Impact of bone marrow fibrosis on outcomes of allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia.

Bone marrow fibrosis (BMF) of unknown etiology was common in hematological malignancies, but its prognostic value for acute myeloid leukemia (AML) is unclear. We interrogated data from 532 newly diagnosed subjects with AML receiving allogeneic hematological stem cell transplantation to evaluate the prognostic impact of BMF on transplant outcomes. Using the European consensus on the grading of BMF at diagnosis, 255 (48%) subjects were BMF-0, 209 (39%), BMF-1 and 68 (13%), BMF-2-3. Subjects with BMF-2-3 had poor overall survival (P < 0.001), disease-free survival (P < 0.001) and a higher incidence of relapse (CIR, P < 0.001). Multi-variable analyses in subjects achieving pre-transplant complete remission showed BMF-2-3 was an independent risk factor for CIR (Hazard Ratio [HR] = 2.17, (95% CI, 1.11, 4,24); P = 0.02). Furthermore, BMF-2-3 group showed delayed neutrophil and platelet engraftment and delayed B cell recovery post-transplantation. These findings demonstrate the significance of BMF in transplant outcomes and attract more attention to AML with BMF.

WT1 gene mutations impact post-transplant relapse in myelodysplastic syndrome with excess blasts 2 patients.

Wilms tumor 1 (WT1) gene mutations are infrequent in myelodysplastic syndrome (MDS), but MDS with WT1 mutations (WT1mut) is considered high risk for acute myeloid leukemia (AML) transformation. The influence of WT1 mutations in patients with MDS after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is unclear. We performed a retrospective analysis of 136 MDS with excess blasts 2 (MDS-EB2) patients with available WT1 status who underwent their first allo-HSCT between 2017 and 2022 in our center. There were 20 (20/136, 15%) cases in the WT1mut group and 116 (116/136, 85%) cases in the WT1 wild-type (WT1wt) group. WT1mut patients had a higher 2-year cumulative incidence of relapse (CIR) than WT1wt cases (26.2% vs. 9.4%, p = 0.037) after allo-HSCT. Multivariate analysis of relapse showed that WT1 mutations (HR, 6.0; p = 0.002), TP53 mutations (HR, 4.2; p = 0.021), and ≥ 5% blasts in bone marrow (BM) at transplantation (HR, 6.6; p = 0.004) were independent risk factors for relapse. Patients were stratified into three groups according to the risk factors. Two-year CIR differed significantly in high-, intermediate-, and low-risk groups (31.8%, 11.6%, and 0%, respectively). Hence, WT1 mutations may be related to post-transplant relapse in patients with MDS-EB2, which warrants further study.

Omics-imaging signature-based nomogram to predict the progression-free survival of patients with hepatocellular carcinoma after transcatheter arterial chemoembolization.

BACKGROUND: Enhanced magnetic resonance imaging (MRI) is widely used in the diagnosis, treatment and prognosis of hepatocellular carcinoma (HCC), but it can not effectively reflect the heterogeneity within the tumor and evaluate the effect after treatment. Preoperative imaging analysis of voxel changes can effectively reflect the internal heterogeneity of the tumor and evaluate the progression-free survival (PFS). AIM: To predict the PFS of patients with HCC before operation by building a model with enhanced MRI images. METHODS: Delineate the regions of interest (ROI) in arterial phase, portal venous phase and delayed phase of enhanced MRI. After extracting the combinatorial features of ROI, the features are fused to obtain deep learning radiomics (DLR)_Sig. DeLong's test was used to evaluate the diagnostic performance of different typological features. K-M analysis was applied to assess PFS in different risk groups, and the discriminative ability of the model was evaluated using the C-index. RESULTS: Tumor diameter and diolame were independent factors influencing the prognosis of PFS. Delong's test revealed multi-phase combined radiomic features had significantly greater area under the curve values than did those of the individual phases (P < 0.05).In deep transfer learning (DTL) and DLR, significant differences were observed between the multi-phase and individual phases feature sets (P < 0.05). K-M survival analysis revealed a median survival time of high risk group and low risk group was 12.8 and 14.2 months, respectively, and the predicted probabilities of 6 months, 1 year and 2 years were 92%, 60%, 40% and 98%, 90%,73%, respectively. The C-index was 0.764, indicating relatively good consistency between the predicted and observed results. DTL and DLR have higher predictive value for 2-year PFS in nomogram. CONCLUSION: Based on the multi-temporal characteristics of enhanced MRI and the constructed Nomograph, it provides a new strategy for predicting the PFS of transarterial chemoembolization treatment of HCC.

