CEAC (oral semustine, etoposide, cytarabine and cyclophosphamide) vs BEAM (carmustine, etoposide, cytarabine, and melphalan) conditioning regimen of autologous stem cell transplantation for diffuse large B-cell lymphoma: a post-hoc, propensity score-matched, cohort study in Chinese patients.

Autologous stem cell transplantation (ASCT) is a salvage therapy for relapsed or refractory diffuse large B-cell lymphoma (DLBCL). We have developed a novel conditioning regimen called CEAC (oral semustine 250 mg/m2 d-6, etoposide 300 mg/m2 d-5 ~ d-2, cytarabine 500 mg/m2 d-5 ~ d-2, and cyclophosphamide 1200 mg/m2 d-5 ~ d-2) In lymphoma patients in China. Here, we conducted a study to compare the conventional BEAM regimen with the CEAC regimen in 110 DLBCL patients. Propensity-score matching was performed in a 1:4 ratio (22 patients received BEAM and 88 received CEAC). Our results showed no significant difference in the overall response rate (95% vs 97%, P = 1.000) and complete response rate (66% vs 73%, P = 0.580) between the two cohorts. The 5-year progression-free survival (PFS), 5-year overall survival (OS), and 5-year cumulative incidence of relapse (CIR) for all patients were 72% (95% CI 62%-82%), 92% (95% CI 86%-97%), and 29% (95% CI 17%-38%), respectively. There was no significant difference in the 5-year PFS (80% vs 70%, P = 0.637), 5-year OS (95% vs 91%, P = 0.496), and 5-year CIR (20% vs 30%, P = 0.733) between cohorts. In terms of safety, the CEAC cohort had a lower incidence rate of grade 1-2 gastrointestinal hemorrhage (P = 0.023) and severe nausea (P = 0.007) compared with the BEAM cohort. In conclusion, the CEAC regimen seems to be a suitable alternative to the BEAM regimen for ASCT in DLBCL patients.

Pediatric chemotherapy versus allo-HSCT for adolescent and adult Philadelphia chromosome-negative ALL in first complete remission: a meta-analysis.

Pediatric-inspired chemotherapy significantly improves survival for adolescent and adult patients with acute lymphoblastic leukemia (ALL). However, the benefits over allogeneic hematopoietic stem cell transplantation (allo-HSCT) remain unclear. To compare clinical outcomes between pediatric-inspired chemotherapy and allo-HSCT in consolidation therapy of adolescent and adult Philadelphia chromosome-negative (Ph-neg) ALL in first complete remission (CR1), related studies from MEDLINE, Embase, and Cochrane Controlled Register of Trials updated to July 2022 were searched. A total of 13 relevant trials including 3161 patients were included in the meta-analysis. Compared with allo-HSCT, pediatric-inspired chemotherapy achieved better OS (hazard risk (HR), 0.53; 95% confidence interval (CI), 0.41 to 0.68) and DFS (HR, 0.64; 95% CI, 0.48 to 0.86), with a significant reduction in NRM (risk ratio (RR), 0.30; 95% CI, 0.18 to 0.51), but no difference in the relapse rate (RR, 1.13; 95% CI, 0.93 to 1.39). When only studies based on intention-to-treat analysis were included, pediatric-inspired chemotherapy consistently conferred a survival advantage. In subgroup analyses, patients with baseline high-risk features demonstrated similar OS and DFS between pediatric-style chemotherapy and allo-HSCT, while pediatric-style chemotherapy had an OS and DFS advantage in standard-risk subgroup. Particularly, patients with positive minimal residual disease (MRD) achieved better OS and DFS if proceeded to allo-HSCT.

Re-induction therapy in patients with acute myeloid leukemia not in complete remission after the first course of treatment.

A standard salvage regimen for patients with acute myeloid leukemia (AML) who are not in complete remission (CR) after initial induction therapy does not exist. We retrospectively investigated re-induction therapy for 151 patients with AML who did not achieve CR after the initial course between January 2014 and March 2021. The re-induction regimen did not correlate with the CR rate after the second course, whereas patients had similar 5-year overall survival (OS) and event-free survival (EFS) based on different re-induction regimens. Multivariable analysis revealed that International European Leukaemia Net (ELN) risk stratification independently predicted both OS and EFS among patients not in CR after the first course, although the re-induction regimen did not predict prognosis. Urgent salvage alloHSCT may improve the prognosis of patients with refractory AML. In summary, our study showed that the re-induction regimen did not significantly predict the prognosis of patients with AML not in CR after the first course of treatment. The development and selection of an efficient treatment algorithm for the treatment of AML remains a pressing research challenge.

