The association between intraoperative anesthesia methods used during gastric cancer surgery and long-term mortality: A retrospective observational study using a Japanese claims database.

PURPOSE: Various basic and clinical studies have investigated the association between the types of anesthetic agents and prognosis. However, the results have varied among studies and remain controversial. In the present study, we aimed to investigate whether the risk of all-cause mortality differs between inhaled or intravenous anesthetics in patients with gastric cancer undergoing gastrectomy. METHODS: Using a Japanese nationwide insurance claims database, we analyzed patients who underwent gastrectomy under general anesthesia for gastric cancer between January 2005 and September 2019. Postoperative outcomes were compared between two groups: those who received inhaled anesthetics (Sevoflurane, Isoflurane, or Desflurane) and those who received intravenous anesthetics (propofol), using a multivariable Cox proportional hazards model. The primary outcome was overall survival. RESULTS: Among 2671 eligible patients, 2105 were in the inhaled anesthetic group, and 566 were in the intravenous anesthetic group. The median (interquartile range) age was 58 (51-63) years, and 1979 (74.1%) were men. The median follow-up period was 795 days. We identified 56 (2.7%) and 16 (2.8%) deaths during the follow-up period in the inhaled and intravenous anesthetic use groups, respectively. There was no difference in postoperative overall survival between the two groups (hazard ratio, 0.97; 95% confidence interval, 0.56-1.70; P = 0.93). CONCLUSIONS: We found no significant difference in the postoperative risks of overall survival between inhaled and intravenous anesthesia in patients with gastric cancer undergoing gastrectomy.

Predictors of Catheter-Related Bladder Discomfort After Surgery: A Literature Review.

Background: Indwelling bladder catheters are routinely used in clinical practice. Patients may experience postoperative indwelling catheter-related bladder discomfort (CRBD). This study aimed to perform a literature review to identify predictors of postoperative CRBD. Methods: We searched PubMed for relevant articles published between 2000 and 2020 using the search items "CRBD", "catheter-related bladder discomfort", and "prediction". Additionally, we searched for articles that matched the research objectives from the references of the extracted articles. We included only prospective observational studies involving human participants and excluded interventional studies, observational studies that did not report sample sizes, or observational studies that did not research on predictors of CRBD. We narrowed our search to the keyword "prediction" and found five references. We selected five studies that met the objectives of the study as the target literature. Results: Using the keywords "CRBD" and "catheter-related bladder discomfort", we identified 69 published articles. The results were narrowed down by the keyword "prediction", and five studies that recruited 1,147 patients remained. The predictors of CRBD can be divided into four factors: 1) patient factors; 2) surgical factors; 3) anesthesia factors; and 4) device and insertion technique factors. Conclusion: Our study suggests that patients with predictors of CRBD should be closely monitored to reduce postoperative patient suffering, and their quality of life should be improved after anesthesia.

Bilateral vocal cords paralysis requiring urgent tracheostomy on COVID-19 patient: a case report.

BACKGROUND: SARS-CoV-2 infection has many manifestations, including otolaryngological symptoms. CASE PRESENTATION: A 60-year-old man with severe dyspnea underwent endotracheal intubation followed by 68 h of mechanical ventilation. After extubation, he left the ICU without any significant complications. Four days after the extubation, he developed dyspnea, which deteriorated the next 2 days, and stridor became evident. A fiberoptic laryngoscope revealed bilateral vocal cord edema and paralysis, which required an emergency airway. We decided to perform an awake tracheostomy under local anesthesia while considering protection for airborne infection to healthcare providers. The tracheostomy was closed when the edema and paralysis of the vocal cords were ameliorated. CONCLUSIONS: A COVID-19 patient who underwent injurious ventilation developed vocal cord paralysis and edema 6 days after extubation, leading to an emergency tracheostomy. Close attention to the upper airway of COVID-19 patients is essential since the pathophysiology of the present incident may be specific to the viral infection.