Transarterial chemoembolization using drug-eluting beads versus lipiodol in the treatment of unresectable hepatocellular carcinoma: propensity score matching.

Background: Since the introduction of drug-eluting beads (DEB), the result comparing transarterial chemoembolization (TACE) using lipiodol, also called conventional transarterial chemoembolization (c-TACE), and DEB-TACE shows considerable controversy. The objective of this study was to compare the safety and efficacy of c-TACE and DEB-TACE to treat unresectable hepatocellular carcinoma (uHCC). Methods: This retrospective study used propensity score matching (PSM) analysis to analyze clinical data from 113 cases of primary hepatocellular carcinoma (HCC) treated at our hospital from September 2016 to July 2021. The safety and efficacy of the two treatment modalities were analyzed after 1:1 matching. The primary endpoint was progression-free survival (PFS); the secondary endpoints included overall survival (OS), disease control rates (DCRs), and objective response rates (ORRs) at 1, 3, 6, and 12 months, and postoperative complications. Results: Twenty-nine patients underwent DEB-TACE and 84 received c-TACE; 28 pairs of patients were eventually matched. After matching, baseline characteristics between groups were comparable. The median PFS of the DEB-TACE group was 10 months compared to 6 months in the c-TACE group (P=0.002). The median OS was 23 months in the DEB-TACE group vs. 14 months in the c-TACE group, but the difference was not statistically significant (P=0.265). The ORR at 1, 3, 6, and 12 months in the DEB-TACE group (69%, 78%, 60%, and 52%) were significantly higher than those in the c-TACE group (39%, 39%, 26%, and 8%) (P<0.05). The DCR at postoperative 3 months was significantly higher in the DEB-TACE group (95%) (P<0.05). There was one case of postoperative liver abscess in the DEB-TACE group, and the patient recovered well after drainage. No serious complications occurred. Conclusions: Compared to c-TACE, DEB-TACE prolonged PFS and exhibited better short-term ORR with a similar level of safety. However, there was no significant advantage in terms of OS.

Prophylactic therapy using epigenetic agents for RUNX1::RUNXT1-positive high-risk AML after Allo-HSCT.

Disease recurrence is the leading cause of treatment failure in patients with RUNX1::RUNXT1-positive acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Post-transplant maintenance therapy, guided by monitoring minimal residual disease (MRD), is commonly administered; however, relapse rates remain high. This prospective study aimed to assess the effectiveness and safety of epigenetic agents as prophylactic therapy in patients with RUNX1::RUNXT1-positive AML. Thirty high-risk patients received prophylactic therapy (n = 17 and n = 13 in the chidamide and AZA groups, respectively) between January 2019 and July 2023. 34 high-risk patients who received preemptive treatment due to molecular relapse were included in the analysis. The two-year relapse-free survival (RFS) and overall survival (OS) were significantly higher in the prophylactic group compared to the preemptive group (82.82% vs. 51.38%, P = 0.014; 86.42% vs. 56.16%, P = 0.025, respectively); 2-year cumulative incidence of relapse rates were 13.8% and 36.40%, respectively (P = 0.037). In conclusion, prophylactic therapy with epigenetic agents may improve long-term prognosis and is well-tolerated in patients with RUNX1::RUNXT1-positive high-risk AML. Timely post-transplant prophylactic therapy may be more effective than preemptive therapy based on positive MRD results.

GSNOR overexpression enhances CAR-T cell stemness and anti-tumor function by enforcing mitochondrial fitness.