MiRKAT: kernel machine regression-based global association tests for the microbiome.

SUMMARY: Distance-based tests of microbiome beta diversity are an integral part of many microbiome analyses. MiRKAT enables distance-based association testing with a wide variety of outcome types, including continuous, binary, censored time-to-event, multivariate, correlated and high-dimensional outcomes. Omnibus tests allow simultaneous consideration of multiple distance and dissimilarity measures, providing higher power across a range of simulation scenarios. Two measures of effect size, a modified R-squared coefficient and a kernel RV coefficient, are incorporated to allow comparison of effect sizes across multiple kernels. AVAILABILITY AND IMPLEMENTATION: MiRKAT is available on CRAN as an R package. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Chimeric antigen receptor T-cell therapy combined with autologous stem cell transplantation improved progression-free survival of relapsed or refractory diffuse large B-cell lymphoma patients: A single-center, retrospective, cohort study.

Autologous hematopoietic stem cell transplantation (ASCT) and chimeric antigen receptor T-cell therapy (CART) are salvage therapies that are utilised for treatment of relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL). However, whether the combination therapy of ASCT and CART (ASCT-CART) can improve the survival of R/R DLBCL remains unknown. Overall, 67 R/R DLBCL patients were included, among which 21 patients underwent ASCT-CART therapy and 46 patients underwent ASCT therapy. The median number of mononuclear cells numbers that were infused in the ASCT-CART and ASCT groups was 4.71 × 108 /kg and 5.36 × 108 /kg, respectively (p = 0.469). The median number of CD34+ cell numbers that were infused in the ASCT-CART and ASCT groups was 2.41 × 106 /kg and 3.05 × 106 /kg, respectively (p = 0.663). The median number of CART cells that were infused was 2.63 × 106 /kg with a median transduction rate of 59.83%. The objective response rates to ASCT-CART and ASCT therapy were 90% and 89%, respectively (p = 1.000). However, the ASCT-CART group showed higher complete remission (CR) rates than the ASCT group (71% vs. 33%; p = 0.003). The ASCT-CART group demonstrated superior 3 year progression-free survival (PFS) (80% vs. 44%; p = 0.036) and lower 3 year relapse/progression rate (15% vs. 56%; p = 0.015) compared to the ASCT group. However, the 3 year overall survival results indicated that there were no differences between the two groups (80% vs. 69%; p = 0.545). For R/R DLBCL patients, ASCT-CART therapy is associated with higher CR rate, better PFS, and lower relapse/progression rate. These data support that ASCT-CART therapy can be used as a salvage therapy for R/R DLBCL patients.

Implementation of an Evidence-Based Guideline of Enteral Nutrition for Infants With Congenital Heart Disease: A Controlled Before-and-After Study.

OBJECTIVES: To describe the implementation process of a nutrition risk screening and assessment guideline for infants with congenital heart disease and to assess the impact of nurses' behavior and the effect on infants' outcomes. DESIGN: A controlled before-and-after implementation study. The three dimensions of the integrated-Promoting Action on Research Implementation in Health Services framework were used to assess barriers and promoting factors. SETTING: Cardiac center at Children's Hospital of Fudan University, Shanghai, China. PATIENTS: Infants with congenital heart disease (n = 142) and nurses (n = 100). INTERVENTIONS: Implementation of an evidenced-based nutrition risk screening and assessment guideline. MEASUREMENTS AND MAIN RESULTS: Implementation processes were assessed on nurses' knowledge, attitude, behavior, and compliance of the guideline. Infants' clinical outcomes were evaluated before-and-after the implementation. Knowledge, attitude, and behavior of nurses about nutrition risk screening and assessment increased significantly after implementing the guideline. Nurses' compliance with the recommendations for nutritional risk screening improved significantly on three criteria; assessment of nutritional status stability (p < 0.001), assessment of nutritional status deterioration (p = 0.003), and nutritional assessment among infants with moderate risk and above (p < 0.001). The nurses' compliance with the recommendations for nutrition assessment improved significantly in eight of the 10 criteria (p < 0.001). The proportion of infants receiving comprehensive nutrition assessment when they were first screened with moderate or high nutritional risk were higher in the intervention group (24.3% vs 83.3%; p < 0.001). The accuracy rates of nutrition risk screening were higher in the intervention group (52.9% vs 81.9%; p < 0.001). CONCLUSIONS: Using the integrated-Promoting Action on Research Implementation in Health Services framework contributed to a successful implementation of the nutrition guideline. The nurses' knowledge, attitude, and behavior toward the nutrition guideline were positive resulting in a significantly higher nutrition assessments in infants with moderate or high nutritional risk.

