Impact of tocilizumab on anti-CD19 chimeric antigen receptor T-cell therapy in B-cell acute lymphoblastic leukemia.

BACKGROUND: Tocilizumab is commonly used for the management of chimeric antigen receptor (CAR) T-cell therapy-associated cytokine release syndrome (CRS). However, it remains unknown whether tocilizumab or its dosage affects the efficacy and safety of CAR T-cell therapy. The objective of this multicenter retrospective study was to explore the impact of tocilizumab on CAR T-cell therapy. METHODS: In total, 93 patients with B-cell acute lymphoblastic leukemia (B-ALL) receiving humanized anti-CD19 CAR T cells were recruited from May 2016 to November 2022. Forty-five patients received tocilizumab (tocilizumab group), whereas 48 patients did not (nontocilizumab group). Thirteen patients received >1 dose of tocilizumab. The primary end point was the effect of tocilizumab on the efficacy and safety of CAR T cells. Additionally, proliferation, killing, and cytokine assays of CAR T cells were performed in vitro in the presence of tocilizumab. RESULTS: The median age of the patients was 33 years, with 47 males and 46 females. Patients in the tocilizumab group showed similar complete response (CR) rate, overall survival (OS), and event-free survival (EFS) compared with the nontocilizumab group. Compared with patients who received ≤1 dose of tocilizumab, receiving >1 dose of tocilizumab did not affect their CR rate, OS, or EFS. In the tocilizumab group, all patients experienced CRS and 26.7% experienced immune effector cell-associated neurotoxicity syndrome (ICANS). In the nontocilizumab group, 64.6% of patients experienced CRS and 8.3% experienced ICANS. Up to 75% of ICANS and 87.5% of grade ≥3 ICANS occurred in the tocilizumab group. In vitro, tocilizumab did not impair the proliferation and killing effects of CAR T cells. CONCLUSIONS: Tocilizumab does not affect the efficacy of CAR T cells but may increase the likelihood of ICANS.

Association between air pollution and male sexual function: A nationwide observational study in China.

This study aimed to explore the associations between air pollution and male sexual function. A total of 5047 male subjects in China were included in this study. The average air pollution exposure (PM2.5, PM10, SO2, CO, NO2, and O3) for the preceding 1, 3, 6, and 12 months before the participants' response was assessed. Male sexual function was evaluated using the International Index of Erectile Function-5 (IIEF-5) and the Premature Ejaculation Diagnostic Tool (PEDT). Generalized linear models were utilized to explore the associations between air pollution and male sexual function. K-prototype algorithm was conducted to identify the association among specific populations. Significant adverse effects on the IIEF-5 score were observed with NO2 exposure during the preceding 1, 3, and 6 months (1 m: ß = -5.26E-05; 3 m: ß = -4.83E-05; 6 m: ß = -4.23E-05, P < 0.05). PM2.5 exposure during the preceding 12 months was found to significantly negatively affect the PEDT after adjusting for confounding variables. Our research indicated negative correlations between air pollutant exposures and male sexual function for the first time. Furthermore, these associations were more pronounced among specific participants who maintain a normal BMI, exhibit extroverted traits, and currently engage in smoking and alcohol consumption.

Clinicopathologic features and survival outcomes of CD30 expression in extranodal natural killer/T-cell lymphoma.

OBJECTIVES: Previous studies have been inconsistent concerning the association between the prognostic value of CD30 expression and extranodal natural killer/T-cell lymphoma (ENKTL). METHODS: CD30 expression in 82 patients with newly diagnosed ENKTL (mean age, 50 years; 73.2% male) was assessed by immunohistochemistry on paraffin-embedded sections. The level of CD30 expression was categorized into negative (0%, no staining) and positive groups. RESULTS: Sixty-seven cases exhibited positive CD30 expression, and the main between-group difference was the Chinese Southwest Oncology Group and Asia Lymphoma Study Group (CA) ENKTL stage and Eastern Cooperative Oncology Group (ECOG) performance status. The cutoff point for CD30 expression was 40% by restricted cubic splines analysis. The overall survival of patients with high expression (>40%) was statistically superior to negative (0%) and low-expression groups. A positive correlation was observed between CD30 and Epstein-Barr virus-encoded small RNA status (r = 0.305). Multivariable analysis suggested that positive CD30 expression (hazard ratio, 0.420 [95% CI, 0.193-0.914]; P = .029) and CA advanced stage (hazard ratio, 2.844 [95% CI, 1.371-5.896]; P = .005) were independent prognostic factors for ENKTL. CONCLUSIONS: Positive CD30 expression was a favorable prognostic factor for ENKTL, and CD30 expression could restratify the survival of patients in clinical subgroups.

