Insulin resistance and sarcopenia: a prognostic longitudinal link to stroke risk in middle-aged and elderly Chinese population.

BACKGROUND: Stroke is the leading cause of death in middle-aged and elderly people in China. Insulin resistance (IR) and sarcopenia are both closely associated with metabolic diseases. However, the relationship between these two indicators and stroke has not been fully investigated. The aim of this study was to investigate the relationship between IR and sarcopenia and the risk of new-onset stroke. METHODS: Using longitudinal data from the China Health and Retirement Longitudinal Study (CHARLS) from 2011 to 2018, Cox proportional hazards models were used to determine the association between IR surrogate indicators and sarcopenia status with stroke incidence. RESULTS: In the present study, during a median 7 years of follow-up, we included 7009 middle-aged and elderly residents, of whom 515 presented with stroke incidence. After adjustment for potential confounders, both baseline IR surrogates and sarcopenia independently predicted stroke risk. In addition, co-morbidities had a higher risk of stroke than other groups. The positive association between TyG-WC and sarcopenia on stroke risk was particularly significant [HR (95% CI): 2.03 (1.52, 2.70)]. In subgroups of different ages and sexes, the combination of IR and sarcopenia is associated with the highest risk of stroke. CONCLUSIONS: We found that IR and sarcopenia synergistically increase the incidence of stroke in older adults. This finding provides new perspectives for stroke detection and intervention and highlights the importance of early detection and management of IR and sarcopenia in older adults.

Association of inflammation and abnormal lipid metabolism with risk of thrombosis and thrombosis progression in patients with polycythemia vera: a retrospective study.

To date, no therapeutic strategy has been shown to be effective in reducing the risk of polycythemia vera (PV) transforming into myelofibrosis or leukemia, and the main goal of current treatment is to prevent thrombotic events. Recent studies have shown that higher levels of inflammation are associated with an increased risk of thrombosis in PV patients, while the correlation between inflammation and abnormal lipid metabolism with the risk of thrombosis in PV has not been reported. In this retrospective study, 148 patients with newly diagnosed PV who visited the Affiliated Hospitals of Nanchang University from January 2013 to June 2023 were categorized into low-risk group and high-risk group according to the risk of thrombosis, and were subsequently divided into thrombosis non-progression group and progression group. The differences of novel inflammatory markers PHR, NHR, MHR, LHR, and SIRI in each group were analyzed and compared with healthy adults who underwent physical examination in the hospitals during the same period. The results showed that PHR, NHR, MHR, and SIRI levels were significantly higher in the PV group than in the control group (P < 0.001), while HDL-C levels were considerably lower (1.09 vs. 1.31, P < 0.001). Comparisons within the groups of PV patients revealed that PHR, MHR, NHR, NLR, and SIRI levels were significantly higher in the high-risk group for thrombosis than in the low-risk group (P < 0.01); the thrombosis PHR, NHR, NLR, and SIRI levels were higher in the group with progression of thrombosis than in the group without progression of thrombosis (P < 0.05), while HDL-C levels were significantly lower (1.02 vs. 1.12, P < 0.001). The results of the ROC curve analysis showed that NHR (AUC = 0.791), HDL-C (AUC = 0.691), PHR (AUC = 0.668), NLR(AUC = 0.658), and SIRI (AUC = 0.638) had high diagnostic efficacy for identifying PV patients with thrombosis progression. Multivariate analysis showed that NHR, NLR, MHR, and LHR were independent risk factors for PV patients with thrombosis progression (P < 0.05). Kaplan-Meier survival curves showed that NHR ≥ 5.82 × 109/mmol, NLR ≥ 6.295, PHR ≥ 280.4 × 109/mmol, MHR ≥ 0.295 × 109/mmol, LHR ≥ 1.41 × 109/mmol, and SIRI ≥ 1.53 × 109/L were risk factors for PFS in PV patients. The study demonstrates for the first time that novel inflammatory markers PHR, NHR, MHR, LHR, and SIRI may be used as new predictors for PV patients with thrombosis progression. NHR has the highest value in predicting thrombosis in PV patients and is superior to NLR which was reported previously.

