The optimal threshold of PD-L1 combined positive score to predict the benefit of PD-1 antibody plus chemotherapy for patients with HER2-negative gastric adenocarcinoma: a meta-analysis.

BACKGROUND: Immune checkpoint inhibitors (ICIs) combined with chemotherapy have become the first-line treatment of metastatic gastric and gastroesophageal adenocarcinomas (GEACs). This study aims to figure out the optimal combined positive score (CPS) cutoff value. METHODS: We searched for randomized phase III trials to investigate the efficacy of ICIs plus chemotherapy for metastatic GEACs compared with chemotherapy alone. Pooled analyses of hazard ratios (HRs) based on PD-L1 expression were performed. RESULTS: A total of six trials (KEYNOTE-062, KEYNOTE-590, KEYNOTE-859, ATTRACTION-04, CheckMate 649, and ORIENT-16) were included, comprising 5,242 patients. ICIs plus chemotherapy significantly improved OS (HR: 0.79, 95% CI 0.72-0.86 in global patients; HR: 0.75, 95% CI 0.57-0.98 in Asian patients) and PFS (HR: 0.74, 95% CI 0.68-0.82 in global patients; HR: 0.64, 95% CI 0.56-0.73 in Asian patients) compared with chemotherapy alone. The differences in OS (ratio of HR: 1.05, 95% CI 0.79-1.40; predictive value: - 5.1%) and PFS (ratio of HR: 1.16, 95% CI 0.98-1.36; predictive value: - 13.5%) were not statistically significant between the global and Asian patients. Subgroup analyses indicated that the optimal CPS threshold was at ≥ 5 for OS and ≥ 10 for PFS with the highest predictive values. CONCLUSIONS: The benefit derived from ICIs plus chemotherapy is similar between Asian and global GEAC patients. However, those with a PD-L1 CPS < 5 or CPS < 10 may not have significant benefits from ICIs therapy. Therefore, it is advisable to routinely assess PD-L1 expression in GEAC patients considered for ICIs treatment.

Toripalimab plus capecitabine in the treatment of patients with residual nasopharyngeal carcinoma: a single-arm phase 2 trial.

Patients with residual nasopharyngeal carcinoma after receiving definitive treatment have poor prognoses. Although immune checkpoint therapies have achieved breakthroughs for treating recurrent and metastatic nasopharyngeal carcinoma, none of these strategies have been assessed for treating residual nasopharyngeal carcinoma. In this single-arm, phase 2 trial, we aimed to evaluate the antitumor efficacy and safety of toripalimab (anti-PD1 antibody) plus capecitabine in patients with residual nasopharyngeal carcinoma after definitive treatment (ChiCTR1900023710). Primary endpoint of this trial was the objective response rate assessed according to RECIST (version 1.1). Secondary endpoints included complete response rate, disease control rate, duration of response, progression-free survival, safety profile, and treatment compliance. Between June 1, 2020, and May 31, 2021, 23 patients were recruited and received six cycles of toripalimab plus capecitabine every 3 weeks. In efficacy analyses, 13 patients (56.5%) had complete response, and 9 patients (39.1%) had partial response, with an objective response rate of 95.7% (95% CI 78.1-99.9). The trial met its prespecified primary endpoint. In safety analyses, 21 of (91.3%) 23 patients had treatment-related adverse events. The most frequently reported adverse event was hand-foot syndrome (11 patients [47.8%]). The most common grade 3 adverse event was hand-foot syndrome (two patients [8.7%]). No grades 4-5 treatment-related adverse events were recorded. This phase 2 trial shows that combining toripalimab with capecitabine has promising antitumour activity and a manageable safety profile for patients with residual nasopharyngeal carcinoma.

Differential diagnosis between dilated cardiomyopathy and ischemic cardiomyopathy based on variational mode decomposition and high order spectra analysis.