High-energy nutrition in paediatric cardiac critical care patients: a randomized controlled trial.

BACKGROUND: Previous studies have shown that feeding a high-energy formula (HF) to infants after cardiac surgery increases energy intake, with fewer side effects on cardiopulmonary function. However, impacts on weight gain and gastrointestinal function remain unclear. AIMS AND OBJECTIVES: To determine the impact of HF compared with standard formula on weight gain and gastrointestinal tolerance in postoperative infants with congenital heart disease. DESIGN: This was a randomized controlled trial. METHODS: The setting of the study was at a 20-bed cardiac intensive care unit at a tertiary children's hospital in China. Study population included infants <1 year of age who underwent cardiac surgery and were allocated to the intervention group (n = 32) or control group (n = 32). The intervention group received HF (100 kcal/100 mL), and the control group received standard formula (67 kcal/100 mL) for 7 days during the stabilized postoperative period at the cardiac intensive care unit. Primary outcomes were weight gain and gastrointestinal intolerance. Secondary outcomes were energy intake and standard intensive care characteristics. RESULTS: Infants who received HF (n = 30) showed less weight loss than those who received standard formula (n = 29); -16 g [95% confidence interval (CI): -74 to 42] versus -181 g (95% CI: -264 to -99), P = 0·001. The evaluation of gastrointestinal intolerance showed that the intervention group had several side effects, such as abdominal distension (n = 1), gastric retention (n = 2) and diarrhoea (n = 1), while the control group had no problems. Enteral energy intake in the intervention group was higher than the control group from day three. CONCLUSION: Infants after cardiac surgery fed with HF gained more weight but had increased feeding intolerance. However, the feeding intolerance symptoms could be relieved by medication and did not affect feeding advancement. RELEVANCE TO CLINICAL PRACTICE: Paediatric intensive care clinicians should consider gradually increasing the energy density of the formula during feeding and assess feeding intolerance signs in some children with malnutrition after cardiac surgery.

Comparison of Stem Cell Transplantation Using Unrelated, Haploidentical, and Sibling Donors for Patients with Acquired Severe Aplastic Anemia: A Single-Center Retrospective Cohort Study.

The preferred donor (haploidentical donor [HID] versus matched unrelated donor [URD]) choice in patients with acquired severe aplastic anemia (SAA) who lack an HLA-matched sibling donor (MSD) and fail upfront immunosuppressive treatment (IST) therapy is unknown. We retrospectively investigated SAA patients (n = 58) who underwent allogeneic stem cell transplantation (allo-SCT) between January 2012 and October 2022. The 5-year overall survival (OS) and 5-year failure-free survival (FFS) were comparable among the URD (n = 8), HID (n = 25), and MSD (n = 25) cohorts (OS: mean, 87.5 ± 11.7% versus 98.0 ± 6.5% versus 83.3 ± 7.6% [P = .926]; FFS: mean, 60.0 ± 18.2% versus 87.0 ± 7.0% versus 78.3 ± 8.6% [P = .222]). Multivariate analysis revealed that primary engraftment failure independently predicted OS and secondary graft failure predicted FFS among SAA patients who underwent allo-SCT, but donor type and age were not predictive of these outcomes. An urgent second SCT for patients with engraftment failure may be an effective salvage treatment. Our findings show that an alternative donor SCT is indicated for eligible SAA patients without an MSD even if age ≥40 years.

Constructing and implementing a performance evaluation indicator set for artificial intelligence decision support systems in pediatric outpatient clinics: an observational study.

