Efficacy of navigation system-assisted distraction osteogenesis for hemifacial microsomia based on artificial intelligence for 3 to 18 years old: study protocol for a randomized controlled single-blind trial.

BACKGROUND: Mandibular distraction osteogenesis (MDO) is a major part of the treatment for hemifacial microsomia patients. Due to the narrow surgical field of the intraoral approach, osteotomy accuracy is highly dependent on the surgeons' experience. Electromagnetic (EM) tracking systems can achieve satisfying accuracy to provide helpful real-time surgical navigation. Our research team developed an EM navigation system based on artificial intelligence, which has been justified in improving the accuracy of osteotomy in the MDO in animal experiments. This study aims to clarify the effect of the EM navigation system in improving the MDO accuracy for hemifacial microsomia patients. METHODS: This study is designed as a single-centered and randomized controlled trial. Altogether, 22 hemifacial microsomia patients are randomly assigned to the experiment and control groups. All patients receive three-dimensional CT scans and preoperative surgical plans. The EM navigation system will be set up for those in the experiment group, and the control group will undergo traditional surgery. The primary outcome is the surgical precision by comparing the osteotomy position of pre- and postoperative CT scan images through the Geomagic Control software. The secondary outcomes include mandibular symmetry (occlusal plane deviation angle, mandibular ramus height, and body length), pain scale, and complications. Other indications, such as the adverse events of the system and the satisfactory score from patients and their families, will be recorded. DISCUSSION: This small sample randomized controlled trial intends to explore the application of an EM navigation system in MDO for patients, which has been adopted in other surgeries such as orthognathic procedures. Because of the delicate structures of children and the narrow surgical view, accurate osteotomy and protection of nearby tissue from injury are essential for successful treatment. The EM navigation system based on artificial intelligence adopted in this trial is hypothesized to provide precise real-time navigation for surgeons and optimally improve patient outcomes, including function and aesthetic results. The results of this trial will extend the application of new navigation technology in pediatric plastic surgery. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2200061565. Registered on 29 June 2022.

Applying artificial intelligence algorithm in the design of a guide plate for mandibular angle ostectomy.

PURPOSE: Surgical guide plates can improve the accuracy of surgery, although their design process is complex and time-consuming. This study aimed to use artificial intelligence (AI) to design standardized mandibular angle ostectomy guide plates and reduce clinician workload. METHODS: An intelligence algorithm was designed and trained to design guide plates, with a safety-ensuring penalty factor added. A single-center retrospective cohort study was conducted to test the algorithm among patients who had visited our hospital between 2020 and 2021 for mandibular angle ostectomy. We included patients diagnosed with mandibular angle hypertrophy and excluded those combined with other facial malformations. The guide plate design method acted as the primary predictor, which was AI algorithm vs. experienced residents. Moreover, the symmetry of plate-guided ostectomy was chosen as the primary outcome. The safety, shape, location, effectiveness, and design duration of the guide plate were also recorded. The independent samples t-test and Pearson's chi-squared test were used and P-values < 0.05 were considered significant. RESULTS: Fifty patients (7 men, 43 women; 27 ± 4 years) were included. The two groups differed significantly in terms of safety (7.02 vs. 5.25, P < 0.05) and design duration (24.98 vs. 1685.08, P ＜ 0.05). The ostectomy symmetry and shape, location, and effectiveness of the guide plates did not differ significantly between the two groups. CONCLUSIONS: The intelligent algorithm can improve safety and save time for guide plate design, ensuring other quality of the guide plates. It has good potential applicability in accurate mandibular angle ostectomy.

Assisted reproductive technology and neurodevelopmental outcomes in offspring: a prospective birth cohort study in East China.