The clinical manifestations of ischemic cardiomyopathy (ICM) bear resemblance to dilated cardiomyopathy (DCM). The definitive diagnosis of DCM necessitates the identification of invasive, costly, and contraindicated coronary angiography. Many diagnostic studies of cardiovascular disease have tried modal decomposition based on electrocardiogram (ECG) signals. However, these studies ignored the connection between modes and other fields, thus limiting the interpretability of modes to ECG signals and the classification performance of models. This study proposes a classification algorithm based on variational mode decomposition (VMD) and high order spectra, which decomposes the preprocessed ECG signal and extracts its first five modes obtained through VMD. After that, these modes are estimated for their corresponding bispectrums, and the feature vector is composed of fifteen features including bispectral, frequency, and nonlinear features based on this. Finally, a dataset containing 75 subjects (38 DCM, 37 ICM) is classified and compared using random forest (RF), decision tree, support vector machine, and K-nearest neighbor. The results show that, in comparison to previous approaches, the technique proposed provides a better categorization for DCM and ICM of ECG signals, which delivers 98.21% classification accuracy, 98.22% sensitivity, and 98.19% specificity. And mode 3 always has the best performance among single mode. The proposed computerized framework significantly improves automatic diagnostic performance, which can help relieve the working pressure on doctors, possible economic burden and health threaten.

Performance assessment of medical service for organ transplant department based on diagnosis-related groups: A programme incorporating ischemia-free liver transplantation in China.

Background: In July 2017, the first affiliated hospital of Sun Yat-sen university carried out the world's first case of ischemia-free liver transplantation (IFLT). This study aimed to evaluate the performance of medical services pre- and post-IFLT implementation in the organ transplant department of this hospital based on diagnosis-related groups, so as to provide a data basis for the clinical practice of the organ transplant specialty. Methods: The first pages of medical records of inpatients in the organ transplant department from 2016 to 2019 were collected. The China version Diagnosis-related groups (DRGs) were used as a risk adjustment tool to compare the income structure, service availability, service efficiency and service safety of the organ transplant department between the pre- and post-IFLT implementation periods. Results: Income structure of the organ transplant department was more optimized in the post-IFLT period compared with that in the pre-IFLT period. Medical service performance parameters of the organ transplant department in the post-IFLT period were better than those in the pre-IFLT period. Specifically, case mix index values were 2.65 and 2.89 in the pre- and post-IFLT periods, respectively (p = 0.173). Proportions of organ transplantation cases were 14.16 and 18.27%, respectively (p < 0.001). Compared with that in the pre-IFLT period, the average postoperative hospital stay of liver transplants decreased by 11.40% (30.17 vs. 26.73 days, p = 0.006), and the average postoperative hospital stay of renal transplants decreased by 7.61% (25.23 vs.23.31 days, p = 0.092). Cost efficiency index decreased significantly compared with that in the pre-IFLT period (p < 0.001), while time efficiency index fluctuated around 0.83 in the pre- and post-IFLT periods (p = 0.725). Moreover, the average postoperative hospital stay of IFLT cases was significantly shorter than that of conventional liver transplant cases (p = 0.001). Conclusion: The application of IFLT technology could contribute to improving the medical service performance of the organ transplant department. Meanwhile, the DRGs tool may help transplant departments to coordinate the future delivery planning of medical service.

Factors associated with treatment outcomes of patients with drug-resistant tuberculosis in China: A retrospective study using competing risk model.

Objectives: Drug-resistant tuberculosis remains a serious public health problem worldwide, particularly in developing countries, including China. This study determined treatment outcomes among a cohort in Guangzhou, China, and identified factors associated with them. Methods: We initiated a retrospective study using drug-resistant TB data in Guangzhou from 2016 to 2020, managed by Guangzhou Chest Hospital. A competing risk model was used to identify the factors associated with treatment failure and death, as well as loss to follow-up (LTFU). Results: A total of 809 patients were included in the study, of which 281 were under treatment. Of the remaining 528 who had clear treatment outcomes, the number and proportion of treatment success, treatment failure, death, and LTFU were 314 (59.5%), 14 (2.7%), 32 (6.0%), and 168 (31.8%), respectively. Being older and having cavities involving the upper lungs were risk factors for treatment failure and death, while non-Guangzhou household registration and interprovincial mobility were risk factors associated with LTFU. Conclusion: Treatment failure and death were significantly associated with cavitation in the lungs, and LTFU was significantly associated with household registration and geographical mobility. Early identification of factors associated with different treatment outcomes is extremely important for policymakers, health experts, and researchers to implement appropriate strategies and measures to treat and manage the TB-infected population in China.

