Validation of the LACE readmission and mortality prediction model in a large surgical cohort: Comparison of performance at preoperative assessment and discharge time points.

STUDY OBJECTIVE: The LACE index (Length of stay, admission Acuity, Charlson comorbidity index, and Emergency department visits within 6 months of current admission) is a practical tool designed to predict the risk of readmission or mortality within 30 days of hospital discharge. We sought to validate and examine its performance in a large surgical population at both the preoperative assessment and discharge time points. DESIGN: Retrospective cohort study. SETTING: We identified all admissions with a surgery or procedure at Vanderbilt University Medical Center (VUMC) between 2010 and 2015. PATIENTS: A total of 192,670 admissions (age ≥ 18) were included in the study. INTERVENTIONS: None. MEASUREMENTS: LACE scores were calculated and analyzed with multivariable logistic regression. Discrimination was assessed with the c-statistic, calibration was assessed with calibration plots, and overall performance evaluated with the Brier score. Four models were created: admissions with any surgery or procedure, surgical admissions using actual length of stay (ALOS), surgical admissions using estimated length of stay (ELOS) and non-surgical procedural admissions. MAIN RESULTS: 192,670 admissions were included. The all admissions model c-statistic was 0.77 with a Brier score of 0.13. Surgical admissions with ALOS and ELOS had a c-statistic of 0.80, 0.82 and a Brier score of 0.10, 0.08 respectively. Non-surgical procedural admissions had a c-statistic of 0.76 and a Brier score of 0.14. Calibration for all models was adequate. CONCLUSIONS: The LACE model for surgical and procedural admissions had good discrimination and adequate calibration. Analysis of the model applied to surgical admissions using ELOS demonstrated slightly better overall performance than ALOS, suggesting that LACE could be utilized for readmission risk stratification at the time of preoperative assessment. Clinical Trial and Registry URL: Not applicable.

Islet Hypersensitivity to Glucose Is Associated With Disrupted Oscillations and Increased Impact of Proinflammatory Cytokines in Islets From Diabetes-Prone Male Mice.

Pulsatile insulin release is the primary means of blood glucose regulation. The loss of pulsatility is thought to be an early marker and possible factor in developing type 2 diabetes. Another early adaptation in islet function to compensate for obesity is increased glucose sensitivity (left shift) associated with increased basal insulin release. We provide evidence that oscillatory disruptions may be linked with overcompensation (glucose hypersensitivity) in islets from diabetes-prone mice. We isolated islets from male 4- to 5-week-old (prediabetic) and 10- to 12-week-old (diabetic) leptin-receptor-deficient (db/db) mice and age-matched heterozygous controls. After an overnight incubation in media with 11 mM glucose, we measured islet intracellular calcium in 5, 8, 11, or 15 mM glucose. Islets from heterozygous 10- to 12-week-old mice were quiescent in 5 mM glucose and displayed oscillations with increasing amplitude and/or duration in 8, 11, and 15 mM glucose, respectively. Islets from diabetic 10- to 12-week-old mice, in contrast, showed robust oscillations in 5 mM glucose that declined with increasing glucose. Similar trends were observed at 4-5-weeks of age. A progressive left shift in maximal insulin release was also observed in islets as db/db mice aged. Reducing glucokinase activity with 1 mM D-mannoheptulose restored oscillations in 11 mM glucose. Finally, overnight low-dose cytokine exposure negatively impacted oscillations preferentially in high glucose in diabetic islets compared with heterozygous controls. Our findings suggest the following: 1) islets from frankly diabetic mice can produce oscillations, 2) elevated sensitivity to glucose prevents diabetic mouse islets from producing oscillations in normal postprandial (11-15 mM glucose) conditions, and 3) hypersensitivity to glucose may magnify stress effects from inflammation or other sources.