scholarly journals Increased neurotoxicity due to activated immune-inflammatory and nitro-oxidative stress pathways in patients with suicide attempts: a systematic review and meta-analysis.

2021 ◽  
Author(s):  
Asara Vasupanrajit ◽  
Ketsupar Jirakran ◽  
Chavit Tunvirachaisakul ◽  
Michael Maes
Keyword(s):  
Oxidative Stress ◽  
Immune Activation ◽  
Suicide Attempts ◽  
Psychiatric Patients ◽  
Meta Analysis ◽  
Random Effect ◽  
Random Effect Model ◽  
Control Group ◽  
Healthy Controls ◽  
New Biomarkers

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&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&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<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<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<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.

scholarly journals Increased Neurotoxicity Due to Activated Immune-Inflammatory and Nitro-Oxidative Stress Pathways in Patients with Suicide Attempts: A Systematic Review and Meta-Analysis

2021 ◽  
Author(s):  
Asara Vasupanrajit ◽  
Ketsupar Jirakran ◽  
Chavit Tunvirachaisakul ◽  
Michael Maes
Keyword(s):  
Oxidative Stress ◽  
Immune Activation ◽  
Suicide Attempts ◽  
Psychiatric Patients ◽  
Meta Analysis ◽  
Random Effect ◽  
Random Effect Model ◽  
Control Group ◽  
Healthy Controls ◽  
New Biomarkers

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.

scholarly journals Inflammation and Nitro-Oxidative Stress in Current Suicidal Attempts and Current Suicidal Ideation: a Systematic Review and Meta-Analysis

2021 ◽  
Author(s):  
Asara Vasupanrajit ◽  
Ketsupar Jirakran ◽  
Chavit Tunvirachaisakul ◽  
Marco Solmi ◽  
Michael Maes
Keyword(s):  
Oxidative Stress ◽  
Suicidal Ideation ◽  
Inflammatory Response ◽  
Suicide Attempts ◽  
Psychiatric Patients ◽  
Meta Analysis ◽  
Random Effect ◽  
Random Effect Model ◽  
Healthy Controls ◽  
Inflammatory Profile

A meta-analysis showed a significant association between activated immune-inflammatory and nitro-oxidative (IO&amp;NS) pathways and suicide attempts (SA). There are no data whether suicidal ideation (SI) is accompanied by activated IO&amp;NS pathways and whether there are differences between SA and SI. The current study searched PubMed, Google Scholar, and Web of Science, for articles published from inception until May 10, 2021, and systematically reviewed and meta-analyzed the association between recent SA/SI (&lt; 3 months) and IO&amp;NS biomarkers. We included studies which compared psychiatric patients with and without SA and SI and controls (either healthy controls or patients without SA or SI) and used meta-analysis (random-effect model with restricted maximum-likelihood) to delineate effect sizes with 95% confidence intervals (CI). Our search included 59 studies comprising 4.034 SA/SI cases and 12.377 controls. Patients with SA/SI showed activated IO&amp;NS pathways (SMD: 0.299; CI: 0.200; 0.397) when compared to controls. The immune profiles were more strongly associated with SA than with SI, particularly when compared to healthy controls, as evidenced by activated IO&amp;NS pathways (SMD: 0.796; CI: 0.503; 1.089), an immune-inflammatory response (SMD: 1.409; CI: 0.637; 1.462), inflammation (SMD: 1.200; CI: 0.584; 1.816), and neurotoxicity (SMD: 0.904; CI: 0.431; 1.378). The effects sizes of the IO&amp;NS, immune-inflammatory response and inflammatory profile were significantly greater in SA than in SI. In conclusion: increased neurotoxicity due to inflammation and nitro-oxidative stress and lowered neuroprotection may explain at least in part why psychiatric patients show increased SA and SI. The IO&amp;NS pathways are more pronounced in recent SA than in SI.

scholarly journals Inflammation and nitro-oxidative stress in current suicidal attempts and current suicidal ideation: a systematic review and meta-analysis

2021 ◽  
Author(s):  
Asara Vasupanrajit ◽  
Ketsupar Jirakran ◽  
Chavit Tunvirachaisakul ◽  
Marco Solmi ◽  
Michael Maes
Keyword(s):  
Oxidative Stress ◽  
Suicidal Ideation ◽  
Web Of Science ◽  
Suicide Attempts ◽  
Psychiatric Patients ◽  
Meta Analysis ◽  
Random Effect ◽  
Random Effect Model ◽  
Healthy Controls ◽  
Effect Model