Factors associated with trajectories of bone marrow lesions over 4 years: data from the Osteoarthritis Initiative.

OBJECTIVE: To identify bone marrow lesion (BML) trajectories over 4 years and their demographic and structural predictors in middle-aged and older adults with or at increased risk of knee osteoarthritis (OA). METHODS: A total of 614 participants (mean age 61 years, 62% female) from the Osteoarthritis Initiative cohort (OAI) were included. BMLs in 15 anatomical locations of the knee were measured annually from baseline to 4 years using the Magnetic Resonance Imaging Osteoarthritis Knee Score (MOAKS) method. BML trajectories were determined using latent class mixed models (LCMMs). Multinomial logistic regression was used to examine baseline characteristics that predicted BML trajectories. RESULTS: Three distinct BML trajectories were identified: "Mild-stable BMLs" (25.9%), "Moderate-stable BMLs" (66.4%), and "Rapid-rise BMLs" (7.7%). Compared to the "Mild-stable BMLs" trajectory, current smokers were more likely to be in the "Moderate-stable BMLs" (odds ratio [OR] 2.089, P < 0.001) and "Rapid-rise" (OR 2.462, P < 0.001) trajectories. Moreover, female sex and meniscal tears were associated with an increased risk of being in the "Rapid-rise BMLs" trajectory (OR 2.023 to 2.504, P < 0.05). Participants who had higher education levels and drank more alcohol were more likely to be in the "Rapid-rise BMLs" trajectory (OR 1.624 to 3.178, P < 0.05) and less likely to be in the "Moderate-stable BMLs" trajectory (OR 0.668 to 0.674, P < 0.05). CONCLUSIONS: During the 4-year follow-up, most participants had relatively stable BMLs, few had enlarged BMLs, and no trajectory of decreased BMLs was identified. Sociodemographic factors, lifestyle, and knee structural pathology play roles in predicting distinct BML trajectories.

Association of prediabetes progression and regression with cognitive decline: Findings from the CHARLS.

AIM: The aim of the study was to describe the association of prediabetes progression and regression with change in cognitive function. METHODS: Data from three waves (2011, 2015 and 2018) of the China Health and Retirement Longitudinal Study (CHARLS) were analysed. Diabetic statuses in 2011 and 2015 were ascertained using the American Diabetes Association criteria. Cognitive function was assessed and standardized at all three waves, where a total score and its two components (episodic memory and metal status) were calculated. We evaluated the association of prediabetes progression and regression (from 2011 to 2015) with changes in cognitive function from 2011 to 2015 and from 2015 to 2018. RESULTS: Of 2590 participants (56% women, mean age 58.6 ± 8.4 years) with prediabetes, 12% progressed to diabetes and 41% regressed to normoglycaemia. Compared with participants who remained as prediabetes, those who progressed to diabetes showed a trend to have accelerated decline in episodic memory (ß = -0.11, 95% confidence interval -0.22 to 0.003, p = 0.057). However, participants who regressed to normoglycaemia did not have less cognitive decline. Neither prediabetes progression nor regression predicted change in cognitive function from 2015 to 2018. In a separate group of participants who remained as normoglycaemia (n = 858), changes in cognitive function from 2011 to 2015 and from 2015 to 2018 were similar to those who remained as prediabetes. CONCLUSION: In people with prediabetes, progression to diabetes may be associated with accelerated cognitive decline but regression to normoglycaemia does not retard cognitive decline. Prediabetes progression and regression may not be predictive of change in cognitive function.

Advances of presepsin in sepsis-associated ARDS.

This article reviews the correlation between presepsin and sepsis and the resulting acute respiratory distress syndrome (ARDS). ARDS is a severe complication of sepsis. Despite the successful application of protective mechanical ventilation, restrictive fluid therapy, and neuromuscular blockade, which have effectively reduced the morbidity and mortality associated with ARDS, the mortality rate among patients with sepsis-associated ARDS remains notably high. The challenge lies in the prediction of ARDS onset and the timely implementation of intervention strategies. Recent studies have demonstrated significant variations in presepsin (PSEP) levels between patients with sepsis and those without, particularly in the context of ARDS. Moreover, these studies have revealed substantially elevated PSEP levels in patients with sepsis-associated ARDS compared to those with nonsepsis-associated ARDS. Consequently, PSEP emerges as a valuable biomarker for identifying patients with an increased risk of sepsis-associated ARDS and to predict in-hospital mortality.

Association of smoking with cartilage loss of knee osteoarthritis: data from two longitudinal cohorts.

