Ventilator-associated pneumonia (VAP) remains the most frequent life-threatening nosocomial infection. Enterobacteriaceae including Escherichia coli are increasingly involved. If a cumulative effect ...of pathogenicity islands (PAIs) has been shown for E. coli virulence in urinary tract or systemic infections, very little is known regarding pathophysiology of E. coli pneumonia. This study aimed to determine the role of each of the 7 PAIs present in pathogenic E. coli strain 536 in pneumonia pathophysiology.
We used mutant strains to screen pathophysiological role of PAI in a rat pneumonia model. We also test individual gene mutants within PAI identified to be involved in pneumonia pathogenesis. Finally, we determined the prevalence of these genes of interest in E. coli isolates from feces and airways of ventilated patients.
Only PAIs I and III were significantly associated with rat pneumonia pathogenicity. Only the antigen-43 (Ag43) gene in PAI III was significantly associated with bacterial pathogenicity. The prevalence of tested genes in fecal and airway isolates of ventilated patients did not differ between isolates. In contrast, genes encoding Ag43, the F17-fimbriae subunits, HmuR and SepA were more prevalent in VAP isolates with statistical significance for hmuR when compared to airway colonizing isolates.
The E. coli PAIs involved in lung pathogenicity differed from those involved in urinary tract and bloodstream infections. Overall, extraintestinal E. coli virulence seems to rely on a combination of numerous virulence genes that have a cumulative effect depending on the infection site.
Background
The extent of the consequences of an episode of severe acute kidney injury (AKI) on long-term outcome of critically ill patients remain debated. We conducted a prospective follow-up of ...patients included in a large multicenter clinical trial of renal replacement therapy (RRT) initiation strategy during severe AKI (the Artificial Kidney Initiation in Kidney Injury, AKIKI) to investigate long-term survival, renal outcome and health related quality of life (HRQOL). We also assessed the influence of RRT initiation strategy on these outcomes.
Results
Follow-up of patients extended from 60 days to a median of 3.35 years interquartile range (IQR), 1.89 to 4.09 after the end of initial study. Of the 619 patients included in the AKIKI trial, 316 survived after 60 days. The overall survival rate at 3 years from inclusion was 39.4% (95% CI 35.4 to 43.4). A total of 46 patients (on the 175 with available data on long-term kidney function) experienced worsening of renal function (WRF) at the time of follow-up overall incidence of 26%, cumulative incidence at 4 years: 20.6% (CI 95% 13.0 to 28.3). Fifteen patients required chronic dialysis (5% of patients who survived after day 90). Among the 226 long-term survivors, 80 (35%) answered the EQ-5D questionnaire. The median index value reported was 0.67 (IQR 0.40 to 1.00) indicating a noticeable alteration of quality of life. Initiation strategy for RRT had no effect on any long-term outcome.
Conclusion
Severe AKI in critically ill patients was associated with a high proportion of death within the first 2 months but less so during long-term follow-up. A quarter of long-term survivors experienced a WRF and suffered from a noticeable impairment of quality of life. Renal replacement therapy initiation strategy was not associated with mortality outcome.
Graphical Abstract
Background
The efficacy of high flow nasal canula oxygen therapy (HFNO) to prevent invasive mechanical ventilation (IMV) is not well established in severe coronavirus disease 2019 (COVID-19). The aim ...of this study was to compare the risk of IMV between two strategies of oxygenation (conventional oxygenation and HFNO) in critically ill COVID 19 patients.
Methods
This was a bicenter retrospective study which took place in two intensive care units (ICU) of tertiary hospitals in the Paris region from March 11, to May 3, 2020. We enrolled consecutive patients hospitalized for COVID-19 and acute respiratory failure (ARF) who did not receive IMV at ICU admission. The primary outcome was the rate of IMV after ICU admission. Secondary outcomes were death at day 28 and day 60, length of ICU stay and ventilator-free days at day 28
.
Data from the HFNO group were compared with those from the standard oxygen therapy (SOT) group using weighted propensity score.