AbstractA meta-analysis showed a significant association between activated immune-inflammatory and nitro-oxidative (IO&NS) pathways and suicide attempts (SA). There is no data on whether suicidal ideation (SI) is accompanied by activated IO&NS pathways and whether there are differences between SA and SI. The current study searched PubMed, Google Scholar, and Web of Science, for articles published from inception until May 10, 2021, and systematically reviewed and meta-analyzed the association between recent SA/SI (< 3 months) and IO&NS biomarkers. We included studies which compared psychiatric patients with and without SA and SI and controls (either healthy controls or patients without SA or SI) and used meta-analysis (random-effect model with restricted maximum-likelihood) to delineate effect sizes with 95% confidence intervals (CI). Our search included 59 studies comprising 4.034 SA/SI cases and 12.377 controls. Patients with SA/SI showed activated IO&NS pathways (SMD: 0.299; CI: 0.200; 0.397) when compared to controls. The immune profiles were more strongly associated with SA than with SI, particularly when compared to healthy controls, as evidenced by activated IO&NS (SMD: 0.796; CI: 0.503; 1.089), immune (SMD: 1.409; CI: 0.637; 1.462), inflammatory (SMD: 1.200; CI: 0.584; 1.816), and neurotoxic (SMD: 0.904; CI: 0.431; 1.378) pathways. The effects sizes of the IO&NS, immune and inflammatory profiles were significantly greater in SA than in SI. In conclusion: increased neurotoxicity due to inflammation and nitro-oxidative stress and lowered neuroprotection explains at least in part why psychiatric patients show increased SA and SI. The IO&NS pathways are more pronounced in recent SA than in SI.

Association between circulating leptin levels and multiple sclerosis: a systematic review and meta-analysis

2018 ◽  
Vol 94 (1111) ◽  
pp. 278-283 ◽  
Author(s):  
Xue-Feng Xie ◽  
Xiao-Hui Huang ◽  
Ai-Zong Shen ◽  
Jun Li ◽  
Ye-Huan Sun
Keyword(s):  
Multiple Sclerosis ◽  
Meta Analysis ◽  
Random Effect ◽  
Random Effect Model ◽  
Control Group ◽  
Sample Type ◽  
Healthy Controls ◽  
Eligibility Criteria ◽  
Effect Model ◽  
Healthy Control

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.

scholarly journals Alteration of Postural Balance in Patients with Fibromyalgia Syndrome—A Systematic Review and Meta-Analysis

Diagnostics ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 127
Author(s):  
David Núñez-Fuentes ◽  
Esteban Obrero-Gaitán ◽  
Noelia Zagalaz-Anula ◽  
Alfonso Javier Ibáñez-Vera ◽  
Alexander Achalandabaso-Ochoa ◽  
...  
Keyword(s):  
Systematic Review ◽  
Postural Balance ◽  
Fibromyalgia Syndrome ◽  
Meta Analysis ◽  
Random Effect ◽  
Random Effect Model ◽  
Healthy Controls ◽  
Functional Balance ◽  
Sensory Organization ◽  
Effect Model

Balance problems are one of the most frequent symptoms in patients with Fibromyalgia Syndrome (FMS). However, the extent and nature of this balance disorder are not known. The objective of this work was to determine the best evidence for the alteration of postural balance in patients with FMS and analyze differences with healthy controls. To meet this objective, a systematic review with meta-analysis was performed. A bibliographical search was carried out in PubMed Medline, Scopus, Web of Science, CINAHL and SciELO. Observational studies that assessed postural balance in patients with FMS compared to healthy subjects in baseline conditions, were selected. In a random-effect model, the pooled effect was calculated with the Standardized Mean Difference (SMD) and its 95% confidence interval (CI). Nineteen studies reporting data of 2347 participants (95% female) were included. FMS patients showed poor balance with a large effect on static (SMD = 1.578; 95% CI = 1.164, 1.992), dynamic (SMD = 0.946; 95% CI = 0.598, 1.294), functional balance (SMD = 1.138; 95% CI = 0.689, 1.588) and on balance confidence (SMD = 1.194; 95% CI = 0.914, 1.473). Analysis of the Sensory Organization Test showed large alteration of vestibular (SMD = 1.631; 95% CI = 0.467, 2.795) and visual scores (SMD = 1.317; 95% CI = 0.153, 2.481) compared to healthy controls. Patients with FMS showed worse scores for different measures of postural balance compared to healthy controls. Concretely, FMS patients appear to have poor vestibular and visual scores with a possible somatosensory dependence.

