Acustimulation combined with pharmacological prophylaxis versus pharmacological prophylaxis alone in postoperative nausea and vomiting (PONV) prophylaxis among patients undergoing laparoscopy abdominal surgery: a research protocol for a randomised controlled trial.

INTRODUCTION: This study evaluates the efficacy of integrating percutaneous electrical nerve stimulation at the pericardium 6 (PC6) acupuncture point through a wearable acustimulation device with standard pharmacological prophylaxis to prevent postoperative nausea and vomiting (PONV) compared with pharmacological prophylaxis alone in patients undergoing laparoscopic abdominal surgery. METHOD AND ANALYSIS: This prospective study will enrol 302 patients scheduled for elective laparoscopic surgery. Participants will be randomly allocated to one of two groups: acustimulation combined with pharmacological prophylaxis or sham stimulation combined with pharmacological prophylaxis. Randomisation will involve a computer-generated sequence, with allocation concealment implemented through sealed envelopes. The acustimulation group will receive electrical stimulation at the PC6 point starting 30 min before surgery and continuing until discharge from the postanaesthesia care unit. Sham group will wear a wristband that does not provide stimulation. The primary outcome is the incidence of PONV. Secondary outcomes include the severity of PONV, incidence rates of nausea and vomiting at different postoperative intervals and indices of gastrointestinal functional recovery. Exploratory outcomes will assess haemodynamic parameters, baroreflex sensitivity, hospital stay duration, costs and both short-term and long-term postoperative recovery. ETHICS AND DISSEMINATION: All participants will provide written informed consent. The study has been approved by the Ethics Committee of Peking Union Medical Hospital (approval number: I-23PJ1712). Results will be published open access. TRIAL REGISTRATION NUMBER: NCT06241547.

Genetic Evidence for Causal Association Between Hypertension and Chronic Pain: A Bidirectional Two-Sample Mendelian Randomization Study.

Objective The extent to which the association between hypertension and chronic pain in observational studies is either causally linked or influenced by other shared risk factors has not been substantially addressed. In the present study, Mendelian randomization (MR) was employed to examine the potential causal relationship between hypertension and risk of chronic pain. Methods The study data were derived from the pooled dataset of the genome-wide association study (GWAS), enabling the evaluation of the causal effects of hypertension on various types of chronic pain including headache as well as chest, abdominal, joint, back, limb, and multisite chronic pain. We performed a bidirectional two-sample MR analysis using random effect inverse variance weighting (IVW), MR-Egger, and weighted median and weighted mode, quantified by the odds ratio (OR). Results Genetically predicted essential hypertension was associated with an increased risk of chronic headache (OR = 1.007, 95% CI: 1.003-1.011, P = 0.002) and limb pain (OR = 1.219, 95% CI: 1.033-1.439, P = 0.019). No potential causal associations were identified between chronic pain and essential hypertension in the reverse direction MR ( P > 0.05). In addition, there was no potential causal association between secondary hypertension and chronic pain (P > 0.05). Conclusion This study provided genetic evidence that a unidirectional causal relationship exists between essential hypertension and the increased risks of chronic headache and limb pain, and no causal relationship was found between secondary hypertension and chronic pain. These findings offer crucial theoretical underpinnings for future research on managing hypertension and chronic pain.

Intraoperative nitrous oxide inhalation to prevent chronic postsurgical pain in video-assisted thoracoscopic surgery: a prospective observational cohort study.

Background: Chronic postsurgical pain (CPSP) is a significant detriment to postsurgical recovery. Previous studies have shown that nitrous oxide (N2O) may produce long-term analgesia and may benefit the prevention of CPSP in Chinese patients. We tested the hypothesis that N2O is a protective factor against chronic pain after video-assisted thoracoscopic surgery (VATS). Methods: Two groups of patients with and without N2O inhalation during VATS in Peking Union Medical College Hospital were recruited. Perioperative information was documented, and postsurgical pain was followed up by telephone. The primary outcome was the presence of CPSP at 6 months postoperatively. Odds ratios (ORs) and their 95% confidence intervals (CIs) were estimated using a multivariate logistic regression model adjusted for relevant confounding factors. Results: A total of 833 patients were eligible, among whom 33.6% were male and 66.4% were female, with an average age of 56.3±11.1 years. A total of 387 (46.5%) patients reported incision-related pain at 6 months after surgery, and 160 (40.0%) out of 400 patients with N2O inhalation during surgery and 227 (52.4%) out of 433 patients without N2O inhalation during surgery developed CPSP. After adjusting for confounding factors, N2O inhalation during surgery was associated with lower odds of CPSP (OR =0.654; 95% CI: 0.480-0.890; P=0.007). Conclusions: N2O inhalation during surgery was associated with lower odds of CPSP in VATS patients, and N2O may benefit the prevention of chronic pain after thoracoscopic surgery.