Artificial intelligence (AI) decision support systems in pediatric healthcare have a complex application background. As an AI decision support system (AI-DSS) can be costly, once applied, it is crucial to focus on its performance, interpret its success, and then monitor and update it to ensure ongoing success consistently. Therefore, a set of evaluation indicators was explicitly developed for AI-DSS in pediatric healthcare, enabling continuous and systematic performance monitoring. The study unfolded in two stages. The first stage encompassed establishing the evaluation indicator set through a literature review, a focus group interview, and expert consultation using the Delphi method. In the second stage, weight analysis was conducted. Subjective weights were calculated based on expert opinions through analytic hierarchy process, while objective weights were determined using the entropy weight method. Subsequently, subject and object weights were synthesized to form the combined weight. In the two rounds of expert consultation, the authority coefficients were 0.834 and 0.846, Kendall's coordination coefficient was 0.135 in Round 1 and 0.312 in Round 2. The final evaluation indicator set has three first-class indicators, fifteen second-class indicators, and forty-seven third-class indicators. Indicator I-1(Organizational performance) carries the highest weight, followed by Indicator I-2(Societal performance) and Indicator I-3(User experience performance) in the objective and combined weights. Conversely, 'Societal performance' holds the most weight among the subjective weights, followed by 'Organizational performance' and 'User experience performance'. In this study, a comprehensive and specialized set of evaluation indicators for the AI-DSS in the pediatric outpatient clinic was established, and then implemented. Continuous evaluation still requires long-term data collection to optimize the weight proportions of the established indicators.

Roles of STAT3 in the pathogenesis and treatment of glioblastoma.

Glioblastoma (GBM) is the most malignant of astrocytomas mainly involving the cerebral hemispheres and the cerebral cortex. It is one of the fatal and refractory solid tumors, with a 5-year survival rate of merely 5% among the adults. IL6/JAK/STAT3 is an important signaling pathway involved in the pathogenesis and progression of GBM. The expression of STAT3 in GBM tissues is substantially higher than that of normal brain cells. The abnormal activation of STAT3 renders the tumor microenvironment of GBM immunosuppression. Besides, blocking the STAT3 pathway can effectively inhibit the growth and metastasis of GBM. On this basis, inhibition of STAT3 may be a new therapeutic approach for GBM, and the combination of STAT3 targeted therapy and conventional therapies may improve the current status of GBM treatment. This review summarized the roles of STAT3 in the pathogenesis of GBM and the feasibility of STAT3 for GBM target therapy.

Circular RNAs: New players involved in the regulation of cognition and cognitive diseases.

Circular RNAs (circRNAs), a type of covalently closed endogenous single-stranded RNA, have been regarded as the byproducts of the aberrant splicing of genes without any biological functions. Recently, with the development of high-throughput sequencing and bioinformatics, thousands of circRNAs and their differential biological functions have been identified. Except for the great advances in identifying circRNA roles in tumor progression, diagnosis, and treatment, accumulated evidence shows that circRNAs are enriched in the brain, especially in the synapse, and dynamically change with the development or aging of organisms. Because of the specific roles of synapses in higher-order cognitive functions, circRNAs may not only participate in cognitive functions in normal physiological conditions but also lead to cognition-related diseases after abnormal regulation of their expression or location. Thus, in this review, we summarized the progress of studies looking at the role of circRNA in cognitive function, as well as their involvement in the occurrence, development, prognosis, and treatment of cognitive-related diseases, including autism, depression, and Alzheimer's diseases.

Sequential autologous and allogeneic stem cell transplantation for treatment of primary plasma cell leukemia: A case report.

Primary plasma cell leukemia (pPCL) is a rare and aggressive form of plasma cell disorder, which accounts for ~70% of all PCL. Survival of pPCL remains poor, and is related with early mortality. There is no standard therapy for patients with pPCL. In the present study, a 26-year-old man who was diagnosed with pPCL was reported. The patient achieved stringent complete remission to the successful treatment of intensive chemotherapy combined with sequential autologous and allogeneic stem cell transplantation (SCT) followed by maintenance therapy with oral administration of ixazomib, thalidomide and dexamethasone (IRD regimen). Development of complex treatment algorithms that combine novel agents, SCT and post-transplantation remission strategies may translate into survival in patients with pPCL.

Efficacy and safety of immune checkpoint inhibitors with or without radiotherapy in metastatic non-small cell lung cancer: A systematic review and meta-analysis.