BACKGROUND: Previous studies have been inconsistent concerning the association between smoking and risk of osteoarthritis (OA). This study aimed to explore the associations of smoking status and change in cartilage volume of OA in two longitudinal cohorts. METHODS: Subjects from the Osteoarthritis Initiative cohort (OAI, n = 593) and the Tasmanian Older Adult Cohort (TASOAC, n = 394) were included in this study. For both cohorts, participants were classified into three groups based on their smoking status, namely 'never', 'former', and 'current' smokers. The outcome measures were the annual rate of change of tibiofemoral cartilage volume over 2 years in OAI and of tibial cartilage volume over 2.6 years in TASOAC. Potential confounders were balanced using the inverse probability of treatment weighting (IPTW) method. RESULTS: Overall, 42.3% and 37.4% of participants were former smokers, and 5.7% and 9.3% were current smokers in the OAI and TASOAC cohorts, respectively. Compared to never smokers, neither former nor current smoking was associated with risk of the annual rate of change of tibiofemoral cartilage volume in OAI (former smoker: ß=-0.068%/year, 95% confidence interval [CI] -0.824 to 0.688, p = 0.860; current smoker: ß=-0.222%/year, 95% CI -0.565 to 0.120, p = 0.204) and tibial cartilage volume in TASOAC (former smoker: ß = 0.001%/year, 95% CI -0.986 to 0.989, p = 0.998; current smoker: ß=-0.839%/year, 95% CI -2.520 to 0.844, p = 0.329). CONCLUSIONS: Our findings from two independent cohorts consistently showed that smoking was not associated with knee cartilage loss in older adults.

Comparative analysis of clinicopathologic characteristics and prognosis between nasal and nonnasal extranodal NK/T-cell lymphoma.

BACKGROUND: The clinicopathologic characteristics and prognosis of nasal and nonnasal extranodal natural killer T-cell lymphoma (ENKTL) are considered to be different. However, the underlying features responsible for these differences are not well clarified especially in the era of asparaginase therapy. METHODS: In total, 1007 newly diagnosed ENKTL patients from 11 medical centers were included in this study. Clinicopathologic characteristics and survival data were collected. The chi-squared test and Kruskal-Wallis test were utilized for the comparison of different groups. Univariable and multivariable Cox proportional hazards models were used to screen prognostic factors. RESULTS: Overall, 869 (86.3%) patients were nasal forms. Compared to patients with nasal ENKTL, nonnasal patients were at more advanced stages and had poor performance status, bone marrow involvement, elevated serum lactate dehydrogenase (LDH), and CD56-negative status (p < 0.05). The 5-year overall survival (OS) for nasal and nonnasal patients were 65.6% and 45.0%, respectively. The OS of nasal forms patients were superior to nonnasal patients, especially in Eastern Cooperative Oncology Group performance status (ECOG PS) (≥2), advanced stage, KPI (HIR/HR), IPI (HIR/HR), PINK (HR), and high EBV DNA load groups. In patients treated with pegaspargase/L-asparaginase-based regimens, the OS of nasal patients was better than that of nonnasal patients. After adjusting the covariates of age, stage, ECOG PS score, LDH, B symptoms, and BM involvement, results showed that the nonnasal site was associated with poor survival of ENKTL. CONCLUSIONS: The clinicopathologic characteristics and prognosis of nasal and nonnasal ENKTL patients are different. Nasal forms patients had superior OS than nonnasal patients, especially in the era of asparaginase.

Causal role of immune cells in schizophrenia: Mendelian randomization (MR) study.

BACKGROUND: Complex immune-brain interactions that affect neural development, survival and function might have causal and therapeutic implications for psychiatric illnesses. However, previous studies examining the association between immune inflammation and schizophrenia (SCZ) have yielded inconsistent findings. METHODS: Comprehensive two-sample Mendelian randomization (MR) analysis was performed to determine the causal association between immune cell signatures and SCZ in this study. Based on publicly available genetic data, we explored causal associations between 731 immune cell signatures and SCZ risk. A total of four types of immune signatures (median fluorescence intensities (MFI), relative cell (RC), absolute cell (AC), and morphological parameters (MP)) were included. Comprehensive sensitivity analyses were used to verify the robustness, heterogeneity, and horizontal pleiotropy of the results. RESULTS: After FDR correction, SCZ had no statistically significant effect on immunophenotypes. It was worth mentioning some phenotypes with unadjusted low P-values, including FSC-A on NKT (ß = 0.119, 95% CI = 0.044 ~ 0.194, P = 0.002), DN (CD4-CD8-) NKT %T cell (ß = 0.131, 95% CI = 0.054 ~ 0.208, P = 9.03 × 10- 4), and SSC-A on lymphocytes (ß = 0.136, 95% CI = 0.059 ~ 0.213, P = 5.43 × 10- 4). The causal effect of SCZ IgD on transitional was estimated to 0.127 (95% CI = 0.051 ~ 0.203, P = 1.09 × 10- 3). SCZ also had a causal effect on IgD+ %B cell (ß = 0.130, 95% CI = 0.054 ~ 0.207, P = 8.69 × 10- 4), and DP (CD4+CD8+) %T cell (ß = 0.131, 95% CI = 0.054 ~ 0.207, P = 8.05 × 10- 4). Furthermore, four immunophenotypes were identified to be significantly associated with SCZ risk: naive CD4+ %T cell (OR = 0.986, 95% CI = 0.979 ~ 0.992, P = 1.37 × 10- 5), HLA DR on CD14- CD16- (OR = 0.738 (95% CI = 0.642 ~ 0.849, P = 2.00 × 10- 5), CD33dim HLA DR+ CD11b- AC (OR = 0.631, 95% CI = 0.529 ~ 0.753, P = 3.40 × 10- 7) and activated & resting Treg % CD4 Treg (OR = 0.937, 95% CI = 0.906 ~ 0.970, P = 1.96 × 10- 4). CONCLUSIONS: Our study has demonstrated the close connection between immune cells and SCZ by genetic means, thus providing guidance for future clinical research.

