OBJECTIVE: Early detection of surgical complications allows for timely therapy and proactive risk mitigation. Machine learning (ML) can be leveraged to identify and predict patient risks for postoperative complications. We developed and validated the effectiveness of predicting postoperative complications using a novel surgical Variational Autoencoder (surgVAE) that uncovers intrinsic patterns via cross-task and cross-cohort presentation learning. MATERIALS AND METHODS: This retrospective cohort study used data from the electronic health records of adult surgical patients over 4 years (2018-2021). Six key postoperative complications for cardiac surgery were assessed: acute kidney injury, atrial fibrillation, cardiac arrest, deep vein thrombosis or pulmonary embolism, blood transfusion, and other intraoperative cardiac events. We compared surgVAE's prediction performance against widely-used ML models and advanced representation learning and generative models under 5-fold cross-validation. RESULTS: 89 246 surgeries (49% male, median [IQR] age: 57 [45-69]) were included, with 6502 in the targeted cardiac surgery cohort (61% male, median [IQR] age: 60 [53-70]). surgVAE demonstrated generally superior performance over existing ML solutions across postoperative complications of cardiac surgery patients, achieving macro-averaged AUPRC of 0.409 and macro-averaged AUROC of 0.831, which were 3.4% and 3.7% higher, respectively, than the best alternative method (by AUPRC scores). Model interpretation using Integrated Gradients highlighted key risk factors based on preoperative variable importance. DISCUSSION AND CONCLUSION: Our advanced representation learning framework surgVAE showed excellent discriminatory performance for predicting postoperative complications and addressing the challenges of data complexity, small cohort sizes, and low-frequency positive events. surgVAE enables data-driven predictions of patient risks and prognosis while enhancing the interpretability of patient risk profiles.

Extracorporeal membrane oxygenation (ECMO) is an essential life-supporting modality for COVID-19 patients who are refractory to conventional therapies. However, the proper treatment decision has been the subject of significant debate and it remains controversial about who benefits from this scarcely available and technically complex treatment option. To support clinical decisions, it is a critical need to predict the treatment need and the potential treatment and no-treatment responses. Targeting this clinical challenge, we propose Treatment Variational AutoEncoder (TVAE), a novel approach for individualized treatment analysis. TVAE is specifically designed to address the modeling challenges like ECMO with strong treatment selection bias and scarce treatment cases. TVAE conceptualizes the treatment decision as a multi-scale problem. We model a patient's potential treatment assignment and the factual and counterfactual outcomes as part of their intrinsic characteristics that can be represented by a deep latent variable model. The factual and counterfactual prediction errors are alleviated via a reconstruction regularization scheme together with semi-supervision, and the selection bias and the scarcity of treatment cases are mitigated by the disentangled and distribution-matched latent space and the label-balancing generative strategy. We evaluate TVAE on two real-world COVID-19 datasets: an international dataset collected from 1651 hospitals across 63 countries, and a institutional dataset collected from 15 hospitals. The results show that TVAE outperforms state-of-the-art treatment effect models in predicting both the propensity scores and factual outcomes on heterogeneous COVID-19 datasets. Additional experiments also show TVAE outperforms the best existing models in individual treatment effect estimation on the synthesized IHDP benchmark dataset.