Background and purpose: Although immune checkpoint inhibitors (ICIs) have become the first-line treatment for metastatic non-small cell lung cancer (mNSCLC), their efficacy is limited. Meanwhile, recent reports suggest that radiotherapy (RT) can activate the systemic antitumor immune response by increasing the release of antigens from tumor tissues. Therefore, in patients with mNSCLC treated with ICIs, investigations were performed to determine whether the addition of RT improved the outcomes. Furthermore, the adverse events rate was evaluated. Methods and materials: Pubmed, Embase, and Cochrane Library were searched using the keywords "radiotherapy," "immune checkpoint inhibitors," and "non-small cell lung cancer" from the date of inception to 2 May 2022. Randomized controlled trials (RCTs) and nonRCTs (NRCTs) comparing the efficacy and safety of RT combined with ICIs versus ICIs alone in metastatic NSCLC were assessed. The primary outcomes were progression-free survival (PFS) and overall survival (OS), and the secondary outcomes were abscopal response rate (ARR), abscopal control rate (ACR), adverse events rate, and pneumonia rate. The analyses were conducted using the Mantel-Haenszel fixed-effects or random-effects model. The I2 statistic was used to determine heterogeneity, whereas funnel plots and Egger's test were used to assess publication bias. Results: In 15 clinical studies, 713 patients received RT combined with ICIs and 1,275 patients received only ICIs. With regard to PFS and OS, the hazard ratios of RT combined with ICIs were 0.79 (0.70, 0.89) and 0.72 (0.63, 0.82), respectively. In terms of ARR and ACR, the odds ratios (ORs) of RT combined with ICIs were 1.94 (1.19, 3.17) and 1.79 (1.08, 2.97), respectively. Subgroup analyses based on study type (RCT/NRCT), RT target (intracranial/extracranial), number of RT sites (single site), previous ICI resistance (yes/no), and sequencing of RT and ICIs (concurrent/post-RT ICIs) revealed that the addition of RT significantly prolonged PFS and OS. However, subgroup analyses based on radiation dose/fractionation indicated that the addition of hypofractionated RT significantly prolonged OS but not PFS. When grouped according to the level of PD-L1 expression, the addition of RT prolonged PFS only in patients who were PD-L1-negative. Furthermore, subgroup analyses of ARR and ACR signified that the combination therapy resulted in better local control of lesions outside the irradiation field in the hypofractionated RT, extracranial RT, and ICI-naïve subgroups. In terms of adverse events, the addition of RT did not significantly increase the adverse events rate but was associated with a higher pneumonia rate [OR values were 1.24 (0.92, 1.67) and 1.76 (1.12, 2.77), respectively]. Conclusion: Meta-analysis of existing data suggests that the addition of RT can significantly prolong PFS and OS in patients with metastatic NSCLC receiving ICIs. In addition to lesions in the irradiation field, RT can improve the local control rate of lesions outside the irradiation field via immune activation. Combination therapy does not increase the overall risk of adverse reactions, except for pneumonia.

Comparative survey among paediatricians, nurses and health information technicians on ethics implementation knowledge of and attitude towards social experiments based on medical artificial intelligence at children's hospitals in Shanghai: a cross-sectional study.

OBJECTIVES: Implementing ethics is crucial to prevent harm and promote widespread benefits in social experiments based on medical artificial intelligence (MAI). However, insufficient information is available concerning this within the paediatric healthcare sector. We aimed to conduct a comparative survey among paediatricians, nurses and health information technicians regarding ethics implementation knowledge of and attitude towards MAI social experiments at children's hospitals in Shanghai. DESIGN AND SETTING: A cross-sectional electronic questionnaire was administered from 1 July 2022 to 31 July 2022, at tertiary children's hospitals in Shanghai. PARTICIPANTS: All the eligible individuals were recruited. The inclusion criteria were as follows: (1) should be a paediatrician, nurse and health information technician, (2) should have been engaged in or currently participating in social experiments based on MAI, and (3) voluntary participation in the survey. PRIMARY OUTCOME: Ethics implementation knowledge of and attitude to MAI social experiments among paediatricians, nurses and health information technicians. RESULTS: There were 137 paediatricians, 135 nurses and 60 health information technicians who responded to the questionnaire at tertiary children's hospitals. 2.4-9.6% of participants were familiar with ethics implementation knowledge of MAI social experiments. 31.9-86.1% of participants held an 'agree' ethics implementation attitude. Health information technicians accounted for the highest proportion of the participants who were familiar with the knowledge of implementing ethics, and paediatricians or nurses accounted for the highest proportion among those who held 'agree' attitudes. CONCLUSIONS: There is a significant knowledge gap and variations in attitudes among paediatricians, nurses and health information technicians, which underscore the urgent need for individualised education and training programmes to enhance MAI ethics implementation in paediatric healthcare.