A cost-effectiveness analysis of capecitabine maintenance therapy versus routine follow-up for early-stage triple-negative breast cancer patients after standard treatment from a perspective of Chinese society.

BACKGROUND: Capecitabine maintenance therapy is safe and efficacious for early-stage triple-negative breast cancer (TNBC) patients, but the cost-effectiveness of its long-term use has not been investigated. Here, we evaluated the cost-effectiveness of capecitabine maintenance therapy, compared with routine follow-up, in early-stage TNBC patients after standard treatment from a perspective of Chinese society. METHODS: A three-state Markov model based on the data from the SYSUCC-001 trial was constructed to estimate the cost-effectiveness of capecitabine maintenance therapy in a month cycle over a period of 30-year time horizon. A 5% annual discount rate was set for all costs and benefits. One-way and probabilistic sensitivity analyses were performed to explore the model uncertainties. The main outcomes include quality-adjusted life years (QALYs), incremental cost-effectiveness ratio (ICER), and the number needed to treat (NNT) to prevent one additional event. RESULTS: Compared with routine follow-up, 1-year capecitabine maintenance therapy yielded an additional 1.29 quality-adjusted life years (QALYs) at an additional cost of $3391.70, with an ICER of $2630.53 (95% CI: $1159.81-$5090.12) per QALY gained. The ICER was considerably lower than the recommended willingness-to-pay (WTP) threshold (i.e., $28,130.00 per QALY). The results were sensitive to the discount rate, drug cost, and treatment cost after relapse. Further, the NNT to prevent one additional relapse case was 29.2 (95% CI: 13.2-196.6), 16.7 (95% CI: 8.4-111.6), and 12.0 (95% CI: 5.7-82.6) at 1, 2, and 5 years, respectively. CONCLUSIONS: One-year capecitabine maintenance therapy for early-stage TNBC after standard treatment, compared with routine follow-up, was found to be highly cost-effective with promising clinical benefits and acceptable increased costs. Real-world studies are warranted to validate our findings in the future.

Add-on individualizing prediction of nasopharyngeal carcinoma using deep-learning based on MRI: A multicentre, validation study.

In nasopharyngeal carcinoma, deep-learning extracted signatures on MR images might be correlated with survival. In this study, we sought to develop an individualizing model using deep-learning MRI signatures and clinical data to predict survival and to estimate the benefit of induction chemotherapy on survivals of patients with nasopharyngeal carcinoma. Two thousand ninety-seven patients from three independent hospitals were identified and randomly assigned. When the deep-learning signatures of the primary tumor and clinically involved gross cervical lymph nodes extracted from MR images were added to the clinical data and TNM staging for the progression-free survival prediction model, the combined model achieved better prediction performance. Its application is among patients deciding on treatment regimens. Under the same conditions, with the increasing MRI signatures, the survival benefits achieved by induction chemotherapy are increased. In nasopharyngeal carcinoma, these prediction models are the first to provide an individualized estimation of survivals and model the benefit of induction chemotherapy on survivals.

Factors associated with positive predictive value of preliminary screening in a two-step screening strategy for colorectal neoplasms in China.

