scholarly journals The Risk of Immune-Related Thyroid Dysfunction Induced by PD-1/PD-L1 Inhibitors in Cancer Patients: An Updated Systematic Review and Meta-Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Yuan Tian ◽  
Ran Li ◽  
Yan Liu ◽  
Meng Li ◽  
Yuxiao Song ◽  
...  

BackgroundThyroid dysfunction is common for cancer patients receiving PD-1/PD-L1 inhibitor therapies. To clarify the incidence risk of thyroid dysfunction would be important for guiding anti-PD-1 and anti-PD-L1 immunotherapy. Therefore, the updated meta-analysis was conducted to evaluate the incidence risk of thyroid dysfunction caused by PD-1/PD-L1 inhibitors.MethodsPD-1/PD-L1 inhibitor related clinical trials were collected by a systematic search of the PubMed. Some relevant studies were identified by a manual search. The incidence risk of all grades and grades 3-5 was analyzed and evaluated by random effect model. The Newcastle Ottawa Scale was used for the quality assessment of all clinical trials.ResultsForty-three clinical trials were collected. Compared with chemotherapy, the risk of hypothyroidism of all grades was significantly higher (OR=7.15, 95%CI:[4.85, 10.55], I2 = 40%, Z=9.91(P <0.00001)) in PD-1/PD-L1 group. Similar results could also be noted, when the control group was placebo or CTLA-4. When PD-1/PD-L1 was combined with other treatments for cancer patients, the risk of hypothyroidism of all grades was also significantly increased. Similar to the analysis results of hypothyroidism, PD-1/PD-L1 inhibitors played the same role in increasing the risk of hyperthyroidism and thyroiditis. Few significant analysis results was noted, when the risk of thyroid dysfunction of grades 3-5 was assessed.ConclusionWhether used alone or in combination with other anti-tumor drugs, PD-1/PD-L1 inhibitors increased the risk of thyroid dysfunction, especially for hypothyroidism. Furthermore, PD-1/PD-L1 was better than chemotherapy and CTLA-4 in increasing the risk of thyroid dysfunction.

2021 ◽  
Vol 11 ◽  
Author(s):  
Yuan Tian ◽  
Alan Huang ◽  
Yue Yang ◽  
Qi Dang ◽  
Qing Wen ◽  
...  

BackgroundUnderstanding the safety and adverse event profiles of PD-1/PD-L1 inhibitors is important in guiding cancer immunotherapy. Consequently, we designed this meta-analysis to evaluate the safety of PD-1/PD-L1 inhibitors in clinical trials involving cancer patients.MethodsFour safety indicators comprising treatment-related adverse events, death, discontinuation of therapy and grades 3–5 adverse events were evaluated using the random effect model. The quality of enrolled trials was assessed using the Newcastle Ottawa Scale (NOS).ResultsForty-four clinical trials were included in the final meta-analysis. Compared with chemotherapy, the risk of death due to the use of PD-1/PD-L1 inhibitors was much lower than that experienced in the control group (OR = 0.65, 95%CI: [0.47, 0.91], I2 = 0%, Z = 2.52 (P = 0.01)). Similar observations were apparent regarding the other three indicators of safety and also when the use of PD-1/PD-L1 inhibitors alone is compared with the combined use of PD-1/PD-L1 and CTLA-4. When used together with chemotherapy, PD-1/PD-L1 inhibitors increased the incidence of the adverse events as compared to the use of chemotherapy alone. Increased risks for adverse events were also noticed with the use of PD-1/PD-L1 inhibitors over the use of a placebo.ConclusionThe use of PD-1/PD-L1 inhibitors alone is associated with a better safety profile compared to either the use of chemotherapy or the use of PD-1/PD-L1 inhibitors with other anticancer regimens.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e21622-e21622
Author(s):  
Chintan Shah ◽  
Harini Bejjanki ◽  
Rohit Bishnoi ◽  
Ankur Jain ◽  
Subhankar Samal ◽  
...  

