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BackgroundThe objective of this study is to develop predictive models for persistent opioid use following lower extremity joint arthroplasty and determine if ensemble learning and an oversampling technique may improve model performance.MethodsWe compared various predictive models to identify at-risk patients for persistent postoperative opioid use using various preoperative, intraoperative, and postoperative data, including surgical procedure, patient demographics/characteristics, past surgical history, opioid use history, comorbidities, lifestyle habits, anesthesia details, and postoperative hospital course. Six classification models were evaluated: logistic regression, random forest classifier, simple-feedforward neural network, balanced random forest classifier, balanced bagging classifier, and support vector classifier. Performance with Synthetic Minority Oversampling Technique (SMOTE) was also evaluated. Repeated stratified k-fold cross-validation was implemented to calculate F1-scores and area under the receiver operating characteristics curve (AUC).ResultsThere were 1042 patients undergoing elective knee or hip arthroplasty in which 242 (23.2%) reported persistent opioid use. Without SMOTE, the logistic regression model has an F1 score of 0.47 and an AUC of 0.79. All ensemble methods performed better, with the balanced bagging classifier having an F1 score of 0.80 and an AUC of 0.94. SMOTE improved performance of all models based on F1 score. Specifically, performance of the balanced bagging classifier improved to an F1 score of 0.84 and an AUC of 0.96. The features with the highest importance in the balanced bagging model were postoperative day 1 opioid use, body mass index, age, preoperative opioid use, prescribed opioids at discharge, and hospital length of stay.ConclusionsEnsemble learning can dramatically improve predictive models for persistent opioid use. Accurate and early identification of high-risk patients can play a role in clinical decision making and early optimization with personalized interventions.

A series of SARS-CoV-2 variants of concern (VOCs) have evolved in humans during the COVID-19 pandemic—Alpha, Beta, Gamma, Delta, and Omicron. Here, we used global proteomic and genomic analyses during infection to understand the molecular responses driving VOC evolution. We discovered VOC-specific differences in viral RNA and protein expression levels, including for N, Orf6, and Orf9b, and pinpointed several viral mutations responsible. An analysis of the host response to VOC infection and comprehensive interrogation of altered virus-host protein-protein interactions revealed conserved and divergent regulation of biological pathways. For example, regulation of host translation was highly conserved, consistent with suppression of VOC replication in mice using the translation inhibitor plitidepsin. Conversely, modulation of the host inflammatory response was most divergent, where we found Alpha and Beta, but not Omicron BA.1, antagonized interferon stimulated genes (ISGs), a phenotype that correlated with differing levels of Orf6. Additionally, Delta more strongly upregulated proinflammatory genes compared to other VOCs. Systematic comparison of Omicron subvariants revealed BA.5 to have evolved enhanced ISG and proinflammatory gene suppression that similarly correlated with Orf6 expression, effects not seen in BA.4 due to a mutation that disrupts the Orf6-nuclear pore interaction. Our findings describe how VOCs have evolved to fine-tune viral protein expression and protein-protein interactions to evade both innate and adaptive immune responses, offering a likely explanation for increased transmission in humans.One sentence summarySystematic proteomic and genomic analyses of SARS-CoV-2 variants of concern reveal how variant-specific mutations alter viral gene expression, virus-host protein complexes, and the host response to infection with applications to therapy and future pandemic preparedness.

BACKGROUND Estimating surgical case duration accurately is an important operating room efficiency metric. OBJECTIVE The primary objective of this 4-year, single academic center retrospective study was to utilize an ensemble learning approach to improve the accuracy of scheduled case duration for spine surgery. The primary outcome measure was case duration. METHODS We compared machine learning models using surgical and patient features to our institutional method, which used historic averages and surgeon adjustment as needed. We implemented multivariable linear regression, random forest, bagging, and XGBoost and calculated average R2, root mean squared error (RMSE), and mean absolute error (MAE) using stratified k-folds cross-validation. We then used the Shapley Additive exPlanations (SHAP) explainer model to determine feature importance. RESULTS 3,315 patients who underwent spine surgery were included. The institution’s current method of predicting case times had poor coefficient of determination with actual times (R2 = 0.19). On k-folds cross-validation, the linear regression model had an R2 of 0.34, RMSE of 165.3, and MAE of 128.4. Among all models, the XGBoost regressor performed the best with an R2 of 0.70, RMSE of 110.9, and MAE of 75.8. Based on SHAP analysis of the XGBoost regression, body mass index, spinal fusions, surgical procedure, and number of spine levels involved were the features with the most impact on the model. CONCLUSIONS Utilizing ensemble learning-based predictive models, specifically XGBoost regression, can improve accuracy of the estimation of spine surgery times. CLINICALTRIAL N/A