Chimeric antigen receptor-T (CAR-T) cell has been developed as a promising agent for patients with refractory or relapsed lymphoma and leukemia, but not all the recipients could achieve a long-lasting remission. The limited capacity of in vivo expansion and memory differentiation post activation is one of the major reasons for suboptimal CAR-T therapeutic efficiency. Nitric oxide (NO) plays multifaceted roles in mitochondrial dynamics and T cell activation, but its function on CAR-T cell persistence and anti-tumor efficacy remains unknown. Herein, we found the continuous signaling from CAR not only promotes excessive NO production, but also suppressed S-nitrosoglutathione reductase (GSNOR) expression in T cells, which collectively led to increased protein S-nitrosylation, resulting in impaired mitochondrial fitness and deficiency of T cell stemness. Intriguingly, enforced expression of GSNOR promoted memory differentiation of CAR-T cell after immune activation, rendered CAR-T better resistance to mitochondrial dysfunction, further enhanced CAR-T cell expansion and anti-tumor capacity in vitro and in a mouse tumor model. Thus, we revealed a critical role of NO in restricting CAR-T cell persistence and functionality, and defined that GSNOR overexpression may provide a solution to combat NO stress and render patients with more durable protection from CAR-T therapy.

Outcomes of acute myeloid leukemia patients undergoing allogeneic hematopoietic stem cell transplantation: validation, comparison and improvement of 2022 ELN genetic risk system.

The 2022 European LeukemiaNet (ELN) updated the previous risk classification published in 2017 but the prognostic significance for allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains unclear. We enrolled 600 acute myeloid leukemia (AML) patients who underwent allo-HSCT to validate ELN-2022 genetic risk system and compared it with ELN-2017. There were 214 (35.67%), 162 (27.0%), and 224 (37.33%) patients in ELN-2022 favorable-, intermediate-, and adverse-risk group respectively and 86 patients (14.33%) experienced a shift in risk stratification compared to ELN-2017. Median and maximum follow-up time were 2.89 (95% CI 2.67 to 3.03) years and 8.78 years. The median overall survival (OS) was 73.8% (95% CI 67.5% to 80.3%), 63.9% (95% CI 56.7% to 72.0%) and 57.6% (95% CI 50.4% to 65.9%) in ELN-2022 favorable-, intermediate-, and adverse-risk group (P < 0.001). OS shortened significantly as the ELN-2022 risk stratification increased but didn't significantly in ELN-2017 intermediate-risk compared to favorable-risk. Both ELN-2022 and ELN-2017 adverse-risk were associated with increased cumulative incidence of relapse (CIR). Time-dependent receiver operating characteristic (ROC) analysis showed that both ELN-2017 and ELN-2022 risk systems had limited prognostic ability for OS. We modified ELN-2022 risk system with pre-transplant minimal residual disease (MRD) and the modified risk system performed a significantly superior efficacy to ELN-2022 system.

Refractory patients with favorable/intermediate-risk acute myeloid leukemia benefit from azacytidine maintenance therapy following allogeneic hematopoietic stem cell transplantation.

Recurrence following allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the major cause of treatment failure in patients with myeloid malignancy. Azacytidine (AZA) maintenance is a promising therapy to prevent relapse and improve survival. We conducted a prospective, one-arm study involving 78 patients with myeloid malignancy at a high risk of recurrence who were enrolled between September 2019 and April 2022. Furthermore, 102 matched historical controls were selected using propensity score matching. With a median follow-up time of 19.6 (3.5-91.7) months, AZA maintenance therapy significantly improved relapse-free survival (RFS; log-rank test, p = 0.01). The AZA and control groups had a 1-year RFS of 87.7% (95% confidence interval [CI], 0.80-0.96) and 72.2% (95% CI, 0.64-0.82), respectively, with a hazard ratio (HR) of 0.21 (95% CI, 0.09-0. 47; p < 0.01). There were no grade 4 adverse effects or deaths related to AZA. Refractory patients with favorable/intermediate-risk acute myeloid leukemia (AML) benefited more from AZA maintenance therapy than those with adverse-risk AML according to the European Leukemia Net guidelines (RFS in favorable/intermediate-risk AML, HR = 0.29, 95% CI, 0.11-0.79; RFS in adverse-risk AML, HR = 0.57, 95% CI, 0.21-1.6; p for interaction = 0.03). Our findings suggest that AZA maintenance therapy following allo-HSCT was safe and could reduce the incidence of relapse, particularly for refractory patients with favorable/intermediate-risk AML.