BACKGROUND: The positive predictive value (PPV) of high risk factor questionnaire (HRFQ) plus fecal immunochemical test (FIT) as preliminary screening strategy for colorectal-related neoplasia is relatively low. We aim to explore independent factors associated with PPVs of HRFQ combined FIT for selecting high risk individuals for colonoscopy. METHODS: A total of 6971 residents were enrolled in a community-based screening program. Participants who had positive results of HRFQ and/or FIT and subsequently received colonoscopy were involved. The associations of socio-demographic factors, lifestyle behaviors, and high risk factors of colorectal cancer with PPVs of HRFQ, FIT, and their combination were evaluated by multivariable logistic regression models. RESULTS: Among 572 involved cases, 249 (43.5%) colorectal neoplasms were detected by colonoscopy, including 71 advanced adenoma (12.4%) and 9 colorectal cancer (CRC) (1.6%). The PPVs of preliminary screening were 43.5% for total colorectal neoplasms, 14.0% for advanced neoplasm, and 1.6% for CRC. Adding positive HRFQ to FIT could improve the PPV from 3.5 to 8.0% for detecting CRC. Preliminarily screened positive individuals who were males [adjusted odds ratio (AOR): 1.95, 95% CI 1.31, 2.90; p < 0.001], elders (> 60 years) (AOR: 1.70, 95% CI 1.17, 2.46; p = 0.005), or ex-/current smokers (AOR: 3.04, 95% CI 1.31, 7.09; p = 0.10) had higher odds of PPVs of detecting colorectal neoplasms. CONCLUSIONS: Combining HRFQ and FIT could largely improve PPVs for screening advanced neoplasm and CRC. Gender and age-specific FIT cut-off values as well as initiating ages for CRC screening might be recommended to improve the accuracy and effectiveness of current screening algorithm.

Akt pathway activation reduces platelet apoptosis and contributes to the increase of platelet counts in solid tumor patients.

Platelets counts increase in various cancer patients, which is associated with poor prognosis. However, the cause of high platelet counts in cancer patients is still not fully understood. Here we demonstrated that compared with healthy controls, there were significant differences in platelet parameters, mean platelet volume (MPV), platelet distribution width (PDW), platelet larger cell ratio (P-LCR), and platelet crit (PCT), reflecting platelet volume in breast cancer patients by clinical retrospective analysis. The mitochondrial transmembrane potential (ΔΨm) depolarization and phosphatidylserine (PS) externalization declined, accompanied by reduced expression of pro-apoptotic factors Bak, Bax and apoptotic executor caspase-3, and elevated of anti-apoptotic factor Bcl-xl in various cancer patients' platelets. Notably, the phosphorylation level of Akt and its downstream target Bad increased in platelets from cancer patients. MK2206, the inhibitor of Akt, reduced the phosphorylation level of Akt and Bad, and induced apoptosis of platelets. When platelets from healthy controls cocultured with the cultural supernatant of cancer cells, the phosphorylation level of Akt and Bad in the platelets was elevated and the cultural supernatant of cancer cells could rescue the apoptosis of platelet induced by MK2206. Therefore, in our study the apoptosis of platelets in cancer patients was declined, which exerted an influence on the rise of platelet counts in breast cancer patients. The cross-talking between tumor and platelets could affect platelet apoptosis by regulating Akt signaling pathway in platelets.

Ten years of China's new healthcare reform: a longitudinal study on changes in health resources.

BACKGROUND: China launched a new round of healthcare-system reform in 2009 and proposed the goal of equal and guaranteed essential medical and health services for all by 2020. We aimed to investigate the changes in China's health resources over the past ten years after the healthcare reform. METHODS: Data were collected from the China Statistical Yearbook and China Health Statistics Yearbook from 2009 to 2018. Four categories and ten indicators of health resources were analyzed. A descriptive analysis was used to present the overall condition. The Health Resource Density Index was applied to showcase health-resource distribution in demographic and geographic dimensions. The global and local Moran's I were used to assess the spatial autocorrelation of health resources. Concentration Index (CI) was used to quantify the equity of health-resource distribution. A Geo-Detector model and Geographic Weighted Regression (GWR) were applied to assess the association between gross domestic product (GDP) per capita and health resources. RESULTS: Health resources have increased over the past ten years. The global and local Moran's I suggested spatial aggregation in the distribution of health resources. Hospital beds were concentrated in wealthier areas, but this inequity decreased yearly (from CI=0.0587 in 2009 to CI=0.0021 in 2018). Primary medical and health institutions (PMHI) and their beds were concentrated in poorer areas (CI remained negative). Healthcare employees were concentrated in wealthier areas (CI remained positive). In 2017, the q-statistics indicated that the explanatory power of GDP per capita to beds, health personnel, and health expenditure was 40.7%, 50.3%, and 42.5%, respectively. The coefficients of GWR remained positive with statistical significance, indicating the positive association between GDP per capita and health resources. CONCLUSIONS: From 2009 to 2018, the total amount of health resources in China has increased substantially. Spatial aggregation existed in the health-resources distribution. Health resources tended to be concentrated in wealthier areas. When allocating health resources, the governments should take economic factors into account.

