Inhaled Amikacin to Prevent Ventilator-Associated Pneumonia.

BACKGROUND: Whether preventive inhaled antibiotics may reduce the incidence of ventilator-associated pneumonia is unclear. METHODS: In this investigator-initiated, multicenter, double-blind, randomized, controlled, superiority trial, we assigned critically ill adults who had been undergoing invasive mechanical ventilation for at least 72 hours to receive inhaled amikacin at a dose of 20 mg per kilogram of ideal body weight once daily or to receive placebo for 3 days. The primary outcome was a first episode of ventilator-associated pneumonia during 28 days of follow-up. Safety was assessed. RESULTS: A total of 850 patients underwent randomization, and 847 were included in the analyses (417 assigned to the amikacin group and 430 to the placebo group). All three daily nebulizations were received by 337 patients (81%) in the amikacin group and 355 patients (83%) in the placebo group. At 28 days, ventilator-associated pneumonia had developed in 62 patients (15%) in the amikacin group and in 95 patients (22%) in the placebo group (difference in restricted mean survival time to ventilator-associated pneumonia, 1.5 days; 95% confidence interval [CI], 0.6 to 2.5; P = 0.004). An infection-related ventilator-associated complication occurred in 74 patients (18%) in the amikacin group and in 111 patients (26%) in the placebo group (hazard ratio, 0.66; 95% CI, 0.50 to 0.89). Trial-related serious adverse effects were seen in 7 patients (1.7%) in the amikacin group and in 4 patients (0.9%) in the placebo group. CONCLUSIONS: Among patients who had undergone mechanical ventilation for at least 3 days, a subsequent 3-day course of inhaled amikacin reduced the burden of ventilator-associated pneumonia during 28 days of follow-up. (Funded by the French Ministry of Health; AMIKINHAL ClinicalTrials.gov number, NCT03149640; EUDRA Clinical Trials number, 2016-001054-17.).

Kidney Increase Natriuresis but Not Glomerular Filtration Under Veno-venous ECMO, a Retrospective Study.

PURPOSE: Acute kidney injury is a frequent complication of acute respiratory distress syndrome (ARDS). We aim to study the evolution of kidney function in patients presenting severe ARDS and requiring veno-venous extracorporeal membrane oxygenation (VV ECMO). METHODS: We conducted a multicenter retrospective study, including adult patients requiring VV ECMO for ARDS. The primary outcome was the evolution of the serum creatinine level after VV ECMO initiation. Secondary outcomes were change in urine output, and urine biochemical parameters after VV ECMO initiation. RESULTS: One hundred and two patients were included. VV ECMO was initiated after a median of 6 days of mechanical ventilation, mainly for ARDS caused by COVID-19 (73%). Serum creatinine level did not significantly differ after VV ECMO initiation (P = .20). VV ECMO was associated with a significant increase in daily urine output (+6.6 mL/kg/day, [3.8;9.3] P < .001), even after adjustment for potential confounding factors; with an increase in natriuresis. The increase in urine output under VV ECMO was associated with a reduced risk of receiving kidney replacement therapy (OR 0.4 [0.2;0.8], P = .026). CONCLUSIONS: VV ECMO initiation in severe ARDS is associated with an increase in daily urine output and natriuresis, without change in glomerular filtration rate.

One-Year Outcomes in Patients With Acute Stroke Requiring Mechanical Ventilation.