RESEARCH QUESTION: Is ART associated with adverse neurodevelopmental outcome in 12-month-old offspring compared with those conceived through natural conception? DESIGN: In this prospective cohort study, 488 infertile women undergoing ART and 1397 women with natural conception were recruited and followed until their offspring were 12 months old. The primary outcome was the neurodevelopment in the offspring. The association between exposure to ART and Gesell developmental scale scores was investigated using multiple linear regression models after adjusting for confounders. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were used to verify the results. RESULTS: In total, 18 (3.7%) and 40 (2.9%) children in the ART and natural conception groups, respectively, had been diagnosed with neurodevelopmental delay at 12 months of age. It was found that gross motor, adaptive behaviour, language and total development quotient scores were comparable between the groups. Following multivariate linear regression and IPTW, social behaviour development quotient scores were found to be slightly higher in the ART group than the natural conception group. Higher social behaviour development quotient scores in the ART group were also observed in the male and the singleton subgroups. CONCLUSIONS: At 12 months, offspring born after ART appeared to have similar motor, language and adaptive behaviour skills, and total development quotient scores, to those born after natural conception. However, social behaviour development in 12-month-old infants was slightly higher in those conceived using ART than in naturally conceived offspring, especially in male or singleton infants. These findings may provide new information in evaluating the potential benefits and risks of ART.

Advances in Robot-Assisted Surgery for Facial Bone Contouring Surgery.

Since our team reported the application of robot-assisted surgery in facial contouring surgery in 2020, further clinical trials with large samples have been conducted. This paper will report the interim results of a single-center, large-sample randomized controlled trial of the first robot developed by our team for facial contouring surgery. Meanwhile, this research field will be systematically reviewed and prospected.

Preliminary reports of augmented-reality assisted craniofacial bone fracture reduction.

BACKGROUND: Zygomaticomaxillary complex fractures involve four fracture ends. It is difficult to fully expose the operative area through a main coronal incision, an intraoral incision, and an eyelid incision. To address the partial visual field loss in craniofacial fracture reduction, we attempted to use an augmented reality (AR) navigation system. METHODS: Patients with zygomaticomaxillary complex fractures underwent three-dimensional (3D) computed tomography (CT) modeling before surgery, and preoperative plans were designed. The control team used traditional optical navigation to perform the surgery. The experimental team used an AR navigation system. From May 2019 to December 2019, 10 patients with zygomaticomaxillary complex fractures were included in this study. Data were collected after surgery and analyzed. RESULTS: There was a significant difference between the two groups in the fracture point error (1.35 vs. 1.61, P = 0.02) and fracture reduction time (15.40 vs. 20.40, P = 0.03). However, there was no difference in the operative duration (6.60 vs. 6.65, P = 0.92), blood loss volume (620.00 vs. 580.00, P = 0.83), or incidence of complications. CONCLUSIONS: The AR navigation system used by the research team has good auxiliary effects for reducing zygomaticomaxillary complex fractures. The new surgical method has better accuracy and a shorter reduction time than the traditional surgical method.

Challenging the fundamental conjectures in nanoparticle drug delivery for chemotherapy treatment of solid cancers.

Nanomedicines for cancer treatment have been studied extensively over the last few decades. Yet, only five anticancer nanomedicines have received approvals from the United States Food and Drug Administration (FDA) for treating solid tumors. This drastic mismatch between effort and return calls into question the basic understanding of this field. Various viewpoints on nanomedicines have been presented regarding their potentials and inefficiencies. However, the underlying logics of nanomedicine research and its inadequate translation to the successful use in the clinic have not been thoroughly examined. Tumor-targeted drug delivery was used to understand the shortfalls of the nanomedicine field in general. The concept of tumor-targeted drug delivery by nanomedicine has been based on two conjectures: (i) increased drug delivery to tumors provides better efficacy, and (ii) decreased drug delivery to healthy organs results in fewer side effects. The clinical evidence gathered from the literature indicates that nanomedicines bearing classic chemotherapeutic drugs, such as Dox, cis-Pt, CPT and PTX, have already reached the maximum drug delivery limit to solid tumors in humans. Still, the anticancer efficacy and safety remain unchanged despite the increased tumor accumulation. Thus, it is understandable to see few nanomedicine-based formulations approved by the FDA. The examination of FDA-approved nanomedicine formulations indicates that their approvals were not based on the improved delivery to tumors but mostly on changes in dose-limiting toxicity unique to each drug. This comprehensive analysis of the fundamentals of anticancer nanomedicines is designed to provide an accurate picture of the field's underlying false conjectures, hopefully, thereby accelerating the future clinical translations of many formulations under research.

