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1.
Radiat Oncol ; 16(1): 201, 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34641928

RESUMO

PURPOSE: To develop a nomogram model for predicting local progress-free survival (LPFS) in esophageal squamous cell carcinoma (ESCC) patients treated with concurrent chemo-radiotherapy (CCRT). METHODS: We collected the clinical data of ESCC patients treated with CCRT in our hospital. Eligible patients were randomly divided into training cohort and validation cohort. The least absolute shrinkage and selection operator (LASSO) with COX regression was performed to select optimal radiomic features to calculate Rad-score for predicting LPFS in the training cohort. The univariate and multivariate analyses were performed to identify the predictive clinical factors for developing a nomogram model. The C-index was used to assess the performance of the predictive model and calibration curve was used to evaluate the accuracy. RESULTS: A total of 221 ESCC patients were included in our study, with 155 patients in training cohort and 66 patients in validation cohort. Seventeen radiomic features were selected by LASSO COX regression analysis to calculate Rad-score for predicting LPFS. The patients with a Rad-score ≥ 0.1411 had high risk of local recurrence, and those with a Rad-score < 0.1411 had low risk of local recurrence. Multivariate analysis showed that N stage, CR status and Rad-score were independent predictive factors for LPFS. A nomogram model was built based on the result of multivariate analysis. The C-index of the nomogram was 0.745 (95% CI 0.7700-0.790) in training cohort and 0.723(95% CI 0.654-0.791) in validation cohort. The 3-year LPFS rate predicted by the nomogram model was highly consistent with the actual 3-year LPFS rate both in the training cohort and the validation cohort. CONCLUSION: We developed and validated a prediction model based on radiomic features and clinical factors, which can be used to predict LPFS of patients after CCRT. This model is conducive to identifying the patients with ESCC benefited more from CCRT.

2.
Biomed Res Int ; 2021: 3047437, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34631878

RESUMO

Our aim was to explore the effects of dietary and behavior interventions on lipometabolism caused by an unhealthy high-fat diet and the best method to rebuild lipid homeostasis of this lifestyle. Apart from normal diet rats, 34 rats were fed with high-fat emulsion for 4 weeks and then intervened for another 4 weeks. Eight of them were classified into high-fat control group, and 9 were sorted into high-fat diet with rice vinegar group. Meanwhile, 10 were put into high-fat diet in swimming group, and 7 were just for refeeding normal diet group. Then, the data of body weight was recorded and analyzed. Indexes of serum samples were tested by kits. AMPKα, HNF1α, and CTRP6 in pancreas, liver, cardiac, and epididymis adipose tissues were detected by western blot. According to our experiments, swimming and refeeding groups reflected a better regulation on lipid homeostasis mainly by upregulating the expression of pancreas AMPKα. To be more specific, the refeeding rats showed lower T-CHO (P < 0.001) and LDL-C (P < 0.05), but higher weight gain (P < 0.001), insulin level (P < 0.01), and pancreas AMPKα (P < 0.01) than high-fat control rats. Compared with rats intervened by swimming or rice vinegar, they showed higher weight gain (P < 0.001), insulin level (P < 0.01), and HNF1α, but lower of CTRP6. In summary, refeeding diet functioned better in regulating the lipometabolic level after high-fat diet. Whatever approach mentioned above we adopted to intervene, the best policy to keep the balance of lipid homeostasis is to maintain a healthy diet.

3.
Br J Haematol ; 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34618912

RESUMO

Patients with classical Hodgkin lymphoma (cHL) who do not achieve complete remission (CR) after second-line chemotherapy have poor clinical outcomes. Besides, conventional salvage chemotherapy regimens have an unsatisfactory CR rate. The present retrospective study reports the efficacy and toxicity of the GVD (gemcitabine, vinorelbine, liposomal doxorubicin) regimen with or without programmed cell death 1 (PD-1) inhibitor for patients with cHL who failed first-line treatment. A total of 103 patients with cHL (GVD+PD-1 group, n = 27; GVD group, n = 76) with response assessment based on positron emission tomography were included. The GVD+PD-1 group tended to have a higher CR rate than GVD group (85·2% vs. 65·8%, P = 0·057) and had a better event-free survival (EFS) (P = 0·034). Subgroup analysis showed that patients with low-risk second-line International Prognostic Score might benefit from the addition of PD-1 inhibitor (GVD+PD-1 vs. GVD, 100·0% vs. 64·7%, P = 0·028) and had better EFS than GVD alone (P = 0·016). Further analysis demonstrated that PD-1 consolidation therapy might provide an EFS benefit (P = 0·007). The toxicity of the GVD+PD-1 regimen was comparable to the GVD regimen, except for higher rates of hypothyroidism and autoimmune pneumonitis, which were manageable. In conclusion, combining a PD-1 inhibitor with a GVD regimen could be a potentially effective second-line therapy for patients with cHL.