BACKGROUND: Long-term outcomes of patients with severe stroke remain poorly documented. We aimed to characterize one-year outcomes of patients with stroke requiring mechanical ventilation in the intensive care unit (ICU). METHODS: We conducted a prospective multicenter cohort study in 33 ICUs in France (2017-2019) on patients with consecutive strokes requiring mechanical ventilation for at least 24 hours. Outcomes were collected via telephone interviews by an independent research assistant. The primary end point was poor functional outcome, defined by a modified Rankin Scale score of 4 to 6 at 1 year. Multivariable mixed models investigated variables associated with the primary end point. Secondary end points included quality of life, activities of daily living, and anxiety and depression in 1-year survivors. RESULTS: Among the 364 patients included, 244 patients (66.5% [95% CI, 61.7%-71.3%]) had a poor functional outcome, including 190 deaths (52.2%). After adjustment for non-neurological organ failure, age ≥70 years (odds ratio [OR], 2.38 [95% CI, 1.26-4.49]), Charlson comorbidity index ≥2 (OR, 2.01 [95% CI, 1.16-3.49]), a score on the Glasgow Coma Scale <8 at ICU admission (OR, 3.43 [95% CI, 1.98-5.96]), stroke subtype (intracerebral hemorrhage: OR, 2.44 [95% CI, 1.29-4.63] versus ischemic stroke: OR, 2.06 [95% CI, 1.06-4.00] versus subarachnoid hemorrhage: reference) remained independently associated with poor functional outcome. In contrast, a time between stroke diagnosis and initiation of mechanical ventilation >1 day was protective (OR, 0.56 [95% CI, 0.33-0.94]). A sensitivity analysis conducted after exclusion of patients with early decisions of withholding/withdrawal of care yielded similar results. We observed persistent physical and psychological problems at 1 year in >50% of survivors. CONCLUSIONS: In patients with severe stroke requiring mechanical ventilation, several ICU admission variables may inform caregivers, patients, and their families on post-ICU trajectories and functional outcomes. The burden of persistent sequelae at 1 year reinforces the need for a personalized, multi-disciplinary, prolonged follow-up of these patients after ICU discharge. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03335995.

High-Dose Steroids for Nonresolving Acute Respiratory Distress Syndrome in Critically Ill COVID-19 Patients Treated With Dexamethasone: A Multicenter Cohort Study.

OBJECTIVES: To determine the impact of high doses of corticosteroids (HDCT) in critically ill COVID-19 patients with nonresolving acute respiratory distress syndrome (ARDS) who had been previously treated with dexamethasone as a standard of care. DESIGN: Prospective observational cohort study. Eligible patients presented nonresolving ARDS related to severe acute respiratory syndrome coronavirus 2 infection and had received initial treatment with dexamethasone. We compared patients who had received or not HDCT during ICU stay, consisting of greater than or equal to 1 mg/kg of methylprednisolone or equivalent for treatment of nonresolving ARDS. The primary outcome was 90-day mortality. We assessed the impact of HDCT on 90-day mortality using univariable and multivariable Cox regression analysis. Further adjustment for confounding variables was performed using overlap weighting propensity score. The association between HDCT and the risk of ventilator-associated pneumonia was estimated using multivariable cause-specific Cox proportional hazard model adjusting for pre-specified confounders. SETTING: We included consecutive patients admitted in 11 ICUs of Great Paris area from September 2020 to February 2021. PATIENTS: Three hundred eighty-three patients were included (59 in the HDCT group, 324 in the no HDCT group). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: At day 90, 30 of 59 patients (51%) in the HDCT group and 116 of 324 patients (35.8%) in the no HDCT group had died. HDCT was significantly associated with 90-day mortality in unadjusted (hazard ratio [HR], 1.60; 95% CI, 1.04-2.47; p = 0.033) and adjusted analysis with overlap weighting (adjusted HR, 1.65; 95% CI, 1.03-2.63; p = 0.036). HDCT was not associated with an increased risk of ventilator-associated pneumonia (adjusted cause-specific HR, 0.42; 95% CI, 0.15-1.16; p = 0.09). CONCLUSIONS: In critically ill COVID-19 patients with nonresolving ARDS, HDCT result in a higher 90-day mortality.

Skin biopsy in adult patients with meningococcal purpura fulminans: a multicenter retrospective cohort study.

