A Novel Inflammatory-Nutritional Prognostic Scoring System for Patients with Diffuse Large B Cell Lymphoma.

Purpose: This study aimed to examine the predictive ability of inflammatory and nutritional markers and further establish a novel inflammatory nutritional prognostic scoring (INPS) system. Patients and Methods: We collected clinicopathological and baseline laboratory data of 352 patients with DLBCL between April 2010 and January 2023 at the First affiliated hospital of Ningbo University. Eligible patients were randomly divided into training and validation cohorts (n = 281 and 71, respectively) in an 8:2 ratio. We used the least absolute shrinkage and selection operator (LASSO) Cox regression model to determine the most important factors among the eight inflammatory-nutritional variables. The impact of INPS on OS was evaluated using the Kaplan-Meier curve and the Log rank test. A prognostic nomogram was developed based on the multivariate Cox regression method. Then, we used the concordance index (C-index), calibration plot, and time-dependent receiver operating characteristic (ROC) analysis to evaluate the prognostic performance and predictive accuracy of the nomogram. Results: Seven inflammatory-nutritional biomarkers, including neutrophil-lymphocyte ratio (NLR), prognostic nutritional index (PNI), body mass index (BMI), monocyte-lymphocyte ratio (MLR), prealbumin, C reactive protein, and D-dimer were selected using the LASSO Cox analysis to construct INPS, In the multivariate analysis, IPI-High-intermediate group, IPI-High group, high INPS were independently associated with OS, respectively. The prognostic nomogram for overall survival consisting of the above two indicators showed excellent discrimination. The C-index for the nomogram was 0.94 and 0.95 in the training and validation cohorts. The time-dependent ROC curves showed that the predictive accuracy of the nomogram for OS was better than that of the NCCN-IPI system. Conclusion: The INPS based on seven inflammatory-nutritional indexes was a reliable and convenient predictor of outcomes in DLBCL patients.

Minimal residual disease status improved the response evaluation in patients with Waldenström's macroglobulinemia.

Introduction: Minimal residual disease (MRD) has been recognized as an important prognostic factor of survival in patients with hematological malignancies. However, the prognostic value of MRD in Waldenström macroglobulinemia (WM) remains unexplored. Methods: We analyzed 108 newly diagnosed WM patients receiving systematic therapy and assessed for MRD by multiparameter flow cytometry (MFC) using bone marrow samples. Results: Of the total patients, 34 (31.5%) achieved undetectable MRD (uMRD). A hemoglobin level of >115 g/L (P=0.03), a serum albumin level of >35 g/L (P=0.01), a ß2-MG level of ≤3 mg/L (P=0.03), and a low-risk International Prognostic Scoring System for WM (IPSSWM) stage (P<0.01) were associated with a higher rate of uMRD. Improvements in monoclonal immunoglobulin (P<0.01) and hemoglobin (P=0.03) levels were more evident in uMRD patients compared with that in MRD-positive patients. The 3-year progression-free survival (PFS) was better in uMRD patients compared with that in MRD-positive patients (96.2% vs. 52.8%; P=0.0012). Landmark analysis also showed that uMRD patients had better PFS compared with MRD-positive patients after 6 and 12 months. Patients who achieved partial response (PR) and uMRD had a 3-year PFS of 100%, which was significantly higher than that of patients with MRD-positive PR (62.6%, P=0.029). Multivariate analysis showed that MRD positivity was an independent factor of PFS (HR: 2.55, P=0.03). Moreover, the combination of the 6th International Workshop on WM assessment (IWWM-6 Criteria) and MRD assessment had a higher 3-year AUC compared with the IWWM-6 criteria alone (0.71 vs. 0.67). Discussion: MRD status assessed by MFC is an independent prognostic factor for PFS in patients with WM, and its determination could improve the precision of response evaluation, especially in patients who achieved PR.

Increased Expression of SRSF1 Predicts Poor Prognosis in Multiple Myeloma.

Background: Multiple myeloma (MM) is a clonal plasma cell disorder which still lacks sufficient prognostic factors. The serine/arginine-rich splicing factor (SRSF) family serves as an important splicing regulator in organ development. Among all members, SRSF1 plays an important role in cell proliferation and renewal. However, the role of SRSF1 in MM is still unknown. Methods: SRSF1 was selected from the primary bioinformatics analysis of SRSF family members, and then we integrated 11 independent datasets and analyzed the relationship between SRSF1 expression and MM clinical characteristics. Gene set enrichment analysis (GSEA) was conducted to explore the potential mechanism of SRSF1 in MM progression. ImmuCellAI was used to estimate the abundance of immune infiltrating cells between the SRSF1high and SRSF1low groups. The ESTIMATE algorithm was used to evaluate the tumor microenvironment in MM. The expression of immune-related genes was compared between the groups. Additionally, SRSF1 expression was validated in clinical samples. SRSF1 knockdown was conducted to explore the role of SRSF1 in MM development. Results: SRSF1 expression showed an increasing trend with the progression of myeloma. Besides, SRSF1 expression increased as the age, ISS stage, 1q21 amplification level, and relapse times increased. MM patients with higher SRSF1 expression had worse clinical features and poorer outcomes. Univariate and multivariate analysis indicated that upregulated SRSF1 expression was an independent poor prognostic factor for MM. Enrichment pathway analysis confirmed that SRSF1 takes part in the myeloma progression via tumor-associated and immune-related pathways. Several checkpoints and immune-activating genes were significantly downregulated in the SRSF1high groups. Furthermore, we detected that SRSF1 expression was significantly higher in MM patients than that in control donors. SRSF1 knockdown resulted in proliferation arrest in MM cell lines. Conclusion: The expression value of SRSF1 is positively associated with myeloma progression, and high SRSF1 expression might be a poor prognostic biomarker in MM patients.

