scholarly journals Efficacy and Safety of Ibrutinib in Central Nervous System Lymphoma: A PRISMA-Compliant Single-Arm Meta-Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Liwei Lv ◽  
Xuefei Sun ◽  
Yuchen Wu ◽  
Qu Cui ◽  
Yuedan Chen ◽  
...  

BackgroundCentral nervous system lymphoma (CNSL) is an aggressive lymphoma. Studies investigating primary CNSL determined that the Bruton tyrosine kinase (BTK) played an important role in pathogenesis. Ibrutinib, an oral BTK inhibitor, is a new treatment strategy for CNSL. The purpose of this meta-analysis was to clarify the effectiveness and safety of ibrutinib in the treatment of CNSL.MethodsA systematic search of PubMed, Embase, Cochrane library, Wanfang Data Knowledge Service Platform, and China National Knowledge Infrastructure databases was conducted through to 31 October 2019. Studies involving patients with CNSL who received ibrutinib that reported the overall response (OR), complete remission (CR), and partial response (PR) were included. The random-effects or fixed-effects model with double arcsine transformation was used for the pooled rates and 95% confidence intervals (CI) were determined for all outcomes.ResultsEight studies including 162 patients were identified and included in the meta-analysis. The pooled OR rate after treatment with ibrutinib was 69% (95% CI, 61–79%, I2 = 47.57%, p = 0.06), while the pooled CR and PR was 52% (95% CI, 35–68%, I2 = 74.95%, p = 0.00) and 17% (95% CI, 7–30%, I2 = 67.85%, p = 0.00), respectively. Among PCNSL patients, including new diagnoses PCNSL and R/R PCNSL, the pooled OR rate was 72% (95% CI, 63–80%, I2 = 49.20%, p = 0.06) while the pooled CR and PR rates were 53% (95% CI, 33–73%, I2 = 75.04%, p = 0.00) and 22% (95% CI, 14–30%, I2 = 46.30%, p = 0.07), respectively. Common adverse events above grade 3 included cytopenia and infections.ConclusionsThe ibrutinib-containing therapy was well tolerated and offered incremental benefit to patients with CNSL. However, randomized-controlled studies that directly compare efficacy and adverse events of ibrutinib are still needed.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42020218974.

2021 ◽  
Author(s):  
Xiaohong Zheng ◽  
Parker Li ◽  
Qianqian Dong ◽  
Yihong Duan ◽  
Shoubo Yang ◽  
...  

Abstract Background Diagnosing primary central nervous system lymphoma (PCNSL) remains a challenge. MicroRNAs (miRNAs) are promising noninvasive markers for the identification of PCNSL. The present study aims to assess the diagnostic value of miRNAs for PCNSL patients as biomarkers. Methods We systematically searched PubMed, Embase and the Cochrane library from inception to June 31, 2020. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), together with the summary receiver operator characteristic (SROC) curve, and area under the SROC curve (AUC) value were used to estimate overall diagnostic performance. We used Q statistic and I2 to test heterogeneity, and used subgroup analyses to investigate the source of heterogeneity. The statistical analyses were independently performed by two investigators using Stata 14.0 and Revman 5.3. Results In total, eleven studies from six records were included in the current meta-analysis with 281 PCNSL patients and 367 controls. Our statistical analysis demonstrated that the pooled sensitivity, specificity, PLR, NLR, DOR, and AUC were 0.91 (95% CI 0.84–0.95), 0.88 (95% CI 0.84–0.91), 7.48 (95% CI 5.71–9.78), 0.11 (95% CI 0.06–0.19), 70 (95% CI 35–142), and 0.90 (95% CI 0.87–0.92), respectively. The studies had substantial heterogeneity (I2 = 54%, 95% CI 0-100). Two subgroup analyses were conducted based on the type of specimen and miRNAs profiled. Conclusions This meta-analysis indicated miRNAs were suitable as noninvasive diagnostic biomarkers for PCNSL with high accuracy. In addition, both cerebrospinal fluid -based and blood-based miRNAs assays for PCNSL detection were considered reliable for clinical application. MicroRNA-21 assays also seemed to be more accurate in the diagnosis of PCNSL. Good quality studies with large samples should be conducted to verify our results.