BACKGROUND: Neisseria meningitidis is the leading responsible bacterium of Purpura Fulminans (PF) accounting for two thirds of PF. Skin biopsy is a simple and minimally invasive exam allowing to perform skin culture and polymerase chain reaction (PCR) to detect Neisseria meningitidis. We aimed to assess the sensitivity of skin biopsy in adult patients with meningococcal PF. METHODS: A 17-year multicenter retrospective cohort study including adult patients admitted to the ICU for a meningococcal PF in whom a skin biopsy with conventional and/or meningococcal PCR was performed. RESULTS: Among 306 patients admitted for PF, 195 had a meningococcal PF (64%) with a skin biopsy being performed in 68 (35%) of them. Skin biopsy was performed in median 1 day after the initiation of antibiotic therapy. Standard culture of skin biopsy was performed in 61/68 (90%) patients and grew Neisseria meningitidis in 28 (46%) of them. Neisseria meningitidis PCR on skin biopsy was performed in 51/68 (75%) patients and was positive in 50 (98%) of them. Among these 50 positive meningococcal PCR, five were performed 3 days or more after initiation of antibiotic therapy. Finally, skin biopsy was considered as contributive in 60/68 (88%) patients. Identification of the meningococcal serogroup was obtained with skin biopsy in 48/68 (71%) patients. CONCLUSIONS: Skin biopsy with conventional culture and meningococcal PCR has a global sensitivity of 88% and should be systematically considered in case of suspected meningococcal PF even after the initiation of antimicrobial treatment.

Effect of Noninvasive Airway Management of Comatose Patients With Acute Poisoning: A Randomized Clinical Trial.

Importance: Tracheal intubation is recommended for coma patients and those with severe brain injury, but its use in patients with decreased levels of consciousness from acute poisoning is uncertain. Objective: To determine the effect of intubation withholding vs routine practice on clinical outcomes of comatose patients with acute poisoning and a Glasgow Coma Scale score less than 9. Design, Setting, and Participants: This was a multicenter, randomized trial conducted in 20 emergency departments and 1 intensive care unit (ICU) that included comatose patients with suspected acute poisoning and a Glasgow Coma Scale score less than 9 in France between May 16, 2021, and April 12, 2023, and followed up until May 12, 2023. Intervention: Patients were randomized to undergo conservative airway strategy of intubation withholding vs routine practice. Main Outcomes and Measures: The primary outcome was a hierarchical composite end point of in-hospital death, length of ICU stay, and length of hospital stay. Key secondary outcomes included adverse events resulting from intubation as well as pneumonia within 48 hours. Results: Among the 225 included patients (mean age, 33 years; 38% female), 116 were in the intervention group and 109 in the control group, with respective proportions of intubations of 16% and 58%. No patients died during the in-hospital stay. There was a significant clinical benefit for the primary end point in the intervention group, with a win ratio of 1.85 (95% CI, 1.33 to 2.58). In the intervention group, there was a lower proportion with any adverse event (6% vs 14.7%; absolute risk difference, 8.6% [95% CI, -16.6% to -0.7%]) compared with the control group, and pneumonia occurred in 8 (6.9%) and 16 (14.7%) patients, respectively (absolute risk difference, -7.8% [95% CI, -15.9% to 0.3%]). Conclusions and Relevance: Among comatose patients with suspected acute poisoning, a conservative strategy of withholding intubation was associated with a greater clinical benefit for the composite end point of in-hospital death, length of ICU stay, and length of hospital stay. Trial Registration: ClinicalTrials.gov Identifier: NCT04653597.

The 16S rRNA lung microbiome in mechanically ventilated patients: a methodological study.