4.
Artigo em Inglês | MEDLINE | ID: mdl-34617215

RESUMO

Recent studies have suggested that exposure to ambient airborne pollutants is associated with inflammatory skin diseases, but the epidemiological evidence regarding the association between air pollution and acne vulgaris is limited. To address that, a hospital-based time-series analysis was conducted in Xi'an, a metropolitan in northwest China. A total of 71,625 outpatient visits for acne from 2010 to 2013 were identified. The mean daily concentrations of PM10, SO2, and NO2 were 142.6 µg/m3, 44.7 µg/m3, and 48.5 µg/m3, and all were higher than WHO air quality guidelines. A generalized additive model was used to analyze the relationship between short-term ambient air pollution exposure and outpatient visits for acne. The gender- and age-specific analyses were conducted as well. The results showed that the increase of SO2 and NO2 concentrations corresponded to a significant rise in the number of outpatient visits for acne at lag 0 in both single-lag and cumulative exposure models. Both SO2 and NO2 were positively associated with acne outpatient visits for both males and females. In age-specific analyses, the effect estimate of PM10 was only significant for adults over 30 years old; SO2 was significantly associated with acne visits in children and adolescents (<21 years) and young adults (21-30 years); and NO2 was significantly associated with acne visits in all age subgroups. In conclusion, short-term exposure to ambient air pollutants (PM10, SO2, or NO2) with the average levels above WHO limits was associated with increased risk of outpatient visits for both teenage acne and adult acne. Moreover, the effects of air pollutants may vary with age.

5.
Nat Med ; 27(10): 1677-1678, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34635853
6.
Artigo em Inglês | MEDLINE | ID: mdl-34519494

RESUMO

Lithium metal batteries with high theoretical capacity critically suffer from low cycling stability and safety issues mostly due to lithium dendrites. Regulating the Li-ion conduction and Li deposition is essential to achieve dendritic-free Li metal anodes. Herein, a synergistic strategy that combines a 3D nanocopper layer and a robust polymer protective layer is proposed. The 3D nanocopper layer in situ formed on the Li surface could achieve a uniform electric field distribution and contribute to reducing the nucleation barrier for Li deposition and refining the grain size of Li crystallites. Meanwhile, the Li-Nafion film with high Li-ion conductivity and good flexibility was used as a protective layer to provide homogeneous ion distribution and adapt to the volume change during the Li deposition. Consequently, the NCuLi∥LiCoO2 full cells exhibited outstanding cycling stability (a capacity retention of 90% over 500 cycles). Our results indicate that the synergistic control of Li-ion conduction and Li deposition is a promising method to achieve dendritic-free Li metal anodes.

7.
Clin Cancer Res ; 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34548316

RESUMO

PURPOSE: B-cell maturation antigen (BCMA) chimeric antigen receptor T (CAR-T) cell therapy results in high remission rates in patients with relapsed/refractory (R/R) multiple myeloma (MM). However, the factors associated with prognosis following CAR-T cell therapy are unknown. EXPERIMENTAL DESIGN: Between July 1, 2018, and July 31, 2020, 61 patients with R/R MM received anti-BCMA CAR-T cell therapy (Chictr.org number, ChiCTR1800017404). Stepwise multivariate Cox regression and competing risk analyses were conducted to identify poor prognosis-associated risk factors. RESULTS: Sixty patients (98.4%) experienced cytokine release syndrome (CRS), including 33, 23, and four cases of CRS grades 1-2, 3, and 4, respectively. The objective response rate (ORR) was 98.3%, and the complete response (CR) rate was 70.3%. With a median follow-up period of 21.1 months, the one-year overall survival (OS) and progression-free survival (PFS) rates were 78.0% and 50.2%, respectively. The median PFS was 12.7 months. Cox modeling revealed that poor PFS was associated with extramedullary disease (hazard ratio (HR)=2.59, 95% confidence interval (95%CI)=1.29-5.21, P=0.008), light chain MM (HR=2.53, 95%CI=1.03-5.97, P=0.035), high-risk cytogenetics (HR=2.80, 95%CI=1.27-6.14, P=0.01), and prior treatment with >3 therapeutic lines (HR=3.14, 95%CI=1.34-7.34, P=0.008). Among the 41 CR cases, competing risk analyses demonstrated higher relapse predispositions in those with extramedullary disease (HR=4.51, 95%CI=1.86 -10.9, P=0.001), light chain MM (HR=4.89, 95%CI=1.52 -15.7, P=0.008), or high-risk cytogenetics (HR=5.09, 95%CI=1.63 -15.9, P=0.005). CONCLUSIONS: Anti-BCMA CAR-T cell therapy is safe and effective for R/R MM. For patients with high-risk factors, improvements to extend remission and more specific individualized therapies are needed.

