Single-Donor and Pooling Strategies for Fecal Microbiota Transfer Product Preparation in Ulcerative Colitis: A Systematic Review and Meta-analysis.

INTRODUCTION: Patients with ulcerative colitis (UC) have a less diverse microbiome than healthy subjects. Multiple studies have evaluated fecal microbiota transfer (FMT) in these patients using different methods of product preparation, doses, and routes of administration. A systematic review and meta-analysis was performed to compare the efficacy of single-donor (SDN) and multidonor (MDN) strategies for product preparation. METHODS: Systematic searches were performed in Web of Science, Scopus, PubMed, and Orbit Intelligence for studies comparing FMT products manufactured using SDN or MDN strategies to placebo in patients with UC. Fourteen controlled studies were selected for meta-analysis (10 randomized and 4 nonrandomized). The treatment response was assessed by using fixed- and random-effects models, and the significance of the indirect difference between the interventions was assessed using a network approach. RESULTS: Considering all 14 studies, MDN and SDN were superior to placebo in terms of treatment response (risk ratios [RRs]: 4.41 and 1.57, respectively [P ≤ 0.001 for both]), and MDN was superior to SDN (RR: 2.81, P = 0.005). Meta-analysis of the 10 studies with high quality of evidence showed that MDN was superior to SDN in terms of treatment response (RR: 2.31, P = 0.042). Results were identical for both models. DISCUSSION: There was a significant clinical benefit (remission) for patients with UC who received FMT with products manufactured by MDN strategies. Reduction of donor effect may lead to a gain in microbial diversity that could improve response to treatment. These results may have implications in the treatment approach of other diseases amenable to microbiome manipulation.JOURNAL/cltg/04.03/01720094-202305000-00002/2FFU1/v/2023-05-23T220055Z/r/image-tiff.

Ventilation practices in burn patients-an international prospective observational cohort study.

BACKGROUND: It is unknown whether lung-protective ventilation is applied in burn patients and whether they benefit from it. This study aimed to determine ventilation practices in burn intensive care units (ICUs) and investigate the association between lung-protective ventilation and the number of ventilator-free days and alive at day 28 (VFD-28). METHODS: This is an international prospective observational cohort study including adult burn patients requiring mechanical ventilation. Low tidal volume (V T) was defined as V T ≤ 8 mL/kg predicted body weight (PBW). Levels of positive end-expiratory pressure (PEEP) and maximum airway pressures were collected. The association between V T and VFD-28 was analyzed using a competing risk model. Ventilation settings were presented for all patients, focusing on the first day of ventilation. We also compared ventilation settings between patients with and without inhalation trauma. RESULTS: A total of 160 patients from 28 ICUs in 16 countries were included. Low V T was used in 74% of patients, median V T size was 7.3 [interquartile range (IQR) 6.2-8.3] mL/kg PBW and did not differ between patients with and without inhalation trauma (p = 0.58). Median VFD-28 was 17 (IQR 0-26), without a difference between ventilation with low or high V T (p = 0.98). All patients were ventilated with PEEP levels ≥5 cmH2O; 80% of patients had maximum airway pressures <30 cmH2O. CONCLUSION: In this international cohort study we found that lung-protective ventilation is used in the majority of burn patients, irrespective of the presence of inhalation trauma. Use of low V T was not associated with a reduction in VFD-28. TRIAL REGISTRATION: Clinicaltrials.gov NCT02312869. Date of registration: 9 December 2014.

Management of severe thermal burns in the acute phase in adults and children.