A narrative review on sacubitril/valsartan and ventricular arrhythmias.

Sacubitril/valsartan, the first angiotensin receptor neprilysin inhibitor approved by the Food and Drug Administration for marketing, has been shown to reduce the risk of cardiovascular death or heart failure hospitalization and improve symptoms in patients with chronic heart failure with a reduced ejection fraction. However, some researchers have also found that sacubitril/valsartan has an antiarrhythmic effect. The mechanism by which sacubitril/valsartan reduces the mortality associated with malignant ventricular arrhythmias is not precise. Many studies have concluded that ventricular arrhythmia is associated with a reduction in myocardial fibrosis. This article reviews the current understanding of the effects of sacubitril/valsartan on the reduction of ventricular arrhythmia and explains its possible mechanisms. The results of this study suggest that sacubitril/valsartan reduces the occurrence of appropriate implantable cardioverter-defibrillator shocks. Meanwhile, sacubitril/valsartan may reduce the occurrence of ventricular arrhythmias by affecting 3 pathways of B-type natriuretic peptide, Angiotensin II, and Bradykinin. The conclusion of this study is that sacubitril/valsartan reduces the number of implantable cardioverter-defibrillator shocks and ventricular arrhythmias in heart failure with reduced ejection fraction patients.

Sestrin2 as a Potential Target for Regulating Metabolic-Related Diseases.

Sestrin2 is a highly conserved protein that can be induced under a variety of stress conditions, including DNA damage, oxidative stress, endoplasmic reticulum (ER) stress, and metabolic stress. Numerous studies have shown that the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway has a crucial role in the regulation of metabolism. Sestrin2 regulates metabolism via a number of pathways, including activation of AMPK, inhibition of the mTOR complex 1 (mTORC1), activation of mTOR complex 2 (mTORC2), inhibition of ER stress, and promotion of autophagy. Therefore, modulation of Sestrin2 activity may provide a potential therapeutic target for the prevention of metabolic diseases such as insulin resistance, diabetes, obesity, non-alcoholic fatty liver disease, and myocardial ischemia/reperfusion injury. In this review, we examined the regulatory relationship between Sestrin2 and the AMPK/mTOR signaling pathway and the effects of Sestrin2 on energy metabolism.

Prognostic Significance of Systemic Immune-Inflammation Index in Patients With Diffuse Large B-Cell Lymphoma.

OBJECTIVE: The systemic immune-inflammation index (SII) based on neutrophil, platelet and lymphocyte counts, is a prognostic biomarker in some solid cancers. However, the prognostic value of SII has not yet been validated. This study was to evaluate the role of SII in predicting survival for patients with diffuse large B cell lymphoma (DLBCL). METHODS: We retrospectively investigated 224 patients with DLBCL between August 2005 and October 2018. Kaplan-Meier analysis and Cox proportional hazard models were used to assess the prognostic value of SII. RESULTS: In the ROC curve analysis, SII had the highest AUC and was more accurate as a prognostic factor. Patients with higher SII tended to have higher level of LDH, more advanced stage, poor PS, and high IPI score compared with low SII group. In univariate analyses, SII, PLR and NLR were all prognostic for progression-free survival and overall survival. Moreover, only SII, older age, HBSAg-positive and IPI were the independent prognostic factors for patients in multivariate analysis. The nomogram based on SII, older age, HBSAg status and IPI showed accurate prognostic ability for predicting 3-years and 5-years survival rates (c-index, 0.791) compared to the IPI alone (c-index, 0.716). CONCLUSION: SII was a powerful tool for predicting outcome in patients with DLBCL. It might assist the separation of high-risk patients among patients with the same IPI.

The Prognostic Impact of Body Mass Index in Patients with Diffuse Large B-Cell Lymphoma: A Meta-Analysis.

OBJECTIVE: Some studies on the relation between body mass index (BMI) and outcome of diffuse large B-cell lymphoma (DLBCL) remain controversial. We performed a meta-analysis to evaluate the overall survival (OS) and progression-free survival (PFS) of DLBCL in overweight (≥25 to <30 kg/m2), obese (≥30 kg/m2) and underweight (<18.5 kg/m2) individuals compared with normal weight patients (≥18.5 to <25 kg/m2). METHODS: PubMed, Web of Science, EMBASE and the Cochrane Library databases were searched to identify relevant studies before February 20, 2020. The summary hazard ratio (HR) and 95% confidence interval (CI) were used for analyzing survival outcomes. RESULTS: Fourteen articles involving 8,753 subjects were included. The pooled analysis indicated that OS of overweight group (HR = 0.86, 95% CI: 0.78-0.95, P = 0.002) was better than of normal weight group, but no association was found in obese patients (HR = 1.11, 95% CI: 0.81-1.53, P = 0.501). Similarly, obese and overweight status had no significant impact on PFS in DLBCL. Underweight patients had poorer OS (HR = 1.99, 95% CI: 1.45-2.74, P < 0.001) and PFS (HR = 1.78, 95% CI: 1.12-2.83, P = 0.014) compared with normal weight group. CONCLUSION: Overweight patients have a better survival than normal weight patients, while underweight patients have a poorer survival in DLBCL.