The Global, Regional, and National Burden of Adult Lip, Oral, and Pharyngeal Cancer in 204 Countries and Territories: A Systematic Analysis for the Global Burden of Disease Study 2019.

Importance: Lip, oral, and pharyngeal cancers are important contributors to cancer burden worldwide, and a comprehensive evaluation of their burden globally, regionally, and nationally is crucial for effective policy planning. Objective: To analyze the total and risk-attributable burden of lip and oral cavity cancer (LOC) and other pharyngeal cancer (OPC) for 204 countries and territories and by Socio-demographic Index (SDI) using 2019 Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study estimates. Evidence Review: The incidence, mortality, and disability-adjusted life years (DALYs) due to LOC and OPC from 1990 to 2019 were estimated using GBD 2019 methods. The GBD 2019 comparative risk assessment framework was used to estimate the proportion of deaths and DALYs for LOC and OPC attributable to smoking, tobacco, and alcohol consumption in 2019. Findings: In 2019, 370 000 (95% uncertainty interval [UI], 338 000-401 000) cases and 199 000 (95% UI, 181 000-217 000) deaths for LOC and 167 000 (95% UI, 153 000-180 000) cases and 114 000 (95% UI, 103 000-126 000) deaths for OPC were estimated to occur globally, contributing 5.5 million (95% UI, 5.0-6.0 million) and 3.2 million (95% UI, 2.9-3.6 million) DALYs, respectively. From 1990 to 2019, low-middle and low SDI regions consistently showed the highest age-standardized mortality rates due to LOC and OPC, while the high SDI strata exhibited age-standardized incidence rates decreasing for LOC and increasing for OPC. Globally in 2019, smoking had the greatest contribution to risk-attributable OPC deaths for both sexes (55.8% [95% UI, 49.2%-62.0%] of all OPC deaths in male individuals and 17.4% [95% UI, 13.8%-21.2%] of all OPC deaths in female individuals). Smoking and alcohol both contributed to substantial LOC deaths globally among male individuals (42.3% [95% UI, 35.2%-48.6%] and 40.2% [95% UI, 33.3%-46.8%] of all risk-attributable cancer deaths, respectively), while chewing tobacco contributed to the greatest attributable LOC deaths among female individuals (27.6% [95% UI, 21.5%-33.8%]), driven by high risk-attributable burden in South and Southeast Asia. Conclusions and Relevance: In this systematic analysis, disparities in LOC and OPC burden existed across the SDI spectrum, and a considerable percentage of burden was attributable to tobacco and alcohol use. These estimates can contribute to an understanding of the distribution and disparities in LOC and OPC burden globally and support cancer control planning efforts.

Cytogenetic abnormalities in NPM1-mutated acute myeloid leukemia.

NPM1mut acute myeloid leukemia (AML) has been identified as a distinct entity of myeloid neoplasms according to the 2017 European LeukemiaNet (ELN) guidelines. It confers a favorable prognosis regardless of cytogenetic abnormalities. We evaluated 418 newly diagnosed AML patients to test the validity of this hypothesis. Seventy-four patients with NPM1mut AML showed a good response to induction and a relatively favorable prognosis. Abnormal karyotypes were observed in 15 patients. Chromosomal abnormalities were significantly associated with a worse prognosis in NPM1mut AML patients (5-year overall survival (OS): 38.9 ± 12.9%, p = .037; event-free survival (EFS): 33.3 ± 12.2%, p = .043, respectively). Four patients with abnormal karyotypes who underwent allogeneic hematopoietic stem cell transplantation (alloHSCT) during CR1 had longer survival than those who received chemotherapy only. Multivariable analysis revealed abnormal karyotypes independently predicted OS and EFS among NPM1mut AML patients. In summary, cytogenetic abnormalities are strong prognostic indicators in NPM1mut AML. Therefore, they should be classified accordingly, and alloHSCT should be performed on selected patients during CR1.

