Benefit of a flash dose of corticosteroids in digestive surgical oncology: a multicenter, randomized, double blind, placebo-controlled trial (CORTIFRENCH).

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 .

Impact of Smoking on Functional Prognosis after Ischemic Stroke according to Deprivation: A Prospective Cohort Study.

BACKGROUND: Smoking influence on poststroke prognosis remains controversial. These conflicting results could be due to some residual confounding factors not fully considered in previous studies, including social deprivation. This study aimed to assess the joint impact of deprivation and smoking on functional outcomes after ischemic stroke. METHODS: Between 2011 and 2014, 1,573 patients with a first-ever stroke were prospectively included in the French multicenter INDIA ("Inegalites sociales et pronostic des accidents vasculaires cerebraux à Dijon et Antilles-Guyane") cohort study. Patients with ischemic stroke and available data on smoking, deprivation, and outcome were considered for the analysis (n = 1,242). Deprivation was assessed using the EPICES "Evaluation de la Précarité et des Inégalites de santé dans les Centres d'Examen de Santé" score. Primary outcome was functional outcome assessed with the modified Rankin Scale (mRS) score at 12 months. Association between smoking and moderate to severe disability (mRS score ≥3) was evaluated with logistic regression model. Interactions between smoking and deprivation were tested. RESULTS: Smokers (n = 189, 15.2%) were younger and more often deprived (EPICES score ≥30.17) than nonsmokers. A significant interaction was found between smoking status and deprivation on disability (p = 0.003). In nondeprived patients, the odds of moderate to severe disability at 12 months were twice as high in smokers as in nonsmokers (adjusted OR = 2.08, 95% CI: 1.04-4.18). This association was not observed in deprived patients (adjusted OR = 0.89, 95% CI: 0.49-1.61). CONCLUSION: The effect of smoking on functional prognosis after ischemic stroke varied according to deprivation status, with poorer outcomes observed in nondeprived patients.

Social deprivation and 1-year survival after stroke: a prospective cohort study.

BACKGROUND: Social deprivation may have a deleterious influence on post-stroke outcomes, but available data in the literature are mixed. AIM: The aim of this cohort study was to evaluate the impact of social deprivation on 1-year survival in patients with first-ever stroke. METHODS: Social deprivation was assessed at individual level with the EPICES score, a validated multidimensional questionnaire, in 1312 patients with ischemic stroke and 228 patients with spontaneous intracerebral hemorrhage, who were prospectively enrolled in six French study centers. Baseline characteristics including stroke severity and pre-stroke functional status were collected. Multivariable Cox models were generated to evaluate the associations between social deprivation and survival at 12 months in ischemic stroke and intracerebral hemorrhage separately. RESULTS: A total of 819 patients (53.2%) were socially deprived (EPICES score ≥ 30.17). In ischemic stroke, mortality at 12 months was higher in deprived than in non-deprived patients (16% vs. 11%, p = 0.006). In multivariable analyses, there was no association between deprivation and death occurring within the first 90 days following ischemic stroke (adjusted hazard ratio [aHR] 0.81, 95% CI 0.54-1.22, p = 0.32). In contrast, an excess in mortality was observed between 90 days and 12 months in deprived compared with non-deprived patients (aHR 1.97, 95% CI 1.14-3.42, p = 0.016). In patients with intracerebral hemorrhage, mortality at 12 months did not significantly differ according to deprivation status. CONCLUSIONS: Social deprivation was associated with delayed mortality in ischemic stroke patients only and, although the exact underlying mechanisms are still to be identified, our findings suggest that deprived patients in particular may benefit from an optimization of post-stroke care.

LDL apheresis as an alternate method for plasma LPS purification in healthy volunteers and dyslipidemic and septic patients.

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.

The epidemiology and management of stroke in French Guiana.

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.

Indications and Outcomes of a Cross-Linked Porcine Dermal Collagen Mesh (Permacol) for Complex Abdominal Wall Reconstruction: A Multicenter Audit.

