Deep learning algorithm reveals two prognostic subtypes in patients with gliomas.

BACKGROUND: Gliomas are highly complex and heterogeneous tumors, rendering prognosis prediction challenging. The advent of deep learning algorithms and the accessibility of multi-omic data represent a new approach for the identification of survival-sensitive subtypes. Herein, an autoencoder-based approach was used to identify two survival-sensitive subtypes using RNA sequencing (RNA-seq) and DNA methylation (DNAm) data from The Cancer Genome Atlas (TCGA) dataset. The subtypes were used as labels to build a support vector machine model with cross-validation. We validated the robustness of the model on Chinese Glioma Genome Atlas (CGGA) dataset. DNAm-driven genes were identified by integrating DNAm and gene expression profiling analyses using the R MethylMix package and carried out for further enrichment analysis. RESULTS: For TCGA dataset, the model produced a high C-index (0.92 ± 0.02), low brier score (0.16 ± 0.02), and significant log-rank p value (p < 0.0001). The model also had a decent performance for CGGA dataset (CGGA DNAm: C-index of 0.70, brier score of 0.21; CGGA RNA-seq: C-index of 0.79, brier score of 0.18). Moreover, we identified 389 DNAm-driven genes of survival-sensitive subtypes, which were significantly enriched in the glutathione metabolism pathway. CONCLUSIONS: Our study identified two survival-sensitive subtypes of glioma and provided insights into the molecular mechanisms underlying glioma development; thus, potentially providing a new target for the prognostic prediction of gliomas and supporting personalized treatment strategies.

Mutational landscape of chronic myelomonocytic leukemia in Chinese patients.

BACKGROUND: Chronic myelomonocytic leukemia (CMML) is a rare and heterogeneous hematological malignancy. It has been shown that the molecular abnormalities such as ASXL1, TET2, SETBP1, and SRSF2 mutations are common in Caucasian population. METHODS: We retrospectively analyzed 178 Chinese CMML patients. The targeted next generation sequencing (NGS) was used to evaluate 114 gene variations, and the prognostic factors for OS were determined by COX regression analysis. RESULTS: The CMML patients showed a unique mutational spectrum, including TET2 (36.5%), NRAS (31.5%), ASXL1 (28.7%), SRSF2 (24.7%), and RUNX1 (21.9%). Of the 102 patients with clonal analysis, the ancestral events preferentially occurred in TET2 (18.5%), splicing factors (16.5%), RAS (14.0%), and ASXL1 (7.8%), and the subclonal genes were mainly ASXL1, TET2, and RAS. In addition, the secondary acute myeloid leukemia (sAML) transformed from CMML often had mutations in DNMT3A, ETV6, FLT3, and NPM1, while the primary AML (pAML) demonstrated more mutations in CEBPA, DNMT3A, FLT3, IDH1/2, NPM1, and WT1. It was of note that a series of clones were emerged during the progression from CMML to AML, including DNMT3A, FLT3, and NPM1. By univariate analysis, ASXL1 mutation, intermediate- and high-risk cytogenetic abnormality, CMML-specific prognostic scoring system (CPSS) stratifications (intermediate-2 and high group), and treatment options (best supportive care) predicted for worse OS. Multivariate analysis revealed a similar outcome. CONCLUSIONS: The common mutations in Chinese CMML patients included epigenetic modifiers (TET2 and ASXL1), signaling transduction pathway components (NRAS), and splicing factor (SRSF2). The CMML patients with DNMT3A, ETV6, FLT3, and NPM1 mutations tended to progress to sAML. ASXL1 mutation and therapeutic modalities were independent prognostic factors for CMML.

Novel biomarkers for the prediction of COVID-19 progression a retrospective, multi-center cohort study.

A pandemic designated as Coronavirus Disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading worldwide. Up to date, there is no efficient biomarker for the timely prediction of the disease progression in patients. To analyze the inflammatory profiles of COVID-19 patients and demonstrate their implications for the illness progression of COVID-19. Retrospective analysis of 3,265 confirmed COVID-19 cases hospitalized between 10 January 2020, and 26 March 2020 in three medical centers in Wuhan, China. Patients were diagnosed as COVID-19 and hospitalized in Leishenshan Hospital, Zhongnan Hospital of Wuhan University and The Seventh Hospital of Wuhan, China. Univariable and multivariable logistic regression models were used to determine the possible risk factors for disease progression. Moreover, cutoff values, the sensitivity and specificity of inflammatory parameters for disease progression were determined by MedCalc Version 19.2.0. Age (95%CI, 1.017 to 1.048; P < 0.001), serum amyloid A protein (SAA) (95%CI, 1.216 to 1.396; P < 0.001) and erythrocyte sedimentation rate (ESR) (95%CI, 1.006 to 1.045; P < 0.001) were likely the risk factors for the disease progression. The Area under the curve (AUC) of SAA for the progression of COVID-19 was 0.923, with the best predictive cutoff value of SAA of 12.4 mg/L, with a sensitivity of 83.9% and a specificity of 97.67%. SAA-containing parameters are novel promising ones for predicting disease progression in COVID-19.