A Literature Review of Factors Related to Postoperative Sore Throat.

Postoperative sore throat can occur as a complication in patients who have undergone surgery under general anesthesia. The incidence of postoperative sore throat ranges from 12.1% to 70%, and its effects include damage to the epithelium and mucosal cells caused by airway securement, damage to the vocal cords, congestion, blood clots, and factors such as an inappropriately large tube, cuff shape, cuff pressure, and airway securement. Notably, there are individual differences in pain thresholds, and the sensation of pain is affected by mental states, such as anxiety, and varies from person to person. Therefore, we conducted a literature review using PubMed to clarify patient factors related to the development of postoperative sore throat. The extracted keywords were "postoperative sore throat," "anesthesia," and "patient factors." We found 16 articles that met our search criteria. We expanded the search period and retrieved 19 cases from 1990 to 2020. We also included references that were judged to be closely related to the list of citations of the retrieved references. The study designs included were randomized controlled trials, clinical trials, meta-analyses, reviews, and systematic reviews. The results showed that female sex, smoking, and age were the most common patient factors. However, we could not find any literature that studied the relationship between postoperative sore throat and mental states such as anxiety.

Update on the Features and Measurements of Experimental Acute Lung Injury in Animals: An Official American Thoracic Society Workshop Report.

Advancements in methods, technology, and our understanding of the pathobiology of lung injury have created the need to update the definition of experimental acute lung injury (ALI). We queried 50 participants with expertise in ALI and acute respiratory distress syndrome using a Delphi method composed of a series of electronic surveys and a virtual workshop. We propose that ALI presents as a "multidimensional entity" characterized by four "domains" that reflect the key pathophysiologic features and underlying biology of human acute respiratory distress syndrome. These domains are 1) histological evidence of tissue injury, 2) alteration of the alveolar-capillary barrier, 3) presence of an inflammatory response, and 4) physiologic dysfunction. For each domain, we present "relevant measurements," defined as those proposed by at least 30% of respondents. We propose that experimental ALI encompasses a continuum of models ranging from those focusing on gaining specific mechanistic insights to those primarily concerned with preclinical testing of novel therapeutics or interventions. We suggest that mechanistic studies may justifiably focus on a single domain of lung injury, but models must document alterations of at least three of the four domains to qualify as "experimental ALI." Finally, we propose that a time criterion defining "acute" in ALI remains relevant, but the actual time may vary based on the specific model and the aspect of injury being modeled. The continuum concept of ALI increases the flexibility and applicability of the definition to multiple models while increasing the likelihood of translating preclinical findings to critically ill patients.

The Japanese respiratory society guidelines for the management of cough and sputum (digest edition).

Cough and sputum are common complaints at outpatient visits. In this digest version, we provide a general overview of these two symptoms and discuss the management of acute (up to three weeks) and prolonged/chronic cough (longer than three weeks). Flowcharts are provided, along with a step-by-step explanation of their diagnosis and management. Most cases of acute cough are due to an infection. In chronic respiratory illness, a cough could be a symptom of a respiratory infection such as pulmonary tuberculosis, malignancy such as a pulmonary tumor, asthma, chronic obstructive pulmonary disease, chronic bronchitis, bronchiectasis, drug-induced lung injury, heart failure, nasal sinus disease, sinobronchial syndrome, eosinophilic sinusitis, cough variant asthma (CVA), atopic cough, chronic laryngeal allergy, gastroesophageal reflux (GER), and post-infectious cough. Antibiotics should not be prescribed for over-peak cough but can be considered for atypical infections. The exploration of a single/major cause is recommended for persistent/chronic cough. When sputum is present, a sputum smear/culture (general bacteria, mycobacteria), cytology, cell differentiation, chest computed tomography (CT), and sinus X-ray or CT should be performed. There are two types of rhinosinusitis. Conventional sinusitis and eosinophilic rhinosinusitis present primarily with neutrophilic inflammation and eosinophilic inflammation, respectively. The most common causes of dry cough include CVA, atopic cough/laryngeal allergy (chronic), GER, and post-infectious cough. In the last chapter, future challenges and perspectives are discussed. We hope that the clarification of the pathology of cough hypersensitivity syndrome will lead to further development of "pathology-specific non-specific therapeutic drugs" and provide benefits to patients with chronic refractory cough.

