ between French Guiana and mainland France.

Abstract Background French Guiana has the highest incidence of ischemic and hemorrhagic stroke of all French territories. However, there is no further information on the epidemiology and management of stroke in French Guiana. Our goal was to describe the characteristics of patients in French Guiana in order to generate hypotheses regarding the determinants explaining the magnitude of this public health problem. Methods We used the data of the French multicentre INDIA prospective cohort study which included consecutive patients aged > 18 years with a first-ever stroke from June 2011 to October 2014. For the present study, only patients with ischemic or hemorrhagic stroke admitted in one of the 3 participating hospitals were analyzed. Results Among the 298 patients (mean age 62.2 ± 14.5 years, 63.7% man) included in French Guiana, 52% were born abroad. Most strokes were ischemic strokes (79%), 14% of which were thrombolyzed. Hypertension (70.2%), history of smoking (22%) and diabetes (25%) were the most common risk factors and 28.4% of patients had known but untreated hypertension. Overall 89 (38%) patients with ischemic stroke were admitted less than 4.5 h after the first symptoms. In-hospital mortality was greater for intracerebral hemorrhage (18.7%) than for ischemic stroke (4.2%). Overall, 84.5% had health insurance coverage and among these, 41.9% had CMU, the universal health insurance for the poor. Conclusions The present study is the first epidemiologic description of stroke in French Guiana. The comparisons of these results show that stroke patients in French Guiana are epidemiologically atypical because they are younger, and more likely to be males than patients in mainland France. Stroke risk factors and delay between stroke and hospital admission were comparable with what is observed in France, suggesting that efforts should focus on primary care and social inequalities of health to alleviate the main determinants of stroke in French Guiana.

Abstract Background The influence of socioeconomic status on patient outcomes is unclear. We assessed the impact of socioeconomic deprivation on severity of illness at intensive care unit (ICU) admission, and on the risk of death at 3 months after ICU admission. Methods The IVOIRE study was a prospective, observational, multicentre cohort study in the ICU of 8 participating hospitals in France, including patients aged ≥ 18 years admitted to the ICU and receiving at least one life support therapy for organ failure. The primary outcomes were severity at admission (assessed by SAPSII score), and mortality at 3 months. Socioeconomic data were obtained from interviews with patients or family. Deprivation was assessed using the EPICES score. Results Among 1294 patents included between 2013 and 2016, 629 (48.6%) were classed as deprived and differed significantly from non-deprived subjects in terms of sociodemographic characteristics and pre-existing conditions. The mean SAPS II score at admission was 50.1 ± 19.4 in deprived patients and 52.3 ± 17.3 in non-deprived patients, with no significant difference by multivariable analysis (β = − 1.85 [95% CI − 3.86; + 0.16, p = 0.072]). The proportion of death was 31.1% at 3 months, without significant differences between deprived and non-deprived patients, even after adjustment for confounders. Conclusions Deprivation is frequent in patients admitted to the ICU and is not associated with disease severity at admission, or with mortality at 3 months between deprived and non-deprived patients. Trial registration The IVOIRE cohort is registered with ClinicalTrials.gov under the identifier NCT01907581, registration date 17/7/2013

IntroductionOur objective was to develop and to evaluate a system to measure latency and threshold of pendular motion perception based on a swinging bed.Materials and methodsThis prospective study included 30 healthy adults (age: 32 ± 12 years). All subjects were tested twice with a 10 min. interval. A second trial was conducted 2 to 15 days after. A rehabilitation swinging bed was connected to an electronic device emitting a beep at the beginning of each oscillation phase with an adjustable time lag. Subjects were blindfolded and auditory cues other than the beep were minimized. The acceleration threshold was measured by letting the bed oscillate freely until a natural break and asking the patient when he did not perceive any motion. The perception latency was determined by asking the patient to indicate whether the beep and the peak of each oscillation were synchronous. The time lag between sound and peak of the head position was swept from -750 to +750 ms by 50 ms increments.ResultsThe mean acceleration threshold was 9.2±4.60 cm/s2. The range width of the synchronous perception interval was estimated as 535±190 ms. The point of subjective synchronicity defined as the center of this interval was -195±106 ms (n = 30). The test-retest evaluation in the same trial showed an acceptable reproducibility for the acceleration threshold and good to excellent for all parameters related to sound-movement latency.ConclusionSwinging bed combined to sound stimulation can provide reproducible information on movement perception in a simple and non-invasive manner with highly reproducible results.

BackgroundMultiple approaches have been proposed to measure low socio-economic status. In France the concept of precariousness, akin to social deprivation, was developed and is widely used. EPICES is a short questionnaire that was developed to measure this concept. This study aimed to evaluate Differential Item Functioning (DIF) in the EPICES questionnaire between contrasted areas: mainland France, French West Indies (FWI) and French Guiana (FG).MethodsThe population was taken from the INDIA study, which aimed to evaluate the impact of social inequalities on stroke characteristics and prognosis. Eligible people were patients referred to neurology or emergency departments for a suspicion of stroke. We assessed the DIF using hybrid ordinal logistic regression method, derived from item response theory.ResultsWe analysed 1 553 stroke patients, including 768 from FWI (49.5%), 289 from FG (18.6%) and 496 from mainland (31.9%). We identified five items with a moderate to large DIF in area comparisons: "meeting with a social worker", "complementary health insurance", "home-owning", "financial difficulties" and "sport activities". Correlation between EPICES score and the latent variable was strong (r = 0.84).ConclusionThis is the first attempt to assess the DIF of the EPICES score between different French populations. We found several items with DIF, which can be explained by individual interpretation or local context. However, the DIFs did not lead to a large difference between the latent variable and the EPICES score, which indicates that it can be used to assess precariousness and social deprivation between contrasted areas.