Oncologic outcomes of single-incision laparoscopic surgery versus conventional laparoscopic surgery for colorectal cancer (CSILS): study protocol for a multicentre, prospective, open-label, noninferiority, randomized controlled trial.

BACKGROUND: In most previous studies, single-incision laparoscopic surgery (SILS) for colorectal cancer (CRC) was feasible and safe in the short term. However, long-term oncologic outcomes remain uncertain, as only a few studies contained long-term survival data. SILS for CRC is still in the early stages of research. Further studies, particularly large-scale, prospective randomized controlled trials, are necessary to assess the value of SILS for CRC. METHODS: This study is a prospective, multicentre, open-label, noninferiority, parallel-group randomized controlled trial that investigates the long-term oncologic outcomes of SILS compared to conventional laparoscopic surgery (CLS) for CRC. A total of 710 eligible patients will be randomly assigned to the SILS group or the CLS group at a 1:1 ratio using a central, dynamic, and stratified block randomization method. Patients with ages ranging from 18 to 85 years old, of both sexes, with CRC above the peritoneal reflection diagnosed as cT1-4aN0-2M0 and a tumour size no larger than 5 cm will be considered for the study. The primary endpoint is 3-year disease-free survival (DFS). The secondary endpoints include: intraoperative outcomes, postoperative recovery, postoperative pain assessment, pathological outcomes, early morbidity and mortality rate, cosmetic effects, quality of life, 3-year overall survival (OS), incidence of incisional hernia, 5-year DFS and 5-year OS. The first two follow-up visits will be scheduled at one month and three months postoperatively, then every three months for the first two years and every six months for the next three years. DISCUSSION: Currently, no randomized controlled trials (RCTs) have been designed to investigate the long-term oncologic outcomes of SILS for CRC. This study is expected to provide clinical evidence of the oncologic outcomes of SILS compared to CLS for CRC to promote its widespread use. TRIAL REGISTRATION: ClinicalTrials.gov:  NCT04527861 (registered on August 27, 2020).

Copy Number Analyses Identified a Novel Gene: APOBEC3A Related to Lipid Metabolism in the Pathogenesis of Preeclampsia.

Background: Preeclampsia is a heterogeneous and complex disease with its pathogenesis mechanism not fully elucidated. A certain subset of patients with preeclampsia exhibit disturbances in lipid metabolism before clinical symptoms. Moreover, there is a tendency for preeclampsia to run in families. Whether genetic factors play a role in abnormal lipid metabolism during the incidence of preeclampsia has not been well investigated. Methods: Preeclampsia patients (n = 110) and healthy age- and gravidity-matched pregnant women (n = 110) were enrolled in this study. Peripheral blood specimens were used for genomic analysis (n = 10/group) or laboratory validation (n = 100/group). We retrospectively obtained the baseline clinical characteristics of 68 preeclampsia patients and 107 controls in early pregnancy (12-14 gestational weeks). Correlation analyses between differential genes and baseline lipid profiles were performed to identify candidate genes. In vitro and in vivo gain-of-function models were constructed with lentivirus and adeno-associated virus systems, respectively, to investigate the role of candidate genes in regulating lipid metabolism and the development of preeclampsia. Results: We observed that preeclampsia patients exhibited significantly elevated plasma TC (P = 0.037) and TG (P < 0.001) levels and increased body mass index (P = 0.006) before the disease onset. Within the region of 27 differential copy number variations, six genes potentially connected with lipid metabolism were identified. The aberrant copies of APOBEC3A, APOBEC3A_B, BTNL3, and LMF1 between preeclampsia patients and controls were verified by quantitative polymerase chain reaction. Especially, APOBEC3A showed a significant positive correlation with TC (P < 0.001) and LDL (P = 0.048) in early pregnancy. Then, our in vitro data revealed that overexpression of APOBEC3A disrupted lipid metabolism in HepG2 cells and affected both cholesterol and fatty acid metabolisms. Finally, in vivo study in a hepatic-specific overexpressed APOBEC3A mouse model revealed abnormal parameters related to lipid metabolism. Pregnant mice of the same model at the end of pregnancy showed changes related to preeclampsia-like symptoms, such as increases in sFlt-1 levels and sFlt-1/PLGF ratios in the placenta and decreases in fetal weight. Conclusion: Our findings established a new link between genetics and lipid metabolism in the pathogenesis of preeclampsia and could contribute to a better understanding of the molecular mechanisms of preeclampsia.