2020 ◽  
pp. 112972982095099
Author(s):  
Xiaohong Wu ◽  
Tiantian Zhang ◽  
Lichan Chen ◽  
Xisui Chen

Background: Recently, some studies have shown that prolonging flush interval is safe and feasible for patients who complete chemotherapy. However, there is no consensus about the optimal flush interval for those patients. Objective: The purpose of this review was to evaluate whether the flush interval could be prolonged based on monthly interval for regular maintenance and to explore the optimal flush interval. Data sources: We searched the following databases for articles published between 1 January 1982 and 21 February 2020: PubMed, Cochrane Library, Web of Science, EMBASE, CINAHL, and Ovid. Study eligibility criteria: Randomized controlled trials, retrospective and prospective cohort studies of flush interval less than 4 weeks versus longer than 4 weeks for patients who completed chemotherapy, were included. Results: Two reviewers extracted information and assessed the quality of the articles independently. In total, 389 articles were retrieved, and 4 studies including 862 cases fulfilled the inclusion criteria. There was no statistical heterogeneity ( I2 = 0, p > 0.05) among the included studies. Hence, the fixed-effects model was used for the meta-analysis. The meta-analysis showed that the total complication rate associated with longer than 4-week interval was higher than that associated with less than 4-week interval. Nevertheless, there was no significant difference between the two groups (7.2% vs 7.6%, p = 0.83). Moreover, the meta-analysis showed that the total complication and catheter occlusion rates associated with the 4-week interval were higher than those associated with the 8-week interval. However, there was no significant difference between the two groups (total complications: 11.4% vs 9.5%, p = 0.68; catheter occlusions: 4.9% vs 4.1%, p = 0.89). Limitations: Only four non-randomized controlled studies were included, and the outcomes of the included studies were reported incompletely. Conclusion: Extending the flush interval to longer than 4 weeks is safe and feasible. Based on previous studies, extending the flush interval to 8 weeks might not increase the incidence of total complications and catheter occlusions. However, there is no conclusion on whether the flush interval could be extended to 3 months or longer.


2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaohong Zheng ◽  
Parker Li ◽  
Qianqian Dong ◽  
Yihong Duan ◽  
Shoubo Yang ◽  
...  

BackgroundDiagnosing primary central nervous system lymphoma (PCNSL) remains a challenge. MicroRNAs (miRNAs) are promising noninvasive markers for the identification of PCNSL. The present study aims to assess the diagnostic value of miRNAs for PCNSL patients as biomarkers.MethodsWe systematically searched PubMed, Embase, and the Cochrane library from inception to January 31, 2021. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), together with the summary receiver operator characteristic (SROC) curve, and the area under the SROC curve (AUC) value were used to estimate the overall diagnostic performance. We used Q statistic and I2 to test heterogeneity and used subgroup analyses to investigate the source of heterogeneity. The statistical analyses were independently performed by two investigators using Stata 14.0 and Revman 5.3.ResultsIn total, 11 studies from 6 records were included in the current meta-analysis with 281 PCNSL patients and 367 controls. Our statistical analysis demonstrated that the pooled sensitivity, specificity, PLR, NLR, DOR, and AUC were 0.91 (95% CI 0.84–0.95), 0.88 (95% CI 0.84–0.91), 7.48 (95% CI 5.71–9.78), 0.11 (95% CI 0.06–0.19), 70 (95% CI 35–142), and 0.90 (95% CI 0.87–0.92), respectively. The studies had substantial heterogeneity (I2 = 54%, 95% CI 0–100). Two subgroup analyses were conducted based on the type of specimen and miRNAs profiled.ConclusionsThis meta-analysis indicated that miRNAs were suitable as noninvasive diagnostic biomarkers for PCNSL with high accuracy. In addition, both cerebrospinal fluid-based and blood-based miRNAs assays for PCNSL detection were considered reliable for clinical application. MicroRNA-21 assays also seemed to be more accurate in the diagnosis of PCNSL. Good quality studies with large samples should be conducted to verify our results.