A Robust Discriminant Framework Based on Functional Biomarkers of EEG and Its Potential for Diagnosis of Alzheimer's Disease.

(1) Background: Growing evidence suggests that electroencephalography (EEG), recording the brain's electrical activity, can be a promising diagnostic tool for Alzheimer's disease (AD). The diagnostic biomarkers based on quantitative EEG (qEEG) have been extensively explored, but few of them helped clinicians in their everyday practice, and reliable qEEG markers are still lacking. The study aims to find robust EEG biomarkers and propose a systematic discrimination framework based on signal processing and computer-aided techniques to distinguish AD patients from normal elderly controls (NC). (2) Methods: In the proposed study, EEG signals were preprocessed firstly and Maximal overlap discrete wavelet transform (MODWT) was applied to the preprocessed signals. Variance, Pearson correlation coefficient, interquartile range, Hoeffding's D measure, and Permutation entropy were extracted as the input of the candidate classifiers. The AD vs. NC discriminant performance of each model was evaluated and an automatic diagnostic framework was eventually developed. (3) Results: A classification procedure based on the extracted EEG features and linear discriminant analysis based classifier achieved the accuracy of 93.18 ± 3.65 (%), the AUC of 97.92 ± 1.66 (%), the F-measure of 94.06 ± 4.04 (%), separately. (4) Conclusions: The developed discrimination framework can identify AD from NC with high performance in a systematic routine.

A comprehensive intervention on feasibility, efficacy, and safety between TAE combined with multi-applicator ablation therapy and TACE in the treatment of large hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common tumors in recent days with high mortality and low early diagnosis rate, resulting in the fourth leading cause of deaths globally. This study aimed to evaluate the feasibility, efficacy, and safety between transcatheter arterial embolization (TAE) therapy followed by multi-applicator ablation and transarterial chemoembolization (TACE) for the treatment of large HCC. METHODS: An intervention study conducted at the Cancer Center of Sun Yat-sen University, Guangzhou, China, with whom had large HCC. A comparison between the two groups (intervention and control group) was evaluated at different time dimensions by repeated-measures analysis of variance, Mann-Whitney U rank-sum test, where Kaplan-Meier and log-rank test calculated for the overall survival (OS), tumor response (TR), and progression-free survival (PFS). RESULTS: This study found the improved survival rate (SR) and PFS after 1-year treatment in the observation group (Group-I) by 56.4% and 12.8%, compared to 38.3% and 8.5% in the control group (Group-II). Likewise, 1- and 2-year OS rates (OSRs) in Group-I were 66.7% and 51.4%, wherein Group-II were 48.9% and 30.0%, respectively. The short-term efficacy of Group-I, such as complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD) were 28.21%, 56.41%, 0, 15.38%, while in Group-II was 2.13%, 68.79%, 6.38% 22.70% respectively, which were significant. The short-term efficacy was more excellent in the Group-I than Group-II. The quality of life (QOL) was better in Group-I than that of Group-II. CONCLUSIONS: TAE combined with multi-applicator ablation therapy is safer, effective with prolonged survival, and less severe adverse reactions compared to TACE therapy for the treatment of large HCC.

Automatic epileptic seizure classification in multichannel EEG time series with linear discriminant analysis.