The prognostic value of controlling nutritional status (CONUT) score-based nomogram on extranodal natural killer/T cell lymphoma patients.

Controlling nutritional status (CONUT) score as an original nutritional assessment tool can be used to assess the prognosis of patients with a variety of malignancies. However, the predictive power of CONUT in extranodal natural killer/T cell lymphoma (ENKTL) patients has never been demonstrated. Our retrospective multicenter study aimed to explore the prognostic value of CONUT in newly diagnosed ENKTL. A total of 1085 newly diagnosed ENKTL patients between 2003 and 2021 were retrospectively retrieved. Cox proportional hazard model was used to explore the prognostic factors of overall survival (OS). The survival rate of ENKTL was evaluated using Kaplan-Meier analysis, and log-rank test was applied to the difference between groups. We investigated the prognostic performance of CONUT, the International Prognostic Index (IPI), the Korean Prognostic Index (KPI), and the Prognostic Index of Natural Killer Cell Lymphoma (PINK) using the receiver operating characteristic (ROC) curve and decision curve analysis (DCA). The median age at diagnosis for the whole cohort was 47 years, and the male to female ratio was 2.2:1. The 5-year OS for all patients was 72.2%. Multivariable analysis showed that CONUT, age, bone marrow involvement, ECOG PS score, and Chinese Southwest Oncology Group and Asia Lymphoma Study Group ENKTL stage were identified as independent predictive factors for OS. Based on multivariable results, a prognostic nomogram was developed. Subgroup analysis demonstrated that patients with severe malnutrition had poorest clinical outcome. In addition, ROC curves and DCA analysis proved that compared with IPI, KPI, and PINK models, the CONUT score-based nomogram showed a better prognostic predictive efficiency of ENKTL. CONUT could effectively stratify the prognosis of ENKTL and the proposed nomogram based on CONUT was an effective prognostic model for prediction.

A novel prognostic model based on ferritin and nomogram-revised risk index could better stratify patients with extranodal natural killer/T-cell lymphoma.

BACKGROUND: Extranodal natural killer (NK)/T-cell lymphoma (ENKTCL) is an aggressive lymphoma with marked heterogeneity, resulting in a distinct prognosis even in patients with the same disease stage. The nomogram-revised risk index (NRI) has been proposed to stratify patients with ENKTCL. Numerous reports have revealed the prognostic role of serum ferritin in various cancers. PURPOSE: We aimed to evaluate the role of NRI in our single cohort of patients with ENKTCL treated uniformly, explore the prognostic value of ferritin, and establish a new prognostic model to better stratify patients with ENKTCL. METHODS: We included 326 patients with ENKTCL with detailed data regarding clinical characteristics and survival outcomes. All patients were treated with asparaginase-based chemotherapy with or without radiotherapy. Multiple R packages were used to analyze the prognostic factors and derive a novel prognostic model. RESULTS: In the training cohort comprising 236 patients with ENKTCL, NRI significantly correlated with progression-free survival (PFS) and overall survival (p < 0.0001). Using a ferritin level of 400 µg/L as the cutoff value, patients with high ferritin levels had significantly inferior PFS (p = 0.00028). Integrating the NRI score and four easily accessible clinical parameters, namely ferritin, hemoglobin, albumin, and D-dimer, a new prognostic model was constructed, stratifying patients with ENKTCL into three risk groups. This new prognostic model was independent of disease stage and NRI and performed better than NRI. Furthermore, this model helped to stratify patients within the same NRI risk groups. Finally, the role of this novel prognostic model was validated in the external validation cohort comprising 90 patients with ENKTCL. CONCLUSIONS: Serum ferritin level could be a novel prognostic factor in patients with ENKTCL. The new prognostic model combining NRI and clinical parameters could better predict the prognosis of ENKTCL, thereby warranting further validation and potentially guiding individualized treatment in future prospective clinical trials.