Occurrence and incidence rate of peripheral intravascular catheter-related phlebitis and complications in critically ill patients: a prospective cohort study (AMOR-VENUS study).

BACKGROUND: The lack of precise information on the epidemiology of peripheral intravascular catheter (PIVC)-related phlebitis and complications in critically ill patients results in the absence of appropriate preventive measures. Therefore, we aimed to describe the epidemiology of the use of PIVCs and the incidence/occurrence of phlebitis and complications in the intensive care unit (ICU). METHODS: This prospective multicenter cohort study was conducted in 23 ICUs in Japan. All consecutive patients aged ≥ 18 years admitted to the ICU were enrolled. PIVCs inserted prior to ICU admission and those newly inserted after ICU admission were included in the analysis. Characteristics of the ICU, patients, and PIVCs were recorded. The primary and secondary outcomes were the occurrence and incidence rate of PIVC-related phlebitis and complications (catheter-related blood stream infection [CRBSI] and catheter failure) during the ICU stay. RESULTS: We included 2741 patients and 7118 PIVCs, of which 48.2% were inserted in the ICU. PIVC-related phlebitis occurred in 7.5% (95% confidence interval [CI] 6.9-8.2%) of catheters (3.3 cases / 100 catheter-days) and 12.9% (95% CI 11.7-14.2%) of patients (6.3 cases / 100 catheter-days). Most PIVCs were removed immediately after diagnosis of phlebitis (71.9%). Grade 1 was the most common phlebitis (72.6%), while grade 4 was the least common (1.5%). The incidence rate of CRBSI was 0.8% (95% CI 0.4-1.2%). In cases of catheter failure, the proportion and incidence rate per 100 intravenous catheter-days of catheter failure were 21% (95% CI 20.0-21.9%) and 9.1 (95% CI 8.7-10.0), respectively. CONCLUSION: PIVC-related phlebitis and complications were common in critically ill patients. The results suggest the importance of preventing PIVC-related complications, even in critically ill patients. TRIAL REGISTRATION: UMIN-CTR, the Japanese clinical trial registry (registration number: UMIN000028019 , July 1, 2017).

Low hematocrit levels: a risk factor for long-term outcomes in patients requiring prolonged mechanical ventilation after cardiovascular surgery. A retrospective study.

While low-risk patients who undergo elective surgery can tolerate low hematocrit levels, the benefits of higher hematocrit levels might outweigh the risk of transfusion in high-risk patients. Therefore, this study aimed to evaluate the effects of perioperative hematocrit levels on mortality in patients requiring prolonged mechanical ventilation (PMV) after a cardiovascular surgery. This single-center retrospective cohort study was conducted on 172 patients who underwent cardiovascular surgery with cardiopulmonary bypass or off-pump coronary artery bypass grafting and required PMV for ≥72 hours in the intensive care unit (ICU) from 2008 to 2012 at the Yokohama City University Medical Center in Yokohama, Japan. Patients were classified according to hematocrit levels on ICU admission: high (≥30%) and low (<30%) groups. Of 172 patients, 86 were included to each of the low-hematocrit and high-hematocrit groups, with median hematocrit levels (first to third quartiles) of 27.4% (25.4%-28.7%) and 33.0% (31.3%-35.5%), respectively. The difference in survival rates was significant between the two groups using the log-rank test (HR 0.55, 95% CI 0.32 to 0.95, p=0.033). Cox regression analysis revealed that ≥30% increase in hematocrit levels on ICU admission was significantly associated with decreased long-term mortality (HR 0.40, 95% CI 0.20 to 0.80, p=0.0095). Lower hematocrit levels on ICU admission was a risk factor for increased long-term mortality, and higher hematocrit levels might outweigh the risk of transfusion in patients requiring PMV after a cardiovascular surgery.