Comparison of autologous, matched sibling, and alternative donor stem cell transplant outcomes for acute myeloid leukemia patients in first remission: A propensity score matching study.

Autologous hematopoietic stem cell transplantation (auto-HSCT), matched sibling donor HSCT (MSD-HSCT), and alternative donor HSCT (AD-HSCT) are viable post-remission treatment options for acute myeloid leukemia (AML). A total of 283 de novo favorable- and intermediate-risk AML patients, based on the ELN 2022 criteria, in first complete remission were initially included for propensity score matching. Following the matching process, 126 patients were selected for further analysis, with 42 patients in each of the auto-HSCT, MSD-HSCT, and AD-HSCT groups. Among the AD-HSCT group, 38 of 42 (90.5%) patients received haploidentical HSCT. In patients with persistent undetectable measurable residual disease (uMRD) before transplant (n = 83), overall survival (OS) was similar across the groups. However, auto-HSCT showed a trend of increased disease-free survival (DFS) compared to AD-HSCT (HR 2.85, P = 0.09), resulting in a 3-year DFS and OS of 79.1% and 82.8%, respectively. In the non-persistent uMRD group (n = 38), auto-HSCT exhibited a tendency to increase the risk of relapse, particularly when compared to AD-HSCT (HR 0.24, P = 0.07), but this did not result in inferior OS. The monthly direct medical cost per patient within the first 2 years after HSCT was significantly lower in auto-HSCT compared to MSD-HSCT (P = 0.015) and AD-HSCT (P < 0.001). Our results provide evidence for the use of auto-HSCT as a viable therapeutic option for favorable- and intermediate-risk de novo AML patients in first complete remission with persistent uMRD. Additionally, our findings demonstrated a notable cost advantage associated with auto-HSCT compared to MSD-HSCT and AD-HSCT.

Efficacy of venetoclax combined with decitabine conditioning regimen for allogeneic hematopoietic stem cell transplantation in high-risk and elderly patients with myeloid neoplasms.

This prospective clinical investigation focused on the addition of venetoclax and decitabine to myeloablative conditioning regimens, targeting high-risk and elderly individuals undergoing allogeneic hematopoietic stem cell transplantation. In total, 19 patients were enrolled in the trial between December 2021 and February 2023, and their progress was monitored for a median follow-up period of 258 days, ranging from 35 to 544 days. In the initial regimen (n=11), venetoclax was administered at a dosage of 400 mg per day from day -14 to day -1, while in the modified regimen (n=8), it was administered from day -14 to day -5. Decitabine was orally administered at a dosage of 20mg/m2/day from day -7 to day -3. Grade 3/4 adverse events observed included hematological events, hypertension, infections, allergy, and increased amylase. In the entire cohort, the overall survival (OS) and relapse-free survival (RFS) rates at 6 months were 63% (95% CI, 45-89) and 63% (95% CI, 45-89), respectively. The non-relapse mortality (NRM) rate at 6 months was 37% (95% CI, 16-58), while the cumulative incidence of relapse (CIR) was 0. However, the incidence of grade II-IV acute graft-versus-host disease (aGVHD) and grade III-IV aGVHD within 100 days was found to be 31% (95% CI, 12-53) and 26% (95% CI, 9-47), respectively. These rates indicate a relatively high occurrence, making it less suitable to administer the regimen to elderly patients. Therefore, further high-quality studies are required to enhance the conditioning regimen specifically for high-risk and elderly patients diagnosed with myeloid neoplasms. Clinical trial registration: ChiCTR2100050272.

MiR-490-3p Sponged by lncRNA NEAT1 Can Attenuate Lung Adenocarcinoma Progression by Suppressing the RhoA/ROCK Signaling Pathway.