Reno-vascular toxicities associated with carfilzomib: Systematic review and meta-analysis.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e21622-e21622
Author(s):  
Chintan Shah ◽  
Harini Bejjanki ◽  
Rohit Bishnoi ◽  
Ankur Jain ◽  
Subhankar Samal ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Phase I ◽  
Meta Analysis ◽  
Random Effect ◽  
Random Effect Model ◽  
Dose Effect ◽  
Phase Iii ◽  
Control Group ◽  
Phase Iii Clinical Trials

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.

scholarly journals Assessment of the Clinical Trials Safety Profile of PD-1/PD-L1 Inhibitors Among Patients With Cancer: An Updated Systematic Review and Meta-Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Yuan Tian ◽  
Alan Huang ◽  
Yue Yang ◽  
Qi Dang ◽  
Qing Wen ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Adverse Events ◽  
Safety Profile ◽  
Meta Analysis ◽  
Random Effect ◽  
Random Effect Model ◽  
Control Group ◽  
Risk Of Death ◽  
Effect Model ◽  
Newcastle Ottawa Scale

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.

scholarly journals Association of homocysteine with ankylosing spondylitis: a systematic review and meta-analysis

2021 ◽  
Vol 61 (1) ◽  
Author(s):  
Hui-hui Li ◽  
Xue-quan Li ◽  
Lin-tao Sai ◽  
Yi Cui ◽  
Jia-hui Xu ◽  
...  
Keyword(s):  
Ankylosing Spondylitis ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Methylenetetrahydrofolate Reductase ◽  
Activity Index ◽  
Meta Analysis ◽  
Random Effect ◽  
Random Effect Model ◽  
Control Group ◽  
China National Knowledge Infrastructure

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.

Effects of melatonin supplementation on oxidative stress: a systematic review and meta-analysis of randomized controlled trials

2020 ◽  
Vol 41 (4) ◽  
Author(s):  
Parivash Ghorbaninejad ◽  
Fatemeh Sheikhhossein ◽  
Farhang Djafari ◽  
Aliyu Jibril Tijani ◽  
Saba Mohammadpour ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Random Effect ◽  
Random Effect Model ◽  
Protein Carbonyl ◽  
Considerable Effect ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
Total Antioxidant

AbstractObjectivesPrevious studies showed that melatonin supplementation may suppress oxidative stress, however, the results have not been consistent. So, we conducted this meta-analysis to assess the precise relationship between melatonin supplementation and oxidative stress.MethodsPubMed and Scopus were searched for randomized controlled trials that investigated the effect of melatonin supplementation on oxidative stress up to March 2020. Heterogeneity was assessed by Cochran’s Q test and I-square (I2) statistic. Data were pooled using the random effect model and standardized mean difference (SMD) was considered as the summary effect size. Also, standard methods were used for assessment of sensitivity analysis and publication bias.ResultsWe included 15 related articles and our findings indicated that melatonin supplementation significantly increased total antioxidant capacity (TAC) level (SMD: 1.03, 95% CI: 0.24, 1.81, p=0.011) and reduced protein carbonyl (PCO) (SMD: −1.78, 95% CI: −2.97, −0.58, p=0.004) and malondialdehyde (MDA) levels (SMD: −0.94, 95% CI: −1.48, −0.40, p=0.001). Additionally, there was considerable effect on TAC level by using ≥20 mg/d melatonin and in people under 35 years old. MDA level also decreased using dosage of below 20 mg/d and in people ≥35 years old.ConclusionsThe present study showed a promising effect of melatonin administration for reducing MDA, PCO, and increasing TAC levels. However, further studies especially with more attention to PCO level assessment are needed to confirm the findings of the present study in larger samples on different populations.

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 ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Cancer Patients ◽  
Thyroid Dysfunction ◽  
Meta Analysis ◽  
Random Effect ◽  
Random Effect Model ◽  
Control Group ◽  
Manual Search ◽  
Incidence Risk ◽  
Newcastle Ottawa Scale

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 &lt;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.

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