INTRODUCTION: To reduce the occurrence of complications in the setting of high-risk patients with contaminated operative field, a wide range of biologic meshes has been developed. Yet, few series have reported outcomes after abdominal wall repair (AWR) using such meshes. Permacol is an acellular porcine dermal collagen matrix with a cross-linked pattern. This study reports short- and long-term outcomes after AWR for incisional hernia using Permacol. MATERIALS AND METHODS: All consecutive patients undergoing single-stage open AWR using Permacol mesh at eight university hospitals were included. Mortality, complication and hernia recurrence rates were assessed. Independent risk factors for complications and hernia recurrence were identified with logistic regression and Fine and Gray analysis, respectively. RESULTS: Overall, 250 patients underwent single-stage AWR with Permacol. Nearly 80% had a VHWG grade 3 or 4 defect. In-hospital mortality and complication rates were 4.8% (n = 12) and 61.6% (n = 154), respectively. Reintervention for complications was required for 74 patients (29.6%). Mesh explantation rate was 4% (n = 10). Independent risk factors for complications were smoking, defect size and VHWG grade. After a mean follow-up time of 16.8 months (± 18.1 months), 63 (25.2%) experienced hernia recurrence. One-, 2- and 3-year RFS were 90%, 74% and 57%, respectively. Previous AWR, mesh location and the need for reintervention were independent predictors of hernia recurrence. DISCUSSION: Single-stage AWR is feasible using Permacol. Mortality and complication rates are high due to patients' comorbidities and the degree of contamination of the operative field. Given the observed recurrence rate, the benefit of biologics remains to be ascertained.

Diagnostic Accuracy of Procalcitonin and C-reactive Protein for the Early Diagnosis of Intra-abdominal Infection After Elective Colorectal Surgery: A Meta-analysis.

OBJECTIVE: Intra-abdominal infections (IAIs) after elective colorectal surgery impact significantly the short- and long-term outcomes. In the era of fast-track surgery, they often come to light after discharge from hospital. Early diagnosis is therefore essential. C-reactive protein levels have proved to be accurate in this setting. Procalcitonin has been evaluated in several studies with conflicting results. This meta-analysis aimed to compare the predictive abilities of C-reactive protein and procalcitonin in the occurrence of IAIs after elective colorectal surgery. METHODS: This meta-analysis included studies analyzing C-reactive protein and/or procalcitonin levels at postoperative days 2, 3, 4, and/or 5 as markers of intra-abdominal infection after elective colorectal surgery. Methodological quality was assessed by the QUADAS2 tool. The area under the curve summary receiver-operating characteristic was calculated for each day and each biomarker, using a random-effects model in cases of heterogeneity. RESULTS: The meta-analysis included 11 studies (2692 patients). An IAI occurred in 8.9% of the patients. On postoperative day 3, area under the curve was 0.80 (95% CI, 0.76-0.85) for C-reactive protein and 0.78 (95% CI, 0.68-0.87) for procalcitonin. On postoperative day 5, their predictive accuracies were 0.87 (95% CI, 0.80-0.93) and 0.90 (95% CI, 0.82-0.98), respectively. The accuracy of C-reactive protein and procalcitonin did not differ at any postoperative day. CONCLUSIONS: Levels of inflammatory markers under the cutoff value between postoperative days 3 and 5 ensure safe early discharge after elective colorectal surgery. Procalcitonin seems not to have added value as compared to C-reactive protein in this setting.

Diagnostic Accuracy of Inflammatory Markers As Early Predictors of Infection After Elective Colorectal Surgery: Results From the IMACORS Study.

BACKGROUND: Intra-abdominal infections are frequent and life-threatening complications after colorectal surgery. An early detection could diminish their clinical impact and permit safe early discharge. OBJECTIVE: This study aimed to find the most accurate marker for the detection of postoperative intra-abdominal infection and the appropriate moment to measure it. METHODS: A prospective, observational study was conducted in 3 centers. Consecutive patients undergoing elective colorectal surgery with anastomosis were included. C-reactive protein and procalcitonin were measured daily until the fourth postoperative day. Postoperative infections were recorded according to the definitions of the Centres for Diseases Control. The areas under the receiver operating characteristic curve were analyzed and compared to assess the diagnostic accuracy of each marker. RESULTS: Five-hundred and one patients were analyzed. The incidence of intra-abdominal infection was 11.8%, with 24.6% of patients presenting at least one infectious complication. Overall mortality was 1.2%. At the fourth postoperative day, C-reactive protein was more discriminating than procalcitonin for the detection of intra-abdominal infection (areas under the ROC curve: 0.775 vs 0.689, respectively, P = 0.03). Procalcitonin levels showed wide dispersion. For the detection of all infectious complications, C-reactive protein was also significantly more accurate than procalcitonin on the fourth postoperative day (areas under the ROC curve: 0.783 vs 0.671, P = 0.0002). CONCLUSIONS: C-reactive protein is more accurate than procalcitonin for the detection of infectious complications and should be systematically measured at the fourth postoperative day. It is a useful tool to ensure a safe early discharge after elective colorectal surgery.