OBJECTIVE: Long noncoding RNAs (lncRNAs) are crucial regulators of lung adenocarcinoma (LUAD) progression. Herein, we explored the role of miR-490-3p and the underlying molecular mechanism involving key lncRNAs and pathways in LUAD. METHODS: Reverse transcription-quantitative PCR (RT-qPCR) was performed to detect the expression of lncRNA NEAT1 and miR-490-3p in LUAD cells and tissues. Western blotting was used to determine protein expression levels of the Ras homologous gene family member A/Rho-related protein kinase (RhoA/ROCK) signal pathway marker. Considering cell functions, Cell Counting Kit-8 (CCK-8), Transwell, and xenograft experiments were employed to evaluate LUAD cell proliferation, migration, and tumor growth, respectively. The relationship between miR-490-3p and lncRNA NEAT1 was analyzed using a luciferase reporter assay. RESULTS: Herein, we found that miR-490-3p expression was significantly low in LUAD cells and tissues. MiR-490-3p overexpression markedly suppressed tumor growth, the RhoA/ROCK signaling pathway, migration, and proliferation of LUAD cells. Moreover, lncRNA NEAT1, which is highly expressed in LUAD, was detected upstream of miR-490-3p. Upregulation of lncRNA NEAT1 exacerbated the behavior of LUAD cells and offset the suppressive influence of miR-490-3p-mediated upregulation on malignant LUAD cell behavior. CONCLUSION: MiR-490-3p sponging by lncRNA NEAT1 could hamper LUAD progression by inhibiting the RhoA/ROCK signaling pathway. These findings provide new insights for LUAD diagnosis and treatment.

Loss of Lkb1 in CD11c+ myeloid cells protects mice from diet-induced obesity while enhancing glucose intolerance and IL-17/IFN-γ imbalance.

Adipose tissue CD11c+ myeloid cell is an independent risk factor associated with obesity and metabolic disorders. However, the underlying molecular basis remains elusive. Here, we demonstrated that liver kinase B1 (Lkb1), a key bioenergetic sensor, is involved in CD11c+ cell-mediated immune responses in diet-induced obesity. Loss of Lkb1 in CD11c+ cells results in obesity resistance but lower glucose tolerance, which accompanies tissue-specific immune abnormalities. The accumulation and CD80's expression of Lkb1 deficient adipose-tissue specific dendritic cells but not macrophages is restrained. Additionally, the balance of IL-17A and IFN-γ remarkably tips towards the latter in fat T cells and CD11c- macrophages. Mechanistically, IFN-γ promotes apoptosis of preadipocytes and inhibits their adipogenesis while IL-17A promotes the adipogenesis in vitro, which might account in part for the fat gain resistant phenotype. In summary, these findings reveal that Lkb1 is essential for fat CD11c+ dendritic cells responding to HFD exposure and provides new insights into the IL-17A/IFN-γ balance in HFD-induced obesity.

Herombopag promotes platelet engraftment and decreases platelet transfusion after allogeneic hematopoietic stem cell transplantation.

The delayed platelet engraftment associated with allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a common complication and often results in increased transplant-related complications. A single-center, prospective, investigator-initiated pilot study was conducted to explore whether herombopag, a second generation thrombopoietin-receptor agonist, would promote platelet engraftment after allo-HSCT. Between 2/2022 and 06/2022, 17 individuals (median age 39; range 15-58 years) with hematological malignancies were enrolled. Herombopag was given for a median of 22 (range 14-61) days at a dose of 7.5 mg/d. The median time to neutrophil >500/µl was 11 (range 9-19) days. The median time to platelet >20 000/µl and >50 000/µl was 13 (range 8-22), and 20 (range 14-45) days, respectively. Compared with historical controls, the cumulative incidence of platelet engraftment after HSCT was significantly higher in the herombopag group (>20 000/µl at day +21, 88% vs 65%, p = .003; >50 000/µl at day +30, 65% vs. 43%, p = .001). Herombopag also reduced the units of platelet transfusion within 30 days post-SCT (3.6 ± 2.5 vs. 5.4 ± 3.2 U, p = .01). In conclusion, it seems likely that herombopag could enhance platelet engraftment after allo-HSCT.