Psychological Status Among Anesthesiologists and Operating Room Nurses During the Outbreak Period of COVID-19 in Wuhan, China.

Background: Coronavirus Disease 2019 (COVID-19) caused by a novel strain of coronavirus (SARS-CoV-2) posed a major threat to public health. Anesthesiologists and operating room (OR) nurses are at high risk of occupational exposure to SARS-CoV-2 and developing COVID-19. We conducted a single-center survey to investigate the psychological status and perceived social support among operation room (OR) medical staffs during the outbreak of Coronavirus Disease 2019 (COVID-19). Methods: A total of 197 OR medical staffs were enrolled in the survey. The authors performed a cohort study during the period of Wuhan lockdown and then conducted a longitudinal follow-up after lifting of lockdown. The Patient Health Questionaire-9 (PHQ-9) was used to assess for depression and Generalized Anxiety Disorder-7 (GAD-7) for anxiety. The Multidimensional Scale of Perceived Social Support (MSPSS) was used to assess perceived social support. We compared the psychological status of OR medical staffs before and after lifting of Wuhan lockdown. Results: During the period of city lockdown, 177 (89.8%) had close contact with confirmed COVID-19 cases. The prevalence of depression and anxiety in OR medical staffs was 41.6 and 43.1% under Wuhan lockdown, while 13.2 and 15.7% after lifting of lockdown (P = 0.002, P = 0.004). Logistic regression analysis showed that being female, living in suburb areas, shortage of protective equipment and close contact with COVID-19 patients were associated with a higher risk of depression and anxiety. Perceived social support was negatively correlated with depression and anxiety severity in the OR medical staffs (P < 0.05). Conclusions: OR medical staffs exhibited high incidence of anxiety and depression faced with the high risk of exposure to COVID-19 patients. More social support and social recognition for anesthesiologists and OR nurses might potentially help them relieve their psychological pressure.

ASXL1 mutations in Chinese patients with essential thrombocythemia.

Essential thrombocythemia (ET) is characterized by thrombotic and hemorrhagic events. The association of clinical characteristics of Chinese ET patients and additional sex combs like 1 (ASXL1) mutations in these patients has remained to be elucidated. In the present study, 72 newly diagnosed Chinese ET patients were enrolled to determine ASXL1 mutations. Mutations in ASXL1, Janus kinase (JAK)2, calreticulin (CALR) and myeloproliferative leukemia (MPL) genes were detected using Sanger sequencing, and data were statistically analyzed. The frequencies of ASXL1, JAK2 V617F, CALR and MPL W515 mutations in ET patients were 19.4% (14/72), 29.2% (21/72), 31.9% (23/72) and 0% (0/72), respectively. Of note, 28 ET patients (38.9%) were negative for JAK2, CALR and MPL mutations; these patients were classified as triple-negative (TN). The frequency of ASXL1 mutations in patients with JAK2 V617F, CALR and TN mutations was 23.8% (5/21), 21.7% (5/23) and 14.3% (4/28), respectively. ASXL1-mutant patients exhibited significant propensities for thrombotic events compared with the ASXL1 wild-type (wt) cohort (42.9 vs. 12.1%; P=0.021). In addition, JAK2 V617F-mutant patients had a higher mean age compared with CALR-mutant (64.76 vs. 52.96 years; P=0.008) or TN patients (64.76 vs. 51.14 years; P=0.002). Furthermore, more white blood cells in the peripheral blood (PB) were observed in JAK2 V617F-mutant patients compared with those in TN patients (12.40 vs. 8.20×109/l; P=0.02). In addition, CALR-mutant patients exhibited more platelets (PLT) in PB than JAK2 V617F-mutant patients (787.91 vs. 562.17×109/l; P=0.047). TN patients had a significantly lower incidence of clinical symptoms, including dizziness, palpitation and chest congestion compared with CALR- or JAK2 V617F-mutant patients (14.1 vs. 39.1%; P=0.043 and 14.1 vs. 38.1%; P=0.050). No significant difference in progression-free survival was observed between ASXL1-mutant and ASXL1-wt patients (P=0.590). In conclusion, ASXL1-mutant ET patients are prone to experiencing thrombotic events. There was no significant difference in the occurrence of thrombotic events among CARL-mutant, JAK2 V617F-mutant and TN patients. Furthermore, ASXL1-mutant/TN patients exhibited a higher number of PLT than ASXL1/JAK2 V617F-double mutant patients. Therefore, ASXL1 mutations may be a risk factor for the occurrence of thrombotic events in ET patients.