Walking test outcomes in adults with genetic neuromuscular diseases: a systematic literature review of their measurement properties.

INTRODUCTION: Neuromuscular diseases (NMDs) include a large group of heterogeneous diseases. NMDs frequently involve gait disorders, which affect quality of life. Several walking tests and tools have been described in the literature, but there is no consensus regarding the use of walking tests and tools in NMDs or of their measurement properties for walking outcomes. The aim of this review is to present an overview of walking tests, including their measurement properties when used in adults with inherited or genetic NMDs. The aim is to help clinicians and researchers choose the most appropriate test for their objective. EVIDENCE ACQUISITION: A systematic review was conducted after consulting MEDLINE (via PubMed), EMBASE, Science direct, Google Scholar and Cochrane Central Register of Controlled Trials databases for published studies in which walking outcome measurement properties were assessed. The validity, reliability, measurement error and responsiveness properties were evaluated in terms of statistical methods and methodological design qualities using the COnsensus-based Standards for the selection of health Measurement Instruments (COSMIN) guidelines. EVIDENCE SYNTHESIS: We included 46 studies in NMDs. These studies included 15 different walking tests and a wide variety of walking outcomes, assessed with six types of walking tools. Overall, the 6MWT was the most studied test in terms of measurement properties. The methodological design and statistical methods of most studies evaluating construct validity, reliability and measurement error were "very good." The majority of outcome measurements were valid and reliable. However, studies on responsiveness as minimal important difference or minimal important change were lacking or were found to have inadequate methodological and statistical methods according to the COSMIN guidelines. CONCLUSIONS: Most walking outcomes were found to be valid and reliable in NMDs. However, in view of the growing number of clinical trials, further studies are needed to clarify additional measurement properties.

Management of patients with high C-reactive protein levels after elective colorectal surgery: Pilot study on a proactive diagnostic and therapeutic approach (GESPACE).

STUDY OBJECTIVE: To evaluate the feasibility and benefit of a diagnostic and therapeutic algorithm for management of patients presenting with a high C-reactive protein (CRP) level after colorectal surgery. PATIENTS AND METHODS: Prospective study including patients with CRP>125mg/L at the 4th postoperative day following elective colorectal surgery. The protocol involved CT-scan of which the results were to orient subsequent management: antibiotics, radiological drainage, endoscopy or surgical redo. Success (primary endpoint) consisted in the proportion of patients with total duration of hospitalization fewer than 15d. Secondary endpoints were: applicability of the protocol in real-life conditions, number of stomas created, duration of hospitalization in an intensive care unit. RESULTS: One hundred and six (106) patients were included: 51 patients (48%) presented with postoperative complications, of which 21 (41%) were severe. No death occurred. Among the included patients, 68% had a hospital stay<15d. Major deviations from the management algorithm occurred in 38% of cases. No patients had an early endoscopy. There was no significant difference with regard to the secondary endpoints according to whether or not the protocol was strictly observed. CONCLUSION: It is necessary to define a protocol for management of patients presenting with high CRP levels after colorectal surgery, the objective being to reduce the impact of complications and to avoid excessive lengthening of hospital stay. The protocol begins with CT-scan, which is to orient subsequent management.

Long-term risk of colorectal cancer after adenoma removal: a population-based cohort study.

BACKGROUND: Previous studies examining the incidence of colorectal cancer after polypectomy have provided discordant findings. The aim of this study was to compare the risk of colorectal cancer after adenoma removal in routine clinical practice with the risk in the general population. DESIGN: Cohort study based on detailed data from a population-based registry that has collected all cases of both colorectal cancers and adenomas diagnosed in a clearly-defined population since 1976. SETTING: French administrative area of Côte-d'Or (Burgundy). METHODS: Residents of the area diagnosed for the first time with colorectal adenoma between 1990 and 1999 were included (n=5779). Initial and follow-up data until December 2003 were used to calculate the colorectal cancer standardised incidence ratio (SIR) and cumulative probabilities after adenoma removal. RESULTS: After a median follow-up of 7.7 years, 87 invasive colorectal cancers were diagnosed whereas 69 cases were expected. Compared with the general population, the overall SIR was 1.26 (95% CI 1.01 to 1.56). The risk of colorectal cancer depended on the characteristics of the initial adenoma (SIR 2.23 (95% CI 1.67 to 2.92) for advanced adenomas and 0.68 (95% CI 0.44 to 0.99) for non-advanced adenomas). In cases of advanced adenomas, the SIR was 1.10 (95% CI 0.62 to 1.82) in patients with colonoscopic follow-up and 4.26 (95% CI 2.89 to 6.04) in those without. The 10-year cumulative probabilities of colorectal cancer were, respectively, 2.05% (95% CI 1.14% to 3.64%) and 6.22% (95% CI 4.26% to 9.02%). CONCLUSIONS: In routine practice, the risk of colorectal cancer after adenoma removal remains high and depends both on initial adenoma features and on colonoscopy surveillance practices. Gastroenterologists should encourage patients to comply with long-term colonoscopic surveillance.