8.
Allergol Immunopathol (Madr) ; 49(5): 78-86, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34476926

RESUMO

Alveolar echinococcosis (AE) is a malignant and fatal parasitic disease caused by the larvae of Echinococcus multilocularis (E. multilocularis), which inhibits the activity and proliferation of natural killer (NK) cells. In this study, the functional alteration of hepatic NK cells and their related molecules were studied. The AE-infected patient's tissue was fixed with formalin, embedded in paraffin, and stained with Masson's trichrome or hematoxylin and eosin (H&E). Single cells from AE-infected patient or E. multilocularis-infected mice were blocked with Fc-receptor (FcR), and stained with monoclonal antibodies, including CD16, CD56, CD3, KIR2DL1, granzyme B, perforin, Interferon gamma (IFN-γ), and tumor necrosis factor-α (TNFα) or isotype control, to measure molecules and cytokines of NK cells and analyzed by flow cytometry. The Sirius red staining was used to quantitate hepatic fibrosis by calculating quantitative collagen deposition. AE can adjust both the number of hepatic CD56+ NK cells and its KIR2DL1 expression processes. Moreover, the overexpression of KIR2DL1 in NK cells could downregulate the functioning of immune cells in the liver area close to parasitic lesions. The number and dysfunction of NK cells in E. multilocularis infection could be related to the molecule dynamics of cell surface inhibitory receptor Ly49A, leading to hepatic damage and progression of fibrosis. This study illustrated significant increase in hepatic fibrogenesis and apparent upregulation of hepatic CD56+ NK cell population and its KIR2DL1 expression in AE-infected patients. This opposite variation might be related to the impaired NK cells functioning, such as granzyme B, IFN-γ, and TNF-α secretion. In addition, the cell surface inhibitory receptor Ly49A was related to the intracellular cytokine secretion functions of NK cells.

10.
Nat Prod Res ; : 1-12, 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34498975

RESUMO

Five new glycosides including mimenghuasu A and B (1-2), isolinarin (3), cyclocitralosides A and B (4-5), along with forty-seven known compounds were isolated from the flower buds of Buddleja officinalis. These structures were elucidated by extensive spectroscopic analysis (UV, IR, 1 D, 2 D NMR, and MS spectra). The anti-inflammatory activities of the isolated compounds were determined by enzyme-linked immunosorbent assay (ELISA) on the expression of TNF-α (LPS-activated RAW264.7 cells) and MTT experiment on LPS-induced HUVECs proliferation effects. Good suppressive effects on the expression of TNF-α were shown by 4 and 5 with IC50 values of 19.35 and 22.10 µM, respectively, compared to positive control indomethacin (IC50 16.40 µM). In addition to this, some isolated compounds exhibited excellent antioxidant activities including compounds 16, 18, 29, 39, and 47 (IC50 µM: 82.59, 72.94, 33.65, 46.67, and 20.81, respectively) with almost the same or stronger potency with reference to vitamin C as positive control (IC50 81.83 µM).

