Association of physical activity trajectories over 8 years and risk of knee replacement: data from the osteoarthritis initiative.

BACKGROUND: To identify physical activity (PA) trajectories in adults with or at risk of knee osteoarthritis and to evaluate the association of PA trajectories with incident knee replacement (KR). METHODS: This study used data from the Osteoarthritis Initiative. The Physical Activity Scale for the Elderly and the KR were assessed annually from baseline to 9 years. Individuals were included if they did not undergo KR surgery at baseline and had data on PA at ≥ 1 visit before KR. Latent class growth mixture Modeling was used to identify the optimal trajectories of PA before KR. Log-binomial regression models were used to assess the association between PA trajectories and the risk of KR. Data analyses were conducted in all individuals and those with radiographic osteoarthritis (ROA) and significant knee pain (Western Ontario and McMaster Osteoarthritis Index pain score of ≥ 5 on a 0-20 scale) at baseline, respectively. RESULTS: Of 4731 participants (mean age 61.1 years, 58.5% female), four distinct and slightly declined PA trajectories were identified. Compared to individuals with a "Low" PA trajectory, those with "Medium-low", "Medium-high", or "High" PA trajectories were not significantly associated with the risk of KR (risk ratios: 0.97-1.19, all p > 0.05). Similar PA trajectories and associations with the risk of KR were observed in the subgroups of individuals with radiographic osteoarthritis and those with significant knee pain at baseline, respectively. CONCLUSION: In participants with or at risk of knee osteoarthritis, PA slightly declines over time and may play no role in the risk of KR.

Chronic pain in multiple sites is associated with cardiovascular dysfunction: an observational UK Biobank cohort study.

BACKGROUND: Chronic pain is associated with development of cardiovascular disease. We investigated the association between how widespread chronic pain is and the development of cardiovascular dysfunction. METHODS: We analysed data from participants enrolled in the UK Biobank study who underwent examinations at baseline, plus first follow-up and two imaging visits. Pain sites (including hip, knee, back, neck/shoulder, or 'all over the body') and pain duration were recorded at each visit. Chronic pain was defined as pain lasting for ≥3 months. Participants were categorised into six groups: no chronic pain, chronic pain in one, two, three, or four sites, or 'all over the body'. Arterial stiffness index was measured at each time point. Carotid intima-media thickness, cardiac index, and left ventricular ejection fraction (LVEF) were measured using ultrasound and heart MRI at two additional imaging visits in a subset of participants. Mixed-effect linear regression models were used for the analyses. RESULTS: The number of chronic pain sites was directly related to increased arterial stiffness index (n=159,360; ß=0.06 per one site increase, 95% confidence interval 0.04 to 0.08). In 23,899 participants, lower LVEF was associated with widespread chronic pain (ß=-0.17 per one site increase, 95% confidence interval -0.27 to -0.07). The number of chronic pain sites was not associated with carotid intima-media thickness (n=30,628) or cardiac index (n=23,899). CONCLUSION: A greater number of chronic pain sites is associated with increased arterial stiffness and poorer cardiac function, suggesting that widespread chronic pain is an important contributor to cardiovascular dysfunction.

Using the sympathetic system, beta blockers and alpha-2 agonists, to address acute respiratory distress syndrome.

Acute Respiratory Distress Syndrome (ARDS) manifests as an acute inflammatory lung injury characterized by persistent hypoxemia, featuring a swift onset, high mortality, and predominantly supportive care as the current therapeutic approach, while effective treatments remain an area of active investigation. Adrenergic receptors (AR) play a pivotal role as stress hormone receptors, extensively participating in various inflammatory processes by initiating downstream signaling pathways. Advancements in molecular biology and pharmacology continually unveil the physiological significance of distinct AR subtypes. Interventions targeting these subtypes have the potential to induce specific alterations in cellular and organismal functions, presenting a promising avenue as a therapeutic target for managing ARDS. This article elucidates the pathogenesis of ARDS and the basic structure and function of AR. It also explores the relationship between AR and ARDS from the perspective of different AR subtypes, aiming to provide new insights for the improvement of ARDS.

A novel prognostic index for extranodal natural killer/T-cell lymphoma in the era of pegaspargase/L-asparaginase.