Optimal duration of prone positioning in patients with acute respiratory distress syndrome: a protocol for a systematic review and meta-regression analysis.

INTRODUCTION: Several systematic reviews and meta-analyses have demonstrated that prolonged (≥16 hours) prone positioning can reduce the mortality associated with acute respiratory distress syndrome (ARDS). However, the effectiveness and optimal duration of prone positioning was not fully evaluated. To fill these gaps, we will first investigate the effectiveness of prone positioning compared with the conventional management of patients with ARDS, regarding outcomes using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Second, if statistical heterogeneity in effectiveness with regard to short-term mortality (intensive care unit death or ≤30-day mortality) is shown, we will conduct a meta-regression analysis to explore the association between duration and effectiveness, and determine the optimal duration of prone positioning. METHOD AND ANALYSIS: Relevant studies are collected using PubMed/MEDLINE, Embase, Cochrane Central Register of Controlled Trials and the WHO International Clinical Trials Platform Search Portal. Randomised controlled trials comparing prone and supine positioning in adults with ARDS will be included in the meta-analysis. Two independent investigators will screen trials obtained by search eligibility and extract data from selected studies to standardised data recording forms. For each selected trial, the risk of bias and quality of evidence will be evaluated using the GRADE system. Meta-regression analyses will be performed to identify the most important factors associated with short-term mortality, and subgroup analysis will be used to analyse the following: duration of mechanical ventilation in the prone position per day, patient severity, tidal volume and cause of ARDS. If heterogeneity or inconsistency among the studies is detected, subgroup analysis will be conducted on factors that may cause heterogeneity. ETHICS AND DISSEMINATION: This study requires no ethical approval. The results obtained from this systematic review and meta-analysis will be disseminated through international conference presentations and publication in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42017078340.

Epidemiology and patterns of tracheostomy practice in patients with acute respiratory distress syndrome in ICUs across 50 countries.

BACKGROUND: To better understand the epidemiology and patterns of tracheostomy practice for patients with acute respiratory distress syndrome (ARDS), we investigated the current usage of tracheostomy in patients with ARDS recruited into the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG-SAFE) study. METHODS: This is a secondary analysis of LUNG-SAFE, an international, multicenter, prospective cohort study of patients receiving invasive or noninvasive ventilation in 50 countries spanning 5 continents. The study was carried out over 4 weeks consecutively in the winter of 2014, and 459 ICUs participated. We evaluated the clinical characteristics, management and outcomes of patients that received tracheostomy, in the cohort of patients that developed ARDS on day 1-2 of acute hypoxemic respiratory failure, and in a subsequent propensity-matched cohort. RESULTS: Of the 2377 patients with ARDS that fulfilled the inclusion criteria, 309 (13.0%) underwent tracheostomy during their ICU stay. Patients from high-income European countries (n = 198/1263) more frequently underwent tracheostomy compared to patients from non-European high-income countries (n = 63/649) or patients from middle-income countries (n = 48/465). Only 86/309 (27.8%) underwent tracheostomy on or before day 7, while the median timing of tracheostomy was 14 (Q1-Q3, 7-21) days after onset of ARDS. In the subsample matched by propensity score, ICU and hospital stay were longer in patients with tracheostomy. While patients with tracheostomy had the highest survival probability, there was no difference in 60-day or 90-day mortality in either the patient subgroup that survived for at least 5 days in ICU, or in the propensity-matched subsample. CONCLUSIONS: Most patients that receive tracheostomy do so after the first week of critical illness. Tracheostomy may prolong patient survival but does not reduce 60-day or 90-day mortality. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02010073 . Registered on 12 December 2013.