Results
Among 138 patients who met the inclusion criteria, 62 (45%) were treated with SOT alone, and 76 (55%) with HFNO. In HFNO group, 39/76 (51%) patients received IMV and 46/62 (74%) in SOT group (OR 0.37 95% CI, 0.18–0.76
p
= 0.007). After weighted propensity score, HFNO was still associated with a lower rate of IMV (OR 0.31 95% CI, 0.14–0.66
p
= 0.002). Length of ICU stay and mortality at day 28 and day 60 did not significantly differ between HFNO and SOT groups after weighted propensity score. Ventilator-free days at days 28 was higher in HNFO group (21 days vs 10 days,
p
= 0.005). In the HFNO group, predictive factors associated with IMV were SAPS2 score (OR 1.13 95%CI, 1.06–1.20
p
= 0.0002) and ROX index > 4.88 (OR 0.23 95%CI, 0.008–0.64
p
= 0.006).
Conclusions
High flow nasal canula oxygen for ARF due to COVID-19 is associated with a lower rate of invasive mechanical ventilation.
The current terrorist threat challenges nations to train numerous non-trauma care providers with different backgrounds in damage control (DC) strategies. The purpose of this work was to propose a ...specific DC training program.
A Task Force of 16 civilian and military physicians met for a 24-hour session, to propose the construction of a DC training program for non-specialised caregivers.
Existing DC training programs are heterogeneous, mainly theoretical and almost only for physicians. A program entitled Damage Control for Terrorist Attack Victims (DC-TAV) was then proposed. Identified training targets were care providers from prehospital and hospital staffs, with no experience in trauma care. The training objectives were the improvement of individual and collective skills in managing terrorist attacks casualties. The tools selected for training concerned e-learning on a dedicated digital teaching platform (including a core section of four modules with types and mechanisms of injury, basic DC techniques, triage, organisation of emergency medical response and two complementary modules for doctors with DC resuscitation including remote transfusion and DC surgery), hands-on workshops with procedural simulation and full-scale simulation exercises, technical (tourniquets, haemostatic gauzes, needle thoracostomy, chest tube drainage, management of airway, coniotomy) and non-technical (leadership, communication, coordination and triage, decision-making, appropriate use of resources) skills. Finally, an evaluation of the DC-TAV program was planned.
The DC-TAV program is an ambitious, civilian-military, nationwide and long-term program, based on a harmonised standard of care and including multidimensional training. Further studies are required to assess its efficacy.
•Patient-important outcomes reflect how a patient feels, functions or survives.•At least one of those is assessed in half of 2019 studies on lung transplantation.•Mortality was the main ...patient-important outcome assessed, while non-mortality outcomes were insufficiently considered.•A core outcome set in lung transplantation should be developed with patients’ input.
Patient-important outcomes (PIOs) have emerged in respiratory medicine, in order to place the patient at the center of research. Mortality is a debated PIO in lung transplantation (LTx). The use of PIO in this specific setting has never been studied. We aimed to systematically review the use of PIOs in LTx research.
MEDLINE, Cochrane Library and Embase databases were searched to include prospective studies published in 2019, involving adult LTx recipients. We excluded articles reporting non-prognostic studies, letters, reviews, commentaries, or case reports. PIOs considered were mortality, pain, physical function, pulmonary, gastrointestinal, neuropsychological, cardiac, sleep or sexual symptoms and quality of life. This systematic review was prospectively registered in the PROSPERO register (CRD42020163425).
Among 1048 references retrieved, 51 were finally included in the analysis. In total, 26 (51%) studies investigated at least one PIO, as a primary outcome in 12 (23.5%) and secondary outcome in 21 (41.2%). In 15 (29.4%) studies, mortality was the most frequently reported PIO; 11 (21.5%) studies evaluated at least one PIO other than mortality, quality of life being this PIO in 6.
PIOs were described in half of prospective articles dealing with adult LTx recipients published in 2019. Outcomes other than mortality were insufficiently considered. A core outcome set of PIOs in LTx should be developed with patient input to guide future research in LTx.
Acute kidney injury is common in critically ill patients, many of whom receive renal-replacement therapy. However, the most effective timing for the initiation of such therapy remains uncertain.