PURPOSE: Characterization of the respiratory tract bacterial microbiome is in its infancy when compared to the gut microbiota. To limit bias mandates a robust methodology. Specific amplification of the hypervariable (V) region of the 16SrRNA gene is a crucial step. Differences in accuracy exist for one V region to another depending on the sampled environment. We aimed to assess the impact of the primer sequences targeting the V4 region currently used for gut microbiota studies in respiratory samples. Materials and methods: The original 515 F-806R primer pair targets the V4 region of the 16SrRNA gene. We compared two different 515 F-806R primer pairs before Illumina 250 paired-end sequencing for bacterial microbiome analyses of respiratory samples from critically-ill ventilated patients. "S-V4" for "Stringent V4" primer pair is used in two ongoing international projects "the Integrative Human microbiome project (iHMP)" and "the Earth microbiome project (EMP)." "R-V4" for "Relaxed V4" primer pair has been modified to reduce biases against specific environmental taxa. The optimal method was determined by concordance with conventional microbiology. Results: Twenty samples from three patients who developed a ventilator-associated pneumonia (VAP) and four who did not (control ventilated patients) were sequenced. Highly different results were obtained. "S-V4" provided the best agreement with the conventional microbiology for endotracheal aspirate: 89% as compared to 56% for "R-V4." The main difference related to poor Enterobacteriaceae detection with "R-V4" primers. Conclusions: Accuracy of the bacterial lung microbiome composition was highly dependent on the primers used for amplification of the 16 s rRNA hypervariable sequence. This work validates for future lung microbiome studies the use of the 515 F-806R "S-V4" primer pair associated to Illumina® MiSeq paired-end sequencing.

Extended prone positioning duration for COVID-19-related ARDS: benefits and detriments.

BACKGROUND: During the COVID-19 pandemic, many more patients were turned prone than before, resulting in a considerable increase in workload. Whether extending duration of prone position may be beneficial has received little attention. We report here benefits and detriments of a strategy of extended prone positioning duration for COVID-19-related acute respiratory distress syndrome (ARDS). METHODS: A eetrospective, monocentric, study was performed on intensive care unit patients with COVID-19-related ARDS who required tracheal intubation and who have been treated with at least one session of prone position of duration greater or equal to 24 h. When prone positioning sessions were initiated, patients were kept prone for a period that covered two nights. Data regarding the incidence of pressure injury and ventilation parameters were collected retrospectively on medical and nurse files of charts. The primary outcome was the occurrence of pressure injury of stage ≥ II during the ICU stay. RESULTS: For the 81 patients included, the median duration of prone positioning sessions was 39 h [interquartile range (IQR) 34-42]. The cumulated incidence of stage ≥ II pressure injuries was 26% [95% CI 17-37] and 2.5% [95% CI 0.3-8.8] for stages III/IV pressure injuries. Patients were submitted to a median of 2 sessions [IQR 1-4] and for 213 (94%) prone positioning sessions, patients were turned over to supine position during daytime, i.e., between 9 AM and 6 PM. This increased duration was associated with additional increase in oxygenation after 16 h with the PaO2/FiO2 ratio increasing from 150 mmHg [IQR 121-196] at H+ 16 to 162 mmHg [IQR 124-221] before being turned back to supine (p = 0.017). CONCLUSION: In patients with extended duration of prone position up to 39 h, cumulative incidence for stage ≥ II pressure injuries was 26%, with 25%, 2.5%, and 0% for stage II, III, and IV, respectively. Oxygenation continued to increase significantly beyond the standard 16-h duration. Our results may have significant impact on intensive care unit staffing and patients' respiratory conditions. TRIAL REGISTRATION: Institutional review board 00006477 of HUPNVS, Université Paris Cité, APHP, with the reference: CER-2021-102, obtained on October 11th 2021. Registered at Clinicaltrials (NCT05124197).

Pictograms for safer medication handling by health care workers: a validation study in nursing students in Poland.