New laboratory evidence for the association between endothelial dysfunction and COVID-19 disease progression.

There is growing evidence that angiotensin-converting enzyme 2 is highly expressed on endothelial cells, endothelial dysfunction plays a critical role in coronavirus disease 2019 (COVID-19) progression, but laboratory evidence is still lacking. This study established a multicenter retrospective cohort of 966 COVID-19 patients from three hospitals in Wuhan, China. We found that male (62.8% vs. 46.5%), old age [72 (17) vs. 60.5 (21)], and coexisting chronic diseases (88.5% vs. 60.0%) were associated with poor clinical prognosis in COVID-19. Furthermore, the deteriorated patients exhibited more severe multiorgan damage, coagulation dysfunction, and extensive inflammation. Additionally, a cross-sectional study including 41 non-COVID-19 controls and 39 COVID-19 patients assayed endothelial function parameters in plasma and showed that COVID-19 patients exhibited elevated vascular cell adhesion molecule-1 (VCAM-1) (median [IQR]: 0.32 [0.27] vs. 0.17 [0.11] µg/ml, p < 0.001), E-selectin (21.06 [12.60] vs. 11.01 [4.63] ng/ml, p < 0.001), tissue-type plasminogen activator (tPA) (0.22 [0.12] vs. 0.09 [0.04] ng/ml, p < 0.001), and decreased plasminogen activator inhibitor-1 (0.75 [1.31] vs 6.20 [5.34] ng/ml, p < 0.001), as compared to normal controls. Moreover, VCAM-1 was positively correlated with d-dimer (R = 0.544, p < 0.001); tPA was positively correlated with d-dimer (R = 0.800, p < 0.001) and blood urea nitrogen (R = 0.638, p < 0.001). Our findings further confirm the strong association between endothelial dysfunction and poor prognosis of COVID-19, which offers a rationale for targeting endothelial dysfunction as a therapeutic strategy for COVID-19.

The application of augmented reality in craniofacial bone fracture reduction: study protocol for a randomized controlled trial.

BACKGROUND: Augmented reality (AR) is a new technology that increases users' perception of the real world. The purpose of this study is to evaluate the efficacy and safety of augmented reality navigation system in treatment with craniofacial fracture reduction. METHODS: This will be a single-center prospective randomized controlled trial. Twenty-two patients will be assigned to two groups of 11, and those with zygomaticomaxillary complex fractures will undergo preoperative three-dimensional CT modeling and have operational plans designed. The control team will use traditional optical navigation to perform the surgery, and the experimental team will use an AR navigation system. The primary outcome measures will be the accuracy of the key points of surgical area between the preoperational surgical plan and post-operation. The secondary outcome measures will be the blood loss, operation time, bone reduction time, hospital time, and complication rate. The findings obtained through this study are expected to evaluate efficacy and safety of the augmented reality navigation system in the treatment of zygomaticomaxillary complex fractures. DISCUSSION: This controlled trial of augmented reality navigation system in treatment with zygomaticomaxillary complex fracture reduction will clarify the efficacy and safety of this technology by measuring the accuracy of the key points of surgical area and blood loss, operation and bone reduction times, hospital stay duration, and complication rates. This is a single-center study, and the results are expected to promote the application of augmented reality in craniofacial fracture reduction to improve surgery accuracy and efficacy. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900022626 . Registered on April 19, 2019.