Functional recovery after total hip/knee replacement in obese people: A systematic review.

OBJECTIVE: Several studies have investigated the influence of body mass index (BMI) on functional gain after total hip replacement (THR) or total knee replacement (TKR) in osteoarthritis, with contradictory results. This systematic literature review was conducted to ascertain whether obesity affects functional recovery after THR or TKR in the short (<1 year), medium (<3 years) and long term (>3 years). METHODS: The study was registered with PROSPERO and conducted according to the PRISMA guidelines. A systematic literature search was conducted across Medline and EMBASE databases for articles published between 1980 and 2020 that investigated patient-reported measures of functional recovery after THR and TKR in participants with osteoarthritis and obesity (defined as BMI ≥30 kg/m2). RESULTS: Twenty-six articles reporting on 68,840 persons (34,955 for THR and 33,885 for TKR) were included in the final analysis: 5 case-control studies, 21 cohort studies (9 for THR only, 10 for TKR only and 2 for both). The average minimum follow-up was 36.4 months, ranging from 6 weeks to 10 years. Most studies found significantly lower pre-operative patient-reported functional scores for participants with obesity. After THR, there was a small difference in functional recovery in favor of those without obesity in the short term (<6 months), but the difference remained below the minimal clinically important difference (MCID) threshold and disappeared in the medium and long term. After TKR, functional recovery was better for those with obesity than those without in the first year, similar until the third year, and then decreased thereafter. CONCLUSIONS: Although there is a paucity of high-quality evidence, our findings show substantial functional gains in people with obesity after total joint replacement. Functional recovery after THR or TKR does not significantly differ, or only slightly differs, between those with and without obesity, and the difference in functional gain is not clinically important. PROSPERO NUMBER: CRD42018112919.

Addition of daptomycin for the treatment of pneumococcal meningitis: protocol for the AddaMAP study.

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.

Management of renal replacement therapy among adults in French intensive care units: A bedside practice evaluation.

Background: This study aimed to investigate renal replacement therapy (RRT) practices in a representative nationwide sample of French intensive care units (ICUs). Methods: From July 1 to October 5 2021, 67 French ICUs provided data regarding their ICU and RRT implementation. We used an online questionnaire to record general data about each participating ICU, including the type of hospital, number of beds, staff ratios, and RRT implementation. Each center then prospectively recorded RRT parameters from 5 consecutive acute kidney injury (AKI) patients, namely the indication, type of dialysis catheter used, type of catheter lock used, type of RRT (continuous or intermittent), the RRT parameters initially prescribed (dose, blood flow, and duration), and the anticoagulant agent used for the circuit. Results: A total of 303 patients from 67 ICUs were analyzed. Main indications for RRT were oligo-anuria (57.4%), metabolic acidosis (52.1%), and increased plasma urea levels (47.9%). The commonest insertion site was the right internal jugular (45.2%). In 71.0% of cases, the dialysis catheter was inserted by a resident. Ultrasound guidance was used in 97.0% and isovolumic connection in 90.1%. Citrate, unfractionated heparin, and saline were used as catheter locks in 46.9%, 24.1%, and 21.1% of cases, respectively. Conclusions: Practices in French ICUs are largely compliant with current national guidelines and international literature. The findings should be interpreted in light of the limitations inherent to this type of study.

Non-beneficial admission to the intensive care unit: A nationwide survey of practices.

INTRODUCTION: In 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. METHODS: ICU 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". RESULTS: Among 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. CONCLUSION: The 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".

Anxiety in bipolar disorder: A review of publication trends.