[Research Progress on the Influence of Blood Tumor Microen-vironment on the Efficacy and the Adverse Reactions of CAR-T Cell Immunotherapy--Review].

The application of chimeric antigen receptor T cell (CAR-T) immunotherapy has ushered in a new era in cancer therapy, especially in the treatment of many kinds of refractory malignant tumors. The curative effect is significant for refractory/recurrent hematologic malignancies, such as acute leukemia, lymphoma, and multiple myeloma (MM). Tumor microenvironment (TME) is closely related to the efficacy and adverse reactions of CAR-T therapy. TME not only affects the activity of CAR-T cells, reduces their anti-tumor ability, but also directly involved in the occurrence and development of CAR-T cell therapy-related adverse reactions, such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Therefore, a deeper understanding of the role of blood TME in the process of CAR-T immunotherapy and the occurrence and development of adverse reactions is helpful for the application of CAR-T therapy in hematological malignancies. In this review, the influence of blood TME on the efficacy and adverse reactions of CAR-T immunotherapy was briefly summarized, aiming to provide evidence-based support for the clinical optimization of therapeutic regimen of refractory/recurrent hematologic malignancies.

Comparative efficacy and safety of different doses of ponatinib versus other tyrosine kinase inhibitors for the treatment of chronic myeloid leukemia: a systematic review and network meta-analysis.

OBJECTIVE: Ponatinib was recommended with caution because of its high risk of causing arterial occlusion events in chronic myeloid leukemia (CML) patients. The purpose of this study was to understand the efficacy and safety of different doses of ponatinib in the treatment of CML, and to compare it with other tyrosine kinase inhibitors (TKIs). METHOD: A network meta-analysis (NMA) was conducted by searching randomized controlled trials (RCTs) of ponatinib in patients with CML to compare the efficacy and safety of ponatinib, and ranked under the cumulative ranking curve (SUCRA) to evaluate the optimal treatment. RESULTS: A total of seven articles with eight RCTs were included in this study, involving 45 mg, 30 mg and 15 mg ponatinib doses. Seven outcome indexes were analyzed. The results showed that 45 mg ponatinib was superior to other doses of ponatinib and other TKIs in CCyR, MCyR and CHR, but the incidence of SAEs and AOEs was significantly higher than other treatment regimens. CONCLUSION: Ponatinib, with an initial dosage of 45 mg and a gradual reduction to 15 mg, may be a more favorable option for patients with CML at all stages of disease progression, rather than just those in the chronic phase of CML.

[Recent Advance of Newly Therapy for Chronic Myeloid Leukemia with BCR-ABLT315I Mutation--Review].

BCR-ABLT315I mutation is the main mechanism of resistance to the first and second generation tyrosine kinase inhibitor (TKI) for patients with chronic myeloid leukemia (CML). Ponatinib as the third generation TKI has been found that can significantly improve the prognosis of CML patients with T315I mutation. However, the latest report has discovered that the T315I compound mutant is even resistant to ponatinib, which aroused the enthusiasm of research on the mechanism of CML resistance and targeted therapy once again. Previous studies have shown that TKI combined with other targeted drugs is effective to CML patients with drug resistance or relapse due to T315I mutation. The latest research has found that the allosteric inhibitor asciminib combined with TKI therapy is equally effective to CML patients with T315I compound mutant, but the specific mechanism is not yet clarified. This review will focus on the latest research progress of therapy for CML with BCR-ABLT315I mutation, hoping to provide reference for researching new drugs and improve therapy for treating CML with T315I mutation.

PPARG, GNG12, and CD19 are potential independent predictors of central nerve recurrence in childhood acute lymphoblastic leukemia.