Spatial mode cleaning and efficient nonlinear pulse compression to sub-50†fs in a gas-filled multipass cell.

We demonstrate a gas-filled multipass cell (MPC) that cleaned the spatial mode of a spatial-filter-free 250 W, 100 kHz, 445 fs driven source based on an Innoslab amplifier and compressed the pulse duration to 41 fs simultaneously. The multipass cell acted as a spatial filter and benefited from its discrete waveguide nature, in which the input beam quality factor M2 was improved from 1.53 to a near-diffraction-limited value of 1.21 at 96% transmission.

Supportive care of female hormones in brain health: what and how?

Female hormones, functioning as neuroactive steroids, are utilized beyond menopausal hormone therapy. The rapid onset of allopregnanolone analogs, such as brexanolone and zuranolone, in treating depression, and the effectiveness of megestrol acetate in addressing appetite and weight gain, prompted the Food and Drug Administration to authorize the use of progesterone for treating postpartum depression and cancer-related cachexia. Progesterone has also been found to alleviate neuropathic pain in animal studies. These off-label applications offer a promising option for patients with advanced cancer who often experience various mood disorders such as depression, persistent pain, social isolation, and physical complications like cachexia. These patients have shown low tolerance to opioids and mood-regulating medications. However, the potential risks and uncertainties associated with hormone therapy treatment modalities can be daunting for both patients and medical professionals. This review aims to offer a comprehensive understanding of the non-reproductive functions and mechanisms of female hormones in brain health.

Transverse interlaminar ultrasound-guided C1-C2 puncture for the intrathecal administration of nusinersen in patients with spinal muscular atrophy.

INTRODUCTION/AIMS: Severe spinal deformities and previous spinal orthopedic instrumentation may result in substantial technical challenges for nusinersen delivery through lumbar puncture in patients with spinal muscular atrophy (SMA). The aim of this paper was to review our experience with ultrasound-guided cervical puncture as an alternative approach for the intrathecal administration of nusinersen. METHODS: This was a retrospective medical record review of transverse interlaminar ultrasound-guided C1-C2 puncture for nusinersen delivery in SMA patients. The details of puncture, complications, and success rate of the procedure were summarized. RESULTS: There were four patients who received a total of 13 cervical punctures for nusinersen delivery. All procedures were technically successful with no major complications. Full doses of nusinersen were delivered intrathecally. DISCUSSION: Transverse interlaminar ultrasound-guided C1-C2 puncture is an alternative approach for administering nusinersen if lumbar puncture fails. The success of the technique requires a thorough preprocedural evaluation of cervical spine imaging, sound knowledge of the cervical sonoanatomy and careful manipulation of the needle.

Impact of previous COVID-19 infection on postoperative complications and functional recovery: a one-year follow-up ambispective cohort study.

BACKGROUND: It's necessary to reassess the patients' short-term and long-term postoperative outcome in the post-COVID-19 era. This study aims to provide more comprehensive evidence regarding the timing of surgery after COVID-19 infection among the vaccinated population upon Omicron variant, considering the duration after acute COVID-19 infection, severity of COVID-19, patients' comorbidities, and the full course quality of postoperative recovery. MATERIALS AND METHODS: This is a single-center cohort study. Patients diagnosed with preoperative COVID-19 infection were consecutively included before surgery. Patients' demographics, surgical characteristics, and COVID-19 related factors were documented. Exposure was the time interval from COVID-19 infection to surgery. The primary outcome was postoperative complications within 30 days. The secondary outcomes included postoperative mortality within 30 days, functional disability at 6 and 12 months after surgery. RESULTS: A total of 4953 patients were included, and postoperative complications occurred in 353 patients (7.1%) within 30 days after surgery. Time interval from COVID-19 infection to surgery was associated with postoperative complications within 30 days after surgery (adjusted odds ratio [aOR] per day: 0.99; 95% CI, 0.99-1.00; P<0.01), as well as postoperative 6- and 12-month functional disability ([aOR]: 1.00; 95% CI, 0.99-1.00; P<0.01; and [aOR] 0.99; 95% CI, 0.98-1.00; P=0.01, respectively). Delaying surgery beyond a time interval of 2 weeks was associated with reduced postoperative 30-day complications ([aOR]: 0.63; 95% CI, 0.43-0.91; P=0.01) and mortality ([aOR]: 0.07; 95% CI, 0.01-0.38; P<0.01). Meanwhile, delaying surgery beyond a time interval of 7 weeks was associated with reduced functional disability at both 6-month ([aOR]: 0.67; 95% CI, 0.58-0.79; P<0.01) and 12-month postoperatively ([aOR]: 0.71; 95% CI, 0.53-0.95; P=0.02). CONCLUSION: A 2 weeks delay after COVID-19 infection is necessary for decreasing short-term postoperative risks, and a longer waiting period could be beneficial for long-term functional recovery.