The risk factors and early predictive model of hematotoxicity after CD19 chimeric antigen receptor T cell therapy.

Hematotoxicity is the most common long-term adverse event after chimeric antigen receptor T cell (CAR-T) therapy. Here, a total of 71 patients with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) or large B-cell lymphoma (LBCL) were used to develop an early hematotoxicity predictive model and verify the accuracy of this model. The incidences of early hematotoxicity at 3 month following CAR-T infusion in B-ALL and LBCL were 45.5% and 38.5%, respectively. Multivariate analyses revealed that the severity of cytokine release syndrome (CRS) was an independent risk factor affecting early hematotoxicity. The analysis between the peak cytokine levels and early hematotoxicity suggested that tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP) were closely associated with early hematotoxicity. Then, an early predictive model of hematotoxicity was constructed based on the peak contents of TNF-α and CRP. This model could diagnose early hematotoxicity with positive predictive values of 87.7% and 85.0% in training and validation cohorts, respectively. Lastly, we constructed the nomogram for clinical practice to predict the risk of early hematotoxicity, which performed well compared with the observed probability. This early predictive model is instrumental in the risk stratification of CAR-T recipients with hematotoxicity and early intervention for high-risk patients.

Batch effects removal for microbiome data via conditional quantile regression.

Batch effects in microbiome data arise from differential processing of specimens and can lead to spurious findings and obscure true signals. Strategies designed for genomic data to mitigate batch effects usually fail to address the zero-inflated and over-dispersed microbiome data. Most strategies tailored for microbiome data are restricted to association testing or specialized study designs, failing to allow other analytic goals or general designs. Here, we develop the Conditional Quantile Regression (ConQuR) approach to remove microbiome batch effects using a two-part quantile regression model. ConQuR is a comprehensive method that accommodates the complex distributions of microbial read counts by non-parametric modeling, and it generates batch-removed zero-inflated read counts that can be used in and benefit usual subsequent analyses. We apply ConQuR to simulated and real microbiome datasets and demonstrate its advantages in removing batch effects while preserving the signals of interest.

Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life Years for 29 Cancer Groups From 2010 to 2019: A Systematic Analysis for the Global Burden of Disease Study 2019.

IMPORTANCE: The Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019) provided systematic estimates of incidence, morbidity, and mortality to inform local and international efforts toward reducing cancer burden. OBJECTIVE: To estimate cancer burden and trends globally for 204 countries and territories and by Sociodemographic Index (SDI) quintiles from 2010 to 2019. EVIDENCE REVIEW: The GBD 2019 estimation methods were used to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life years (DALYs) in 2019 and over the past decade. Estimates are also provided by quintiles of the SDI, a composite measure of educational attainment, income per capita, and total fertility rate for those younger than 25 years. Estimates include 95% uncertainty intervals (UIs). FINDINGS: In 2019, there were an estimated 23.6 million (95% UI, 22.2-24.9 million) new cancer cases (17.2 million when excluding nonmelanoma skin cancer) and 10.0 million (95% UI, 9.36-10.6 million) cancer deaths globally, with an estimated 250 million (235-264 million) DALYs due to cancer. Since 2010, these represented a 26.3% (95% UI, 20.3%-32.3%) increase in new cases, a 20.9% (95% UI, 14.2%-27.6%) increase in deaths, and a 16.0% (95% UI, 9.3%-22.8%) increase in DALYs. Among 22 groups of diseases and injuries in the GBD 2019 study, cancer was second only to cardiovascular diseases for the number of deaths, years of life lost, and DALYs globally in 2019. Cancer burden differed across SDI quintiles. The proportion of years lived with disability that contributed to DALYs increased with SDI, ranging from 1.4% (1.1%-1.8%) in the low SDI quintile to 5.7% (4.2%-7.1%) in the high SDI quintile. While the high SDI quintile had the highest number of new cases in 2019, the middle SDI quintile had the highest number of cancer deaths and DALYs. From 2010 to 2019, the largest percentage increase in the numbers of cases and deaths occurred in the low and low-middle SDI quintiles. CONCLUSIONS AND RELEVANCE: The results of this systematic analysis suggest that the global burden of cancer is substantial and growing, with burden differing by SDI. These results provide comprehensive and comparable estimates that can potentially inform efforts toward equitable cancer control around the world.