BACKGROUND: Although anxiety is highly prevalent in people with bipolar disorders and has deleterious impact on the course of the illness, past reviews have shown that many aspects of the topic remain under-researched. This scoping review aims to provide a comprehensive overview of the literature addressing anxiety in bipolar disorder (A-BD) between 2011 and 2020, assess if the interest in the topic has increased over the period and map the publication trends. METHODS: Three databases were systematically searched, and all articles were screened at the title/abstract and full text level based on inclusion and exclusion criteria. Of these, 1099 articles were included in the study. The annual number of articles on A-BD published between 2011 and 2020 was calculated and articles addressing it as a primary topic (n = 310) were classified into 4 categories and 11 subcategories to identify gaps in the knowledge. RESULTS: The results show no clear increase in the number of annual publications during the period and much of the available literature is of a descriptive nature. Less is known about the processes underlying the comorbidity and about treatment approaches. LIMITATIONS: Given the large scope of the research question, no quality assessment of the evidence was made. Only articles in English or French were considered. CONCLUSIONS: These results highlight the need to change the focus of research efforts to better understand and address this unique set of conditions in clinical settings.

Role of the interstitium during septic shock: a key to the understanding of fluid dynamics?

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.

Team-family conflicts over end-of-life decisions in ICU: A survey of French physicians' beliefs.

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.

Influence of socio-economic status on functional recovery after ARDS caused by SARS-CoV-2: the multicentre, observational RECOVIDS study.

PURPOSE: Survivors after acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19) are at high risk of developing respiratory sequelae and functional impairment. The healthcare crisis caused by the pandemic hit socially disadvantaged populations. We aimed to evaluate the influence of socio-economic status on respiratory sequelae after COVID-19 ARDS. METHODS: We carried out a prospective multicenter study in 30 French intensive care units (ICUs), where ARDS survivors were pre-enrolled if they fulfilled the Berlin ARDS criteria. For patients receiving high flow oxygen therapy, a flow ≥ 50 l/min and an FiO2 ≥ 50% were required for enrollment. Socio-economic deprivation was defined by an EPICES (Evaluation de la Précarité et des Inégalités de santé dans les Centres d'Examens de Santé - Evaluation of Deprivation and Inequalities in Health Examination Centres) score ≥ 30.17 and patients were included if they performed the 6-month evaluation. The primary outcome was respiratory sequelae 6 months after ICU discharge, defined by at least one of the following criteria: forced vital capacity < 80% of theoretical value, diffusing capacity of the lung for carbon monoxide < 80% of theoretical value, oxygen desaturation during a 6-min walk test and fibrotic-like findings on chest computed tomography. RESULTS: Among 401 analyzable patients, 160 (40%) were socio-economically deprived and 241 (60%) non-deprived; 319 (80%) patients had respiratory sequelae 6 months after ICU discharge (81% vs 78%, deprived vs non-deprived, respectively). No significant effect of socio-economic status was identified on lung sequelae (odds ratio (OR), 1.19 [95% confidence interval (CI), 0.72-1.97]), even after adjustment for age, sex, most invasive respiratory support, obesity, most severe P/F ratio (adjusted OR, 1.02 [95% CI 0.57-1.83]). CONCLUSIONS: In COVID-19 ARDS survivors, socio-economic status had no significant influence on respiratory sequelae 6 months after ICU discharge.

Ultrasound guidance allows faster peripheral IV cannulation in children under 3 years of age with difficult venous access: a prospective randomized study.

OBJECTIVES: Ultrasound-guided peripheral venous access (USG-PIVA) presents many advantages over the reference 'blind' technique in both adults and children in emergency situations. AIM: To compare USG-PIVA with the blind technique in children <3 years undergoing general anesthesia. METHODS: After obtaining the approval of the ethics committee and informed consent from the parents, we included all children <3 years scheduled to undergo general anesthesia [surgery, magnetic resonance imaging (MRI)], who presented difficult venous access. The children were randomized into two groups: the US group (USG-PIVA) and the B group (blind). The primary endpoint was time to cannulation (from tourniquet placement to successful IV cannulation), compared between USG-PIVA group and B group by intention-to-treat analysis. Secondary outcomes were success rate at the first puncture, number of punctures, and diameter of the catheters. Cannulations requiring >15 min were considered as failures. In case of failure in group B, USG-PIVA was attempted for a further 15 min. RESULTS: Twenty children were included in each group. Groups were comparable for sex, age, and BMI. Significant differences were observed in median time to cannulation (63.5 s vs 420.5 s, USG-PIVA vs B respectively, P < 0.001); median number of punctures (1 vs 2.5, USG-PIVA vs B, P = 0.004); and success rate at first cannulation (85% vs 35%, USG-PIVA vs B, P = 0.0012). In contrast, overall success rate did not differ significantly between groups (90% vs 85%, USG-PIVA vs B, P = 0.63). CONCLUSIONS: Ultrasound-guided peripheral venous access leads to faster peripheral IV access and should therefore be recommended in children presenting with difficult venous access.