Efficacy and Safety of Pharmacological Treatment in Patients with Complex Regional Pain Syndrome: A Systematic Review and Meta-Analysis.

Complex regional pain syndrome (CRPS) is a disabling condition that usually affects the extremities after trauma or surgery. At present, there is no FDA-approved pharmacological treatment for patients with CRPS. We performed this systematic review and meta-analysis to evaluate the efficacy and safety of pharmacological therapies and determine the best strategy for CRPS. We searched the databases, including PubMed, Embase, Cochrane, Web of Science, Scopus, and ClinicalTrials.gov, for published eligible randomized controlled trials (RCTs) comparing pharmacological treatment with placebo in CRPS patients. Target patients were diagnosed with CRPS according to Budapest Criteria in 2012 or the 1994 consensus-based IASP CRPS criteria. Finally, 23 RCTs comprising 1029 patients were included. We used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach to rate certainty (confidence in evidence and quality of evidence). Direct meta-analysis showed that using bisphosphonates (BPs) (mean difference [MD] -2.21, 95% CI -4.36--0.06, p = 0.04, moderate certainty) or ketamine (mean difference [MD] -0.78, 95% CI -1.51--0.05, p = 0.04, low certainty) could provide long-term (beyond one month) pain relief. However, there was no statistically significant difference in the efficacy of short-term pain relief. Ketamine (rank p = 0.55) and BPs (rank p = 0.61) appeared to be the best strategies for CRPS pain relief. Additionally, BPs (risk ratio [RR] = 1.86, 95% CI 1.34-2.57, p < 0.01, moderate certainty) and ketamine (risk ratio [RR] = 3.45, 95% CI 1.79-6.65, p < 0.01, moderate certainty) caused more adverse events, which were mild, and no special intervention was required. In summary, among pharmacological interventions, ketamine and bisphosphonate injection seemed to be the best treatment for CRPS without severe adverse events.

Bioinformatics analysis revealed underlying molecular mechanisms associated with asthma severity and identified GABAergic related pathway as a potential therapy for Th2-high endotype asthma.

Background: Asthma, a principally T helper 2 (Th2) cell mediated immunological disease, is categorized into Th2-high and Th2-low endotypes. The influence of these endotypes on clinical characteristics and treatment responsiveness in asthma is yet to be completely understood. This study delves into the underlying molecular mechanisms of Th2 endotypes on asthma. Methods: Transcriptomics data of airway epithelial and corresponding clinical information were sourced from the GEO. The co-expression modules were established by WGCNA. Cytoscape was applied to construct PPI networks, and hub genes were determined via the Cytohubba plugin. Additionally, a functional enrichment analysis was conducted on the co-expressed genes from the relevant modules. The relative abundances levels of 22 different types of immune cells in asthma patients were evaluated by CIBERSORT algorithm. Results: There were 471 genes in the pink module significantly correlated with Th2 endotype. Overall, 151 DEGs were identified in the various Th2 endotypes, and 66 were obtained through intersection with the pink module. In the PPI network, the ten most important genes that regulate Th2 endotypes were selected as hub genes. In Th2-high endotype asthma, the hub genes were significantly related to γ-aminobutyric acid (GABA) pathways, indicating that hub genes can mainly regulate Th2-high endotype asthma through GABAergic system. Conclusions: The severity of asthma is influenced by different Th2 endotypes. GABAergic related hub genes may provide innovative insights for the treatment of Th2-high asthma.

