Validation of cell-cycle arrest biomarkers for acute kidney injury using clinical adjudication.

RATIONALE: We recently reported two novel biomarkers for acute kidney injury (AKI), tissue inhibitor of metalloproteinases (TIMP)-2 and insulin-like growth factor binding protein 7 (IGFBP7), both related to G1 cell cycle arrest. OBJECTIVES: We now validate a clinical test for urinary [TIMP-2]·[IGFBP7] at a high-sensitivity cutoff greater than 0.3 for AKI risk stratification in a diverse population of critically ill patients. METHODS: We conducted a prospective multicenter study of 420 critically ill patients. The primary analysis was the ability of urinary [TIMP-2]·[IGFBP7] to predict moderate to severe AKI within 12 hours. AKI was adjudicated by a committee of three independent expert nephrologists who were masked to the results of the test. MEASUREMENTS AND MAIN RESULTS: Urinary TIMP-2 and IGFBP7 were measured using a clinical immunoassay platform. The primary endpoint was reached in 17% of patients. For a single urinary [TIMP-2]·[IGFBP7] test, sensitivity at the prespecified high-sensitivity cutoff of 0.3 (ng/ml)(2)/1,000 was 92% (95% confidence interval [CI], 85-98%) with a negative likelihood ratio of 0.18 (95% CI, 0.06-0.33). Critically ill patients with urinary [TIMP-2]·[IGFBP7] greater than 0.3 had seven times the risk for AKI (95% CI, 4-22) compared with critically ill patients with a test result below 0.3. In a multivariate model including clinical information, urinary [TIMP-2]·[IGFBP7] remained statistically significant and a strong predictor of AKI (area under the curve, 0.70, 95% CI, 0.63-0.76 for clinical variables alone, vs. area under the curve, 0.86, 95% CI, 0.80-0.90 for clinical variables plus [TIMP-2]·[IGFBP7]). CONCLUSIONS: Urinary [TIMP-2]·[IGFBP7] greater than 0.3 (ng/ml)(2)/1,000 identifies patients at risk for imminent AKI. Clinical trial registered with www.clinicaltrials.gov (NCT 01573962).

Extravascular lung water predicts progression to acute lung injury in patients with increased risk*.

OBJECTIVES: To compare the extravascular lung water index and other markers of disease severity in patients with acute lung injury vs. patients at risk for development of acute lung injury and to determine their ability to predict progression to acute lung injury in patients at risk. DESIGN: Extravascular lung water index, dead space fraction, PaO2/FIO2, and other markers of disease severity were measured prospectively in 29 patients daily for 5 days after admission to the intensive care unit. Patients had acute lung injury as defined by the American European Consensus Committee criteria or had risk factors for development of it. SETTING: The intensive care units of an academic tertiary referral hospital. MEASUREMENTS AND MAIN RESULTS: The mean extravascular lung water index on day 1 for patients who progressed to acute lung injury was higher than for those who did not (15.5 ± 7.4 mL/kg vs. 8.7 ± 2.3 mL/kg; p = .04). None of the other physiologic parameters tested discriminated progression to acute lung injury to include the mean physiologic dead space (0.61 ± 0.06] vs. 0.59 ± 0.10; p = .67), PaO2/FIO2 ratio (322 ± 35 vs. 267 ± 98; p = .15), and static lung compliance (30.9 ± 13.5 vs. 38.5 ± 11.7; p = .24). An extravascular lung water index cutoff value on day 1 of 10 mL/kg had a 63% sensitivity, 88% specificity, positive predictive value of 83%, and negative predictive value of 70% to predict progression to acute lung injury. There was no difference in extravascular lung water index between those who progressed to acute lung injury vs. those who had acute lung injury (14.3 ± 4.7 vs. 15.5 ± 7.4; p = .97). CONCLUSIONS: Elevated extravascular lung water index is a feature of early acute lung injury and discriminates between those with acute lung injury and those without. Furthermore, extravascular lung water index predicts progression to acute lung injury in patients with risk factors for development of acute lung injury 2.6 ± 0.3 days before the patients meet American European Consensus Committee criteria for it. These 2.6 ± 0.3 days may then represent missed opportunity for therapeutic intervention and improved outcome.

Rapid Deployment of Multiple Tactics to Address Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine Uptake in Healthcare Employees With a Focus on Those Who Identify as Black, Indigenous, and People of Color.