Disparity Analysis of Clinical Features and Prognostic Evaluation of Hemophagocytic Lymphohistiocytosis in Pediatric and Adult Patients: A Retrospective Multicenter Study of 525 Cases in HHLWG.

INTRODUCTION: Hemophagocytic lymphohistiocytosis (HLH) is a rare immune disorder with rapid progression and high mortality. There have been few large cohort study comparisons of pediatric and adult HLH until now. This study was designed to explore the disparity of clinical presentations and evaluate the prognosis in pediatric and adult HLH patients. METHODS: Totally, 525 newly diagnosed HLH patients were included and divided into 4 groups according to age: <6, 6-18, 18-60, and >60 years (geriatric patients). Mann-Whitney U test, Kruskal-Wallis test, χ2 test, and Bonferroni's adjustment were used to explore the difference between age groups. Overall survival (OS) was estimated by using Kaplan-Meier method. The Cox proportional hazard model was used to analyze the univariable and multivariable association between prognostic factors and OS. RESULTS: Geriatric patients had the lowest levels of hemoglobin, platelet, albumin, and the highest level of creatinine, while patients <6 years of age had the lowest values of fibrinogen, IgA, IgM and highest values of triglyceride. The trigger of HLH in patients <18 years of age was mainly EBV infection. However, lymphoma and non-EBV-driven infection were the more frequent drivers in patients aged 18-60 and >60 years, respectively. Geriatric patients were associated with highest mortality (58.8%), and 5-year OS was 43%. By contrast, 5-year OS of patients <6, 6-18, and 18-60 years was 86.1%, 74%, and 58.9%, respectively. Additionally, among patients with different etiologies (EBV, non-EBV-driven infection, and uncertain causes) and treatment regimens (HLH-04, HLH-94, and glucocorticoid regimen), geriatric patients showed lowest 5-year OS. Multivariate analysis revealed that creatinine and alanine aminotransferase were independent risk factors affecting the survival of patients aged 0-6 years, while albumin and IgG were independent factors affecting survival of geriatric patients. CONCLUSION: Our study showed a wide heterogeneity of clinical presentations, etiology distribution, prognostic factors, and survival outcomes in pediatric and adult HLH patients.

Prognostic value of prognostic nutritional index on extranodal natural killer/T-cell lymphoma patients: A multicenter propensity score matched analysis of 1022 cases in Huaihai Lymphoma Working Group.

Prognostic nutritional index (PNI), comprised of serum albumin level and lymphocyte count, is associated with the prognosis of several malignant diseases, while the prognostic value of PNI in extranodal natural killer/T cell lymphoma, nasal type (ENKTL) remains unclear. This retrospective multicenter study aimed to investigate the value of PNI in predicting the prognosis of newly diagnosed ENKTL patients by using propensity score matched analysis (PSM). A total of 1022 newly diagnosed ENKTL patients were retrieved from Huaihai Lymphoma Working Group and clinicopathological variables were collected. MaxStat analysis was used to calculate the optimal cut-off points of PNI and other continuous variables. The median age at diagnosis was 47 years and 69.4% were males, with the 5-year OS of 71.7%. According to the MaxStat analysis, 41 was the optimal cut-off point for PNI. The Pseudo R2 before matching was 0.250, and it decreased to less than 0.019 after matching. Confounding factors of the two groups were well balanced after PSM. Multivariable analysis revealed that PNI, Korean Prognostic Index (KPI), eastern cooperative oncology group performance status (ECOG PS), the prognostic index of natural killer lymphoma (PINK) and hemoglobin were independent prognostic factors for ENKTL. The results of subgroup analysis demonstrated that patients with low PNI could predict worse prognosis and re-stratify patients in ECOG PS ≥ 2, EBER-positive, the International Prognostic Index (IPI) (HIR + HR), and PINK (HR) groups. PNI combined with IPI, PINK and KPI could improve the prediction efficiency. In conclusion, PNI could accurately stratify the prognosis of ENKTL by PSM analysis and patients with low PNI had poorer prognosis.

Prevalence and the age of onset patterns of stroke in Jiangsu Province, China.