A systematic review and meta-analysis of published randomized controlled trials of combination of clopidogrel and aspirin in transient ischemic attack or minor stroke.

The use of antiplatelet agents in patients with ischemic stroke is recommended. In this study, we compared the efficacy and safety of the treatment of clopidogrel plus aspirin (ASA) and that of ASA alone in patients with mild stroke/transient ischemic attack (TIA). Randomized controlled trial (RCT) studies of Clop + ASA vs. ASA therapy in the patients with minor stroke/TIA were identified by electronic bibliographic searches. The primary result was recurrent stroke, while myocardial infarction (MI) as well as vascular mortalities were the secondary result, and major hemorrhagic events were the safety result. A comparative analysis of binary outcomes was performed on the treatment groups, with the employment of fixed effect models and the measurement of risk ratios (95% CI). Five RCT studies involving 9,527 patients were included. Compared with the group with ASA treatment, there was significant reduction in the incidence of recurrent stroke in the group with Clop + ASA (RR=0.76, 95% CI=0.67-0.87, P<0.0001), and there was no significant increase in the incidence of vascular mortalities and MI (RR=1.08, 95% CI=0.83-1.41, P=0.56) and no significant change in major hemorrhagic events (RR=1.55, 95% CI=0.72-3.36, P=0.26). Therefore, the treatment with Clop + ASA seems safe as well as effective for decreasing stroke recurrence. In addition, this is related to a statistically insignificant trend in increasing vascular mortalities, MI, and primary hemorrhagic events. These findings need to be confirmed in prospective studies.

Comparing efficacy and survivals of initial treatments for elderly patients with newly diagnosed multiple myeloma: a network meta-analysis of randomized controlled trials.

OBJECTIVE: The aim of this study was to evaluate the efficacy and clinical outcome of initial therapies for elderly patients with multiple myeloma (MM). METHODS: Randomized controlled trials (RCTs) were obtained through a comprehensive search. Response rate, progression-free survival (PFS) and overall survival (OS) were the interested outcome measures. Network meta-analysis (NMA) using graph theory methodology to construct an NMA model, and sensitivity analysis were performed. RESULTS: Nineteen RCTs containing 7,235 participants and 17 treatments were included in the NMA. As compared to the classic melphalan plus prednisone (MP) regimen, the majority of other initial regimens showed higher rates of complete response/near complete response, overall response rate (ORR) and better PFS as well as OS. These four outcomes favored the two lenalidomide plus dexamethasone regimens (continuous lenalidomide and 18 cycles of lenalidomide plus dexamethasone), especially continuous lenalidomide plus dexamethasone regimen, over the majority of other regimens including the two established standard treatments (MP plus thalidomide or bortezomib) for elderly patients with newly diagnosed MM. CONCLUSION: Continuous lenalidomide plus dexamethasone ranked as the best regimen in terms of ORR and OS for the treatment of elderly patients with newly diagnosed MM.

Bortezomib-based vs non-bortezomib-based post-transplantation treatment in multiple myeloma patients: a systematic review and meta-analysis of Phase III randomized controlled trials.

OBJECTIVE: To evaluate the efficacy and safety of bortezomib-based vs non-bortezomib-based post-transplantation therapy in patients with multiple myeloma. METHODS: Data of relevant randomized controlled trials assessing the effect of bortezomib as post-transplantation consolidation or maintenance therapy was obtained through a comprehensive search. The outcome measures included response rate, progression-free survival, overall survival, and adverse events (AEs). The hazard ratio (HR), Cochran-Mantel-Haenszel odds ratio (OR), and 95% confidence interval (95% CI) were applied to evaluate the effect of bortezomib in relation to the end points such as progression-free survival, overall survival, response rate, and AEs. RESULTS: Three randomized controlled trials comprising 1,518 participants were included in this study. Pooled ORs for the rates of overall response, and complete response and near complete response, were 1.85 and 1.75, respectively. Pooled HR for progression-free survival favored bortezomib-based therapy over non-bortezomib-based therapy (0.73, 95% CI: 0.67-0.81), while no statistically significant difference could be found between the two groups regarding the pooled HR for 3-year overall survival. Moreover, incidence rates of overall adverse events and grade 3 and 4 peripheral neuropathy were similar in the bortezomib-based groups and the non-bortezomib-based groups (P=0.12 and P=0.41, respectively). The corresponding cumulative meta-analyses of the rates of overall response rate, complete response and near complete response, and grades 3 and 4 peripheral neuropathy supported the superiority of bortezomib-based maintenance therapy over consolidation therapy. CONCLUSION: Bortezomib-based therapy after autologous stem cell transplantation, with tolerable AEs, could obviously improve the response as well as the outcome of multiple myeloma patients, particularly when bortezomib was administered as maintenance therapy.