BACKGROUND AND OBJECTIVE: Medication use often causes errors that are dangerous to the health of patients. Previous studies indicate that the use of pharmaceutical pictograms can effectively reduce medication errors. The purpose of this study was to determine the comprehensibility, representativeness, and recall rate of nine medication safety pictograms in a sample of nursing students in Poland in order to validate these images. METHODS: A pictogram validation study was conducted in two phases among nursing students at the Hipolit Cegielski State University of Applied Sciences, Gniezno, Poland. All experimental protocols were approved by the Children's Hospital of Eastern Ontario Research Ethics Board (REB Protocol No: 19/122X). All methods were carried out in accordance with relevant guidelines and regulations. In phase 1, the participants' first exposure to the pictograms, the students were asked to guess the meaning of the pictograms without any additional information in order to assess the pictograms' comprehensibility. To be considered valid, according to ISO standards, the pictograms had to be correctly understood by at least 66.7% of participants. After testing all pictograms, students were given explanations and meanings of the pictograms and asked to rate the representativeness of pictograms. To do so, participants were asked to select a number on a seven-point Likert-style scale to indicate the perceived strength of the relationship between the pictogram and its intended meaning for each pictogram. To be considered valid, a pictogram had to be rated at least five on this scale by at least 66.7% of participants. Phase 2 took place four weeks later, during which recall of the intended meaning and representativeness were assessed following the same procedure. RESULTS: A total of 66 third-year nursing students participated in both phases. In phase 1, of the nine pictograms, six met ISO requirements for comprehensibility and seven met ISO requirements for representativeness. In phase 2, all nine pictograms were correctly understood and rated at least 5 by at least 66.7% of participants. Therefore, all nine pictograms are considered valid. CONCLUSIONS: The nine medication safety pictograms can be deployed, but must be combined with training and a written hazard statement to improve comprehension.

Assessment of a massive open online course (MOOC) incorporating interactive simulation videos on residents' knowledge retention regarding mechanical ventilation.

BACKGROUND: Understanding respiratory physiology and mechanical ventilation is a challenge for healthcare workers, particularly, medical residents. A team of French-speaking experts developed an innovative MOOC incorporating interactive simulation-based videos and serious games aiming at improving knowledge and skills in mechanical ventilation. Our objective was to evaluate the long-term knowledge retention regarding key concepts presented in this MOOC. METHODS: French residents registered for the MOOC 2020's winter session were invited to participate in a two-step study. The first step consisted in evaluating students' pre-course knowledge of respiratory physiology and mechanical ventilation fusing a 20 five-item multiple choice questions test with a total score ranging from 0 to 100. For the second step, the same students answered the same test (after shuffling the questions) six months after the completion of the course. We assessed the impact of this MOOC on the students' knowledge retention by comparing pre-course and post-course scores. RESULT: Of the 102 residents who agreed to participate in the study, 80 completed the course and their mean ± SD pre-course score was 76.0 ± 8.0. Fifty-one respondents also completed the second and their post-course score was significantly higher than the baseline one (83.1 ± 7.3 vs. 77.5 ± 7.6, p < 0.001). Scores of the first and second rounds did not differ upon comparing respondents' background specialty or number of years of residency. For the vast majority of individual questions (96%), the success rate was higher at the post-course than at the pre-course assessment. CONCLUSION: An innovative MOOC incorporating simulation-based videos was effective in teaching medical residents basic mechanical ventilation knowledge and skills, especially in the field of respiratory physiology and ventilatory modes. We observed effective long-term knowledge retention with a higher score at the post-course assessment six months after the completion of the course compared with the pre-course score.

Positive effects of lumbar puncture simulation training for medical students in clinical practice.

BACKGROUND: Lumbar puncture (LP) is an invasive medical procedure that can be done by any doctor. Several simulation-based trainings have been built however the evaluations of the theoretical knowledge and the impact of the simulation-based training have never been performed in real life. The objective was to evaluate the impact of a LP training on the theoretical knowledge improvement and the performance of a LP in clinical practice. METHODS: Before and after medical students' training, theoretical knowledge and confidence level were assessed. Over a 6 months period, the impact of simulation training was evaluated by the success rate of students' first LP carried out in hospitalized patients and compared to the results of a no-training control. RESULTS: Students' theoretical knowledge and confidence level showed significant improvement after simulation training on 115 students (p < 0.0001). The evaluation in real life based on 41 students showed that the success rate of the first LP in patients was higher in the LP simulation group compared to the control group (67% vs 14%, p = 0.0025). The technical assistance was also less frequently needed in the LP simulation group (19% vs 57%, respectively, p = 0.017). The rate of students who participated in this educational study was low. DISCUSSION: Simulation-based teaching was an effective way to improve students' theoretical and practical knowledge. Whether this approach translates to other procedural skills in real clinical settings merits further study. The low participation rate in the study is due to the fact that students are not used to be included in educational studies and to the complexity of evaluation in routine clinical practice.