2020 ◽  
Author(s):  
Lili Zhou ◽  
Hai Yi ◽  
Dan Chen ◽  
Qian Zhang ◽  
Fangyi Fan ◽  
...  

Abstract BackgroundPrimary central nervous system lymphoma (PCNSL) is a highly aggressive non-hodgkin’s lymphoma with unfavorable prognosis. Currently, the diagnosis of PCNSL relies on brain excisional biopsy, which is an invasive procedure, carries the risk of complications such as intracranial hemorrhage and functional impairment. Finding effective biomarkers will help us to diagnose PCNSL faster and safer.MethodsThis systematic review will be conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol (PRISMA-P) 2015 guideline.We will search databases including PubMed, Cochrane Library, Medline, Web of Science, EMBASE and CNKI. The studies that demonstrated the diagnostic value of certain biomarkers in CSF for PCNSL will be included. For quantitative value, the standardized mean diffenence (SMD) and their 95% confidence intervals (CI) will be calculated. The outcomes are the mean difference of biomarker levels in CSF between PCNSL patients and controls.DiscussionIn this systematic review we will analyze the studies of the biomarkers in cerebrospinal fluid for diagnosis of PCNSL. This research can help us to identify the biomarkers with diagnostic value for PCNSL, making diagnosis of PCNSL easier, faster and safer.Systematic review registrationPROSPERO CRD42020218143.


2020 ◽  
Author(s):  
xueyi sun ◽  
xianfei ding ◽  
huoyan liang ◽  
xiaojuan zhang ◽  
shaohua liu ◽  
...  

Abstract Background: Multiple studies have reported that mesenchymal stem cell (MSC) therapy has beneficial effects in experimental models of sepsis. However, this finding remains inconclusive. This study was performed to systematically determine the connection between MSC therapy and mortality in sepsis animal models by pooling and analyzing data from newly published studies. Methods: A detailed search of related studies from 2009 to 2019 was conducted in four databases, including MEDLINE, EMBASE, Cochrane Library, and Web of Science. After browsing and filtering out articles that met the inclusion criteria for statistical analysis, the inverse variance method of the fixed effects model was used to calculate the pooled odds ratios (ORs) and their 95% confidence intervals (CIs). Results: Twenty-nine animal studies, including 1,266 animals, were identified. None of the studies were judged to have a low risk of bias. The meta-analysis demonstrated that MSC therapy was related to a significantly lower mortality rate (OR 0.29, 95% CI 0.22–0.38, P <0.001). Subgroup analyses performed based on the MSC injection dose (<1.0 × 10 6 cells, OR=0.33, 95% CI 0.20–0.56, P <0.001; 1.0 × 10 6 cells, OR=0.24, 95% CI 0.16–0.35, P <0.001) and injection time (<1 hour, OR=0.24, 95% CI 0.13–0.45, P <0.001; 1 hour, OR=0.28, 95% CI 0.17–0.46, P <0.001) demonstrated that treatment with MSCs significantly reduced the mortality rate of animals with sepsis. Conclusion: This up-to-date meta-analysis showed a connection between MSC therapy and lower mortality in sepsis animal models, supporting the potential therapeutic effect of MSC treatment in future clinical trials. The results in this study contradict a previous meta-analysis with regards to the ideal dose of MSC therapy. Thus, further research is required to support these findings.


Vaccines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 939
Author(s):  
Jiaxin Chen ◽  
Yuangui Cai ◽  
Yicong Chen ◽  
Anthony P. Williams ◽  
Yifang Gao ◽  
...  