OBJECTIVE: To identify biomarkers that can predict the recurrence of the central nervous system (CNS) in children with acute lymphoblastic leukemia (ALL). MATERIALS AND METHODS: The transcriptome and clinical data of ALL in children were downloaded from the TARGET database. Transcriptome data were analyzed by bioinformatics method to identify core (hub) genes and establish a risk assessment model. Univariate Cox analysis was performed on each clinical data, and multivariate Cox regression analysis was performed on the obtained results and risk score. The children ALL phase I samples from TARGET database were used for validation. RESULTS: Univariate multivariate Cox analysis of 10 hub genes identified showed that PPARG (HR = 0.78, 95%CI = 0.67-0.91, p = 0.007), CD19 (HR = 1.15, 95%CI = 1.05-1.26, p = 0.003) and GNG12 (HR = 1.25, 95%CI = 1.04-1.51, p = 0.017) had statistical differences. The risk score was statistically significant in univariate (HR = 3.06, 95%CI = 1.30-7.19, p = 0.011) and multivariate (HR = 1.81, 95%CI = 1.16-2.32, p = 0.046) Cox regression analysis. The survival analysis results of the high and low-risk groups were different when the validation dataset was substituted into the model (p = 0.018). Then, we constructed a Nomogram which had a concordance index of survival prediction of 0.791(95%CI= 0.779-0.803). In addition, the CNS involvement grading status at first diagnosis CNS3 vs. CNS1 (HR = 5.74, 95%CI = 2.01-16.4, p = 0.001), T cell vs B cell (HR = 1.63, 95% CI = 1.06-2.49, p = 0.026) were also statistically significant. CONCLUSIONS: PPARG, GNG12, and CD19 may be predictors of CNS relapse in childhood ALL.

The Predictive Value of Neutrophil-Lymphocyte Ratio in Patients with Polycythemia Vera at the Time of Initial Diagnosis for Thrombotic Events.

Objective: To investigate and discuss the predictive value of the neutrophil-to-lymphocyte ratio (NLR) in patients with polycythemia vera (PV) at the time of initial diagnosis, as well as its clinical significance in predicting the occurrence of thrombotic events and the progression of future thrombotic events during follow-ups, with the goal of providing a reference for the early identification of high-risk PV patients and the early intervention necessary to improve the prognosis of PV patients. Method: A total of 170 patients diagnosed with PV for the first time were enrolled in this study. The risk factors affecting the occurrence and development of thrombotic events in these patients were statistically analyzed. Results: NLR (P = 0.030), WBC count (P = 0.045), and history of previous thrombosis (P < 0.001) were independent risk factors for thrombotic events at the time of initial diagnosis. Age ≥ 60 years (P = 0.004), NLR (P = 0.025), history of previous thrombosis (P < 0.001), and fibrinogen (P = 0.042) were independent risk factors for the progression of future thrombotic events during follow-ups. The receiver operating characteristic curve (ROC curves) showed that NLR was more effective in predicting the progression of future thrombotic events than age ≥ 60 years, history of previous thrombosis, and fibrinogen. Kaplan-Meier survival analysis showed progression-free survival time of thrombotic events in the high NLR value group (NLR ≥ 4.713) (median survival time 22.033 months, 95% CI: 4.226-35.840), which was significantly lower compared to the low NLR value group (NLR < 4.713) (median overall survival time 66.000 months, 95% CI: 50.670-81.330); the observed difference was statistically significant (P < 0.001). The 60-month progression-free survival in the low NLR value group was 58.8%, while it was 32.8% in the high NLR value group. Conclusion: Peripheral blood NLR levels in patients with PV resulted as an independent risk factor for the occurrence of thrombotic events at the time of initial diagnosis and for the progression of future thrombotic events during follow-ups. Peripheral blood NLR levels at the time of initial diagnosis and treatment had better diagnostic and predictive value for the progression of future thrombotic events in patients with PV than age ≥ 60 years, history of previous thrombosis, and fibrinogen.