Risk factors associated with hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation.

Hemorrhagic cystitis (HC) is a common complication of allogeneic hematopoietic stem cell transplantation (HSCT). The incidence is about 7% to 68%, and some patients have to suffer a long period of frequent, urgent, and painful urination, which brings great pain. This study aimed to analyze risk factors of HC and its effect on patient survival. We collected the medical records of 859 patients who underwent HSCT at our hospital between August 2016 and August 2020. Patients with and without HC were matched using propensity score matching at a 1:1 ratio based on sex, age, and diagnosis, and logistic regression analyses were used to identify factors associated with HC. We used Kaplan-Meier curves to analyze the survival rates of patients in the HC and non-HC groups. We also analyzed the relationship between BK viral load and the occurrence of HC using receiver operating characteristic curve (ROC) analysis. After propensity score matching, there were 131 patients each in the HC and non-HC groups. In the HC group, 89 patients (67.9%) had mild HC (stage II°) and 43 (32.1%) had severe HC (stage III-IV). The median interval between stem cell transplantation and HC development was 31 (3-244) days. Univariate analysis indicated that donor age, hematopoietic stem cell source, HLA, acute graft-versus-host disease, busulfan, anti-thymocyte globulin (ATG), total body irradiation, cytomegalovirus (CMV) (urine), and BK polyomavirus (BKV) (urine) were significantly associated with HC. ATG, CMV (urine), and BKV (urine) were independent risk factors for HC based on the multivariate analysis. The Kaplan-Meier survival analysis showed no significant difference between the HC and non-HC groups (P = .14). The 1- and 2-year survival rates in the HC group were 78.4% and 69.6%, respectively, and the corresponding rates in the non-HC group were 84.4% and 80.7%, respectively. ROC analysis indicated that a urine BKV load of 1 × 107 copies/mL was able to stratify the risk of HC. In conclusion, when the BKV load is >1 × 107, we need to be aware of the potential for the development of HC.

Curative Analysis of Patients with Hepatocellular Carcinoma Using Transcatheter Arterial Chemoembolization Combined with Radiofrequency Ablation.

BACKGROUND Transcatheter arterial chemoembolization (TACE) combined with radiofrequency ablation (RFA) can improve the survival of patients with hepatocellular carcinoma (HCC). The purpose was to explore the characteristics of high-risk and low-risk groups of HCC patients receiving combination therapy using a decision tree model. MATERIAL AND METHODS This retrospective cohort study investigated HCC patients treated with a combination of TACE and RFA at our hospital from 2012 to 2018. Decision tree analysis was used to study the 1-year prognosis of patients, and patients were divided into high-risk and low-risk groups. RESULTS We included a total of 142 patients with HCC, 21.83% female and 78.17% male, with the median age of 60 years old. The median follow-up was 13.5 months; 39.44% of patients had progressive disease or death (high-risk group) and 60.56% of patients did not have progressive disease or survival (low-risk group). The area under the curve (AUC) of the decision tree model was 0.846. There were significant differences in sex (P=0.003), age (P=0.038), tumor number (P=0.043), number of RFAs in the first treatment cycle (P.

Vascular normalization therapy with targeted localized vessel bevacizumab infusion in hepatocellular carcinoma after transarterial chemoembolization failure.