Background: Nervous and muscular adverse events (NMAEs) have garnered considerable attention after the vaccination against coronavirus disease (COVID-19). However, the incidences of NMAEs remain unclear. We aimed to calculate the pooled event rate of NMAEs after COVID-19 vaccination. Methods: A systematic review and meta-analysis of clinical trials on the incidences of NMAEs after COVID-19 vaccination was conducted. The PubMed, Medline, Embase, Cochrane Library, and Chinese National Knowledge Infrastructure databases were searched from inception to 2 June 2021. Two independent reviewers selected the study and extracted the data. Categorical variables were analyzed using Pearson’s chi-square test. The pooled odds ratio (OR) with the corresponding 95% confidence intervals (CIs) were estimated and generated with random or fixed effects models. The protocol of the present study was registered on PROSPERO (CRD42021240450). Results: In 15 phase 1/2 trials, NMAEs occurred in 29.2% vs. 21.6% (p < 0.001) vaccinated participants and controls. Headache and myalgia accounted for 98.2% and 97.7%, and their incidences were 16.4% vs. 13.9% (OR = 1.97, 95% CI = 1.28–3.06, p = 0.002) and 16.0% vs. 7.9% (OR = 3.31, 95% CI = 2.05–5.35, p < 0.001) in the vaccine and control groups, respectively. Headache and myalgia were more frequent in the newly licensed vaccines (OR = 1.97, 95% CI = 1.28–3.06, p = 0.02 and OR = 3.31, 95% CI = 2.05–5.35, p < 0.001) and younger adults (OR = 1.40, 95% CI = 1.12–1.75, p = 0.003 and OR = 1.54, 95% CI = 1.20–1.96, p < 0.001). In four open-label trials, the incidences of headache, myalgia, and unsolicited NMAEs were 38.7%, 27.4%, and 1.5%. Following vaccination in phase 3 trials, headache and myalgia were still common with a rate of 29.5% and 19.2%, although the unsolicited NMAEs with incidence rates of ≤ 0.7% were not different from the control group in each study. Conclusions: Following the vaccination, NMAEs are common of which headache and myalgia comprised a considerable measure, although life-threatening unsolicited events are rare. NMAEs should be continuously monitored during the ongoing global COVID-19 vaccination program.


PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e10859
Author(s):  
Lili Qin ◽  
Yueqi Wang ◽  
Na Yang ◽  
Yangyu Zhang ◽  
Tianye Zhao ◽  
...  

Background Tissue inhibitor of metalloproteinase 1 (TIMP-1) has recently been shown to be dependent on or independent of Matrix metalloproteinases (MMPs) in its roles in tumorigenesis and progression. This appreciation has prompted various studies assessing the prognostic value of TIMP-1 in patients with gastrointestinal cancer, however, the conclusions were still inconsistent. The aim of this study was to assess the prognostic value of TIMP-1-immunohistochemistry (IHC) staining and pretreatment serum/plasma TIMP-1 level in gastrointestinal cancer survival as well as the association between TIMP-1 and clinicopathologic features. Methods The meta-analysis was registered in the International Prospective Register of Systematic Reviews (PROSPERO; Registration NO. CRD42020185407) and followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. A highly sensitive literature search was performed in electronic databases including PubMed, EMBASE and the Cochrane Library. Heterogeneity analysis was conducted using both chi-square-based Q statistics and the I2 test. The pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to assess the prognostic value of TIMP-1 using the fixed-effects model. Odds ratios (ORs) with 95% CIs were calculated to evaluate the associations between TIMP-1 and clinicopathological characteristics. The meta-analysis was conducted using STATA 12.0 software. Results A total of 3,958 patients from twenty-two studies were included in the meta-analysis. Elevated TIMP-1 levels were significantly associated with poor survival in gastrointestinal cancer (TIMP-1-IHC staining: HR = 2.04, 95% CI [1.59–2.61], I2 = 35.7%, PQ = 0.156; pretreatment serum/plasma TIMP-1 levels: HR = 2.02, 95% CI [1.80–2.28], I2 = 0%, PQ = 0.630). Moreover, clinicopathological parameter data analysis showed that elevated TIMP-1 levels were significantly associated with lymph node metastasis (N1/N2/N3 vs N0: OR = 2.92, 95% CI [1.95–4.38]) and higher TNM stages (III/IV vs I/II: OR = 2.73, 95% CI [1.23–6.04]). Conclusion Both TIMP-1-positive IHC staining and high serum/plasma TIMP-1 levels are poor prognostic factors for the survival of gastrointestinal cancer. In addition, TIMP-1 overexpression was correlated with more advanced clinicopathological features.


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