Machine learning approach for predicting post-intubation hemodynamic instability (PIHI) index values: towards enhanced perioperative anesthesia quality and safety.

BACKGROUND: Adequate preoperative evaluation of the post-intubation hemodynamic instability (PIHI) is crucial for accurate risk assessment and efficient anesthesia management. However, the incorporation of this evaluation within a predictive framework have been insufficiently addressed and executed. This study aims to developed a machine learning approach for preoperatively and precisely predicting the PIHI index values. METHODS: In this retrospective study, the valid features were collected from 23,305 adult surgical patients at Peking Union Medical College Hospital between 2012 and 2020. Three hemodynamic response sequences including systolic pressure, diastolic pressure and heart rate, were utilized to design the post-intubation hemodynamic instability (PIHI) index by computing the integrated coefficient of variation (ICV) values. Different types of machine learning models were constructed to predict the ICV values, leveraging preoperative patient information and initiatory drug infusion. The models were trained and cross-validated based on balanced data using the SMOTETomek technique, and their performance was evaluated according to the mean absolute error (MAE), root mean square error (RMSE), mean absolute percentage error (MAPE) and R-squared index (R2). RESULTS: The ICV values were proved to be consistent with the anesthetists' ratings with Spearman correlation coefficient of 0.877 (P < 0.001), affirming its capability to effectively capture the PIHI variations. The extra tree regression model outperformed the other models in predicting the ICV values with the smallest MAE (0.0512, 95% CI: 0.0511-0.0513), RMSE (0.0792, 95% CI: 0.0790-0.0794), and MAPE (0.2086, 95% CI: 0.2077-0.2095) and the largest R2 (0.9047, 95% CI: 0.9043-0.9052). It was found that the features of age and preoperative hemodynamic status were the most important features for accurately predicting the ICV values. CONCLUSIONS: Our results demonstrate the potential of the machine learning approach in predicting PIHI index values, thereby preoperatively informing anesthetists the possible anesthetic risk and enabling the implementation of individualized and precise anesthesia interventions.

Deep Learning Detection and Segmentation of Facet Joints in Ultrasound Images Based on Convolutional Neural Networks and Enhanced Data Annotation.

The facet joint injection is the most common procedure used to release lower back pain. In this paper, we proposed a deep learning method for detecting and segmenting facet joints in ultrasound images based on convolutional neural networks (CNNs) and enhanced data annotation. In the enhanced data annotation, a facet joint was considered as the first target and the ventral complex as the second target to improve the capability of CNNs in recognizing the facet joint. A total of 300 cases of patients undergoing pain treatment were included. The ultrasound images were captured and labeled by two professional anesthesiologists, and then augmented to train a deep learning model based on the Mask Region-based CNN (Mask R-CNN). The performance of the deep learning model was evaluated using the average precision (AP) on the testing sets. The data augmentation and data annotation methods were found to improve the AP. The AP50 for facet joint detection and segmentation was 90.4% and 85.0%, respectively, demonstrating the satisfying performance of the deep learning model. We presented a deep learning method for facet joint detection and segmentation in ultrasound images based on enhanced data annotation and the Mask R-CNN. The feasibility and potential of deep learning techniques in facet joint ultrasound image analysis have been demonstrated.

A Common Neuronal Ensemble in the Lateral Habenula Regulates Ciprofol Anesthesia in Mice.

General anesthetics were first used over 170 years ago; however, the mechanisms of how general anesthetics induce loss of consciousness (LOC) remain unclear. Ciprofol, a novel intravenous anesthetic, has been developed by incorporating cyclopropyl into the chemical structure of propofol. This modification offers the benefits of rapid onset and minimal injection pain. Recent studies have revealed that the glutamatergic neurons of the lateral habenula (LHb) play a crucial role in modulating the LOC induced by propofol and sevoflurane. Nevertheless, the specific involvement of LHb in the anesthetic effects of ciprofol remains uncertain. Here, using targeted recombination in active populations (TRAP) combined with electroencephalogram/electromyography recordings and the righting reflex behavioral test, our study revealed that intravenous infusion of ciprofol for 1 h could lead to the induction of c-Fos expression in the LHb in mice. The combination of TRAP and gene ablation, aimed at selectively ablating ciprofol-activated neurons in the LHb, has been shown to facilitate the emergence of ciprofol anesthesia and decrease the proportion of delta waves during the emergence phase. Chemogenetic inhibition of these neurons produced a comparable effect, whereas chemogenetic activation resulted in the opposite outcome. Chemogenetic activation of ciprofol-activated neurons in the LHb delays the emergence of anesthesia and induces a deep hypnotic state during the emergence phase. Taken together, our findings suggest that LHb ciprofol-activated neurons modulate the state of consciousness and could potentially be targeted to manipulate consciousness during ciprofol anesthesia.