Oseltamivir Resistance in Severe Influenza A(H1N1)pdm09 Pneumonia and Acute Respiratory Distress Syndrome: A French Multicenter Observational Cohort Study.

In a multicenter cohort study including 22 oseltamivir-treated patients with influenza A(H1N1)pdm09 acute respiratory distress syndrome, prevalence of the H275Y substitution in the neuraminidase, responsible for highly reduced sensitivity to oseltamivir, was 23%. Patients infected with the H275Y mutant virus had higher day 28 mortality than others (80% vs 12%; P = .011).

Impact of panelists' experience on script concordance test scores of medical students.

BACKGROUND: The evaluation process of French medical students will evolve in the next few years in order to improve assessment validity. Script concordance testing (SCT) offers the possibility to assess medical knowledge alongside clinical reasoning under conditions of uncertainty. In this study, we aimed at comparing the SCT scores of a large cohort of undergraduate medical students, according to the experience level of the reference panel. METHODS: In 2019, the authors developed a 30-item SCT and sent it to experts with varying levels of experience. Data analysis included score comparisons with paired Wilcoxon rank sum tests and concordance analysis with Bland & Altman plots. RESULTS: A panel of 75 experts was divided into three groups: 31 residents, 21 non-experienced physicians (NEP) and 23 experienced physicians (EP). Among each group, random samples of N = 20, 15 and 10 were selected. A total of 985 students from nine different medical schools participated in the SCT examination. No matter the size of the panel (N = 20, 15 or 10), students' SCT scores were lower with the NEP group when compared to the resident panel (median score 67.1 vs 69.1, p < 0.0001 if N = 20; 67.2 vs 70.1, p < 0.0001 if N = 15 and 67.7 vs 68.4, p < 0.0001 if N = 10) and with EP compared to NEP (65.4 vs 67.1, p < 0.0001 if N = 20; 66.0 vs 67.2, p < 0.0001 if N = 15 and 62.5 vs 67.7, p < 0.0001 if N = 10). Bland & Altman plots showed good concordances between students' SCT scores, whatever the experience level of the expert panel. CONCLUSIONS: Even though student SCT scores differed statistically according to the expert panels, these differences were rather weak. These results open the possibility of including less-experienced experts in panels for the evaluation of medical students.

Reducing pain by using venous blood gas instead of arterial blood gas (VEINART): a multicentre randomised controlled trial.

INTRODUCTION: Venous sampling for blood gas analysis has been suggested as an alternative to arterial sampling in order to reduce pain. The main objective was to compare pain induced by venous and arterial sampling and to assess whether the type of sampling would affect clinical management or not. METHODS: We performed an open-label randomised multicentre prospective study in four French EDs during a 4-week period. Non-hypoxaemic adults, whose medical management required blood gas analysis, were randomly allocated using a computer-generated randomisation list stratified by centres with an allocation ratio of 1:1 using random blocks to one of the two arms: venous or arterial sampling. The primary outcome was the maximal pain during sampling, using the visual analogue scale. Secondary outcomes pertained to ease of sampling as rated by the nurse drawing the blood, and physician satisfaction regarding usefulness of biochemical data. RESULTS: 113 patients were included: 55 in the arterial and 58 in the venous sampling group. The mean maximal pain was 40.5 mm±24.9 mm and 22.6 mm±20.2 mm in the arterial group and the venous group, respectively, accounting for a mean difference of 17.9 mm (95% CI 9.6 to 26.3) (p<0.0001). Ease of blood sampling was greater in the venous group as compared with the arterial group (p=0.02). The usefulness of the results, evaluated by the prescriber, did not significantly differ (p=0.25). CONCLUSIONS: Venous blood gas is less painful for patients than ABG in non-hypoxaemic patients. Venous blood gas should replace ABG in this setting. TRIAL REGISTRATION NUMBER: NCT03784664.