OBJECTIVES: To provide recommendations to facilitate the management of severe thermal burns during the acute phase in adults and children. DESIGN: A committee of 20 experts was asked to produce recommendations in six fields of burn management, namely, (1) assessment, admission to specialised burns centres, and telemedicine; (2) haemodynamic management; (3) airway management and smoke inhalation; (4) anaesthesia and analgesia; (5) burn wound treatments; and (6) other treatments. At the start of the recommendation-formulation process, a formal conflict-of-interest policy was developed and enforced throughout the process. The entire process was conducted independently of any industry funding. The experts drew up a list of questions that were formulated according to the PICO model (Population, Intervention, Comparison, and Outcomes). Two bibliography experts per field analysed the literature published from January 2000 onwards using predefined keywords according to PRISMA recommendations. The quality of data from the selected literature was assessed using GRADE® methodology. Due to the current paucity of sufficiently powered studies regarding hard outcomes (i.e. mortality), the recommendations are based on expert opinion. RESULTS: The SFAR guidelines panel generated 24 statements regarding the management of acute burn injuries in adults and children. After two scoring rounds and one amendment, strong agreement was reached for all recommendations. CONCLUSION: Substantial agreement was reached among a large cohort of experts regarding numerous strong recommendations to optimise the management of acute burn injuries in adults and children.

[Telemedicine and initial medical regulation of severe burns]. / Télémédecine et régulation médicale initiale du brûlé grave.

The evaluation of the patient and his burned body surface is one of the fundamental prerequisites for his care on site as well as for the initiation of his care journey. New tools such as the E-burn application and telemedicine improve this assessment and remote medical assistance management by reducing the risk of under-sorting or over-sorting. Telemedicine limits inappropriate secondary inter-hospital transfers and the resulting increased mortality. It is carried out according to standards that ensure safety and confidentiality for the patient and caregivers.

[Burn: epidemiology, evaluation, organisation of care]. / Brûlures : épidémiologie, évaluation, offre de soins.

Burn: epidemiology, evaluation, organisation of care. Burn is a trauma regarding 9 000 inpatients a year in France. One third of them are infants (less than 5 years). Burn occurs seasonally and on basis of an emergency admittance. For the non-specialist, the main goal is to estimate burn area the most accurately possible (new technologies can help) and recognize signs of seriousness in order to guide the patient at best. Despite a strict and rigorous organization of burn care promoted by French healthcare regulatory authorities, more than 50% of inpatient is admitted outside burn centers (ie non specialized units).

Brûlures : épidémiologie, évaluation, offre de soins. La brûlure est un traumatisme qui concerne chaque année 9 000 hospitalisés, dont un tiers d'entre eux sont des enfants (âgés de moins de 5 ans pour la plupart), avec une saisonnalité marquée. Ces patients nécessitent une prise en charge d'urgence. Faire une évaluation rigoureuse de la surface brûlée et savoir reconnaître les signes de gravité éventuels sont indispensables à une prise en charge adaptée. Les nouvelles technologies offrent une aide précieuse à la prise en charge et permettent de joindre un professionnel de la brûlure capable de donner un avis spécialisé. En dépit d'une organisation imposée par l'État, plus de 50 % de ces patients sont encore traités en dehors des filières spécialisées.

Establishment of indicators to improve clinical analysis prescribing patterns.

An appropriate medical analysis prescribing pattern is part of the medical biologists' work as it enhances patient care and reduces costs. In this study, we use four indicators to aim to evaluate the relevance of clinical analysis prescription. We confronted clinical data and medical analysis prescribed in June 2013 in the emergency department (ED) and found that prescriptions were justified in 73% of TnT prescriptions but only in less than 50% of NTproBNP (27%), APTT (37%), PR (33%) or INR (23%) prescriptions. We noted that staff training, an improved communication between biologists and clinical physicians, and better computing devices, have led to better prescribing patterns. From 2013 to 2015, inappropriate associations of PR and APTT have significantly declined in the intensive care unit. At the same period, amounts of medical analysis as well as department spendings decreased in the ED. The use of indicators is essential to evaluate and monitor the relevance of medical analysis patterns. In this work, we propose to combine a global indicator (cost/day of hospitalization or medical analysis amount/month) with a regular follow up on inadequate prescribed analysis associations. These indicators will need to be adjusted to each clinical department.