BACKGROUND: Hepatocellular carcinoma (HCC) is a highly vascularized tumor in which abnormal blood vessels contribute to poor treatment efficacy and prognosis. In this study, we assessed the efficacy, safety, and potential ability of bevacizumab to normalize tumor vascularity in patients with advanced HCC. METHODS: Patients with histologically or clinically confirmed advanced HCC that were refractory to conventional transarterial chemoembolization (c-TACE) received a transarterial infusion of bevacizumab (5 mg/kg), followed by c-TACE (named as BEVA-TACE). The primary endpoint was overall survival (OS), which was defined as the time from a patient identified as TACE refractory to the occurrence of death. The secondary endpoints included progression-free survival (PFS) and the disease control rate (DCR). RESULTS: From January 2014 to December 2017, 20 patients with Barcelona Clinic Liver Cancer (BCLC) staging scores C (80.0%) or D (20.0%) received BEVA-TACE. The median OS time was 9.2 months [95% confidence interval (CI): 2.1-22.6 months]. The median PFS time was 6.3 months (95% CI: 1.0-10.5 months). Despite the late stage, 1 patient (5.0%) had a complete response (CR), 6 patients (30.0%) had a partial response (PR), and 10 patients (50.0%) had stable disease (SD) [overall response rate (ORR) 30.0%; DCR 85.0%]. The most common adverse events (AEs) were postembolic syndrome (25%), hyperbilirubinemia (10.0%), and melena (10.0%). Severe III-IV oral mucositis and hypertension were observed in only 1 patient (5.0%) during the follow-up period. CONCLUSIONS: BEVA-TACE showed clinical efficacy, and patients with TACE-refractory HCC had acceptable AE rates. A low dose of targeted localized vessel bevacizumab infusion may normalize the condition of tumor blood vessels in patients with advanced HCC.

Moderate to Severe Marrow Fibrosis As a More Advanced Risk Factor for MDS and MDS-AML Patients With Excess of Blasts Receiving Allogeneic Hematopoietic Stem Cell Transplantation.

Marrow fibrosis (MF) is usually accompanied with primary myelodysplastic syndromes (MDS) and no consensus has been reached on the relationship between MF and prognosis. We retrospectively analyzed 239 MDS and MDS derived acute myeloid leukemia patients with known grade of MF who received allogeneic stem cell transplantation (allo-HSCT). Of these, it included 121 (50.6%) without fibrosis (MF-0), 81 (33.9%) with mild fibrosis (MF-1), 37 (15.5%) with moderate to severe fibrosis (MF-2/3). MF-2/3 was associated with more pronounced dysmegakaryopoiesis (P =.002), more frequent karyotype abnormality (P = .039) and increased leukemic transformation. Spliceosome and ras pathway mutation occurred more frequently in patients with MF-2/3. After allo-HSCT, neutrophil and platelet engraftment was significantly delayed in patients with MF-2/3 than those with MF-1 and MF-0 (P = .031, P = .05, respectively). The estimated 3-year overall survival (OS) rates and disease-free survival (DFS) rates were significantly lower in patients with MF-2/3 than in those with MF-0 or MF-1 (P = .018, P = .018, respectively). Notably, in the subgroup of patients with more than 10% bone marrow blasts, MF-2/3 was independently associated with shorter OS and DFS (P = .012, P = .012, respectively) and has improved outcomes for these patients who achieved complete remission (CR) before allo-HSCT. Overall, MF-2/3 as an additional risk factor have the inferior prognosis for MDS and MDS-AML patients with bone marrow blasts ≥10%. Using pretransplantation cytoreductive therapy to obtain CR for these patients may benefit from allo-HSCT.

Effects of ginkgo biloba extract on the cognitive function and expression profile of inflammatory factors in a rat model of hemorrhagic stroke.

Hemorrhagic stroke is a major risk factor for cognitive impairment. Our study aimed to measure the effect of ginkgo biloba extract (EGB761) on the cognitive ability and inflammatory expression in hemorrhagic stroke model SD rats and to analyze their relationship. Forty SD rats were divided randomly into an SD group (normal control SD rats), an SD+EGB761 group (normal control SD rats supplemented with 45 mg/kg EGB761), a CO group (hemorrhagic stroke model SD rats using collagenase), and a CO+EGB761 group (hemorrhagic stroke model SD rats supplemented with 45 mg/kg EGB761) consisting of 10 rats, respectively. The Y-electric maze test was selected to measure the cognitive function in four groups. Furthermore, enzyme-linked immunosorbent assay and real-time PCR were, respectively, applied for detecting the protein and gene expression profiles of inflammatory factors in primary cultured microglia. Compared with rats in the SD group, the average time of electrical simulation for mastering criteria was prolonged in the CO group (P<0.05). Furthermore, expression levels of proinflammatory cytokines interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor-α and anti-inflammatory cytokines IL-4, IL-10, and tumor necrosis factor-ß were significantly increased and decreased, respectively, in rats of the CO group compared with the SD group (P<0.05). The results of electrical simulation time, inflammatory factors protein, and gene expression profile in rats of the CO+EGB761 group compared with the CO group were opposite to above contrast (P<0.05). Ginkgo biloba extract could alleviate the cognitive dysfunction after hemorrhagic stroke in SD rats; this is associated with regulating the expression of inflammatory factors secreted by microglia.