11.
PLoS Pathog ; 17(9): e1009889, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34492079

RESUMO

Hepatitis C virus (HCV) infection induces the degradation and decreases the secretion of apolipoprotein B (ApoB). Impaired production and secretion of ApoB-containing lipoprotein is associated with an increase in hepatic steatosis. Therefore, HCV infection-induced degradation of ApoB may contribute to hepatic steatosis and decreased lipoprotein secretion, but the mechanism of HCV infection-induced ApoB degradation has not been completely elucidated. In this study, we found that the ApoB level in HCV-infected cells was regulated by proteasome-associated degradation but not autophagic degradation. ApoB was degraded by the 20S proteasome in a ubiquitin-independent manner. HCV induced the oxidation of ApoB via oxidative stress, and oxidized ApoB was recognized by the PSMA5 and PSMA6 subunits of the 20S proteasome for degradation. Further study showed that ApoB was degraded at endoplasmic reticulum (ER)-associated lipid droplets (LDs) and that the retrotranslocation and degradation of ApoB required Derlin-1 but not gp78 or p97. Moreover, we found that knockdown of ApoB before infection increased the cellular lipid content and enhanced HCV assembly. Overexpression of ApoB-50 inhibited lipid accumulation and repressed viral assembly in HCV-infected cells. Our study reveals a novel mechanism of ApoB degradation and lipid accumulation during HCV infection and might suggest new therapeutic strategies for hepatic steatosis.

12.
Endocrine ; 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34542801

RESUMO

PURPOSE: Adulthood and childhood obesity are both associated with reproductive diseases and gynecological cancers in females. However, the causal factors associated with these observations have yet to be identified. Mendelian randomization is a process that is independent of inverse bias and confounding and can act as a random control trial in which genetic groups are settled during meiosis, thus representing an effective tool with which to investigate causality. METHODS: We carried out several Mendelian randomization trials based on the combined genetic scores of 75 adult-associated and 15 childhood-associated body mass index (BMI) single nucleotide polymorphisms (SNPs), databases for several gynecological cancers and reproductive diseases from the UK Biobank (with 194,153 participants), using the traditional inverse-variance weighted (IVW) method as the main method. RESULTS: Elevated adult-associated BMI scores (odds ratio [OR] = 1.003; 95% confidence interval [CI]: 1.001-1.004) and childhood-associated BMI scores (OR = 1.003; 95% CI: 1.001-1.004) were related to a higher risk of the polycystic ovarian syndrome (PCOS), as determined by the traditional IVW method. The random IVW method further revealed a nominal negative causal association between childhood-associated BMI and subsequent endometriosis (OR = 0.995; 95% CI: 0.991-0.999). CONCLUSIONS: Consistent with observational consequences, our findings indicated that adulthood obesity may play role in the development of PCOS and that childhood obesity can increase the risk of PCOS but may reduce the incidence of endometriosis in later life. Further research is now needed to validate our findings and identify the precise mechanisms involved.

13.
Thorac Cancer ; 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34545707

RESUMO

BACKGROUND: The aim of this study was to quantitatively analysis the diagnostic performance of adenomatous polyposis coli (APC) gene promoter methylation in serum or sputum/bronchoalveolar lavage fluid (BLAF) as a biomarker for lung cancer identification through pooling of open published data. METHODS: The relevant electronic MEDLINE, EMBASE, Ovid, web of science and CNKI databases were systematically searched to identify the studies related to APC gene promoter methylation for lung cancer diagnosis. Data of true positive (tp), false positive (fp), false negative (fn) and true negative (tn) were extracted from the publications included in the study. The pooled diagnostic sensitivity, specificity and area under summary receiver operating characteristic (SROC) curve (AUC-SROC) of APC gene promoter methylation were calculated. Publication bias was evaluated by Begg's funnel plot and Egger's line regression test. RESULTS: Fourteen studies associated with APC gene promoter methylation and lung cancer were identified in the databases and finally included in the meta-analysis. The data was pooled using a random effect model due to significant statistical heterogeneity across the 14 studies (p < 0.05). Using the APC gene promoter methylation as a reference for lung cancer identification, the pooled diagnostic sensitivity and specificity were 0.43 (95% CI: 0.40-0.45), and 0.92 (95% CI: 0.90-0.95), respectively with combined diagnostic positive likelihood ratio (+LR) and negative likelihood ratio (-LR) of 7.15 (95% CI: 3.62-14.12) and 0.63 (95% CI: 0.57-0.71). The pooled diagnostic odds ratio (DOR) and AUC-SROC of APC gene promoter methylation for lung cancer diagnosis were 9.84 (95% CI: 5.77-16.79) and 0.7, respectively. The Begg's funnel plot and Egger's line regression test both indicated statistical publication bias (t = 5.40, p < 0.05). CONCLUSIONS: APC gene promoter methylation in serum or sputum/BLAF is a potential biomarker for lung cancer diagnosis with high specificity. However, due to its low sensitivity, it may not be suitable for lung cancer screening in the general population.