Feasibility of monomodal analgesia with IV alfentanil during burn dressing changes at bedside (in spontaneously breathing non-intubated patients).

INTRODUCTION: The severe pain related to repeated burn dressing changes at bedside is often difficult to manage. However these dressings can be performed at bedside on spontaneously breathing non-intubated patients using powerful intravenous opioids with a quick onset and a short duration of action such as alfentanil. The purpose of this study is to demonstrate the efficacy and safety of the protocol which is used in our burn unit for pain control during burn dressing changes. PATIENTS AND METHODS: Cohort study began after favorable opinion from local ethic committee has been collected. Patient's informed consent was collected. No fasting was required. Vital signs for patients were continuously monitored (non-invasive blood pressure, ECG monitoring, cutaneous oxygen saturation, respiratory rate) all over the process. Boluses of 500 (±250) mcg IV alfentanil were administered. A continuous infusion was added in case of insufficient analgesia. Adverse reactions were collected and pain intensity was measured throughout the dressing using a ten step verbal rating scale (VRS) ranging from 0 (no pain) to 10 (worst pain conceivable). RESULTS: 100 dressings (35 patients) were analyzed. Median age was 45 years and median burned area 10%. We observed 3 blood pressure drops, 5 oxygen desaturations (treated with stimulation without the necessity of ventilatory support) and one episode of nausea. Most of the patients (87%) were totally conscious during the dressing and 13% were awakened by verbal stimulation. Median total dose of alfentanil used was 2000µg for a median duration of 35min. Pain scores during the procedure were low or moderate (VRS mean=2.0 and maximal VRS=5). Median satisfaction collected 2h after the dressing was 10 on a ten step scale. CONCLUSION: Pain control with intravenous alfentanil alone is efficient and appears safe for most burn bedside repeated dressings in hospitalized patients. It achieves satisfactory analgesia during and after the procedure. It is now our standard analgesic method to provide repeated bedside dressings changes for burned patients.

Innate danger signals in acute injury: From bench to bedside.

The description of the systemic inflammatory response syndrome (SIRS) as a reaction to numerous insults marked a turning point in the understanding of acute critical states, which are intensive care basic cases. This concept highlighted the final inflammatory response features whichever the injury mechanism is: infectious, or non-infectious such as extensive burns, traumas, major surgery or acute pancreatitis. In these cases of severe non-infectious insult, many endogenous mediators are released. Like infectious agents components, they can activate the immune system (via common signaling pathways) and initiate an inflammatory response. They are danger signals or alarmins. These molecules generally play an intracellular physiological role and acquire new functions when released in extracellular space. Many progresses brought new information on these molecules and on their function in infectious and non-infectious inflammation. These danger signals can be used as biomarkers and provide new pathophysiological and therapeutic approaches, particularly for immune dysfunctions occurring after an acute injury. We present herein the danger model, the main danger signals and the clinical consequences.

S100A8/A9 mRNA induction in an ex vivo model of endotoxin tolerance: roles of IL-10 and IFNγ.