Hypertonic Saline Alleviates Brain Edema After Traumatic Brain Injury via Downregulation of Aquaporin 4 in Rats.

BACKGROUND Hypertonic saline (HS) has been successfully used for treatment of various forms of brain edema. Decreased expression of aquaporin (AQP)4 and pro-inflammatory cytokines such as tumor necrosis factor (TNF)-a and interleukin (IL)-1b have been linked to edema pathogenesis. This study examined the effect of 3% HS on brain edema in a rat model of traumatic brain injury (TBI). MATERIAL AND METHODS Sprague-Dawley rats were subjected to TBI induced by a controlled cortical impactor. The HS group was injected with 3% NaCl until the end of the study period. AQP4, TNF-α, IL-1ß, and caspase-3 levels were measured by Western blotting, immunohistochemistry, enzyme-linked immunosorbent assay, and quantitative real-time PCR. Brain water content was also measured. Apoptotic cells in brain tissue were detected with terminal deoxynucleotidyl transferase dUTP nick-end labeling. Brain water content decreased following treatment with 3% HS relative to the TBI group. RESULTS This was accompanied by decreases in AQP4, TNF-α, and IL-1ß mRNA and protein levels. TBI resulted in increases in caspase-3 mRNA expression and the number of apoptotic cells; treatment with 3% HS suppressed apoptosis as compared to the TBI group. CONCLUSIONS Treatment with 3% HS ameliorated TBI-induced brain edema, possibly by suppressing brain edema, pro-inflammatory cytokine expression, and apoptosis.

Comparative Study of Percutaneous Transhepatic Biliary Stent Placement with or without Iodine-125 Seeds for Treating Patients with Malignant Biliary Obstruction.

PURPOSE: To prospectively evaluate safety and efficacy of biliary stent placement with iodine-125 (125I) seeds in patients with malignant obstructive jaundice (MOJ). MATERIALS AND METHODS: From July 2011 to June 2014, 55 patients were enrolled (group A, 11 men and 17 women, mean age 70.93 y ± 8.58; group B, 14 men and 13 women, mean age 70.26 y ± 9.71). All patients were randomly assigned to placement of a biliary stent with 125I seeds (group A) or biliary stent only (group B). After stent placement, outcomes were measured regarding relief of MOJ. Clinical success rate, survival time, and safety were recorded. P < .05 was considered to indicate significant difference. RESULTS: Stents were successfully placed in all 55 patients. MOJ was relieved in all patients, and there were no significant differences in complications related to stent insertion between the 2 groups. Mean and median stent patency were 191 days ± 19.8 (95% confidence interval [CI], 152-230 d) and 179 days ± 191.4 (95% CI, 87-267 d) in group A and 88.3 days ± 16.3 (95% CI, 61-114 d) and 77 days ± 88.2 (95% CI, 65-86 d) in group B (P < .001, log-rank test). Mean and median survival time were 222.6 days ± 21.0 (95% CI, 181-263 d) and 241 days ± 18.2 (95% CI, 179-270 d) in group A and 139.1 days ± 14.5 (95% CI, 110-167 d) and 142 days ± 16.3 (95% CI, 83-177 d) in group B (P < .001, log-rank test). CONCLUSIONS: 125I seeds combined with biliary stent placement could significantly improve stent patency. The procedure seems to be safe and to extend survival compared with self-expandable biliary stent placement.