Isoandrographolide inhibits NLRP3 inflammasome activation and attenuates silicosis in mice.

Silicosis is an irreversible occupational disease caused by silica particle exposure. Abundant evidences suggest that NLRP3-mediated inflammation acts an essential role in fibrogenesis and the pathogenesis of silicosis. In the current work, we firstly reported that (8R-12S)-isoandrographolide (ISA), a diterpenoid lactone ingredient of Chinese traditional medicinal plant Andrographis paniculata (Burm.f.) Nees, could reduce pulmonary inflammation and fibrosis by inhibiting NLRP3, and thereby ameliorate silicosis. ISA administration significantly alleviated lung injury, and attenuated inflammatory response, EMT, as well as collagen deposition in the lung of silica-induced mice. Further studies verified that ISA inhibited the expressions of NLRP3 inflammasome-related proteins NLRP3, ASC and caspase-1 in vivo and in vitro, leading to the attenuation of inflammation and EMT. Additionally, the molecular docking assay indicated that ISA possibly interacted with the residues of LYS26 and GLU47 of NLRP3, implying that ISA might directly bond to protein NLRP3. Of note, ISA revealed a lower cytotoxicity but more potent therapeutic effect than andrographolide (AD), the major active extract of A. paniculata, which has been traditionally used to treat inflammation-related diseases. Taken together, our study clarified a novel role of ISA in attenuating inflammation and fibrosis in silicosis, and indicated a bright future of ISA as a lead compound for developing therapeutic drug for silicosis.

Assessment of Robot-Assisted Mandibular Contouring Surgery in Comparison With Traditional Surgery: A Prospective, Single-Center, Randomized Controlled Trial.

BACKGROUND: Few clinical studies on robot-assisted surgery (RAS) for mandibular contouring have been reported. OBJECTIVES: The aim of this study was to follow the long-term effectiveness and safety of RAS for craniofacial bone surgery. METHODS: This small-sample, early-phase, prospective, randomized controlled study included patients diagnosed with mandibular deformity requiring mandibular contouring surgery. Patients of both genders aged 18 to 30 years without complicated craniofacial repair defects were enrolled and randomly assigned in a 1:1 ratio by a permuted-block randomized assignments list generated by the study statistician. The primary outcomes were the positioning accuracy and accuracy of the osteotomy plane angle 1 week after surgery. Surgical auxiliary measurement index, patient satisfaction scale, surgical pain scale, perioperative period, and complications at 1 week, 1 month, and 6 months after surgery were also analyzed. RESULTS: One patient was lost to follow-up, resulting in a total of 14 patients in the traditional surgery group and 15 in the robot-assisted group (mean [standard deviation] age, 22.65 [3.60] years). Among the primary outcomes, there was a significant difference in the positioning accuracy (2.91 mm vs 1.65 mm; P < 0.01) and angle accuracy (13.26º vs 4.85º; P < 0.01) between the 2 groups. Secondary outcomes did not significantly differ. CONCLUSIONS: Compared to traditional surgery, robot-assisted mandibular contouring surgery showed improved precision in bone shaving, as well as higher safety.

A nomogram for preoperative prediction of prolonged air leak after pulmonary malignancy resection.

