scholarly journals The Efficacy and Safety of Programmed Death-1 and Programmed Death Ligand 1 Inhibitors for the Treatment of Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Shukang He ◽  
Weichao Jiang ◽  
Kai Fan ◽  
Xiaobei Wang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Group Treatment ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Control Group ◽  
Efficacy And Safety ◽  
Programmed Death Ligand 1 ◽  
Programmed Death ◽  
Programmed Death 1

BackgroundHepatocellular carcinoma (HCC) is often diagnosed at an advanced stage where only systemic treatment can be offered. The emergence of immune checkpoint inhibitors (ICIs) provides hope for the treatment of HCC. In this study, we performed a meta-analysis to provide evidence for the efficacy and safety of ICIs in the treatment of HCC.MethodsThe following databases and websites were searched: Embase, PubMed, Cochrane Library and ClinicalTrials.gov. The primary endpoints were response rate (RR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS).ResultsFinally, twelve studies were included in this meta-analysis. When the corresponding outcome indicators and their 95% confidence intervals (CIs) were pooled directly, the overall RR, DCR, PFS and OS were 0.17 (0.15-0.19, I2 = 56.2%, P=0.009), 0.58 (0.55-0.61, I2 = 75.9%, P<0.001), 3.27 months (2.99-3.55, I2 = 73.0%, P=0.001), 11.73 months (10.79-12.67, I2 = 90.3%, P<0.001). Compared to the control group, treatment with ICIs significantly improved RR, PFS and OS, the OR and HRs were 3.11 (2.17-4.44, P<0.001), 0.852 (0.745-0.974, P=0.019) and 0.790 (0.685-0.911, P=0.001), respectively. However, no significant improvement in DCR was found in ICIs treatment in this meta-analysis.ConclusionHCC patients would benefit from ICIs treatment, however, more studies are needed in the future to provide more useful evidence for the treatment of HCC by programmed death-1 (PD-1) or programmed death ligand 1 (PD-L1) inhibitors.

scholarly journals Case Report: Complete Response of Primary Massive Hepatocellular Carcinoma to Anti-Programmed Death Ligand-1 Antibody Following Progression on Anti-Programmed Death-1 Antibody

2021 ◽  
Vol 12 ◽  
Author(s):  
Gang Liu ◽  
Wenxuan Zhou ◽  
Xiaoli Li ◽  
Lijie Guo ◽  
Tingting He ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Combination Therapy ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Complete Response ◽  
Programmed Death Ligand 1 ◽  
Programmed Death ◽  
Progression Of Disease ◽  
Antibody Immunotherapy ◽  
Programmed Death 1

Hepatocellular carcinoma (HCC) is an aggressive liver tumor that occurs due to chronic liver disease, and it has a high mortality rate and limited treatment options. Immune checkpoint inhibitors have been successfully introduced and used in cancer therapy, among which inhibitors of programmed death ligand-1 (PD-L1) and its receptor programmed death-1 (PD-1) are commonly administered for HCC as combination therapy, including combined anti-angiogenic and immunotherapy combination therapy. We report a case of a primary massive HCC patient with portal hepatic vein tumor thrombus who had a good response to atezolizumab in combination with bevacizumab, following progression of disease on combined immunotherapy with pembrolizumab and lenvatinib. This case demonstrates for the first time that an HCC patient who is resistant to anti-PD-1 antibody immunotherapy can benefit from anti-PD-L1 antibody immunotherapy, providing a potentially promising strategy for the treatment of HCC.

scholarly journals Intravenous dexmedetomidine during spinal anaesthesia for caesarean section: A meta-analysis of randomized trials

2017 ◽  
Vol 45 (3) ◽  
pp. 924-932 ◽  
Author(s):  
Zeqing Bao ◽  
Chengmao Zhou ◽  
Xianxue Wang ◽  
Yu Zhu
Keyword(s):  
Caesarean Section ◽  
Spinal Anaesthesia ◽  
Randomized Trials ◽  
Meta Analysis ◽  
Relevant Literature ◽  
Nausea And Vomiting ◽  
Cochrane Library ◽  
Control Group ◽  
Efficacy And Safety ◽  
The Cochrane Library