Efficacy of continuous versus intermittent subglottic secretion drainage in preventing ventilator-associated pneumonia in patients requiring mechanical ventilation: A single-center randomized controlled trial.

OBJECTIVE: Aspiration of subglottic secretion is a widely used intervention to prevent ventilator-associated pneumonia (VAP). This study aimed to compare the efficacy of continuous and intermittent subglottic secretion drainage (SSD) in preventing VAP. METHODS: A single-center randomized controlled trial was conducted on adult postoperative patients who were expected to undergo mechanical ventilation for more than 48 hours. Primary outcome measure was incidence of VAP and secondary outcome measures were length of mechanical ventilation and intensive-care unit (ICU) stay. RESULTS: Fifty-nine patients received continuous SSD, while 60 patients received intermittent SSD. Of these 119 patients, 88 (74%) were excluded and 15 and 16 patients were allocated to receive continuous and intermittent SSD, respectively. VAP was detected in 4 (26.7%) and 7 (43.8%) patients in the continuous and intermittent groups, respectively, (p=0.320). The length of mechanical ventilation was significantly shorter (p=0.034) in the continuous group (99.5±47.1 h) than in the intermittent group (159.9±94.5 h). The length of ICU stay was also shorter (p=0.0097) in the continuous group (6.3±2.1 days) than the intermittent group (9.8±4.8 days). CONCLUSIONS: Although continuous SSD did not reduce the incidence of VAP, it reduced the length of mechanical ventilation and ICU stay when compared to intermittent SSD.

Effect of pressure-controlled inverse ratio ventilation on dead space during robot-assisted laparoscopic radical prostatectomy: A randomised crossover study of three different ventilator modes.

BACKGROUND: Pressure-controlled inverse inspiratory to expiratory ratio ventilation (PC-IRV) is thought to be beneficial for reducing the dead space volume. OBJECTIVE: To investigate the effects of PC-IRV on the components of dead space during robot-assisted laparoscopic radical prostatectomy (RLRP). DESIGN: A randomised crossover study of three different ventilator modes. SETTING: A single university hospital from September 2014 to April 2015. PATIENTS: Twenty consecutive study participants undergoing RLRP. INTERVENTIONS: Patients were ventilated sequentially with three different modes in random order for 30 min: volume control ventilation (VCV; inspiratory to expiratory ratio 0.5), pressure control ventilation (PCV; inspiratory to expiratory ratio 0.5) and PC-IRV. Inverse inspiratory to expiratory ratio was adjusted individually by observing the expiratory flow-time wave to prevent the risk of dynamic pulmonary hyperinflation. MAIN OUTCOME MEASURES: The primary outcome included physiological dead space (VDphys), airway dead space (VDaw), alveolar dead space (VDalv) and shunt dead space (VDshunt). VDphys was calculated by Enghoff's method. We also analysed respiratory dead space (VDresp) and VDaw using a novel analytical method. Then, VDalv and VDshunt were calculated by VDalv = VDresp - VDaw and VDshunt = VDphys - VDresp, respectively. RESULTS: The VDphys/expired tidal volume (VTE) ratio in PC-IRV (29.2 ±â€Š4.7%) was significantly reduced compared with that in VCV (43 ±â€Š8.5%) and in PCV (35.9 ±â€Š3.9%). The VDshunt/VTE in PC-IRV was significantly smaller than that in VCV and PCV. VDaw/VTE in PC-IRV was also significantly smaller than that in VCV but not that in PCV. There was no significant change in VDalv/VTE. CONCLUSION: PC-IRV with the inspiratory to expiratory ratio individually adjusted by the expiratory flow-time wave decreased VDphys/VTE in patients undergoing RLRP. TRIAL REGISTRATION: University Hospital Medical Information Network in Japan 000014004.

Correction to: Potentially modifiable factors contributing to outcome from acute respiratory distress syndrome: the LUNG SAFE study.

