Background: Despite the acknowledged benefits of immune checkpoint inhibitor (ICI)-based combination therapy (either with other checkpoint inhibitors, chemotherapy, targeted therapy, or radiotherapy), little is known about the impact of age on the efficacy of ICI-based combination therapy in non-small-cell lung cancer (NSCLC) patients. We conducted a systematic review and meta-analysis to investigate the differences in the benefits of ICI-based combination therapy for NSCLC by age (cut-off age, 65 years). Methods: We systematically searched randomized controlled trials (RCTs) of ICI plus other therapies including other ICIs, chemotherapies, targeted therapies, or radiotherapies, in the PubMed, Embase, and Cochrane databases with available hazard ratios (HRs) and 95% confidence intervals (CIs) for death and disease progression according to patient age. The search deadline was May 25, 2020. First, we calculated the pooled HRs of younger and older patients based on the HRs from each trial. Second, we assessed the pooled ratio of HRs reported in older patients to the HRs reported in younger patients for progression or death by the random-effects model. An estimated pooled HR ratio was lower than 1 indicating a better effect in older patients and higher than 1 indicating a better effect in younger patients. Results: A total of 10 eligible RCTs were included in our meta-analysis. The pooled HR for overall survival (OS) comparing ICI combined with other therapies to non-ICI regimens was 0.67 (95%CI 0.58-0.78) for younger patients and 0.79 (95%CI 0.70-0.90) for older patients. The pooled HRs ratio for OS reported in older patients compared to younger patients was 1.16 (95%CI 0.99-1.34), indicating no statistically significant difference between younger and older patients. Consistent with the findings related to OS, the analysis also demonstrated that ICI-based immunotherapy could significantly prolong progression-free survival (PFS) in younger and older patients (HR = 0.55; 95% CI 0.47-0.66, and HR = 0.64; 95% CI 0.57-0.71). The same results could also be observed Yan et al. Age and ICI-Based Combination Therapy in the pooled HRs ratio for PFS (HR = 1.15, 95%CI 0.91-1.46) indicating comparable efficacy of ICI-based combination therapy in younger and older patients with NSCLC. Conclusion: ICI-based combination therapy vs. non-ICI treatment had comparable efficacy in younger and older NSCLC patients with a cutoff age of 65 years.

BACKGROUND: Although the flow diverter has advantages in the treatment of intracranial aneurysms, pooled studies that directly compare it with conventional endovascular treatments are rare. PURPOSE: Our aim was to compare the safety and efficacy of flow-diverter and conventional endovascular treatments in intracranial aneurysms.DATA SOURCES: We performed a comprehensive search of the literature using PubMed, EMBASE, and the Cochrane Database. STUDY SELECTION:We included only studies that directly compared the angiographic and clinical outcomes of flow-diverter and conventional endovascular treatments.DATA ANALYSIS: Random effects or fixed effects meta-analysis was used to pool the cumulative rate of short-and long-term angiographic and clinical outcomes.DATA SYNTHESIS: Eighteen studies with 1001 patients with flow diverters and 1133 patients with conventional endovascular treatments were included; 1015 and 1201 aneurysm procedures were performed, respectively. The flow-diverter group had aneurysms of a larger size (standard mean difference, 0.22; 95% CI, 0.03-0.41; P ¼ .026). There was a higher risk of complications in the flow-diverter group compared with the conventional endovascular group (OR, 1.4; 95% CI, 1.01-1.96; P ¼ .045) during procedures. The follow-up angiographic results of flow-diverter treatment indicated a higher rate of complete occlusion (OR, 2.55; 95% CI, 1.70-3.83; P , .001) and lower rates of recurrence (OR, 0.24; 95% CI, 0.12-0.46; P , .001) and retreatment (OR, 0.31; 95% CI, 0.21-0.47; P , .001).LIMITATIONS: Limitations include a retrospective, observational design in some studies, high heterogeneity, and selection bias. CONCLUSIONS:Compared with the conventional endovascular treatments, the placement of a flow diverter may lead to more procedure-related complications, but there is no difference in safety, and it is more effective in the long term.ABBREVIATIONS: BAC ¼ balloon-assisted coiling; CEV ¼ conventional endovascular; FD ¼ flow diverter; IA ¼ intracranial aneurysm; SAC ¼ stent-assisted coiling; SMD ¼ standard mean difference R apid technologic advances in endovascular treatments have been transforming the treatment modalities of intracranial aneurysms (IAs) in recent years. The Guglielmi detachable coil (Stryker), introduced in the early 1990s, provided an alternative to traditional surgical clipping in the treatment of IAs. 1 After that, reconstructive techniques such as balloon-assisted coiling (BAC) and stent-assisted coiling (SAC), were initially used. 2,3 Most recently, low-profile visualized intraluminal support (LVIS; MicroVention), a self-expandable, recyclable, braided stent, has also been widely adopted in clinical practice. 4 Compared with these standard and conventional stent methods, flow diverters (FDs), like the Pipeline Embolization Device (PED; Medtronic) approved by the US Food and Drug Administration in 2011, 5,6 have greater metal coverage and have broader indications for the treatment of complex aneurysms, such as large and giant ICA aneurysms and fusiform, disse...

Background: Liver transplantation (LT) represents the most effective treatment for many end-stage liver diseases. While donation after cardiac death (DCD) donor livers are used due to organ shortage, acute rejection (ACR) remains an important risk factor affecting the survival of recipients following transplantation. Although immunosuppressive agents can be used, they are associated with complications. Bone marrow mesenchymal stem cells (BMMSCs) are used in the treatment of organ transplantation; however, there is limited colonization in the target organs and a short survival time following BMMSCs application. Thus, an optimized BMMSCs application method is required to suppress immune rejection and promote the long-term survival of allogeneic liver transplant recipients. Methods: BMMSCs were isolated and modified with heme oxygenase 1 (HO-1) gene. HO-1/BMMSCs were perfused into the donor liver in vitro using a normothermic machine perfusion (NMP) system, followed by LT. The severity of ACR was evaluated based on the liver histopathology. Gene chip technology was used to detect differential gene expression, and the flow cytometry was used to analyze changes in natural killer (NK) T cells. Results: NMP can induce BMMSCs to colonize the donor liver during in vitro preservation, and the survival of HO-1/BMMSCs in the liver grafts was significantly longer than that of BMMSCs. When the donor liver contained HO-1/BMMSCs, the ACR is obviously controlled, and the survival time was significantly prolonged. The application of HO-1/BMMSCs reduces the number of NKT cells in the liver grafts, increases the expression of the NKT cell co-inhibitory receptors, and reduces the level of NKT cell expression of IFN-γ. Thus, NK cell and CD8+ T cell activation was inhibited, which reduced acute of rejection of the transplanted liver. Conclusions: The NMP system preserves the DCD donor liver in vitro, and also allows large quantities of BMMSCs to colonize the liver. HO-1-modified BMMSCs are able to improve and prolong the local immunosuppressive effect of BMMSCs following transplantation by reducing the number of NKT cells and up-regulating NKT cell co-inhibitory receptor expression. This results in the transmission of inhibitory signals to NKT cells, reduced NKT cell IFN-γ levels, and the inhibition of ACR.