Objective To evaluate the efficacy and safety of spinal anaesthesia using dexmedetomidine for caesarean section. Methods PubMed, The Cochrane Library, and CNKI were searched for relevant literature. Results The incidence of nausea and vomiting in the dexmedetomidine group was significantly lower than that in the control group (OR = 0.21, 95% CI: 0.12–0.35, P < 0.00001). No difference was found in the incidence of pruritus between the two groups (OR = 1.21, 95% CI: 0.36–4.09, P = 0.76).The dexmedetomidine group had a higher incidence of bradycardia than did the control group (OR = 2.20, 95% CI: 1.02–4.77, P = 0.05). The incidence of shivering in the dexmedetomidine group was significantly lower than that in the control group (OR = 0.20, 95% CI: 0.13–0.32, P < 0.00001). The incidence of hypotension was not different between the two groups (OR = 0.88, 95% CI: 0.49–1.56, P = 0.65). Conclusion Dexmedetomidine can decrease the incidence of nausea, vomiting, bradycardia, and shivering with spinal anaesthesia during caesarean section.

scholarly journals Efficacy and safety of daratumumab in the treatment of multiple myeloma: a systematic review and meta-analysis

2021 ◽  
Vol 49 (8) ◽  
pp. 030006052110381
Author(s):  
Yin Wang ◽  
Yanqing Li ◽  
Ye Chai
Keyword(s):  
Multiple Myeloma ◽  
Meta Analysis ◽  
Complete Response ◽  
Library Science ◽  
Cochrane Library ◽  
Control Group ◽  
Efficacy And Safety ◽  
Risk Patients ◽  
Grade 3 ◽  
Combination Regimens

Objective To systematically evaluate the efficacy and safety of combination regimens containing daratumumab in patients with multiple myeloma (MM). Methods A systematic search of publications listed on electronic databases (PubMed®, The Cochrane Library, Science Direct and Web of Science) between inception and 13 November 2020 was conducted to find randomized controlled trials (RCTs) that included patients with MM that were treated with combination regimens containing daratumumab. Results A total of seven RCTs were included ( n = 4268 patients). Meta-analysis showed that compared with the control group, the group containing daratumumab showed a significantly better overall response rate and a complete response or better. Daratumumab improved efficacy in both standard-risk and cytogenetically high-risk patients with MM. The prevalence of neutropenia (≥grade 3) and pneumonia was significantly higher in the daratumumab group compared with the control group. Conclusion The available evidence demonstrated that the clinical application of combination regimens containing daratumumab improved the efficacy in patients with MM and had acceptable safety.

scholarly journals Clinical efficacy on glycemic control and safety of mesenchymal stem cells in patients with diabetes mellitus: Systematic review and meta-analysis of RCT data

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0247662
Author(s):  
Jingjing He ◽  
Desheng Kong ◽  
Zhifen Yang ◽  
Ruiyun Guo ◽  
Asiamah Ernest Amponsah ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Treatment Group ◽  
Random Effects ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Control Group ◽  
Efficacy And Safety ◽  
Significant Difference