BACKGROUND: Prolonged air leak (PAL) is one of the most common postoperative complications after lung surgery. This study aimed to identify risk factors of PAL after lung resection and develop a preoperative predictive model to estimate its risk for individual patients. METHODS: Patients with pulmonary malignancies or metastasis who underwent pulmonary resection between January 2014 and January 2018 were included. PAL was defined as an air leak more than 5 days after surgery, risk factors were analyzed. Forward stepwise multivariable logistic regression analysis was performed to identify independent risk factors, and a derived nomogram was built. Data from February 2018 to September 2018 were collected for internal validation. RESULTS: A total of 1,511 patients who met study criteria were enrolled in this study. The overall incidence of PAL was 9.07% (137/1,511). Age, percent forced expiratory volume in 1 second, surgical type, surgical approach and smoking history were included in the final model. A nomogram was developed according to the multivariable logistic regression results. The C-index of the predictive model was 0.70, and the internal validation value was 0.77. The goodness-of-fit test was non-significant for model development and internal validation. CONCLUSIONS: The predictive model and derived nomogram achieved satisfied preoperative prediction of PAL. Using this nomogram, the risk for an individual patient can be estimated, and preventive measures can be applied to high-risk patients.

Association of homocysteine with IVF/ICSI outcomes stratified by MTHFR C677T polymorphisms: a prospective cohort study.

RESEARCH QUESTION: What is the association between homocysteine (Hcy) and IVF/intracytoplasmic sperm injection (ICSI) outcomes, stratified by methylenetetrahydrofolate reductase (MTHFR) C677T polymorphisms? DESIGN: This prospective cohort study recruited 1011 infertile women undergoing IVF/ICSI treatment for the first time at the International Peace Maternity and Child Health Hospital between June 2015 and March 2018. RESULTS: The concentration of total serum Hcy was significantly negatively associated with clinical pregnancy and implantation rate. When adjusted for maternal and paternal age and educational level, maternal body mass index, and FSH and oestradiol concentrations, logistic regression analysis showed that women with higher Hcy had a higher risk of unsuccessful pregnancy. After stratification by MTHFR C677T polymorphisms and adjustment for confounding factors, a higher risk of unsuccessful pregnancy and a significantly lower implantation rate only existed in women with higher Hcy concentration in the MTHFR C677T TT genotype. There was no significant association between Hcy concentrations and other ovarian stimulation outcomes (oocytes retrieved, metaphase II stage oocytes, fertilization rate, cleavage rate, high-quality embryo rate) or neonatal outcomes (preterm birth, gestational age at delivery, Caesarean section, birthweight, small for gestational age, large for gestational age or birth defects). CONCLUSIONS: Hcy is highly negatively associated with clinical pregnancy and implantation rate during the first IVF/ICSI cycle, especially in women carrying the MTHFR C677T TT genotype. Other factors with impacts on reproductive outcomes, such as stage of embryo transferred, other factors involved in folate metabolism, preimplantation genetic testing, etc., should be taken into account in further research.

Integration of Genomic and Transcriptomic Markers Improves the Prognosis Prediction of Acute Promyelocytic Leukemia.

PURPOSE: The current stratification system for acute promyelocytic leukemia (APL) is based on the white blood cell (WBC) and the platelet counts (i.e., Sanz score) over the past two decades. However, the borderlines among different risk groups are sometimes ambiguous, and for some patients, early death and relapse remained challenges. Besides, with the evolving of the treatment strategy from all-trans-retinoic acid (ATRA) and chemotherapy to ATRA-arsenic trioxide-based synergistic targeted therapy, the precise risk stratification with molecular markers is needed. EXPERIMENTAL DESIGN: This study performed a systematic analysis of APL genomics and transcriptomics to identify genetic abnormalities in 348 patients mainly from the APL2012 trial (NCT01987297) to illustrate the potential molecular background of Sanz score and further optimize it. The least absolute shrinkage and selection operator algorithm was used to analyze the gene expression in 323 cases to establish a scoring system (i.e., APL9 score). RESULTS: Through combining NRAS mutations, APL9 score, and WBC, 321 cases can be stratified into two groups with significantly different outcomes. The estimated 5-year overall (P = 0.00031), event-free (P < 0.0001), and disease-free (P = 0.001) survival rates in the revised standard-risk group (95.6%, 93.8%, and 98.1%, respectively) were significantly better than those in the revised high-risk group (82.9%, 77.4%, and 88.4%, respectively), which could be validated using The Cancer Genome Atlas dataset. CONCLUSIONS: We have proposed a two-category system for improving prognosis in patients with APL. Molecular markers identified in this study may also provide genomic insights into the disease mechanism for improved therapy.