Intraoperative mechanical ventilation and incidence of pneumothorax in lymphangioleiomyomatosis.

Patients with lymphangioleiomyomatosis (LAM) are considered high risk for most surgeries and require specific anesthetic considerations mainly because of the common spontaneous pneumothorax (PTX). To explore whether intraoperative mechanical ventilation could increase the risk of PTX in those patients, we included 12 surgical patients with LAM in this study, of whom four (33.3%) experienced postoperative PTX. According to our results, patients with higher CT grade, poorer pulmonary function, and a history of preoperative PTX might be more likely to develop postoperative PTX. However, intraoperative mechanical ventilation did not show obvious influence, which might help clinicians reconsider the perioperative management of LAM patients.

[Clinicians' Practice and Opinions on Sedation Therapy in End-Stage Patients].

Objective To investigate clinicians' practice and opinions on sedation therapy in end-stage patients at Peking Union Medical College Hospital. Methods From August,2022 to April,2023,an online questionnaire survey was conducted among clinicians involved in end-stage patient management. Results A total of 205 questionnaires were distributed,with an effective response rate of 56.1%.Among the clinicians,55.7% of them had experience of applying sedation therapy in end-stage patients;85.2% of clinicians believed that sedation could relieve the suffering of terminal patients from physical refractory symptoms;75.7% of clinicians considered that sedation therapy could be used to relieve agony from psycho-existential distress.Most clinicians had concerns about sedation therapy due to the lack of legal support(86.1%)and the lack of understanding of patients or families(59.1%).The majority (90.4%) of clinicians were willing to receive training on palliative sedation. Conclusions A majority of clinicians agree that sedation therapy could relieve the physical distress and psycho-existential distress in end-stage patients.However,most clinicians have concerns about the application of sedation therapy due to the lack of legal support.It is necessary to enhance the training on palliative sedation.

NMDA Receptors Regulate Oxidative Damage in Keratinocytes during Complex Regional Pain Syndrome in HaCaT Cells and Male Rats.

Complex regional pain syndrome (CRPS), a type of primary chronic pain, occurs following trauma or systemic disease and typically affects the limbs. CRPS-induced pain responses result in vascular, cutaneous, and autonomic nerve alterations, seriously impacting the quality of life of affected individuals. We previously identified the involvement of keratinocyte N-methyl-d-asparagic acid (NMDA) receptor subunit 2 B (NR2B) in both peripheral and central sensitizations in CRPS, although the mechanisms whereby NR2B functions following activation remain unclear. Using an in vivo male rat model of chronic post-ischemia pain (CPIP) and an in vitro oxygen-glucose deprivation/reoxygenation (OGD/R) cell model, we discovered that oxidative injury occurs in rat keratinocytes and HaCaT cells, resulting in reduced cell viability, mitochondrial damage, oxidative damage of nucleotides, and increased apoptosis. In HaCaT cells, OGD/R induced increases in intracellular reactive oxygen species levels and disrupted the balance between oxidation and antioxidation by regulating a series of antioxidant genes. The activation of NMDA receptors via NMDA exacerbated these changes, whereas the inhibition of the NR2B subunit alleviated them. Co-administration of ifenprodil (an NR2B antagonist) and NMDA (an NMDA receptor agonist) during the reoxygenation stage did not result in any significant alterations. Furthermore, intraplantar injection of ifenprodil effectively reversed the altered gene expression that was observed in male CPIP rats, thereby revealing the potential mechanisms underlying the therapeutic effects of peripheral ifenprodil administration in CRPS. Collectively, our findings indicate that keratinocytes undergo oxidative injury in CRPS, with NMDA receptors playing regulatory roles.

An ambulatory dental treatment of a child with Rett syndrome and limited mouth opening under muscle relaxant-free general anesthesia: a case report.