We ...conducted a multinational, randomized, controlled trial involving critically ill patients with severe acute kidney injury. Patients were randomly assigned to receive an accelerated strategy of renal-replacement therapy (in which therapy was initiated within 12 hours after the patient had met eligibility criteria) or a standard strategy (in which renal-replacement therapy was discouraged unless conventional indications developed or acute kidney injury persisted for >72 hours). The primary outcome was death from any cause at 90 days.
Of the 3019 patients who had undergone randomization, 2927 (97.0%) were included in the modified intention-to-treat analysis (1465 in the accelerated-strategy group and 1462 in the standard-strategy group). Of these patients, renal-replacement therapy was performed in 1418 (96.8%) in the accelerated-strategy group and in 903 (61.8%) in the standard-strategy group. At 90 days, death had occurred in 643 patients (43.9%) in the accelerated-strategy group and in 639 (43.7%) in the standard-strategy group (relative risk, 1.00; 95% confidence interval CI, 0.93 to 1.09; P = 0.92). Among survivors at 90 days, continued dependence on renal-replacement therapy was confirmed in 85 of 814 patients (10.4%) in the accelerated-strategy group and in 49 of 815 patients (6.0%) in the standard-strategy group (relative risk, 1.74; 95% CI, 1.24 to 2.43). Adverse events occurred in 346 of 1503 patients (23.0%) in the accelerated-strategy group and in 245 of 1489 patients (16.5%) in the standard-strategy group (P<0.001).
Among critically ill patients with acute kidney injury, an accelerated renal-replacement strategy was not associated with a lower risk of death at 90 days than a standard strategy. (Funded by the Canadian Institutes of Health Research and others; STARRT-AKI ClinicalTrials.gov number, NCT02568722.).
In the context of increasing microbial resistance and limited new antimicrobials, we aimed to study the antimicrobial effects of cranberry proanthocyanidin extracts on Escherichia coli growth, ...adhesion to epithelial cells, and lung infection.
Experimental in vitro and in vivo investigation.
University research laboratory.
Seventy-eight 6- to 8-week-old male Balb/C mice.
In vitro, the effect of increasing concentrations of cranberry proanthocyanidin on bacterial growth of different clinical E. coli isolates was evaluated. Ex vivo, adhesion of E. coli to fresh human buccal epithelial cells was measured in the presence or absence of cranberry proanthocyanidin using microscopy. In vivo, lung bacterial count, pulmonary immune response (neutrophil murine chemokine keratinocyte-derived cytokine measurement and polymorphonuclear recruitment in bronchoalveolar lavage fluid), and lethality were evaluated in a pneumonia mouse model with E. coli precultured with or without cranberry proanthocyanidin. E. coli isolates originated from ventilated ICU patients with respiratory tract colonization or ventilator- associated pneumonia. They differed in number of virulence genes.
A significant inhibition of bacterial growth was observed with increasing concentration of cranberry proanthocyanidin, affecting both time to maximal growth and maximal growth rate (p<0.0001 for both). The minimal concentration at which this effect occurred was 250 μg/mL. Cranberry proanthocyanidin significantly reduced E. coli adhesion to fresh buccal epithelial cells by up to 80% (p<0.001). Bacterial counts in homogenized lungs and bronchoalveolar lavage fluid were decreased after cranberry proanthocyanidin exposition (p<0.05 and p<0.01, respectively). Cranberry proanthocyanidin also decreased KC concentrations and polymorphonuclear cell recruitment in bronchoalveolar lavage fluid (p<0.05 for both). At identical inoculum, mortality was reduced by more than half in mice inoculated with E. coli exposed to cranberry proanthocyanidin (p<0.01).
Cranberry proanthocyanidins exhibit potent effects on growth, adhesion, and virulence of oropharyngeal and lung isolates of E. coli, suggesting that cranberry proanthocyanidin could be of clinical interest to reduce oropharyngeal colonization and prevent lung infection.