Correction to: Intensive Care Med (2016) 42:1865-1876 DOI 10.1007/s00134-016-4571-5.

Intraoperative Venovenous Extracorporeal Membrane Oxygenation During Thoracic Surgery That Requires 1-Lung Ventilation: A Case Report.

We report 3 cases of thoracic surgery that required 1-lung ventilation where venovenous extracorporeal membrane oxygenation was prophylactically used because severe hypoxemia and ventilatory failure were anticipated intraoperatively. The surgery was successfully completed in all 3 cases. However, we had to withdraw the extracorporeal membrane oxygenation support in 1 case because of uncontrollable hemorrhage. Venovenous extracorporeal membrane oxygenation is a feasible option when severe hypoxemia and/or ventilatory failure is anticipated during 1-lung ventilation.

Novel ultrasound-guided inter-semispinal plane block: a comparative pilot study in healthy volunteers.

We previously reported that a novel multifidus cervicis plane (MCP) block could anesthetize the dorsal rami of the cervical spinal nerves. While MCP sonoanatomy is easily detectable in most patients, it is sometimes difficult to recognize the MCP injection plane, especially in elderly patients. Thus, we proposed the inter-semispinal plane (ISP) block as an alternative for the MCP block. The aim of this study was to evaluate the utility of the ISP block by evaluating the area and duration of anesthesia, compared with that of the MCP block in eight healthy volunteers. Each participant underwent unilateral ultrasound-guided MCP block and ISP block. For each block, 20 ml of ropivacaine 0.2% was injected, and the area of anesthesia was determined using the pinprick test. The anesthetic area ranged from C4 to T2 (3/8; 37.5%), T3 (2/8; 25%), or T4 (3/8; 37.5%) in the MCP block, and from C4 to T1 (1/8; 12.5%), T2 (3/8; 37.5%), T3 (2/8; 25%), or T4 (1/8; 12.5%) in the ISP block. The mean (standard deviation) duration of sensory loss following MCP and ISP blocks was 329 (77) min and 349 (70) min, respectively. Thus, the ISP block may be a reliable alternative to the MCP block.

Geo-economic variations in epidemiology, patterns of care, and outcomes in patients with acute respiratory distress syndrome: insights from the LUNG SAFE prospective cohort study.

BACKGROUND: Little information is available about the geo-economic variations in demographics, management, and outcomes of patients with acute respiratory distress syndrome (ARDS). We aimed to characterise the effect of these geo-economic variations in patients enrolled in the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE). METHODS: LUNG SAFE was done during 4 consecutive weeks in winter, 2014, in a convenience sample of 459 intensive-care units in 50 countries across six continents. Inclusion criteria were admission to a participating intensive-care unit (including transfers) within the enrolment window and receipt of invasive or non-invasive ventilation. One of the trial's secondary aims was to characterise variations in the demographics, management, and outcome of patients with ARDS. We used the 2016 World Bank countries classification to define three major geo-economic groupings, namely European high-income countries (Europe-High), high-income countries in the rest of the world (rWORLD-High), and middle-income countries (Middle). We compared patient outcomes across these three groupings. LUNG SAFE is registered with ClinicalTrials.gov, number NCT02010073. FINDINGS: Of the 2813 patients enrolled in LUNG SAFE who fulfilled ARDS criteria on day 1 or 2, 1521 (54%) were recruited from Europe-High, 746 (27%) from rWORLD-High, and 546 (19%) from Middle countries. We noted significant geographical variations in demographics, risk factors for ARDS, and comorbid diseases. The proportion of patients with severe ARDS or with ratios of the partial pressure of arterial oxygen (PaO2) to the fractional concentration of oxygen in inspired air (FiO2) less than 150 was significantly lower in rWORLD-High countries than in the two other regions. Use of prone positioning and neuromuscular blockade was significantly more common in Europe-High countries than in the other two regions. Adjusted duration of invasive mechanical ventilation and length of stay in the intensive-care unit were significantly shorter in patients in rWORLD-High countries than in Europe-High or Middle countries. High gross national income per person was associated with increased survival in ARDS; hospital survival was significantly lower in Middle countries than in Europe-High or rWORLD-High countries. INTERPRETATION: Important geo-economic differences exist in the severity, clinician recognition, and management of ARDS, and in patients' outcomes. Income per person and outcomes in ARDS are independently associated. FUNDING: European Society of Intensive Care Medicine, St Michael's Hospital, University of Milan-Bicocca.