14.
Front Endocrinol (Lausanne) ; 12: 710221, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34531826

RESUMO

Mounting evidence has shown that intrauterine hyperglycemia exposure during critical stages of development may be contributing to the increasing prevalence of diabetes. However, little is known about the mechanisms responsible for offspring metabolic disorder. In this present study, we explored intrauterine hyperglycemia exposure on fetal pancreatic metabolome, and its potential link to impaired glucose tolerance in adult offspring. Here, using a GDM mouse model, we found the metabolome profiling of pancreas from male and female fetus showing altered metabolites in several important pathways, including 5-methylcytosine, α-KG, branched-chain amino acids, and cystine, which are associated with epigenetic modification, insulin secretion, and intracellular redox status, respectively. This finding suggests that intrauterine exposure to hyperglycemia could cause altered metabolome in pancreas, which might be a metabolism-mediated mechanism for GDM-induced intergenerational diabetes predisposition.

15.
J Hematol Oncol ; 14(1): 145, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34526099

RESUMO

The consensus recommendations in 2018 from The Chinese Society of Hematology (CSH) on indications, conditioning regimens and donor selection for allogeneic hematopoietic stem cell transplantation (allo-HSCT) facilitated the standardization of clinical practices of allo-HSCT in China and progressive integration with the world. There have been new developments since the initial publication. To integrate recent developments and further improve the consensus, a panel of experts from the CSH recently updated the consensus recommendations, which are summarized as follows: (1) there is a new algorithm for selecting appropriate donors for allo-HSCT candidates. Haploidentical donors (HIDs) are the preferred donor choice over matched sibling donors (MSDs) for patients with high-risk leukemia or elderly patients with young offspring donors in experienced centers. This replaces the previous algorithm for donor selection, which favored MSDs over HIDs. (2) Patients with refractory/relapsed lymphoblastic malignancies are now encouraged to undergo salvage treatment with novel immunotherapies prior to HSCT. (3) The consensus has been updated to reflect additional evidence for the application of allo-HSCT in specific groups of patients with hematological malignancies (intermediate-risk acute myeloid leukemia (AML), favorable-risk AML with positive minimal residual disease, and standard-risk acute lymphoblastic leukemia). (4) The consensus has been updated to reflect additional evidence for the application of HSCT in patients with nonmalignant diseases, such as severe aplastic anemia and inherited diseases. (5) The consensus has been updated to reflect additional evidence for the administration of anti-thymocyte globulin, granulocyte colony-stimulating factors and post-transplantation cyclophosphamide in HID-HSCT.

16.
Mol Neurobiol ; 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34480336

RESUMO

The Notch signaling pathway plays an important role in the regulation of neurogenesis. The objective of this study was to investigate whether the Notch signaling pathway was involved in the neurogenesis impairment and long-term neurocognitive dysfunction caused by neonatal exposure to ketamine. On postnatal day 7 (PND-7), male Sprague-Dawley (SD) rats were intraperitoneally injected with 40 mg/kg ketamine four consecutive times (40 mg/kg × 4) at 1-h intervals. Notch ligand Jagged1 (0.5 mg/kg) and lentivirus overexpressing the Notch1 intracellular domain (LV-NICD1) were microinjected into the hippocampal dentate gyrus (DG) 1 h or 4 days before ketamine administration, respectively. The expression of Notch1 signaling pathway-related proteins was detected by Western blotting 24 h after ketamine administration. The proliferation and differentiation of the neural stem cells (NSCs) in the hippocampal DG were evaluated by double immunofluorescence staining 24 h after treatment. Moreover, changes in hippocampus-dependent spatial memory of 2-month-old rats were investigated with the Morris water maze test. Ketamine anesthesia in neonatal rats decreased the expression levels of Jagged1, Notch1, NICD1, and hairy enhancer of split 1 (Hes1); inhibited the proliferation and astrocytic differentiation of NSCs; and promoted the differentiation of neurons. Neonatal exposure to ketamine caused deficits in hippocampus-dependent spatial reference memory tasks in 2-month-old rats. Microinjection of Jagged1 or LV-NICD1 reversed the inhibitory effect of ketamine on the expression of Notch1-related proteins in the hippocampal DG, attenuated the ketamine-mediated decrease in NSC proliferation and differentiation, and improved the cognitive function of 2-month-old rats after neonatal exposure to ketamine. These results suggest that neonatal exposure to ketamine in rats inhibits the proliferation and differentiation of hippocampal NSCs and impairs neurocognitive function in adulthood. The Notch1 signaling pathway may be involved in the impairment of hippocampus-dependent learning and memory during adulthood caused by neonatal exposure to ketamine. These findings contribute to further understanding the neurotoxicity induced by neonatal exposure to ketamine and the underlying mechanisms.