Different phenotypes have been identified in acute respiratory distress syndrome (ARDS). Existence of several phenotypes in coronavirus disease (COVID-19) related acute respiratory distress syndrome ...is unknown. We sought to identify different phenotypes of patients with moderate to severe ARDS related to COVID-19.
We conducted an observational study of 416 COVID-19 patients with moderate to severe ARDS at 21 intensive care units in Belgium and France. The primary outcome was day-28 ventilatory free days. Secondary outcomes were mortality on day 28, acute kidney injury, acute cardiac injury, pulmonary embolism, and deep venous thrombosis. Multiple factor analysis and hierarchical classification on principal components were performed to distinguish different clinical phenotypes.
We identified three different phenotypes in 150, 176, and 90 patients, respectively. Phenotype 3 was characterized by short evolution, severe hypoxemia, and old comorbid patients. Phenotype 1 was mainly characterized by the absence of comorbidities, relatively high compliance, and long duration of symptoms, whereas phenotype 2 was characterized female sex, and the presence of mild comorbidities such as uncomplicated diabetes or chronic hypertension. The compliance in phenotype 2 was lower than that in phenotype 1, with higher plateau and driving pressure. Phenotype 3 was associated with higher mortality compared to phenotypes 1 and 2.
In COVID-19 patients with moderate to severe ARDS, we identified three clinical phenotypes. One of these included older people with comorbidities who had a fulminant course of disease with poor prognosis. Requirement of different treatments and ventilatory strategies for each phenotype needs further investigation.
France has recently witnessed a nationwide outbreak of measles. Data on severe forms of measles in adults are lacking. We sought to describe the epidemiologic, clinical, treatment, and prognostic ...aspects of the disease in adult patients who required admission to an intensive care unit (ICU). We performed a retrospective analysis of a cohort of 36 adults admitted to a total of 64 ICUs throughout France for complications of measles from January 1, 2009, to December 31, 2011. All cases of measles were confirmed by serologic testing and/or reverse transcription polymerase chain reaction.The cohort consisted of 21 male and 15 female patients, with a median age of 29.2 years (25th-75th interquartile range IQR, 27.2-34.2 yr) and a median Simplified Acute Physiology Score (SAPS II) of 13 (IQR, 9-18). Among the 26 patients whose measles vaccination status was documented, none had received 2 injections. One patient had developed measles during childhood. Underlying comorbid conditions included chronic respiratory disease in 9 patients, immunosuppression in 7 patients, and obesity in 3 patients, while measles affected 5 pregnant women.Respiratory complications induced by measles infection led to ICU admission in 32 cases, and measles-related neurologic complications led to ICU admission in 2 cases. Two patients were admitted due to concurrent respiratory and neurologic complications.Bacterial superinfection of measles-related airway infection was suspected in 28 patients and was documented in 8. Four cases of community-acquired pneumonia, 6 cases of ventilator-associated pneumonia, 1 case of tracheobronchitis, and 2 cases of sinusitis were microbiologically substantiated.Of 11 patients who required mechanical ventilation, 9 developed acute respiratory distress syndrome (ARDS). Among the patients with ARDS, extraalveolar air leak complications occurred in 4 cases. Five patients died, all of whom were severely immunocompromised.On follow-up, 1 patient had severe chronic respiratory failure related to lung fibrosis, and 2 patients had mild lower limb paraparesis along with bladder dysfunction, both of which were ascribable to measles-induced encephalitis and myelitis. Among the 5 pregnant patients, the course of measles infection was uneventful, albeit 1 patient underwent emergent cesarean delivery because of fetal growth restriction.Measles is a disease with protean and potentially deceptive clinical manifestations, especially in the immunocompromised patient. Measles-associated pneumonitis and its complications, and less commonly postinfectious encephalomyelitis, are the main source of morbidity and mortality. In contrast with the usually benign course of the disease in immunocompetent patients, measles occurring in immunocompromised patients gives rise to lethal complications including ARDS, with or without bacterial superinfection. Other patients potentially at high risk for severe measles are young adults and pregnant women. Measles pneumonitis may predispose to air leak disease in patients using mechanical ventilation. To date, vaccination remains the most potent tool to control measles infection.
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