e21622 Background: Carfilzomib (Carf) is a novel proteasome inhibitor that is approved for patients with relapsed multiple myeloma (RMM) who have failed ≥ 1 prior lines of therapy. The incidence and seriousness of Carf associated reno-vascular toxicities (RVT) is not well known. We performed systematic review of Carf literature with meta-analysis to determine its incidence and overall risk. Methods: Initial search of literature led to a total of 175 Carf related articles. However, we used a total of 29 publications; phase I/II, phase II and phase III clinical trials (n = 3) which used Carf as monotherapy or in combination. We excluded phase I studies. Incidence rates and odds ratios (OR) were calculated with either fixed effect or random effect model based on the heterogeneity of included studies. Toxicity such as hypertension (HTN), renal failure (RF) and venous thromboembolism (VTE) were reported according to CTCAE v4.0. Results: A total of 4560 patients with various hematological and solid malignancies were included. Incidences of toxicities were: 15.9% and 4.7 % for HTN, 11.2% and 3.44% for RF, 6.47% and 2.22% for VTE, respectively for all grades and high grades in each category. When compared to control group taken from phase III clinical trials, the risk of HTN and RF due to Carf was significantly higher [OR = 2.91 and 3.32 in HTN (P < 0.001)], [OR = 1.71 and 1.79 (P < 0.05) for RF], respectively for all grade and high grade in each category. Moreover, incidence of HTN with higher than standard dose of carf (27 mg/m2 twice weekly) was significantly higher (P < 0.001). RF and VTE did not have the dose effect. Concomitant use of immunomodulator (IMiD) significantly increased, as expected, the incidence of VTE (P < 0.001). There was no variation in the incidence of RVT among newly diagnosed versus RMM (P = 0.4). Conclusions: Overall incidence and risk of hypertension and renal toxicities seems to be high when using Carf. Higher doses of Carf seem to lead to higher incidence of HTN, while the risk of VTE is higher with concomitant IMiD use. The pathophysiology for these complications is poorly understood, however it could be secondary to endothelial effect of carf. Physician should be vigilant about these effects as it can lead to poor overall outcomes.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e21674-e21674
Author(s):  
Chintan Shah ◽  
Rohit Bishnoi ◽  
Harini Bejjanki ◽  
Ankur Jain ◽  
Subhankar Samal ◽  
...  

e21674 Background: Carfilzomib (Carf)is a novel proteasome inhibitor (PI) that is approved for patients with relapsed multiple myeloma (RMM) who have failed ≥ 1 prior lines of therapy. The incidence and seriousness of Carf associated cardiotoxicity (CT) is not well defined. We hypothesize that CT is more frequent than that seen with other PIs. We performed systematic review of Carf literature with meta-analysis to determine its incidence and overall risk. Methods: Initial search of literature led to a total of 175 Carf related articles. However, we used 29 publicatons; phase I/II, phase II and phase III (n = 3) clinical trials in which Carf was used as monotherapy or in combination with other chemo agents. We excluded phase I studies and studies without CT data. Incidence rates and odds ratios (OR) were calculated with either fixed effect or random effect model based on the heterogeneity of included studies. Toxicity was reported according to CTCAE v4.0. Results: A total of 4560 patients with various hematological and solid malignancies were included. Incidence of all grades and high grades (≥ 3) CT (including arrhythmias, CHF with LVEF drop, and coronary syndrome) were 7.8% and 4.72%, respectively. When compared to control group taken from phase III clinical trials, the risk of developing CT due to Carf was significantly higher with OR of 1.90 and 2.03 (P < 0.01) for all grades and high grades, respectively. Moreover, incidence of CT was significantly higher in Carf combination therapy (9.85%) compared to Carf monotherapy (5.40%) (P = 0.01). Furthermore, incidence of high grade CT was 7.5% and 5% with and without concomitant immunomodulatory agent (IMiD), respectively (P = 0.004). There was no variation in the incidence of CT among newly diagnosed versus RMM (P = 0.6), and no Carf dose effect. Mortality rate associated with cardiotoxicity was 1.5%. Conclusions: Overall incidence of Carf related CT seems to be higher than that reported with other PIs. Although, the pathophysiology is poorly understood, this trend could potentially be secondary to irreversible nature of proteasome inhibition by Carf. There seems to be a significant increase in CT with combination of Carf and an IMiD. Prior therapies and higher Carf doses have no effect on CT incidence.