Background Diabetes mellitus as a chronic metabolic disease is threatening human health seriously. Although numerous clinical trials have been registered for the treatment of diabetes with stem cells, no articles have been published to summarize the efficacy and safety of mesenchymal stem cells (MSCs) in randomized controlled trials (RCTs). Methods and findings The aim of this study was to systematically review the evidence from RCTs and, where possible, conduct meta-analyses to provide a reliable numerical summary and the most comprehensive assessment of therapeutic efficacy and safety with MSCs in diabetes. PubMed, Web of Science, Ovid, the Cochrane Library and CNKI were searched. The retrieval time was from establishment of these databases to January 4, 2020. Seven RCTs were eligible for analysis, including 413 participants. Meta-analysis results showed that there were no significant differences in the reduction of fasting plasma glucose (FPG) compared to the baseline [mean difference (MD) = -1.05, 95% confidence interval (CI) (-2.26,0.16), P<0.01, I2 = 94%] and the control group [MD = -0.62, 95%CI (-1.46,0.23), P<0.01, I2 = 87%]. The MSCs treatment group showed a significant decrease in hemoglobin (Hb) A1c [random-effects, MD = -1.32, 95%CI (-2.06, -0.57), P<0.01, I2 = 90%] after treatment. Additionally, HbA1c reduced more significantly in MSC treatment group than in control group [random-effects, MD = -0.87, 95%CI (-1.53, -0.22), P<0.01, I2 = 82%] at the end of follow-up. However, as for fasting C-peptide levels, the estimated pooled MD showed that there was no significant increase [MD = -0.07, 95%CI (-0.30, 0.16), P<0.01, I2 = 94%] in MSCs treatment group compared with that in control group. Notably, there was no significant difference in the incidence of adverse events between MSCs treatment group and control group [relative risk (RR) = 0.98, 95%CI (0.72, 1.32), P = 0.02, I2 = 70%]. The most commonly observed adverse reaction in the MSC treatment group was hypoglycemia (29.95%). Conclusions This meta-analysis revealed MSCs therapy may be an effective and safe intervention in subjects with diabetes. However, due to the limited studies, a number of high-quality as well as large-scale RCTs should be performed to confirm these conclusions.

scholarly journals Efficacy and Safety of Tanshinone for Chronic Kidney Disease: A Meta-Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Yao Zhou ◽  
Shi-min Jiang ◽  
Li Li ◽  
Ying Wang ◽  
Lei Ding ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Treatment Group ◽  
Kidney Disease ◽  
Subgroup Analysis ◽  
Protein Level ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Control Group ◽  
Efficacy And Safety ◽  
Urine Protein

Objective. To systematically evaluate the efficacy and safety of tanshinone for chronic kidney disease (CKD). Methods. Randomized controlled trials (RCTs) on the treatment of CKD using tanshinone were searched using 4 Chinese databases (China National Knowledge Infrastructure (CNKI), Value In Paper (VIP), Wanfang, and Chinese Biology Medicine (CBM)) and 3 English databases (PubMed, Cochrane Library, and Excerpta Medica Database (Embase)). The results included data on blood urine nitrogen (BUN), serum creatinine (Scr), glomerular filtration rate (GFR), 24 h urine protein, microalbuminuria (mALB), β2-macroglobulin (β2-MG), cystatin C (CysC), and safety events. The data were analyzed using Revman 5.3 and Stata 12.0 software. Results. Twenty-one studies were entered into this meta-analysis, which involved 1857 patients including 954 cases from the tanshinone treatment group and 903 cases from the control group. BUN levels in the tanshinone treatment group were significantly reduced compared with the control (standardized mean difference (SMD) = −0.65, 95% confidence interval (CI): −0.81 to −0.49, p<0.01). In addition, subgroup analysis indicated that tanshinone had a significant effect in reducing Scr levels at 14, 21, and 28 days. Scr levels in the tanshinone treatment group were significantly reduced compared with the control group (SMD = −1.40, 95% CI: −2.09 to −0.71, p<0.01); subgroup analysis based on treatment time also yielded the same results. GFR in the tanshinone treatment group was better than that in the control group (SMD = 0.83, 95% CI: 0.59 to 1.07, p<0.01). In terms of urine protein levels, 24 h urine protein level, mALB, and β2-MG of CKD patients were reduced to some degree compared with controls, and CysC levels in the tanshinone treatment group were also significantly reduced compared with the control group (SMD = −0.24, 95% CI: −0.44 to −0.03, p<0.05). Safety in the tanshinone treatment group did not differ significantly from that of the control group (risk ratio (RR) = 7.78, 95% CI: 0.99 to 61.05, p>0.05). Conclusion. This meta-analysis showed that tanshinone could control urine protein level in CKD patients, improve kidney function, and delay the evolution of CKD without significant side effects. However, the results were limited and should be interpreted with caution because of the low quality of the included studies. In the future, more rigorous clinical trials need to be conducted to provide sufficient and accurate evidence.