Arsenic trioxide replacing or reducing chemotherapy in consolidation therapy for acute promyelocytic leukemia (APL2012 trial).

As all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) are widely accepted in treating acute promyelocytic leukemia (APL), deescalating toxicity becomes a research hotspot. Here, we evaluated whether chemotherapy could be replaced or reduced by ATO in APL patients at different risks. After achieving complete remission with ATRA-ATO-based induction therapy, patients were randomized (1:1) into ATO and non-ATO groups for consolidation: ATRA-ATO versus ATRA-anthracycline for low-/intermediate-risk patients, or ATRA-ATO-anthracycline versus ATRA-anthracycline-cytarabine for high-risk patients. The primary end point was to assess disease-free survival (DFS) at 3 y by a noninferiority margin of -5%; 855 patients were enrolled with a median follow-up of 54.9 mo, and 658 of 755 patients could be evaluated at 3 y. In the ATO group, 96.1% (319/332) achieved 3-y DFS, compared to 92.6% (302/326) in the non-ATO group. The difference was 3.45% (95% CI -0.07 to 6.97), confirming noninferiority (P < 0.001). Using the Kaplan-Meier method, the estimated 7-y DFS was 95.7% (95% CI 93.6 to 97.9) in ATO and 92.6% (95% CI 89.8 to 95.4) in non-ATO groups (P = 0.066). Concerning secondary end points, the 7-y cumulative incidence of relapse (CIR) was significantly lower in ATO (2.2% [95% CI 1.1 to 4.2]) than in non-ATO group (6.1% [95% CI 3.9 to 9.5], P = 0.011). In addition, grade 3 to 4 hematological toxicities were significantly reduced in the ATO group during consolidation. Hence, ATRA-ATO in both chemotherapy-replacing and -reducing settings in consolidation is not inferior to ATRA-chemotherapy (https://www.clinicaltrials.gov/, NCT01987297).

Advances in biomarker development and potential application for preeclampsia based on pathogenesis.

Preeclampsia (PE) is a pregnancy-specific complication that seriously threatens the health and safety of mothers and infants. The etiology of PE has not been fully elucidated, and no effective treatments are currently available. A pregnant woman with PE often has to make a tough choice on either endangering her own health to give a birth or being forced to terminate her pregnancy. It is recommended by the International Federation of Gynecology and Obstetrics that the combination of maternal high-risk factors and biomarkers could form a good strategy for predicting the risk of PE. Such a combination may also enable more effective monitoring and early clinical intervention in high-risk populations to reduce the risk of PE. Therefore, biomarkers validated by extensive clinical research may be formally applied for clinical PE risk prediction. In this review, we summarized data from clinical research on potential biomarkers and classified them according to the current four major hypotheses, namely placental or trophoblast ischemia and hypoxia, vascular endothelial injury, oxidative stress, and immune dysregulation. Additionally, we also discussed the underlying mechanisms by which these potential biomarkers may be involved in the pathogenesis of PE. Finally, we propose that multiple biomarkers reflecting different aspects of the disease pathogenesis should be used in combination to detect the high-risk PE population in support of clinically targeted intervention and prevention of PE. It is expected that tests made of more sensitive and reliable PE biomarkers based on the aforementioned major hypotheses could potentially improve the accuracy of PE prediction in the future.

Moving Average Based Index for Judging the Peak of the COVID-19 Epidemic.