2020 ◽  
Vol 27 (4) ◽  
pp. 272-281
Author(s):  
Khalid Hamid Changal ◽  
Muhammad Shayan Khan ◽  
Rehana Bashir ◽  
Mujeeb Abdul Sheikh

Introduction: Endothelial dysfunction is an early marker of atherosclerosis. Flow-mediated dilation (FMD), measured by ultrasonography, is used to noninvasively assess endothelial dysfunction. Preparations of curcumin, a naturally occurring pigment found in turmeric, may improve FMD and thus endothelial dysfunction. We did a systematic review and meta-analysis to analyze the effect of curcumin preparations on endothelial dysfunction. Methods: Five randomized clinical trials met the inclusion criteria for meta-analysis. The primary outcome was an improvement in FMD, as measured at brachial artery, after supplementations with curcumin preparations compared to the control group. Standardized mean difference and Hedges’ g were used for effect size (ES) measurement. An ES of 0.2–0.5 is considered small, 0.5–0.8 is medium, and more than 0.8 is large. Publication bias was studied too. Results: We found supplementation with curcumin preparations had an overall ES (standard difference in means) of 1.379 (95% CI 0.485–2.274, p = 0.003) on FMD. The overall Hedges’ g was 1.353 (95% CI 0.47–2.235, p = 0.03). This analysis suggests a positive and large ES of curcumin preparations on FMD using a random effect model. Smokers had a smaller increase in FMD compared to nonsmokers (ES 0.379 vs. 1.639, p = 0.034). Conclusion: This meta-analysis of 5 randomized clinical trials indicates a significant effect of curcumin preparations to increase the FMD compared to placebo and thus endothelial function. This effect is not strongly noticed in smokers.


2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Somayeh Es-haghee ◽  
Fatemeh Shabani ◽  
Jessie Hawkins ◽  
Mohammad Ali Zareian ◽  
Fatemeh Nejatbakhsh ◽  
...  

ObjectivesPremenstrual syndrome (PMS) is a common disturbance among women of childbearing age. Aromatherapy is a commonly used form of complementary and alternative medicine (CAM) to treat PMS. The purpose of this study is to quantify and summarize the effects of aromatherapy on premenstrual syndrome symptoms. Methods. PubMed, Scopus, and Cochrane Library databases were searched through relevant search terms until October 2020. The effect sizes were pooled as weighted mean difference (WMD) and 95% confidence interval (CI) using the random effect model. Egger tests and visual inspection of the funnel plot were performed to identify the existence of publication bias. The I-squared (I2) test was applied to measure heterogeneity. Results. Eight studies (n = 8) were included in this analysis. The quantitative synthesis of evidence found that aromatherapy decreases PMS scores (WMD –13.83; 95% CI (−22.04, −5.63), I2 = 94.5%), total psychological symptoms of PMS (WMD –3.51; 95% CI (−4.84, −2.18), I2 = 82.6%), anxiety of PMS (WMD–1.78; 95% CI (−3.17, −0.38), I2 = 94.2%), depression of PMS (WMD–2.0; 95% CI (−3.65, −0.34), I2 = 93.7%), and fatigue of PMS (WMD – 1.44; 95% CI (−2.44, −0.44), I2 = 89.7%) compared to the control group. Conclusion. Aromatherapy is an effective tool for the relief of PMS symptoms. Additional randomized controlled clinical trials with different durations and essential oils should be conducted to confirm our findings.


Author(s):  
Mary Obasi ◽  
Arielle Abovich ◽  
Jacqueline B. Vo ◽  
Yawen Gao ◽  
Stefania I. Papatheodorou ◽  
...  