Daily medical education for confined students during coronavirus disease 2019 pandemic: A simple videoconference solution.

The outbreak of coronavirus disease 2019 caused by severe acute respiratory syndrome coronavirus 2 infection has recently spread globally and is now a pandemic. As a result, university hospitals have had to take unprecedented measures of containment, including asking nonessential staff to stay at home. Medical students practicing in the surgical departments find themselves idle, as nonurgent surgical activity has been canceled, until further notice. Likewise, universities are closed and medical training for students is likely to suffer if teachers do not implement urgent measures to provide continuing education. Thus, we sought to set up a daily medical education procedure for surgical students confined to their homes. We report a simple and free teaching method intended to compensate for the disappearance of daily lessons performed in the surgery department using the Google Hangouts application. This video conference method can be applied to clinical as well as anatomy lessons.

Long-term Quality of Life in Adult Patients Surviving Purpura Fulminans: An Exposed-Unexposed Multicenter Cohort Study.

BACKGROUND: Long-term health-related quality of life (HR-QOL) of patients surviving the acute phase of purpura fulminans (PF) has not been evaluated. METHODS: This was a French multicenter exposed-unexposed cohort study enrolling patients admitted in 55 intensive care units (ICUs) for PF from 2010 to 2016. Adult patients surviving the acute phase of PF (exposed group) were matched 1:1 for age, sex, and Simplified Acute Physiology Score II with septic shock survivors (unexposed group). HR-QOL was assessed during a phone interview using the 36-Item Short-Form Health Survey (SF-36) questionnaire, the Hospital Anxiety and Depression (HAD) scale, the Impact of Event Scale-Revised (IES-R), and the activity of daily living (ADL) and instrumental ADL (IADL) scales. The primary outcome measure was the physical component summary (PCS) of the SF-36 questionnaire. RESULTS: Thirty-seven survivors of PF and 37 of septic shock were phone-interviewed at 55 (interquartile range [IQR], 35-83) months and 44 (IQR, 35-72) months, respectively, of ICU discharge (P = .23). The PCS of the SF-36 was not significantly different between exposed and unexposed patients (median, 47 [IQR, 36-53] vs 54 [IQR, 36-57]; P = .18). There was also no significant difference between groups regarding the mental component summary of the SF-36, and the HAD, IES-R, ADL and IADL scales. Among the 37 exposed patients, those who required limb amputation (n = 12/37 [32%]) exhibited lower PCS (34 [IQR, 24-38] vs 52 [IQR, 42-56]; P = .001) and IADL scores (7 [IQR, 4-8] vs 8 [IQR, 7-8]; P = .021) compared with nonamputated patients. CONCLUSIONS: Long-term HR-QOL does not differ between patients surviving PF and those surviving septic shock unrelated to PF. Amputated patients have an impaired physical HR-QOL but a preserved mental health. CLINICAL TRIALS REGISTRATION: NCT03216577.

Longer symptom onset to aspiration time predicts success of needle aspiration in primary spontaneous pneumothorax.