Days before surgery, add-ons may be scheduled to fill unused surgical block time at an outpatient surgery center. At times, outpatient surgery centers have time limitations for end of block time and discharge from the postanesthesia care unit (PACU). The objective of our study was to develop machine learning models that predicted the following composite outcome: (1) surgery finished by end of operating room block time and (2) patient was discharged by end of recovery room nursing shift. We compared various machine learning models to logistic regression. By evaluating various performance metrics, including F1 scores, we hypothesized that models using ensemble learning will be superior to logistic regression.Data were collected from patients at an ambulatory surgery center. The primary outcome measurement was determined to have a value of 1 (versus 0) if they met both criteria: (1) surgery ends by 5 pm and (2) patient is discharged from the recovery room by 7 pm. We developed models to determine if a procedure would meet both criteria if it were scheduled at 1 pm, 2 pm, 3 pm, or 4 pm. We implemented regression, random forest, balanced random forest, balanced bagging, neural network, and support vector classifier, and included the following features: surgery, surgeon, service line, American Society of Anesthesiologists score, age, sex, weight, and scheduled case duration. We evaluated model performance with Synthetic Minority Oversampling Technique (SMOTE). We compared the following performance metrics: F1 score, area under the receiver operating characteristic curve (AUC), specificity, sensitivity, precision, recall, and Matthews correlation coefficient.Among 13,447 surgical procedures, the median total perioperative time (actual case duration and PACU length stay) was 165 minutes. When SMOTE was not used, when predicting whether surgery will end by 5 pm and patient will be discharged by 7 pm, the average F1 scores were best with random forest, balanced bagging, and balanced random forest classifiers. When SMOTE was used, these models had improved F1 scores compared to no SMOTE. The balanced bagging classifier performed best with F1 score of 0.78, 0.80, 0.82, and 0.82 when predicting our outcome if cases were to start at 1 pm, 2 pm, 3 pm, or 4 pm, respectively.We demonstrated improvement in predicting the outcome at a range of start times when using ensemble learning versus regression techniques. Machine learning may be adapted by operating room management to allow for a better determination whether an add-on case at an outpatient surgery center could be appropriately booked.

The emergence of SARS-CoV-2 variants of concern suggests viral adaptation to enhance human-to-human transmission1,2. Although much effort has focused on the characterization of changes in the spike protein in variants of concern, mutations outside of spike are likely to contribute to adaptation. Here, using unbiased abundance proteomics, phosphoproteomics, RNA sequencing and viral replication assays, we show that isolates of the Alpha (B.1.1.7) variant3 suppress innate immune responses in airway epithelial cells more effectively than first-wave isolates. We found that the Alpha variant has markedly increased subgenomic RNA and protein levels of the nucleocapsid protein (N), Orf9b and Orf6—all known innate immune antagonists. Expression of Orf9b alone suppressed the innate immune response through interaction with TOM70, a mitochondrial protein that is required for activation of the RNA-sensing adaptor MAVS. Moreover, the activity of Orf9b and its association with TOM70 was regulated by phosphorylation. We propose that more effective innate immune suppression, through enhanced expression of specific viral antagonist proteins, increases the likelihood of successful transmission of the Alpha variant, and may increase in vivo replication and duration of infection4. The importance of mutations outside the spike coding region in the adaptation of SARS-CoV-2 to humans is underscored by the observation that similar mutations exist in the N and Orf9b regulatory regions of the Delta and Omicron variants., Nature, 602 (7897), ISSN:0028-0836, ISSN:1476-4687

Emergence of SARS-CoV-2 variants, including the globally successful B.1.1.7 lineage, suggests viral adaptations to host selective pressures resulting in more efficient transmission. Although much effort has focused on Spike adaptation for viral entry and adaptive immune escape, B.1.1.7 mutations outside Spike likely contribute to enhance transmission. Here we used unbiased abundance proteomics, phosphoproteomics, mRNA sequencing and viral replication assays to show that B.1.1.7 isolates more effectively suppress host innate immune responses in airway epithelial cells. We found that B.1.1.7 isolates have dramatically increased subgenomic RNA and protein levels of Orf9b and Orf6, both known innate immune antagonists. Expression of Orf9b alone suppressed the innate immune response through interaction with TOM70, a mitochondrial protein required for RNA sensing adaptor MAVS activation, and Orf9b binding and activity was regulated via phosphorylation. We conclude that B.1.1.7 has evolved beyond the Spike coding region to more effectively antagonise host innate immune responses through upregulation of specific subgenomic RNA synthesis and increased protein expression of key innate immune antagonists. We propose that more effective innate immune antagonism increases the likelihood of successful B.1.1.7 transmission, and may increase in vivo replication and duration of infection.