Abstract Purpose Cardiotoxicity affects 5–16% of cancer patients who receive anthracyclines and/or trastuzumab. Limited research has examined interventions to mitigate cardiotoxicity. We examined the role of statins in mitigating cardiotoxicity by performing a systematic review and meta-analysis of published studies. Methods A literature search was conducted using PubMed, Embase, Web of Science, ClinicalTrials.gov, and Cochrane Central. A random-effect model was used to assess summary relative risks (RR), weighted mean differences (WMD), and corresponding 95% confidence intervals. Testing for heterogeneity between the studies was performed using Cochran’s Q test and the I2 test. Results Two randomized controlled trials (RCTs) with a total of 117 patients and four observational cohort studies with a total of 813 patients contributed to the analysis. Pooled results indicate significant mitigation of cardiotoxicity after anthracycline and/or trastuzumab exposure among statin users in cohort studies [RR = 0.46, 95% CI (0.27–0.78), p = 0.004, $${ }I^{2}$$ I 2  = 0.0%] and a non-significant decrease in cardiotoxicity risk among statin users in RCTs [RR = 0.49, 95% CI (0.17–1.45), p = 0.20, $$I^{2}$$ I 2  = 5.6%]. Those who used statins were also significantly more likely to maintain left ventricular ejection fraction compared to baseline after anthracycline and/or trastuzumab therapy in both cohort studies [weighted mean difference (WMD) = 6.14%, 95% CI (2.75–9.52), p < 0.001, $$I^{2}$$ I 2  = 74.7%] and RCTs [WMD = 6.25%, 95% CI (0.82–11.68, p = 0.024, $$I^{2}$$ I 2  = 80.9%]. We were unable to explore publication bias due to the small number of studies. Conclusion This meta-analysis suggests that there is an association between statin use and decreased risk of cardiotoxicity after anthracycline and/or trastuzumab exposure. Larger well-conducted RCTs are needed to determine whether statins decrease risk of cardiotoxicity from anthracyclines and/or trastuzumab. Trial Registration Number and Date of Registration PROSPERO: CRD42020140352 on 7/6/2020.


2018 ◽  
Vol 94 (1111) ◽  
pp. 278-283 ◽  
Author(s):  
Xue-Feng Xie ◽  
Xiao-Hui Huang ◽  
Ai-Zong Shen ◽  
Jun Li ◽  
Ye-Huan Sun

AimLeptin, synthesised by adipocytes, has been identified as a hormone that can influence inflammatory activity. Several studies have investigated leptin levels in patients with multiple sclerosis (MS), but the results are not consistent. This study aims to derive a more precise evaluation on the relationship between circulating leptin levels and MS.DesignA comprehensive literature searched up to July 2017 was conducted to evaluate the association of circulating leptin levels and MS. The random-effect model was applied to calculate pooled standardised mean difference (SMD) and its 95% CI.Main outcome measuresCirculating leptin levels of patients with MS and healthy controls.ResultsOf 2155 studies identified, 33 met eligibility criteria and 9 studies with 645 patients with MS and 586 controls were finally included in the meta-analysis. Meta-analysis revealed that, compared with the healthy control group, the MS group had significantly higher plasma/serum leptin levels, with the SMD of 0.70% and 95% CI (0.24 to 1.15). Subgroup analyses suggested that the leptin levels of patients with MS were associated with region, age, study sample size, measurement type, gender and blood sample type.ConclusionOverall, our study suggests that patients with MS have a significantly higher leptin level than in healthy controls. Further mechanism studies and longitudinal large cohort studies are still needed to further reveal the role of leptin in the pathogenesis of MS.


2020 ◽  
Vol 12 (4) ◽  
pp. 246-255
Author(s):  
Omid Asbaghi ◽  
Sara Kashkooli ◽  
Mohammad Reza Amini ◽  
Hossein Shahinfar ◽  
Kurosh Djafarian ◽  
...  

This meta-analysis was performed to assess the effect of L-carnitine supplementation on lipid profile. A systematic search were conducted in PubMed and Scopus to identify randomized clinical trials (RCTs) which evaluated the effects of L-carnitine on lipid profile. Pooled effect sizes were measured using random-effect model (Dersimonian-Laird). Meta-analysis showed that L-carnitine supplementation significantly reduced total cholesterol (TC) (weighted mean difference [WMD]: -8.17 mg/dL; 95% CI,-14.68 to -1.65, I2=52.2%, P = 0.041). Baseline level of TC was a source of heterogeneity, with a greater effect in studies with a baseline level of more than 200 mg/d (WMD: -11.93 mg/dL; 95% CI, -20.80 to-3.05). L-carnitine also significantly decreased low-density lipoprotein-cholesterol (LDL-C) (WMD:-5.22 mg/dL; 95% CI, -9.54 to -0.91, I2=66.7%, P = 0.010), and LDL-C level <100 mg/dL), trial duration,and L-carnitine dosage were potential sources of heterogeneity. L-carnitine supplementation appeared to have no significant effect on high-density lipoprotein-cholesterol (HDL-C) (WMD: -0.51 mg/dL;95% CI, -2.45 to 1.44) and triglyceride (TG) (WMD: 2.80 mg/dL; 95% CI, -8.09 to 13.69). This meta-analysisrevealed that L-carnitine may have favorable effects on lipid profile, especially LDL-C and TC. However, further RCTs are needed to confirm the veracity of these results, particularly among hyperlipidemic patients.