OBJECTIVES: Little was known regarding the current age of onset patterns of stroke. This study aimed to examine the prevalence of stroke and explore the age of onset patterns of stroke in Jiangsu Province, China. MATERIALS AND METHODS: Participants were recruited from April 2012 to April 2013 in Jiangsu Province, China. Survival analysis models were used to evaluate the hazards of stroke by a single year of age. Kaplan-Meier analysis and the log-rank test were used to explore the disparities of the age of onset patterns of stroke. RESULTS: This population-based study was conducted among 39,887 participants aged ≥ 18 years in Jiangsu Province, China. Of the 740 (1.9%) events of stroke, 13.2% suffered from hemorrhagic stroke (HS) and 86.8% suffered from ischemic stroke (IS). The prevalence of HS and IS were 0.3% and 1.7%, respectively. The estimated mean age of onset of stroke was 71.98 (95% CI: 71.97-71.99) years by the survival model. Up to age of 45 years, the estimated hazards of stroke onset were at a relatively low level. From the age of 45 years, the increases in hazards accelerated and peaked at age 75 years. Urban, smoking, and drinking males had a higher risk of stroke than their counterparts (P < 0.05). However, no such difference was found among females. CONCLUSIONS: The findings emphasize the importance of implementing stroke prevention interventions in Jiangsu Province, China, especially for urban, smoking, and drinking males. It is of great significance to strengthen comprehensive management of health-related behaviors, including smoking cessation and moderate consumption of alcohol to have sustained beneficial effects on stroke risk. Chenlu He and Qian Chen contributed equally to this work.

[Establishment and verification of LIPS score combined with APACHE II score and oxygenation index to predict the occurrence model of ARDS].

OBJECTIVE: To construct and verify the occurrence model of acute respiratory distress syndrome (ARDS) using lung injury prediction score (LIPS) combined with acute physiology and chronic health evaluation II (APACHE II) score and oxygenation index (PaO2/FiO2). METHODS: Using a prospective cohort study method, 244 patients with complete medical records who were admitted to the intensive care unit (ICU) of Peking University Third Hospital from December 2020 to July 2022 were selected as research objects according to the inclusion and exclusion criteria. They were divided into training set (173 cases) and validation set (71 cases). Patients' gender, age, body mass index (BMI), various causes (shock, sepsis, craniocerebral injury, pulmonary contusion, multiple trauma, aspiration, pneumonia, acute abdomen, hypoproteinemia, acidosis, major surgery, etc.), underlying diseases (diabetes, malignant tumor, cerebrovascular disease, liver disease, kidney disease) and laboratory test indicators were collected. According to the above data, the LIPS score, APACHE II score, sequential organ failure assessment (SOFA) and PaO2/FiO2, etc within 24 hours after admission to the ICU were calculated. Univariate analysis was used to screen the influencing factors for the occurrence of ARDS, and the factors with P < 0.2 were included in the multivariate Logistic regression analysis to screen out the independent predictive factors for the occurrence of ARDS. According to the results of multivariate Logistic regression analysis, the risk score of patients with ARDS was obtained to construct the risk prediction model of ARDS, the receiver operator characteristic curve (ROC curve) was drawn, and the area under the ROC curve (AUC) was calculated. The established ARDS prediction model was externally validated, and ROC curves were drawn to evaluate the predictive accuracy of the prediction model for the occurrence of ARDS in critically ill patients, and the AUC of the validation set was calculated to analyze the predictive performance of each risk factor on the occurrence of ARDS. RESULTS: A total of 173 patients were enrolled in the training set, including 121 patients without ARDS and 52 patients with ARDS; 77 cases of acute abdomen, 64 cases of sepsis, 60 cases of shock, 51 cases of acidosis, 40 cases of hypoproteinemia, 37 cases of diabetes, 34 cases of craniocerebral injury, 34 cases of abnormal liver function, 28 cases of multiple trauma, 23 cases of malignant tumor, 23 cases of spinal orthopedic surgery, 17 cases of obesity, 12 cases of pneumonia, 11 cases of pulmonary contusion, and 7 cases of chronic kidney disease, chemotherapy in 6 cases, and aspiration in 2 cases. The rates of shock, sepsis, acute abdomen, acidosis, abnormal liver function, lung contusion, pneumonia and aspiration, gender, age, LIPS score, APACHE II score, and SOFA score in the ARDS group were significantly higher than those in the non-ARDS group (all P < 0.05), moreover, PaO2/FiO2 ratio was significantly lower than that of non-ARDS group (P < 0.01). Multivariate Logistic regression analysis showed that LIPS score, APACHE II score, and PaO2/FiO2 ratio were independent risk factors for ARDS in ICU patients with high risk factors for ARDS, and the odds ratio (OR) was 1.768 [95% confidence interval (95%CI) was 1.380-2.266], 1.242 (95%CI was 1.089-1.417), 0.985 (95%CI was 0.978-0.991), all P < 0.05. ROC curve analysis showed that the AUC of the ARDS prediction model training set was 0.920, the sensitivity was 86.5%, and the specificity was 86.8%; the AUC of the verification set was 0.896, the sensitivity was 96.8%, and the specificity was 76.6%. CONCLUSIONS: LIPS score, APACHE II score and PaO2/FiO2 are independent risk factors for the occurrence of ARDS in ICU patients with high risk factors for ARDS. The ARDS risk prediction model established based on these three indicators has a good predictive ability for the occurrence of ARDS in critically ill patients, wihich needs to be verified by multicenter cohort studies.