A pneumonia outbreak caused by a novel coronavirus (COVID-19) has spread around the world. A total of 2,314,621 laboratory-confirmed cases, including 157,847 deaths (6.8%) were reported globally by 20 April 2020. Common symptoms of COVID-19 pneumonia include fever, fatigue, and dry cough. Faced with such a sudden outbreak of emerging infectious disease, traditional models for predicting the peak of the epidemic often show inconsistent results. With the aim to timely judge the epidemic peak and provide support for decisions for resuming production and returning to normal life based on publicly reported data, we used a seven-day moving average of log-transformed daily new cases (LMA) to establish a new index named the "epidemic evaluation index" (EEI). We used SARS epidemic data from Hong Kong to verify the practicability of the new index, and then applied it to the COVID-19 epidemic analysis. The results showed that the epidemic peaked, respectively, on 9 February and 5 February 2020, in Hubei Province and other provinces in China. The proposed index can be applied for judging the epidemic peak. While the global COVID-19 epidemic reached its peak in the middle of April, the epidemic peaks in some countries have not yet appeared. Global and united efforts are still needed to eventually eliminate the epidemic.

Cardiac risk prediction model for pregnant women with structural heart disease in Eastern China.

OBJECTIVE: To develop a model for predicting cardiac risk among pregnant women with structural heart disease in Eastern China. METHODS: The model was built using data from pregnant women (development cohort, n=566; validation cohort, n=314) who delivered at Shanghai Obstetrical Cardiology Intensive Care Center, Renji Hospital, Shanghai, between 2002 and 2015. Independent predictors of adverse cardiac events were determined by logistic regression. Discrimination and calibration of the model, termed the Renji score, were compared with the CARPREG score, ZAHARA score, and modified WHO risk classification. RESULTS: There were 87 (15.4%) adverse cardiac events in the development cohort. Independent predictors of adverse cardiac events included left ventricular systolic dysfunction (ejection fraction, <40%), prior cardiac event or arrhythmia, moderate-to-severe pulmonary arterial hypertension (≥50 mm Hg), mechanical valve replacement, moderate-to-severe mitral stenosis. Surgical intervention before pregnancy was protective against cardiac events. As compared with other risk assessment systems, the Renji score performed better in predicting cardiac events, with a concordance statistic of 0.844 (95% confidence interval [CI], 0.800-0.889) for the development cohort and 0.779 (95% CI, 0.684-0.873) for the validation cohort. CONCLUSION: The Renji score was applicable to predicting cardiac events among pregnant women with structural heart disease in Eastern China.

A Clinical Score to Predict Severe Acute Kidney Injury in Chinese Patients after Cardiac Surgery.

BACKGROUND/AIMS: Cardiac surgery-associated severe acute kidney injury (SAKI) is associated with high mortality and poor quality of life. A prognostic score for SAKI may enable prevention of complications. METHODS: This observational study of 2,552 patients undergoing cardiac surgery from January 2006 to December 2011 in our institution established associations between predictor variables and postoperative SAKI from a cohort of 1,692 patients and developed a clinical score that was assessed in a validation cohort of 860 patients. RESULTS: Postoperative SAKI occurred in 262 -patients (10.3%). We identified 7 independent and significant risk factors in the derivation model (adjusted OR 95% CI): age ≥81 years (vs. age < 40 years, 4.30, 1.52-12.21), age 61-80 years (vs. age < 40 years, 2.84, 1.24-6.52), age 41-60 years (vs. age < 40 years, 1.62, 0.68-3.87), hypertension (1.65, 1.13-2.39), previous cardiac surgery (3.62, 1.27-10.32), -hyperuricemia (2.02, 1.40-2.92), prolonged operation time (1.32, 1.17-1.48), postoperative central venous pressure < 6 mm H2O (3.53, 2.38-5.23), and low postoperative cardiac output (4.78, 2.97-7.69). The 7-variable risk prediction model had acceptable performance characteristics in the validation cohort (C statistic 0.80, 95% CI 0.74-0.85). The difference in the C statistic was 0.21 (95% CI 0.12-0.29, p < 0.001) compared with the Cleveland Clinic score. CONCLUSION: We developed and validated a practical risk prediction model for SAKI after cardiac surgery based on routinely available perioperative clinical and laboratory data. The prediction model can be easily applied at the bedside and provides a simple and interpretable estimation of risk.