Aim: This multicenter retrospective study aimed to develop a novel prognostic system for extranodal natural killer/T-cell lymphoma (ENKTL) patients in the era of pegaspargase/L-asparaginase. Materials & methods: A total of 844 newly diagnosed ENKTL patients were included. Results: Multivariable analysis confirmed that Eastern Cooperative Oncology Group performance status, lactate dehydrogenase, Chinese Southwest Oncology Group and Asia Lymphoma Study Group ENKTL (CA) system, and albumin were independent prognostic factors. By rounding up the hazard ratios from four significant variables, a maximum of 7 points were assigned. The model of Huaihai Lymphoma Working Group-Natural killer/T-cell Lymphoma prognostic index (NPI) was identified with four risk groups and the 5-year overall survival was 88.2, 66.7, 54.3 and 30.5%, respectively. Conclusion: Huaihai Lymphoma Working Group-NPI provides a feasible stratification system for patients with ENKTL in the era of pegaspargase/L-asparaginase.

[Box: see text].

Clinicopathological analysis of immunohistochemical CD47 and signal-regulatory protein-α expression in Extranodal Natural killer/T-cell lymphoma.

BACKGROUND: The interaction between CD47 and signal-regulatory protein-alpha (SIRPα) inhibits phagocytosis, and their clinicopathological characteristics have been evaluated in various diseases. However, the significance of CD47 and SIRPα expression, as well as the combined effect, in Extranodal Natural killer/T-cell Lymphoma (ENKTL) remains uncertain. METHODS: In total, 76 newly diagnosed ENKTL patients (mean age 49.9 years, 73.7% male) were included in this study. CD47 and SIRPα expression were examined by immunohistochemistry. Survival analyses were conducted through Kaplan-Meier curves and the Cox regression model. RESULTS: Seventy-one (93.4%) cases were categorized as the CD47 positive group and 59 (77.6%) cases were categorized as the SIRPα positive group. CD47-negative cases had more advanced-stage illness (P = 0.001), while SIRPα-positive cases showed significantly lower levels of high-density lipoprotein (P < 0.001). In univariable analysis, CD47, SIRPα expression, and their combination were significantly associated with prognosis (P < 0.05). In multivariable analysis, only positive SIRPα expression remained significantly associated with superior overall survival (Hazard ratio [HR] 0.446; 95% confidence interval [CI] 0.207-0.963; P = 0.004). Furthermore, SIRPα expression could re-stratify the survival of patients in ECOG (< 2), advanced CA stage, PINK (HR), CD38-positive, PD1-positive, and CD30-positive groups. CONCLUSIONS: SIRPα status was a potential independent prognostic factor for ENKTL. The prognostic significance of CD47 expression and the interaction between CD47 and SIRPα in ENKTL need further investigation.

Socioeconomic status, individual behaviors and risk for Lymphomas: a Mendelian randomization study.

Background: The association of socioeconomic status and individual behavior (SES/IB) with human health is receiving increasing attention. However, the causal effects between SES/IB and lymphomas remain unclear. Methods: A two-sample Mendelian randomization (MR) study was used to assess the causal effects of 25 SES/IB traits (dietary habits, physical activity, smoking/drinking behaviors, sleeping behaviors, leisure sedentary behaviors, risky behaviors, and reproductive behaviors) on six distinct types of lymphomas, including Hodgkin lymphoma (HL), follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), mature T/NK-cell lymphomas, marginal zone B-cell lymphoma (MZL), and mantle cell lymphoma (MCL). The inverse variance weighted (IVW) method was the primary approach used for the MR analysis. A series of sensitivity analyses were also conducted to ensure the robustness of the findings. Results: Two-sample MR revealed six SES/IB traits causally associated with lymphomas, including relative fat intake, drive time, television watching time, computer use time, vigorous physical activity, and number of children ever born. After false discovery rate (FDR) correction, the causal associations between longer television watching time and DLBCL (OR: 4.048, 95% CI: 1.688 to 9.708, P fdr=0.009), and the number of children ever born with both FL (OR: 0.008, 95% CI: 1.412E-04 to 0.484, P fdr=0.021) and DLBCL (OR: 0.001, 95% CI:1.587E-05 to 0.081, P fdr=0.002) were identified. Conclusions: These findings suggest that certain lifestyle and behavioral factors have a measurable impact on specific lymphoma types.

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.

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.

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.

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.