LASSO Model Better Predicted the Prognosis of DLBCL than Random Forest Model: A Retrospective Multicenter Analysis of HHLWG.

Background: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous non-Hodgkin's lymphoma with great clinical challenge. Machine learning (ML) has attracted substantial attention in diagnosis, prognosis, and treatment of diseases. This study is aimed at exploring the prognostic factors of DLBCL by ML. Methods: In total, 1211 DLBCL patients were retrieved from Huaihai Lymphoma Working Group (HHLWG). The least absolute shrinkage and selection operator (LASSO) and random forest algorithm were used to identify prognostic factors for the overall survival (OS) rate of DLBCL among twenty-five variables. Receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were utilized to compare the predictive performance and clinical effectiveness of the two models, respectively. Results: The median follow-up time was 43.4 months, and the 5-year OS was 58.5%. The LASSO model achieved an Area under the curve (AUC) of 75.8% for the prognosis of DLBCL, which was higher than that of the random forest model (AUC: 71.6%). DCA analysis also revealed that the LASSO model could augment net benefits and exhibited a wider range of threshold probabilities by risk stratification than the random forest model. In addition, multivariable analysis demonstrated that age, white blood cell count, hemoglobin, central nervous system involvement, gender, and Ann Arbor stage were independent prognostic factors for DLBCL. The LASSO model showed better discrimination of outcomes compared with the IPI and NCCN-IPI models and identified three groups of patients: low risk, high-intermediate risk, and high risk. Conclusions: The prognostic model of DLBCL based on the LASSO regression was more accurate than the random forest, IPI, and NCCN-IPI models.

Visceral fat area and albumin based nutrition-related prognostic index model could better stratify the prognosis of diffuse large B-cell lymphoma in rituximab era.

Background: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease and the existing prognosis systems based on clinical variables are difficult to stratify patients accurately. Nutritional indices play a meaningful role in prognosis of solid tumors, whereas the effect on DLBCL is still equivocal. This retrospective study aimed to develop a novel model based on nutritional indices and other clinical variables to accurately differentiate the prognosis of DLBCL. Methods: A total of 129 patients pathologically diagnosed with DLBCL in Affiliated Hospital of Xuzhou Medical University from 2014 to 2018 were retrospectively recruited. The total fat area (TFA), visceral fat area (VFA) and subcutaneous fat area (SFA) at the third lumbar vertebra level spine were obtained by computed tomography (CT) to assess the effect of nutritional status on the prognosis of DLBCL. Principal component analysis was used to reduce the dimension of nutritional indices, and continuous variables were evaluated according to X-Tile and Restricted cubic spline. Univariable and multivariable Cox proportional hazard analyses were performed on potential variables. Kaplan-Meier method was utilized to evaluate survival probabilities and the differences between groups were assessed by log-rank test. Results: X-Tile analysis divided VFA and albumin into two and three groups when applying 114.7 cm2 of VFA, 38.3 and 42.4 g/L of albumin as the optimal cut-off points, respectively. The final scoring model of nutrition-related prognostic index (NPI) comprised four independent prognostic variables. The C-index of the final model was 0.823 [95% CI (0.749~0.897)] by bootstrap resampling. Finally, a maximum score of 6 points was obtained. Compared with IPI, NCCN-IPI and GELTAMO-IPI, NPI showed better accuracy in discerning the prognostic risk of patients. Conclusion: VFA and albumin were associated with the prognosis of DLBCL, and the NPI model based on nutritional indices could better stratify the prognosis of DLBCL.

Clinicopathologic Features and Genomic Signature of De Novo CD5 + Diffuse Large B-Cell Lymphoma : A Multicenter Collaborative Study.