BACKGROUND: An electroencephalogram (EEG) is the most dominant method for detecting epileptic seizures. However, the existing techniques use single-channel EEGs from public databases and the sample size is small. OBJECTIVE: This study proposes a strategy to distinguish multichannel EEGs for health control, particularly the interictal and ictal multichannel EEGs of epileptic patients. METHOD: We calculated five features (variance, Pearson correlation coefficient, Hoeffding's D measure, Shannon entropy, inter-quartile range), which are based on maximal overlap discrete wavelet transform. These features were then fed into linear discriminant analysis for classification purposes. Finally, the proposed method was tested on data on 34 healthy people, 21 interictal patients and 30 ictal patients taken from a hospital. RESULTS: Our experimental results show that the accuracy between healthy and epileptic seizures was 96.88% and the area under the curve (AUC) is 1. The accuracy between interictal and epileptic seizures was 94.12% and the AUC was 0.97. We also obtained an accuracy and AUC equal to 1 for discrimination of interictal EEGs from normal. Finally, we obtained an AUC of 0.83 and an accuracy of 85.88% for discrimination in these three classes. Therefore, our study achieves sufficient performance. CONCLUSIONS: Our proposed method can serve as an auxiliary tool for clinicians who wish to make clinical decisions and reduces the burden of detecting epileptic seizures.

A novel approach to determine two optimal cut-points of a continuous predictor with a U-shaped relationship to hazard ratio in survival data: simulation and application.

BACKGROUND: In clinical and epidemiological researches, continuous predictors are often discretized into categorical variables for classification of patients. When the relationship between a continuous predictor and log relative hazards is U-shaped in survival data, there is a lack of a satisfying solution to find optimal cut-points to discretize the continuous predictor. In this study, we propose a novel approach named optimal equal-HR method to discretize a continuous variable that has a U-shaped relationship with log relative hazards in survival data. METHODS: The main idea of the optimal equal-HR method is to find two optimal cut-points that have equal log relative hazard values and result in Cox models with minimum AIC value. An R package 'CutpointsOEHR' has been developed for easy implementation of the optimal equal-HR method. A Monte Carlo simulation study was carried out to investigate the performance of the optimal equal-HR method. In the simulation process, different censoring proportions, baseline hazard functions and asymmetry levels of U-shaped relationships were chosen. To compare the optimal equal-HR method with other common approaches, the predictive performance of Cox models with variables discretized by different cut-points was assessed. RESULTS: Simulation results showed that in asymmetric U-shape scenarios the optimal equal-HR method had better performance than the median split method, the upper and lower quantiles method, and the minimum p-value method regarding discrimination ability and overall performance of Cox models. The optimal equal-HR method was applied to a real dataset of small cell lung cancer. The real data example demonstrated that the optimal equal-HR method could provide clinical meaningful cut-points and had good predictive performance in Cox models. CONCLUSIONS: In general, the optimal equal-HR method is recommended to discretize a continuous predictor with right-censored outcomes if the predictor has an asymmetric U-shaped relationship with log relative hazards based on Cox regression models.

A Case-control Study on Risk Factors for Severe Hand, Foot and Mouth Disease.

The objective of this study was to identify potential risk factors for severe hand, foot and mouth disease (HFMD). In this case-control study, 459 severe HFMD patients and 246 mild HFMD patients from Guangdong province and Henan province, China were included. Data comprising demographic characteristics, clinical symptoms and signs, laboratory findings and other factors were collected. Univariate analysis revealed 30 factors associated with severe cases. Further multivariate analysis indicated four independent risk factors: fatigue (p < 0.01, odd ratio [OR] = 204.7), the use of glucocorticoids (p = 0.03, OR = 10.44), the use of dehydrant drugs (p < 0.01, OR = 73.7) and maculopapular rash (p < 0.01, OR = 84.4); and one independent protective factor: herpes or ulcers in mouth (p = 0.01, OR = 0.02). However, more systematic research and validation are needed to understand the underlying risk factors for severe HFMD.