The Acute Kidney Injury Network's proposed definition for acute kidney injury (increment of serum creatinine ≥0.3 mg/dL or 50% from baseline within 48 hrs or urine output 6 hrs despite fluid resuscitation when applicable) predicts meaningful clinical outcomes. Retrospective cohort study. A 350-bed community teaching hospital. The study population consisted of 471 patients with no recent history of renal replacement therapy who were admitted to the medical intensive care unit during 1 yr. Medical records of all patients were reviewed using a data abstraction tool. Demographic information, diagnoses, risk factors for acute kidney disease, physiologic and laboratory data, and outcomes were recorded. Of 496 patients, 471 were not receiving renal replacement therapy in the weeks before medical intensive care unit admission; 213 had changes ≥.3 mg/dL in serum creatinine within 48 hrs and/or urine output of ≤.5 mL/kg/hr for >6 hrs. Detailed fluid challenge information was available for only 123 patients, who met acute kidney injury criteria, and three patients reversed after administration of ≥500 mL of intravenous fluid and/or blood products. All patients whose creatinine increased ≥50% also had increments ≥0.3 mg/dL. The 120 patients with acute kidney injury were older (mean ± se: 69.3 ± 1.7 vs. 62.9 ± 1.3, p < .01), were more ill (Acute Physiology and Chronic Health Evaluation II score 18.7 ± .6 vs. 13.3 ± .4, p < .01), and had multiple comorbidities (two or more organs, 65% vs. 51.3%, p < .01) compared with those without acute kidney injury. The mortality rate of patients who met criteria for acute kidney injury was significantly higher than that of patients who did not have acute kidney injury (45.8 vs. 16.4%, p < .01). In multivariate logistic regression analyses, acute kidney injury was an independent predictor of mortality (adjusted odds ratio 3.7, 95% confidence interval 2.2–6.1). Acute kidney injury was a better predictor of in-hospital mortality than was Acute Physiology and Chronic Health Evaluation II score, advanced age, or presence of nonrenal organ failures. Median hospital stay was twice as long in patients with acute kidney injury (14 vs. 7 days, p < .01), and only patients with acute kidney injury required hemodialysis during hospitalization. The oliguria criterion of acute kidney injury did not affect the odds of in-hospital mortality. The Acute Kidney Injury Network definition of acute kidney injury predicts hospital mortality, need for renal replacement therapy, and prolonged hospital stay in critically ill patients. An increment of serum creatinine ≥0.3 mg/dL in 48 hrs alone predicts clinical outcomes as well as the full Acute Kidney Injury Network definition.

Spirometrically-defined chronic obstructive pulmonary disease (COPD) is considered progressive but its natural history is inadequately studied. We hypothesized that spirometrically-defined COPD states could undergo beneficial transitions. Participants in the Lovelace Smokers’ Cohort (n = 1553), primarily women, were longitudinally studied over 5 years. Spirometric states included normal postbronchodilator spirometry, COPD Stage I, Unclassified state, and COPD Stage II+, as defined by GOLD guidelines. Beneficial transitions included either a decrease in disease severity, including resolution of spirometric abnormality, or maintenance of non-diseased state. ‘All smokers’ (n = 1553) and subgroups with normal and abnormal spirometry at baseline (n = 956 and 597 respectively) were separately analyzed. Markov-like model of transition probabilities over an average follow-up period of 5 years were calculated. Among ‘all smokers’, COPD Stage I, Unclassified, and COPD Stage II+ states were associated with probabilities of 16, 39, and 22 % respectively for beneficial transitions, and of 16, 35, and 4 % respectively for resolution. Beneficial transitions were more common for new-onset disease than for pre-existing disease (p < 0.001). Beneficial transitions were less common among older smokers, men, or those with bronchial hyperresponsiveness but more common among Hispanics and smokers with excess weight. This observational study of ever smokers, shows that spirometrically-defined COPD states, may not be uniformly progressive and can improve or resolve over time. The implication of these findings is that the spirometric diagnosis of COPD can be unstable. Furthermore, COPD may have a pre-disease state when interventions might help reverse or change its natural history. NA.

Infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) or seasonal influenza may lead to respiratory failure requiring intubation and mechanical ventilation. The pathophysiology of this respiratory failure is attributed to local immune dysregulation, but how the immune response to viral infection in the lower airways of the human lung differs between individuals with respiratory failure and those without is not well understood. We used quantitative multiparameter flow cytometry and multiplex cytokine assays to evaluate matched blood and bronchoalveolar lavage (BAL) samples from control human subjects, subjects with symptomatic seasonal influenza who did not have respiratory failure, and subjects with severe seasonal influenza or SARS-CoV-2 infection with respiratory failure. We find that severe cases are associated with an influx of nonclassical monocytes, activated T cells, and plasmablast B cells into the lower airways. Cytokine concentrations were not elevated in the lower airways of moderate influenza patients compared with controls; however, 28 of 35 measured cytokines were significantly elevated in severe influenza, severe SARS-CoV-2 infection, or both. We noted the largest elevations in IL-6, IP-10, MCP-1, and IL-8. IL-1 family cytokines and RANTES were higher in severe influenza infection than severe SARS-CoV-2 infection. Interestingly, only the concentration of IP-10–correlated between blood and BAL during severe infection. Our results demonstrate inflammatory immune dysregulation in the lower airways during severe viral pneumonia that is distinct from lower airway responses seen in human patients with symptomatic, but not severe, illness and suggest that measurement of blood IP-10 concentration may predict this unique dysregulation.

Primary graft dysfunction (PGD) is the leading cause of morbidity and mortality in the first 30 days after lung transplantation. Risk factors for the development of PGD include donor and recipient characteristics, but how multiple variables interact to impact the development of PGD and how clinicians should consider these in making decisions about donor acceptance remain unclear. This was a single-center retrospective cohort study to develop and evaluate machine learning pipelines to predict the development of PGD grade 3 within the first 72 hours of transplantation using donor and recipient variables that are known at the time of donor offer acceptance. Among 576 bilateral lung recipients, 173 (30%) developed PGD grade 3. The cohort underwent a 75% to 25% train-test split, and lasso regression was used to identify 11 variables for model development. A K-nearest neighbor's model showing the best calibration and performance with relatively small confidence intervals was selected as the final predictive model with an area under the receiver operating characteristics curve of 0.65. Machine learning models can predict the risk for development of PGD grade 3 based on data available at the time of donor offer acceptance. This may improve donor-recipient matching and donor utilization in the future.

The development of donor-specific antibodies (DSA) after lung transplantation is common and results in adverse outcomes. In kidney transplantation, Belatacept has been associated with a lower incidence of DSA, but experience with Belatacept in lung transplantation is limited. We conducted a 2-center pilot randomized controlled trial of de novo immunosuppression with Belatacept after lung transplantation to assess the feasibility of conducting a pivotal trial. Twenty-seven participants were randomized to Control (Tacrolimus, Mycophenolate Mofetil, and prednisone, n = 14) or Belatacept-based immunosuppression (Tacrolimus, Belatacept, and prednisone until day 89 followed by Belatacept, Mycophenolate Mofetil, and prednisone, n = 13). All participants were treated with rabbit anti-thymocyte globulin for induction immunosuppression. We permanently stopped randomization and treatment with Belatacept after 3 participants in the Belatacept arm died compared to none in the Control arm. Subsequently, 2 additional participants in the Belatacept arm died for a total of 5 deaths compared to none in the Control arm (log rank p = 0.016). We did not detect a significant difference in DSA development, acute cellular rejection, or infection between the 2 groups. We conclude that the investigational regimen used in this study is associated with increased mortality after lung transplantation.