Tubulitis in a patient treated with nivolumab: Case report and literature review

2018 ◽  
Vol 2 (2-3) ◽  
pp. 107-112
Author(s):  
Viral Vakil ◽  
Mark Birkenbach ◽  
Katti Woerner ◽  
Lihong Bu
Keyword(s):  
Acute Kidney Injury ◽  
Immune Checkpoint Inhibitors ◽  
Kidney Biopsy ◽  
Tubulointerstitial Nephritis ◽  
Checkpoint Inhibitors ◽  
Kidney Injury ◽  
Programmed Death Ligand 1 ◽  
Programmed Death ◽  
Metastatic Urothelial Carcinoma ◽  
Programmed Death 1

Kidney injury associated with use of immune checkpoint inhibitors that target the programmed death-1 molecule commonly manifests as acute tubulointerstitial nephritis on kidney biopsy. We present a case of a 66-year-old man who developed acute kidney injury at 6 months after initiation of treatment with anti-programmed death-1 antibody, nivolumab, for treatment of metastatic urothelial carcinoma. A renal biopsy showed focal moderate-to-severe lymphocytic tubulitis with minimal interstitial inflammation. Programmed death ligand-1 immunopositivity was detected only in tubules exhibiting lymphocytic tubulitis. The patient’s renal function improved to baseline with conservative management consisting of discontinuation of nivolumab followed by prednisone treatment.

scholarly journals Prognostic Role and Clinical Significance of Tumor-Infiltrating Lymphocyte (TIL) and Programmed Death Ligand 1 (PD-L1) Expression in Triple-Negative Breast Cancer (TNBC): A Systematic Review and Meta-Analysis Study

Diagnostics ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 704 ◽  
Author(s):  
Parisa Lotfinejad ◽  
Mohammad Asghari Jafarabadi ◽  
Mahdi Abdoli Shadbad ◽  
Tohid Kazemi ◽  
Fariba Pashazadeh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Prognostic Value ◽  
Triple Negative ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Cochrane Library ◽  
P Value ◽  
Programmed Death Ligand 1 ◽  
Programmed Death

This meta-analysis aimed to evaluate the prognostic value of tumor-infiltrating lymphocytes (TILs) and programmed death-ligand 1 (PD-L1), their associations with the clinicopathological characteristics, and the association between their levels in patients with triple-negative breast cancer (TNBC). PubMed, EMBASE, Scopus, ProQuest, Web of Science, and Cochrane Library databases were searched to obtain the relevant papers. Seven studies with 1152 patients were included in this study. Like the level of TILs, there were no significant associations between PD-L1 expression and tumor size, tumor stage, lymph node metastasis, histological grade, and Ki67 (All p-values ≥ 0.05). Furthermore, there was no significant association between PD-L1 expression with overall survival (OS) and disease-free survival (DFS). In assessment of TILs and survival relationship, the results showed that a high level of TILs was associated with long-term OS (hazard ratios (HR) = 0.48, 95% CI: 0.30 to 0.77, p-value < 0.001) and DFS (HR = 0.53, 95% CI: 0.35 to 0.78, p-value < 0.001). The results displayed that tumoral PD-L1 expression was strongly associated with high levels of TILs in TNBC patients (OR = 8.34, 95% CI: 2.68 to 25.95, p-value < 0.001). In conclusion, the study has shown the prognostic value of TILs and a strong association between tumoral PD-L1 overexpression with TILs in TNBC patients.

scholarly journals Association of Leptin and Adiponectin with Risk and Prognosis of Hepatocellular Carcinoma: A Combination of Traditional, Survival and Dose-response Meta-analysis