Author(s):  
Asara Vasupanrajit ◽  
Ketsupar Jirakran ◽  
Chavit Tunvirachaisakul ◽  
Michael Maes

Background: Suicide attempts (SA) frequently occur in patients with mood disorders and schizophrenia, which are both accompanied by activated immune-inflammatory and nitro-oxidative (IO&amp;NS) pathways. Methods: We searched PubMed, Google Scholar, and Web of Science, for articles published from inception until February 1, 2021. We included studies that compared blood biomarkers in psychiatric patients with (SA+) and without SA (SA-) and heathy controls and we combined different IO&amp;NS biomarkers into immune, inflammatory, and neurotoxic profiles and used meta-analysis (random-effect model with restricted maximum-likelihood) to delineate effect sizes with 95% confidence interval (CI).Findings: Our search included 51 studies comprising 4.945 SA+ patients and 24.148 controls. We stratified the control group into healthy controls and SA- patients. SA+ patients showed significantly (p&lt;0.001) increased immune activation (SMD: 1.044; CI: 0.599-1.489), inflammation (SMD: 1.109; CI: 0.505, 1.714), neurotoxicity (SMD: 0.879; CI: 0.465, 1.293), and lowered neuroprotection (SMD: 0.648; CI: 0.354, 0.941) as compared with healthy controls. When compared with SA- patients, those with SA+ showed significant (p&lt;0.001) immune activation (SMD: 0.290; CI: 0.183, 0.397), inflammation (SMD: 0.311; CI: 0.191, 0.432), and neurotoxicity (SMD: 0.315; CI: 0.198, 0.432), and lowered neuroprotection (SMD: 0.341; CI: 0.167, 0.515). Patients with current, but not lifetime, SA showed significant (p&lt;0.001) levels of inflammation and neurotoxicity as compared with controls. Conclusions: Patients with immune activation are at a higher risk of SA which may be explained by increased neurotoxicity due to inflammation and nitro-oxidative stress. This meta-analysis discovered new biomarkers of SA and therapeutic targets to treat individuals with SA.


2021 ◽  
Vol 61 (1) ◽  
Author(s):  
Hui-hui Li ◽  
Xue-quan Li ◽  
Lin-tao Sai ◽  
Yi Cui ◽  
Jia-hui Xu ◽  
...  

Abstract Background Hyperhomocysteinemia is associated with autoimmune diseases such as ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA). Current findings regarding plasma/serum homocysteine (HCY) levels in AS patients are inconsistent. This study aims to systematically evaluate the association between circulating HCY levels and AS. Methods Online electronic databases (PubMed, Web of Science, Embase, ScienceDirect, China National Knowledge Infrastructure (CNKI), and Wanfang data) were used to retrieve all relevant articles published up to May 7, 2020. The pooled standardized mean difference (SMD) with 95% confidence interval (CI) was calculated using the random-effect model, Stata16 software. Results Nine articles containing 778 AS patients and 522 controls were included in this meta-analysis. No significant differences in HCY levels were found between AS and control groups (pooled SMD = 0.46, 95% CI = − 0.30 to 1.23, P = 0.23). However, subgroup analysis suggested that HCY levels were significantly higher (P < 0.05) in the AS group treated with methotrexate (MTX) compared with the control group. In contrast, HCY levels were significantly (P < 0.05) lower in the AS group receiving anti-TNF-α treatment compared with the control group. No significant differences were detected between HCY levels and disease activity scores (Bath AS disease activity index, BASDAI), and methylenetetrahydrofolate reductase (MTHFR) C677T genotype. Conclusion This meta-analysis indicates that HCY levels are similar between AS and controls, and do not correlate with disease activity. However, different medical treatments cause fluctuations of circulating HCY levels in AS patients. Further and larger-scale studies are needed to confirm these findings. Trial registration This study was registered at international prospective register of systematic reviews (PROSPERO), registration number: CRD42020184426.


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