Adenovirus vector expressing keratinocyte growth factor using CAG promoter impairs pulmonary function of mice with elastase-induced emphysema.

Pulmonary emphysema impairs quality of life and increases mortality. It has previously been shown that administration of adenovirus vector expressing murine keratinocyte growth factor (KGF) before elastase instillation prevents pulmonary emphysema in mice. We therefore hypothesized that therapeutic administration of KGF would restore damage to lungs caused by elastase instillation and thus improve pulmonary function in an animal model. KGF expressing adenovirus vector, which prevented bleomycin-induced pulmonary fibrosis in a previous study, was constructed. Adenovirus vector (1.0 × 109 plaque-forming units) was administered intratracheally one week after administration of elastase into mouse lungs. One week after administration of KGF-vector, exercise tolerance testing and blood gas analysis were performed, after which the lungs were removed under deep anesthesia. KGF-positive pneumocytes were more numerous, surfactant protein secretion in the airspace greater and mean linear intercept of lungs shorter in animals that had received KGF than in control animals. Unexpectedly, however, arterial blood oxygenation was worse in the KGF group and maximum running speed, an indicator of exercise capacity, had not improved after KGF in mice with elastase-induced emphysema, indicating that KGF-expressing adenovirus vector impaired pulmonary function in these mice. Notably, vector lacking KGF-expression unit did not induce such impairment, implying that the KGF expression unit itself may cause the damage to alveolar cells. Possible involvement of the CAG promoter used for KGF expression in impairing pulmonary function is discussed.

Potentially modifiable factors contributing to outcome from acute respiratory distress syndrome: the LUNG SAFE study.

PURPOSE: To improve the outcome of the acute respiratory distress syndrome (ARDS), one needs to identify potentially modifiable factors associated with mortality. METHODS: The large observational study to understand the global impact of severe acute respiratory failure (LUNG SAFE) was an international, multicenter, prospective cohort study of patients with severe respiratory failure, conducted in the winter of 2014 in a convenience sample of 459 ICUs from 50 countries across five continents. A pre-specified secondary aim was to examine the factors associated with outcome. Analyses were restricted to patients (93.1 %) fulfilling ARDS criteria on day 1-2 who received invasive mechanical ventilation. RESULTS: 2377 patients were included in the analysis. Potentially modifiable factors associated with increased hospital mortality in multivariable analyses include lower PEEP, higher peak inspiratory, plateau, and driving pressures, and increased respiratory rate. The impact of tidal volume on outcome was unclear. Having fewer ICU beds was also associated with higher hospital mortality. Non-modifiable factors associated with worsened outcome from ARDS included older age, active neoplasm, hematologic neoplasm, and chronic liver failure. Severity of illness indices including lower pH, lower PaO2/FiO2 ratio, and higher non-pulmonary SOFA score were associated with poorer outcome. Of the 578 (24.3 %) patients with a limitation of life-sustaining therapies or measures decision, 498 (86.0 %) died in hospital. Factors associated with increased likelihood of limitation of life-sustaining therapies or measures decision included older age, immunosuppression, neoplasia, lower pH and increased non-pulmonary SOFA scores. CONCLUSIONS: Higher PEEP, lower peak, plateau, and driving pressures, and lower respiratory rate are associated with improved survival from ARDS. TRIAL REGISTRATION: ClinicalTrials.gov NCT02010073.