OBJECTIVES: Septic syndromes are the leading cause of death in intensive care units. They are characterized by the development of immune dysfunctions such as endotoxin tolerance (ET), whose intensity and duration are associated with increased risk of nosocomial infections and mortality. Alarmins S100A8 and S100A9 have been shown to be increased after septic shock. Importantly, a delayed S100A9 mRNA increase predicts hospital-acquired infection in patients. The aim of this study was to investigate the regulation of S100A8 and S100A9 mRNA expression in an ex vivo model of ET. SUBJECTS AND MEASUREMENTS: ET was reproduced ex vivo by priming healthy peripheral blood mononuclear cells (number of donors  = 9 to 10) with low-dose endotoxin (2 ng/ml) before stimulation with high dose endotoxin (100 ng/ml). S100A8 and S100A9 mRNA levels were measured by quantitative real-time polymerase chain reactions. MAIN RESULTS: ET was established by observing decreased TNFα and increased IL-10 transcriptomic responses to two subsequent endotoxin challenges. Interestingly, ET was associated with increased S100A8 and S100A9 mRNA expression ex vivo. We showed that IL-10 played a role in this process, since S100A8 and S100A9 mRNA increases were significantly abrogated by IL-10 blockade in the model. Conversely, treatment with rIFN-γ, a pro-inflammatory and immunostimulating molecule known to block ET induction, was able to restore normal S100A8 and S100A9 mRNA in this model. CONCLUSIONS: In this ex vivo model, we observed that S100A8 and S100A9 mRNA expression was significantly increased during ET. This reproduced ex vivo the observations we had previously made in septic shock patients. Interestingly, IL-10 blockade and rIFN-γ treatment partially abrogated S100A8/A9 mRNA increases in this model. Pending confirmation in larger, independent clinical studies, these preliminary results suggest that S100A8 and S100A9 mRNA levels might be used as surrogate markers of ET and as stratification tools for personalized immunotherapy in septic shock patients.

Working time and workload of nurses: the experience of a burn center in a high income country.

We conducted a one-month study of the working time and workload of nurses in a 15 beds burn center (including 8 intensive care beds). Nurses' tasks were categorized according to their nature (medical care, local treatments, post anesthetic monitoring, administrative time related to health care, administrative time unrelated to health care, cleaning, rest). The time taken to complete a given task was measured for each task. The time devoted to walk and unavailable for patients care was also measured. Our study revealed that work distribution was far from optimal since administrative tasks occupy more than 30% of workload. This represents inefficiency and the literature shows that when time is saved from administrative work it is reinvested in health care. One third of the administrative tasks are unrelated to care and thus could be performed by non-specialized clerks. The other two third of the administrative workload are closely linked to care. An answer to reduce administrative time lost to care activities is the implementation of dedicated ICU software which carries several other advantages such as reducing the use of paper, improving the safety of prescriptions, automating repetitive and unrewarding tasks and saving physician time. This expensive solution can be quickly repaid through costs containment due to the time saved. A significant part of the working time is spent walking but reducing the ambulatory time may be considered only through structural improvements.

Delayed increase of S100A9 messenger RNA predicts hospital-acquired infection after septic shock.

OBJECTIVE: Septic shock remains a serious disease with high mortality and increased risk of hospital-acquired infection. The prediction of outcome is of the utmost importance for selecting patients for therapeutic strategies aiming to modify the immune response. The aim of this study was to assess the capability of S100A9 messenger RNA in whole blood from patients with septic shock to predict survival and the occurrence of hospital-acquired infection. DESIGN: Cohort study. SETTING: Two intensive care units in a university hospital. SUBJECTS: The study included patients with septic shock (n = 166) and healthy volunteers (n = 44). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: For the patients with septic shock patients, overall mortality was 38% and the mean Simplified Acute Physiologic Scale II on shock onset was 52. Using quantitative reverse transcriptase-polymerase chain reactions, we found that median S100A9 messenger RNA was significantly lower in healthy volunteers than in patients with septic shock (p < .0001) between days 1 and 3 after onset of the septic shock and not significantly different between nonsurvivor and survivor patients (p = .1278). However, median S100A9 messenger RNA measured on days 7-10 was significantly higher in patients who were about to contract hospital-acquired infections compared with those who were not (p = .009). In the multivariate analysis, the S100A9 marker increased the probability of contracting hospital-acquired infections with an odds ratio of 1.12 per unit (p = .0054). CONCLUSIONS: S100A9 messenger RNA is increased in septic shock and its delayed overexpression is associated with the occurrence of secondary hospital-acquired infection. This biomarker may be of major interest in identifying patients with increased risk of hospital-acquired infection who could benefit from targeted therapy aimed at restoring their immune functions.