OBJECTIVE: Extracorporeal membrane oxygenation (ECMO) resource allocation tools are currently lacking. We developed machine learning (ML) models for predicting COVID-19 patients at risk of receiving ECMO to guide patient triage and resource allocation. MATERIAL AND METHODS: We included COVID-19 patients admitted to intensive care units for >24 h from March 2020 to October 2021, divided into training and testing development and testing-only holdout cohorts. We developed ECMO deployment timely prediction model ForecastECMO using Gradient Boosting Tree (GBT), with pre-ECMO prediction horizons from 0 to 48 h, compared to PaO2/FiO2 ratio, Sequential Organ Failure Assessment score, PREdiction of Survival on ECMO Therapy score, logistic regression, and 30 pre-selected clinical variables GBT Clinical GBT models, with area under the receiver operator curve (AUROC) and precision recall curve (AUPRC) metrics. RESULTS: ECMO prevalence was 2.89% and 1.73% in development and holdout cohorts. ForecastECMO had the best performance in both cohorts. At the 18-h prediction horizon, a potentially clinically actionable pre-ECMO window, ForecastECMO, had the highest AUROC (0.94 and 0.95) and AUPRC (0.54 and 0.37) in development and holdout cohorts in identifying ECMO patients without data 18 h prior to ECMO. DISCUSSION AND CONCLUSIONS: We developed a multi-horizon model, ForecastECMO, with high performance in identifying patients receiving ECMO at various prediction horizons. This model has potential to be used as early alert tool to guide ECMO resource allocation for COVID-19 patients. Future prospective multicenter validation would provide evidence for generalizability and real-world application of such models to improve patient outcomes.

Major postoperative complications are devastating to surgical patients. Some of these complications are potentially preventable via early predictions based on intraoperative data. However, intraoperative data comprise long and fine-grained multivariate time series, prohibiting the effective learning of accurate models. The large gaps associated with clinical events and protocols are usually ignored. Moreover, deep models generally lack transparency. Nevertheless, the interpretability is crucial to assist clinicians in planning for and delivering postoperative care and timely interventions. Towards this end, we propose a hierarchical model combining the strength of both attention and recurrent models for intraoperative time series. We further develop an explanation module for the hierarchical model to interpret the predictions by providing contributions of intraoperative data in a fine-grained manner. Experiments on a large dataset of 111,888 surgeries with multiple outcomes and an external high-resolution ICU dataset show that our model can achieve strong predictive performance (i.e., high accuracy) and offer robust interpretations (i.e., high transparency) for predicted outcomes based on intraoperative time series.

Given the risks and cost of hospitalization, there has been significant interest in exploiting machine learning models to improve perioperative care. However, due to the high dimensionality and noisiness of perioperative data, it remains a challenge to develop accurate and robust encoding for surgical predictions. Furthermore, it is important for the encoding to be interpretable by perioperative care practitioners to facilitate their decision making process. We proposeclinical variational autoencoder (cVAE), a deep latent variable model that addresses the challenges of surgical applications through two salient features. (1) To overcome performance limitations of traditional VAE, it isprediction-guided with explicit expression of predicted outcome in the latent representation. (2) Itdisentangles the latent space so that it can be interpreted in a clinically meaningful fashion. We apply cVAE to two real-world perioperative datasets to evaluate its efficacy and performance in predicting outcomes that are important to perioperative care, including postoperative complication and surgery duration. To demonstrate the generality and facilitate reproducibility, we also apply cVAE to the open MIMIC-III dataset for predicting ICU duration and mortality. Our results show that the latent representation provided by cVAE leads to superior performance in classification, regression and multi-task predictions. The two features of cVAE are mutually beneficial and eliminate the need of a predictor. We further demonstrate the interpretability of the disentangled representation and its capability to capture intrinsic characteristics of hospitalized patients. While this work is motivated by and evaluated in the context of clinical applications, the proposed approach may be generalized for other fields using high-dimensional and noisy data and valuing interpretable representations.

Graph matching plays a central role in such fields as computer vision, pattern recognition, and bioinformatics. Graph matching problems can be cast as two types of quadratic assignment problems (QAPs): Koopmans-Beckmann's QAP or Lawler's QAP. In our paper, we provide a unifying view for these two problems by introducing new rules for array operations in Hilbert spaces. Consequently, Lawler's QAP can be considered as the Koopmans-Beckmann's alignment between two arrays in reproducing kernel Hilbert spaces (RKHS), making it possible to efficiently solve the problem without computing a huge affinity matrix. Furthermore, we develop the entropy-regularized Frank-Wolfe (EnFW) algorithm for optimizing QAPs, which has the same convergence rate as the original FW algorithm while dramatically reducing the computational burden for each outer iteration. We conduct extensive experiments to evaluate our approach, and show that our algorithm significantly outperforms the state-of-the-art in both matching accuracy and scalability.