BACKGROUND: Needle aspiration (NA) is recommended as first-line treatment of primary spontaneous pneumothorax (PSP). We aimed to assess NA success and the effect of a longer symptom onset to NA time. METHODS: A discovery phase was retrospectively conducted in the intensive care unit of Louis Mourier Hospital (January 2000 to December 2011) followed by a prospective validation cohort (January 2012 to August 2015). The primary outcome was immediate NA success defined by the absence of need for chest tube insertion within 24 hours of the procedure. RESULTS: In the discovery phase, 130 patients were admitted for PSP and 98 had NA as first-line treatment (75%). The immediate success rate of NA was 34.7% and was higher when it was performed ≥48 hours after symptom onset (57.7% vs 25%; p=0.004). In the prospective cohort, 87 patients were admitted for PSP; 71 (82%) had NA as first-step treatment. The immediate success rate was 40.8%. NA was more successful when it was performed after 48 hours of symptoms' onset (34.5% vs 7.1%; p=0.005). A delay between the first symptom and NA procedure ≥48 hours was associated with a higher success of NA (OR=13.54; 95% CI 1.37 to 133). A smaller pneumothorax estimated by Light's index was associated with NA success (OR=0.95; 95% CI 0.92 to 0.98). To what extent some of these pneumothoraces would have had a spontaneous resolution remains unknown. CONCLUSION: When managing PSP with NA, a longer symptom onset to NA time was associated with NA success. TRIAL REGISTRATION NUMBER: NCT02528734.

An Oxygen-Sensing Two-Component System in the Burkholderia cepacia Complex Regulates Biofilm, Intracellular Invasion, and Pathogenicity.

Burkholderia dolosa is a member of the Burkholderia cepacia complex (BCC), which is a group of bacteria that cause chronic lung infection in patients with cystic fibrosis (CF) and can be associated with outbreaks carrying high morbidity and mortality. While investigating the genomic diversity of B. dolosa strains collected from an outbreak among CF patients, we previously identified fixL as a gene showing signs of strong positive selection. This gene has homology to fixL of the rhizobial FixL/FixJ two-component system. The goals of this study were to determine the functions of FixLJ and their role in virulence in B. dolosa. We generated a fixLJ deletion mutant and complemented controls in B. dolosa strain AU0158. Using a fixK-lacZ reporter we found that FixLJ was activated in low oxygen in multiple BCC species. In a murine pneumonia model, the B. dolosa fixLJ deletion mutant was cleared faster from the lungs and spleen than wild-type B. dolosa strain AU0158 at 7 days post infection. Interestingly, the fixLJ deletion mutant made more biofilm, albeit with altered structure, but was less motile than strain AU0158. Using RNA-seq with in vitro grown bacteria, we found ~11% of the genome was differentially expressed in the fixLJ deletion mutant relative to strain AU0158. Multiple flagella-associated genes were down-regulated in the fixLJ deletion mutant, so we also evaluated virulence of a fliC deletion mutant, which lacks a flagellum. We saw no difference in the ability of the fliC deletion mutant to persist in the murine model relative to strain AU0158, suggesting factors other than flagella caused the phenotype of decreased persistence. We found the fixLJ deletion mutant to be less invasive in human lung epithelial and macrophage-like cells. In conclusion, B. dolosa fixLJ is a global regulator that controls biofilm formation, motility, intracellular invasion/persistence, and virulence.

Pathophysiology of Escherichia coli pneumonia: Respective contribution of pathogenicity islands to virulence.

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.

Antibiotic resistance and virulence: Understanding the link and its consequences for prophylaxis and therapy.

"Antibiotic resistance is usually associated with a fitness cost" is frequently accepted as common knowledge in the field of infectious diseases. However, with the advances in high-throughput DNA sequencing that allows for a comprehensive analysis of bacterial pathogenesis at the genome scale, including antibiotic resistance genes, it appears that this paradigm might not be as solid as previously thought. Recent studies indicate that antibiotic resistance is able to enhance bacterial fitness in vivo with a concomitant increase in virulence during infections. As a consequence, strategies to minimize antibiotic resistance turn out to be not as simple as initially believed. Indeed, decreased antibiotic use may not be sufficient to let susceptible strains outcompete the resistant ones. Here, we put in perspective these findings and review alternative approaches, such as preventive and therapeutic anti-bacterial immunotherapies that have the potential to by-pass the classic antibiotics.