BACKGROUND: In the third quarter of 2021, government entities enacted vaccine requirements across multiple employment sectors, including healthcare. Experience from previous vaccination campaigns within healthcare emphasize the need to translate community modalities of vaccine outreach and education that partner with Black communities, Indigenous communities, and communities of Color stakeholders to increase vaccine confidence broadly. METHODS: This was an observational feasibility study conducted from August through October 2021 that deployed and measured the effect of a multimodal approach to increasing vaccine uptake in healthcare employees. Vaccine data were acquired through the Center for Disease Control Immunization Information Systems across Oregon and Washington. Rates of complete vaccination before the intervention were compared with rates after as a measure of feasibility of this intervention. These data were subdivided by race/ethnicity, age, gender, and job class. Complete vaccination was defined as completion of a 2-dose mRNA SARS-CoV-2 vaccine series or a 1-dose adenoviral vector SARS-CoV-2 vaccine. RESULTS: Overall preintervention and postintervention complete vaccination rates were 83.7% and 93.5%, respectively. Of those employees who identified as a certain race, black employees demonstrated the greatest percentage difference increase, 18.5% (preintervention, 72.1%; postintervention, 90.6%), followed by Hispanic employees, 14.1% (preintervention, 79.4%; postintervention, 93.5%), and employees who identify as 2 or more races, 13.9% (preintervention, 78.7%; postintervention, 92.6%). CONCLUSIONS: We found that a multimodal approach to improving vaccination uptake in employees was feasible. For organizations addressing vaccine requirements for their workforce, we recommend a multimodal strategy to increase vaccine confidence and uptake.

Intensive care unit outcomes among patients with lung cancer in the surveillance, epidemiology, and end results-medicare registry.

PURPOSE: Lung cancer is the leading cause of cancer-related mortality. Intensive care unit (ICU) use among patients with cancer is increasing, but data regarding ICU outcomes for patients with lung cancer are limited. PATIENTS AND METHODS: We used the Surveillance, Epidemiology, and End Results (SEER) -Medicare registry (1992 to 2007) to conduct a retrospective cohort study of patients with lung cancer who were admitted to an ICU for reasons other than surgical resection of their tumor. We used logistic and Cox regression to evaluate associations of patient characteristics and hospital mortality and 6-month mortality, respectively. We calculated adjusted associations for mechanical ventilation receipt with hospital and 6-month mortality. RESULTS: Of the 49,373 patients with lung cancer admitted to an ICU for reasons other than surgical resection, 76% of patients survived the hospitalization, and 35% of patients were alive 6 months after discharge. Receipt of mechanical ventilation was associated with increased hospital mortality (adjusted odds ratio, 6.95; 95% CI, 6.89 to 7.01; P < .001), and only 15% of these patients were alive 6 months after discharge. Of all ICU patients with lung cancer, the percentage of patients who survived 6 months from discharge was 36% for patients diagnosed in 1992 and 32% for patients diagnosed in 2005, whereas it was 16% and 11% for patients who received mechanical ventilation, respectively. CONCLUSION: Most patients with lung cancer enrolled in Medicare who are admitted to an ICU die within 6 months of admission. To improve patient-centered care, these results should guide shared decision making between patients with lung cancer and their clinicians before an ICU admission.

Lactic acidosis: recognition, kinetics, and associated prognosis.

Lactic acidosis is a common condition encountered by critical care providers. Elevated lactate and decreased lactate clearance are important for prognostication. Not all lactate in the intensive care unit is due to tissue hypoxia or ischemia and other sources should be evaluated. Lactate, in and of itself, is unlikely to be harmful and is a preferred fuel for many cells. Treatment of lactic acidosis continues to be aimed the underlying source.

Baclofen and gamma-hydroxybutyrate withdrawal.

INTRODUCTION: Benzodiazepine treatment of life-threatening gamma-hydroxybutyrate (GHB) withdrawal is frequently unsatisfactory. Animal studies suggest strongly that treatment with GABA(B) agonists, such as baclofen, will be a more effective strategy. METHODS: A case report from the medical intensive care unit (ICU) of the university tertiary care hospital. RESULTS: A 61-year-old woman was admitted to the medical ICU for severe withdrawal symptoms from chronic GHB use. This manifested as delirium, tremor, and seizures despite only small decreases in GHB dose and treatment with benzodiazepines. The addition of baclofen allowed the rapid sequential decreases in the GHB dose without seizure or delirium and resulted in long-term improvement of her tremor. CONCLUSIONS: Baclofen, a GABA(B) agonist, may be a useful agent in the treatment of severe GHB withdrawal.