2020 ◽  
Author(s):  
Lilong Zhang ◽  
Qihang Yuan ◽  
Man Li ◽  
Dongqi Chai ◽  
Wenhong Deng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Meta Analysis ◽  
Healthy Control Group ◽  
Cochrane Library ◽  
Control Group ◽  
Linear Relationships ◽  
Increased Risk ◽  
Healthy Control ◽  
Carcinoma Risk

Abstract Background: The association between leptin, adiponectin levels and the risk as well as prognosis of hepatocellular carcinoma has been investigated by an increasing number of studies, but the results were controversial.Methods: A meta-analysis was performed to assess the correlation between leptin, adiponectin levels and risk and prognosis of hepatocellular carcinoma (CRD42020195882). Through June 14, 2020, PubMed, Cochrane Library, Embase databases, Clinicaltrials, and Opengrey were searched, including references of qualifying articles. Titles, abstracts, and main texts were reviewed by at least 2 independent readers. Stata 16.0 was used to calculate statistical data.Results: Thirty studies were included in this meta-analysis and results showed that hepatocellular carcinoma group had significantly higher leptin levels than the cancer-free control group (SMD = 1.83, 95% CI (1.09, 2.58), P = 0.000) , the healthy control group (SMD = 4.32, 95% CI (2.41, 6.24), P = 0.000) and the cirrhosis group (SMD = 1.85, 95% CI (0.70, 3.01), P = 0.002). Hepatocellular carcinoma group had significantly higher adiponectin levels than the healthy control group (SMD = 1.57, 95% CI (0.37, 2.76), P = 0.010), but no statistical difference compared with the cancer-free control group (SMD = 0.24, 95% CI (-0.35, 0.82), P = 0.430) and the cirrhosis group (SMD = -0.51, 95% CI (-1.30, 0.29), P= 0.213). The leptin rs7799039 polymorphism was associated with increased risk of hepatocellular carcinoma (G vs A: OR = 1.28, 95% CI (1.10, 1.48), P = 0.002). There were linear relationships between adiponectin levels and the risk of hepatocellular carcinoma (OR = 1.066, 95% CI (1.03, 1.11), P = 0.001). In addition, the results showed that high/positive expression of adiponectin was significantly related to lower overall survival in hepatocellular carcinoma patients (HR = 1.70, 95% CI (1.22, 2.37), P = 0.002); however, there was no significantly association between the leptin levels and overall survival (HR = 0.92, 95% CI (0.53, 1.59), P = 0.766).Conclusion: The study shows that high leptin levels are associated with a higher risk of hepatocellular carcinoma. Adiponectin levels are proportional to hepatocellular carcinoma risk, and are related to the poor prognosis.

Advanced papillary thyroid carcinoma responding to nivolumab

2020 ◽  
pp. 107815522092996
Author(s):  
Miguel Michel Ocampo ◽  
Jaren Lerner ◽  
Shawnt Tosonian ◽  
Constantin A Dasanu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Case Report ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Second Line ◽  
Papillary Thyroid ◽  
Programmed Death ◽  
Programmed Death 1

Introduction Clinical indications of immune checkpoint inhibitors have expanded to a variety of malignancies. Approximately one in six patients with hepatocellular carcinoma respond to programmed death 1 inhibitors nivolumab and pembrolizumab. Case report We report herein a patient with synchronous metastatic hepatocellular carcinoma and advanced papillary thyroid carcinoma treated with nivolumab in the second-line therapy. Management and outcome: The hepatocellular carcinoma showed a durable response to the second-line agent nivolumab. Remarkably, the patient’s papillary thyroid carcinoma also responded to this programmed death 1 inhibitor. Discussion To our knowledge, this is the first case report showing the efficacy of nivolumab in the treatment of metastatic papillary thyroid carcinoma. Further studies with immune checkpoint inhibitors in papillary thyroid carcinoma seem warranted.

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