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Objectives: Long-term survival for patients treated with prolonged mechanical ventilation is generally poor; however, patient-level factors associated with long-term mortality are unclear. Our objective was to systematically review the biomedical literature and synthesize data for prognostic factors that predict long-term mortality in prolonged mechanical ventilation patients.Data Sources: We searched PubMed, CINAHL, and Cochrane Library from 1988 to 2015 for studies on prolonged mechanical ventilation utilizing a comprehensive strategy without language restriction.Study Selection: We included studies of adults 1) receiving mechanical ventilation for more than or equal to 14 days, 2) admitted to a ventilator weaning unit, or 3) received a tracheostomy for acute respiratory failure. We analyzed articles that used a multivariate analysis to identify patient-level factors associated with long-term mortality (≥ 6 mo from when the patient met criteria for receiving prolonged mechanical ventilation).Data Extraction: We used a standardized data collection tool and assessed study quality with a customized Newcastle-Ottawa Scale. We abstracted the strength of association between each prognostic factor and long-term mortality. Individual prognostic factors were then designated as strong, moderate, weak, or inconclusive based on an a priori previously published schema.Data Synthesis: A total of 7,411 articles underwent relevance screening; 419 underwent full article review. We identified 14 articles that contained a multivariate analysis. We abstracted 19 patient-level factors that showed association with long-term mortality. Six factors demonstrated strong strength of evidence for association with the primary outcome: age, vasopressor requirement, thrombocytopenia, preexisting kidney disease, failed ventilator liberation, and acute kidney injury ± hemodialysis requirement. All factors, except preexisting kidney disease and failed ventilator liberation, were measured at the time the patients met criteria for prolonged mechanical ventilation.Conclusions: Despite the magnitude of the public health challenge posed by the prolonged mechanical ventilation population, only 14 articles in the biomedical literature have tested patient-level factors associated with long-term mortality. Further research is needed to inform optimal patient selection for prolonged mechanical ventilation. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To examine trends in utilization and outcomes among patients with the acute respiratory distress syndrome (ARDS) requiring prolonged venovenous extracorporeal membrane oxygenation (VV ECMO) support. DESIGN: Retrospective observational cohort study. SETTING: Adult patients in the Extracorporeal Life Support Organization registry. PATIENTS: Thirteen thousand six hundred eighty-one patients that required ECMO for the support of ARDS between January 2012 and December 2022. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Mortality while supported with VV ECMO and survival to hospital discharge based on ECMO duration were examined utilizing multivariable logistic regression. Among the 13,681 patients supported with VV ECMO, 4,040 (29.5%) were supported for greater than or equal to 21 days and 975 (7.1%) for greater than or equal to 50 days. Patients supported with prolonged VV ECMO were less likely to be discharged alive from the hospital compared with those with short duration of support (46.5% vs. 59.7%; p < 0.001). However, among patients supported with VV ECMO greater than or equal to 21 days, duration of extracorporeal life support was not significantly associated with mortality (odds ratio [OR], 0.99; 95% CI, 0.98-1.01; p = 0.87 and adjusted OR, 0.99; 95% CI, 0.97-1.02; p = 0.48). Even in those supported with VV ECMO for at least 120 days (n = 113), 52 (46.0%) of these patients were ultimately discharged alive from the hospital. CONCLUSIONS: Prolonged VV ECMO support of ARDS has increased and accounts for a substantial portion of cases. Among patients that survive for greater than or equal to 21 days while receiving VV ECMO support, duration is not predictive of survival to hospital discharge and clinical recovery may occur even after very prolonged VV ECMO support. [ABSTRACT FROM AUTHOR]

Objectives: To determine the safety and efficacy of a rapidly deployed intensivist-led venovenous extracorporeal membrane oxygenation cannulation program in a preexisting extracorporeal membrane oxygenation program.Design: A retrospective observational before-and-after study of 40 patients undergoing percutaneous cannulation for venovenous extracorporeal membrane oxygenation in an established cannulation program by cardiothoracic surgeons versus a rapidly deployed medical intensivist cannulation program.Setting: An adult ICU in a tertiary academic medical center in Camden, NJ.Patients: Critically ill adult subjects with severe respiratory failure undergoing percutaneous cannulation for venovenous extracorporeal membrane oxygenation.Interventions: Percutaneous cannulation for venovenous extracorporeal membrane oxygenation performed by cardiothoracic surgeons compared with cannulations performed by medical intensivists.Measurements and Main Results: Venovenous extracorporeal membrane oxygenation cannulation site attempts were retrospectively reviewed. Subject demographics, specialty of physician performing cannulation, type of support, cannulation configuration, cannula size, imaging guidance, success rate, and complications were recorded and summarized. Twenty-two cannulations were performed by three cardiothoracic surgeons in 11 subjects between September 2019 and February 2020. The cannulation program rapidly transitioned to an intensivist-led and performed program in March 2020. Fifty-seven cannulations were performed by eight intensivists in 29 subjects between March 2020 and December 2020. Mean body mass index for subjects did not differ between groups (33.86 vs 35.89; p = 0.775). There was no difference in days on mechanical ventilation prior to cannulation, configuration, cannula size, or discharge condition. There was no difference in success rate of cannulation on first attempt per cannulation site (95.5 vs 96.7; p = 0.483) or major complication rate per cannulation site (4.5 vs 3.5; p = 1).Conclusions: There is no difference between success and complication rates of percutaneous venovenous extracorporeal membrane oxygenation canulation when performed by cardiothoracic surgeons versus medical intensivist in an already established extracorporeal membrane oxygenation program. A rapidly deployed cannulation program by intensivists for venovenous extracorporeal membrane oxygenation can be performed with high success and low complication rates. [ABSTRACT FROM AUTHOR]

The article presents the authors' comments on critical care spending and ICU beds per capita in the U.S., with specific reference to the study "ICU Occupancy and Mechanical Ventilator Use in the United States," by H. Wunsch and colleagues published in this issue of the journal. The study carried out an experiment to determine hourly bed occupancy and mechanical ventilator use in the country.

Background: Swi6 acts as a transcription factor in budding yeast, functioning in two different heterodimeric complexes, SBF and MBF, that activate the expression of distinct but overlapping sets of genes. Swi6 undergoes regulated changes in nucleocytoplasmic localization throughout the cell cycle that correlate with changes in gene expression. This study investigates how nucleocytoplasmic transport by multiple transport factors may influence specific Swi6 activities. Results: Here we show that the exportin Crm1 is important for Swi6 nuclear export and activity. Loss of a putative Crm1 NES or inhibition of Crm1 activity results in changes in nucleocytoplasmic Swi6 localization. Alteration of the Crm1 NES in Swi6 results in decreased MBF-mediated gene expression, but does not affect SBF reporter expression, suggesting that export of Swi6 by Crm1 regulates a subset of Swi6 transcription activation activity. Finally, alteration of the putative Crm1 NES in Swi6 results in cells that are larger than wild type, and this increase in cell size is exacerbated by deletion of Msn5. Conclusions: These data provide evidence that Swi6 has at least two different exportins, Crm1 and Msn5, each of which interacts with a distinct nuclear export signal. We identify a putative nuclear export signal for Crm1 within Swi6, and observe that export by Crm1 or Msn5 independently influences Swi6-regulated expression of a different subset of Swi6-controlled genes. These findings provide new insights into the complex regulation of Swi6 transcription activation activity and the role of nucleocytoplasmic shuttling in regulated gene expression. [ABSTRACT FROM AUTHOR]