BACKGROUND: Rett Syndrome (RTT) is a rare, severe, and progressive developmental disorder with intellectual disability. Anesthesia in RTT patients presents a range of challenges. We report a child with RTT who received dental treatment under muscle relaxant-free general anesthesia in our ambulatory center. CASE PRESENTATION: A 15-year-old girl with RTT was admitted to our dental clinic with multiple dental caries and residual roots. Dental treatment was scheduled under ambulatory general anesthesia. After anesthesia induction, a nasal tube was initiated under the guidance of a fiberoptic bronchoscope. Multimodal analgesia, body temperature monitoring, and postoperative nausea and vomiting prevention were applied. No muscle relaxants were used throughout the process. The endotracheal tube was successfully removed after the operation and the patient was discharged home the same day. CONCLUSION: An individualized anesthesia strategy enabled a quick and safe recovery for this RTT patient after dental treatment under muscle relaxant-free general anesthesia.

Effects of ferric derisomaltose on postoperative anaemia in adult spinal deformity surgery: a study protocol for a randomised controlled trial.

INTRODUCTION: Postoperative anaemia is prevalent in adult spinal deformity (ASD) surgery in association with unfavourable outcomes. Ferric derisomaltose, a novel iron supplement, offers a promising solution in rapidly treating postoperative anaemia. However, the clinical evidence of its effect on patients receiving spinal surgery remains inadequate. This randomised controlled trial aims to evaluate the safety and efficacy of ferric derisomaltose on postoperative anaemia in ASD patients. METHODS AND ANALYSIS: This single-centre, phase 4, randomised controlled trial will be conducted at Department of Orthopaedics at Peking Union Medical College Hospital and aims to recruit adult patients who received ASD surgery with postoperative anaemia. Eligible participants will be randomly assigned to receive ferric derisomaltose infusion or oral ferrous succinate. The primary outcome is the change in haemoglobin concentrations from postoperative days 1-14. Secondary outcomes include changes in iron parameters, reticulocyte parameters, postoperative complications, allogeneic red blood cell infusion rates, length of hospital stay, functional assessment and quality-of-life evaluation. ETHICS AND DISSEMINATION: This study has been approved by the Research Ethics Committee of Peking Union Medical College Hospital and registered at ClinicalTrials.gov. Informed consent will be obtained from all participants prior to enrolment and the study will be conducted in accordance with the principles of the Declaration of Helsinki. The results of this study are expected to be disseminated through peer-reviewed journals and academic conferences. TRIAL REGISTRATION NUMBER: NCT05714007.

Development and validation of an interpretable Markov-embedded multilabel model for predicting risks of multiple postoperative complications among surgical inpatients: a multicenter prospective cohort study.

BACKGROUND: When they encounter various highly related postoperative complications, existing risk evaluation tools that focus on single or any complications are inadequate in clinical practice. This seriously hinders complication management because of the lack of a quantitative basis. An interpretable multilabel model framework that predicts multiple complications simultaneously is urgently needed. MATERIALS AND METHODS: The authors included 50 325 inpatients from a large multicenter cohort (2014-2017). The authors separated patients from one hospital for external validation and randomly split the remaining patients into training and internal validation sets. A MARKov-EmbeDded (MARKED) multilabel model was proposed, and three models were trained for comparison: binary relevance, a fully connected network (FULLNET), and a deep neural network. Performance was mainly evaluated using the area under the receiver operating characteristic curve (AUC). The authors interpreted the model using Shapley Additive Explanations. Complication-specific risk and risk source inference were provided at the individual level. RESULTS: There were 26 292, 6574, and 17 459 inpatients in the training, internal validation, and external validation sets, respectively. For the external validation set, MARKED achieved the highest average AUC (0.818, 95% CI: 0.771-0.864) across eight outcomes [compared with binary relevance, 0.799 (0.748-0.849), FULLNET, 0.806 (0.756-0.856), and deep neural network, 0.815 (0.765-0.866)]. Specifically, the AUCs of MARKED were above 0.9 for cardiac complications [0.927 (0.894-0.960)], neurological complications [0.905 (0.870-0.941)], and mortality [0.902 (0.867-0.937)]. Serum albumin, surgical specialties, emergency case, American Society of Anesthesiologists score, age, and sex were the six most important preoperative variables. The interaction between complications contributed more than the preoperative variables, and formed a hierarchical chain of risk factors, mild complications, and severe complications. CONCLUSION: The authors demonstrated the advantage of MARKED in terms of performance and interpretability. The authors expect that the identification of high-risk patients and the inference of the risk source for specific complications will be valuable for clinical decision-making.