De novo CD5 + diffuse large B-cell lymphoma (DLBCL) has poor survival in the era of immunochemotherapy. Accurate gene-based typing and prognostic stratification can enhance the development of effective individualized treatments. Therefore, we conducted a multicenter retrospective study to evaluate the clinicopathologic characteristics, genomic profiles, and prognostic parameters of 61 patients with CD5 + DLBCL and 60 patients with CD5 - DLBCL, with the goal of facilitating accurate prognostic stratification and potential individualized treatment strategies. Compared with patients with CD5 - DLBCL, older age, advanced stage, higher incidence of central nervous system involvement, and MYC/BCL-2 and p53 overexpression were more prevalent in CD5 + DLBCL. Most patients with CD5 + DLBCL had lymph nodes with non-germinal center B-cell-like or activated B-cell-like subtype according to immunohistochemistry or Lymph2Cx assay. Next-generation sequencing showed that the proportion of MCD subtype (based on the co-occurrence of MYD88 and CD79B mutations) in the CD5 + DLBCL cohort was higher than that in the CD5 - DLBCL cohort (54.2% vs. 13.0%, P =0.005). Compared with the CD5 - cohort, CD5 + DLBCL patients showed poor 5-year overall survival (70.9% vs. 39.0%, P <0.001). Kaplan-Meier survival analysis indicated that cell of origin, MYC/BCL-2, p53, and BCL-6 expression did not have a prognostic impact on patients with CD5 + DLBCL. Multivariate analysis showed that age above 76 years, advanced stage, higher incidence of central nervous system involvement, and hypoalbuminemia were independent factors for poor prognosis in CD5 + DLBCL patients. In summary, CD5 + DLBCL displays poor prognosis, distinctive clinicopathologic characteristics and predominant genetic features of activated B-cell-like and MCD subtypes with worse survival outcome.

Disparity Analysis of Clinicopathologic Hallmarks between Transformed DLBCL and Primary DLBCL.

BACKGROUND: A variety of indolent lymphomas, particularly marginal zone lymphoma (MZL) and follicular lymphoma (FL) can be histologically transformed to diffuse large B-cell lymphoma (DLBCL). Little is known about the disparity of clinicopathologic characteristics between transformed DLBCL (tDLBCL) and primary DLBCL (pDLBCL). METHODS: This retrospective study analyzed the clinicopathological hallmarks of 10 tDLBCL (7 MZL and 3 FL) and 40 pDLBCL from the Affiliated Hospital of Xuzhou Medical University. RESULTS: Patients of tDLBCL had a higher ECOG score, more B-symptoms, and lower serum albumin level than those in pDLBCL (60.0% vs. 7.50%, 40.0% vs. 10.0%, and 90.0% vs. 10.0%, respectively, p < 0.01). Pathologically, tDLBCL had more c-Myc and BCL-2 dual-expression than that in pDLBCL (60.0% vs. 25.0%, p < 0.01). The positive rate of CD5 expression and the proportion of high Ki-67 score in tDLBCL were higher than those in pDLBCL (50.0% vs. 7.5%, 50.0% vs. 32.5%, respectively, p < 0.01). The median overall survival and progression-free survival were 14 months and 11 months in tDLBCL, 35 months and 28 months in pDLBCL (p < 0.05 and p < 0.001). CONCLUSIONS: Our results demonstrate that tDLBCL manifested aggressive clinical course and pathological features of Myc/BCL-2 expression, CD5 expression, and high Ki-67 score.

Value of the prognostic nutritional index (PNI) in patients with newly diagnosed, CD5-positive diffuse large B-cell lymphoma: A multicenter retrospective study of the Huaihai Lymphoma Working Group.

BACKGROUND: CD5-positive diffuse large B-cell lymphoma (DLBCL) is a clinically rare subtype of DLBCL with aggressive clinical manifestations and a poor prognosis. It has been demonstrated that the prognostic nutritional index (PNI), an indicator of nutritional status and systemic inflammation, is a significant prognostic factor for several types of lymphoma. The objective of this multicenter retrospective study was to explore the prognostic value of the PNI in patients with CD5-positive DLBCL. METHODS: In total, 207 patients with CD5-positive DLBCL were recruited from 11 centers of the Huaihai Lymphoma Working Group. Maximally selected rank statistics analysis was used to identify optimal cutoff points for the PNI. A Cox proportional hazards model was used for univariable and multivariable analyses. Kaplan-Meier curves were used to calculate survival rates and draw survival curves, and the log-rank test was used to compare differences between groups. RESULTS: The median age at diagnosis was 61 years, and the 5-year overall survival rate was 47.5%. According to the maximally selected rank statistics analysis, a score of 49.7 was the optimal cutoff point for the PNI. Subgroup analysis showed that the PNI could re-stratify patients in BCL-2-negative, MYC-negative, high-intermediate-risk and high-risk International Prognostic Index, BCL-6-positive and BCL-6-negative, high Ki-67 score (≥0.9), Ann Arbor stage III/IV, Eastern Cooperative Oncology Group performance status ≥2, and germinal center B subgroups. Multivariable analysis revealed that PNI, age, Eastern Cooperative Oncology Group performance status, albumin level, and red blood cell count were independent prognostic factors for CD5-positive DLBCL. CONCLUSIONS: The PNI was a significant prognostic indicator for CD5-positive DLBCL and was able to re-stratify the prognosis for clinicopathologic subgroups of patients with CD5-positive DLBCL.