In a pig-to-baboon kidney transplant model, both preformed and induced anti-non-Gal antibodies are strongly associated with the pathogenesis of AHXR when anti-Gal antibodies are neutralized.

IntroductionProlonged ventilation and failed extubation are associated with increased harm and cost. The added value of heart and respiratory rate variability (HRV and RRV) during spontaneous breathing trials (SBTs) to predict extubation failure remains unknown.MethodsWe enrolled 721 patients in a multicenter (12 sites), prospective, observational study, evaluating clinical estimates of risk of extubation failure, physiologic measures recorded during SBTs, HRV and RRV recorded before and during the last SBT prior to extubation, and extubation outcomes. We excluded 287 patients because of protocol or technical violations, or poor data quality. Measures of variability (97 HRV, 82 RRV) were calculated from electrocardiogram and capnography waveforms followed by automated cleaning and variability analysis using Continuous Individualized Multiorgan Variability Analysis (CIMVA™) software. Repeated randomized subsampling with training, validation, and testing were used to derive and compare predictive models.ResultsOf 434 patients with high-quality data, 51 (12%) failed extubation. Two HRV and eight RRV measures showed statistically significant association with extubation failure (P <0.0041, 5% false discovery rate). An ensemble average of five univariate logistic regression models using RRV during SBT, yielding a probability of extubation failure (called WAVE score), demonstrated optimal predictive capacity. With repeated random subsampling and testing, the model showed mean receiver operating characteristic area under the curve (ROC AUC) of 0.69, higher than heart rate (0.51), rapid shallow breathing index (RBSI; 0.61) and respiratory rate (0.63). After deriving a WAVE model based on all data, training-set performance demonstrated that the model increased its predictive power when applied to patients conventionally considered high risk: a WAVE score >0.5 in patients with RSBI >105 and perceived high risk of failure yielded a fold increase in risk of extubation failure of 3.0 (95% confidence interval (CI) 1.2 to 5.2) and 3.5 (95% CI 1.9 to 5.4), respectively.ConclusionsAltered HRV and RRV (during the SBT prior to extubation) are significantly associated with extubation failure. A predictive model using RRV during the last SBT provided optimal accuracy of prediction in all patients, with improved accuracy when combined with clinical impression or RSBI. This model requires a validation cohort to evaluate accuracy and generalizability.Trial registrationClinicalTrials.gov NCT01237886. Registered 13 October 2010.

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Background ICU care is costly, and there is a large variation in cost among patients. Methods This is an observational study conducted at two ICUs in an academic centre. We compared the demographics, clinical data, and outcomes of the highest decile of patients by total costs, to the rest of the population. Results A total of 7,849 patients were included. The high-cost group had a longer median ICU length of stay (26 versus 4 days, P < 0.001) and amounted to 49% of total costs. In-hospital mortality was lower in the high-cost group (21.1% versus 28.4%, P < 0.001). Fewer high-cost patients were discharged home (23.9% versus 45.2%, P < 0.001), and a large proportion were transferred to long-term care (35.1% versus 12.1%, P < 0.001). Patients with younger age or a diagnosis of subarachnoid hemorrhage, acute respiratory failure, or complications of procedures were more likely to be high cost. Conclusions High-cost users utilized half of the total costs. While cost is associated with LOS, other drivers include younger age or admission for respiratory failure, subarachnoid hemorrhage, or after a procedural complication. Cost-reduction interventions should incorporate strategies to optimize critical care use among these patients.