19.
Reprod Sci ; 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34580843

RESUMO

High maternal serum estradiol (E2) levels in the first trimester of pregnancy are associated with a high incidence of low birth weight (LBW) and small for gestational age (SGA). This study aimed to investigate the effect of first-trimester high maternal serum E2 levels on fetal growth and the underlying mechanisms in multiple pregnancies. Maternal serum E2 levels of women at 8 weeks of gestation were measured. The expression levels of imprinted genes and DNMT1 were determined by RT-qPCR, and KvDMR1 methylation in embryo tissue, placenta, and newborn cord blood samples was examined by bisulfite sequencing PCR. The effect of E2 on CDKN1C expression was investigated in HTR8 cells. The incidence of SGA was significantly higher in multiple pregnancies reduced to singleton than that in primary singleton pregnancies (11.4% vs. 2.9%) (P < 0.01) and multiple pregnancies reduced to twins than primary twins (38.5% vs. 27.3%) (P < 0.01). The maternal serum E2 level at 8 weeks of gestation increased with the number of fetuses and was negatively correlated with offspring birth weight. CDKN1C and DNMT1 expression was significantly upregulated in embryo tissue, placenta, and cord blood from multiple pregnancies. Furthermore, there was a positive correlation between CDKN1C mRNA expression and KvDMR1 methylation levels. In HTR8 cells, DNMT1 mediated the estrogen-induced upregulation of CDKN1C, which might contribute to SGA. To minimize the risks of LBW and SGA, our findings suggest that abnormally high maternal serum E2 levels should be avoided during the first trimester of multiple pregnancies from assisted reproductive technology (ART).

20.
Cancer Med ; 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34581023

RESUMO

PURPOSE: Some studies have indicated that using 500 mg/m2 rituximab combined with CHOP-14 may be beneficial for elderly men but not women with diffuse large B-cell lymphoma (DLBCL). The purpose of this study was to investigate the potential benefit of escalated doses of rituximab with CHOP-21 as the first-line treatment in male patients with DLBCL. METHODS: We performed a retrospective cohort study to analyze the survival benefit of rituximab 500 mg/m2 plus the CHOP-21 regimen (Escalated-R-CHOP-21) as the first-line treatment compared with using rituximab 375 mg/m2 plus the CHOP-21 regimen (Standard-R-CHOP-21) in men with DLBCL. We used propensity score matching to maximize the balance of the observed covariables. The primary endpoints of this study were the progression-free survival (PFS) rate and overall survival (OS) rate at 3 years. RESULTS: After a median follow-up of 47 months (IQR 31-65), no significant difference in PFS and OS was found for men treated with Escalated-R-CHOP-21 compared with Standard-R-CHOP-21 [3-year PFS: 69.7% versus 71.9%, p = 0.867; 3-year OS: 83.0% versus 82.4%, p = 0.660]. After 1:1 propensity score matching, we found that the patients using Escalated-R-CHOP-21 had statistically significant survival benefits relative to Standard-R-CHOP-21 among the 96 matched elderly male patients for 3-year PFS [75.5% (95% CI 62.8-88.2) versus 58.2% (95% CI 44.3-72.1); p = 0.019] and 3-year OS [86.6% (95% CI 76.4-96.8) versus 65.8% (95% CI 52.1-79.5); p = 0.017]. However, no differences in survival were observed for younger male patients. Furthermore, the dose effect in PFS of Escalated-R-CHOP-21 was more obvious for elderly male patients with no high-risk extranodal sites (p = 0.005 and interaction p = 0.030). CONCLUSION: Escalated-R-CHOP-21 could be a safe and effective option for treating elderly male patients with DLBCL. This study provides new insight into optimizing the standard treatment regimen, which may have important therapeutic implications in elderly male patients with DLBCL.

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